International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors 69 84 EN MIHO KURE Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROSHI TAZAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOJI DEMIYA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HIROYA KONDO Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YUSUKE MOCHIZUKI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TADASHI KOMATSUBARA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences AKI YOSHIDA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOJI UOTANI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences JOE HASEI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOMOHIRO FUJIWARA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYUKI KUNISADA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YASUO URATA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences SHUNSUKE KAGAWA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIFUMI OZAKI Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TOSHIYOSHI FUJIWARA Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells.<br> Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1.<br> Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors.<br> Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 106 12 2025 Thorough characterization of a new curvulavirid from a Japanese strain of Cryphonectria nitschkei 002177 EN Sabitree Shahi ​Institute of Plant Science and Resources, Okayama University Sakae Hisano ​Institute of Plant Science and Resources, Okayama University Wasiatus Sa'diyah ​Institute of Plant Science and Resources, Okayama University Yoshihiro Takaki ​Institute for Extra-cutting-edge Science and Technology Avant-garde Research (X-star), Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Hideki Kondo ​Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki ​Institute of Plant Science and Resources, Okayama University A new curvulavirid was isolated from a Japanese strain of the filamentous ascomycete Cryphonectria nitschkei and thoroughly characterized. The virus termed Cryphonectria nitschkei curvulavirus 1 (CnCvV1) has a bi-segmented dsRNA genome. CnCvV1 dsRNA1 encodes an RNA-dependent RNA polymerase (592 amino acids), while dsRNA2 possesses two ORFs, one that encodes a protein associated with the genomic dsRNA and the other that encodes a hypothetical protein of unknown function. CnCvV1 could be experimentally introduced into another virus-free strain of C. nitschkei and two strains of different fungal species within the genus Cryphonectria (Cryphonectria parasitica and Cryphonectria carpinicola). Based on phenotypic comparison, the virus caused asymptomatic infection in the three newly established fungal strains. However, there was a reduced colony growth rate and increased CnCvV1 accumulation in an RNA silencing-deficient mutant (Δdcl2), relative to the wt strain EP155 of a model virus host fungus (C. parasitica). These findings suggest that CnCvV1 is targeted by RNA silencing in C. parasitica. This study provides a foundation for further exploration of curvulavirids that have been biologically understudied. 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.

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

Springer Science and Business Media LLC Acta Medica Okayama 0925-5710 122 5 2025 Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy 689 699 EN Kenta Hayashino Department of Hematology and Oncology, Okayama University Keisuke Seike Department of Hematology and Oncology, Okayama University Taro Masunari Department of Hematology, Chugoku Central Hospital Risa Hashida Division of Hematology, Ehime Prefectural Central Hospital Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Science Center Yuki Fujiwara Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Toshiki Terao Department of Hematology and Oncology, Okayama University Wataru Kitamura Department of Hematology and Oncology, Okayama University Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Chihiro Kamoi Department of Hematology and Oncology, Okayama University Takumi Kondo Department of Hematology and Oncology, Okayama University Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Noboru Asada Department of Hematology and Oncology, Okayama University Daisuke Ennishi Department of Hematology and Oncology, Okayama University Keiko Fujii Department of Hematology and Oncology, Okayama University Nobuharu Fujii Department of Hematology and Oncology, Okayama University Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2–4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR. 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.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 15 1 2025 Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy 38590 EN Chiaki Yagi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunya Hanzawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Kadowaki Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Yoshida Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masaki Sakamoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yuki Hamada Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryoma Sugimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoko Ohtani Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kento Kumon Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Hashimoto Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Nobuhiko Kanaya Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Kagawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Tazawa Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Oncolytic adenoviruses replicate selectively in tumor cells and induce immunogenic cell death, but predictive biomarkers for early therapeutic response are lacking. This study evaluated extracellular vesicle-encapsulated adenoviral E1A-DNA (EV-E1A-DNA) as a minimally invasive biomarker for monitoring responses to telomerase-specific oncolytic adenoviruses OBP-301 and OBP-502. EVs were isolated from human and murine cancer cell lines and from the serum of treated mice using ultracentrifugation. EV-associated E1A-DNA levels were measured by quantitative polymerase chain reaction and found to correlate with cytotoxicity in vitro and tumor regression in vivo. In xenograft models, serum EV-E1A-DNA levels at 2 days post-treatment showed strong correlations with final tumor volume and survival, supporting their utility as an early predictive biomarker. In immunocompetent mice pre-immunized with wild-type adenovirus, free viral DNA was undetectable in serum due to neutralizing antibodies, whereas EV-E1A-DNA remained detectable. This “stealth effect” indicates that EVs protect viral components from immune clearance. These results demonstrate that EV-E1A-DNA is a sensitive and virus-specific biomarker that enables early assessment of therapeutic efficacy, even in the presence of antiviral immunity. This strategy offers a promising liquid biopsy approach for personalized monitoring of oncolytic virotherapy and may be applicable to other virus-based therapies. No potential conflict of interest relevant to this article was reported.

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

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.

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

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 Animal dsRNA and ssRNA(−) Viruses Subcommittee, 2025 002112 EN Holly R. Hughes Centers for Disease Control and Prevention Matthew J. Ballinger Biological Sciences, Mississippi State University Yiming Bao National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences Nicolas Bejerman Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Instituto Nacional de Tecnología Agropecuaria (INTA) Kim R. Blasdell CSIRO Health and Biosecurity Thomas Briese Center for Infection and Immunity, and Department of Epidemiology, Mailman School of Public Health, Columbia University Julia Brignone Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Jean Paul Carrera Instituto Conmemorativo Gorgas de Estudios de la Salud Lander De Coninck Division of Clinical and Epidemiological Virology, KU Leuven William Marciel de Souza Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky Humberto Debat Instituto Nacional de Tecnología Agropecuaria (INTA) Ralf G. Dietzgen QAAFI, The University of Queensland Ralf Dürrwald Robert Koch Institut Mert Erdin Department of Virology, University of Helsinki Anthony R. Fooks Animal and Plant Health Agency (APHA) Kristian M. Forbes Department of Biological Sciences, University of Arkansas Juliana Freitas-Astúa Embrapa Cassava and Fruits Jorge B. Garcia Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Jemma L. Geoghegan Department of Microbiology and Immunology, University of Otago Rebecca M. Grimwood Department of Microbiology and Immunology, University of Otago Masayuki Horie Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University Timothy H. Hyndman School of Veterinary Medicine, Murdoch University Reimar Johne German Federal Institute for Risk Assessment John D. Klena Viral Special Pathogens Branch, The Centers for Disease Control and Prevention Hideki Kondo Institute of Plant Science and Resources, Okayama University Eugene V. Koonin Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health Alexei Y. Kostygov University of Ostrava 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 Michael Letko Paul G. Allen School for Global Health, Washington State University Jun-Min Li Institute of Plant Virology, Ningbo University Yiyun Liu National Genomics Data Center, China National Center for Bioinformation; Beijing Institute of Genomics, Chinese Academy of Sciences; University of Chinese Academy of Sciences Maria Laura Martin Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Nathaniel Mull Department of Natural Sciences, Shawnee State University Yael Nazar Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Norbert Nowotny College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health Márcio Roberto Teixeira Nunes Universidade Federal do Pará Arnfinn Lodden Økland Pharmaq Analytiq Dennis Rubbenstroth Institute of Diagnostic Virology, Friedrich-Loeffler-Institut Brandy J. Russell Centers for Disease Control and Prevention Eric Schott Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science Stephanie Seifert Paul G. Allen School for Global Health, Washington State University Carina Sen Instituto Nacional de Enfermedades Virales Humanas Dr. Julio I. Maiztegui. INEVH -ANLIS Elizabeth Shedroff Viral Special Pathogens Branch, The Centers for Disease Control and Prevention Tarja Sironen Department of Virology, University of Helsinki Teemu Smura Department of Virology, University of Helsinki Camila Prestes Dos Santos Tavares Integrated Group of Aquaculture and Environmental Studies, Federal University of Paraná Robert B. Tesh Department of Pathology, The University of Texas Medical Branch Natasha L. Tilston Department of Microbiology and Immunology, Indiana University School of Medicine Noël Tordo Institut Pasteur Nikos Vasilakis Department of Pathology, The University of Texas Medical Branch Peter J. Walker University of Queensland Fei Wang Wuhan Institute of Virology, Chinese Academy of Sciences Anna E. Whitfield North Carolina State University Shannon L.M. Whitmer Viral Special Pathogens Branch, The Centers for Disease Control and Prevention Yuri I. Wolf Computational Biology Branch, Division of Intramural Research National Library of Medicine, National Institutes of Health Han Xia Wuhan Institute of Virology, Chinese Academy of Sciences Gong-Yin Ye Institute of Insect Sciences, Zhejiang University Zhuangxin Ye Institute of Plant Virology, Ningbo University Vyacheslav Yurchenko University of Ostrava Mingli Zhao Department of Pathobiology and Population Sciences, Royal Veterinary College RNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(−) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses. 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 from the Plant Viruses Subcommittee, 2025 002114 EN Luisa Rubino Istituto per la Protezione Sostenibile delle Piante, CNR Peter Abrahamian USDA-ARS, BARC, National Germplasm Resources Laboratory Wenxia An Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University Miguel A. Aranda Centro de Edafología y Biología Aplicada del Segura-CSIC José T. Ascencio-Ibañez Department of Molecular and Structural Biochemistry, North Carolina State University Nicolas Bejerman Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET Arnaud G. Blouin Plant Protection Department Thierry Candresse UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE Tomas Canto Margarita Salas Center for Biological Research (CIB-CSIC) Spanish Council for Scientific Research (CSIC) Mengji Cao National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University John P. Carr Department of Plant Sciences, University of Cambridge Won Kyong Cho Agriculture and Life Sciences Research Institute, Kangwon National University Fiona Constable Agriculture Victoria Research, Department of Energy, Environment and Climate Action and School of Applied Systems Biology, La Trobe University Indranil Dasgupta University of Delhi South Campu Humberto Debat Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET Ralf G. Dietzgen Queensland Alliance for Agriculture and Food Innovation, The University of Queensland Michele Digiaro CIHEAM, Istituto Agronomico Mediterraneo of Bari Livia Donaire Centro de Edafología y Biología Aplicada del Segura-CSIC Toufic Elbeaino CIHEAM, Istituto Agronomico Mediterraneo of Bari Denis Fargette Virus South Data Fiona Filardo Queensland Department of Primary Industries Matthias G. Fischer Max Planck Institute for Marine Microbiology Nuria Fontdevila Plant Protection Department Adrian Fox Fera Science Ltd (Fera), York Biotech Campus Juliana Freitas-Astua Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation Marc Fuchs Plant Pathology, Cornell University Andrew D.W. Geering Queensland Alliance for Agriculture and Food Innovation, The University of Queensland Mahan Ghafari Department of Biology, University of Oxford Anders Hafrén Swedish University of Agriculture John Hammond USDA-ARS, USNA, Floral and Nursery Plants Research Unit Rosemarie Hammond USDA-ARS, BARC, Molecular Plant Pathology Laboratory Beata Hasiów-Jaroszewska Institute of Plant Protection-NRI Eugenie Hebrard PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro Carmen Hernández Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC Jean-Michel Hily Institut Français de la Vigne et du Vin Ahmed Hosseini Vali-e-Asr University of Rafsanjan, Department of Plant Protection Roger Hull Retired from John Innes Centre Alice K. Inoue-Nagata Embrapa Hortaliças Ramon Jordan USDA-ARS, USNA, Floral and Nursery Plants Research Unit Hideki Kondo Institute of Plant Science and Resources, Okayama University Jan F. Kreuze International Potato Center (CIP) Mart Krupovic Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit Kenji Kubota Institute for Plant Protection, NARO Jens H. Kuhn Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health Scott Leisner Department of Biological Sciences, University of Toledo Jean-Michel Lett CIRAD, UMR PVBMT Chengyu Li Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University Fan Li State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University Jun Min Li Institute of Plant Virology, Ningbo University Paola M. López-Lambertini Instituto de Patología Vegetal (IPAVE), INTA, Unidad de Fitopatología y Modelización Agrícola (UFYMA) INTA-CONICET Juan J. Lopez-Moya Centre for Research in Agricultural Genomics, CRAG (CSIC-IRTA-UAB-UB) Francois Maclot UMR 1332 Biologie du Fruit et Pathologie, University of Bordeaux, INRAE Kristiina Mäkinen Department of Agricultural Sciences, University of Helsinki Darren Martin Institute of Infectious Disease and Molecular Medicine, University of Cape Town Sebastien Massart Plant Pathology Laboratory, TERRA Gembloux Agro-Bio Tech, University of Liege W. Allen Miller Department of Plant Pathology, Entomology and Microbiology, Iowa State University Musa Mohammadi Department of Plant Protection, Gorgan University of Agricultural Sciences and Natural Resources Dimitre Mollov USDA-APHIS, Plant Protection and Quarantine Emmanuelle Muller CIRAD, AGAP Institut; AGAP Institut, University of Montpellier; CIRAD, INRAE Tatsuya Nagata Instituto de Ciências Biológicas, Universidade de Brasília Jesús Navas-Castillo Instituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Científicas Yutaro Neriya Utsunomiya University Francisco M. Ochoa-Corona Oklahoma State University, Institute for Biosecurity & Microbial Forensics Kazusato Ohshima Saga University Vicente Pallás Instituto de Biología Molecular y Celular de Plantas (IBMCP), Universitat Politècnica de Valencia-CSIC Hanu Pappu Department of Plant Pathology, Washington State University Karel Petrzik Institute of Plant Molecular Biology Mikhail Pooggin PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD Maria Isabella Prigigallo Istituto per la Protezione Sostenibile delle Piante, CNR Pedro L. Ramos-González Applied Molecular Biology Laboratory, Instituto Biológico de São Paulo Simone Ribeiro Embrapa Recursos Genéticos e Biotecnologia Katja R. Richert-Pöggeler Julius Kühn Institute, Federal Research Centre for Cultivated Plants, Institute for Epidemiology and Pathogen Diagnostics Philippe Roumagnac CIRAD, UMR PHIM Avijit Roy USDA-ARS, BARC, Molecular Plant Pathology Laboratory, Beltsville, MD, USA Sead Sabanadzovic Department of Agricultural Science and Plant Protection, Mississippi State University Dana Šafářová Department of Cell Biology and Genetics, Faculty of Science, Palacký University Olomouc Pasquale Saldarelli Istituto per la Protezione Sostenibile delle Piante, CNR Hélène Sanfaçon Summerland Research and Development Centre, Agriculture and Agri-Food Canada Cecilia Sarmiento Department of Chemistry and Biotechnology, Tallinn University of Technology Takahide Sasaya Strategic Planning Headquarters, NARO Kay Scheets Department of Plant Pathology, Ecology and Evolution, Oklahoma State University Willem E.W. Schravesande Molecular Plant Pathology, University of Amsterdam Susan Seal Natural Resources Institute, University of Greenwich Yoshifumi Shimomoto Kochi Agricultural Research Center Merike Sõmera Department of Chemistry and Biotechnology, Tallinn University of Technology Livia Stavolone Istituto per la Protezione Sostenibile delle Piante, CNR Lucy R. Stewart Currently unaffiliated Pierre-Yves Teycheney CIRAD, UMR PVBMT & UMR PVBMT, Université de la Réunion John E. Thomas Queensland Alliance for Agriculture and Food Innovation, The University of Queensland Jeremy R. Thompson Plant Health and Environment Laboratory Antonio Tiberini Council for Agricultural Research and Economics, Research Centre for Plant Protection and Certification Yasuhiro Tomitaka Institute for Plant Protection, NARO Ioannis Tzanetakis Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System Marie Umber INRAE, UR ASTRO Cica Urbino PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro Harrold A. van den Burg Molecular Plant Pathology, University of Amsterdam René A.A. Van der Vlugt Wageningen University and Research Arvind Varsani The Biodesign Center for Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University Adriaan Verhage Rijk Zwaan Breeding B.V. Dan Villamor Department of Entomology and Plant Pathology, Division of Agriculture, University of Arkansas System Susanne von Bargen Humboldt-Universität zu Berlin, Thaer-Institute of Agricultural and Horticultural Sciences Peter J. Walker The University of Queensland Thierry Wetzel Dienstleistungszentrum Ländlicher Raum Rheinpfalz Anna E. Whitfield North Carolina State University Stephen J. Wylie Food Futures Institute, Murdoch University Caixia Yang Liaoning Key Laboratory of Urban Integrated Pest Management and Ecological Security, Shenyang University F. Murilo Zerbini Dep. de Fitopatologia/BIOAGRO, Universidade Federal de Viçosa Song Zhang National Citrus Engineering and Technology Research Center, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Citrus Research Institute, Southwest University In March 2025, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote, newly proposed taxa were added to those under the mandate of the Plant Viruses Subcommittee. In brief, 1 new order, 3 new families, 6 new genera, 2 new subgenera and 206 new species were created. Some taxa were reorganized. Genus Cytorhabdovirus in the family Rhabdoviridae was abolished and its taxa were redistributed into three new genera Alphacytorhabdovirus, Betacytorhabdovirus and Gammacytorhabdovirus. Genus Waikavirus in the family Secoviridae was reorganized into two subgenera (Actinidivirus and Ritunrivirus). One family and four previously unaffiliated genera were moved to the newly established order Tombendovirales. Twelve species not assigned to a genus were abolished. To comply with the ICTV mandate of a binomial format for virus species, eight species were renamed. Demarcation criteria in the absence of biological information were defined in the genus Ilarvirus (family Bromoviridae). This article presents the updated taxonomy put forth by the Plant Viruses Subcommittee and ratified by the ICTV. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6223 238 2025 Grafting-through functionalization of graphene oxide with cationic polymers for enhanced adsorption of anionic dyes and viruses 120296 EN Ryota Kimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pilar Ferré-Pujol Research Core for Interdisciplinary Sciences, Okayama University Yuta Nishina Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Graphene oxide (GO) is a sheet-like carbon material with abundant oxygen-containing functional groups on its surface. GO has been extensively studied as an adsorbent for heavy metals and organic compounds. However, effective strategies for negatively charged materials have yet to be established. This study aimed to synthesize composites of GO and cationic polymers for the selective adsorption of negatively charged materials; a challenge in this approach is the strong electrostatic interactions between GO and cationic polymers, which can lead to aggregation. This study addresses this issue by employing the grafting-through method. GO was initially modified with allylamine to introduce a polymerizable site, followed by radical polymerization to covalently bond polymers to the GO surface, effectively preventing aggregation. Adsorption experiments demonstrated that the GO-polymer composite selectively adsorbs anionic dye, such as methyl orange. Virus adsorption tests showed significantly enhanced performance compared to pristine GO. These results emphasize the critical role of controlled surface modification and charge manipulation in optimizing the adsorption performance of GO. This study establishes a simple and effective approach for synthesizing GO-cationic polymer composites, contributing to the development of advanced materials for water purification applications. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-1702 351 2025 Evidence for the replication of a plant rhabdovirus in its arthropod mite vector 199522 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Miki Fujita Institute of Plant Science and Resources (IPSR), Okayama University Paul Telengech Institute of Plant Science and Resources (IPSR), Okayama University Kazuyuki Maruyam Institute of Plant Science and Resources (IPSR), Okayama University Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University Aline Daniele Tassi Tropical Research and Education Center, University of Florida Ronald Ochoa Systematic Entomology Laboratory, USDA Ida Bagus Andika College of Plant Protection, Northwest A&F University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Transmission of plant viruses that replicate in the insect vector is known as persistent-propagative manner. However, it remains unclear whether such virus-vector relationships also occur between plant viruses and other biological vectors such as arthropod mites. In this study, we investigated the possible replication of orchid fleck virus (OFV), a segmented plant rhabdovirus, within its mite vector (Brevipalpus californicus s.l.) using quantitative RT-qPCR, western blotting and next-generation sequencing. Time-course RT-qPCR and western blot analyses showed an increasing OFV accumulation pattern in mites after virus acquisition. Since OFV genome expression requires the transcription of polyadenylated mRNAs, polyadenylated RNA fractions extracted from the viruliferous mite samples and OFV-infected plant leaves were used for RNA-seq analysis. In the mite and plant datasets, a large number of sequence reads were aligned to genomic regions of OFV RNA1 and RNA2 corresponding to transcribed viral gene mRNAs. This includes the short polyadenylated transcripts originating from the leader and trailer regions at the ends of the viral genome, which are believed to play a crucial role in viral transcription/replication. In contrast, a low number of reads were mapped to the non-transcribed regions (gene junctions). These results strongly suggested that OFV gene expression occurs both in mites and plants. Additionally, deep sequencing revealed the accumulation of OFV-derived small RNAs in mites, although their size profiles differ from those found in plants. Taken together, our results indicated that OFV replicates within a mite vector and is targeted by the RNA-silencing mechanism. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4915 16 7 2024 Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses 1152 EN Michael Louie R. Urzo Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños Timothy D. Guinto Microbiology Division, Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños Ana Eusebio-Cope Fit-for-Future Genetic Resources Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Baños Bernard O. Budot Institute of Weed Science, Entomology, and Plant Pathology, College of Agriculture and Food Science, University of the Philippines Los Baños Mary Jeanie T. Yanoria Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Baños Gilda B. Jonson Traits for Challenged Environments Unit, Rice Breeding Innovations Department, International Rice Research Institute (IRRI), University of the Philippines Los Baños Masao Arakawa Faculty of Agriculture, Meijo University Hideki Kondo Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University Nobuhiro Suzuki Plant-Microbe Interactions Group, Institute of Plant Science and Resources (IPSR), Okayama University Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0022-538X 99 3 2025 A capsidless (+)RNA yadokarivirus hosted by a dsRNA virus is infectious as particles, cDNA, and dsRNA e02166-24 EN Muhammad Fadli Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Sakae Hisano Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Guy Novoa Department of Structure of Macromolecules, Centro Nacional Biotecnología (CNB-CSIC), Campus de Cantoblanco José R. Castón Department of Structure of Macromolecules, Centro Nacional Biotecnología (CNB-CSIC), Campus de Cantoblanco Hideki Kondo Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Capsidless yadokariviruses (members of the order Yadokarivirales) with (+)RNA genomes divert the capsid of their partner icosahedral double-stranded RNA (dsRNA) viruses in different families of the order Ghabrivirales into the replication site. A yadokarivirus, AfSV2, has been reported from a German strain of the ascomycete fungus Aspergillus foetidus coinfected by two dsRNA viruses, a victorivirus (AfSV1, family Pseudototiviridae) and an alternavirus (AfFV, family Alternaviridae). Here, we identified AfSV1 as the partner of AfSV2 in a Japanese A. foetidus strain after showing the infectiousness of AfSV2 in three forms: virus particles (heterocapsid), transforming full-length complementary DNA (cDNA), and purified replicated form (RF) dsRNA that is believed to be inactive as a translational template. Virion transfection of virus-free A. foetidus protoplasts resulted in the generation of two strains infected either by AfSV1 alone or by both AfSV1 and AfSV2. Transformants with AfSV2 full-length cDNA launched AfSV2 infection only in the presence of AfSV1, but not those with AfSV2 RNA-directed RNA polymerase mutant cDNA. The purified fractions containing AfSV2 RF dsRNA also launched infection when transfected into protoplasts infected by AfSV1. Treatment with dsRNA-specific RNase III, but not with proteinase K, S1 nuclease, or DNase I, abolished the infectivity of AfSV2 RF dsRNA. Furthermore, we confirmed the infectiousness of gel-purified AfSV2 RF dsRNA in the presence of AfSV1. Taken together, our results show the unique infectious entity of AfSV2 and the expansion of yadokarivirus partners in the family Pseudototiviridae and provide interesting evolutionary insights. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6223 234 2025 Reversible chemical modifications of graphene oxide for enhanced viral capture and release in water 120015 EN Pilar Ferré-Pujol Research Institute for Interdisciplinary Science, Okayama University Seiji Obata Research Institute for Interdisciplinary Science, Okayama University Jésus Raya Institut de Chimie, UMR 7177 CNRS, Université de Strasbourg Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Hiroyuki Katayama Department of Urban Engineering, School of Engineering, The University of Tokyo Takashi Kato Research Center for Water Environment Technology, School of Engineering, The University of Tokyo Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Detecting low concentrations of viruses in sewage water is crucial for monitoring the spread of emerging viral diseases. However, current detection methods, which involve concentrating viruses using traditional materials such as gauze or cotton, have limitations in effectively accomplishing this task. This study demonstrates that graphene oxide (GO), a two-dimensional carbon material, possesses strong viral adsorption capabilities. However, it lacks efficiency for effective viral release. Therefore, we designed a series of new GO-based materials, which exhibited a viral adsorption similar to pristine GO, while significantly enhancing their release performance by attaching alkyl chains and hydrophilic functional groups. Among the synthesized materials, 1,8-aminooctanol grafted to GO (GO-NH2C8OH) has emerged as the most promising candidate, achieving a viral release rate higher than 50 %. This superior performance can be attributed to the synergistic effect of the alkyl chain and the terminal OH group, which enhances both its affinity for viruses and water dispersibility. Furthermore, we have successfully applied GO-NH2C8OH in a new protocol for concentrating viruses from sewage wastewater. This approach has demonstrated a 200-fold increase in virus concentration, allowing PCR detection of this type of pathogens present in wastewater below the detection limit by direct analysis, underscoring its significant potential for virus surveillance. No potential conflict of interest relevant to this article was reported.

