Okayama University Medical SchoolActa Medica Okayama0386-300X8022026Involvement of ADAM12 in TGF-β1-Induced Proliferation of Rheumatoid Arthritis Synovial Fibroblasts7583ENDetingLinDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroHoritaDepartment of Orthopaedic Surgery, Faculty of Medical Development Field, Okayama UniversityMasahitoWatanabeDepartment of Orthopaedic Surgery, Muscat Orthopaedic ClinicJoeHaseiMedical Information and Assistive Technology Development, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiOhtsukiMedical Technology, Graduate School of Health Sciences, Okayama UniversityNoriakiOtsukaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChinatsuIchikawaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNoriyukiShimizuDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShuichiNaniwaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroNishidaDivision of Chronic Pain Medicine and Division of Comprehensive Rheumatology, Locomotive Pain Center, Faculty of Medical Development Field, Okayama UniversityOriginal Article10.18926/AMO/70450A disintegrin and metalloproteinase 12 (ADAM12) is known to be involved in chondrocyte proliferation and is upregulated in the synovial tissue of osteoarthritis (OA). However, the underlying mechanisms of ADAM12 on rheumatoid arthritis (RA) synovial cell proliferation remain unknown. Here, we investigated the role of ADAM12 in the proliferation of RA synovial fibroblasts (RASFs). The expression and localization of ADAM12 in RA synovial tissues were examined by immunohistochemistry and compared with OA and healthy control (HC) synovial tissues. The effect of inflammatory cytokines (TNF-α, TGF-β1, and PDGF-BB) on ADAM12 expression in RASFs from RA patients was examined by real-time RT-PCR. The effect of ADAM12 knock-down by ADAM12 siRNA and ADAM12 overexpression on cell proliferation of RASFs were examined by WST-1 assay. ADAM12 was identified predominantly in RA synovial tissue rather than OA and HC synovial tissues. Stimulation with TGF-β1 upregulated the expression of ADAM12 and cell proliferation of RASFs. ADAM12 siRNA suppressed TGF-β1-induced cell proliferation of RASFs, while ADAM12 overexpression promoted the cell proliferation of RASFs. 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Rheumatol Int (2006) 26: 244-251.Elsevier BVActa Medica Okayama2211-7156252026Peptide nanomicelles for NIR light-dependent siRNA delivery103265ENTaufik Fatwa NurHakimDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityShoumuFujimotoDepartment of Applied Chemistry, Kindai UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe peptide amphiphile PA8, derived from the GAVILRR peptide, was developed as a carrier for small interfering RNA (siRNA) delivery; however, its RNA interference (RNAi) efficacy was limited owing to predominant endocytotic uptake. In this study, the RNAi efficiency of PA8 nanomicelle/siRNA complexes was enhanced by modifying the nanomicelles with the photosensitizer DY750 and the tumor-homing peptide iRGD. The conjugation of DY750 to the nanomicelles facilitated endosomal escape of the nanomicelle/siRNA complexes, enabling the cytosolic release of siRNA. Additionally, the incorporation of iRGD improved RNAi delivery efficiency in the AsPC-1 pancreatic ductal adenocarcinoma cell line. PA8-DY750-iRGD nanomicelle complexes loaded with siRNA against polo-like kinase 1 (PLK1) achieved an 80% reduction in PLK1 mRNA levels in AsPC-1 cells and a moderate 28% knockdown in NCI-N87 gastric cancer cells. Notably, no RNAi effect was observed in noncancerous 1C3D3 pancreatic cells or HEK293T kidney cells, underscoring the selectivity of this system for AsPC-1 cells. These findings highlight the potential of PA8-DY750-iRGD nanomicelle complexes as a targeted therapeutic platform for specific cancers, particularly pancreatic cancer.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221612026Liquid–liquid phase separation by caged coacervating peptides10464ENAkinariBandoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityYuukiKanazakiDepartment of Applied Chemistry, Kindai UniversityRikaTojoDepartment of Applied Chemistry, Kindai UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityLiquid–liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced π–π interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5′-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0143-41601352026Regulation of brain-specific kinases 1 and 2 (BRSK1/2) by Ca2+/calmodulin103134ENNaoyukiWashidaMoeKataokaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityAnna R.BrunApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityUryuTakezakiApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKoHijikawaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityHarukiYamauchiApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatomiOhtsukaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasakiMagariApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRyoMorishitaCellFree Sciences Co., Ltd.HiroshiTokumitsuApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWe conducted a genome-wide calmodulin (CaM) interaction screening of 462 GST-fused human protein kinases to identify novel CaM-dependent protein kinases (CaMKs). In addition to known CaMKs, including myosin light chain kinases, CaMK2γ, and death-associated kinase 2, we identified the brain-specific protein kinase 2 (BRSK2, also known as SAD-A) as a novel CaM interactant. Proximity biotinylation and CaM–sepharose chromatography assays revealed that rat BRSK isoforms (BRSK1/2) interact with CaM in a Ca2+-dependent manner in vitro. We found that CaM suppresses the activation-loop phosphorylation of BRSK1 (at Thr189) and BRSK2 (at Thr175) by liver kinase B1 (LKB1), an activating kinase, in a Ca2+-dependent manner (IC50 of ∼7 µM), thereby inhibiting BRSK activation. LKB1-catalyzed phosphorylation of the catalytic domain mutant of BRSK1 (residues 1–294) at Thr189 was suppressed by the addition of Ca2+/CaM, consistent with direct CaM binding of the kinase domain, as well as wild-type BRSK1. We confirmed that the LKB1 activity was not directly suppressed by Ca2+/CaM, supporting the hypothesis that the direct interaction of Ca2+/CaM with the kinase domain blocks the phosphorylation/activation of BRSK1/2 by LKB1. The kinase activity and PP2Cα-catalyzed dephosphorylation of LKB1-phosphorylated BRSK1 were not altered by Ca2+/CaM, although it was demonstrated to bind to Ca2+/CaM like that of unphosphorylated BRSK1. This unrecognized mechanism of BRSK1/2 regulation, involving the direct role of Ca2+/CaM binding, which inhibits phosphorylation/activation by LKB1, may open a new Ca2+ signal transduction pathway in neurons.No potential conflict of interest relevant to this article was reported.岡山大学教育推進機構 教師教育開発センターActa Medica Okayama2186-1323162026大学院共通科目『リーダーシップとSDGs』の教育モデル構築と成果分析 理論学習・ピアレビュー・省察活動によるリーダーシップ教育の新展開221235ENMamoruISHIDAFaculty of General Education and Global Studies, Okayama UniversityShinichiOTSUNEGraduate student, Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTakuyaNAKAZAWAGraduate student, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/CTED/70371 岡山大学大学院では、博士課程人材のリーダーシップ育成に向け、共通科目『リーダーシップとSDGs』を設計・実践している。本科目はSDGsに貢献するリーダー育成に主眼を置き、理論学習・ピアレビュー・省察・グループディスカッション等の手法を組み合わせ、学生同士の学び合い・自己成長の促進を目的としている。本稿では、学部・研究科ごとに学習成果を分析し、理論に基づく省察的学びと協働的な批評活動がリーダーシップ理解や成長に有用であることを明らかにした。本研究は、学術的理論と実践的活動を織り交ぜたモデル構築と、その継続的改善の意義を示している。No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama1043-18023732026A Cysteine-Specific Cationization Strategy for Versatile Antibody Production against Intrinsically Disordered Proteins580589ENRyuiSakaguchiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAiMiyamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRikakoKutsumaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakeruMoriGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityDaichiNakashimaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMireiMasuiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTomokoHonjoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMidoriFutamiDepartment of Bioscience, Faculty of Life Science, Okayama University of ScienceMarikoMoriiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshiyukiOshikiDivision of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama UniversityJunichiroFutamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySeveral autoantigens relevant to the immune system, especially those targeted by autoantibodies induced by antitumor responses, tend to be rich in disordered regions and are prone to aggregation. This inherent instability presents significant challenges for the production, purification, and analysis of autoantigens in laboratory settings. Cysteine-specific cationization can effectively solubilize and purify these challenging proteins, allowing the isolation of full-length water-soluble antigens in their denatured state. The purified antigens enable accurate multiplex autoantibody assays using a suspension Luminex bead array platform. However, well-validated positive control antibodies are essential to ensuring precise clinical diagnosis. In this study, we prepared and characterized a panel of control antibodies by immunizing rabbits with cysteine-specific S-cationized antigens. The resulting antibodies predominantly recognized linear epitopes and were highly effective as quality control reagents in autoantibody array assays. Additionally, these antibodies maintained their ability to bind to their native, unmodified intracellular counterparts, highlighting the usefulness of this approach for producing antibodies against intrinsically disordered proteins. Although a modest immune response against the S-cationized modification site was observed, it remained minimal and did not affect the usefulness of the antibodies for assay validation. We propose this versatile cysteine-specific cationization platform for managing unstable proteins rich in disordered regions, supporting antigen production for diagnostics, and antibody development for research and validation purposes.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026裏表紙・英文目次ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026投稿規程・奥付ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-3227620262025 年度次世代医療機器開発人材育成プログラム BIZEN デバイスデザインコースの取り組み5968ENTsuneakiTSUZUKICenter for Innovative Clinical Medicine, Okayama University HospitalDaisukeUCHIDACenter for Innovative Clinical Medicine, Okayama University HospitalToshioKISHIMOTOOrganization for Research and Innovation Strategy, Okayama UniversityYoshinariSENGOKUCenter for Innovative Clinical Medicine, Okayama University HospitalToshioKORENAGAOrganization for Research and Innovation Strategy, Okayama UniversityYuHITOBECenter for Innovative Clinical Medicine, Okayama University HospitalYasuyukiYOSHIBAAcademic Field of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunSAKURAICenter for Innovative Clinical Medicine, Okayama University Hospital10.18926/interdisciplinary/70331No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-3227620262025 年度における「先進病院実習」の取り組み4957ENMizukiMORITAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasakiMAGARIFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinWangFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToyohikoWATANABEFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasatakaOITAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNahokoHARADAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKeisukeSHISHIDOFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/70330No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026わが国のアドバンス・ケア・プランニングにおける地域住民への動機づけと評価についてのナラティブ・レビュー3947ENTakakoHASUIJapanese Red Cross Hokkaido College of NursingNaokoNAKAYAMAKanagawa University of Human Services10.18926/interdisciplinary/70329No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026HIV 検査技術と日本における HIV 検査体制の変遷2737ENDechengWANGGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/70328No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026Shared Decision Making における患者参加の諸相と課題の考察1725ENMihoYOSHIDAGraduate School of Interdisciplinary Science and Engineering in Health Systems Okayama University10.18926/interdisciplinary/70327This paper traces the historical development of decision-making models in healthcare while exploring the meaning and practical significance of “patient participation” within the shared decision-making (SDM) framework. SDM is a recommended approach to clinical decision-making that emphasizes mutual information sharing and deliberation between physicians and patients. Traditional models often assume that patients can clearly articulate their values, preferences, and treatment goals. However, in actual clinical settings, particularly in cases of serious illness or life-threatening situations, patients frequently face emotional distress and psychological burdens, which can hinder their active participation in decision-making and the expression of their preferences. Based on SDM theory and practice reports, this study argues that SDM should not be viewed merely as a process that promotes patient choice. Even when patients choose not to actively participate and ultimately delegate decisions to healthcare providers or family members, such a choice can represent autonomous decision-making if it arises through meaningful communication and mutual understanding. This perspective calls for a more comprehensive and flexible interpretation of patient participation in SDM practice.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026介護技術論試論―高齢者介護を事例として―716ENYasuyukiYOSHIBAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/70326In the first part of this paper, it was confirmed that the term “kaigo” (nursing care) was coined and its meaning defined during discussions on enacting social welfare legislation accompanying societal aging, as the care aspect was being “differentiated” from the “family’s health and welfare functions.” The paper also examined how the term “kaigo gijutsu”(nursing care technique) has been defined and used. In the latter part, based on the author’s own definition of “kaigo gijutsu”(nursing care technology), an attempt was made to analyze examples of technology utilization in nursing care settings, focusing on papers published in specialized welfare and nursing care technology journals. Through this preliminary study, it was shown that the author’s definition of “nursing care technology” clearly distinguishes between the means for care activities—such as welfare equipment—and the care recipients and caregivers who make use of them, and that this definition is useful for grasping the essence of challenges in nursing care settings.