Elmer Press, Inc. Acta Medica Okayama 1923-4155 16 1 2025 Local Control of Conjunctival Malignant Melanoma by Proton Beam Therapy in a Patient With No Metastasis in Six Years From in Situ to Nodular Lesions 28 36 EN Toshihiko Matsuo Regenerative and Reconstructive Medicine (Ophthalmology), Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takeshi Ogata Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital Takahiro Waki Department of Radiology, Proton Beam Center, Tsuyama Chuo Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kota Tachibana Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tomokazu Fuji Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takuya Adachi Department of Gastroenterology and Hepatology, Okayama University Hospital Osamu Yamasaki Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Conjunctival malignant melanoma is extremely rare, with no standard of care established at moment. Here we report a 65-year-old woman, as a hepatitis B virus (HBV) carrier, who presented concurrently a liver mass and lower bulbar conjunctival pigmented lesions in the right eye. Needle liver biopsy and excisional conjunctival biopsy showed hepatocellular carcinoma and conjunctival malignant melanoma in situ, respectively. The priority was given to segmental liver resection for hepatocellular carcinoma after transcatheter arterial chemoembolization. In 1 year, she underwent second and third resection of bulbar conjunctival pigmented lesions, and the pathological examinations constantly showed melanoma in situ. In the course, she showed gradual widening of pigmented lesions to upper bulbar conjunctiva and lower palpebral conjunctiva and lower eyelid. About 2.5 years from the initial visit, the lower eyelid lesion was resected for a genomic DNA-based test of BRAF mutations which turned out to be absent, and then, she began to have intravenous anti-programmed cell death-1 (PD-1), nivolumab every 3 or 4 weeks. She developed iritis in the right eye with conjunctival melanoma as an immune-related adverse event, 3 months after the beginning of nivolumab, and so she used daily topical 0.1% betamethasone eye drops to control the intraocular inflammation. She showed no metastasis in 6 years of follow-up, but later in the course, 5 years from the initial visit, she developed abruptly a non-pigmented nodular lesion on the temporal side of the bulbar conjunctiva along the corneal limbus, accompanied by two pigmented nodular lesions in the upper and lower eyelids in a few months. She thus, underwent proton beam therapy toward the conjunctival melanoma and achieved the successful local control. Proton beam therapy is a treatment option in place of orbital exenteration, and multidisciplinary team collaboration is desirable to achieve better cosmetic and functional outcomes in conjunctival malignant melanoma. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 22 2024 Microdetection of Nucleocapsid Proteins via Terahertz Chemical Microscope Using Aptamers 7382 EN Xue Ding Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mana Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hirofumi Inoue Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several methods have been employed, including the detection of viral ribonucleic acid (RNA), nucleocapsid (N) proteins, spike proteins, and antibodies. RNA detection, primarily through polymerase chain reaction tests, targets the viral genetic material, whereas antigen tests detect N and spike proteins to identify active infections. In addition, antibody tests are performed to measure the immune response, indicating previous exposure or vaccination. Here, we used the developed terahertz chemical microscope (TCM) to detect different concentrations of N protein in solution by immobilizing aptamers on a semiconductor substrate (sensing plate) and demonstrated that the terahertz amplitude varies as the concentration of N proteins increases, exhibiting a highly linear relationship with a coefficient of determination (R2 = 0.9881), indicating that a quantitative measurement of N proteins is achieved. By optimizing the reaction conditions, we confirmed that the amplitude of the terahertz wave was independent of the solution volume. Consequently, trace amounts (0.5 μL) of the N protein were successfully detected, and the detection process only took 10 min. Therefore, this study is expected to develop a rapid and sensitive method for the detection and observation of the SARS-CoV-2 virus at a microdetection level. It is anticipated that this research will significantly contribute to reducing the spread of novel infectious diseases in the future. No potential conflict of interest relevant to this article was reported.

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

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis 24968 EN Thuy Ha Vu Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Keiichiro Nakamura Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kunitoshi Shigeyasu Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Chiaki Kashino Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Okamoto Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kotaro Kubo Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuhiko Kamada Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hisashi Masuyama Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis. No potential conflict of interest relevant to this article was reported.

Institute of Electrical and Electronics Engineers Acta Medica Okayama 2169-3536 12 2024 Detecting Unintended Redirects to Malicious Websites on Android Devices Based on URL-Switching Interval 153285 153294 EN Toshihiro Yamauchi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Rintaro Orito Graduate School of Natural Science and Technology, Okayama University Koji Ebisu Graduate School of Natural Science and Technology, Okayama University Masaya Sato Faculty of Computer Science and Systems Engineering, Okayama Prefectural University Website clicks that redirect Android-phone users to malicious websites with fake virus alerts or phishing attacks are increasing exponentially. Although a uniform resource locator (URL) blocklist is considered a suitable countermeasure to such attacks, it is difficult to efficiently identify malicious websites. To the best of our knowledge, no research has focused on detecting attacks that redirect Android-phone users to malicious websites. Therefore, we propose a redirect-detection method that focuses on the URL bar-switching interval of Android-based Google Chrome browser. The proposed method, which can be easily installed as an Android application, uses the Android accessibility service to detect unintended redirects to malicious websites without collecting information about these websites in advance. This paper details the design, implementation, and evaluation results of the proposed application on an actual Android device. We determined the threshold values for the number of times the URL bar switches and the elapsed time to determine redirects to malicious websites for the proposed method. Based on the results, we investigated the causes of false-positive detection of redirects to benign websites and offer solutions on handling them. We also present the threshold values that can minimize the false positive and negative rates, as well as the detection accuracy of the proposed method based on these threshold values. Additionally, we present the evaluations results based on the access logs of actual users participating in the WarpDrive project experiment, which indicate that the proposed method minimizes false positives and successfully detects most redirects to malicious websites. No potential conflict of interest relevant to this article was reported.

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

Elmer Press, Inc. Acta Medica Okayama 1923-4155 15 11 2024 Intravitreal Fluconazole Injection for Fungal Endophthalmitis as Treatment Option in a Patient With End-Stage Liver and Kidney Diseases 359 366 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yasuyuki Kobayashi Department of Urology, Okayama University Hospital Shingo Nishimura Department of Urology, Okayama University Hospital Naoko Yoshioka Department of Gastroenterology and Hepatology, Kawasaki Medical School Yasushi Takahashi Department of Internal Medicine, Ochiai Hospital Yasutaka Iguchi Department of Internal Medicine, Ochiai Hospital Endogenous endophthalmitis is an infectious disease of the intraocular tissue that is a consequence of bloodstream infection. The efficacy of intravitreal fluconazole injection to assist low-dose oral fluconazole in fungal endophthalmitis remains unknown in older adults with advanced liver and renal disease. In this case report, a 78-year-old man with hepatitis C virus-related liver cirrhosis and hepatocellular carcinoma who also had end-stage renal disease with temporary nephrostomy noticed blurred vision and showed a large retinal infiltrate with vitreous opacity in the right eye. In the clinical diagnosis of endogenous fungal endophthalmitis, he had an intravitreal injection of 0.1% fluconazole in 0.2 - 0.3 mL every 2 weeks four times in total, in addition to a minimum dose of oral fluconazole. One month before the ophthalmic presentation, he developed a fever and computed tomography scan showed ureterolithiasis with hydronephrosis on the right side, indicating that the renal pelvic stone fell into the ureter. He underwent nephrostomy tube insertion on the right side in the diagnosis of obstructive urinary tract infection. In the course, a potassium hydroxide (KOH) preparation of the urine sediments which were obtained from the nephrostomy tube showed yeast-like fungi, suggestive of Candida, 1 week before the development of eye symptoms. One week after the ophthalmic presentation, the nephrostomy tube at 14 Fr (French gauge) which had been inserted 1 month previously was replaced with a new tube with a larger size at 16 Fr because urine excretion from the tube was reduced. Immediately after the exchange of the nephrostomy tube, a large volume of urine was excreted from the tube. In a week, he had no systemic symptoms and serum C-reactive protein became low. In the meantime, the retinal infiltrate became inactive and vitreous opacity resolved. Intravitreal fluconazole injection is a treatment option for fungal endophthalmitis in the case that a patient cannot undergo vitrectomy and cannot take a maximum dose of fluconazole because of poor renal function. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 2 2 2023 Effectiveness of psychological first aid in infectious disease pandemics: An overview of systematic reviews e107 EN Masahide Koda Co‐Learning Community Healthcare Re‐Innovation Office, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Horinouchi Department of Psychiatry, Hokkaido University Graduate School of Medicine Nozomu Oya Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Morio Aki Department of Psychiatry, Graduate School of Medicine, Kyoto University Akihisa Iriki Osaka Psychiatric Medical Center Kazufumi Yoshida Department of Health Promotion and Human Behavior, Graduate School of Medicine/School of Public Health, Kyoto University Yusuke Ogawa Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University Hironori Kuga National Center for Cognitive Behavior Therapy and Research, National Center of Neurology and Psychiatry Tomohiro Nakao Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University There is insufficient research on the usefulness of psychological interventions, such as psychological first aid (PFA), during outbreaks. We searched for and critically appraised systematic reviews that examined the effectiveness of PFA during infectious disease outbreaks, such as the novel coronavirus disease (COVID-19). Systematic reviews that examined the efficacy of PFA in the severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus, Ebola virus disease, and COVID-19 outbreaks were searched through PubMed on February 19, 2021. The three included systematic reviews were critically appraised and assessed using AMSTAR-2. One review's overall confidence in its findings was evaluated as “high,” which suggested that PFA training had a favorable effect on healthcare personnel. Furthermore, the review also demonstrated that PFA was commonly used during outbreaks and could be delivered through multiple methods, such as a phone or video call. Although it was anticipated that PFA would improve subjective well-being, reports showed no evidence of reduced depression or insomnia. Future studies should examine additional numbers of PFA recipients and conduct quasi-experimental studies to better understand the effectiveness of PFA. Evidence on its effectiveness in infectious disease outbreaks is still lacking, along with research and evaluation methods. Quasi-experimental studies, such as comparisons with other psychological interventions, are required to better understand the effectiveness of PFA. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia 20521 EN Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 x 1011 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-3224 15 2024 Vaccine and antiviral drug promise for preventing post-acute sequelae of COVID-19, and their combination for its treatment 1329162 EN Tomonari Sumi Research Institute for Interdisciplinary Science, Okayama University Kouji Harada Department of Computer Science and Engineering, Toyohashi University of Technology Introduction: Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer from unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with the utmost urgency.<br> Methods: A mathematical model of the immune response to vaccination and viral infection with SARS-CoV-2, incorporating immune memory cells, was developed.<br> Results and discussion: Similar to our previous model, persistent infection was observed by the residual virus in the host, implying the possibility of chronic inflammation and delayed recovery from tissue injury. Pre-infectious vaccination and antiviral medication administered during onset can reduce the acute viral load; however, they show no beneficial effects in preventing persistent infection. Therefore, the impact of these treatments on the PASC, which has been clinically observed, is mainly attributed to their role in preventing severe tissue damage caused by acute viral infections. For PASC patients with persistent infection, vaccination was observed to cause an immediate rapid increase in viral load, followed by a temporary decrease over approximately one year. The former was effectively suppressed by the coadministration of antiviral medications, indicating that this combination is a promising treatment for PASC. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2379-5042 9 8 2024 New lineages of RNA viruses from clinical isolates of Rhizopus microsporus revealed by fragmented and primer-ligated dsRNA sequencing (FLDS) analysis EN Wasiatus Sa'diyah Institute of Plant Science and Resources, Okayama University Yan-Jie Zhao Department of Life and Environmental Sciences, Laboratory of Fungal Interaction and Molecular Biology (Donated by IFO), University of Tsukuba Yuto Chiba Department of Life and Environmental Sciences, Laboratory of Fungal Interaction and Molecular Biology (Donated by IFO), University of Tsukuba Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Sayaka Ban Medical Mycology Research Center, Chiba University Takashi Yaguchi Medical Mycology Research Center, Chiba University Syun-Ichi Urayama Department of Life and Environmental Sciences, Laboratory of Fungal Interaction and Molecular Biology (Donated by IFO), University of Tsukuba Daisuke Hagiwara Department of Life and Environmental Sciences, Laboratory of Fungal Interaction and Molecular Biology (Donated by IFO), University of Tsukuba Rhizopus microsporus is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of R. microsporus for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families Mitoviridae, Narnaviridae, and Endornaviridae, ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families Virgaviridae and Phasmaviridae, and the proposed family "Ambiguiviridae." All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family Mitoviridae, whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen R. microsporus harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of R. microsporus may expand the repertoire of natural therapeutic agents for mucormycosis in the future. No potential conflict of interest relevant to this article was reported.

Elmer Press, Inc. Acta Medica Okayama 1923-4155 15 8 2024 Anterior Uveitis After Discontinuation of Janus Kinase Inhibitor, Ruxolitinib 208 214 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Naoto Ikeda Department of Internal Medicine, Kaneda Hospital Yasumasa Monobe Department of Pathology, General Medical Center, Kawasaki Medical School Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Primary myelofibrosis shows widespread fibrosis in the bone marrow and is part of myeloproliferative neoplasms in which gene mutations in hematopoietic stem cells lead to abnormal clonal expansion of one or more lineage of myeloid and erythroid cells and megakaryocytes. Janus kinase (JAK) inhibitors are the main therapeutic regimen for primary myelofibrosis which harbors gene mutations, resulting in continuous activation of JAK-STAT signaling pathway. Since JAK inhibitors modulate immunological state, the administration would have a potential for uveitis. A 67-year-old patient presented with weight loss of 10 kg in the past 2 years after his retirement. He showed normocytic anemia with anisocytosis and abnormal shape, as well as hepatosplenomegaly. Suspected of hematological malignancy, bone marrow biopsy led to the diagnosis of primary myelofibrosis (grade 2) with bizarre megakaryocytes and relative maintenance of myeloid and erythroid lineage. He started to have blood transfusion. Genomic DNA analysis of the peripheral blood showed a pathogenic variant in the exon 9 of calreticulin (CALR) gene while pathogenic variants in Janus kinase-2 (JAK2), and myeloproliferative leukemia virus oncogene (MPL) were absent. He began to have oral ruxolitinib 10 mg daily at the timepoint of 5 months after the initial visit and the dose was increased to 20 mg daily 8 months later but was discontinued further 4 months later because he showed the limited effect of ruxolitinib. He had blood transfusion every week or every 2 weeks in the following 2 months until he noticed blurred vision in the right eye. The right eye showed thick fibrin membrane formation in the anterior chamber in front of the pupil which prevented the fundus from visualization. The left eye showed no inflammation and optic nerve atrophy, sequel to tuberculous meningitis in childhood. The patient started to use 0.1% betamethasone six times daily and 1% atropine once daily as eye drops. A week later, fibrin membrane disappeared and the pupillary area with total iris posterior synechia was visible in the right eye. He regained the vision in the right eye and did not show relapse of uveitis only with topical 0.1% betamethasone. Uveitis might be related with the administration and discontinuation of ruxolitinib. No potential conflict of interest relevant to this article was reported.

National Academy of Sciences Acta Medica Okayama 0027-8424 121 25 2024 Argonaute-independent, Dicer-dependent antiviral defense against RNA viruses e2322765121 EN Yukiyo Sato Institute of Plant Science and Resources, Okayama University Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Antiviral RNA interference (RNAi) is conserved from yeasts to mammals. Dicer recognizes and cleaves virus-derived double-stranded RNA (dsRNA) and/or structured single-stranded RNA (ssRNA) into small-interfering RNAs, which guide effector Argonaute to homologous viral RNAs for digestion and inhibit virus replication. Thus, Argonaute is believed to be essential for antiviral RNAi. Here, we show Argonaute-independent, Dicer-dependent antiviral defense against dsRNA viruses using Cryphonectria parasitica (chestnut blight fungus), which is a model filamentous ascomycetous fungus and hosts a variety of viruses. The fungus has two dicer-like genes (dcl1 and dcl2) and four argonaute-like genes (agl1 to agl4). We prepared a suite of single to quadruple agl knockout mutants with or without dcl disruption. We tested these mutants for antiviral activities against diverse dsRNA viruses and ssRNA viruses. Although both DCL2 and AGL2 worked as antiviral players against some RNA viruses, DCL2 without argonaute was sufficient to block the replication of other RNA viruses. Overall, these results indicate the existence of a Dicer-alone defense and different degrees of susceptibility to it among RNA viruses. We discuss what determines the great difference in susceptibility to the Dicer-only defense. No potential conflict of interest relevant to this article was reported.

National Academy of Sciences Acta Medica Okayama 0027-8424 121 25 2024 Replication of single viruses across the kingdoms, Fungi, Plantae, and Animalia e2318150121 EN Paul Telengech Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Kiwamu Hyodo Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Hiroaki Ichikawa Institute of Agrobiological Sciences, National Agriculture and Food Research Organization Ryusei Kuwata Faculty of Veterinary Medicine, Okayama University of Science Hideki Kondo Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University It is extremely rare that a single virus crosses host barriers across multiple kingdoms. Based on phylogenetic and paleovirological analyses, it has previously been hypothesized that single members of the family Partitiviridae could cross multiple kingdoms. Partitiviridae accommodates members characterized by their simple bisegmented double-stranded RNA genome; asymptomatic infections of host organisms; the absence of an extracellular route for entry in nature; and collectively broad host range. Herein, we show the replicability of single fungal partitiviruses in three kingdoms of host organisms: Fungi, Plantae, and Animalia. Betapartitiviruses of the phytopathogenic fungusRosellinia necatrix could replicate in protoplasts of the carrot (Daucus carota), Nicotiana benthamiana and Nicotiana tabacum, in some cases reaching a level detectable by agarose gel electrophoresis. Moreover, betapartitiviruses showed more robust replication than the tested alphapartitiviruses. One of the fungal betapartitiviruses, RnPV18, could persistently and stably infect carrot plants regenerated from virion-transfected protoplasts. Both alpha- and betapartitiviruses, although with different host preference, could replicate in two insect cell lines derived from the fall armyworm Spodoptera frugiperda and the fruit fly Drosophila melanogaster. Our results indicate the replicability of single partitiviruses in members of three kingdoms and provide insights into virus adaptation, host jumping, and evolution. No potential conflict of interest relevant to this article was reported.

The Japan Society of Histochemistry and Cytochemistry Acta Medica Okayama 0044-5991 57 2 2024 Membrane-Targeted palGFP Predominantly Localizes to the Plasma Membrane but not to Neurosecretory Vesicle Membranes in Rat Oxytocin Neurons 85 88 EN Hirotaka Sakamoto Department of Biology, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Ayumu Inutsuka Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University Recent advances in viral vector technology, specifically using adeno-associated virus (AAV) vectors, have significantly expanded possibilities in neuronal tracing. We have utilized the Cre/loxP system in combination with AAV techniques in rats to explore the subcellular localization of palmitoylation signal-tagged GFP (palGFP) in oxytocin-producing neurosecretory neurons. A distinctive branching pattern of single axons was observed at the level of the terminals in the posterior pituitary. Despite challenges in detecting palGFP signals by fluorescent microscopy, immunoelectron microscopy demonstrated predominant localization on the plasma membrane, with a minor presence on the neurosecretory vesicle membrane. These findings suggest that membrane-anchored palGFP may undergo exocytosis, translocating from the plasma membrane to the neurosecretory vesicle membrane. In this study, we observed characteristic axon terminal structures in the posterior pituitary of oxytocin neurons. This study indicates the importance of understanding the plasma membrane-specific sorting system in neuronal membrane migration and encourages future studies on the underlying mechanisms. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-8993 1828 2024 Protective effect of scallop-derived plasmalogen against vascular dysfunction, via the pSTAT3/PIM1/NFATc1 axis, in a novel mouse model of Alzheimer’s disease with cerebral hypoperfusion 148790 EN Yun Zhai Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Zhihong Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuting Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haibo Yu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hongming Sun Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ying Tang Department of Neurology, The First Affiliated Hospital of Harbin Medical University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University A strong relationship between Alzheimer’s disease (AD) and vascular dysfunction has been the focus of increasing attention in aging societies. In the present study, we examined the long-term effect of scallop-derived plasmalogen (sPlas) on vascular remodeling-related proteins in the brain of an AD with cerebral hypoperfusion (HP) mouse model. We demonstrated, for the first time, that cerebral HP activated the axis of the receptor for advanced glycation endproducts (RAGE)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/provirus integration site for Moloney murine leukemia virus 1 (PIM1)/nuclear factor of activated T cells 1 (NFATc1), accounting for such cerebral vascular remodeling. Moreover, we also found that cerebral HP accelerated pSTAT3-mediated astrogliosis and activation of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, probably leading to cognitive decline. On the other hand, sPlas treatment attenuated the activation of the pSTAT3/PIM1/NFATc1 axis independent of RAGE and significantly suppressed NLRP3 inflammasome activation, demonstrating the beneficial effect on AD. No potential conflict of interest relevant to this article was reported.

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

PeerJ Acta Medica Okayama 2167-8359 12 2024 Heterogeneity of the effect of the COVID-19 pandemic on the incidence of Metabolic Syndrome onset at a Japanese campus e17013 EN Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Background. The coronavirus disease 2019 (COVID-19) outbreak began in China in December 2019, with the World Health Organization declaring a state of emergency in January 2020. Worldwide implementation of lockdown measures to slow the spread of the virus led to reduced physical activity, disrupted eating habits, mental health issues, and sleep disturbances, which increased the risk of lifestyle -related diseases such as metabolic syndrome (MetS). During the COVID-19 pandemic, healthcare workers, especially intensive care workers, experienced longer working hours and burnout, which further increased the risk of lifestyle -related diseases. Accordingly, it is important to identify individuals at a risk of new -onset MetS during a pandemic, which could direct preventive interventions. This study aimed to assess the heterogeneous impact of the COVID-19 pandemic on the incidence of new -onset MetS based on the conditional average treatment effect (CATE) and to identify at -risk populations. <br> Methods. This study analyzed health checkup data obtained from Okayama University Shikata Campus workers using paired baseline and follow-up years. Baseline data encompassed 2017 to 2019, with respective follow-up data from 2018 to 2020. Furthermore, as the COVID-19 pandemic in Japan began in January 2020, workers who underwent follow-up health checkups in 2018 to 2019 and 2020 were considered as "unexposed"and "exposed,"respectively. As the Shikata campus has several departments, comparisons among departments were made. The primary outcome was new -onset MetS at follow-up. Predictor variables included baseline health checkup results, sex, age, and department (administrative, research, medical, or intensive care department). X -learner was used to calculate the CATE. <br> Results. This study included 3,572 eligible individuals (unexposed, n = 2,181; exposed, n = 1,391). Among them, 1,544 (70.8%) and 866 (62.3%) participants in the unexposed and exposed groups, respectively, were females. The mean age (+/- standard deviation) of the unexposed and exposed groups was 48.2 +/- 8.2 and 47.8 +/- 8.3 years, respectively. The COVID-19 pandemic increased the average probability of new -onset MetS by 4.4% in the overall population. According to the department, the intensive care department showed the highest CATE, with a 15.4% increase. Moreover, there was large heterogeneity according to the department. The high-CATE group was characterized by older age, urinary protein, elevated liver enzymes, higher triglyceride levels, and a history of hyperlipidemia treatment. <br> Conclusions. This study demonstrated that the COVID-19 pandemic increased the incidence of new -onset MetS, with this effect showing heterogeneity at a single Japanese campus. Regarding specific populations, workers in the intensive care department showed an increased risk of new -onset MetS. At -risk populations require specific preventive interventions in case the current COVID-19 pandemic persists or a new pandemic occurs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression 151 161 EN Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Mochizuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66924 Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors’ growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Impacts of Age and Gender on Brain Edema in a Mouse Water Intoxication Model 115 122 EN Emi Nakamura-Maruyama Department of Physiology2, Kawasaki Medical School Keiichiro Irie Department of Neurological Surgery, Kagawa University Faculty of Medicine Kazuhiko Narita Department of Physiology2, Kawasaki Medical School Naoyuki Himi Department of Physiology2, Kawasaki Medical School Osamu Miyamoto Department of Physiology2, Kawasaki Medical School Takehiro Nakamura Department of Physiology2, Kawasaki Medical School Original Article 10.18926/AMO/66914 Brain edema causes abnormal fluid retention and can be fatal in severe cases. Although it develops in various diseases, most treatments for brain edema are classical. We analyzed the impacts of age and gender on the characteristics of a water intoxication model that induces pure brain edema in mice and examined the model’s usefulness for research regarding new treatments for brain edema. C57BL/6J mice received an intraperitoneal administration of 10% body weight distilled water, and we calculated the brain water content by measuring the brain-tissue weight immediately after dissection and after drying. We analyzed 8-OHdG and caspase-3 values to investigate the brain damage. We also applied this model in aquaporin 4 knockout (AQP4−) mice and compared these mice with wild-type mice. The changes in water content differed by age and gender, and the 8-OHdG and caspase-3 values differed by age. Suppression of brain edema by AQP4− was also confirmed. These results clarified the differences in the onset of brain edema by age and gender, highlighting the importance of considering the age and gender of model animals. Similar studies using genetically modified mice are also possible. Our findings indicate that this water intoxication model is effective for explorations of new brain edema treatments. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Evaluation of the Efficacy and Safety of Tenofovir Disoproxil Fumarate in Intercepting Mother-to-Child Transmission of Hepatitis B Virus 107 113 EN Dongxiang Han Department of Obstetrics, Shijiazhuang Maternity & Child Healthcare Hospital Jianxiu Du Department of Laboratory Medicine, Shijiazhuang Maternity & Child Healthcare Hospital Wei Wang Department of Obstetrics, Shijiazhuang Maternity & Child Healthcare Hospital Cui Wang Department of Functional, Shijiazhuang Maternity & Child Healthcare Hospital Original Article 10.18926/AMO/66913 Vertical transmission of hepatitis B virus (HBV), especially in Asia, is a key target in the global elimination of HBV. This study assessed the effects of tenofovir disoproxil fumarate (TDF) in pregnant women for mother-to-infant transmission of HBV. A total of 122 pregnant women at our hospital met the inclusion criteria for high HBV DNA viral loads. They were randomly divided into TDF-treatment (n=70) and placebo (n=52) groups. Maternal liver function and serum HBV DNA load were tested before and after treatment. Clinical and laboratory data of infants were assayed at delivery and 7-months post-partum visit and compared between the two groups. There was no difference in clinical characteristics of participants between the two groups. There were no significant differences in liver function markers, including alanine aminotransferase, total bilirubin, blood creatinine, and blood urea nitrogen levels before and after TDF treatment. The serum HBV DNA viral load of the TDF-treated group became significantly lower than those of the control group and their own pre-medication levels. Infants showed no significant difference in body growth, including weight, height, head size, and five-min Apgar score. At 7 months after birth, 94.29% of infants in the TDF group and 86.54% of control-group infants had protective HBsAb levels ≥ 10 mIU/ml (p>0.05). The HBV infection rate of infants in the TDF-treated group was lower than that in the non-treated group. In high-HBV-DNA-load pregnant women, TDF administered from 28 weeks gestational age to delivery was associated with a lower risk of mother-to-infant transmission of HBV. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 1661-6596 25 6 2024 Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System 3523 EN Shigenori Sasaki Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Katoh Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system. No potential conflict of interest relevant to this article was reported.

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

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

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study 29 36 EN Takahiro Kitayama Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Tanaka Department of Radiology, Okayama City Hospital Yuichiro Kanie Department of Radiology, Okayama University Hospital Yohei Marukawa Department of Radiology, Okayama Saiseikai General Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Takehiro Tanaka Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soshi Takao Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takao Hiraki Department of Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Original Article 10.18926/AMO/66668 This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD. No potential conflict of interest relevant to this article was reported.

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

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 1 2024 Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders 1 9 EN Takeshi Okatani Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuria Egusa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Sayako Yoshida Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/ lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1369-5274 75 2023 Continued mycovirus discovery expanding our understanding of virus lifestyles, symptom expression, and host defense 102337 EN Yukiyo Sato Institute for Plant Sciences, University of Cologne Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University High-throughput sequencing technologies have greatly expanded the RNA virome in general and have led to an exponential increase in new fungal viruses, also known as mycoviruses. Mycoviruses are omnipresent in fungi and usually induce symptomless infections. Some mycoviruses infecting fungi pathogenic to plants, insects, and mammals are known to modify host virulence positively and negatively and attract particular interests. In addition, fungal viruses continue to provide intriguing research materials and themes that lead to discoveries of peculiar viruses as infectious entities and insights into virus evolution and diversity. In this review, we outline the diversity and neolifestyle of recently discovered fungal RNA viruses, and phenotypic alterations induced by them. Furthermore, we discuss recent advances in research regarding the fungal antiviral defense and viral counterdefense, which are closely associated with host phenotype alterations. We hope that this article will enhance understanding of the interesting and growing fungal virology field. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2218-273X 13 12 2023 Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity 1706 EN Hirokazu Katoh Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the host genome. Although mutations and silencing mechanisms impair their original role in viral replication, HERVs are believed to play roles in various biological processes. Long interspersed nuclear elements (LINEs) are non-LTR retrotransposons that have a lifecycle resembling that of retroviruses. Although LINE expression is typically silenced in somatic cells, it also contributes to various biological processes. The aberrant expression of HERVs and LINEs is closely associated with the development of cancer and/or immunological diseases, suggesting that they are integrated into various pathways related to the diseases. HERVs/LINEs control gene expression depending on the context as promoter/enhancer elements. Some RNAs and proteins derived from HERVs/LINEs have oncogenic potential, whereas others stimulate innate immunity. Non-retroviral endogenous viral elements (nrEVEs) are a novel type of virus-like element in the genome. nrEVEs may also be involved in host immunity. This article provides a current understanding of how these elements impact cellular physiology in cancer development and innate immunity, and provides perspectives for future studies. No potential conflict of interest relevant to this article was reported.