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026The effects of cold compresses on itching in patients with atopic dermatitis: A cross-over controlled pilot trial16ENYukiHIRAMIFormer Department of Nursing, Graduate School of Health Sciences, Okayama UniversityNahokoHARADADepartment of Nursing Science, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMihoONODepartment of Nursing, Faculty of Health, Kagawa Prefectural University of Health SciencesMasahideKODACo-learning Community Healthcare Re-innovation Office, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKiyokoFUKAIProfessor Emeritus, Okayama University, Graduate School of Nursing, The Jikei University School of Medicine10.18926/interdisciplinary/70325This cross-over controlled trial aimed to evaluate the effectiveness and safety of two types of cold compresses (towels and ice packs) in alleviating itching among patients with atopic dermatitis. The study recruited 19 participants diagnosed with atopic dermatitis and suffering from chronic itching for over 6 months. Each participant received both types of cold compress interventions. Itching sensations were assessed repeatedly using a visual analogue scale before and after the application of the cold compress. The mean and standard deviation of itching scores for the towel intervention were 16.9 ± 19.1 (baseline) and 11.4 ± 16.1 (post-application). For the ice pack intervention, the scores were 13.6 ± 14.7 (baseline) and 6.2 ± 9.8 (post-application). Although there was a reduction in mean itching scores following the application of cold compresses, the differences were not statistically significant for either intervention. Despite the lack of statistical significance, this study suggests that cold compresses, which are user-friendly and inexpensive, may safely reduce subjective itching in patients with atopic dermatitis without causing pain or discomfort. However, further research with a larger sample size is needed to confirm these findings.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322762026表紙・目次ENNo potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama0022-26236952026Discovery of Thermal Sensitizers That Inhibit Heat-Induced SAFB Granule Formation59445955ENYujiFurutaniFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNatsukiShimasakiFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRikoYamadaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazunoriWatanabeFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHyperthermia is a minimally invasive cancer treatment based on heat stress-induced apoptosis. Its therapeutic efficacy, however, is often limited by tumor heterogeneity and acquired thermotolerance. Therefore, combination strategies involving hyperthermia and chemotherapy have been developed to enhance the therapeutic efficacy. Previously, we showed that SB366791 enhanced heat-induced apoptosis by inhibiting heat stress-induced scaffold attachment factor B (SAFB) granule formation, although its proapoptotic activity was insufficient. Therefore, we screened to identify novel compounds that enhance heat-induced apoptosis by suppressing SAFB granule formation. We identified four hit compounds that inhibited SAFB granule formation, all exhibiting thermal enhancement ratios > 1.0─that significantly enhanced heat-induced apoptosis efficiency. Additionally, the tumor volume in mice treated with a combination of Z19024498 and hyperthermia was significantly smaller than that in mice treated with hyperthermia or Z19024498. These results indicate that the identified compounds, specifically Z19024498, have potential as thermal sensitizers for hyperthermia therapy.No potential conflict of interest relevant to this article was reported.大阪府保険医協会Acta Medica Okayama547132026『光が見える』人工網膜の可能性 ― 有機色素分子を部材とする世界初の医療機器「光電変換色素薄膜型人工網膜OUReP」1321ENToshihikoMatsuoTetsuyaUchidaHiroshiIshikane 網膜色素変性や加齢黄斑変性では、光を細胞膜電位に変換する網膜視細胞が死んでいるが、視神経として脳に連絡する神経節細胞は生き残っている。人工網膜は視細胞を代替する人工物で、光を受け電流を出力する電極アレイ型が主流であるが、電流は拡散するため解像度向上が難しい。そこで人工網膜の解像度向上を目指して、光を電位差に変換する光電変換色素分子を絶縁体のポリエチレン薄膜表面に共有結合した光電変換色素薄膜型の人工網膜OURePを開発してきた。この人工網膜OURePは光受容と電位出力の一体型で外部起電力は不要、手術では薄膜を鋏で切って眼内に植込む大きさを自由に選べる。使い捨てインジェクタを使って薄膜を丸め眼球の網膜下に硝子体手術で植込み、網膜下に植込んだ人工網膜OURePは光を受けて電位差を出力し隣接する網膜組織の神経細胞の活動電位を誘発する。クリーンルームで製造品質管理を行い、安全性と有効性を証明して、医師主導治験を準備している。今後、日本の国民皆保険が維持できるよう比較安価な適正価格の人工網膜治療を提供したい。No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2590-1230272025Inscribed-type spherical speed reducer with uniform reduction ratio in all directions106742ENSeiyaNaramuraFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityKoichiTonegawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySoShimookaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTomoakiYanoFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityAkioGofukuOkayama Prefectural UniversityNagayoshiKasashimaNational Institute of Advanced Industrial Science and TechnologyTetsushiKamegawaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityA spherical motor is an actuator that can generate rotational motion about all three orthogonal axes. However, it is difficult to obtain high output torque from most electromagnetic spherical motors, primarily due to limitations inherent in electromagnetic actuators, such as restricted magnetic force and thermal constraints. Since its torque cannot be increased using planar gears, spherical speed reducers that transmit rotational torque along three orthogonal axes through sphere-to-sphere contact are required. One major limitation of conventional spherical speed reducers is that their size increases significantly as the reduction ratio becomes higher. To address this issue, we propose a novel inscribed-type spherical speed reducer, in which the deceleration mechanism is integrated within the output sphere. This configuration enables a more compact design, reducing the overall size to approximately half that of conventional designs. To predict the angular velocity and transmitted torque, theoretical models for the rotation and torque transmission of the speed reducer were developed. According to the proposed model, the reduction ratio of the spherical speed reducer is 1/3. To verify the validity of these models, experiments were conducted to measure angular velocity and torque. The theoretical results agreed well with the experimental results. In addition, the theoretical torque exhibited an average relative error of 1.63 % compared to the experimental result. Therefore, it was confirmed that the rotation and torque transmission models were valid. These results demonstrate that a reduction ratio can be obtained in all directions of the 3-DOF of the spherical speed reducer, unlike conventional 1-DOF reducers.No potential conflict of interest relevant to this article was reported.眼科臨床紀要会Acta Medica Okayama1882-517619022026斜視の遺伝子研究113125ENToshihikoMatsuoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University共同性斜視は遺伝要因と環境要因からなる多因子疾患で、内斜視と外斜視に大別される。遺伝要因は家族歴、一卵性双生児の表現型一致率から推定され、環境要因には妊娠・分娩時の低酸素状態がある。一方、遺伝要因がある非共同性（麻痺性）斜視として上斜筋腱低形成を呈する特発性上斜筋麻痺がある。遺伝統計学の連鎖解析を使って、内斜視と外斜視の小家系群で4番染色体MGST2を疾患感受性遺伝子候補と同定し、MGST2ノックアウトマウスを作成した。小動物用MRIで解析すると、そのホモ接合体では野生型と比べて眼球形状が有意に横長で体積が大きいことを見出した。次いで遺伝統計学別法の全ゲノム関連解析を内斜視、外斜視、特発性上斜筋麻痺を対象として行った。Infinium Asian Screening Array-24 v1.0でSNPを決めた内斜視253検体、外斜視356検体、上斜筋麻痺102検体を疾患群とした。対照集団としては、バイオバンクジャパン (BBJ) の疾患群とは違うアレイ(OmniExpress)でSNPを決めた182,476検体「BBJ (180K)」、疾患群と同じアレイでSNPを決めたBBJの53409検体「BBJ (ASA)」および長浜コホート3570検体を使った。３対照集団との比較で共通して検出された遺伝子は、上斜筋麻痺群で神経細胞移動に関与するDAB1であった。最も大きい対照集団「BBJ (180K)」との比較では内斜視、外斜視、上斜筋麻痺を含む疾患群全体で眼発生に関与するRARB (retinoic acid receptor β) が検出された。斜視関連遺伝子は眼球形態に関与する可能性がある。特発性上斜筋麻痺は共同性斜視とは独立した疾患と理解されるが、共通の遺伝基盤もあるかもしれない。No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2079-63741612026Magnetic Detection of Cancer Cells Using Tumor-Homing Peptide-Modified Magnetic Nanoparticles45ENShengliZhouDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYujiFurutaniDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKeiYamashitaDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySakuyaKakoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihikoKiwaDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMagnetic nanoparticles (MNPs) provide a platform for target detection because of their magnetic responsiveness to alternating magnetic fields (AMFs). We developed a detection method using MNPs modified with tumor-homing peptides (THPs), PL1 and PL3, which selectively bind to protein components enriched in malignant tissues. THP-MNPs were synthesized using maleimide-PEG-NHS linkers and characterized using transmission electron microscopy. Human glioblastoma cancer U87MG and normal tissue-derived HEK293 cells were incubated with THP-MNPs, and the magnetic signals were measured using a high-temperature superconducting quantum interference device (SQUID) magnetometer under an AMF (1.06 kHz). Dark-field microscopy confirmed the preferential binding of THP-MNPs to U87MG cells. In the absence of cells, THP-MNPs exhibited AMF-dependent signal enhancement, which correlated with particle size reduction due to THP release. This increase was completely suppressed in the presence of U87MG cells, indicating a strong THP-mediated interaction. PL3-MNPs exhibited superior discrimination between malignant and non-malignant cells. These results demonstrate that SQUID-based magnetic measurements using THP-MNPs enable rapid and label-free cancer cell detection.No potential conflict of interest relevant to this article was reported.American Chemical Society (ACS)Acta Medica Okayama0006-296064202025Characterization of Autonomous and Ca2+/Calmodulin-Dependent Activities of CaMKK Isoforms In Vitro and in Mouse Tissues43094317ENSatomiOhtsukaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYerunChenApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasakiMagariApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTeruhikoIshikawaDepartment of Science Education, Graduate School of Education, Okayama UniversityHiroyukiSakagamiDepartment of Anatomy, Kitasato University School of MedicineFutoshiSuizuClinical Examination Department, Kagawa Prefectural University of Health SciencesHiroshiTokumitsuApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityCa2+/CaM-dependent protein kinase kinase (CaMKK) phosphorylates and activates downstream kinases, including CaMKI, CaMKIV, PKB, and AMPK, regulating various cellular functions such as neuronal morphogenesis, metabolic control, and pathophysiological pathways, such as cancer progression. CaMKKα/1 is tightly regulated by an autoinhibitory mechanism. CaMKKβ/2 activity is highly Ca2+/CaM-independent (autonomous activity) in vitro and Ca2+/CaM-dependent in cultured cells. Whether these two activity states of CaMKKβ/2 exist in vivo and the detailed regulatory mechanisms for the transition of both activity states remain unclear due to the difficulty in distinguishing the two activity states. In this study, we detected Ca2+-dependent and autonomous CaMKK activity in HeLa cells and successfully separated both activity states of CaMKKβ/2 in mouse brain and testis extracts using a recently developed CaMKK inhibitor (TIM-063)-coupled sepharose, which binds to the catalytic domain in the active state but not in the autoinhibited state. Furthermore, lambda protein phosphatase treatment converted the Ca2+/CaM-dependent form to the autonomous form of CaMKKβ/2, which was not affected by Ala mutation of Ser128, Ser132, and Ser136. The two activity forms of CaMKKβ/2 had equivalent Ca2+/CaM-binding ability. The findings demonstrate the presence of autonomous and Ca2+/CaM-dependent forms of CaMKKβ/2 independently in mouse tissues and cultured cells. The transition of these states of CaMKKβ/2 may be dynamically regulated by the phosphorylation/dephosphorylation of serine residues in the N-terminal regulatory domain.No potential conflict of interest relevant to this article was reported.Ceramic Society of JapanActa Medica Okayama1348-653513412026Structure and acid resistance of fluoride-treated hydroxyapatite particles3137ENSatoshiHayakawaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazukiAndoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTomohikoYoshiokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTopical fluoride is used in clinical dentistry to prevent dental caries. The primary reaction product formed on the tooth surface after topical fluoride application is calcium fluoride (CaF2). In this study, we investigated the effect of deposited CaF2 on the acid resistance of fluoride-treated hydroxyapatite (HAp). Commercial HAp particles were treated with two types of fluoride-containing acetic acid-sodium acetate (Ac-AcNa) buffer solutions, with and without the addition of phosphate ions. X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) analyses confirmed the formation of fluorine-substituted hydroxyapatite (F-HAp), along with a hydration layer containing calcium phosphate and CaF2. Phase composition analysis revealed that the presence of phosphate ions in the fluoride treatment solution reduced the amount of CaF2 deposited. Acid resistance evaluation and phase composition analysis indicated that the initial dissolution rate of the fluoride-treated HAp in Ac-AcNa buffer solutions decreased on surfaces densely covered with CaF2 particles.No potential conflict of interest relevant to this article was reported.Ceramic Society of JapanActa Medica Okayama1348-653513412026Preparation of brookite-type titanium dioxide particle layer on titanium surfaces via hydrothermal treatment and evaluation of in vitro apatite-forming ability2430ENSatoshiHayakawaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYushiNakamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySeiyaKojimaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNoriyukiNagaokaAdvanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental SchoolTakuyaKataokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTomohikoYoshiokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityIn this study, we prepared a brookite-type titanium dioxide particle layer on the surface of titanium substrates via hydrothermal treatment in aqueous urea solutions containing sodium chloride (NaCl) and examined its in vitro apatite-forming ability. Increasing the urea concentration suppressed the formation of anatase-type titanium dioxide on the titanium substrate, forming a particle layer composed of pure brookite-type titanium dioxide. The size and packing density of brookite-type titanium dioxide particles formed on the titanium substrate increased with the NaCl concentration in a 7.0 mol·dm−3 urea solution. When titanium substrates hydrothermally treated in aqueous solutions of 7.0 mol·dm−3 urea and 2.0 mol·dm−3 NaCl were soaked in a simulated body fluid for various periods up to 7 d, the substrate surface was densely covered with hemispherical apatite particles (5.3 µm in diameter) within 3 d, indicating that the brookite-type titanium dioxide particle layer had an excellent apatite-forming ability comparable to that of the anatase-type titanium dioxide particle layer.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0010-94521942026Increasing visual uncertainty modulates multisensory decision-making5062ENXiangfuYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWeipingYangDepartment of Psychology, Faculty of Education, Hubei UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimichiEjimaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe brain integrates and transforms information from multiple senses to make optimal decisions, a process that is critical for navigating complex environments with perceptual uncertainty. Despite a growing consensus that individuals adapt flexibly to uncertain sensory input, whether increasing visual uncertainty influences the decision process itself or other, non-decision sensory processes during multisensory decision-making are unclear. Here, an audiovisual categorization task was used to examine the responses of human participants (N = 30) to visual and audiovisual stimuli under low-, medium-, and high-uncertainty conditions. Modeling the behavioral data using a drift‒diffusion model indicated that increased visual uncertainty in the audiovisual context decreased the evidence accumulation rate but had no effect on non-decision processes. Electrophysiological recordings confirmed and expanded upon these results: increased visual uncertainty in the audiovisual context reduced the amplitude during the late decision-making stage (300–380 msec) but had no effect on the amplitude during the early sensory encoding stage (140–220 msec). More importantly, electroencephalography analyses revealed that audiovisual integration in the early sensory encoding stage occurred robustly across all visual uncertainty conditions, whereas audiovisual integration in the late stage occurred only under medium and high visual uncertainty conditions. This study demonstrated that increased visual uncertainty modulates the decision process itself rather than early sensory encoding during multisensory decision-making. Moreover, multisensory integration strategies dynamically adapt to increasing visual uncertainty by engaging different mechanisms to maintain effective decision-making.