Japanese Society of Breeding Acta Medica Okayama 1344-7610 73 5 2023 Genomic traces of Japanese malting barley breeding in two modern high-quality cultivars, ‘Sukai Golden’ and ‘Sachiho Golden’ 435 444 EN Shin Taketa Institute of Plant Science and Resources, Okayama University June-Sik Kim Institute of Plant Science and Resources, Okayama University Hidekazu Takahashi Faculty of Food and Agricultural Sciences, Fukushima University Shunsuke Yajima NODAI Genome Research Center, Tokyo University of Agriculture Yuichi Koshiishi NODAI Genome Research Center, Tokyo University of Agriculture Toshinori Sotome Tochigi Prefectural Agricultural Experiment Station Tsuneo Kato Tochigi Prefectural Agricultural Experiment Station Keiichi Mochida Bioproductivity Informatics Research Team, RIKEN Center for Sustainable Resource Science Two modern high-quality Japanese malting barley cultivars, ‘Sukai Golden’ and ‘Sachiho Golden’, were subjected to RNA-sequencing of transcripts extracted from 20-day-old immature seeds. Despite their close relation, 2,419 Sukai Golden-specific and 3,058 Sachiho Golden-specific SNPs were detected in comparison to the genome sequences of two reference cultivars: ‘Morex’ and ‘Haruna Nijo’. Two single nucleotide polymorphism (SNP) clusters respectively showing the incorporation of (1) the barley yellow mosaic virus (BaYMV) resistance gene rym5 from six-row non-malting Chinese landrace Mokusekko 3 on the long arm of 3H, and (2) the anthocyanin-less ant2 gene from a two-row Dutch cultivar on the long arm of 2H were detected specifically in ‘Sukai Golden’. Using 221 recombinant inbred lines of a cross between ‘Ishukushirazu’ and ‘Nishinochikara’, another BaYMV resistance rym3 gene derived from six-row non-malting Japanese cultivar ‘Haganemugi’ was mapped to a 0.4-cM interval on the proximal region of 5H. Haplotype analysis of progenitor accessions of the two modern malting cultivars revealed that rym3 of ‘Haganemugi’ was independently introduced into ‘Sukai Golden’ and ‘Sachiho Golden’. Residual chromosome 5H segments of ‘Haganemugi’ surrounding rym3 were larger in ‘Sukai Golden’. Available results suggest possibilities for malting quality improvement by minimizing residual segments surrounding rym3. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer EN Yoshinori KAJIWARA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3417 13 20 2023 Evolutionary-Game-Theory-Based Epidemiological Model for Prediction of Infections with Application to Demand Forecasting in Pharmaceutical Inventory Management Problems 11308 EN Yu Nishihata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ziang Liu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tatsushi Nishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pharmaceuticals play a critical role in the eradication of infectious diseases. Effective pharmaceutical inventory management is important for controlling epidemics since medical resources such as pharmaceuticals, medical staff, and hospitals are limited. In this study, a novel epidemiological model is proposed to evaluate the resource requirements for pharmaceuticals and is applied to analyze different pharmaceutical inventory management strategies. We formulate the relationship between the number of infected individuals and the risk of infection to account for virus mutation. Evolutionary game theory is integrated into an epidemiological model to represent human behavioral choices. The proposed model can be developed to forecast the demand for pharmaceuticals and analyze how human behavior affects the demand of pharmaceuticals. This study found that making people aware of the risk of disease has a positive impact on both reducing the number of infections and managing the pharmaceutical inventory. The main contribution of this study is to enhance areas of research in pharmaceutical inventory management. This study revealed that the correct recognition of the risk of disease leads to appropriate pharmaceutical management. There are a few studies on the application of infectious disease models to inventory control problems. This study provides clues toward proper pharmaceutical management. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1742-464X 291 6 2023 Hepatitis C virus NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes 1119 1130 EN Hiromichi Dansako Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masanori Ikeda Division of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University Yasuo Ariumi Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases Yosuke Togashi Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobuyuki Kato Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University During the replication of viral genomes, RNA viruses produce double-stranded RNA (dsRNA), through the activity of their RNA-dependent RNA polymerases (RdRps) as viral replication intermediates. Recognition of viral dsRNA by host pattern recognition receptors – such as retinoic acid-induced gene-I (RIG-I)-like receptors and Toll-like receptor 3 – triggers the production of interferon (IFN)-β via the activation of IFN regulatory factor (IRF)-3. It has been proposed that, during the replication of viral genomes, each of RIG-I and melanoma differentiation-associated gene 5 (MDA5) form homodimers for the efficient activation of a downstream signalling pathway in host cells. We previously reported that, in the non-neoplastic human hepatocyte line PH5CH8, the RdRp NS5B derived from hepatitis C virus (HCV) could induce IFN-β expression by its RdRp activity without the actual replication of viral genomes. However, the exact mechanism by which HCV NS5B produced IFN-β remained unknown. In the present study, we first showed that NS5B derived from another Flaviviridae family member, GB virus B (GBV-B), also possessed the ability to induce IFN-β in PH5CH8 cells. Similarly, HCV NS5B, but not its G317V mutant, which lacks RdRp activity, induced the dimerization of MDA5 and subsequently the activation of IRF-3. Interestingly, immunofluorescence analysis showed that HCV NS5B produced dsRNA. Like HCV NS5B, GBV-B NS5B also triggered the production of dsRNA and subsequently the dimerization of MDA5. Taken together, our results show that HCV NS5B triggers an MDA5-mediated innate immune response by producing dsRNA without the replication of viral genomes in human hepatocytes. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 17 1 2022 COVID-19 and Spanish Flu, the Representative Pandemics of the 21st and 20th Centuries 65 72 EN Sumio Shinoda Collaborative Research Center for Infectious Diseases in India, Okayama University We are still in the early stage of 21st century and the two pandemics Spanish flu and COVID-19 are the presentative pandemics in 20th and 21st centuries, respectively. The Spanish flu pandemic raged from 1918 to 1920, just after World War I. It was the first influenza pandemic worldwide; since then, humankind has experienced many such pandemics. Spanish flu is caused by a virus. However, since virology was not well established at that time, the new clinical system was needed to cope with “unknown pathogen”; during the pandemic, high infection rates were recorded, but our predecessors managed to somehow tackle the situation. With respect to the ongoing COVID-19 pandemic, both the virus and its genome were clarified quickly. Nonetheless, it has turned out to be quite an intriguing infectious disease, with the high rates in developed countries, such as the US and those in Europe, which have aging societies, and low rates in developing countries such as those in Africa, where the population is largely young. Here, I compared and discuss the two pandemics, COVID-19 and Spanish flu. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-1702 334 2023 Exploration of the yadokari/yadonushi nature of YkV3 and RnMBV3 in the original host and a model filamentous fungus 199155 EN Yukiyo Sato Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Sakae Hisano Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University The yadokari/yadonushi nature is a recently discovered virus lifestyle; “yadokari” refers to the ability of capsidless positive-sense (+) RNA viruses (yadokariviruses) to utilize the capsids of phylogenetically distant double-stranded RNA (dsRNA) viruses possibly as the replication site, while “yadonushi” refers to the ability of dsRNA viruses to provide capsids to yadokariviruses. This virus–virus interaction, however, has been only studied with limited pathosystems. Here, we established a new study model with a capsidless (+)RNA yadokarivirus YkV3 (family Yadokariviridae) and its capsid donor RnMBV3 (family Megabirnaviridae) in the original host fungus Rosellinia necatrix and a model filamentous fungal host Cryphonectria parasitica. YkV3 has a simple genome structure with one open reading frame of 4305 nucleotides encoding a single polyprotein with an RNA-dependent RNA polymerase and a 2A-like self-cleavage peptide domain. Reverse genetics of YkV3 in R. necatrix showed that YkV3 tolerates a nucleotide substitution in the extreme 5′-terminus. The insertion of two termination codons immediately downstream of the 2A-like cleavage site abolished YkV3 viability, suggesting the importance of the C-terminal portion of the polyprotein of unknown function. Transfection of RnMBV3 and YkV3 into an RNA silencing-deficient mutant Δdcl2 of C. parasitica showed the replication competency of both viruses. Comparison between the wild-type and Δdcl2 strains of C. parasitica in virus accumulation suggested that RnMBV3 and YkV3 are susceptible to RNA silencing in C. parasitica. Taken together, we have established a platform to further explore the yadokari/yadonushi nature using genetically manipulable host fungal and virus strains. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Disease Progression-Related Markers for Aged Non-Alcoholic Fatty Liver Disease Patients 377 385 EN Kosaku Morimoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Oyama Department of Gastroenterology and Hepatology, 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 Hideki Onishi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/65748 Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals. Serum levels of pro- and anti-inflammatory cytokines were measured by multiple enzyme-linked immunosorbent assay. Two standard NAFLD or fibrosis progression-related markers — the FIB-4 index and APRI score — were analyzed along with cytokine levels to define the best approach to discriminate advanced fibrosis. Ninety-eight NAFLD patients were enrolled: 59 and 39 patients with fibrosis stages 1-2 and 3-4 respectively. In addition to the FIB-4 index and APRI score, the following factors showed significant differences between stages 1-2 and stages 3-4 in a multivariate analysis: platelet counts, IP-10, and RANTES. The fibrosis stage, FIB-4, APRI, PDGF-BB, and RANTES were related to the prognosis. In aged patients, IP-10, GM-CSF, and RANTES differed between stages 1-2 and stages 3-4. FIB-4 and APRI were beneficial for their correlation with fibrosis. However, to stratify either young or elderly advanced fibrosis patients, and to identify patients likely to have a bad outcome, RANTES was the best marker. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 4 2023 Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis 341 345 EN Motoyuki Otsuka Department of Gastroenterology and Hepatology, Academic Field of Medicine, Density and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/65739 Hepatitis B virus is a pathogenic virus that infects 300 million people worldwide and causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Hepatitis B virus encodes four proteins. Among them, the HBx protein plays a central role in the HBV pathogenesis. Because the HBx protein is considered to play a central role in the induction of viral replication and hepatocarcinogenesis, the regulation of its function could be a key factor in the development of new interventions against hepatitis B. In this review, HBx protein-related viral replication and hepatocarcinogenesis mechanisms are described, with a focus on the recently reported viral replication mechanisms related to degradation of the Smc5/6 protein complex. We also discuss our recent discovery of a compound that inhibits HBx protein-induced degradation of the Smc5/6 protein complex, and that exerts inhibitory effects on both viral replication and hepatocarcinogenesis. Finally, prospects for future research on the HBx protein are described. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 17 1 2022 Effectiveness of and Immune Responses to SARS-CoV-2 mRNA Vaccines and Their Mechanisms 7 20 EN Eiichi Gohda Okayama University Following the online publication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome in January 2020, two lipid nanoparticle-encapsulated mRNA vaccines, BNT162b2 and mRNA-1273, were rapidly developed and are now being used worldwide to prevent coronavirus disease 2019 (COVID-19). The mRNA of both vaccines encodes the full-length spike protein of SARS-CoV-2, which binds to the host cell receptor angiotensin-converting enzyme 2 and is believed to mediate virus entry into cells. After intramuscular injection of the vaccine, the spike protein is produced in the cells. Both humoral and cellular immune responses to the spike protein are elicited for protection against COVID-19. The efficacy of the two mRNA vaccines against COVID-19 with wild-type SARS-CoV-2 is more than 90% and is slightly decreased with the Delta variant, which is currently the predominant variant in many countries. In this review, the effectiveness of and immune responses to COVID-19 mRNA vaccines and their mechanisms are summarized and discussed. Potential waning immunity and an additional dose of COVID-19 mRNA vaccines are also discussed. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2023 Oncolytic virus–mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer EN Hiroyuki ARAKI Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-4915 15 4 2023 Impact of Borna Disease Virus Infection on the Transcriptome of Differentiated Neuronal Cells and Its Modulation by Antiviral Treatment 942 EN Da Teng Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine Keiji Ueda Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine Tomoyuki Honda Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Borna disease virus (BoDV-1) is a highly neurotropic RNA virus that causes neurobehavioral disturbances such as abnormal social activities and memory impairment. Although impairments in the neural circuits caused by BoDV-1 infection induce these disturbances, the molecular basis remains unclear. Furthermore, it is unknown whether anti-BoDV-1 treatments can attenuate BoDV-1-mediated transcriptomic changes in neuronal cells. In this study, we investigated the effects of BoDV-1 infection on neuronal differentiation and the transcriptome of differentiated neuronal cells using persistently BoDV-1-infected cells. Although BoDV-1 infection did not have a detectable effect on intracellular neuronal differentiation processes, differentiated neuronal cells exhibited transcriptomic changes in differentiation-related genes. Some of these transcriptomic changes, such as the decrease in the expression of apoptosis-related genes, were recovered by anti-BoDV-1 treatment, while alterations in the expression of other genes remained after treatment. We further demonstrated that a decrease in cell viability induced by differentiation processes in BoDV-1-infected cells can be relieved with anti-BoDV-1 treatment. This study provides fundamental information regarding transcriptomic changes after BoDV-1 infection and the treatment in neuronal cells. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Urinary Retention Suggesting Aseptic Meningitis: Meningitis-Retention Syndrome Without Physical Signs of Meningeal Irritation 199 201 EN Tomohiro Nagano Department of Hematology, Japanese Red Cross Okayama Hospital Shinobu Hosokawa Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Hideaki Miyahara Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Kotaro Yamada Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Takayuki Umeno Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Hirohisa Kano Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Hiroe Kayatani Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Makoto Sakugawa Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Yasushi Takehisa Department of Neurology, Japanese Red Cross Okayama Hospital Tadasu Takenaka Department of Urology, Japanese Red Cross Okayama Hospital Makoto Takeuchi Department of Hematology, Japanese Red Cross Okayama Hospital Akihiro Bessho Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital Case Report 10.18926/AMO/65150 Meningitis-retention syndrome (MRS) is the combination of aseptic meningitis and acute urinary retention that occurs in the absence of other neurological diseases. The cause(s) of MRS remain unclear. A 57-year-old Japanese woman was referred to our hospital for the evaluation of persistent fever and headache. The fever’s cause was initially unclear, but the presence of urinary retention raised concern about possible aseptic meningitis despite no physical indications of meningeal irritation. Only typical cases of MRS have been reported thus far to our knowledge, and it is important that clinicians are aware of MRS when it presents in this atypical form. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 2 2023 Predictive Factors for Recovery from Alcoholic Liver Failure 169 177 EN Kanae Inoue Department of Gastroenterology, Okayama City Hospital Rio Fujita Department of Gastroenterology, Okayama City Hospital Takatoshi Nagahara Department of Gastroenterology, Okayama City Hospital Shiho Murakami Department of Gastroenterology, Okayama City Hospital Yuta Nagai Department of Gastroenterology, Okayama City Hospital Rina Moriwake Department of Gastroenterology, Okayama City Hospital Nozomi Miyake Department of Gastroenterology, Okayama City Hospital Akiko Wakuta Department of Gastroenterology, Okayama City Hospital Kazuya Kariyama Department of Gastroenterology, Okayama City Hospital Mamoru Nishimura Department of Gastroenterology, Okayama City Hospital Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Original Article 10.18926/AMO/65146 Alcoholic liver disease is a risk factor for non-virus-related hepatocellular carcinoma (HCC), which is increasing in prevalence. This study aimed to identify the factors for recovery from alcoholic liver failure. Sixty-two consecutive patients hospitalized for alcoholic liver failure at Okayama City Hospital were enrolled. The characteristics of patients who survived to the 1-month follow-up and whose liver function improved to Child–Pugh A at 3 months (CPA3) and 12 months (CPA12) were compared with the rest of the patients. The survivors at 1 month (50 patients) were significantly younger than the deceased patients and had better liver and renal function with higher levels of γ-glutamyl transferase (GGT). The same factors, except renal function, were correlated with achieving CPA3. High AST, ALT, and GGT levels as well as short spleen length, total abstinence, and good Child–Pugh scores at admission were identified as factors for achieving CPA12. The extent of alcohol intake before admission was not identified as a risk factor in any analysis. In conclusion, baseline liver function is crucial for survival and achieving CPA3, whereas high transaminase and γ-GTP levels, the absence of splenomegaly, and total abstinence are significant factors for achieving CPA12. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1553-7366 19 2 2023 Capsid structure of a fungal dsRNA megabirnavirus reveals its previously unidentified surface architecture e1011162 EN Han Wang The Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University Lakha Salaipeth Institute of Plant Science and Resources, Okayama University Naoyuki Miyazaki Life Science Center of Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Kenta Okamoto The Laboratory of Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a non-enveloped icosahedral double-stranded (ds)RNA virus that infects the ascomycete fungus Rosellinia necatrix, a causative agent that induces a lethal plant disease white root rot. Herein, we have first resolved the atomic structure of the RnMBV1 capsid at 3.2 angstrom resolution using cryo-electron microscopy (cryo-EM) single-particle analysis. Compared with other non-enveloped icosahedral dsRNA viruses, the RnMBV1 capsid protein structure exhibits an extra-long C-terminal arm and a surface protrusion domain. In addition, the previously unrecognized crown proteins are identified in a symmetry-expanded cryo-EM model and are present over the 3-fold axes. These exclusive structural features of the RnMBV1 capsid could have been acquired for playing essential roles in transmission and/or particle assembly of the megabirnaviruses. Our findings, therefore, will reinforce the understanding of how the structural and molecular machineries of the megabirnaviruses influence the virulence of the disease-related ascomycete fungus. Author summaryA fungal plant soil-borne pathogen, Rosellinia necatrix, which can cause devastating disease white root rot in many highly valued fruit trees, is difficult to be controlled with conventional approaches such as fungicide applications. Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a dsRNA virus isolated from the R. necatrix field strain, W779, and this virus can be a viro-control candidate to confer hypovirulence in its host R. necatrix. To make use of RnMBV1 in the white root rot disease control, more molecular and structural investigations will offer us more insights. Here, we have performed cryo-electron microscopy (cryo-EM) single-particle analysis, to obtain the first atomic models of RnMBV1 particles. Based on the atomic structures, we found unique both surface and interior features. In addition, we found a previously unidentified protein on the viral surface. These aforementioned structural features might play important roles in the viral life cycles, and will enable us to apply this fungal virus as a viro-control approach. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 1 2022 RSウイルス 48 51 EN Kazuhiro Uda Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 24 5 2023 Revisiting Cryptocyanine Dye, NK-4, as an Old and New Drug: Review and Future Perspectives 4411 EN Shihui Liu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University NK-4 plays a key role in the treatment of various diseases, such as in hay fever to expect anti-allergic effects, in bacterial infections and gum abscesses to expect anti-inflammatory effects, in scratches, cuts, and mouth sores from bites inside the mouth for enhanced wound healing, in herpes simplex virus (HSV)-1 infections for antiviral effects, and in peripheral nerve disease that causes tingling pain and numbness in hands and feet, while NK-4 is used also to expect antioxidative and neuroprotective effects. We review all therapeutic directions for the cyanine dye NK-4, as well as the pharmacological mechanism of NK-4 in animal models of related diseases. Currently, NK-4, which is sold as an over-the-counter drug in drugstores, is approved for treating allergic diseases, loss of appetite, sleepiness, anemia, peripheral neuropathy, acute suppurative diseases, wounds, heat injuries, frostbite, and tinea pedis in Japan. The therapeutic effects of NK-4’s antioxidant and neuroprotective properties in animal models are now under development, and we hope to apply these pharmacological effects of NK-4 to the treatment of more diseases. All experimental data suggest that different kinds of utility of NK-4 in the treatment of diseases can be developed based on the various pharmacological properties of NK-4. It is expected that NK-4 could be developed in more therapeutic strategies to treat many types of diseases, such as neurodegenerative and retinal degenerative diseases. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 1 2023 Metformin and Its Immune-Mediated Effects in Various Diseases 755 EN Ichiro Nojima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Metformin has been a long-standing prescribed drug for treatment of type 2 diabetes (T2D) and its beneficial effects on virus infection, autoimmune diseases, aging and cancers are also recognized. Metformin modulates the differentiation and activation of various immune-mediated cells such as CD4+ and CD+8 T cells. The activation of adenosine 5 '-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) pathway may be involved in this process. Recent studies using Extracellular Flux Analyzer demonstrated that metformin alters the activities of glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and glutaminolysis, which tightly link to the modulation of cytokine production in CD4+ and CD+8 T cells in various disease states, such as virus infection, autoimmune diseases, aging and cancers. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Viral Sequences Are Repurposed for Controlling Antiviral Responses as Non-Retroviral Endogenous Viral Elements 503 510 EN Hirohito Ogawa Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Honda Department of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Review 10.18926/AMO/64025 Eukaryotic genomes contain numerous copies of endogenous viral elements (EVEs), most of which are considered endogenous retrovirus (ERV) sequences. Over the past decade, non-retroviral endogenous viral elements (nrEVEs) derived from ancient RNA viruses have been discovered. Several functions have been proposed for these elements, including antiviral defense. This review summarizes the current understanding of nrEVEs derived from RNA viruses, particularly endogenous bornavirus-like elements (EBLs) and endogenous filovirus-like elements (EFLs). EBLs are one of the most extensively studied nrEVEs. The EBL derived from bornavirus nucleoprotein (EBLN) is thought to function as a non-coding RNA or protein that regulates host gene expression or inhibits virus propagation. Ebolavirus and marburgvirus, which are filoviruses, induce severe hemorrhagic fever in humans and nonhuman primates. Although the ecology of filoviruses remains unclear, bats are believed to be potential reservoirs. Based on the knowledge from EBLs, it is postulated that EFLs in the bat genome help to maintain the balance between filovirus infection and the bat’s defense system, which may partially explain why bats act as potential reservoirs. Further research into the functions of nrEVEs could reveal novel antiviral systems and inspire novel antiviral approaches. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Current Insights into Mesenchymal Signatures in Glioblastoma 489 502 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomotsugu Ichikawa Department of Neurological Surgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Review 10.18926/AMO/64024 Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2372-7705 27 2022 Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer 3 13 EN Hiroyuki Araki 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 Nobuhiko Kanaya Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Kajiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motohiko Yamada 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 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 Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adeno-carcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telo-merase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracel-lular adenosine triphosphate and high-mobility group box pro-tein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpres-sion augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2150-7511 2022 Three-Layered Complex Interactions among Capsidless (+)ssRNA Yadokariviruses, dsRNA Viruses, and a Fungus EN Yukiyo Sato Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Sakae Hisano Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Carlos Jose Lopez-Herrera Instituto de Agricultura Sostenible C.S.I.C., Alameda del Obispo Hideki Kondo Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University We have previously discovered a virus neo-lifestyle exhibited by a capsidless positive-sense (+), single-stranded (ss) RNA virus YkV1 (family Yadokariviridae) and an unrelated double-stranded (ds) RNA virus YnV1 (proposed family "Yadonushiviridae") in a phytopathogenic ascomycete, Rosellinia necatrix. YkV1 has been proposed to replicate in the capsid provided by YnV1 as if it were a dsRNA virus and enhance YnV1 replication in return. Recently, viruses related to YkV1 (yadokariviruses) have been isolated from diverse ascomycetous fungi. However, it remains obscure whether such viruses generally show the YkV1-like lifestyle. Here, we identified partner viruses for three distinct yadokariviruses, YkV3, YkV4a, and YkV4b, isolated from R. necatrix that were coinfected with multiple dsRNA viruses phylogenetically distantly related to YnV1. We first established transformants of R. necatrix carrying single yadokarivirus cDNAs and fused them with infectants by single partner candidate dsRNA viruses. Consequently, YkV3 and YkV4s replicated only in the presence of RnMBV3 (family Megabirnaviridae) and RnMTV1 (proposed family "Megatotiviridae"), respectively. The partners were mutually interchangeable between the two YkV4 strains and three RnMTV1 strains but not between other combinations involving YkV1 or YkV3. In contrast to YkV1 enhancing YnV1 accumulation, YkV4s reduced RnMTV1 accumulation to different degrees according to strains. Interestingly, YkV4 rescued the host R. necatrix from impaired growth induced by RnMTV1. YkV3 exerted no apparent effect on its partner (RnMBV3) or host fungus. Overall, we revealed that while yadokariviruses generally require partner dsRNA viruses for replication, each yadokarivirus partners with a different dsRNA virus species in the three diverse families and shows a distinct symbiotic relation in a fungus. IMPORTANCE A capsidless (+)ssRNA virus YkV1 (family Yadokariviridae) highjacks the capsid of an unrelated dsRNA virus YnV1 (proposed family "Yadonushiviridae") in a phytopathogenic ascomycete, while YkV1 trans-enhances YnV1 replication. Herein, we identified the dsRNA virus partners of three yadokariviruses (YkV3, YkV4a, and YkV4b) with genome organization different from YkV1 as being different from YnV1 at the suborder level. Their partners were mutually interchangeable between the two YkV4 strains and three strains of the partner virus RnMTV1 (proposed family "Megatotiviridae") but not between other combinations involving YkV1 or YkV3. Unlike YkV1, YkV4s reduced RnMTV1 accumulation and rescued the host fungus from impaired growth induced by RnMTV1. YkV3 exerted no apparent effect on its partner (RnMBV3, family Megabirnaviridae) or host fungus. These revealed that while each yadokarivirus has a species-specific partnership with a dsRNA virus, yadokariviruses collectively partner extremely diverse dsRNA viruses and show three-layered complex mutualistic/antagonistic interactions in a fungus. No potential conflict of interest relevant to this article was reported.

CELL PRESS Acta Medica Okayama 2589-0042 25 8 2022 Immune response to SARS-CoV-2 in severe disease and long COVID-19 104723 EN Tomonari Sumi Research Institute for Interdisciplinary Science, Okayama University Kouji Harada Department of Computer Science and Engineering, Toyohashi University of Technology COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10% decrease in innate immune cell activity and inhibition of type-I interferon signaling by autoantibodies drastil ally increased the viral load. It was reported that the numbers of certain dendritic cell subsets remained less than half those in healthy donors even seven months after infection. Hence, the inflammatory response was ongoing. Our model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID. No potential conflict of interest relevant to this article was reported.