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2076-342515112025Sensory Modality-Dependent Interplay Between Updating and Inhibition Under Increased Working Memory Load: An ERP Study1178ENYuxiLuoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAoGuoDepartment of Psychology, Institute of Education, China West Normal UniversityJinglongWuFaculty of Biomedical Engineering, Shenzhen University of Advanced TechnologyJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityBackground/Objectives: Working memory (WM) performance relies on the coordination of updating and inhibition functions within the central executive system. However, their interaction under varying cognitive loads, particularly across sensory modalities, remains unclear. Methods: This study examined how sensory modality modulates flanker interference under increasing WM loads. Twenty-two participants performed a visual n-back task at three load levels (1-, 2-, and 3-back) while ignoring visual (within-modality) or auditory (cross-modality) flankers. Results: Behaviorally, increased WM load (2- and 3-back) led to reduced accuracy (AC) and prolonged reaction times (RTs) in both conditions. In addition, flanker interference was observed under the 2-back condition in both the visual within-modality (VM) and audiovisual cross-modality (AVM) tasks. However, performance impairment emerged at a lower load (2-back) in the VM condition, whereas in the AVM condition, it only emerged at the highest load (3-back). Significant performance impairment in the AVM condition occurred at higher WM loads, suggesting that greater WM load is required to trigger interference. Event-related potential (ERP) results showed that N200 amplitudes increased significantly for incongruent flankers under the highest WM load (3-back) in the visual within-modality condition, reflecting greater inhibitory demands. In the cross-modality condition, enhanced N200 was not observed across all loads and even reversed at low load (1-back). Moreover, the results also showed that P300 amplitude increased with load in the within-modality condition but decreased in the cross-modality condition. Conclusions: These results demonstrated that the interaction between updating and inhibition is shaped by both WM load and sensory modality, further supporting a sensory modality-specific resource allocation mechanism. The cross-modality configurations may enable more efficient distribution of cognitive resources under high load, reducing interference between concurrent executive demands.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1662-453X192025Effects of visual spatial frequency on audiovisual interaction: an event-related potential study1599114ENFengxiaWuSchool of Artificial Intelligence, Changchun University of Science and TechnologyYannaRenDepartment of Psychology, College of Humanities and Management, Guizhou University of Traditional Chinese MedicineTengfeiHaoSchool of Artificial Intelligence, Changchun University of Science and TechnologyJingjingYangSchool of Artificial Intelligence, Changchun University of Science and TechnologyQiongWuDepartment of Psychology, Suzhou University of Science and TechnologyJiajiaYangCognitive Neuroscience Laboratory, Graduate School of Natural Science and Technology, Okayama UniversityMengWangSchool of Artificial Intelligence, Changchun University of Science and TechnologySpatial frequency is a fundamental characteristic of visual signals that modulates the audiovisual integration behavior, but the neural mechanisms underlying spatial frequency are not well established. In the present study, the high temporal resolution of event-related potentials was used to investigate how visual spatial frequency modulates audiovisual integration. A visual orientation discrimination task was used, and the spatial frequency of visual stimuli was manipulated under three conditions. Results showed that the influence of visual spatial frequency on audiovisual integration is a dynamic process. The earliest audiovisual integration occurred over the left temporal-occipital regions in the early sensory stage (60–90 ms) for high spatial frequency conditions but was absent for low and middle spatial frequency conditions. In addition, audiovisual integration over fronto-central regions was delayed as spatial frequency increased (from 230–260 ms to 260–320 ms). The integration effect was also observed over parietal and occipital regions at 350–380 ms, and its strength gradually decreased at higher spatial frequencies. These discrepancies in the temporal and spatial distributions of audiovisual integration imply that the role of spatial frequency varies between early sensory and late cognitive stages. The findings of this study offer the first neural demonstration that spatial frequency modulates audiovisual integration, thus providing a basis for studying complex multisensory integration, especially in semantic and emotional domains.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama1120-17971402025Improvements of lateral penumbra at various depth regions in proton pencil beam scanning with a multileaf collimator: Dose verifications and plan comparisons105684ENYukiTominagaDepartment of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy ClinicYushiWakisakaDepartment of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy ClinicTakahiroKatoDepartment of Radiological Sciences, School of Health Sciences, Fukushima Medical UniversityKeisukeYasuiSchool of Medical Sciences, Fujita Health UniversityRyoheiKatoDepartment of Radiation Physics and Technology, Southern Tohoku Proton Therapy CenterMasayaIchiharaMedical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of OsakaMasashiTomidaDepartment of Proton Beam Technology Room, Narita Memorial Proton CenterMotoharuSasakiGraduate School of Biomedical Sciences, Tokushima UniversityMasatakaOitaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTeijiNishioMedical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of OsakaPurpose: In scanned proton therapy, the current consensus is that the effective range of the collimator’s contribution to lateral penumbra improvement is up to approximately 150 mm depth. We characterized the penumbra variations for scanned proton beams with or without a new type of multileaf collimator (MLC) under various air gaps, depth, and with or without range shifter (RS).<br>
Methods: Eighty-six uniform dose plans were created (38 RS-negative and 48 RS-positive plans) for nine box targets of 60 × 60 × 54 mm3 at 0–280 mm depths in water. They were created with or without MLC, with 50–300 mm air gaps. The penumbra and average doses of MLC-positive and MLC-negative plans at the organs at risk (OAR) region of each box plan were compared. Besides, several plan doses were validated by measurements with penumbra (with an average of 80–20 % dose point widths for both side profiles) differences and 2D gamma analysis.<br>
Results: The MLC-positive plans reduced the penumbra and mean OAR doses by 1.0–5.1 mm and 3.3–13.5 %, respectively, compared to MLC-negative plans even at >150 mm depths. The penumbra differences in measurements were <±1.5 mm for all plans. The mean gamma scores at 2 %/2 mm were 97.9 ± 2.3 % and 97.4 ± 3.1 % for the MLC-negative and MLC-positive plans, respectively.<br>
Conclusions: The MLC-positive beams improved the penumbra and reduced the OAR dose in every depth region and air gap. We have shown that PBS with MLCs can be useful at more than 150 mm regions, depending on the machine.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1613-68102025Atomic-Level Insights into Thermal Carbonization of Ethynyl-Containing Boron Compoundse13537ENKentaroOhkuraResearch Institute for Interdisciplinary Science, Okayama UniversitySatoshiHayakawaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaokiTakahashiGraduate School of Environment Life Natural Science and Technology, Okayama UniversityKenYamazakiGraduate School of Environment Life Natural Science and Technology, Okayama UniversityJunKanoGraduate School of Environment Life Natural Science and Technology, Okayama UniversityYutaNishinaResearch Institute for Interdisciplinary Science, Okayama UniversityThis study reports the design, synthesis, and characterization of boron-doped carbon (BDC) derived from a triethynylborane-pyridine complex. Triethynylborane is stabilized by coordination with pyridine, facilitating its synthesis and handling in ambient conditions. The complex is subjected to thermal treatment at various temperatures to form BDC. Powder XRD and single-crystal XRD analyses reveal that BDC prepared at 200 °C retains an ordered structure, while higher temperatures induce alkyne structural changes without significant weight or surface area alterations. Coin cells are assembled using BDC as the anode, demonstrating unique Li-ion and Na-ion storage properties distinct from graphite. These results suggest that the BDC reflects the precursor's crystal structure, enabling novel electrochemical behavior. These findings offer insight into the development of advanced BDC materials for energy storage applications.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2730-6151512025Proliferation of a bloom-forming phytoplankton via uptake of polyphosphate-accumulating bacteria under phosphate-limiting conditionsycaf192ENSeiyaFukuyamaInstitute of Plant Science and Resources, Okayama UniversityFumikoUsamiInstitute of Plant Science and Resources, Okayama UniversityRyuichiHirotaGraduate School of Integrated Sciences for Life, Hiroshima UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ShizukaOharaGraduate School of Integrated Sciences for Life, Hiroshima UniversityKenKondoResearch Institute of Environment, Agriculture and Fisheries , Osaka PrefectureYukiGomibuchiDepartment of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of TechnologyTakuoYasunagaDepartment of Physics and Information Technology, Faculty of Computer Science and Systems Engineering, Kyushu Institute of TechnologyToshimitsuOndukaHatsukaichi Branch, Fisheries Technology Institute , Fisheries Research and Education AgencyAkioKurodaGraduate School of Integrated Sciences for Life, Hiroshima UniversityKazuhikoKoikeGraduate School of Integrated Sciences for Life, Hiroshima UniversityShokoUekiInstitute of Plant Science and Resources, Okayama UniversityHarmful algal blooms negatively impact the ecosystem and fisheries in affected areas. Eutrophication is a major factor contributing to bloom occurrence, and phosphorus is particularly important in limiting the growth of bloom-forming algae. Although algae efficiently utilize orthophosphate (Pi) as a phosphorous source over other molecular forms, Pi is often limited in the marine environment. While uptake and utilization of soluble inorganic and organic phosphorous by bloom-forming algae has been extensively studied, the details of geochemical and biological phosphorous cycling remain to be elucidated. Here, we report for the first time that the bloom-forming alga Heterosigma akashiwo can phagocytose bacteria and grow under phosphate-depleted conditions. The addition of Vibrio comitans to Pi-depleted H. akashiwo enabled the alga propagate to high cell densities, whereas other bacterial strains had only a minor effect. Importantly, V. comitans accumulates polyphosphate—a linear polymer of Pi—at high levels. The extent of algal proliferation induced by the addition of Vibrio species and polyphosphate-accumulating Escherichia coli correlated strongly with their polyphosphate content, indicating that bacterial polyphosphate served as an alternative PO43− source for H. akashiwo. The direct uptake of polyphosphate-accumulating bacteria through algal phagocytosis may represent a novel biological phosphorous-cycling pathway in marine ecosystems. The role of polyphosphate-accumulating marine bacteria as a hidden phosphorous source required for bloom formation warrants further investigation.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Study on neural mechanisms underlying multisensory spatiotemporal integration across visual, auditory, and tactile modalitiesENZIMOLIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025テラヘルツ波ケミカル顕微鏡による低分子生体関連物質の検出と高感度プロトコルの開発ENCHANGJIANGLIUGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025大規模ネットワークにおける多重故障の高速迂回に関する研究ENHERINIAINA Joseph Hermann DorisGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama1477-052023272025Fluorescence detection of DNA with a single-base mismatch by a Tm-independent peptide nucleic acid (PNA) twin probe65576563ENKokiIshiiDepartment of Applied Chemistry, Kindai UniversityHajimeShigetoHealth and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)ShoheiYamamuraHealth and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)YoshitaneImaiDepartment of Applied Chemistry, Kindai UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Kindai UniversityThere is a need to develop efficient methods for detecting target nucleic acids to enable the rapid diagnosis and early treatment of diseases. We previously demonstrated that a peptide nucleic acid (PNA) twin probe, consisting of two PNAs each containing a fluorescent dye, with pyrene at one end, detects target DNA sequence-specifically through pyrene excimer emission. In this study, to advance the development of this probe system, we further investigated the fluorescence properties of the PNA twin probe P1 and P2, and found that the excimer fluorescence was significantly reduced when a mismatched base in the DNA sequence was present at the site of P1 closest to the pyrene. In other words, this probe was found to detect single-base mismatches without taking into account the thermal stability of the PNA/DNA hybrid. The detection limit of this PNA twin probe for the single-base-mismatched DNA was 2.7 nM. In the future, this probe should lead to a method to detect point mutations in endogenous nucleic acids within cells.No potential conflict of interest relevant to this article was reported.Ceramic Society of JapanActa Medica Okayama1348-653513392025Preparation and structural characterization of nanoporous silica/magnesium(II)-whitlockite composite particles555561ENTakuyaKataokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityDaikiHirotaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityEijiFujiiIndustrial Technology Center of Okayama PrefectureTomohikoYoshiokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatoshiHayakawaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe preparation of particles composed of nanoporous silica (NS) and Mg2+-whitlockite (Mg-WH) would provide valuable insights for designing particles for biomedical applications. In this study, NS and Mg-WH composite particles were successfully synthesized. The addition of chitosan during synthesis possibly promoted the crystallization of calcium phosphate phases in the composite particles. Pore size distribution analysis of the particles showed a maximum at 3.2 nm. Investigating the adsorption of methylene blue onto the particles in a phosphate buffer (pH 7.4) showed that the saturated adsorption amount of methylene blue on the particles was significantly higher than that on commercial hydroxyapatite. The composite particles provided important results for potential applications as drug carriers for bone regeneration and repair.No potential conflict of interest relevant to this article was reported.Ceramic Society of JapanActa Medica Okayama1348-653513312025Comparative study of the effects of fluoride treatment with cyclic variations in pH on the structures of stoichiometric, calcium-deficient, and carbonated hydroxyapatites1524ENSatoshiHayakawaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYuOkadaGraduate School of Natural Science and Technology, Okayama UniversityTomohikoYoshiokaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe primary objective of this study was to analyze the effects of fluoride treatment with cyclic variations in pH on the structure of stoichiometric hydroxyapatite (HAp), calcium-deficient HAp (CDHAp), and carbonated HAp (CHAp) powders. The structures of HAp, CDHAp, and CHAp before and after fluoride treatment were investigated using X-ray diffraction, Fourier-transform infrared, Raman, and nuclear magnetic resonance spectroscopic analyses. The fluoride treatment with cyclic variations in pH increased the calcium deficiency in HAp and CHAp but decreased in CDHAp. During fluoride treatment, fluoridated CDHAp or fluoridated calcium-deficient CHAp was formed on the surface of the HAp samples via dissolution and crystal growth, accompanied by the selective elution of component ions and partial substitution of OH− groups in the HAp hexagonal lattice with F− ions. No evidence of the formation of Ca(OH)2 and OH− groups outside the HAp crystal lattice was obtained. A new perspective on the formation of structured water at the surface termination of the OH columns (disordered region), with possible interactions with adsorbed water molecules or nonspecifically adsorbed F− ions was provided. The top surface of the fluoridated CDHAp consisted of an amorphous fluoride-rich hydrated layer, which included calcium phosphate and CaF2.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama1422-006726172025Augmentation of the Benzyl Isothiocyanate-Induced Antiproliferation by NBDHEX in the HCT-116 Human Colorectal Cancer Cell Line8145ENRuitongSunGraduate School of Environmental and Life Science, Okayama UniversityAinaYanoGraduate School of Environmental and Life Science, Okayama UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShintaroMunemasaGraduate School of Environmental and Life Science, Okayama UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityToshiyukiNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityIncreased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC–glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC–GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0924-42473902025Extension-type flexible pneumatic actuator with a large extension force using a cross-link mechanism based on pantographs116594ENSoShimookaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityKazumaTadachiMechanical and Systems Engineering Program, School of Engineering, Okayama UniversityTetsushiKamegawaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityIn this study, we propose an extension-type flexible pneumatic actuator (EFPA) with a high extension force and no buckling. In a previous study, soft actuators that extended in the axial direction by applying a supply pressure were unable to generate the extension’s pushing force because the actuators buckled owing to their high flexibility. To generate a pushing force, the circumferential stiffness of an extension-type flexible soft actuator must be reinforced. Therefore, a cross-linked EFPA (CL-EFPA) was developed, inspired by a pantograph that restrains the EFPA three-dimensionally using the proposed link mechanism. The proposed CL-EFPA consists of three EFPAs and a cross-linking mechanism for integrating each EFPA circumference. The pushing force of the CL-EFPA is approximately 3.0 times compared with that generated by the previous EFPA with plates to restrain its plane. To perform various bending motions, attitude control was performed using an analytical model and a system that included valves, sensors, and controllers.No potential conflict of interest relevant to this article was reported.Fuji Technology Press Ltd.Acta Medica Okayama1883-80493712025Fan-Shaped Pneumatic Soft Actuator that Can Operate Bending Motion for Ankle-Joint Rehabilitation Device4353ENSoShimookaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityHirosatoYokoyaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasanoriHamadaDepartment of Rehabilitation Medicine, Okayama University HospitalShunShiomiDepartment of Rehabilitation Medicine, Okayama University HospitalTakenoriUeharaDepartment of Orthopaedic Surgery, NHO Okayama Medical CenterTakahiroHirayamaDepartment of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTetsushiKamegawaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityNowadays, owing to declining birthrates and an aging population, patients and the elderly requiring rehabilitation are not getting enough physical activity. In addressing this issue, devices for rehabilitating them have been researched and developed. However, rehabilitation devices are almost exclusively used for patients who can get up, rather than those who are bedridden. In this study, we aim to develop a rehabilitation device that can provide passive exercise for bedridden patients. The ankle joint was selected as the target joint because the patients who have undergone surgery for cerebrovascular disease remain bedridden, and early recovery in the acute stage is highly desirable. We proposed and tested a fan-shaped pneumatic soft actuator (FPSA) that can expand and bend stably at angles when supply pressure is applied as an actuator for a rehabilitation device to encourage patient exercise. However, the previous FPSA’s movement deviates from the arch of the foot owing to increased supply pressure. In the ideal case, FPSA should push the arch of the foot in an arc motion. This study proposes and tests the FPSA that can operate a bending motion to provide passive exercise to the ankle joint using tensile springs and a winding mechanism powered by a servo motor. The proposed FPSA has a significant advantage of exhibiting no hysteresis in its pressure-displacement characteristics. The configuration and static analytical model of the improved FPSA are described.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0094-24055282025Commissioning of respiratory‐gated 4D dynamic dose calculations for various gating widths without spot timestamp in proton pencil beam scanninge18026ENYukiTominagaDepartment of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy ClinicYushiWakisakaDepartment of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy ClinicTakahiroKatoDepartment of Radiological Sciences, School of Health Sciences, Fukushima Medical UniversityMasayaIchiharaMedical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of OsakaKeisukeYasuiSchool of Medical Sciences, Fujita Health UniversityMotoharuSasakiGraduate School of Biomedical Sciences, Tokushima UniversityMasatakaOitaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTeijiNishioMedical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of OsakaBackground: Proton pencil beam scanning (PBS) is susceptible to dose degradation because of interplay effects on moving targets. For cases of unacceptable motion, respiratory-gated (RG) irradiation is an effective alternative to free breathing (FB) irradiation. However, the introduction of RG irradiation with larger gate widths (GW) is hindered by interplay effects, which are analogous to those observed with FB irradiation. Accurate estimation of interplay effects can be performed by recording spot timestamps. However, our machine lacks this feature, making it imperative to find an alternative approach. Thus, we developed an RG 4-dimensional dynamic dose (RG-4DDD) system without spot timestamps.<br>
Purpose: This study aimed to investigate the accuracy of calculated doses from the RG-4DDD system for PBS plans with varying breathing curves, amplitudes, and periods for 10%–50% GW.<br>
Methods: RG-4DDDs were reconstructed using in-house developed software that assigned timestamps to individual spots, integrated start times for spills with breathing curves, and utilized deformable registrations for dose accumulation. Three cubic verification plans were created using a heterogeneous phantom. Additionally, typical liver and lung cases were employed for patient plan validation. Single- and multi-field-optimized (SFO and IMPT) plans (ten beams in total) were created for the liver and lung cases in a homogeneous phantom. Lateral profile measurements were obtained under both motion and no-motion conditions using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films on the CIRS dynamic platform. Breathing curves from the cubic plans were used to assess nine patterns of sine curves, with amplitudes of 5.0–10.0 mm (10.0–20.0 mm target motions) and periods of 3–6 sec. Patient field verifications were conducted using a representative patient curve with an average amplitude of 6.4 mm and period of 3.2 sec. Additional simulations were performed assuming a ± 10% change in assigned timestamps for the dose rate (DR), spot spill (0.08-s), and gate time delay (0.1-s) to evaluate the effect of parameter selection on our 4DDD models. The 4DDDs were compared with measured values using the 2D gamma index and absolute doses over that required for dosing 95% of the target.<br>
Results: The 2D-array measurements showed that average gamma scores for the reference (no motion) and 4DDD plans for all GWs were at least 99.9 ± 0.2% and 98.2 ± 2.4% at 3%/3 mm, respectively. The gamma scores of the 4DDDs in film measurements exceeded 95.4% and 92.9% at 2%/2 mm for the cubic and patient plans, respectively. The 4DDD calculations were acceptable under DR changes of ±10% and both spill and gate time delays of ±0.18 sec. For the 4DDD plan using all GWs for all measurement points, the absolute point differences for all validation plans were within ±5.0% for 99.1% of the points.<br>
Conclusions: The RG-4DDD calculations (less than 50% GW) of the heterogeneous and actual patient plans showed good agreement with measurements for various breathing curves in the amplitudes and periods described above. The proposed system allows us to evaluate actual RG irradiation without requiring the ability to record spot timestamps.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1071-269060102024Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells12151227ENMasakiyoSakaguchiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRieKinoshitaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNahokoTomonobuDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYoshihikoSakaguchiDepartment of Microbiology, Tokushima Bunri UniversityJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolHitoshiMurataDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKen-ichiYamamotoDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTettaTakahashiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYumaGoharaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToshikiOchiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineFanJiangDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNi Luh Gede YoniKomalasariFaculty of Medicine, Udayana UniversityYouyiChenDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of MedicineI Made WinarsaRumaFaculty of Medicine, Udayana UniversityI WayanSumardikaFaculty of Medicine, Udayana UniversityJinZhouMedical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of TechnologyTomokoHonjoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityFutoshiKuribayashiDepartment of Biochemistry, Kawasaki Medical SchoolKazumiSagayamaOrganization for Research and Innovation Strategy, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineEisakuKondoDivision of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical UniversityYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityThe first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy.No potential conflict of interest relevant to this article was reported.IOS PressActa Medica Okayama0926-96302025Assessing the Proportion of Clinical Trial Eligibility Criteria Expressible with Standard EHR Data Elements18921893ENRisaOkazakiDepartment of Pharmacy, Okayama University HospitalKunihisaKamikawaCenter for Innovative Clinical Medicine, Okayama University HospitalHidekiUnoCenter for Innovative Clinical Medicine, Okayama University HospitalHirotoOkudaDivision of Clinical Research of New Drugs and Therapeutics, Center for Innovative Clinical Medicine, Okayama University HospitalShihokoNambaDivision of Clinical Research of New Drugs and Therapeutics, Center for Innovative Clinical Medicine, Okayama University HospitalMitsunobuKanoGraduate School of Interdisciplinary Science and Technology in Health Systems, Okayama UniversityMizukiMoritaGraduate School of Interdisciplinary Science and Technology in Health Systems, Okayama UniversityPatient recruitment for clinical trials often requires substantial human effort and experiences delays, leading to increased drug development costs. Leveraging electronic health records (EHRs) may improve the accuracy of estimates of potentially recruitable patients. We evaluated the feasibility of using EHRs by analyzing the proportion of computable eligibility criteria.