American Institute of Mathematical Sciences Acta Medica Okayama 1547-1063 19 11 2022 Global stability of an age-structured infection model in vivo with two compartments and two routes 11047 11070 EN Tsuyoshi Kajiwara Graduate School of Environmental and Life Sciences, Okayama University Toru Sasaki Faculty of Environmental and Life Science, Okayama University Yoji Otani School of Engineering, Okayama University In this paper, for an infection age model with two routes, virus-to-cell and cell-to-cell, and with two compartments, we show that the basic reproduction ratio R-0 gives the threshold of the stability. If R-0 > 1, the interior equilibrium is unique and globally stable, and if R-0 <= 1, the disease free equilibrium is globally stable. Some stability results are obtained in previous research, but, for example, a complete proof of the global stability of the disease equilibrium was not shown. We give the proof for all the cases, and show that we can use a type reproduction number for this model. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-1702 319 2022 Phylogenic analysis of new viral cluster of large phages with unusual DNA genomes containing uracil in place of thymine in gene-sharing network, using phages S6 and PBS1 and relevant uncultured phages derived from sewage metagenomics 198881 EN Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Iyo Takemura-Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kazuyoshi Gotoh Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shin-ichiro Kato Research Institute of Molecular Genetics, Kochi University Yoshihiko Sakaguchi Department of Microbiology, Kitasato University School of Medicine Hironobu Murakami School of Veterinary Medicine, Azabu University Tomoki Fukuyama School of Veterinary Medicine, Azabu University Mao Kaneki School of Veterinary Medicine, Azabu University Osamu Matsushita Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Bacteriophages (phages) are the most diverse and abundant life-form on Earth. Jumbophages are phages with double-stranded DNA genomes longer than 200 kbp. Among these, some jumbophages with uracil in place of thymine as a nucleic acid base, which we have tentatively termed "dU jumbophages" in this study, have been reported. Because the dU jumbophages are considered to be a living fossil from the RNA world, the evolutionary traits of dU jumbophages are of interest. In this study, we examined the phylogeny of dU jumbophages. First, tBLASTx analysis of newly sequenced dU jumbophages such as Bacillus phage PBS1 and previously isolated Staphylococcus phage S6 showed similarity to the other dU jumbophages. Second, we detected the two partial genome sequences of uncultured phages possibly relevant to dU jumbophages, scaffold_002 and scaffold_007, from wastewater metagenomics. Third, according to the gene-sharing network analysis, the dU jumbophages, including phages PBS1 and S6, and uncultured phage scaffold_002 formed a cluster, which suggested a new viral subfamily/family. Finally, analyses of the phylogenetic relationship with other phages showed that the dU jumbophage cluster, which had two clades of phages infecting Gram-negative and Gram-positive bacteria, diverged from the single ancestral phage. These findings together with previous reports may imply that dU jumbophages evolved from the same origin before divergence of Gram-negative and Gram-positive bacteria. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-4915 14 8 2022 A Transfectable Fusagravirus from a Japanese Strain of Cryphonectria carpinicola with Spherical Particles 1722 EN Subha Das Institute of Plant Science and Resources, Okayama University Sakae Hisano Institute of Plant Science and Resources, Okayama University Ana Eusebio-Cope Institute of Plant Science and Resources, Okayama University Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University A novel dsRNA virus (Cryphonectria carpinicola fusagravirus 1, CcFGV1), isolated from a Japanese strain (JS13) of Cryphonectria carpinicola, was thoroughly characterized. The biological comparison of a set of isogenic CcFGV1-infected and -free (JS13VF) strains indicated asymptomatic infection by CcFGV1. The sequence analysis showed that the virus has a two open reading frame (ORF) genome of 9.6 kbp with the RNA-directed RNA polymerase domain encoded by ORF2. The N-terminal sequencing and peptide mass fingerprinting showed an N-terminally processed or degraded product (150 kDa) of the 5'-proximal ORF1-encoded protein (1462 amino acids) to make up the CcFGV1 spherical particles of similar to 40 nm in diameter. Interestingly, a portion of CcFGV1 dsRNA co-fractionated with a host protein of 70 kDa. The purified CcFGV1 particles were used to transfect protoplasts of JS13VF as well as the standard strain of an experimental model filamentous fungal host Cryphonectria parasitica. CcFGV1 was confirmed to be associated with asymptomatic infection of both fungi. RNA silencing was shown to target the virus in C. parasitica, resulting in reduced CcFGV1 accumulation by comparing the CcFGV1 content between RNA silencing-competent and -deficient strains. These results indicate the transfectability of spherical particles of a fusagravirus associated with asymptomatic infection. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2458 22 1 2022 Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan 1517 EN Kazuhiro Uda Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mitsuru Tsuge Department of Pediatrics Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Masato Yashiro Department of Pediatrics, Okayama University Hospital Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. Methods The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. Results A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. Conclusions Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 10 7 2022 The Effectiveness of Pre-Operative Screening Tests in Determining Viral Infections in Patients Undergoing Oral and Maxillofacial Surgery 1348 EN Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuka Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuaki Hasegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Tomoya Nakamura Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Ai Fujimura Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Ayaka Fujisawa Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake 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 Yumika Mukainaka 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 Yoshihiko Furuki Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8, $905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV. No potential conflict of interest relevant to this article was reported.

FRONTIERS MEDIA SA Acta Medica Okayama 2235-2988 12 2022 Mycovirus Hunting Revealed the Presence of Diverse Viruses in a Single Isolate of the Phytopathogenic Fungus Diplodia seriata From Pakistan 913619 EN Haris Ahmed Khan Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Paul Telengech Institute of Plant Science and Resources, Okayama University Hideki Kondo Institute of Plant Science and Resources, Okayama University Muhammad Faraz Bhatti Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Diplodia seriata in the family Botryosphaeriaceae is a cosmopolitan phytopathogenic fungus and is responsible for causing cankers, fruit rot and leaf spots on economically important plants. In this study, we characterized the virome of a single Pakistani strain (L3) of D. seriata. Several viral-like contig sequences were obtained via a previously conducted next-generation sequencing analysis. Multiple infection of the L3 strain by eight RNA mycoviruses was confirmed through RT-PCR using total RNA samples extracted from this strain; the entire genomes were determined via Sanger sequencing of RT-PCR and RACE clones. A BLAST search and phylogenetic analyses indicated that these eight mycoviruses belong to seven different viral families. Four identified mycoviruses belong to double-stranded RNA viral families, including Polymycoviridae, Chrysoviridae, Totiviridae and Partitiviridae, and the remaining four identified mycoviruses belong to single-stranded RNA viral families, i.e., Botourmiaviridae, and two previously proposed families "Ambiguiviridae" and "Splipalmiviridae". Of the eight, five mycoviruses appear to represent new virus species. A morphological comparison of L3 and partially cured strain L3ht1 suggested that one or more of the three viruses belonging to Polymycoviridae, "Splipalmiviridae" and "Ambiguiviridae" are involved in the irregular colony phenotype of L3. To our knowledge, this is the first report of diverse virome characterization from D. seriata. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 3 2022 Analysis of Immunity against Measles, Mumps, Rubella, and Varicella Zoster in Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience 247 253 EN Shohei Yoshida Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chihiro Kamoi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wataru Kitamura Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noboru Asada Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63718 Vaccine-preventable disease (VPD) infections are more severe in immunocompromised hosts. Vaccination against measles, mumps, rubella, and varicella zoster (VZV) (MMRV) is therefore recommended for hematopoietic stem cell transplantation (HCT) recipients. However, studies on adult HCT recipients with VPD infections are limited. At our institution, we have systematically conducted serological MMRV tests as a part of check-up examinations during long-term follow-up (LTFU) after HCT since 2015. This retrospective study aimed to evaluate changes in the serostatus between before and 2 years after allogeneic HCT. Among 161 patients, the pre-transplant seropositivity was 82.7% for measles, 86.8% for mumps, 84.2% for rubella, and 94.3% for VZV. Among 56 patients who underwent LTFU including serological MMRV tests at 2 years after HCT, the percentages maintaining seroprotective antibody levels for measles, mumps, rubella and VZV were 71.5% (40/56), 51.8% (29/56), 48.2% (27/56), and 60.7% (34/56), respectively. Vaccination was recommended for 22 patients, and 12 were vaccinated. Among the 12 vaccinated patients, rates of seroconversion were examined in 2-6 patients for each of the four viruses. They were 100% (3/3) for measles, 33.3% (1/3) for mumps, 50% (3/6) for rubella, and 0% (0/2) for VZV. Further studies are warranted to clarify the effect of vaccination in adult HCT recipients. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 1660-4601 19 8 2022 Misconceptions and Rumors about Ebola Virus Disease in Sub-Saharan Africa: A Systematic Review 4714 EN Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ngangu Patrick Ntontolo Department of Family Medicine and Primary Health, Protestant University of Congo Nlandu Roger Ngatu Department of Public Health, Kagawa University Faculty of Medicine Januka Khatiwada Social Work Institute Tomoko Suzuki Department of Public Health, School of Medicine, International University of Health and Welfare Koji Wada Department of Public Health, School of Medicine, International University of Health and Welfare Kei Kitahara Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunya Ikeda Department of Public Health, School of Medicine, International University of Health and Welfare Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We sought to summarize knowledge, misconceptions, beliefs, and practices about Ebola that might impede the control of Ebola outbreaks in Africa. We searched Medline, EMBASE, CINAHL, and Google Scholar (through May 2019) for publications reporting on knowledge, attitudes, and practices (KAP) related to Ebola in Africa. In total, 14 of 433 articles were included. Knowledge was evaluated in all 14 articles, and they all highlighted that there are misconceptions and risk behaviors during an Ebola outbreak. Some communities believed that Ebola spreads through the air, mosquito bites, malice from foreign doctors, witchcraft, and houseflies. Because patients believe that Ebola was caused by witchcraft, they sought help from traditional healers. Some people believed that Ebola could be prevented by bathing with salt or hot water. Burial practices where people touch Ebola-infected corpses were common, especially among Muslims. Discriminatory attitudes towards Ebola survivors or their families were also prevalent. Some Ebola survivors were not accepted back in their communities; the possibility of being ostracized from their neighborhoods was high and Ebola survivors had to lead a difficult social life. Most communities affected by Ebola need more comprehensive knowledge on Ebola. Efforts are needed to address misconceptions and risk behaviors surrounding Ebola for future outbreak preparedness in Africa. No potential conflict of interest relevant to this article was reported.

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

Okayama University Medical School Acta Medica Okayama 0386-300X 76 2 2022 Overexpression of Adenovirus E1A Reverses Transforming Growth Factor-β-induced Epithelial-mesenchymal Transition in Human Esophageal Cancer Cells 203 215 EN Tomoya Masuda 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 Yuuri Hashimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Ieda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/63425 The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression. No potential conflict of interest relevant to this article was reported.

Lippincott Williams & Wilkins Acta Medica Okayama 0025-7974 101 7 2022 Silica-associated systemic lupus erythematosus with lupus nephritis and lupus pneumonitis A case report and a systematic review of the literature e28872 EN Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuko Fuchimoto Department of Respiratory Medicine, Okayama Rosai Hospital Tomoyo Mifune Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaru Kinomura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Miyamoto Department of Respiratory Medicine, Okayama Rosai Hospital Sae Wada Department of Respiratory Medicine, Okayama Rosai Hospital Taisaku Koyanagi Department of Respiratory Medicine, Okayama Rosai Hospital Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takumi Kishimoto Department of Respiratory Medicine, Okayama Rosai Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction Several epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of silica-associated SLE have not been well studied. Patient concerns A 67-year-old man with silicosis visited a primary hospital because of a fever and cough. His respiratory condition worsened, regardless of antibiotic medication, and he was referred to our hospital. Diagnosis The patient showed leukopenia, lymphopenia, serum creatinine elevation with proteinuria and hematuria, decreased serum C3 level, and was positive for anti-double stranded DNA antibody, anti-nuclear antibody, and direct Coombs test. He was diagnosed with SLE. Renal biopsy was performed, and the patient was diagnosed with lupus nephritis (class IV-G(A/C) + V defined by the International Society of Nephrology/Renal Pathology Society classification). Computed tomography revealed acute interstitial pneumonitis, bronchoalveolar lavage fluid showed elevation of the lymphocyte fraction, and he was diagnosed with lupus pneumonitis. Interventions Prednisolone (50 mg/day) with intravenous cyclophosphamide (500 mg/body) were initiated. Outcomes The patient showed a favorable response to these therapies. He was discharged from our hospital and received outpatient care with prednisolone slowly tapered off. He had cytomegalovirus and herpes zoster virus infections during treatment, which healed with antiviral therapy. Review: We searched for the literature on sSLE, and selected 11 case reports and 2 population-based studies. The prevalence of SLE manifestations in sSLE patients were comparative to that of general SLE, particularly that of elderly-onset SLE. Our renal biopsy report and previous reports indicate that lupus nephritis of sSLE patients show as various histological patterns as those of general SLE patients. Among the twenty sSLE patients reported in the case articles, three patients developed lupus pneumonitis and two of them died of it. Moreover, two patients died of bacterial pneumonia, one developed aspergillus abscesses, one got pulmonary tuberculosis, and one developed lung cancer. Conclusion Close attention is needed, particularly for respiratory system events and infectious diseases, when treating patients with silica-associated SLE using immunosuppressive therapies. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0168-1702 307 2 2022 A new tetra-segmented splipalmivirus with divided RdRP domains from Cryphonectria naterciae, a fungus found on chestnut and cork oak trees in Europe 198606 EN Yukiyo Sato Institute of Plant Science and Resources, Okayama University Sabitree Shahi Institute of Plant Science and Resources, Okayama University Paul Telengech Institute of Plant Science and Resources, Okayama University Sakae Hisano Institute of Plant Science and Resources, Okayama University Carolina Cornejo Swiss Federal Research Institute WSL, Forest Health & Biotic Interactions Daniel Rigling Swiss Federal Research Institute WSL, Forest Health & Biotic Interactions Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Positive-sense (+), single-stranded (ss) RNA viruses with divided RNA-dependent RNA polymerase (RdRP) domains have been reported from diverse filamentous ascomycetes since 2020. These viruses are termed splipalmiviruses or polynarnaviruses and have been characterized largely at the sequence level, but ill-defined biologically. Cryphonectria naterciae, from which only one virus has been reported, is an ascomycetous fungus potentially plant-pathogenic to chestnut and oak trees. We molecularly characterized multiple viruses in a single Portuguese isolate (C0614) of C. naterciae, taking a metatranscriptomic and conventional double-stranded RNA approach. Among them are a novel splipalmivirus (Cryphonectria naterciae splipalmivirus 1, CnSpV1) and a novel fusagravirus (Cryphonectria naterciae fusagravirus 1, CnFGV1). This study focused on the former virus. CnSpV1 has a tetra-segmented, (+)ssRNA genome (RNA1 to RNA4). As observed for other splipalmiviruses reported in 2020 and 2021, the RdRP domain is separately encoded by RNA1 (motifs F, A and B) and RNA2 (motifs C and D). A hypothetical protein encoded by the 5′-proximal open reading frame of RNA3 shows similarity to a counterpart conserved in some splipalmiviruses. The other RNA3-encoded protein and RNA4-encoded protein show no similarity with known proteins in a blastp search. The tetra-segment nature was confirmed by the conserved terminal sequences of the four CnSpV1 segments (RNA1 to RNA4) and their 100% coexistence in over 100 single conidial isolates tested. The experimental introduction of CnSpV1 along with CnFGV1 into a virus free strain C0754 of C. naterciae vegetatively incompatible with C0614 resulted in no phenotypic alteration, suggesting asymptomatic infection. The protoplast fusion assay indicates a considerably narrow host range of CnSpV1, restricted to the species C. naterciae and C. carpinicola. This study contributes to better understanding of the molecular and biological properties of this unique group of viruses. No potential conflict of interest relevant to this article was reported.

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

岡山大学農学部 Acta Medica Okayama 2186-7755 111 2022 Silene 属植物が保持する性染色体ビッグデータと性操作する菌 15 20 EN Naoko Fujita Course of Applied Plant Science, The Faculty of Agriculture, Okayama University Silene latifolia (Caryophyllaceae) is a dioecious plant that has long been used for study on sex chromosomes in plants. The advantage but also disadvantage of S. latifolia as a model system is the size of the Y chromosome that contains an extremely large male-specific region (approx. > 500 Mb). This feature implies that the evolutionary history of sex chromo-somes remains in the S. latifolia Y chromosome, while the size makes analyses esoteric. Another advantage is that plants in the genus Silene show variation in reproductive systems; most are gynodioecy (females and hermaphrodites), which is thought of as an evolutionary status before establishment of dioecy (males and females), with a few hermaphrodites and dioecy, suggesting that the genus Silene may represent an epitome of the sex chromosome evolution. Microbotryum is a biotrophic fungi, whose infection causes masculinization of the female flower, as if the fungus acts as the Y chromo-some. Though the underlying molecular mechanisms remain unknown, recent high-throughput sequence technologies provide many candidate genes for sex determination in plants and sex conversion by the fungus. In this article, I review and introduce studies of the Y chromosome in S. latifolia plant, the evolution of sex chromosomes in the genus Silene, the masculinization of female flowers caused by a fungus infection, and a virus vector that can be used for genetic analysis of the key genes involved in these processes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-4915 14 1 2022 Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B 160 EN Hirohito Ogawa Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Fujikura School of Veterinary Medicine, Kitasato University Hikaru Namba Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuko Yamashita Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyuki Honda Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masao Yamada Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Human herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to secrete the virus in their saliva, which is thus considered a source for virus transmission. HHV-6B primarily propagates in T cells because its entry receptor, CD134, is mainly expressed by activated T cells. The virus then spreads to the host's organs, including the salivary glands, nervous system, and liver. However, CD134 expression is not detected in these organs. Therefore, HHV-6B may be entering cells via a currently unidentified cell surface molecule, but the mechanisms for this have not yet been investigated. In this study, we investigated a CD134-independent virus entry mechanism in the parotid-derived cell line HSY. First, we confirmed viral infection in CD134-membrane unanchored HSY cells. We then determined that nectin cell adhesion molecule 2 (nectin-2) mediated virus entry and that HHV-6B-insensitive T-cells transduced with nectin-2 were transformed into virus-permissive cells. We also found that virus entry was significantly reduced in nectin-2 knockout parotid-derived cells. Furthermore, we showed that HHV-6B glycoprotein B (gB) interacted with the nectin-2 V-set domain. The results suggest that nectin-2 acts as an HHV-6B entry-mediated protein. No potential conflict of interest relevant to this article was reported.

耳鼻と臨床会 Acta Medica Okayama 04477227 67 1 2021 口蓋扁桃摘出術後の創傷治癒遅延を契機に判明した HIV 感染症の1例 26 30 EN Akifumi Kariya Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital Hisashi Ishihara Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital Naoki Akisada Department of Head and Neck Surgery, Shikoku Cancer Center Iku Fujisawa Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sayaka Fuji Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital Seiko Akagi Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital Ayako Takeuchi Department of Otorhinolaryngology, Japanese Red Cross Okayama Hospital HIV（human immunodeficiency virus）は感染すると宿主の免疫能を低下させ、進行すると AIDS（acquired immunodeficiency syndrome）を引き起こす。HIV 感染症は多彩な症状を呈することが知られており、創傷治癒遅延もその一つである。今回われわれは口蓋扁桃摘出術後の創傷治癒遅延から HIV 感染症と判明した症例を経験した。HIV 感染症は早期の治療開始が予後改善のために推奨されており、早期発見が重要である。手術前 HIV スクリーニング検査は創傷治癒遅延を防ぐ意味でも重要と考えられるが、現行の保険制度上は認められない場合があり、保険適用範囲の拡大が望まれる。 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1345-2630 88 2 2022 Plant viruses and viroids in Japan 105 127 EN Shin-ichi Fuji Faculty of Bioresource Sciences, Akita Prefectural University Tomofumi Mochizuki Graduate School of Life and Environmental Sciences, Osaka Prefecture University Mitsuru Okuda Office of the President, National Agriculture and Food Research Organization (NARO) Shinya Tsuda Department of Clinical Plant Science, Faculty of Bioscience and Applied Chemistry Satoshi Kagiwada Department of Clinical Plant Science, Faculty of Bioscience and Applied Chemistry, Hosei University Ken-Taro Sekine Faculty of Agriculture, University of the Ryukyus Masashi Ugaki Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo Keiko T. Natsuaki Tokyo University of Agriculture Masamichi Isogai Faculty of Agriculture, Iwate University Tetsuo Maoka Institute for Plant Protection, National Agriculture and Food Research Organization (NIPP, NARO) Minoru Takeshita Department of Agricultural and Environmental Sciences, Faculty of Agriculture, University of Miyazak Nobuyuki Yoshikawa Agri-Innovation Center, Iwate University Kazuyuki Mise Graduate School of Agriculture, Kyoto University Takahide Sasaya 3 Department of Research Promotion, Institute for Plant Protection, National Agriculture and Food Research Organization (NIPP, NARO) Hideki Kondo Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University Kenji Kubota Division of Core Technology for Pest Control Research, Institute for Plant Protection, National Agriculture and Food Research Organization (NIPP, NARO) Yasuyuki Yamaji Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo Toru Iwanami Faculty of Agriculture, Tokyo University of Agriculture Kazusato Ohshima Department of Biological Resource Science, Faculty of Agriculture, Saga University Kappei Kobayashi Faculty of Agriculture, Ehime University Tatsuji Hataya Research Faculty of Agriculture, Hokkaido University Teruo Sano Hirosaki University Nobuhiro Suzuki Group of Plant-Microbe Interactions, Institute of Plant Science and Resources, Okayama University An increasing number of plant viruses and viroids have been reported from all over the world due largely to metavirogenomics approaches with technological innovation. Herein, the official changes of virus taxonomy, including the establishment of megataxonomy and amendments of the codes of virus classification and nomenclature, recently made by the International Committee on Taxonomy of Viruses were summarized. The continued efforts of the plant virology community of Japan to index all plant viruses and viroids occurring in Japan, which represent 407 viruses, including 303 virus species and 104 unclassified viruses, and 25 viroids, including 20 species and 5 unclassified viroids, as of October 2021, were also introduced. These viruses and viroids are collectively classified into 81 genera within 26 families of 3 kingdoms (Shotokuvirae, Orthornavirae, Pararnavirae) across 2 realms (Monodnaviria and Riboviria). This review also overviewed how Japan’s plant virus/viroid studies have contributed to advance virus/viroid taxonomy. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 23 2021 Multifaceted Analysis of IL-23A-and/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes 12659 EN Kota Tachibana Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Nina Tang Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hitoshi Urakami Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Ai Kajita Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Mina Kobashi Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hayato Nomura Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Minori Sasakura Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Satoru Sugihara Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Fan Jiang Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Mamoru Ouchida Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-alpha, IL-17A, and interferon (IFN)-gamma, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2021 Study on the intestinal conditions of chicken orally administrated with Lactobacillus acidophilus strain L-55 under the parasite infection or virus vaccination EN PHAM HOANG SON HUNG Graduate School of Environmental and Life Science, Okayama University No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0022-538X 95 17 2021 Proof of Concept of the Yadokari Nature: a Capsidless Replicase-Encoding but Replication-Dependent Positive-Sense Single-Stranded RNA Virus Hosted by an Unrelated Double-Stranded RNA Virus e00467-21 EN Subha Das Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Md Mahfuz Alam Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Rui Zhang Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Sakae Hisano Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Viruses typically encode their own capsids that encase their genomes. However, a capsidless positive-sense single stranded RNA [(+)ssRNA] virus, YkV1, depends on an unrelated double-stranded RNA (dsRNA) virus, YnV1, for encapsidation and replication. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2571-841X 4 3 2021 Lymphoepithelial Carcinoma in the Lateral Tongue: The Case Report 24 EN Sawako Ono Department of Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidenori Marunaka Department of Otolaryngology Head and Neck Surgery, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Hospital Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Nishida Department of Pathology, Okayama University Hospital Tomohiro Toji Department of Pathology, Okayama University Hospital 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 Tadashi Yoshino Department of Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lymphoepithelial carcinoma (LEC) of the tongue is a rare subtype of squamous cell carcinoma. Histologically, it is an undifferentiated carcinoma with rich lymphocyte and plasma cell infiltration. The most common location for LEC in the head and neck is the salivary glands, and LEC of the oral cavity is extremely rare. The second case report of LEC in the lateral tongue is presented. In addition, a review of the literature was performed, and the relationship between LEC and Epstein-Barr virus infection was considered. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1345-2630 87 6 2021 Identification and characterization of host factors involved in plant RNA virus replication 415 417 EN Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-302X 12 2021 Identification of a Novel Quinvirus in the Family Betaflexiviridae That Infects Winter Wheat 715545 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Naoto Yoshida Agricultural Research Institute, HOKUREN Federation of Agricultural Cooperatives Miki Fujita Institute of Plant Science and Resources (IPSR), Okayama University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR), Okayama University Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University Hiroshi Hisano Institute of Plant Science and Resources (IPSR), Okayama University Tetsuo Tamada Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika College of Plant Health and Medicine, Qingdao Agricultural University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Yellow mosaic disease in winter wheat is usually attributed to the infection by bymoviruses or furoviruses; however, there is still limited information on whether other viral agents are also associated with this disease. To investigate the wheat viromes associated with yellow mosaic disease, we carried out de novo RNA sequencing (RNA-seq) analyses of symptomatic and asymptomatic wheat-leaf samples obtained from a field in Hokkaido, Japan, in 2018 and 2019. The analyses revealed the infection by a novel betaflexivirus, which tentatively named wheat virus Q (WVQ), together with wheat yellow mosaic virus (WYMV, a bymovirus) and northern cereal mosaic virus (a cytorhabdovirus). Basic local alignment search tool (BLAST) analyses showed that the WVQ strains (of which there are at least three) were related to the members of the genus Foveavirus in the subfamily Quinvirinae (family Betaflexiviridae). In the phylogenetic tree, they form a clade distant from that of the foveaviruses, suggesting that WVQ is a member of a novel genus in the Quinvirinae. Laboratory tests confirmed that WVQ, like WYMV, is potentially transmitted through the soil to wheat plants. WVQ was also found to infect rye plants grown in the same field. Moreover, WVQ-derived small interfering RNAs accumulated in the infected wheat plants, indicating that WVQ infection induces antiviral RNA silencing responses. Given its common coexistence with WYMV, the impact of WVQ infection on yellow mosaic disease in the field warrants detailed investigation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Knowledge, Attitude and Practice of Sudanese Health Care Providers toward Ebola Virus Outbreak 487 493 EN Ezzan Kunna Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University Taro Yamamoto Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University Sabin Nundu Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University Calliope Akintije Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University Isam Elkhidir Department of Microbiology and Parasitology, Faculty of Medicine, University of Khartoum Original Article 10.18926/AMO/62401 Ebola virus disease (EVD) is a highly contagious and fatal disease in humans. Healthcare providers (HCPs) are often at the frontline of epidemics and can thus be in jeopardy of contracting EVD. Sudan is at a great risk of an EVD outbreak, as it borders countries that experienced EVD outbreaks. It is therefore imperative in Sudan to assess the HCPs’ awareness and knowledge, attitude, and practice (KAP) about EVD for its control and man-agement and for preparedness. A KAP survey was conducted among 387 HCPs (physicians, nurses and labora-tory technicians) in the three main tertiary hospitals in Khartoum, Sudan. The majority of the survey respon-dents (54.5%) were females, < 30 years old (76.3%), and single (77.4%). Most (94%) had heard about EVD, 62% from classical media. Only 14% had received education or training regarding EVD. About 40% reported being adherent to universal precautions and 72% were willing to deal with EVD patients under safety precau-tions. Only 10% knew of any available standard national guidelines for EVD. Nearly half of the HCPs (47%) rated the potential risk of an EVD outbreak in Sudan as high, and 52% rated health authorities’ effort against it as weak. These findings revealed the HCPs’ insufficient knowledge of EVD and the necessary universal precau-tions. This lack of knowledge would negatively affect the HCPs’ preparedness toward any potential EVD out-break. There is a dire need to train HCPs in Sudan on the management of EVD, including preventive and con-trol measures. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1023-3830 2021 Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus EN Takahiro Namba Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mitsuru Tsuge Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masato Yashiro Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yukie Saito Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Keyue Liu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiro Nishibori Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuneo Morishima Department of Pediatrics, Aichi Medical University Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Objective<br> High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs).<br> <br> Methods<br> Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively.<br> <br> Results<br> Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs.<br> <br> Conclusion<br> Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 8 2021 Comparative Study on Epstein-Barr Virus-Positive Mucocutaneous Ulcer and Methotrexate-Associated Lymphoproliferative Disorders Developed in the Oral Mucosa: A Case Series of 10 Patients and Literature Review 1375 EN Kyoichi Obata Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsuo Okui Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Koki Umemori Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Ryumon Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kisho Ono Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayumi Yao Department of Dentistry and Dental Surgery, Tsuyama Chuo Hospital Norie Yoshioka Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Sasaki Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is an iatrogenic immunodeficiency-associated lymphoproliferative disorder that occurs mainly with MTX use. This disorder has been associated with Epstein-Barr virus (EBV) infection. In 2017, the WHO newly defined the disease concept of EBV-positive mucocutaneous ulcer (EBV-MCU) as a good-prognosis EBV-related disease. Here, we report 10 cases of MTX-LPD or EBV-MCU in the oral mucosa. This retrospective, observational study was conducted with MTX-LPD or EBV-MCU in the oral mucosa patients who visited us during the nine year period from 2012 to 2021. We gathered the basic information, underlying disease, histopathological evaluation, treatment and prognosis for the subjects. All were being treated with MTX for rheumatoid arthritis. EBV infection was positive in all cases by immunohistochemistry. A complete or partial response was obtained in all cases with the withdrawal of MTX. Our results suggests that the most common risk factor for developing EBV-MCU is the use of immunosuppressive drugs. The most common site of onset is the oral mucosa, which may be attributed to the mode of EBV infection and the high incidence of chronic irritation of the oral mucosa. A small number of patients had been diagnosed with MTX-LPD, but we consider that these cases were EBV-MCU based on our study. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0959-8049 153 2021 Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (Telomelysin) with radiotherapy in oesophageal cancer patients unfit for standard treatments 98 108 EN Yasuhiro Shirakawa 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 Tanabe 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 Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takeshi Koujima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kuniaki Katsui Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, 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 Purpose: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments.<br> <br> Methods: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy.<br> <br> Results: Of the 13 patients, 7, 3 and 3 patients were treated with 10(10), 10(11) and 10(12) virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8 thorn cells and increased PD-L1 expression.<br> <br> Conclusion: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments. (C) 2021 Elsevier Ltd. All rights reserved. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0304-8608 166 2021 A second capsidless hadakavirus strain with 10 positive-sense single-stranded RNA genomic segments from Fusarium nygamai 2711 2722 EN Haris Ahmed Khan Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Yukiyo Sato Institute of Plant Science and Resources, Okayama University Hideki Kondo Institute of Plant Science and Resources, Okayama University Atif Jamal Crop Diseases Research Institute, National Agricultural Research Centre Muhammad Faraz Bhatti Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University A unique capsidless virus with a positive-sense, single-stranded RNA genome (hadakavirus 1, HadV1), a member of the extended picorna-like supergroup, was isolated previously from the phytopathogenic fungus Fusarium oxysporum. Here, we describe the molecular and biological characterisation of a second hadakavirus strain from Fusarium nygamai, which has not been investigated in detail previously as a virus host. This virus, hadakavirus 1 strain 1NL (HadV1-1NL), has features similar to the first hadakavirus, HadV1-7n, despite having a different number of segments (10 for HadV1-1NL vs. 11 for HadV1-7n). The 10 genomic RNA segments of HadV1-1NL range in size from 0.9 kb to 2.5 kb. All HadV1-1NL segments show 67% to 86% local nucleotide sequence identity to their HadV1-7n counterparts, whereas HadV1-1NL has no homolog of HadV1-7n RNA8, which encodes a zinc-finger motif. Another interesting feature is the possible coding incapability of HadV1-1NL RNA10. HadV1-1NL was predicted to be capsidless based on the RNase A susceptibility of its replicative form dsRNA. Phenotypic comparison of multiple virus-infected and virus-free single-spore isolates indicated asymptomatic infection by HadV1-1NL. Less-efficient vertical transmission via spores was observed as the infected fungal colonies from which the spores were derived became older, as was observed for HadV1-7n. This study shows a second example of a hadakavirus that appears to have unusual features. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 1756-0500 14 1 2021 Genome sequence analysis of new plum pox virus isolates from Japan 266 EN Tomoaki Mori Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Chiaki Warner Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Serika Ohno Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Koichi Mori Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takamasa Tobimatsu Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Sera Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Objective To find mutations that may have recently occurred in Plum pox virus (PPV), we collected six PPV-infected plum/peach trees from the western part of Japan and one from the eastern part. After sequencing the full-length PPV genomic RNAs, we compared the amino acid sequences with representative isolates of each PPV strain. Results All new isolates were found to belong to the PPV-D strain: the six isolates collected from western Japan were identified as the West-Japan strain while the one collected from eastern Japan as the East-Japan strain. Amino acid sequence analysis of these seven isolates suggested that the 1407th and 1529th amino acid residues are characteristic of the West-Japan and the East-Japan strains, respectively. Comparing them with the corresponding amino acid residues of the 47 non-Japanese PPV-D isolates revealed that these amino acid residues are undoubtedly unique. A further examination of the relevant amino acid residues of the other 210 PPV-D isolates collected in Japan generated a new hypothesis regarding the invasion route from overseas and the subsequent diffusion route within Japan: a PPV-D strain might have invaded the western part of Japan from overseas and spread throughout Japan. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 1756-0500 14 1 2021 Development of a method to rapidly assess resistance/susceptibility of Micro-Tom tomatoes to Tomato yellow leaf curl virus via agroinoculation of cotyledons 237 EN Tomoaki Mori Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kosuke Takenaka Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Fumiya Domoto Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Yasuhiro Aoyama Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University Takashi Sera Department of Applied Chemistry and Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Objective: Tomato yellow leaf curl virus (TYLCV) is one of the pathogens severely damaging tomato crops. Therefore, methods to treat or prevent TYLCV infection need to be developed. For this purpose, a method to conveniently and quickly assess infection of tomatoes by TYLCV is desired. In the present study, we established a quick method to evaluate TYLCV infection using cotyledons of Micro-Tom, a miniature tomato cultivar.<br> Results: First, we constructed a binary plasmid harboring 1.5 copies of the TYLCV genome and transformed Agrobacterium with the plasmid. By injecting agroinoculum from the resulting transformant into the branches of Micro-Tom, we confirmed the susceptibility of Micro-Tom to TYLCV. To shorten the evaluation process of TYLCV infection further, we agroinoculated cotyledons of Micro-Tom 10 days after sowing seeds. We consistently observed typical symptoms of TYLCV infection on true leaves 10 days after agroinoculation. Molecular analysis detected TYLCV progeny DNA in all leaves demonstrating symptoms 6 days after agroinoculation. Therefore, our new protocol enabled assessment of TYLCV infection within 20 days after sowing seeds. Thus, agroinoculation of Micro-Tom cotyledons will accelerate the process of screening TYLCV-resistant Micro-Toms and enable screening of larger numbers of plants more quickly, contributing to the development of TYLCV-resistant tomatoes. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 3 2020 Ｃ型肝炎ウイルス（HCV）：抗 HCV 剤の開発と抗 HCV 療法 131 143 EN Nobuyuki Kato Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 2 2021 A Case of Dual-pathology Hepatocellular Carcinoma (HCC) and Cholangiolocellular Carcinoma (CoCC) after Eradication of Hepatitis C Virus (HCV) Infection 213 218 EN Manabi Miyashita Department of Hepatology, National Hospital Organaization of Iwakuni Clinical Center Yousuke Saragai Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Tsuyoshi Fujimoto Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Shouichi Tanaka Department of Gastroenterology, National Hospital Organaization of Iwakuni Clinical Center Hideki Aoki Department of Surgery, National Hospital Organaization of Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organaization of Iwakuni Clinical Center Case Report 10.18926/AMO/61903 A 75-year-old Japanese man visited our hospital for further examination of liver tumors. He had a history of successful hepatitis C virus (HCV) eradication and therapy for hepatocellular carcinoma (HCC) at another hospital. Magnetic resonance imaging (MRI) revealed two tumors in the liver. He underwent anterior inferior (S5) and posterior inferior (S6) subsegmentectomy of the liver. Microscopic examination found that one tumor was HCC while the other was cholangiolocellular carcinoma (CoCC). We experienced a rare case of liver cancer with two synchronous pathologies, HCC and CoCC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-7737 10 2 2021 Identification of an RNA Silencing Suppressor Encoded by a Symptomless Fungal Hypovirus, Cryphonectria Hypovirus 4 100 EN Annisa Aulia Institute of Plant Science and Resources (IPSR), Okayama University Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University Sakae Hisano Institute of Plant Science and Resources (IPSR), Okayama University Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Bradley I. Hillman Plant Biology and Pathology, Rutgers University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Previously, we have reported the ability of a symptomless hypovirus Cryphonectria hypovirus 4 (CHV4) of the chestnut blight fungus to facilitate stable infection by a co-infecting mycoreovirus 2 (MyRV2)—likely through the inhibitory effect of CHV4 on RNA silencing (Aulia et al., Virology, 2019). In this study, the N-terminal portion of the CHV4 polyprotein, termed p24, is identified as an autocatalytic protease capable of suppressing host antiviral RNA silencing. Using a bacterial expression system, CHV4 p24 is shown to cleave autocatalytically at the di-glycine peptide (Gly214-Gly215) of the polyprotein through its protease activity. Transgenic expression of CHV4 p24 in Cryphonectria parasitica suppresses the induction of one of the key genes of the antiviral RNA silencing, dicer-like 2, and stabilizes the infection of RNA silencing-susceptible virus MyRV2. This study shows functional similarity between CHV4 p24 and its homolog p29, encoded by the symptomatic prototype hypovirus CHV1. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 3 2021 Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity 1053 EN Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Hospital Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 The Optimal Timing of Antiretroviral Therapy Initiation in HIV-Infected Patients with Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Trial 109 113 EN Xiaolei Xu Division of Infectious Diseases, Chongqing Public Health Medical Center Yanqiu Lu Division of Infectious Diseases, Chongqing Public Health Medical Center Vijay Harypursat Division of Infectious Diseases, Chongqing Public Health Medical Center Feng Sun Division of Infectious Diseases, Chongqing Public Health Medical Center Ting Zhao Division of Infectious Diseases, Chongqing Public Health Medical Center Yanming Zeng Division of Infectious Diseases, Chongqing Public Health Medical Center Xiaoqing He Division of Infectious Diseases, Chongqing Public Health Medical Center Yaokai Chen Division of Infectious Diseases, Chongqing Public Health Medical Center Clinical Study Protocol 10.18926/AMO/61443 The optimal timing of antiretroviral therapy (ART) initiation in human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (HIV/CM) is controversial. We designed a clinical trial to inves-tigate the optimal timing for ART initiation in HIV/CM patients. This will be a multicenter, prospective, and randomized clinical trial. Each enrolled patient will be randomized into either the early ART arm or the deferred ART arm. We will compare the mortality and incident rates of immune reconstitution inflammatory syndrome between the two arms. We hope to elucidate the optimal timing for ART initiation in HIV/CM patients. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 15 10 2021 Local perspectives on Ebola during its tenth outbreak in DR Congo: A nationwide qualitative study e0241120 EN Basilua Andre Muzembo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ngangu Patrick Ntontolo Department of Family Medicine and Primary health, Protestant University of Congo Nlandu Roger Ngatu Department of Public Health, Kagawa University Faculty of Medicine Januka Khatiwada Department of Public Health, School of Medicine, International University of Health and Welfare Kabamba Leon Ngombe Department of Public Health, University of Kamina Oscar Luboya Numbi School of Public Health, University of Lubumbashi Kabamba Michel Nzaji School of Public Health, University of Lubumbashi Kabinda Jeff Maotela Centre National de Transfusion Sanguine Mukonkole Jean Ngoyi Research Unit, ISTM-Lubumbashi Tomoko Suzuki Department of Public Health, School of Medicine, International University of Health and Welfare Koji Wada Department of Public Health, School of Medicine, International University of Health and Welfare Shunya Ikeda Department of Public Health, School of Medicine, International University of Health and Welfare Background</br> The Democratic Republic of Congo (DR Congo) struggled to end the tenth outbreak of Ebola virus disease (Ebola), which appeared in North Kivu in 2018. It was reported that rumors were hampering the response effort. We sought to identify any rumors that could have influenced outbreak containment and affected prevention in unaffected areas of DR Congo.</br> Methods</br> We conducted a qualitative study in DR Congo over a period of 2 months (from August 1 to September 30, 2019) using in-depth interviews (IDIs) and focus group discussions (FGDs). The participants were recruited from five regional blocks using purposeful sampling. Both areas currently undergoing outbreaks and presently unaffected areas were included. We collected participants’ opinions, views, and beliefs about the Ebola virus. The IDIs (n = 60) were performed with key influencers (schoolteachers, religious and political leaders/analysts, and Ebola-frontline workers), following a semi-structured interview guide. FGDs (n = 10) were conducted with community members. Interviews were recorded with a digital voice recorder and simultaneous note-taking. Participant responses were categorized in terms of their themes and subthemes.</br> Results</br> We identified 3 high-level themes and 15 subthemes (given here in parentheses): (1) inadequate knowledge of the origin or cause of Ebola (belief in a metaphysical origin, insufficient awareness of Ebola transmission via an infected corpse, interpretation of disease as God’s punishment, belief in nosocomial Ebola, poor hygiene, and bathing in the Congo River). Ebola was interpreted as (2) a plot by multinational corporations (fears of genocide, Ebola understood as a biological weapon, concerns over organ trafficking, and Ebola was taken to be the result of business actions). Finally Ebola was rumored to be subject to (3) politicization (political authorities seen as ambivalent, exclusion of some community leaders from response efforts, distrust of political authorities, and distrust in the healthcare system).</br> Conclusions</br> Due to the skepticism against Ebola countermeasures, it is critical to understand widespread beliefs about the disease to implement actions that will be effective, including integrating response with the unmet needs of the population. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1615-5262 20 2021 Web access monitoring mechanism via Android WebView for threat analysis 833 847 EN Yuta Imamura Graduate School of Natural Science and Technology, Okayama University Rintaro Orito Graduate School of Natural Science and Technology, Okayama University Hiroyuki Uekawa Graduate School of Natural Science and Technology, Okayama University Kritsana Chaikaew Faculty of Engineering, Kasetsart University Pattara Leelaprute Faculty of Engineering, Kasetsart University Masaya Sato Graduate School of Natural Science and Technology Toshihiro Yamauchi Graduate School of Natural Science and Technology, Okayama University Many Android apps employ WebView, a component that enables the display of web content in the apps without redirecting users to web browser apps. However, WebView might also be used for cyberattacks. Moreover, to the best of our knowledge, although some countermeasures based on access control have been reported for attacks exploiting WebView, no mechanism for monitoring web access via WebView has been proposed and no analysis results focusing on web access via WebView are available. In consideration of this limitation, we propose a web access monitoring mechanism for Android WebView to analyze web access via WebView and clarify attacks exploiting WebView. In this paper, we present the design and implementation of this mechanism by modifying Chromium WebView without any modifications to the Android framework or Linux kernel. The evaluation results of the performance achieved on introducing the proposed mechanism are also presented here. Moreover, the result of threat analysis of displaying a fake virus alert while browsing websites on Android is discussed to demonstrate the effectiveness of the proposed mechanism. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2020 Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression EN Terutaka Tanimoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Solitary Cardiac Metastasis of Hepatocellular Carcinoma 525 530 EN Hideki Aoki Department of Surgery, National Hospital Organization Iwakuni Clinical Center Masashi Utsumi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Yuji Kimura Department of Surgery, National Hospital Organization Iwakuni Clinical Center Yosuke Takahashi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Seiichi Nagahisa Department of Surgery, National Hospital Organization Iwakuni Clinical Center Seitaro Nishimura Department of Surgery, National Hospital Organization Iwakuni Clinical Center Yuta Une Department of Surgery, National Hospital Organization Iwakuni Clinical Center Megumi Watanabe Department of Surgery, National Hospital Organization Iwakuni Clinical Center Fumitaka Taniguchi Department of Surgery, National Hospital Organization Iwakuni Clinical Center Takashi Arata Department of Surgery, National Hospital Organization Iwakuni Clinical Center Koh Katsuda Department of Surgery, National Hospital Organization Iwakuni Clinical Center Kohji Tanakaya Department of Surgery, National Hospital Organization Iwakuni Clinical Center Case Report 10.18926/AMO/61212 Cardiac metastasis originating from hepatocellular carcinoma (HCC) is a rare condition with a poor prognosis. No therapeutic standards for cardiac metastasis originating from HCC have been established. At 19 months after a curative hepatectomy, a 64-year-old Japanese hepatitis B virus-positive male patient experienced solitary cardiac metastasis originating from HCC. The cardiac tumor was discovered in the right ventricle. The patient received three courses of radiotherapy and chemotherapy and survived > 3 years after the initial diagnosis of cardiac metastasis. His case demonstrates that radiotherapy combined with chemotherapy can be an effective treatment for cardiac metastasis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 6 2020 Reality of Gastric Cancer in Young Patients: The Importance and Difficulty of the Early Diagnosis, Prevention and Treatment 461 466 EN Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/61204 Gastric cancer usually arises in middle-aged to older patients, and is rarely found in younger patients. The clin-ical characteristics, etiology, prognosis, preventive methods and treatment of gastric cancer in young patients have not been fully investigated because of its low prevalence. In this review, we discuss the current under-standing and clinical problems associated with gastric cancer in young patients. Helicobacter pylori (H. pylori), which is a major cause of gastric cancer, especially in older populations, is closely associated with gastric cancer in young patients as well as in older patients. Gastric cancer in young patients tends to be diagnosed at an advanced stage with alarm symptoms. However, young patients with advanced gastric cancer tend to have a favorable general condition and organ function, so they can tolerate intensive systematic chemotherapy. Unfortunately, the prognosis of gastric cancer in young patients with an advanced stage is not favorable. We should not take this rare disease lightly, given its poor prognosis if patients are diagnosed at an unresectable stage. The evaluation of the H. pylori infection status and performance of H. pylori eradication therapy to prevent gastric cancer in young patients as well as the development of more intensive chemotherapy regimens for unre-sectable gastric cancer in young patients are warranted. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0042-6822 554 2021 Cryphonectria nitschkei chrysovirus 1 with unique molecular features and a very narrow host range 55 62 EN Sabitree Shahi Institute of Plant Science and Resources, Okayama University Sotaro Chiba Graduate School of Bioagricultural Sciences, Nagoya University Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Cryphonectria nitschkei chrysovirus 1 (CnCV1), was described earlier from an ascomycetous fungus, Cryphonectria nitschkei strain OB5/11, collected in Japan; its partial sequence was reported a decade ago. Complete sequencing of the four genomic dsRNA segments revealed molecular features similar to but distinct from previously reported members of the family Chrysoviridae. Unique features include the presence of a mini-cistron preceding the major large open reading frame in each genomic segment. Common features include the presence of CAA repeats in the 5′-untranslated regions and conserved terminal sequences. CnCV1-OB5/11 could be laterally transferred to C. nitschkei and its relatives C. radicalis and C. naterciae via coculturing, virion transfection and protoplast fusion, but not to fungal species other than the three species mentioned above, even within the genus Cryphonectria, suggesting a very narrow host range. Phenotypic comparison of a few sets of CnCV1-infected and -free isogenic strains showed symptomless infection in new hosts. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2041-1723 11 1 2020 Establishment of Neurospora crassa as a model organism for fungal virology 5627 EN Shinji Honda Faculty of Medical Sciences, University of Fukui Ana Eusebio-Cope Institute of Plant Science and Resources, Okayama University Shuhei Miyashita Graduate School of Agricultural Science, Tohoku University Ayumi Yokoyama Faculty of Medical Sciences, University of Fukui Annisa Aulia Institute of Plant Science and Resources, Okayama University Sabitree Shahi Institute of Plant Science and Resources, Okayama University Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University The filamentous fungus Neurospora crassa is used as a model organism for genetics, developmental biology and molecular biology. Remarkably, it is not known to host or to be susceptible to infection with any viruses. Here, we identify diverse RNA viruses in N. crassa and other Neurospora species, and show that N. crassa supports the replication of these viruses as well as some viruses from other fungi. Several encapsidated double-stranded RNA viruses and capsid-less positive-sense single-stranded RNA viruses can be experimentally introduced into N. crassa protoplasts or spheroplasts. This allowed us to examine viral replication and RNAi-mediated antiviral responses in this organism. We show that viral infection upregulates the transcription of RNAi components, and that Dicer proteins (DCL-1, DCL-2) and an Argonaute (QDE-2) participate in suppression of viral replication. Our study thus establishes N. crassa as a model system for the study of host-virus interactions. The fungus Neurospora crassa is a model organism for the study of various biological processes, but it is not known to be infected by any viruses. Here, Honda et al. identify RNA viruses that infect N. crassa and examine viral replication and RNAi-mediated antiviral responses, thus establishing this fungus as a model for the study of host-virus interactions. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2020 Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer EN Takeshi Koujima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 Respiratory syncytial ウイルス細気管支炎に合併した乳び胸の一例 83 86 EN Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Toshio Shiotani Departments of Thoracic, Breast and Endocrine surgery, Okayama University Hospital Takafumi Sugimine Department of Pediatrics, National Hospital Organization Iwakuni Clinical Center Tadashi Moriwake Department of Pediatrics, National Hospital Organization Iwakuni Clinical Center 　Chylothorax is a condition in which chyle leaks into the thoracic cavity. The causes of chylothorax can be nontraumatic, traumatic or idiopathic. The most common cause of nontraumatic chylothorax is obstruction of the thoracic duct by tumor. Traumatic chylothorax is caused by disruption of the thoracic duct, most often due to cardiac surgery or a thoracic surgical procedure, although in rare cases by cough or vomiting. We report the case of a 3-month-old boy with respiratory syncytial (RS) virus infection who presented with right chylothorax. No obstructive tumor mass was identified in the thoracic duct. Clinical symptoms of Noonan syndrome and Down syndrome, which often accompany lymphatic anomaly, were not found. Therefore, we speculate that his severe cough caused a high thoracic pressure and a disruption of the thoracic duct. He was treated by thoracocentesis and MCT milk. One month later, pleural effusion disappeared and did not recur. RS virus infection might be a rare cause of chylothorax in infants. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 C型肝炎ウイルス（HCV）：RNAゲノムの多様性と変異性 60 67 EN Nobuyuki Kato Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-302X 11 2020 Molecular Characterization of a Novel Polymycovirus From Penicillium janthinellum With a Focus on Its Genome-Associated PASrp 592789 EN Yukiyo Sato Institute of Plant Science and Resources, Okayama University Atif Jamal Crop Diseases Research Institute, National Agricultural Research Centre Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University The genus Polymycovirus of the family Polymycoviridae accommodates fungal RNA viruses with different genomic segment numbers (four, five, or eight). It is suggested that four members form no true capsids and one forms filamentous virus particles enclosing double-stranded RNA (dsRNA). In both cases, viral dsRNA is associated with a viral protein termed "proline-alanine-serine-rich protein" (PASrp). These forms are assumed to be the infectious entity. However, the detailed molecular characteristics of PASrps remain unclear. Here, we identified a novel five-segmented polymycovirus, Penicillium janthinellum polymycovirus 1 (PjPmV1), and characterized its purified fraction form in detail. The PjPmV1 had five dsRNA segments associated with PASrp. Density gradient ultracentrifugation of the PASrp-associated PjPmV1 dsRNA revealed its uneven structure and a broad fractionation profile distinct from that of typical encapsidated viruses. Moreover, PjPmV1-PASrp interacted in vitro with various nucleic acids in a sequence-non-specific manner. These PjPmV1 features are discussed in view of the diversification of genomic segment numbers of the genus Polymycovirus. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0168-8162 30 1-3 2003 Orchid Fleck Virus: Brevipalpus californicus Mite Transmission, Biological Properties and Genome Structure 215 223 EN Hideki Kondo Research Institute for Bioresources, Okayama University Takanori Maeda Research Institute for Bioresources, Okayama University Tetsuo Tamada Research Institute for Bioresources, Okayama University Orchid fleck virus (OFV) causes necrotic or chlorotic ring spots and fleck symptoms in many orchid species world-wide. The virus has non-enveloped, bacilliform particles of about 40 nm × 100–150 nm and is sap-transmissible to several plant species. OFV is transmitted by the mite Brevipalpus californicus (Banks) in a persistent manner and efficiently transmitted by both adults and nymphs, but not by larvae. Viruliferous mites retain their infectivity for 3 weeks on a virus-immune host. The genome of OFV consists of two molecules of 6431 (RNA1) and 6001 nucleotides (RNA2). The RNAs have conserved and complementary terminal sequences. RNA1 contains five open reading frames (ORF), and RNA2 encodes a single ORF. Although some of the encoded proteins of OFV have sequences similar to those of proteins of plant rhabdoviruses, OFV differs from viruses in the family Rhabdoviridae in having a bipartite genome. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 154 1 2008 Identification and characterization of structural proteins of orchid fleck virus 37 45 EN Hideki Kondo Research Institute for Bioresources, Okayama University Takanori Maeda College of Bioresource Sciences, Nihon University Tetsuo Tamada Research Institute for Bioresources, Okayama University Orchid fleck virus (OFV) has a bipartite negative-sense RNA genome with sequence similarities to plant rhabdoviruses. The non-enveloped bullet-shaped particles of OFV are similar to those of the internal ribonucleoprotein (RNP)-M protein structure of rhabdoviruses, but they are about half the size of typical plant rhabdoviruses. Purified preparations contained intact bullet-shaped and filamentous particles. The filamentous particles showed a tightly coiled coil structure or a coiled structure with a helical twist, which resembles the RNP complex of rhabdoviruses. OFV bullet-shaped particles were structurally stable in solutions containing 2% Triton X-100 and 0.8 M NaCl. Western blot analyses revealed that the bullet-shaped particles contained N, P and M proteins, while filamentous particles contained mainly N and P proteins. In addition, a small amount of the L protein was detected in both types of particles. Thus, the structural proteins of OFV have properties similar to those of rhabdoviruses, except that the particles are non-enveloped and are relatively resistant to detergent-treatment under high-salt conditions. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0032-0862 70 1 2020 Pathogenetic roles of beet necrotic yellow vein virus RNA5 in the exacerbation of symptoms and yield reduction, development of scab‐like symptoms, and Rz1‐resistance breaking in sugar beet 219 232 EN Tetsuo Tamada Institute of Plant Science and Resources (IPSR), Okayama University Hirokatsu Uchino Research Center, Nippon Beet Sugar Mfg. Co., Ltd. Toshimi Kusume Hokkaido Central Agricultural Experiment Station Minako Iketani‐Saito Hokkaido Central Agricultural Experiment Station Sotaro Chiba Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika Institute of Plant Science and Resources (IPSR), Okayama University Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Beet necrotic yellow vein virus (BNYVV) generally has a four‐segmented positive‐sense RNA genome (RNAs 1–4), but some European and most Asian strains have an additional segment, RNA5. This study examined the effect of RNA5 and RNA3 on different sugar beet cultivars using a Polymyxa‐mediated inoculation system under field and laboratory conditions. In field tests, the degree of sugar yield served as an index for assessing the virulence of BNYVV strains. Japanese A‐II type isolates without RNA5 caused mostly 15%–90% sugar yield reductions, depending on the susceptibility of sugar beet cultivars, whereas the isolates with RNA5 induced more than 90% yield losses in the seven susceptible cultivars, but small yield losses in one Rz1‐resistant and Rizor cultivars. However, a laboratory‐produced isolate containing RNA5 but lacking RNA3 caused higher yield losses in Rizor than in susceptible plants, and induced scab‐like symptoms on the root surface of both susceptible and resistant plants. In laboratory tests, A‐II type isolates without RNA5 had low viral RNA accumulation levels in roots of Rizor and Rz1‐resistant plants at early stages of infection, but in the presence of RNA5, viral RNA3 accumulation levels increased remarkably. This increased RNA3 accumulation was not observed in roots of the WB42 accession with the Rz2 gene. In contrast, the presence of RNA3 did not affect RNA5 accumulation levels. Collectively, this study demonstrated that RNA5 is involved in the development of scab‐like symptoms and the enhancement of RNA3 accumulation, and suggests these characteristics of RNA5 are associated with Rz1‐resistance breaking. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0168-1702 244 2018 A neo-virus lifestyle exhibited by a (+)ssRNA virus hosted in an unrelated dsRNA virus: Taxonomic and evolutionary considerations 75 83 EN Sakae Hisano Institute of Plant Science and Resources (IPSR), Okayama University Rui Zhang Institute of Plant Science and Resources (IPSR), Okayama University Md. Iqbal Faruk Institute of Plant Science and Resources (IPSR), Okayama University Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Recent studies illustrate that fungi as virus hosts provides a unique platform for hunting viruses and exploring virus/virus and virus/host interactions. Such studies have revealed a number of as-yet-unreported viruses and virus/virus interactions. Among them is a unique intimate relationship between a (+)ssRNA virus, yado-kari virus (YkV1) and an unrelated dsRNA virus, yado-nushi virus (YnV1). YkV1 dsRNA, a replicated form of YkV1, and RNA-dependent RNA polymerase, are trans-encapsidated by the capsid protein of YnV1. While YnV1 can complete its replication cycle, YkV1 relies on YnV1 for its viability. We previously proposed a model in which YkV1 diverts YnV1 capsids as the replication sites. YkV1 is neither satellite virus nor satellite RNA, because YkV1 appears to encode functional RdRp and enhances YnV1 accumulation. This represents a unique mutualistic virus/virus interplay and similar relations in other virus/host fungus systems are detectable. We propose to establish the family Yadokariviridae that accommodates YkV1 and recently discovered viruses phylogenetically related to YkV1. This article overviews what is known and unknown about the YkV1/YnV1 interactions. Also discussed are the YnV1 Phytoreo_S7 and YkV1 2A-like domains that may have been captured via horizontal transfer during the course of evolution and are conserved across extant diverse RNA viruses. Lastly, evolutionary scenarios are envisioned for YkV1 and YnV1. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2058-5276 1 1 2016 A capsidless ssRNA virus hosted by an unrelated dsRNA virus 15001 EN Rui Zhang Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Sakae Hisano Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Akio Tani Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Hideki Kondo Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Satoko Kanematsu NARO Institute of Fruit Tree Science Nobuhiro Suzuki Agrivirology Laboratory, Institute of Plant Science and Resources, Okayama University Viruses typically encode the capsid that encases their genome, while satellite viruses do not encode a replicase and depend on a helper virus for their replication1. Here, we report interplay between two RNA viruses, yado-nushi virus 1 (YnV1) and yado-kari virus 1 (YkV1), in a phytopathogenic fungus, Rosellinia necatrix2. YkV1 has a close phylogenetic affinity to positive-sense, single-stranded (+)ssRNA viruses such as animal caliciviruses3, while YnV1 has an undivided double-stranded (ds) RNA genome with a resemblance to fungal totiviruses4. Virion transfection and infectious full-length cDNA transformation has shown that YkV1 depends on YnV1 for viability, although it probably encodes functional RNA-dependent RNA polymerase (RdRp). Immunological and molecular analyses have revealed trans-encapsidation of not only YkV1 RNA but also RdRp by the capsid protein of the other virus (YnV1), and enhancement of YnV1 accumulation by YkV1. This study demonstrates interplay in which the capsidless (+)ssRNA virus (YkV1), hijacks the capsid protein of the dsRNA virus (YnV1), and replicates as if it were a dsRNA virus. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2372-7705 18 2020 Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression 14 23 EN Terutaka Tanimoto 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 Takeshi Ieda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Nouso Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Morimichi Tani Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Oyama Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Noda Department of Pediatric Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2372-7705 18 2020 Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer 262 271 EN Wataru Ishikawa 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 Toshihiro Ogawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoyasu Tabuchi 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 Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Nishizaki 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 Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 10 1 2020 Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis 14928 EN Ichiro Nojima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Eikawa Department of Hematology/Oncology, Hess Cancer Institute, Icahn School of Medicine At Mount Sinai Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiko Hada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuo Kajitani Department of Internal Medicine, Diabetes Center, Okayama City Hospital Sanae Teshigawara Diabetes Center, Okayama S Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Atsuhito Tone Diabetes Center, Okayama Saiseikai General Hospital Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Heiichiro Udono Department of Immunology, 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 The metabolic changes and dysfunction in CD8+T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8+splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8+splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8+PD-1+T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8+PD-1+T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 2150-7511 11 3 2020 Hadaka Virus 1: a Capsidless Eleven-Segmented Positive-Sense Single-Stranded RNA Virus from a Phytopathogenic Fungus, Fusarium oxysporum e00450-20 EN Yukiyo Sato Institute of Plant Science and Resources, Okayama University Wajeeha Shamsi Institute of Plant Science and Resources, Okayama University Atif Jamal Crop Diseases Research Institute, National Agricultural Research Centre Muhammad Faraz Bhatti Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST) Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University The search for viruses infecting fungi, or mycoviruses, has extended our knowledge about the diversity of RNA viruses, as exemplified by the discovery of polymycoviruses, a phylogenetic group of multisegmented RNA viruses with unusual forms. The genomic RNAs of known polymycoviruses, which show a phylogenetic affinity for animal positive-sense single-stranded RNA [(+)RNA] viruses such as caliciviruses, are comprised of four conserved segments with an additional zero to four segments. The double-stranded form of polymycovirus genomic RNA is assumed to be associated with a virally encoded protein (proline-alanine-serine-rich protein [PASrp]) in either of two manners: a capsidless colloidal form or a filamentous encapsidated form. Detailed molecular characterizations of polymycoviruses, however, have been conducted for only a few strains. Here, a novel polymyco-related virus named Hadaka virus 1 (HadV1), from the phytopathogenic fungus Fusarium oxysporum, was characterized. The genomic RNA of HadV1 consisted of an 11-segmented positive-sense RNA with highly conserved terminal nucleotide sequences. HadV1 shared the three conserved segments with known polymycoviruses but lacked the PASrp-encoding segment. Unlike the known polymycoviruses and encapsidated viruses, HadV1 was not pelleted by conventional ultracentrifugation, possibly due to the lack of PASrp. This result implied that HadV1 exists only as a soluble form with naked RNA. Nevertheless, the 11 genomic segments of HadV1 have been stably maintained through host subculturing and conidiation. Taken together, the results of this study revealed a virus with a potential novel virus lifestyle, carrying many genomic segments without typical capsids or PASrp-associated forms. IMPORTANCE Fungi collectively host various RNA viruses. Examples include encapsidated double-stranded RNA (dsRNA) viruses with diverse numbers of genomic segments (from 1 to 12) and capsidless viruses with nonsegmented (+)RNA genomes. Recently, viruses with unusual intermediate features of an infectious entity between encapsidated dsRNA viruses and capsidless (+)RNA viruses were found. They are called polymycoviruses, which typically have four to eight dsRNA genomic segments associated with one of the virus-encoded proteins and are phylogenetically distantly related to animal (+)RNA caliciviruses. Here, we identified a novel virus phylogenetically related to polymycoviruses, from the phytopathogenic fungus Fusarium oxysporum. The virus, termed Hadaka virus 1 (HadV1), has 11 (+)RNA genomic segments, the largest number in known (+)RNA viruses. Nevertheless, HadV1 lacked a typical structural protein of polymycoviruses and was not pelleted by standard ultracentrifugation, implying an unusual capsidless nature of HadV1. This study reveals a potential novel lifestyle of multisegmented RNA viruses. No potential conflict of interest relevant to this article was reported.