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy27502ENTakeruMoriGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMioKitagawaDepartment of Radiology, Sapporo Medical University School of MedicineTomokazuHasegawaDepartment of Radiology, Sapporo Medical University School of MedicineMasanoriSomeyaDepartment of Radiology, Sapporo Medical University School of MedicineTakaakiTsuchiyaDepartment of Radiology, Sapporo Medical University School of MedicineToshioGochoDepartment of Radiology, Sapporo Medical University School of MedicineTomokoHonjoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMireiDateGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMarikoMoriiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAiMiyamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunichiroFutamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe PACIFIC regimen, comprising chemoradiotherapy (CRT) followed by maintenance with the immune checkpoint inhibitor (ICI) durvalumab, has become the standard of care for patients with unresectable non-small cell lung cancer (NSCLC). Although ICI is used to prevent recurrence by targeting residual microtumors, biomarkers capable of monitoring immune activity during this phase remain lacking. Here, we evaluated whether temporal changes in serum autoantibody levels can predict treatment efficacy. This retrospective study included 20 patients with unresectable stage II or III NSCLC who received the PACIFIC regimen. Serum autoantibodies against 130 antigens were quantified before CRT, after CRT, and two weeks after the first ICI dose. The primary outcome was progression-free survival (PFS), and its association with autoantibody dynamics was examined. We observed an immediate and strong autoantibody response (spark response [SR]) after ICI initiation in patients with favorable treatment outcomes. Patients with SR and programmed death ligand 1 (PD-L1) expression ≥ 50% showed better PFS (two-year PFS; 72.9% vs. 18.2%, p = 0.0021). These findings suggest that serial monitoring of serum autoantibodies can provide a noninvasive approach to assess immune activity and predict treatment outcomes in patients receiving CRT or ICI therapy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0952-34803892025Ultrahigh‐Field MR‐Compatible Mechanical Tactile Stimulator for Investigating Somatosensory Processing in Small‐Bodied Animalse70105ENChenyuWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHirohikoImaiInnovation Research Center for Quantum Medicine, Gifu University School of MedicineMasakiFukunagaSection of Brain Function Information, National Institute for Physiological SciencesHirokiYamamotoGraduate School of Human and Environmental Studies, Kyoto UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazuhikoSekiDepartment of Neurophysiology, National Center of Neurology and PsychiatryTakashiHanakawaDepartment of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of MedicineTatsuyaUmedaDepartment of Integrated Neuroanatomy and Neuroimaging, Kyoto University Graduate School of MedicineJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityCommon marmosets (Callithrix jacchus), small-bodied New World primates that share similar sensory processing pathways with human beings, have gained great interests. Their small body size allows imaging of brain activity with high spatial resolution and on a whole-brain scale using ultrahigh-field (UHF) magnetic resonance imaging (MRI) scanners. However, the strong magnetic field and the small size of the hand and forearm pose challenges in delivering tactile stimulation during fMRI experiments. In the present study, we developed an MR-compatible tactile dual-point stimulator to provide high-precision mechanical stimulation for exploring somatosensory processing in small-bodied animals. The study population consisted of a water phantom and three male common marmosets. Cerebral blood volume (CBV) weighted fMRI data were obtained with a gradient echo (GE), echo-planar imaging (EPI) sequence at 7T scanner. The output performance of the device was tested by a pressure sensor. The MR compatibility of the device was verified by measuring the temporal signal-to-noise ratio (tSNR) of a water phantom. To test the effectiveness of tactile stimulation, we conducted block designed tactile stimulation experiments on marmosets. A one-way repeated measures ANOVA was conducted for comparing the tSNR results. We performed one-sample t-tests to investigate the negative response of the forearm and hand stimulation with a threshold of t > 1.96 (p < 0.05). Performance tests revealed that mechanical stimulation (averaged force: 31.69 g) was applied with a delay of 12 ms. Phantom experiments confirmed that there was no significant difference in the tSNR among three (10 Hz, 1 Hz, and no-stimulus) conditions (F (2, 798) = 0.71, p = 0.49). The CBV activity results showed that the stimulator successfully elicited hand and forearm somatosensory activations in primary somatosensory areas. These results indicated that the device is well suited for small-bodied animal somatosensory studies.No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama2433-41465712025イノベーションの発生源研究の再検討120ENQiHuangDaijiFujii10.18926/OER/69001 本論文は，イノベーションの発生源に関する先行研究を振り返り，「いつ」「どこで」「誰によって」イノベーションが生み出されるのかを理論的に考察することを目的とする。考察の結果，「B to B」の文脈においては，イノベーションの発生源が企業ユーザーへ移行するメカニズムとして，取引コスト理論，期待利益仮説，情報粘着性の仮説，企業内部の独自能力（吸収能力），および外部の産業構造（製品アーキテクチャ・エコシステム）といった複数の要素からなる経済的合理性の観点から分析されていることが明らかになった。一方，「B to C」の文脈では，エンドユーザーがイノベーションに向かう動機として，「ニッチ市場に対するメーカーの消極的な対応」「創造的活動の楽しさ」「ユーザーコミュニティとの繋がり」「知識・スキルの向上」など多種多様な要素が存在し，中でも創造的活動の楽しさが根源的な動機づけの1つであると確認された。一方で，イノベーターを突き動かす心理的要因をブラックボックス化したまま放置することは，単なる知的好奇心の問題に留まらず，社会科学としての経営学にとっても重要な問題であると考えられる。今後のイノベーションの発生源研究においては，起業家をはじめとするイノベーター個人の心理的側面にいかに目を向け，創造的活動におけるポジティブな感情が働くメカニズムをイノベーションの発生メカニズムにいかに位置づけるか，その研究アプローチの提示が求められる。No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0014-5793599132025Characterization of molecular mechanisms of CaMKKα/1 oligomerization19141924ENShunUenoyamaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHayatoNittaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversitySatomiOhtsukaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasakiMagariApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityFutoshiSuizuDepartment of Medical Technology, Kagawa Prefectural University of Health SciencesHiroshiTokumitsuCalcium/calmodulin-dependent protein kinase kinase (CaMKK) is an activating kinase for calcium/calmodulin-dependent protein kinase type 1 (CaMKI), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), RAC-alpha serine/threonine-protein kinase (PKB), and AMP-activated protein kinase (AMPK) that has been reported to form an active oligomer in cells. Glutathione S-transferase (GST) pulldown assay from the extracts of COS-7 cells expressing GST- and His6-CaMKKα/1 mutants showed that the C-terminal region containing the autoinhibitory and calmodulin (CaM)-binding sequence (residues 438–463) is required for CaMKKα/1 homo-oligomerization. This was confirmed by the fact that the GST-CaMKKα/1 C-terminal domain (residues 435–505) directly interacted with EGFP-CaMKKα/1 residues 435–505 as well as with wild-type CaMKKα/1. Notably, once oligomerized in cells, CaMKKα/1 is neither exchangeable between the oligomeric complexes nor dissociated by Ca2+/CaM binding. These results support stable oligomerization of CaMKK in the cells by intermolecular self-association of its C-terminal region containing a regulatory domain.No potential conflict of interest relevant to this article was reported.MDPI AGActa Medica Okayama2079-77371452025Mutagenesis Targeting the S153 Residue Within the Transmembrane β-Hairpin of Mosquito-Larvicidal Mpp46Ab Affects Its Toxicity and the Synergistic Toxicity with Cry4Aa489ENTohruHayakawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySyunYamaokaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMamiAsakuraGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMinakoHiranoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToruIdeGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWe constructed a library of Mpp46Ab mutants, in which S153 within the transmembrane β-hairpin was randomly replaced by other amino acids. Mutagenesis and subsequent primary screening yielded 10 different Mpp46Ab mutants in addition to the wild type. Remarkably, S153 was replaced with a more hydrophobic amino acid in most of the mutants, and the S153I mutant in particular exhibited significantly increased toxicity. Electrophysiologic analysis using artificial lipid bilayers revealed that the single-channel conductance and PK/PCl permeability ratio were significantly increased for S153I pores. This suggests that the formation of highly ion-permeable and highly cation-selective toxin pores increases the influx of cations and water into cells, thereby facilitating osmotic shock. In addition, the S153F, S153L, and S153I mutants exhibited significantly reduced synergistic toxicity with Cry4Aa. Electrophysiologic analysis showed that the S153F, S153L, and S153I mutants form toxin pores with a significantly reduced PK/PNa permeability ratio and a significantly increased PK/PCa permeability ratio compared to wild-type pores. Thus, our results suggest that pore formation is central to the insecticidal activity of Mpp46Ab and that the ion permeability of toxin pores is a potential indicator correlated with both toxicity and synergistic toxicity with other toxins.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama2772-4174132025Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers100242ENHayakiMaemotoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRyoheiSuzakiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKeijiItakaDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitymRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1526-99142662025Quantitative quality control of 3D water tank using image analysise70119ENYukiTanimotoDepartment of Radiology, NHO Kure Medical Center and Chugoku Cancer CenterKoheiSugimotoDepartment of Radiological Technology, Faculty of Health Science and Technology, Kawasaki University of Medical WelfareKazunobuKoshiDepartment of Radiology, NHO Fukuyama Medical CenterAkiraHiroshigeDepartment of Radiology, NHO Shikoku Cancer CenterShoheiYoshidaDepartment of Radiology, NHO Shikoku Cancer CenterYoshikiFujitaDepartment of Radiology, NHO Shikoku Cancer CenterAtsukiNakahiraDepartment of Radiology, NHO Shikoku Cancer CenterDaikiNakanishiDivision of Radiology, Department of Medical Technology, Kyushu University HospitalHirofumiHondaDepartment of Radiological Technology, Ehime University HospitalMasatakaOitaDepartment of Healthcare Science, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityBackground and objective: Accurate beam data acquisition using three-dimensional (3D) water tanks is essential for beam commissioning and quality control (QC) in clinical radiation therapy. This study introduces a novel method for quantitative QC of the system, utilizing MV images and webcam videos. The stability of the motor drive speed and the positional accuracy of the fixture were evaluated under two measurement modes: “continuous mode” and “step-by-step mode.”<br>
Methods: A TRUFIX mounting system (PTW Freiburg Inc., Germany) was used to attach the center of the steel ball to its top, ensuring alignment with the water surface of the tank. To assess deviations from the radiation isocenter, MV images were acquired and compared with digitally reconstructed radiographs (DRRs). These evaluations were performed at different speed settings (slow, medium, and fast) using ET CT Body Marker (BRAINLAB Inc., USA) mounted on the drive unit. A webcam was utilized to capture the images, and custom-developed tracking software was employed to analyze deviations in driving speed and positional errors.<br>
Results: The mean error of the radiation isocenter was 0.37 ± 0.09 mm. As the motor drive speed increased, the discrepancy between the set speed and the actual speed observed in the analysis also became larger. In “continuous mode,” the deviation from the displayed value was greater than that observed in “step-by-step mode.”<br>
Conclusion: It is demonstrated that the proposed analysis method can quantitatively evaluate radiation isocenter misalignment, tank setup position deviation, and both the indicated drive speed values and their stability. At higher drive speeds, the “step-by-step mode” showed smaller deviations from the indicated values.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-03331812024Standardization of radiation therapy quality control system through mutual quality control based on failure mode and effects analysis7885ENYukiTanimotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasatakaOitaFaculty of Interdisciplinary Science and Engineering in Health Systems, Department of Healthcare Science, Okayama UniversityKazunobuKoshiDepartment of Radiology, NHO Fukuyama Medical CenterKiyoshiIshiwakiDepartment of Radiology, NHO Iwakuni Medical CenterFutoshiHiramatsuDepartment of Radiology, NHO Hamada Medical CenterToshihisaSasakiDepartment of Radiology, NHO Higashi-Hiroshima Medical CenterHirokiIseDepartment of Radiology, NHO Iwakuni Medical CenterTakashiMiyagawaDepartment of Radiology, NHO Kanmon Medical CenterTakeshiMaedaDepartment of Radiology, NHO Kochi National HospitalShinsukeOkahiraDepartment of Radiology, NHO Yamaguchi-Ube Medical CenterTakashiHamaguchiDepartment of Radiology, NHO Okayama Medical CenterTatsuyaKawaguchiDepartment of Radiology, NHO Shikoku Medical Center for Children and AdultsNorihiroFunadaDepartment of Radiology, NHO Hamada Medical CenterShuheiYamamotoDepartment of Radiology, NHO Fukuyama Medical CenterAkiraHiroshigeDepartment of Radiology, NHO Shikoku Cancer CenterYukiMukaiDepartment of Radiology, NHO Shikoku Cancer CenterShoheiYoshidaDepartment of Radiology, NHO Shikoku Cancer CenterYoshikiFujitaDepartment of Radiology, NHO Shikoku Cancer CenterAtsukiNakahiraDepartment of Radiology, NHO Shikoku Cancer CenterHirofumiHondaDepartment of Radiological Technology, Ehime University HospitalThe advancement of irradiation technology has increased the demand for quality control of radiation therapy equipment. Consequently, the number of quality control items and required personnel have also increased. However, differences in the proportion of qualified personnel to irradiation techniques have caused bias in quality control systems among institutions. To standardize the quality across institutions, researchers should conduct mutual quality control by analyzing the quality control data of one institution at another institution and comparing the results with those of their own institutions. This study uses failure mode and effects analysis (FMEA) to identify potential risks in 12 radiation therapy institutions, compares the results before and after implementation of mutual quality control, and examines the utility of mutual quality control in risk reduction. Furthermore, a cost-effectiveness factor is introduced into FMEA to evaluate the utility of mutual quality control.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025肺腫瘍に対する定位放射線治療におけるターゲット設定の不確かさに関する研究ENDaikiNAKANISHIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Study of the Brain Topological Processing Mechanisms in the Human Sensorimotor SystemENCHENYUWANGGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Study on neural mechanisms of attention effects on auditory-tactile multisensory processingENWEICHAOANGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Study on the Influence of Object Compliance on Softness and Pleasantness PerceptionENBINYUEGAOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025高温超伝導SQUIDを用いた磁気ナノ粒子の磁気緩和ダイナミクス評価と応用探索ENKeiYAMASHITAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025Improved linear epitope-specific autoantibody discovery and quantitative assay systemENMireiDATE (MASUI)Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2025A Novel Drug Delivery System for Boron Neutron Capture Therapy (BNCT) in Cancer TheranosticsENABDUL BASITH FITHRONIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.老年人文学研究会Acta Medica Okayama2435-574732024迷惑をかけたくない意識の形成―教育との関係―2254ENXiaofanDENG10.18926/JHG/68714No potential conflict of interest relevant to this article was reported.