AME Publishing Co. Acta Medica Okayama 2218-676X 9 8 2020 Neurosurgery for brain metastasis from breast cancer 5063 5076 EN Yusuke Tomita Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiko Kurozumi 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 Yosuke Shimazu Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Breast cancer is the most common malignancy among women worldwide, and the main cause of death in patients with breast cancer is metastasis. Metastasis to the central nervous system occurs in 10% to 16% of patients with metastatic breast cancer, and this rate has increased because of recent advancements in systemic chemotherapy. Because of the various treatments available for brain metastasis, accurate diagnosis and evaluation for treatment are important. Magnetic resonance imaging (MRI) is one of the most reliable preoperative examinations not only for diagnosis of metastatic brain tumors but also for estimation of the molecular characteristics of the tumor based on radiographic information such as the number of lesions, solid or ring enhancement, and cyst formation. Surgical resection continues to play an important role in patients with a limited number of brain metastases and a relatively good performance status. A single brain metastasis is a good indication for surgical treatment followed by radiation therapy to obtain longer survival. Surgical removal is also considered for two or more lesions if neurological symptoms are caused by brain lesions of >3 cm with a mass effect or associated hydrocephalus. Although maximal safe resection with minimal morbidity is ideal in the surgical treatment of brain tumors, supramarginal resection can be achieved in select cases. With respect to the resection technique, en bloc resection is generally recommended to avoid leptomeningeal dissemination induced by piecemeal resection. An operating microscope, neuronavigation, and intraoperative neurophysiological monitoring are essential in modern neurosurgical procedures, including tumor resection. More recently, supporting surgical instruments have been introduced. The use of endoscopic surgery has dramatically increased, especially for intraventricular lesions and in transsphenoidal surgery. An exoscope helps neurosurgeons to comfortably operate regardless of patient positioning or anatomy. A tubular retractor can prevent damage to the surrounding brain tissue during surgery and is a useful instrument in combination with both an endoscope and exoscope. Additionally, 5-aminolevulinic acid (5-ALA) is a promising reagent for photodynamic detection of residual tumor tissue. In the near future, novel treatment options such as high-intensity focused ultrasound (HIFU), laser interstitial thermal therapy (LITT), oncolytic virus therapy, and gene therapy will be introduced. No potential conflict of interest relevant to this article was reported.

BMFH Press Acta Medica Okayama 21866953 39 3 2020 Oral administration of the probiotic bacterium Lactobacillus acidophilus strain L-55 modulates the immunological parameters of the laying hen inoculated with a Newcastle disease virus-based live attenuated vaccine 117 122 EN Dung Thi Ho Graduate School of Environmental and Life Science, Okayama University Toshimitsu Hatabu Graduate School of Environmental and Life Science, Okayama University Yosuke Sunada Research & Development, Ohayo Dairy Products Co., Ltd. Yasuhiro Kondo Graduate School of Environmental and Life Science, Okayama University Probiotic supplements containing living bacteria have attracted interest as a potential source of health benefits for humans and livestock. The aim of this study was to determine whether administration of Lactobacillus acidophilus strain L-55 (LaL-55) enhances the immune response among chicks exposed to a Newcastle disease virus (NDV)-based live attenuated vaccine. Oral administration of LaL-55 augmented the elevation in the total numbers of leukocytes and lymphocytes following inoculation with the NDV-based live attenuated vaccine. Monocyte counts increased after LaL-55 administration independent of inoculation with the NDV vaccine. Among chicks that were administered LaL-55, there was a dose-dependent increase in the NK cell activity measured by a 51Cr release assay at 2 weeks after the secondary NDV vaccine inoculation. Two weeks after the secondary inoculation with the NDV vaccine, interferon (IFN)-γ-mRNA expression was significantly elevated in mononuclear splenocytes from chicks that were administered LaL-55. Meanwhile, LaL-55 administration did not change the mRNA levels of IFN-α, IFN-β, and interleukin-1β. These results may suggest that coadministration of LaL-55 with an NDV vaccine augments the immune response against the virus. Therefore, LaL-55 may help protect against viral diseases in poultry. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 22143882 2021 2020 Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer 280 288 EN Nobuyuki Yanagisawa Department of Pathology, St. Marianna University School of Medicine Yokohama-City Seibu Hospital, Yokohama Takefumi Satoh Department of Urology, Kitasato University School of Medicine Ken-ichi Tabata Department of Urology, Kitasato University School of Medicine Hideyasu Tsumura Department of Urology, Kitasato University School of Medicine Yasutomo Nasu Department of Urology, Okayama University Masami Watanabe Department of Urology, Okayama University Timothy C. Thompson Department of Genitourinary Medical Oncology - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center Isao Okayasu Department of Pathology, Kitasato University School of Medicine Yoshiki Murakumo Department of Pathology, Kitasato University School of Medicine Shiro Baba Department of Pathology, Kitasato University School of Medicine Masatsugu Iwamura Department of Urology, Kitasato University School of Medicine ObjectiveCytopathic effects and local immune response were analyzed histologically in prostatic carcinoma (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). MethodsFour high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n = 3) or without neoadjuvant therapy (NT, n = 4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. ResultsssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of ssDNA LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ = 0.656, p < 0.0001) as well as CD4+ T cells and CD20+ B cells (ρ = 0.644, p < 0.0001) in PCa with GT. ConclusionsEnhanced cytopathic effect and local immune response were might be indicated in PCa patients with HSV-tk/GCV gene therapy. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-478X 1 2020 Dicer monitoring in a model filamentous fungus host, Cryphonectria parasitica 100001 EN Annisa Aulia Institute of Plant Science and Resources, Okayama University Midori Tabara Tokyo University of Agriculture and Technology, Department of Applied Biological Sciences Paul Telengech Institute of Plant Science and Resources, Okayama University Toshiyuki Fukuhara Tokyo University of Agriculture and Technology, Department of Applied Biological Sciences Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University The ascomycete Cryphonectria parasitica has served as a model filamentous fungus for studying virus host interactions because of its susceptibility to diverse viruses, its genetic manipulability and the availability of many biological and molecular tools. Cryphonectria prasitica is known to activate antiviral RNA silencing upon infection by some viruses via transcriptional up-regulation of key RNA silencing genes. Here, utilizing a newly developed GFP-based reporter system to monitor dicer-like 2 (dcl2) transcript levels, we show different levels of antiviral RNA silencing activation by different viruses. Some viruses such as mycoreovirus 1, a suppressor-lacking mutant of Cryphonectria hypovirus 1 (CHV1-Δp69) and Rosellinia necatrix partitivirus 11 (RnPV11) highly induced RNA silencing, while others such as CHV3, Rosellinia necatrix victorivirus 1 and RnPV19 did not. There was considerable variation in dcl2 induction by different members within the family Hypoviridae with positive-sense single-stranded RNA genomes or Partitiviridae with double-stranded RNA genomes. Northern blotting and an in vitro Dicer assay developed recently by us using mycelial homogenates validated the reporter assay results for several representative virus strains. Taken together, this study represents a development in the monitoring of Dicer activity in virus-infected C. parasitica. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2213-0071 31 2020 Pediatric airway compromise due to thyroid storm associated with influenza A infection: A case report 101182 EN Taiki Higaki Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takafumi Obara Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Tsuyoshi Nojima Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Hirotsugu Yamamoto Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Takaaki Osako Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Hiromichi Naitou Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Okayama University, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Thyroid storm is a potentially fatal intensification of thyrotoxicosis normally marked by tachycardia, hyperthermia, impaired mental status, and severe agitation. It can be initiated by numerous causes. Failure to promptly diagnose the condition may lead to high mortality. Early diagnosis and treatment of thyroid storm are essential to prevent further life-threatening complications. A 10-year-old girl was admitted to our emergency center for intensive care. The patient presented tachypnea with stridor, paradoxical abdominal breathing, and “barking” cough. The patient was diagnosed as upper airway obstruction complicated by thyroid storm associated with influenza infection. Following immediate airway management, the patient was administered a short-acting beta-blocker, hydrocortisone, thiamazole, and saturated solution of potassium iodide was initiated. The patient was extubated on day 8 and transferred to a local hospital on day 11 without adverse complications. When examining patients with influenza infection, emergency doctors should be more attentive not to miss other critical diagnoses. The present case was initially diagnosed as croup due to influenza infection. Sharing our experience may help emergency physicians treat similar cases of pediatric airway compromise due to thyroid storm. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 4 2020 Decreased Serum Antioxidant Marker is Predictive of Early Recurrence in the Same Segment after Radical Ablation for Hepatocellular Carcinoma 275 283 EN Taiko Muro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Nakamura Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Onishi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yasunaka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Oyama Department of Gastroenterology and Hepatology, 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 Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/60364 Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a promising method for controlling tumors, although it does not entirely eliminate recurrence. Oxidative stress is associated with the progression of hepatocarcinogenesis, while also acting as an anticancer response. The objective of the present study was to investigate the factors influencing post-RFA outcomes. We recruited 235 newly diagnosed HCC patients who received RFA for single tumors. The patients with recurrence were sub-grouped into early and segmental recurrence groups. The characteristics of the sub-grouped patients were evaluated, including by measuring oxidative stress marker reactive oxygen metabolites and antioxidant marker OXY-adsorbent tests. The factors associated with poor survival were a high Child-Pugh score and early recurrence within 2 years in the same segment. The patients who experienced recurrence within 2 years in the same segment showed a larger tumor diameter than did others. According to a multivariate analysis, the OXY values were also significantly low in these patients. In conclusion, maintaining the antioxidant reservoir function with a high OXY value might be necessary to prevent early recurrence within the RFA-treated segment. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-302X 11 2020 Diverse Partitiviruses From the Phytopathogenic Fungus,Rosellinia necatrix 1064 EN Paul Telengech Institute of Plant Science and Resources, Okayama University Sakae Hisano Institute of Plant Science and Resources, Okayama University Cyrus Mugambi Institute of Plant Science and Resources, Okayama University Kiwamu Hyodo Institute of Plant Science and Resources, Okayama University Juan Manuel Arjona-Lopez Institute of Plant Science and Resources, Okayama University Carlos Jose Lopez-Herrera Institute for Sustainable Agriculture,Spanish Research Council Satoko Kanematsu Institute of Fruit Tree Science, National Agriculture and Food Research Organization (NARO) Hideki Kondo Institute of Plant Science and Resources, Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources, Okayama University Partitiviruses (dsRNA viruses, familyPartitiviridae) are ubiquitously detected in plants and fungi. Although previous surveys suggested their omnipresence in the white root rot fungus,Rosellinia necatrix, only a few of them have been molecularly and biologically characterized thus far. We report the characterization of a total of 20 partitiviruses from 16R. necatrixstrains belonging to 15 new species, for which "Rosellinia necatrix partitivirus 11-Rosellinia necatrix partitivirus 25" were proposed, and 5 previously reported species. The newly identified partitiviruses have been taxonomically placed in two genera,Alphapartitivirus, andBetapartitivirus. Some partitiviruses were transfected into reference strains of the natural host,R. necatrix, and an experimental host,Cryphonectria parasitica, using purified virions. A comparative analysis of resultant transfectants revealed interesting differences and similarities between the RNA accumulation and symptom induction patterns ofR. necatrixandC. parasitica. Other interesting findings include the identification of a probable reassortment event and a quintuple partitivirus infection of a single fungal strain. These combined results provide a foundation for further studies aimed at elucidating mechanisms that underly the differences observed. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2372-7705 17 2020 Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer 107 117 EN Takeshi Koujima 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 Takeshi Ieda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Araki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuro Fushimi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma Hiroyuki Mizuguchi Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pancreatic ductal adenocarcinoma (PDAC) cells have an exceptional ability to invade nerves through pronounced crosstalk between nerves and cancer cells; however, the mechanism of PDAC cell invasion remains to be elucidated. Here, we demonstrate the therapeutic potential of telomerase-specific oncolytic adenoviruses, OBP -301 and tumor suppressor p53-armed OBP-702, against human PDAC cells. Highly invasive PDAC cells exhibited higher levels of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression independent of KRAS expression; ERK1/2 inhibitor or small interfering RNA (siRNA) treatment significantly reduced the migration and invasion of PDAC cells, suggesting that the ERK signaling pathway is associated with the invasiveness of PDAC cells. OBP-702 infection suppressed ERK signaling and inhibited PDAC cell migration and invasion more efficiently than OBP-301. OBP-702 also effectively inhibited PDAC cell invasion even when invasiveness was enhanced by administration of motility stimulators, such as nerve and neurosecretory factors. Moreover, noninvasive whole-body imaging analyses showed that OBP-702 significantly suppressed tumor growth in an orthotopic PDAC xenograft model, although both viruses were equally effective against subcutaneous tumors, suggesting that OBP-702 can influence the orthotopic tumor microenvironment. Our data suggest that oncolytic virus-mediated disruption of ERK signaling is a promising antitumor strategy for attenuating the invasiveness of PDAC cells. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 0893-3952 33 12 2020 Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer 2437 2448 EN Tomoka Ikeda Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Okayama University Graduate School of Health Sciences Misa Sakamoto Okayama University Graduate School of Health Sciences Tomoyasu Tachibana Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital Asami Nishikori Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 3 2020 Intravenous Vitamin C as Ancillary Treatment for Cranial Polyneuritis and Meningitis due to Varicella Zoster Virus Reactivation 257 260 EN Takashi Hongo Department of Emergency Medicine, Okayama Saiseikai General Hospital Fusao Ikeda Department of Internal Medicine, Okayama Saiseikai General Hospital Shinichi Fujioka Department of Internal Medicine, Okayama Saiseikai General Hospital Riku Akatsuka Department of Internal Medicine, Okayama Saiseikai General Hospital Tosifumi Fujiwara Department of Emergency Medicine, Okayama Saiseikai General Hospital Kazuhide Yamamoto Department of Internal Medicine, Okayama Saiseikai General Hospital Case Report 10.18926/AMO/59960 A 65-year-old Japanese woman developed vesicular eruptions on her right ear due to varicella zoster virus (VZV) reactivation, followed by cranial polyneuritis and meningitis affecting her right cranial nerves V, VII, VIII, IX, and X. After acyclovir administration, her facial paralysis worsened. Intravenous methylprednisolone and vitamin C were administered on Day 4 post-admission. Her symptoms steadily improved, and by Day 45 she had fully recovered. Cranial polyneuritis is a rare complication of VZV reactivation, and there is no established method of treatment. This is the first report of full recovery from cranial polyneuritis using intravenous vitamin C as ancillary treatment. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 12 2 2020 Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy EN Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Joe Hasei Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuya Yano Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic 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 Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas. No potential conflict of interest relevant to this article was reported.

Frontiers Media Acta Medica Okayama 1664-302X 11 2020 Virome Analysis of Aphid Populations That Infest the Barley Field: The Discovery of Two Novel Groups of Nege/Kita-Like Viruses and Other Novel RNA Viruses 509 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Miki Fujita Institute of Plant Science and Resources (IPSR), Okayama University Hiroshi Hisano Institute of Plant Science and Resources (IPSR), Okayama University Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika College of Plant Health and Medicine, Qingdao Agricultural University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Aphids (order Hemiptera) are important insect pests of crops and are also vectors of many plant viruses. However, little is known about aphid-infecting viruses, particularly their diversity and relationship to plant viruses. To investigate the aphid viromes, we performed deep sequencing analyses of the aphid transcriptomes from infested barley plants in a field in Japan. We discovered virus-like sequences related to nege/kita-, flavi-, tombus-, phenui-, mononega-, narna-, chryso-, partiti-, and luteoviruses. Using RT-PCR and sequence analyses, we determined almost complete sequences of seven nege/kitavirus-like virus genomes; one of which was a variant of the Wuhan house centipede virus (WHCV-1). The other six seem to belong to four novel viruses distantly related to Wuhan insect virus 9 (WhIV-9) or Hubei nege-like virus 4 (HVLV-4). We designated the four viruses as barley aphid RNA virus 1 to 4 (BARV-1 to -4). Moreover, some nege/kitavirus-like sequences were found by searches on the transcriptome shotgun assembly (TSA) libraries of arthropods and plants. Phylogenetic analyses showed that BARV-1 forms a clade with WHCV-1 and HVLV-4, whereas BARV-2 to -4 clustered with WhIV-9 and an aphid virus, Aphis glycines virus 3. Both virus groups (tentatively designated as Centivirus and Aphiglyvirus, respectively), together with arthropod virus-like TSAs, fill the phylogenetic gaps between the negeviruses and kitaviruses lineages. We also characterized the flavi/jingmen-like and tombus-like virus sequences as well as other RNA viruses, including six putative novel viruses, designated as barley aphid RNA viruses 5 to 10. Interestingly, we also discovered that some aphid-associated viruses, including nege/kita-like viruses, were present in different aphid species, raising a speculation that these viruses might be distributed across different aphid species with plants being the reservoirs. This study provides novel information on the diversity and spread of nege/kitavirus-related viruses and other RNA viruses that are associated with aphids. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 23290501 17 2020 Hair cell transduction efficiency of single- and dual-AAV serotypes in adult murine cochleae 1167 1177 EN Ryotaro Omichi Department of Otolaryngology–Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidekane Yoshimura Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa Seiji B. Shibata Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa Luk H. Vandenberghe Grousbeck Gene Therapy Center, Ocular Genomics Institute, Schepens Eye Research Institute and Mass Eye and Ear Richard J.H. Smith Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 01604120 138 2020 Enhanced expression of nicotinamide nucleotide transhydrogenase (NNT) and its role in a human T cell line continuously exposed to asbestos 105654 EN Shoko Yamamoto Department of Hygiene, Kawasaki Medical School Suni Lee Department of Hygiene, Kawasaki Medical School Hidenori Matsuzaki Department of Life Science, Faculty of Life and Environmental Science, Prefectural University of Hiroshima Naoko Kumagai-Takei Department of Hygiene, Kawasaki Medical School Kei Yoshitome Department of Hygiene, Kawasaki Medical School Nagisa Sada Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yurika Shimizu Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tastsuo Ito Department of Hygiene, Kawasaki Medical School Yasumitsu Nishimura Department of Hygiene, Kawasaki Medical School Takemi Otsuki Department of Hygiene, Kawasaki Medical School The effects of asbestos fibers on human immune cells have not been well documented. We have developed a continuously exposed cell line model using the human T-lymphotropic virus 1 (HTLV-1)-immortalized human T cell line MT-2. Sublines continuously exposed to chrysotile (CH) or crocidolite (CR) showed acquired resistance to asbestos-induced apoptosis following transient and high-dose re-exposure with fibers. These sublines in addition to other immune cells such as natural killer cells or cytotoxic T lymphocytes exposed to asbestos showed a reduction in anti-tumor immunity. In this study, the expression of genes and molecules related to antioxidative stress was examined. Furthermore, complexes related to oxidative phosphorylation were investigated since the production of reactive oxygen species (ROS) is important when considering the effects of asbestos in carcinogenesis and the mechanisms involved in resistance to asbestos-induced apoptosis. In sublines continuously exposed to CH or CR, the expression of thioredoxin decreased. Interestingly, nicotinamide nucleotide transhydrogenase (NNT) expression was markedly enhanced. Thus, knockdown of NNT was then performed. Although the knockdown clones did not show any changes in proliferation or occurrence of apoptosis, these clones showed recovery of ROS production with returning NADPH/NADP+ ratio that increased with decreased production of ROS in continuously exposed sublines. These results indicated that NNT is a key factor in preventing ROS-induced cytotoxicity in T cells continuously exposed to asbestos. Considering that these sublines showed a reduction in anti-tumor immunity, modification of NNT may contribute to recovery of the anti-tumor effects in asbestos-exposed T cells. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 01466615 92 12 2020 The aim of the measurement of Epstein‐Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites 3689 3696 EN Tomoko Miyake Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiji Iwatsuki Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoji Hirai Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takenobu Yamamoto Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihisa Hamada Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyasu Fujii Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideaki mamura Department of Pediatrics, Faculty of Medicine, University of Miyazaki Shin Morizane Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Epstein‐Barr virus (EBV) DNA load in the blood increases in posttransplant lymphoproliferative disorders and chronic active EBV infection. In this report, we analyzed the EBV DNA load in the peripheral blood mononuclear cells (PBMCs) and plasma of patients with hydroa vacciniforme (HV) and/or hypersensitivity to mosquito bites (HMB) to understand the clinical significance of EBV DNA load. All 30 patients showed high DNA loads in the PBMCs over the cut‐off level. Of 16 plasma samples, extremely high in two samples obtained from patients with hemophagocytic lymphohistiocytosis (HLH). The amount of cell‐free DNA in plasma was correlated to the serum levels of lactate dehydrogenase and inversely correlated to platelet counts. These results indicate that the EBV DNA load in PBMCs can provide one of the diagnostic indicators for HV and HMB and marked elevation of cell‐free EBV DNA in plasma might be related to cytolysis such as that observed in HLH. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 12 2 2020 Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies 335 EN Takashi Oka Department of Hematology, Oncology & Respiratory Med., Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken-Ichi Matsuoka Department of Hematology, Oncology & Respiratory Med., Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atae Utsunomiya Department of Hematology, Imamura General Hospital Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoratic Tissue Research Acta Medica Okayama 1346-4280 59 2 2019 A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects 64 6471 EN Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Veterinary Science Acta Medica Okayama 0916-7250 81 8 2019 Risk assessment for hepatitis E virus infection from domestic pigs introduced into an experimental animal facility in a medical school 1191 1196 EN Hirohito Ogawa Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Hirayama Department of Animal Resources, Advanced Science Research Center, Okayama University Satsuki Tanaka Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norio Yata Department of Animal Resources, Advanced Science Research Center, Okayama University Hikaru Namba Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuko Yamashita Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenzo Yonemitsu Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University Ken Maeda Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University Katsumi Mominoki Department of Animal Resources, Advanced Science Research Center, Okayama University Masao Yamada Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Hepatitis E virus (HEV) is known to cause zoonotic infections from pigs, wild boars and deer. Domestic pigs have been used as an experimental animal model in medical research and training; however, the risks of HEV infection from pigs during animal experiments are largely unknown. Here, we retrospectively investigated the seroprevalence and detection rates of viral RNA in 73 domestic pigs (average 34.5 kg) introduced into an animal experimental facility in a medical school during 2012-2016. We detected anti-HEV immunoglobulin G antibodies in 24 of 73 plasma samples (32.9%), though none of the samples were positive for viral RNA. Plasma samples of 18 pigs were sequentially monitored and were classified into four patterns: sustained positive (5 pigs), sustained negative (5 pigs), conversion to positive (6 pigs) and conversion to negative (2 pigs). HEV genomes were detected in 2 of 4 liver samples from pigs that were transported from the same farm during 2016-2017. Two viral sequences of the overlapping open reading frame (ORF) 2/3 region (97 bp) were identical and phylogenetically fell into genotype 3. A 459-bp length of the ORF2 region of an amplified fragment from a pig transported in 2017 was clustered with the wbJYG1 isolate (subgenotype 3b) with 91.5% (420/459 bp) nucleotide identity. Based on our results, we suggest that domestic pigs introduced into animal facilities carry a potential risk of HEV infection to researchers, trainees and facility staff. Continuous surveillance and precautions are important to prevent HEV infection in animal facilities. No potential conflict of interest relevant to this article was reported.

Microbiology Society Acta Medica Okayama 0022-1317 100 9 2019 ICTV Virus Taxonomy Profile: Megabirnaviridae 1269 1270 EN Yukiyo Sato Institute of Plant Science and Resources, Okayama University Naoyuki Miyazaki Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba Satoko Kanematsu National Agriculture and Food Research Organization (NARO) Headquarters Jiatao Xie College of Plant Science and Technology, Huazhong Agricultural University Said A. Ghabrial Department of Plant Pathology, University of Kentucky Bradley I. Hillman Department of Plant Biology and Pathology, Rutgers University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Megabirnaviridae is a family of non-enveloped spherical viruses with dsRNA genomes of two linear segments, each of 7.2-8.9 kbp, comprising 16.1 kbp in total. The genus Megabirnavirus includes the species Rosellinia necatrix megabirnavirus 1, the exemplar isolate of which infects the white root rot fungus (Rosellinia necatrix) to which it confers hypovirulence. Megabirnaviruses are characterized by their bisegmented genome with large 5'-untranslated regions (1.6 kb) upstream of both 5'-proximal coding strand ORFs, and large protrusions on the particle surface. This is a summary of the ICTV Report on the family Megabirnaviridae, which is available at ictv.global/report/megabirnaviridae. No potential conflict of interest relevant to this article was reported.

Humana Press Acta Medica Okayama 2014 Detection and analysis of non-retroviral RNA virus-like elements in plant, fungal, and insect genomes. 73 88 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR)Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Endogenous non-retroviral RNA like sequences (NRVSs) have been discovered in the genome of a wide range of eukaryotes. These are considered as fossil RNA viral elements integrated into host genomes by as-yet-known mechanisms, and in many cases, those fossils are estimated to be millions-of-years-old. It is likely that the number of NRVS records will increase rapidly due to the growing availability of whole-genome sequences for many kinds of eukaryotes. Discovery of the novel NRVSs and understanding of their phylogenetic relationship with modern viral relatives provide important information on deep evolutionary history of RNA virus-host interactions. In this chapter, therefore, the common strategies for the identification and characterization of endogenous NRVSs from plants, insects, and fungi are described. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1345-2630 79 5 2013 Biological and genetic diversity of plasmodiophorid-transmitted viruses and their vectors 307 320 EN Tetsuo Tamada Institute of Plant Science and Resources (IPSR)Okayama University Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University About 20 species of viruses belonging to five genera, Benyvirus, Furovirus, Pecluvirus, Pomovirus and Bymovirus, are known to be transmitted by plasmodiophorids. These viruses have all positive-sense, single-stranded RNA genomes that consist of two to five RNA components. Three species of plasmodiophorids are recognized as vectors: Polymyxa graminis, P. betae, and Spongospora subterranea. The viruses can survive in soil within the long-lived resting spores of the vector. There are biological and genetic variations in both virus and vector species. Many of the viruses are causal agents of important diseases in major crops such as rice, wheat, barley, rye, sugar beet, potato, and groundnut. Control is dependent on the development of resistant cultivars. During the last half century, several virus diseases have rapidly spread worldwide. For six major virus diseases, we address their geographical distribution, diversity, and genetic resistance. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 159 1 2013 Complete genome sequence of Habenaria mosaic virus, a new potyvirus infecting a terrestrial orchid (Habenaria radiata) in Japan 163 166 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Takanori Maeda College of Bioresource SciencesNihon University I Wayan Gara Institute of Plant Science and Resources (IPSR)Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR)Okayama University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR)Okayama University Tetsuo Tamada Institute of Plant Science and Resources (IPSR)Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University The complete genomic sequence of Habenaria mosaic virus (HaMV), which infects terrestrial orchids (Habenaria radiata), has been determined. The genome is composed of 9,499 nucleotides excluding the 3'-terminal poly(A) tail, encoding a large polyprotein of 3,054 amino acids with the genomic features typical of a potyvirus. Putative proteolytic cleavage sites were identified by sequence comparison to those of known potyviruses. The HaMV polyprotein showed 58 % amino acid sequence identity to that encoded by the most closely related potyvirus, tobacco vein banding mosaic virus. Phylogenetic analysis of the polyprotein amino acid sequence and its coding sequences confirmed that HaMV formed a cluster with the chilli veinal mottle virus group, most of which infect solanaceous plants. These results suggest that HaMV is a distinct member of the genus Potyvirus. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0304-8608 160 8 2015 Cymbidium chlorotic mosaic virus, a new sobemovirus isolated from a spring orchid (Cymbidium goeringii) in Japan. 2099 104 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Shogo Takemoto Institute of Plant Science and Resources (IPSR)Okayama University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR)Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR)Okayama University Ida Bagus Andika Institute of Plant Science and Resources (IPSR)Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Cymbidium chlorotic mosaic virus (CyCMV), isolated from a spring orchid (Cymbidium goeringii), was characterized molecularly. CyCMV isometric virions comprise a single, positive-strand RNA genome of 4,083 nucleotides and 30-kDa coat protein. The virus genome contains five overlapping open reading frames with a genomic organization similar to that of sobemoviruses. BLAST searches and phylogenetic analysis revealed that CyCMV is most closely related to papaya lethal yellowing virus, a proposed dicot-infecting sobemovirus (58.8 % nucleotide sequence identity), but has a relatively distant relationship to monocot-infecting sobemoviruses, with only modest sequence identities. This suggests that CyCMV is a new monocot-infecting member of the floating genus Sobemovirus. No potential conflict of interest relevant to this article was reported.

John Wiley & Sons Acta Medica Okayama 24750328 3 4 2019 Multidisciplinary oncolytic virotherapy for gastrointestinal cancer 396 404 EN Toshiyoshi Fujiwara Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Replication-selective tumor-specific viruses represent a novel approach for treating neoplastic diseases. These vectors are designed to induce virus-mediated lysis of tumor cells after selective intracellular virus propagation. For targeting cancer cells, the use of tissue- or cell-specific promoters that are expressed in diverse tumor types but silent in normal cells is required. Human telomerase is highly active in more than 85% of primary cancers, regardless of tissue origin, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (telomelysin, OBP-301) in which the hTERT promoter element drives expression of E1 genes. As only tumor cells that express the telomerase can activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication and oncolytic cell death. Upon US Food and Drug Administration approval, a phase 1 dose-escalation study of intratumoral injection of telomelysin for various solid tumors has been completed to confirm the safety, tolerability, and feasibility of the agent. Moreover, we found that adenoviral E1B 55-kDa protein in telomelysin inhibits the radiation-induced DNA repair machinery. Thus, tumor cells infected with telomelysin could be rendered sensitive to ionizing radiation. Recently, we assessed the safety and efficacy of intratumoral injection of telomelysin with radiotherapy in esophageal cancer patients not suited for standard treatments. This review highlights some very promising clinical advances in cancer therapeutic technologies using telomerase-specific oncolytic virotherapy. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2019 Oncolytic Herpes Virus Armed with Vasculostatin in Combination with Bevacizumab Abrogates Glioma Invasion via the CCN1 and AKT Signaling Pathways EN Yusuke Tomita Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Elsevier Science Acta Medica Okayama 01681702 177 1 2013 Characterization of burdock mottle virus, a novel member of the genus Benyvirus, and the identification of benyvirus-related sequences in the plant and insect genomes. 75 86 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Shuichi Hirano Institute of Plant Science and Resources (IPSR), Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences Makoto Hirai Department of Parasitology, Graduate School of Medicine, Gunma University Takanori Maeda Formerly College of Bioresource Sciences, Nihon University Tetsuo Tamada Institute of Plant Science and Resources (IPSR), Okayama University The complete nucleotide sequence of the burdock mottle virus (BdMoV) isolated from an edible burdock plant (Arctium lappa) in Japan has been determined. BdMoV has a bipartite genome, whose organization is similar to RNA1 and RNA2 of benyviruses, beet necrotic yellow vein virus (BNYVV), beet soil-borne mosaic virus (BSBMV), and rice stripe necrosis virus (RSNV). BdMoV RNA1 (7038 nt) contains a single open reading frame (ORF) encoding a 249-kDa polypeptide that consists of methyl-transferase, helicase, papain-like protease, AlkB-like, and RNA-dependent RNA polymerase domains. The AlkB-like domain sequence is not present in the proteins encoded by other known benyviruses, but is found in replication-associated proteins of viruses mainly belonging to the families Alfaflexiviridae and Betaflexiviridae. BdMoV RNA2 (4315 nt) contains six ORFs that are similar to those of benyviruses: these are coat protein (CP), CP readthrough, triple gene block movement and cysteine-rich proteins. Phylogenetic analyses showed that BdMoV is more closely related to BNYVV and BSBMV than to RSNV. Database searches showed that benyvirus replicase-related sequences are present in the chromosomes of a chickpea plant (Cicer arietinum) and a blood-sucking insect (Rhodnius prolixus). Some other benyvirus-related sequences are found in the transcriptome shotgun libraries of a few species of plants and a bark beetle. Our results show that BdMoV is a distinct species of the genus Benyvirus and that ancestral and extant benyviruses may have infected or currently infect a wide range of hosts, including plants and insects. No potential conflict of interest relevant to this article was reported.

Elsevier Science Acta Medica Okayama 01681702 213 2016 Sequence and phylogenetic analyses of novel totivirus-like double-stranded RNAs from field-collected powdery mildew fungi 353 364 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Sakae Hisano Institute of Plant Science and Resources (IPSR), Okayama University Sotaro Chiba Institute of Plant Science and Resources (IPSR), Okayama University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika Institute of Plant Science and Resources (IPSR), Okayama University Kazuhiro Toyoda Graduate School of Environmental and Life Science, Okayama University Fumihiro Fujimori Department of Environmental Education, Tokyo Kasei University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University The identification of mycoviruses contributes greatly to understanding of the diversity and evolutionary aspects of viruses. Powdery mildew fungi are important and widely studied obligate phytopathogenic agents, but there has been no report on mycoviruses infecting these fungi. In this study, we used a deep sequencing approach to analyze the double-stranded RNA (dsRNA) segments isolated from field-collected samples of powdery mildew fungus-infected red clover plants in Japan. Database searches identified the presence of at least ten totivirus (genus Totivirus)-like sequences, termed red clover powdery mildew-associated totiviruses (RPaTVs). The majority of these sequences shared moderate amino acid sequence identity with each other (<44%) and with other known totiviruses (<59%). Nine of these identified sequences (RPaTV1a, 1b and 2-8) resembled the genome of the prototype totivirus, Saccharomyces cerevisiae virus-L-A (ScV-L-A) in that they contained two overlapping open reading frames (ORFs) encoding a putative coat protein (CP) and an RNA dependent RNA polymerase (RdRp), while one sequence (RPaTV9) showed similarity to another totivirus, Ustilago maydis virus H1 (UmV-H1) that encodes a single polyprotein (CP-RdRp fusion). Similar to yeast totiviruses, each ScV-L-A-like RPaTV contains a -1 ribosomal frameshift site downstream of a predicted pseudoknot structure in the overlapping region of these ORFs, suggesting that the RdRp is translated as a CP-RdRp fusion. Moreover, several ScV-L-A-like sequences were also found by searches of the transcriptome shotgun assembly (TSA) libraries from rust fungi, plants and insects. Phylogenetic analyses show that nine ScV-L-A-like RPaTVs along with ScV-L-A-like sequences derived from TSA libraries are clustered with most established members of the genus Totivirus, while one RPaTV forms a new distinct clade with UmV-H1, possibly establishing an additional genus in the family. Taken together, our results indicate the presence of diverse, novel totiviruses in the powdery mildew fungus populations infecting red clover plants in the field. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 24056502 16 2019 Effect of intravenous immunoglobulin therapy on anti-NT5C1A antibody-positive inclusion body myositis after successful treatment of hepatitis C: A case report 100204 EN Motonori Takamiya Department of Neurology, Kagawa Prefectural Central Hospital Yoshiaki Takahashi Department of Neurology, Kagawa Prefectural Central Hospital Mizuki Morimoto Department of Neurology, Kagawa Prefectural Central Hospital Nobutoshi Morimoto Department of Neurology, Kagawa Prefectural Central Hospital Satoshi Yamashita Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Inclusion body myositis (IBM) is the commonest idiopathic inflammatory myopathy of older persons. Pathophysiological mechanism of IBM remains unknown; however, an association of IBM with chronic hepatitis C virus (HCV) infection and serum autoantibodies against skeletal muscle protein 5′-nucleotidase 1A (NT5C1A) has recently been reported. No effective treatment for IBM has yet been developed. We here present a 70-year-old man who was anti-NT5C1A antibody-positive in association with IBM and chronic hepatitis C. The initial treatment of ombitasvir/paritaprevir/ritonavir for his chronic hepatitis C was successful; however, his symptoms of IBM did not improve. On the contrary, his quadriplegic paralysis became more severe and he developed dysphagia. Next, steroid pulse therapy was initiated for IBM and, although his hyper-creatine phosphokinase-emia improved, his symptoms did not; indeed, they worsened. Subsequent intravenous immunoglobulin therapy (IVIg) resulted in obvious improvement in his dysphagia. Thereafter IVIg therapy was repeated at approximately 2-monthly intervals. His dysphagia remained improved for more than 1 year; however, his quadriplegia continued to progress slowly. Although IBM can reportedly be associated with hepatitis C, we inferred that there was no direct relationship between these conditions in our patient because his IBM did not improve after treatment of his hepatitis C. Although his IBM-associated quadriplegia did not improve, IVIg therapy did result in improvement in his dysphagia. No potential conflict of interest relevant to this article was reported.

Academic Press Acta Medica Okayama 00426822 533 2019 Two novel fungal negative-strand RNA viruses related to mymonaviruses and phenuiviruses in the shiitake mushroom (Lentinula edodes) 125 136 EN Yu-Hsin Lin Institute of Plant Science and Resources (IPSR), Okayama University Miki Fujita Institute of Plant Science and Resources (IPSR), Okayama University Sotaro Chiba Graduate School of Bioagricultural Sciences, Nagoya University Kiwamu Hyodo Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika Institute of Plant Science and Resources (IPSR), Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Abstract There is still limited information on the diversity of (−)ssRNA viruses that infect fungi. Here, we have discovered two novel (−)ssRNA mycoviruses in the shiitake mushroom (Lentinula edodes). The first virus has a monopartite RNA genome and relates to that of mymonaviruses (Mononegavirales), especially to Hubei rhabdo-like virus 4 from arthropods and thus designated as Lentinula edodes negative-strand RNA virus 1. The second virus has a putative bipartite RNA genome and is related to the recently discovered bipartite or tripartite phenui-like viruses (Bunyavirales) associated with plants and ticks, and designated as Lentinula edodes negative-strand RNA virus 2 (LeNSRV2). LeNSRV2 is likely the first segmented (−)ssRNA virus known to infect fungi. Its smaller RNA segment encodes a putative nucleocapsid and a plant MP-like protein using a potential ambisense coding strategy. These findings enhance our understanding of the diversity, evolution and spread of (−)ssRNA viruses in fungi. No potential conflict of interest relevant to this article was reported.

Elsevier Science Acta Medica Okayama 01681702 262 2019 A novel insect-infecting virga/nege-like virus group and its pervasive endogenization into insect genomes 37 47 EN Hideki Kondo Institute of Plant Science and Resources (IPSR), Okayama University Sotaro Chiba Asian Satellite Campuses Institute, Nagoya University Kazuyuki Maruyama Institute of Plant Science and Resources (IPSR), Okayama University Ida Bagus Andika Institute of Plant Science and Resources (IPSR), Okayama University Nobuhiro Suzuki Institute of Plant Science and Resources (IPSR), Okayama University Insects are the host and vector of diverse viruses including those that infect vertebrates, plants, and fungi. Recent wide-scale transcriptomic analyses have uncovered the existence of a number of novel insect viruses belonging to an alphavirus-like superfamily (virgavirus/negevirus-related lineage). In this study, through an in silico search using publicly available insect transcriptomic data, we found numerous virus-like sequences related to insect virga/nege-like viruses. Phylogenetic analysis showed that these novel viruses and related virus-like sequences fill the major phylogenetic gaps between insect and plant virga/negevirus lineages. Interestingly, one of the phylogenetic clades represents a unique insect-infecting virus group. Its members encode putative coat proteins which contained a conserved domain similar to that usually found in the coat protein of plant viruses in the family Virgaviridae. Furthermore, we discovered endogenous viral elements (EVEs) related to virga/nege-like viruses in the insect genomes, which enhances our understanding on their evolution. Database searches using the sequence of one member from this group revealed the presence of EVEs in a wide range of insect species, suggesting that there has been prevalent infection by this virus group since ancient times. Besides, we present detailed EVE integration profiles of this virus group in some species of the Bombus genus of bee families. A large variation in EVE patterns among Bombus species suggested that while some integration events occurred after the species divergence, others occurred before it. Our analyses support the view that insect and plant virga/nege-related viruses might share common virus origin(s). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Sudden, Sharp Turn in an AIDS Patient’s Course Following the Onset of Fulminant Type 1 Diabetes 263 267 EN Yuichiro Shimoyama Department of Intensive Care Unit, Osaka Medical College Hospital Osamu Umegaki Department of Intensive Care Unit, Osaka Medical College Hospital Yukimasa Ooi Department of Internal Medicine, Osaka Medical College Hospital Sho Shigemoto Department of Internal Medicine, Osaka Medical College Hospital Tomoyuki Agui Department of Surgery, Osaka Medical College Hospital Noriko Kadono Department of Intensive Care Unit, Osaka Medical College Hospital Toshiaki Minami Department ofAnesthesiology, Osaka Medical College Hospital Case Report 10.18926/AMO/56870 A previously healthy 40-year-old Japanese male was urgently admitted with a 2-month history of dysphagia, 30-kg weight loss, and fever. Human immunodeficiency virus (HIV) antibodies and cytomegalovirus antigenemia were positive. Pneumocystis pneumonia and cytomegalovirus pneumonia were suspected. The patient was diagnosed with acquired immune deficiency syndrome (AIDS). Cytomegalovirus antigenemia became negative 20 days after the positive result. On hospital day 41, he experienced cardiopulmonary arrest. The clinical diagnosis was fulminant type 1 diabetes mellitus. He later developed hypoglycemia and was diagnosed with adrenal insufficiency accompanied by septic shock. He died of multiple organ failure 29 h post-admission to our ICU. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2019 Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice EN Kazuki Hatayama Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2019 Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response EN Hirotaka Imai Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 130 3 2018 東アジアと中南米にみられるEBウイルス関連T/NKリンパ増殖異常症：種痘様水疱症と蚊刺過敏症を中心に 123 128 EN Keiji Iwatsuki Professor of Special Mission （Research）, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Conventional-dose Versus Half-dose Sulfamethoxazole-trimethoprim for the Prophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Disease: A Non-blind, Randomized Controlled Trial 85 89 EN Yoshiyuki Abe Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Kazutoshi Fujibayashi Medical Technology Innovation Center, Juntendo University Yuji Nishizaki Medical Technology Innovation Center, Juntendo University Naotake Yanagisawa Medical Technology Innovation Center, Juntendo University Shuko Nojiri Clinical Research and Trial Center, Juntendo University Hospital Soichiro Nakano Geriatric General Medicine, Juntendo Tokyo Koto Geriatric Medical Center Kurisu Tada Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Ken Yamaji Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Naoto Tamura Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Clinical Study Protocol 10.18926/AMO/56464 Pneumocystis pneumonia (PCP) due to Pneumocystis jirovecii infection is the leading cause of fatal opportunistic infections in immunocompromised patients. We will determine whether a daily sulfamethoxazole-trimethoprim (SMX/TMP) dose of 200/40 mg was non-inferior to 400/80 mg for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. This is a randomized, open-label, multicenter controlled trial. The primary outcome is the rate of PCP prevention at 52 weeks. The secondary outcome is the discontinuation rate of SMX/TMP. The trial will evaluate the optimal dose of SMX/TMP for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 1 2019 Predictive Factors for Successful Vaccination Against Hepatitis B Surface Antigen in Patients Who Have Undergone Orthotopic Liver Transplantation 41 50 EN Ailee Ikeda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yasunaka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Oyama Department of Gastroenterology and Hepatology, 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 Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Onishi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fusao Ikeda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidenori Shiraha Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Yoshida Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Kuise Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Nobuoka Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Yoshida Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzo Umeda Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56457 Post-orthotopic liver transplantation (OLT) hepatitis B recurrence is well-controlled with a nucleos(t)ide analogue and hepatitis B immunoglobulin (HBIG) combination, but the high cost and the potential risk of unknown infection associated with HBIG remain unresolved issues. Low-cost recombinant hepatitis B virus (HBV) vaccine administration is a potential solution to these problems. We retrospectively analyzed the rate and predictive factors of HBV vaccine success in 49 post-OLT patients: liver cirrhosis-type B (LC-B), n=28 patients; acute liver failure-type B (ALF-B), n=8; and non-HBV-related end-stage liver disease (non-B ESLD) who received a liver from anti-hepatitis B core antibody-positive donors, n=13. A positive anti-hepatitis B surface antibody response was achieved in 29% (8/28) of the LC-B group, 88% (7/8) of the ALF-B group, and 44% (4/9) of the adult non-B ESLD group. All four non-B ESLD infants showed vaccine success. The predictive factors for a good response in LC-B were young age, marital donor, and high donor age. ALF-B and non-B ESLD infants are thus good vaccination candidates. LC-B patients with marital donors are also good candidates, perhaps because the donated liver maintains an efficient immune memory to HBV, as the donors had already been infected in adulthood and showed adequate anti-HBV immune responses. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 4 2018 Mixed HCV Infection of Genotype 1B and Other Genotypes Influences Non-response during Daclatasvir + Asunaprevir Combination Therapy 401 406 EN Nozomu Wada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fusao Ikeda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chizuru Mori Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichi Takaguchi Department of Internal Medicine, Kagawa Prefectural Central Hospital Shin-ichi Fujioka Department of Internal Medicine, Okayama Saiseikai General Hospital Haruhiko Kobashi Department of Internal Medicine, Okayama Red Cross Hospital Yoichi Morimoto Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Kazuya Kariyama Department of Liver Disease Center, Okayama City Hospital Kosaku Sakaguchi Department of Internal Medicine, Fukuyama City Hospital Noriaki Hashimoto Department of Internal Medicine, Mihara Red Cross Hospital Akio Moriya Department of Gastroenterology, Mitoyo General Hospital Mitsuhiko Kawaguchi Department of Internal Medicine, Kawaguchi Medical Clinic Hirokazu Miyatake Department of Internal Medicine, Hiroshima City Hospital Hiroaki Hagihara Department of Gastroenterology, Sumitomo Besshi Hospital Junichi Kubota Department of Internal Medicine, Tajiri Hospital Hiroki Takayama Department of Gastroenterology, Tsuyama Central Hospital Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yasunaka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Iwasaki Health Service Center, Okayama University Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56178 Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 4 2018 Epidemiology of Pediatric Acute Encephalitis/Encephalopathy in Japan 351 357 EN Shinichiro Goto Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Nosaka Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yorifuji Department of Human Ecology, Okayama University Graduate School of Environmental and Life Science Tomoaki Wada Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Fujii Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Yashiro Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Washio Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuneo Morishima Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56170 We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 72 3 2018 A New Hepatitis Virus Test with Microliter-scale Fingertip Blood Collection in Japan 283 287 EN Shihoko Namba Center for Innovative Clinical Medicine, Okayama University Hospital Fusao Ikeda Department of Gastroenterology and Hepatology,Okayama University Hospital Koichi Takaguchi Department of Internal Medicine, Kagawa Prefectural Central Hospital Yasuyuki Shimomura Department of Gastroenterology and Hepatology,Okayama University Hospital Tetsuya Yasunaka Department of Gastroenterology and Hepatology,Okayama University Hospital Hiroyuki Okada Department of Gastroenterology and Hepatology,Okayama University Hospital Original Article 10.18926/AMO/56074 We investigated whether a small amount of blood collected by fingertip blood sampling would be adequate in a mass examination for hepatitis virus infection in Japan. A cross-sectional survey was conducted at health fairs in Kasaoka City and Shodoshima Island, where participants took the hepatitis screening test. A total of 114 consecutive individuals who took the hepatitis screening test were enrolled. Twenty microliters of plasma was successfully obtained from all participants. Among the participants, two had positive results for HBs antigen and two were positive for anti-HCV; all four were > 60 years old and rarely visited the hospital. Thirty-three and 38 patients chronically infected with HBV and HCV, respectively, were examined for confirmatory assays at participating hospitals. All subjects with undetectable serum levels of HBs antigen and anti-HCV had undetectable levels of both markers in fingertip blood, and the levels in serum and fingertip blood were significantly correlated (p<0.01). The lower detection limit of HBs antigen was defined as 0.005 IU/ml, and the cut-off value of anti-HCV was 1.0 by using 10-μl fingertip blood samples. The fingertip blood sampling described herein may be adequate in mass examinations for hepatitis virus testing in Japan. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2017 Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models EN Yoshiharu Nagaoka Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