老年人文学研究会Acta Medica Okayama2435-574732024西田幾多郎臨終記121ENRyozoSUZUKIKoichiroYAMAMOTOMikakoOBIKA10.18926/JHG/68713No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025裏表紙・英文目次ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025投稿規程・奥付ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-3227520252024年度次世代医療機器開発人材育成プログラムBIZENデバイスデザインコースの取り組み4755ENTsuneakiTSUZUKICenter for Innovative Clinical Medicine, Okayama University HospitalDaisukeUCHIDACenter for Innovative Clinical Medicine, Okayama University HospitalToshioKISHIMOTOOrganization for Research Strategy and Development, Okayama UniversityYoshinariSENGOKUCenter for Innovative Clinical Medicine, Okayama University HospitalToshioKORENAGAOrganization for Research Strategy and Development, Okayama UniversityYuHITOBECenter for Innovative Clinical Medicine, Okayama University HospitalYasuyukiYOSHIBAAcademic Field of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunSAKURAICenter for Innovative Clinical Medicine, Okayama University Hospital10.18926/interdisciplinary/68626No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025イノベーションループの実践：2024年度先進病院実習報告と未来課題3945ENNahokoHARADAAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universitySatoshiTAKAHASHIAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityTomoakiMORIAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityHarukaHIKASAAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityKeisukeSHISHIDOAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityMasakiMAGARIAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityToyohikoWATANABEAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityJinWangAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama universityMizukiMORITAAcademic Field of Interdisciplinary Science and Engineering in Health Systems Health Sciences, Okayama university10.18926/interdisciplinary/68625No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025第16回 高度医療都市を創出する未来技術国際シンポジウム3537ENJiajiaYANGGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/68624No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025岡山大学中央図書館・個人文庫「杏村文庫」の調査：詩人との交友を中心に2933ENRyozoSUZUKIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/68623No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025PrEP の利用に関する先行研究レビュー日本と中国を中心に1927ENDechengWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/68622No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025関係的自律理論に基づいた終末期に関する意思決定支援の検討1118ENSumiyoSONOYAMAThe University of Shimane10.18926/interdisciplinary/68621In contemporary end-of-life care, it is difficult for patients to make decisions without the influence of society, family, and other factors. In many cases, patients have the capacity to make the decisions; nevertheless, they have difficulty expressing their own will because of the influence of their relationships and environment. Patient concerns about the burden of care and also the social and economic impacts on family members often hinder their use of imagination and decision-making. Therefore, this study has examined how patients with decision-making capacities could achieve autonomy under the influence of their relationships with their surroundings. The method of decision-making support provided by nurses to patients was examined using relational autonomy theory. Relational autonomy theory attempts to reconceptualize autonomy through feminists who criticize individualist theories of autonomy.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025知の探索時間についての企業の意思決定プロセス19ENTakeshiSHIMIZUGraduate School of Interdisciplinary Science and Engineering in Health Systems Okayama University10.18926/interdisciplinary/68620In order for companies to innovate through business co-creation, it is necessary to explore a wide range of external knowledge and technologies. However, there is no clear answer as to how much time should be spent for exploration. Under these circumstances, companies must take into account constraints such as the amount of management resources that can be invested, and make decisions about the time to spend for exploration. The purpose of this paper is to clarify the process of how companies that have introduced corporate accelerator program recognize the relationship between the program period and the results of business co-creation, and how they make decisions about the program period. We conducted a case study of several companies that have introduced corporate accelerator program in Japan. In addition, this paper established a hypothesis about decision-making about the time for exploration from case studies.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322752025表紙・目次ENNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44181562025Robustness of Machine Learning Predictions for Determining Whether Deep Inspiration Breath-Hold Is Required in Breast Cancer Radiation Therapy668ENWlla E.Al-HammadDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasahiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityJamal, GhaidaAl JamalDepartment of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and TechnologyMamikoFujikuraDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyoKamizakiRadiological Technology, Graduate School of Health Sciences, Okayama UniversityKazuhiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversitySuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihideNakamuraDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityYoshinoriTanabeRadiological Technology, Graduate School of Health Sciences, Okayama UniversityKoheiSugimotoRadiological Technology, Graduate School of Health Sciences, Okayama UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityMajdBarhamDepartment of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National UniversityNouhaTekikiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Deep inspiration breath-hold (DIBH) is a commonly used technique to reduce the mean heart dose (MHD), which is critical for minimizing late cardiac side effects in breast cancer patients undergoing radiation therapy (RT). Although previous studies have explored the potential of machine learning (ML) to predict which patients might benefit from DIBH, none have rigorously assessed ML model performance across various MHD thresholds and parameter settings. This study aims to evaluate the robustness of ML models in predicting the need for DIBH across different clinical scenarios. Methods: Using data from 207 breast cancer patients treated with RT, we developed and tested ML models at three MHD cut-off values (240, 270, and 300 cGy), considering variations in the number of independent variables (three vs. six) and folds in the cross-validation (three, four, and five). Robustness was defined as achieving high F2 scores and low instability in predictive performance. Results: Our findings indicate that the decision tree (DT) model demonstrated consistently high robustness at 240 and 270 cGy, while the random forest model performed optimally at 300 cGy. At 240 cGy, a threshold critical to minimize late cardiac risks, the DT model exhibited stable predictive power, reducing the risk of overestimating DIBH necessity. Conclusions: These results suggest that the DT model, particularly at lower MHD thresholds, may be the most reliable for clinical applications. By providing a tool for targeted DIBH implementation, this model has the potential to enhance patient-specific treatment planning and improve clinical outcomes in RT.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44181562025Improving Diagnostic Performance for Head and Neck Tumors with Simple Diffusion Kurtosis Imaging and Machine Learning Bi-Parameter Analysis790ENSuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasahiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityYoshihideNakamuraDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukaFukumuraDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiNakamitsuRadiological Technology, Graduate School of Health Sciences, Okayama UniversityWlla E.Al-HammadDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityYudaiShimizuDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinoriTanabeRadiological Technology, Graduate School of Health Sciences, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityMajdBarhamDepartment of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National UniversityNouhaTekikiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNurul N.KamaruddinDepartment of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMikiHisatomiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshinobuYanagiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground/Objectives: Mean kurtosis (MK) values in simple diffusion kurtosis imaging (SDI)-a type of diffusion kurtosis imaging (DKI)-have been reported to be useful in the diagnosis of head and neck malignancies, for which pre-processing with smoothing filters has been reported to improve the diagnostic accuracy. Multi-parameter analysis using DKI in combination with other image types has recently been reported to improve the diagnostic performance. The purpose of this study was to evaluate the usefulness of machine learning (ML)-based multi-parameter analysis using the MK and apparent diffusion coefficient (ADC) values-which can be acquired simultaneously through SDI-for the differential diagnosis of benign and malignant head and neck tumors, which is important for determining the treatment strategy, as well as examining the usefulness of filter pre-processing. Methods: A total of 32 pathologically diagnosed head and neck tumors were included in the study, and a Gaussian filter was used for image pre-processing. MK and ADC values were extracted from pixels within the tumor area and used as explanatory variables. Five ML algorithms were used to create models for the prediction of tumor status (benign or malignant), which were evaluated through ROC analysis. Results: Bi-parameter analysis with gradient boosting achieved the best diagnostic performance, with an AUC of 0.81. Conclusions: The usefulness of bi-parameter analysis with ML methods for the differential diagnosis of benign and malignant head and neck tumors using SDI data were demonstrated.No potential conflict of interest relevant to this article was reported.American Association for Cancer Research (AACR)Acta Medica Okayama0008-54728562025Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy10821096ENToshifumiNinomiyaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoyaKemmotsuDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFumiakiMukoharaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasakiMagariApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAiMiyamotoMedical Protein Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoukiUedaDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakamasaIshinoDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJojiNagasakiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomohiroFujiwaraDepartment of Orthopaedic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHidetakaYamamotoDepartment of Pathology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHidetoshiHayashiDepartment of Medical Oncology, Kindai University Faculty of MedicineKotaTachibanaDepartment of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJojiIshidaDepartment of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoshihiroOtaniDepartment of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShotaTanakaDepartment of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Science, Okayama UniversityIsamuOkamotoDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityYosukeTogashiDepartment of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBrain metastasis is a poor prognostic factor in patients with cancer. Despite showing efficacy in many extracranial tumors, immunotherapy with anti–PD-1 mAb or anti–CTLA4 mAb seems to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti–PD-1 and anti–CTLA4 mAbs has a potent antitumor effect on brain metastasis, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. In this study, we analyzed the tumor-infiltrating lymphocytes in murine models of brain metastasis that responded to anti–CTLA4 and anti–PD-1 mAbs. Activated CD4+ T follicular helper (TFH) cells with high CTLA4 expression characteristically infiltrated the intracranial TME, which were activated by combination anti–CTLA4 and anti–PD-1 treatment. The loss of TFH cells suppressed the additive effect of CTLA4 blockade on anti–PD-1 mAb. B-cell–activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo proinflammatory M1-like macrophages, in the intracranial TME induced B-cell and TFH-cell infiltration and activation. Furthermore, the intracranial TME of patients with non–small cell lung cancer featured TFH- and B-cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell cross-talk in the intracranial TME that facilitates an additive antitumor effect of CTLA4 blockade with anti–PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for brain metastases.<br>
Significance: B-cell and CD4+ T follicular helper cell activation via BAFF/APRIL from abundant myeloid cells in the intracranial tumor microenvironment enables a combinatorial effect of CTLA4 and PD-1 blockade in brain metastases.No potential conflict of interest relevant to this article was reported.岡山大学農学部附属山陽圏フィールド科学センターActa Medica Okayama0910-874243-452023序iiiiENNo potential conflict of interest relevant to this article was reported.ScienceMattersActa Medica Okayama2297-8240292016S-nitrosylation of laforin inhibits its phosphatase activity and is implicated in Lafora diseaseENRikakoToyotaYasukoHonjoGraduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima UniversityRisaImajoGraduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima UniversityAyanoSatohGraduate School of Natural Science and Technology, Okayama University; Research Institute for Radiation Biology and Medicine, Hiroshima UniversityRecently, the relation between S-nitrosylation by nitric oxide (NO), which is over�produced under pathological conditions and neurodegenerative diseases, includingAlzheimer’s and Parkinson’s diseases, has become a focus of attention. Although mostcases of Parkinson’s disease are known to be caused by mutations in the Parkin gene, arecent finding has indicated that S-nitrosylation of Parkin affects its enzymatic activityand leads to the Parkinsonian phenotype. Therefore, it is important to understand thefunction of S-nitrosylated proteins in the pathogenesis of neurodegenerative diseases.Lafora disease (LD, OMIM 254780) is a neurodegenerative disease characterized by theaccumulation of insoluble glucans called Lafora bodies (LBs). LD is caused by mutationsin genes that encode the glucan phosphatase, Laforin, or the E3 ubiquitin ligase, Malin.In this study, we hypothesized that LD may be caused by S-nitrosylation of Laforin,which is similar to the finding that Parkinson’s disease is caused by S-nitrosylation ofParkin. To test this hypothesis, we first determined whether Laforin was S-nitrosylatedusing a biotin switch assay, and compared the three main functions of unmodified andS-nitrosylated Laforin, namely glucan- and Malin-binding activity and phosphataseactivity. Furthermore, we examined whether the numbers of LBs were changed byNO in the cells expressing wild-type Laforin. Here, we report for the first time thatS-nitrosylation of Laforin inhibited its phosphatase activity and that LB formation wasincreased by an NO donor. Our results suggest a possible hypothesis for LD pathogenesis; that is, the decrease in phosphatase activity of Laforin by S-nitrosylation leads toincreased LB formation. Therefore, LD may be caused not only by mutations in theLaforin or Malin genes, but also by the S-nitrosylation of Laforin.