岡山大学農学部 Acta Medica Okayama 2186-7755 107 2018 リンゴ小球形潜在ウイルスベクターを用いたサクラ属果樹のウイルス 誘導性ジーンサイレンシングに 関する研究 11 17 EN Takashi Kawai Graduate School of Environmental and Life Science, Okayama University Virus-induced gene silencing (VIGS) has been used as a rapid and effective tool for functional analysis of genes in various plants, including woody fruit tree species. In this study, we attempted to develop a VIGS-based gene evaluation system for seven Prunus species, including apricot (P. armeniaca L.), sweet cherry (P. avium L.), almond [P. dulcis (Mill.) D. A. Webb.], peach (P. persica Batsch), Japanese apricot (P. mume Siebold & Zucc.), Japanese plum (P. salicina Lindl.), and European plum (P. domestica L.), with the Apple latent spherical virus (ALSV) vectors. ALSV vectors carrying part of the apricot PHYTOENE DESATURASE (PDS) gene sequence were amplified in Nicotiana benthamiana, and inoculated into the cotyledons of Prunus seedlings by particle bombardment. Typical PDS-silenced phenotypes, characterized by uniform discoloration of the upper leaves, were observed in sweet cherry and some cultivars of apricot and almond several weeks after inoculation. In contrast, attempted ALSV infections of Japanese apricot, Japanese plum, European plum, and the other cultivars of apricot and almond were unsuccessful. Furthermore, although the infection rate of ALSV in peach was high, severe viral infection symptoms were observed in the infected leaves. These results collectively suggested that the efficiency of ALSV infection and VIGS could vary depending on species and/or cultivar in Prunus. The possible use of the ALSV-mediated VIGS system for functional analysis of genes in Prunus is discussed. No potential conflict of interest relevant to this article was reported.

American Institute of Physics Acta Medica Okayama 0094-243X 1707 2016 Mathematical Formulation and Numerical Simulation of Bird Flu Infection Process within a Poultry Farm 050013 EN Arrival Rince Putri Graduate School Environmental and Life Science, Okayama University Tertia Delia Nova Andalas University Masaji Watanabe Graduate School Environmental and Life Science, Okayama University Bird flu infection processes within a poultry farm are formulated mathematically. A spatial effect is taken into account for the virus concentration with a diffusive term. An infection process is represented in terms of a traveling wave solutions. For a small removal rate, a singular perturbation analysis lead to existence of traveling wave solutions, that correspond to progressive infection in one direction. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-4915 9 12 2017 Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum). 371 EN Hirohito Ogawa Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Kajihara Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University Naganori Nao Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University Asako Shigeno Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University Daisuke Fujikura Division of Infection and Immunity, Research Center for Zoonosis Control, Hokkaido University Bernard M. Hang’ombe Department of Paraclinical Studies, School of Veterinary Medicine, University of Zambia Aaron S. Mweene Department of Disease Control, School of Veterinary Medicine, University of Zambia Alisheke Mutemwa Provincial Veterinary Office, Department of Veterinary Services, Ministry of Fisheries and Livestock David Squarre Department of National Parks and Wildlife, Ministry of Tourism and Arts Masao Yamada Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideaki Higashi Division of Infection and Immunity, Research Center for Zoonosis Control, Hokkaido University Hirofumi Sawa Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University Ayato Takada Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University Bats are important reservoirs for emerging zoonotic viruses. For extensive surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106) exhibited remarkable cytopathic changes. Based on the ultrastructural property in negative staining and cross-reactivity in immunofluorescence assays, the virus was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06-106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined by next-generation sequencing, showed the presence of 28 open reading frames. Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat adenovirus species in the genus Mastadenovirus. The virus shared similar characteristics of low G + C contents with recently isolated members of species Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than 15% based on the distance matrix analysis of DNA polymerase amino acid sequences. According to the taxonomic criteria, we propose the tentative new species name "Bat mastadenovirus H". Because EhAdV 06-106 exhibited a wide in vitro cell tropism, the virus might have a potential risk as an emerging virus through cross-species transmission. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2017 Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from Myanmar EN Thar Htet San Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 5 2017 Genetic Factors of Low-responsiveness to Hepatitis B Virus Vaccine Confirms the Importance of Human Leukocyte Antigen Class II Types in a Japanese Young Adult Population 433 436 EN Nobuyasu Yukimasa Department of Medical Technology, Kagawa Prefectural University of Health Sciences Shota Kohama Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences Wataru Oboshi Department of Medical Technology, Kagawa Prefectural University of Health Sciences Shoichi Sato Clinical Laboratory, Chiba Emergency Medical Center Takehiro Nakamura Department of Medical Technology, Kagawa Prefectural University of Health Sciences Short Communication 10.18926/AMO/55442 We investigated the genetic mechanisms underlying the association between human leukocyte antigen (HLA) types and the immune response to hepatitis B virus (HBV) vaccination in 84 healthy Japanese adults, and found that the HLA-DRB1＊04 and HLA-DQB1＊03 frequencies were higher in the low responders (<10 mIU/ml; n=9, 10.7%) compared to the responders (≥10 mIU/ml, n=75, 89.3%). The combination of DRB1＊04 and DQB1＊03 was associated with a low response to vaccination. The DRB1＊04 and DQB1＊03 haplotypes’ frequencies were significantly higher in the low responders compared to responders. Novel candidate HLA types may be important in Japanese individuals. No potential conflict of interest relevant to this article was reported.

Cambridge Univ. Press for the Society for General Microbiology Acta Medica Okayama 0022-1317 93 7 2012 Development of hepatitis C virus production reporter-assay systems using two different hepatoma cell lines 1422 1431 EN Midori Takeda Department of Tumor Virology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Ikeda Department of Tumor Virology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Ariumi Department of Tumor Virology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaji Wakita Department of Virology II, National Institute of Infectious Disease Nobuyuki Kato Department of Tumor Virology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 　A hepatitis C virus (HCV) infection system was developed previously using the HCV JFH-1 strain (genotype 2a) and HuH-7 cells, and this cell culture is so far the only robust production system for HCV. In patients with chronic hepatitis C, the virological effects of pegylated interferon and ribavirin therapy differ depending on the HCV strain and the genetic background of the host. Recently, we reported the hepatoma-derived Li23 cell line, in which the JFH-1 life cycle is reproduced at a level almost equal to that in HuH-7-derived RSc cells. To monitor the HCV life cycle more easily, we here developed JFH-1 reporter-assay systems using both HuH-7- and Li23-derived cell lines. To identify any genetic mutations by long-term cell culture, HCV RNAs in HuH-7 cells were amplified 130 days after infection and subjected to sequence analysis to find adaptive mutation(s) for robust virus replication. We identified two mutations, H2505Q and V2995L, in the NS5B region. V2995L but not H2505Q enhanced JFH-1 RNA replication. However, we found that H2505Q but not V2995L enhanced HCV RNA replication of strain O (genotype 1b). We also selected highly permissive D7 cells by serial subcloning of Li23 cells. The expression levels of claudin-1 and Niemann-Pick C1-like 1 in D7 cells are higher than those in parental Li23 cells. In this study, we developed HCV JFH-1 reporter-assay systems using two distinct hepatoma cell lines, HuH-7 and Li23. The mutations in NS5B resulted in different effects on strains O and JFH-1 HCV RNA replication. No potential conflict of interest relevant to this article was reported.

Elsevier Science Acta Medica Okayama 0168-1702 167 1 2012 Identification of host genes showing differential expression profiles with cell-based long-term replication of hepatitis C virus RNA 74 85 EN Hiroe Sejima Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyoko Mori Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Ariumi Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masanori Ikeda Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuyuki Kato Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 　Persistent hepatitis C virus (HCV) infection frequently causes hepatocellular carcinoma. However, the mechanisms of HCV-associated hepatocarcinogenesis and disease progression are unclear. Although the human hepatoma cell line, HuH-7, has been widely used as the only cell culture system for robust HCV replication, we recently developed new human hepatoma Li23 cell line-derived OL, OL8, OL11, and OL14 cells, in which genome-length HCV RNA (O strain of genotype 1b) efficiently replicates. OL, OL8, OL11, and OL14 cells were cultured for more than 2 years. We prepared cured cells from OL8 and OL11 cells by interferon-γ treatment. The cured cells were also cultured for more than 2 years. cDNA microarray and RT-PCR analyses were performed using total RNAs prepared from these cells. We first selected several hundred highly or moderately expressed probes, the expression levels of which were upregulated or downregulated at ratios of more than 2 or less than 0.5 in each set of compared cells (e.g., parent OL8 cells versus OL8 cells cultured for 2 years). From among these probes, we next selected those whose expression levels commonly changed during a 2-year culture of genome-length HCV RNA-replicating cells, but which did not change during a 2-year culture period in cured cells. We further examined the expression levels of the selected candidate genes by RT-PCR analysis using additional specimens from the cells cultured for 3.5 years. Reproducibility of the RT-PCR analysis using specimens from recultured cells was also confirmed. Finally, we identified 5 upregulated genes and 4 downregulated genes, the expression levels of which were irreversibly altered during 3.5-year replication of HCV RNA. These genes may play roles in the optimization of the environment in HCV RNA replication, or may play key roles in the progression of HCV-associated hepatic diseases. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2017 Frequent downregulation of BACH2 expression in Epstein?Barr virus-positive diffuse large B-cell lymphoma EN Mai Nojima Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Georg Thieme Acta Medica Okayama 2194-9379 66 7 2016 Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids 371 376 EN S. Yoshihara Department of Pediatrics, Dokkyo Medical University H. Fukuda Department of Pediatrics, Dokkyo Medical University M. Tamura Department of Pediatrics, Dokkyo Medical University O. Arisaka Department of Pediatrics, Dokkyo Medical University M. Ikeda Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences N. Fukuda Grimm Pediatrics and Allergy Clinic T. Tsuji Department of Pediatrics, JA Hiroshima General Hospital S. Hasegawa Department of Pediatrics, Yamaguchi University Graduate School of Medicine N. Kanno Department of Pediatrics, Nishikata Hospital M. Teraoka Department of Pediatrics, Kurashiki Municipal Hospital H. Wakiguchi Department of Pediatrics, Yamaguchi University Graduate School of Medicine Y. Aoki Department of Pediatrics, Nagato General Hospital A. Terada Terada Kid’s Allergy & Asthma Clinic M. Hasegawa Department of Pediatrics, Yamaguchi Grand Medical Center A. Manki Department of Pediatrics, Okayama City Hospital H. Igarashi Department of Pediatrics, Nogi Hospital Background: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma.<br/> Objectives: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 μg/day) and fluticasone propionate (100 μg/day), in infants and preschool children with asthma.<br/> Methods: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 μg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE).<br/> Results: Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs.<br/> Conclusions: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 3 2016 平成27年度岡山医学会賞 胸部・循環研究奨励賞（砂田賞） 171 174 EN Nobuyuki Nosaka Department of Pediatrics, 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 128 2 2016 平成27年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞） 99 102 EN Hiromichi Dansako Department of Tumor Virology, 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 128 2 2016 平成27年度岡山医学会賞 総合研究奨励賞（結城賞） 91 94 EN Ai Kajita Department of Dermatology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

岡山実験動物研究会 Acta Medica Okayama 32 2016 鳥類細胞における一過性遺伝子発現のためのプロモーターの比較 28 32 EN Toshiyuki Kudo Genome editing technology by the CRISPR/Cas9, which was developed in 2012, is applicable in a variety of species. In birds, because the techniques of gene transfer and gene disruption has not been established, CRISPR/Cas9 method using adeno-associated virus (AAV) vector is the ideal combination as genome editing in vivo. However, in the use of AAV vectors, there is a problem to be solved that there is a limit on the size of the gene can be introduced. Therefore, it is important to minimize as much as possible the size of the gene. One strategy is to change the Cas9 gene into smaller ones, the other one is to minimize the promoter sequence. In this study, for the purpose of minimization of the promoter sequence to be introduced, the activities of the promoters to be general-purpose in mammals were verified in avian cells. CMV, CAG, and miCMV promoter shorten the CMV are all had sufficient activity in avian cells. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2016 Rab13 Is Involved in the Entry Step of Hepatitis C Virus Infection EN Midori Takeda No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2016 Molecular Mechanism Underlying the Suppression of CPB2 Expression Caused by Persistent Hepatitis C Virus RNA Replication EN Hiroe Sejima No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2016 Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice EN Nobuyuki Nosaka No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 2 2016 Rab13 Is Involved in the Entry Step of Hepatitis C Virus Infection 111 118 EN Midori Takeda Masanori Ikeda Shinya Satoh Hiromichi Dansako Takaji Wakita Nobuyuki Kato Original Article 10.18926/AMO/54190 Membrane transport probably participates in the lifecycle of hepatitis C virus (HCV). Rab proteins are essential host factors for HCV RNA replication, but these proteins’ roles in other steps of the HCV lifecycle are not clear. The tight junction (TJ) plays a key role in HCV infection. Rab13 regulates the endocytic recycling of the TJ-associated proteins. Here we investigated whether Rab13 is involved in the HCV entry step. We used HuH-7-derived RSc cells and Li23-derived D7 cells. To evaluate the effect of Rab13 in HCV infection, we transfected the cells with siRNA targeting Rab13 before HCV infection. The down-regulation of Rab13 inhibited HCV infection. The D7 cells had showed a greater inhibitory effect against HCV infection compared to that in the RSc cells by Rab13 knockdown. Next, to evaluate the effect of Rab13 after infection, we inoculated the cells with HCV before transfection of the siRNA. The down-regulation of Rab13 did not show any effects after HCV infection. We further examined whether Rab13 would influence HCV RNA replication by using HCV replicon-harboring cells. The results revealed that Rab13 did not affect the step of HCV RNA replication. These results suggest that Rab13 plays an important role in the step of HCV entry. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 2 2016 Molecular Mechanism Underlying the Suppression of CPB2 Expression Caused by Persistent Hepatitis C Virus RNA Replication 75 88 EN Hiroe Sejima Shinya Satoh Hiromichi Dansako Masao Honda Shuichi Kaneko Masanori Ikeda Nobuyuki Kato Original Article 10.18926/AMO/54186 The mechanisms of hepatitis C virus (HCV)-associated hepatocarcinogenesis and disease progression are unclear. We previously observed that the expression level of carboxypeptidase B2 (CPB2) gene was remarkably suppressed by persistent HCV RNA replication in human hepatoma cell line Li23-derived cells. The results of the present study demonstrated that the CPB2 expression in patients with chronic hepatitis C was inversely correlated with several risk factors of hepatic fibrosis or steatosis, although ectopic CPB2 expression did not suppress the expression of fibrogenic or lipogenic genes. The suppressed CPB2 expression was restored by treatment with 5-azacytidine. To clarify the mechanism underlying this phenomenon, we analyzed the CPB2 promoter, and the results revealed that (1) hepatocyte nuclear factor 1 (HNF1), especially HNF1α, was essential for the CPB2 promoter, and (2) CPB2 promoter was not methylated by persistent HCV RNA replication. The expression levels of HNF1α and HNF1β were also not changed by persistent HCV RNA replication. These results suggest the existence of 5-azacytidine-inducible or -reducible unknown factor(s) that can control the CPB2 expression. To evaluate this idea we performed a microarray analysis, and several gene candidates corresponding to the suggested factor(s) were identified. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Virus genotypes and responses of serum-specific antibodies in children with primary mumps and mumps reinfection EN Rika Sakata No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 1 2016 Entecavir Reduces Hepatocarcinogenesis in Chronic Hepatitis B Patients 1 12 EN Tetsuya Yasunaka Fusao Ikeda Nozomu Wada Yuki Morimoto Shin-ichi Fujioka Junichi Toshimori Haruhiko Kobashi Kazuya Kariyama Yoichi Morimoto Hiroki Takayama Tomonori Seno Koichi Takaguchi Akio Moriya Hirokazu Miyatake Ryoichi Okamoto Kazuhisa Yabushita Akinobu Takaki Kazuhide Yamamoto Original Article 10.18926/AMO/53996 Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged &#8805; 35 years, HBV DNA &#8805; 4 log copies/mL and positive HBeAg at diagnosis (n=184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p=0.013). Among the patients aged &#8805; 35 years with HBV DNA &#8805; 4 log copies/mL and negative HBeAg (n=237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p>0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged&#8805;35 years with HBV DNA &#8805;4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development. No potential conflict of interest relevant to this article was reported.

PUBLIC LIBRARY SCIENCE Acta Medica Okayama 1932-6203 9 3 2014 Genetic Characterization of Hepatitis C Virus in Long-Term RNA Replication Using Li23 Cell Culture Systems e91156 EN Nobuyuki Kato Hiroe Sejima Youki Ueda Kyoko Mori Shinya Satoh Hiromichi Dansako Masanori Ikeda Background　 　 The most distinguishing genetic feature of hepatitis C virus (HCV) is its remarkable diversity and variation. To understand this feature, we previously performed genetic analysis of HCV in the long-term culture of human hepatoma HuH-7-derived HCV RNA-replicating cell lines. On the other hand, we newly established HCV RNA-replicating cell lines using human hepatoma Li23 cells, which were distinct from HuH-7 cells. 　 Methodology/Principal Findings　 　 Li23-derived HCV RNA-replicating cells were cultured for 4 years. We performed genetic analysis of HCVs recovered from these cells at 0, 2, and 4 years in culture. Most analysis was performed in two separate parts: one part covered from the 5′-terminus to NS2, which is mostly nonessential for RNA replication, and the other part covered from NS3 to NS5B, which is essential for RNA replication. Genetic mutations in both regions accumulated in a time-dependent manner, and the mutation rates in the 5′-terminus-NS2 and NS3-NS5B regions were 4.0–9.0×10−3 and 2.7–4.0×10−3 base substitutions/site/year, respectively. These results suggest that the variation in the NS3-NS5B regions is affected by the pressure of RNA replication. Several in-frame deletions (3–105 nucleotides) were detected in the structural regions of HCV RNAs obtained from 2-year or 4-year cultured cells. Phylogenetic tree analyses clearly showed that the genetic diversity of HCV was expanded in a time-dependent manner. The GC content of HCV RNA was significantly increased in a time-dependent manner, as previously observed in HuH-7-derived cell systems. This phenomenon was partially due to the alterations in codon usages for codon optimization in human cells. Furthermore, we demonstrated that these long-term cultured cells were useful as a source for the selection of HCV clones showing resistance to anti-HCV agents. 　 Conclusions/Significance　 　 Long-term cultured HCV RNA-replicating cells are useful for the analysis of evolutionary dynamics and variations of HCV and for drug-resistance analysis. No potential conflict of interest relevant to this article was reported.

PUBLIC LIBRARY SCIENCE Acta Medica Okayama 1932-6203 8 8 2013 New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication e72519 EN Youki Ueda Midori Takeda Kyoko Mori Hiromichi Dansako Takaji Wakita Hye-Sook Kim Akira Sato Yusuke Wataya Masanori Ikeda Nobuyuki Kato BACKGROUND: Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed. 　 METHODOLOGY/PRINCIPAL FINDINGS: 　 　 Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.　 　 CONCLUSIONS/SIGNIFICANCE:　 　 We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin. No potential conflict of interest relevant to this article was reported.

Okayama University Acta Medica Okayama 7 2015 Anticancer virus solution provides an alternative to surgery EN Toshiyoshi Fujiwara No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Lyapunov Functionals for Virus-Immune Models with Infinite Delay – One-strain and Multistrain Models EN Yoji Otani No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 Rituximab併用CHOP療法が奏効した肝原発びまん性大細胞型Ｂ細胞リンパ腫の１例 209 212 EN Hiroshi Okada Soichiro Fujii Kentaro Watanabe Terunobu Shigematu Katsuhiro Miyashita Morihiro Okazaki Haruhiko Kobashi Motohiro Yokoyama Tadashi Yoshino 　A 78-year-old Japanese man was referred to our hospital after experiencing black feces. No abnormal finding was detected in the endoscopic examination of his stomach and large intestines. Computed tomography (CT) of the abdomen revealed a tumor lesion in the right lobe of the liver. A needle biopsy of the tumor under ultrasound guidance was performed. A pathological examination of the biopsy specimen showed a diffuse proliferation of lymphoma cells, which was compatible with diffuse large B-cell lymphoma (DLBCL). F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT demonstrated increased FDG uptake only in the liver tumor. We made the diagnosis of primary DLBCL of the liver. After six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), the patient achieved complete remission and has maintained remission for 2 years since the diagnosis. The R-CHOP regimen might be effective therapy for primary DLBCL of the liver. No potential conflict of interest relevant to this article was reported.

Blackwell Pub. Acta Medica Okayama 1742-464X 2015 The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly EN Hiromichi Dansako Youki Ueda Nobuaki Okumura Shinya Satoh Masaya Sugiyama Masashi Mizokami Masanori Ikeda Nobuyuki Kato During viral replication, the innate immune response is induced through the recognition of viral replication intermediates by host factor(s). One of these host factors, cyclic GMP-AMP synthetase (cGAS), was recently reported to be involved in the recognition of viral DNA derived from DNA viruses. However, it is uncertain whether cGAS is involved in the recognition of hepatitis B virus (HBV), which is a hepatotropic DNA virus. In the present study, we demonstrated that HBV genome-derived dsDNA induced the innate immune response through cGAS and its adaptor protein, STING, in human hepatoma Li23 cells expressing high levels of cGAS. In addition, we demonstrated that HBV infection induced ISG56 through the cGAS-STING signaling pathway. This signaling pathway also showed an antiviral response towards HBV through the suppression of viral assembly. From these results, we conclude that the cGAS-STING signaling pathway is required for not only the innate immune response against HBV but also the suppression of HBV assembly. The cGAS-STING signaling pathway may thus be a novel target for anti-HBV strategies. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Effectiveness of Extending Treatment Duration in Therapy with Pegylated Interferon and Ribavirin for Genotype 2 Hepatitis C Virus Infection EN Shintarou Nanba No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 4 2015 Effectiveness of Extending Treatment Duration in Therapy with Pegylated Interferon and Ribavirin for Genotype 2 Hepatitis C Virus Infection 237 244 EN Shintarou Nanba Fusao Ikeda Shin-ichi Fujioka Yasuyuki Araki Kouichi Takaguchi Noriaki Hashimoto Hiroyuki Seki Akinobu Takaki Yoshiaki Iwasaki Kazuhide Yamamoto Original Article 10.18926/AMO/53560 The effectiveness of extending treatment duration as response guided therapy was previously reported for chronic hepatitis C (CHC) genotype 1, but is still controversial for genotype 2. The present study is a retrospective cohort study to investigate the effectiveness of extending treatment duration in therapy with pegylated interferon and ribavirin for patients with CHC genotype 2 by focusing on the timing at which patients obtained undetectable HCV RNA. A total of 306 patients who obtained undetectable HCV RNA by week 24 of treatment and completed 24 weeks of treatment were enrolled. Rapid virological response (RVR) to standard therapy was achieved by 122 patients (51ｵ), and 89ｵ of them obtained sustained virological response (SVR), while 69ｵ of non-RVR patients achieved SVR. Non-RVR patients with undetectable HCV RNA at week 8, and insufficient adherence＜80ｵ pegylated interferon and ribavirin during the first 24 weeks, significantly improved their SVR rate by extended therapy. Among patients receiving extended therapy, drug adherences did not differ between SVR and non-SVR patients, indicating that extending treatment duration might compensate for insufficient antiviral effects due to insufficient drug adherences. This finding might be useful in creating a guideline for extending treatment duration for patients with CHC genotype 2. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Simultaneous immunostaining with anti-S100P and anti-SV40 antibodies revealed the origin of BK virus-infected decoy cells in voided urine samples EN Sanae Ariyasu No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication EN Yuki Ueda No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Survival Rates and Prognostic Factors of Epstein-Barr Virus-Associated Hydroa Vacciniforme and Hypersensitivity to Mosquito Bites EN Tomoko Miyake No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2015 Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study EN Takeshi Tomoda No potential conflict of interest relevant to this article was reported.