No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0278-69151972025Fraglide-1 from traditional Chinese aromatic vinegar: A natural AhR antagonist for atopic dermatitis115301ENKosukeKatoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMikiAkamatsuGraduate School of Environmental and Life Science, Okayama UniversitySayaKakimaruGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMayukoKoreishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasahiroTakagiSchool of Materials Science, Japan Advanced Institute of Science and TechnologyMasahiroMiyashitaGraduate School of Agriculture, Kyoto UniversityYoshiyukiMurataGraduate School of Environmental and Life Science, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshioTsujinoGraduate School of Science, Technology and Innovation, Kobe UniversityTraditional Chinese Zhenjiang aromatic vinegar (Kozu) contains Fraglide-1 (FG1), a bioactive lactone with demonstrated peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antioxidant activities. This study explored FG1's novel ability to antagonize the aryl hydrocarbon receptor (AhR) signaling pathway, which regulates artemin expression and contributes to itching and inflammation in atopic dermatitis. Through molecular docking simulations and cell-based assays in human keratinocytes, we demonstrated FG1's potent antagonistic activity against AhR signaling. FG1 effectively suppressed FICZ-induced inflammatory responses, including artemin expression, with potency (half maximal inhibitory concentration, IC50 = 5.1 μM) comparable to the synthetic antagonist StemRegenin 1 (SR1) while demonstrating a superior safety profile (median lethal concentration, LC50 > 100 μM vs. 27.5 μM for SR1). These findings expand our understanding of bioactive compounds from traditional fermented foods and their regulatory effects on AhR signaling, providing a foundation for future studies on FG1's role in modulating skin inflammation.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-65962632025LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes1007ENShuichiNaniwaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityKeiichiroNishidaLocomotive Pain Center, Okayama University HospitalAkiYoshidaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityYoshihisaNasuLocomotive Pain Center, Okayama University HospitalRyuichiNakaharaLocomotive Pain Center, Okayama University HospitalTakashiOhtsukiDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityYoshifumiHottaDepartment of Orthopaedic Surgery, Sayo Central HospitalNoriyukiShimizuDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityChinatsuIchikawaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityDetingLinDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityNoriakiOtsukaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama UniversityToshifumiOzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityWe investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by siAGRN transfection partially reduced the nuclear protein expression of β-catenin, which was increased with intense CTS. LRP4 knockdown by siLRP4 transfection increased the expression of LRP5/6, SOX9, RUNX2, ADAMTS-4, and Agrin. These results suggested that intense CTS increases the expression of Agrin, which might interfere with the role of LRP4 in the inhibition of LRP5/6 and their downstream β-catenin signaling, leading to cartilage degeneration.No potential conflict of interest relevant to this article was reported.岡山大学農学部Acta Medica Okayama2186-77551142025Effects of dark respiration on dry matter production of various crop species110ENKuniyukiSaitohGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityTomohiroMurakamiGraduate School of Natural Science and Technology, Okayama UniversityYumiNakamuraSchool of Agriculture, Okayama UniversityMisaNishiboriSchool of Agriculture, Okayama UniversityYukiTakagoshiGraduate School of Natural Science and Technology, Okayama UniversityYoshihikoHiraiGraduate School of Environmental, Life, Natural Science and Technology, Okayama University Eleven crops were cultivated: maize, sunflower, soybean, groundnuts, sesame, kenaf, barley, wheat, rice, potato, and sweet potato. The crop growth rate (CGR) and specific dark-respiration rate (Rs) were measured, and growth efficiency GE =CGR/(CGR+R) (R, respiratory loss) was calculated. In each crop, whole-plant Rs reached a maximum in the earlier stages of growth, declined rapidly until the early reproductive growth, and remained almost constant during the ripening period. The Rs of leaves was higher than that of stems during the reproductive growth period, except for maize and potato. The Rs of storage organs was highest in the earlier stages, followed by a rapid decline to similar or lower values than those of leaves and stems during the ripening period. The GE in whole plant was higher than 60% in wheat, maize, barley, sunflower, rice, kenaf, sesame, but lower in soybean, sweet potato and groundnuts, and lowest in potato, which was affected by the higher respiratory loss. The GE in whole plant during the reproductive growth period was significantly lower, which we attributed to increased maintenance costs due to the increase of non-assimilative organs, and decrease in the dry weight of vegetative organs. A positive correlation was observed between the carbohydrate content of storage organs and GE, indicating that a crop with higher carbohydrate content in storage organs tended to have a higher GE. Crops with higher protein and crude fat content in storage organs tended to have lower GE. The GE over the growing season was low for kenaf, a fiber crop which contains high molecular weight compounds such as lignin and cellulose, and lower for sesame, groundnuts, and soybean, which contain high oil and protein and have high respiration costs for the synthesis of storage materials, suggesting that these higher respiration costs are related to lower dry matter production and hence lower yields.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-328X1512025The Impact of Task Context on Pleasantness and Softness Estimations: A Study Based on Three Touch Strategies63ENBinyueGaoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimichiEjimaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinglongWuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThis study investigated the two distinct perceptions (pleasantness and softness) of deformable stimuli with different degrees of compliance under conditions with and without a contextual task. Three tactile strategies-grasping, pinching, and pressing-were used to perceive the stimuli. In Experiment 1 (without a contextual task), participants estimated the perceived intensity of softness or pleasantness for each stimulus. In Experiment 2 (with a contextual task), the participants sequentially perceived two stimuli with different compliance levels and indicated which stimulus they perceived as softer and pleasant. The results showed that the psychophysical relationship between compliance and perceived softness was consistent across all tactile strategies in both experiments, with softness estimates increasing as compliance increased. However, the relationship between compliance and pleasantness differed between the two experiments. In Experiment 1, pleasantness estimates increased monotonically with increased compliance. However, in Experiment 2, across all tactile strategies, pleasantness began to decrease within the compliance range of 0.25-2.0 cm2/N, exhibiting an inverted U-shaped trend. These findings indicate that the relationship between compliance and pleasantness is task-dependent, particularly demonstrating significantly different trends when a contextual task is introduced. In contrast, the relationship between compliance and softness remained consistently monotonic.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2079-63741512025Mapping Surface Potential in DNA Aptamer-Neurochemical and Membrane-Ion Interactions on the SOS Substrate Using Terahertz Microscopy46ENKoseiMoritaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYutaMitsudaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySotaYoshidaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihikoKiwaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityIn this study, we utilized a terahertz chemical microscope (TCM) to map surface potential changes induced by molecular interactions on silicon-on-sapphire (SOS) substrates. By functionalizing the SOS substrate with DNA aptamers and an ion-selective membrane, we successfully detected and visualized aptamer-neurochemical complexes through the terahertz amplitude. Additionally, comparative studies of DNA aptamers in PBS buffer and artificial cerebrospinal fluid (aCSF) were performed by computational structure modeling and terahertz measurements. Beyond neurochemicals, we also investigated calcium ions, measuring their concentrations in PDMS-fabricated micro-wells using minimal sample volumes. Our results highlight the capability of TCM as a powerful, label-free, and sensitive platform for the probing and mapping of surface potential arising from molecular interactions, with broad implications for biomedical diagnostics and research.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0196-65535312025Effectiveness of sensing gloves–applied virtual reality education system on hand hygiene practice: A randomized controlled trial6569ENMahiroIzumiQuality Assurance Center, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHideharuHagiyaDepartment of Infectious Diseases, Okayama University HospitalYukiOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshiakiSoejimaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinnosukeFukushimaDepartment of Infectious Diseases, Okayama University HospitalMitsunobuShibataQuality Assurance Center, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatoshiHirotaQuality Assurance Center, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihiroKoyamaDepartment of Health Data Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkioGofukuQuality Assurance Center, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityBackground: We developed a virtual reality (VR) education system and evaluated its clinical utility for promoting hand hygiene practices.<br>
Methods: This prospective, 2-week, randomized controlled study conducted at Okayama University Hospital, Japan, from November 2023 to January 2024, involved 22 participants (18 medical students and 4 residents). A fully immersive 360° VR system (VIVE Pro Eye) using a head-mounted display and sensing gloves was used to develop 3 health care tasks in a virtual patient room—Environmental Cleaning, Gauze Exchange, and Urine Collection. After monitoring all participants' baseline usage data of portable hand-rubbing alcohol in the first week, we randomly assigned them into 1:1 groups (VR training and video lecture groups). The primary outcome was differences in hand-rubbed alcohol use before and after intervention.<br>
Results: Before the intervention, alcohol use did not significantly differ between both groups. After the intervention, a significant increase in alcohol use was observed in the VR training group (median: 8.2 g vs 16.2 g; P = .019) but not in the video lecture group.<br>
Conclusions: Our immersive 360° VR education system enhanced hand hygiene practices. Infection prevention and control practitioners and digital technology experts must collaborate to advance the development of superior educational devices and content.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama1756-46461252025Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways106672ENSakiOkamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySayaKakimaruGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMayukoKoreishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMikaSakamotoNational Institute of Genetics, ROISYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityHideyaAndoDepartment of Applied Chemistry and Biotechnology, Okayama University of ScienceYoshioTsujinoGraduate School of Science, Technology, and Innovation, Kobe UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityResveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2073-44091412025Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy60ENAbdul BasithFithroniGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHarukiInoueGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShengliZhouGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTaufik Fatwa NurHakimGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiTadaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMinoruSuzukiInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityYoshinoriSakuraiInstitute for Integrated Radiation and Nuclear Science, Kyoto UniversityManabuIshimotoJ-BEAM, Inc.NaoyukiYamadaNihon Fukushi Fuiin Holding, Co., Ltd.RaniSauriasariFaculty of Pharmacy, Universitas IndonesiaWolfgang A. G.SauerweinDeutsche Gesellschaft für Bor-Neutroneneinfangtherapie DGBNCT e.V., University Hospital Essen, Klinik für StrahlentherapieKazunoriWatanabeGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityEijiMatsuuraGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityBoron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction 10B (n, alpha) 7Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either 10B-Carb or 10B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any 10B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with 10B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-342514122024The Impact of Selective Spatial Attention on Auditory-Tactile Integration: An Event-Related Potential Study1258ENWeichaoAnGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNanZhangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShengnanLiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinglongWuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityBackground: Auditory-tactile integration is an important research area in multisensory integration. Especially in special environments (e.g., traffic noise and complex work environments), auditory-tactile integration is crucial for human response and decision making. We investigated the influence of attention on the temporal course and spatial distribution of auditory-tactile integration. Methods: Participants received auditory stimuli alone, tactile stimuli alone, and simultaneous auditory and tactile stimuli, which were randomly presented on the left or right side. For each block, participants attended to all stimuli on the designated side and detected uncommon target stimuli while ignoring all stimuli on the other side. Event-related potentials (ERPs) were recorded via 64 scalp electrodes. Integration was quantified by comparing the response to the combined stimulus to the sum of the responses to the auditory and tactile stimuli presented separately. Results: The results demonstrated that compared to the unattended condition, integration occurred earlier and involved more brain regions in the attended condition when the stimulus was presented in the left hemispace. The unattended condition involved a more extensive range of brain regions and occurred earlier than the attended condition when the stimulus was presented in the right hemispace. Conclusions: Attention can modulate auditory-tactile integration and show systematic differences between the left and right hemispaces. These findings contribute to the understanding of the mechanisms of auditory-tactile information processing in the human brain.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-342514122024Contributions of the Primary Sensorimotor Cortex and Posterior Parietal Cortex to Motor Learning and Transfer1184ENChenyuWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityBackground: Transferring learned manipulations to new manipulation tasks has enabled humans to realize thousands of dexterous object manipulations in daily life. Two-digit grasp and three-digit grasp manipulations require different fingertip forces, and our brain can switch grasp types to ensure good performance according to motor memory. We hypothesized that several brain areas contribute to the execution of the new type of motor according to the motor memory. However, the motor memory mechanisms during this transfer period are still unclear. In the present functional magnetic resonance imaging (fMRI) study, we aimed to investigate the cortical mechanisms involved in motor memory during the transfer phase of learned manipulation tasks. Methods: Using a custom-built T-shaped object with an adjustable weight distribution, the participants performed grasp and lift manipulation tasks under different conditions to simulate the learning and transfer phases. The learning phase consisted of four grasp-and-lift repetitions with one motor type, followed by a transfer phase with four repetitions involving different motors (adding or removing a digit). Results: By comparing brain activity in the learning and transfer phases, we identified three regions (the superior frontal gyrus, supramarginal gyrus, and postcentral gyrus) associated with motor memory during the transfer of learned manipulations. Conclusions: Our findings improve the understanding of the role of the posterior parietal cortex in motor memory, highlighting how sensory information from memory and real-time input is integrated to generate novel motor control signals that guide the precise reapplication of control strategies. Furthermore, we believe that these areas contribute to motor learning from motor memory and may serve as key regions of interest for investigating neurodegenerative diseases.No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama2635-0998232023All-in-one terahertz taste sensor: integrated electronic and bioelectronic tongues620626ENJinWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKenjiSakaiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihikoKiwaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTaste sensors, also known as electronic tongues or bioelectronic tongues, are designed to evaluate food and beverages, as well as for medical diagnostics. These devices mimic the ability of the human tongue to detect and identify different tastes in liquid samples, such as sweet, sour, salty, bitter, and umami. In this study, a novel all-in-one terahertz taste sensor was proposed, which differs from traditional electrochemical approaches. This sensor utilizes terahertz technology for imaging and sensing chemical reactions on the terahertz semiconductor emitter surface. The surface can be functionalized with ion-sensitive membranes, proteins, DNA aptamers, and organic receptors, enabling the detection of various substances, such as solution pH, physiological ions, sugars, toxic chemicals, drugs, and explosives. Terahertz taste sensors offer several advantages, including being label-free, high sensitivity and selectivity, rapid response, minimal sample consumption, and the ability to detect non-charged chemical substances. By integrating multiple receptors or sensing materials on a single chip, the all-in-one terahertz taste sensor has significant potential for future taste substance detection, nutrition evaluation, metabolite and drug monitoring, and biomarker sensing.No potential conflict of interest relevant to this article was reported.Fuji Technology Press Ltd.Acta Medica Okayama1883-80493512023Development of Automatic Inspection Systems for WRS2020 Plant Disaster Prevention Challenge Using Image Processing6573ENYuyaShimizuOkayama UniversityTetsushiKamegawaOkayama UniversityYongdongWangOkayama UniversityHajimeTamuraOkayama UniversityTaigaTeshimaOkayama UniversitySotaNakanoOkayama UniversityYukiTadaOkayama UniversityDaikiNakanoOkayama UniversityYuichiSasakiOkayama UniversityTaigaSekitoOkayama UniversityKeisukeUtsumiOkayama UniversityRaiNagaoOkayama UniversityMizukiSembaOkayama UniversityIn this article, an approach used for the inspection tasks in the WRS2020 Plant Disaster Prevention Challenge is explained. The tasks were categorized into three categories: reading pressure gauges, inspecting rust on a tank, and inspecting cracks in a tank. For reading pressure gauges, the “you only look once” algorithm was used to focus on a specific pressure gauge and check the pressure gauge range strings on the gauge using optical character recognition algorithm. Finally, a previously learned classifier was used to read the values shown in the gauge. For rust inspection, image processes were used to focus on a target plate that may be rusted for rust detection. In particular, it was necessary to report the rust area and distribution type. Thus, the pixel ratio and grouping of rust were used to count the rust. The approach for crack inspection was similar to that for rust. The target plate was focused on first, and then the length of the crack was measured using image processing. Its width was not measured but was calculated using the crack area and length. For each system developed to approach each task, the results of the preliminary experiment and those of WRS2020 are shown. Finally, the approaches are summarized, and planned future work is discussed.No potential conflict of interest relevant to this article was reported.IARIAActa Medica Okayama1942-2644173-42024Deep Reinforcement Learning Enabled Adaptive Virtual Machine Migration Control in Multi-Stage Information Processing Systems116125ENYukinobuFukushimaFaculty of Environmental, Life, Natural Science and Technology Okayama UniversityYukiKoujitaniGraduate School of Natural Science and Technology Okayama UniversityKazutoshiNakaneGraduate School of Information Science Nagoya UniversityYuyaTarutaniGraduate School of Engineering Osaka UniversityCelimugeWuGraduate School of Informatics and Engineering The Univ. of Electro-Commun.YushengJiInformation Systems Architecture Research Division National Institute of InformaticsTokumiYokohiraFaculty of Interdisciplinary Science and Engineering in Health Systems Okayama UniversityTutomuMuraseGraduate School of Information Science Nagoya UniversityThis paper tackles a Virtual Machine (VM) migration control problem to maximize the progress (accuracy) of information processing tasks in multi-stage information processing systems. The conventional methods for this problem are effective only for specific situations, such as when the system load is high. In this paper, in order to adaptively achieve high accuracy in various situations, we propose a VM migration method using a Deep Reinforcement Learning (DRL) algorithm. It is difficult to directly apply a DRL algorithm to the VM migration control problem because the size of the solution space of the problem dynamically changes according to the number of VMs staying in the system while the size of the agent’s action space is fixed in DRL algorithms. To cope with this difficulty, the proposed method divides the VM migration control problem into two problems: the problem of determining only the VM distribution (i.e., the proportion of the number of VMs deployed on each edge server) and the problem of determining the locations of all the VMs so that it follows the determined VM distribution. The former problem is solved by a DRL algorithm, and the latter by a heuristic method. This approach makes it possible to apply a DRL algorithm to the VM migration control problem because the VM distribution is expressed by a vector with a fixed number of dimensions and can be directly outputted by the agent. The simulation results confirm that our proposed method can adaptively achieve quasi-optimal accuracy in various situations with different link delays, types of the information processing tasks and the number of VMs.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Establishment and Analysis of Novel In Vitro 3D Cell Culture Models of the Fibrotic Tumor Microenvironment in Pancreatic CancerENHiroyoshiTANAKAOkayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024戦前から戦後期における内モンゴル地域の医療衛生の近代化と日本の影響―戦中期留日医学生ホルチンビリクらを中心にーENXUEFENGBAOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024MGST2遺伝子欠失マウスにおける磁気共鳴画像法による眼の形態学的解析ENCHAOMULIGEGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024放射線治療品質管理の重要性と標準化に向けた実践に関する研究ENYukiTANIMOTOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024The neural substrates of temporal prediction forming tactile perception in humansENRONGXIARENGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Effects of Subjective Cognitive Decline on Audiovisual Integration and Cross-modal TrainingENSHENGNANLIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024The neural substrates of motion inhibitory control during Go/No-Go response inhibition taskENNANZHANGGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Computer Vision Systems for Estimating Food Consumption in a Hospital SettingENYUITA ARUM SARIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Computer Vision-based Motion Segmentation and Its Application for Sperm Quality EstimationENSIGIT ADINUGROHOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Development of Peptide Nanomicelle for siRNA Delivery into Cancer CellsENTAUFIK FATWA NUR HAKIMGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2024Application of novel tumor-homing peptide-modified magnetic nanoparticles for magnetic hyperthermia and tumor cell detectionENSHENGLIZHOUGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1661-659625222024Distribution and Incorporation of Extracellular Vesicles into Chondrocytes and Synoviocytes11942ENTakashiOhtsukiDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityIkumiSatoDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityRenTakashitaDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityShintaroKodamaDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityKentaroIkemuraDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityGabrielOpokuDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityShogoWatanabeDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityTakayukiFurumatsuDepartment of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiroshiYamadaDepartment of Neuroscience, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMitsuruAndoLaboratory of Biomaterials, Institute for Life and Medical Sciences, Kyoto UniversityKazunariAkiyoshiDepartment of Immunology, Graduate School of Medicine, Kyoto UniversityKeiichiroNishidaDepartment of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityOsteoarthritis (OA) is a chronic disease affecting over 500 million people worldwide. As the population ages and obesity rates rise, the societal burden of OA is increasing. Pro-inflammatory cytokines, particularly interleukin-1β, are implicated in the pathogenesis of OA. Recent studies suggest that crosstalk between cartilage and synovium contributes to OA development, but the mechanisms remain unclear. Extracellular vesicles (EVs) were purified from cell culture-conditioned medium via ultracentrifugation and confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We demonstrated that EVs were taken up by human synoviocytes and chondrocytes in vitro, while in vivo experiments revealed that fluorescent-labelled EVs injected into mouse joints were incorporated into chondrocytes and synoviocytes. EV uptake was significantly inhibited by dynamin-mediated endocytosis inhibitors, indicating that endocytosis plays a major role in this process. Additionally, co-culture experiments with HEK-293 cells expressing red fluorescent protein (RFP)-tagged CD9 and the chondrocytic cell line OUMS-27 confirmed the transfer of RFP-positive EVs across a 600-nm but not a 30-nm filter. These findings suggest that EVs from chondrocytes are released into joint fluid and taken up by cells within the cartilage, potentially facilitating communication between cartilage and synovium. The results underscore the importance of EVs in OA pathophysiology.No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama2433-41465622024なぜ中間組織が必要なのか116ENDaijiFujiiTamakoOshima10.18926/OER/67705 This paper challenges a fundamental question, ‘Why is an intermediate organization necessary?’ Due to transaction costs and market failures on the one hand and the limitations of organizational control mechanisms on the other hand, many‘ intermediate organizations’ are observed in the real world. How can we tackle to explain the governance mechanism considered to be‘ intermediate?’
If we are to discuss such socioeconomic orders, this paper assumes that we should not be able to link micro-level explanations and macro-level ones concerning the third mode of governance mechanisms all at once. We need to stick to the meso-level at fi rst. The theoretical elaboration since Ouchi’s（1980） discussion of clan-type governance and cumulative empirical research on industrial agglomerations have allowed us to construct a more sophisticated theory called community capital.
In effective communities, members are ‘embedded as insiders’ who serve the purpose of the community, share experiences of failures and successes, and find and deepen their common identity. This limited membership is bound by‘ mutual trust to rely on each other’ for‘ distribution of short-term risks.’ In contrast to social norms that need to be abstract enough to be widely shared, the communal norms that are concrete enough to allow the members to understand without hesitation how they should behave in localized contexts are cumulatively cultivated along socializing process. Among the norms, sense of mutual obligation to incur intermittent costs for the whole community is a crucial norm for the sustainable development of the community. However, as a practical matter, membership control, mutual trust and short-term risk allocation may serve the communities in the short run, but they do not guarantee long-term accumulation of shared capital. As a result, the limits of community capital may need to be discussed once again, especially today when market liquidity is increasing, and its failures tend to become more apparent in a variety of areas.No potential conflict of interest relevant to this article was reported.Institute of Electrical and Electronics EngineersActa Medica Okayama2169-3536122024A Protection Scheme With Speech Processing Against Audio Adversarial Examples146551146559ENYuyaTarutaniFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTaiseiYamamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYukinobuFukushimaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityTokumiYokohiraFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMachine learning technologies have improved the accuracy of speech recognition systems, and devices using those systems, such as smart speakers and AI assistants, are now in wide use. However, speech recognition systems have security vulnerabilities. In particular, a known machine learning vulnerability called audio adversarial examples (AAEs), which causes misrecognition in speech recognition systems, has become a problem. We propose a scheme for using speech processing to protect speech recognition systems from AAEs, preventing misrecognitions by slight processing of input speech that does not affect the recognition of normal speech. We use two kinds of processing: speed and frequency. Evaluation results show that the proposed scheme can reduce the success rate of attack speech to about 1% while maintaining about 85% recognition rates for normal speech.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0928-070711222024Electrochemically assisted sol-gel deposition of bioactive gels for biomedical applications419424ENTomohikoYoshiokaBiomaterials Laboratory, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaokiMiyamotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatoshiHayakawaBiomaterials Laboratory, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySo far, the sol-gel process has been available to prepare precursor gels of bioactive glasses with various compositions. In this report, we described a novel coating method of bioactive gels on a titanium substrate where the sol-gel transition is controlled by applying external electric fields. The application of a constant current of 10 mA/cm2 in an acidic sol containing pre-hydrolyzed tetraethoxysilane, calcium nitrate, and ammonium dihydrogen phosphate led to the deposition of gels on the titanium cathodes due to the generation of OH– by water electrolysis as a catalyst of the sol-gel transition. The obtained gels, which were characterized to be amorphous and consisted of Si, Ca, and P, covered the titanium substrates as a coating. The bioactivity of the gels deposited was confirmed by soaking in a simulated body fluid (SBF) up to 7 days, suggesting that the electrochemically assisted sol-gel process is promising for providing bioactive coatings on metallic implants.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1420-304929112024In Vitro Study of Tumor-Homing Peptide-Modified Magnetic Nanoparticles for Magnetic Hyperthermia2632ENShengliZhouDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKanameTsutsumiuchiCollege of Bioscience and Biotechnology, Chubu UniversityRitsukoImaiCollege of Bioscience and Biotechnology, Chubu UniversityYukikoMikiCollege of Bioscience and Biotechnology, Chubu UniversityAnnaKondoCollege of Bioscience and Biotechnology, Chubu UniversityHiroshiNakagawaCollege of Bioscience and Biotechnology, Chubu UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityCancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama2234-943X142024Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis1371307ENFanJiangDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYouyiChenDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of MedicineNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNi Luh Gede YoniKomalasariFaculty of Medicine, Udayana UniversityCarlos IchiroKasano-CamonesFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityKazumiNinomiyaFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityHitoshiMurataDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-IchiYamamotoDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaGoharaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshikiOchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesI. Made WinarsaRumaFaculty of Medicine, Udayana UniversityI. WayanSumardikaFaculty of Medicine, Udayana UniversityJinZhouMedical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of TechnologyTomokoHonjoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshihikoSakaguchiDepartment of Microbiology, Tokushima Bunri UniversityAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolFutoshiKuribayashiDepartment of Biochemistry, Kawasaki Medical SchoolJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityEisakuKondoDivision of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical UniversityYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-beta 1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-beta 1 hastens the invasive outgrowth of TNBC cells at the molecular level.<br>
Methods LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively.<br>
Results Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-kappa B (NF-kappa B). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-beta activated kinase 1 (TAK1) were required for the activation of NF-kappa B through I kappa beta kinase kinase (IKK alpha/beta) phosphorylation.<br>
Conclusion Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-beta 1-TRAF4-TAK1-IKK alpha/beta-I kappa beta alpha-NF-kappa B-MMP9, is crucial for TNBC cell invasiveness.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-34251452024Go/No-Go Ratios Modulate Inhibition-Related Brain Activity: An Event-Related Potential Study414ENNanZhangGraduate of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWeichaoAnGraduate of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYinghuaYuGraduate of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinglongWuGraduate of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiajiaYangGraduate of Interdisciplinary Science and Engineering in Health Systems, Okayama University(1) Background: Response inhibition refers to the conscious ability to suppress behavioral responses, which is crucial for effective cognitive control. Currently, research on response inhibition remains controversial, and the neurobiological mechanisms associated with response inhibition are still being explored. The Go/No-Go task is a widely used paradigm that can be used to effectively assess response inhibition capability. While many studies have utilized equal numbers of Go and No-Go trials, how different ratios affect response inhibition remains unknown; (2) Methods: This study investigated the impact of different ratios of Go and No-Go conditions on response inhibition using the Go/No-Go task combined with event-related potential (ERP) techniques; (3) Results: The results showed that as the proportion of Go trials decreased, behavioral performance in Go trials significantly improved in terms of response time, while error rates in No-Go trials gradually decreased. Additionally, the NoGo-P3 component at the central average electrodes (Cz, C1, C2, FCz, FC1, FC2, PCz, PC1, and PC2) exhibited reduced amplitude and latency; (4) Conclusions: These findings indicate that different ratios in Go/No-Go tasks influence response inhibition, with the brain adjusting processing capabilities and rates for response inhibition. This effect may be related to the brain's predictive mechanism model.No potential conflict of interest relevant to this article was reported.IARIAActa Medica Okayama2308-44132024Application of a Deep Reinforcement Learning Algorithm to Virtual Machine Migration Control in Multi-Stage Information Processing Systems1318ENYukinobuFukushimaOkayama UniversityYukiKoujitaniOkayama UniversityKazutoshiNakaneNagoya UniversityYutaTarutaniOkayama UniversityCelimugeWuThe Univ. of Electro-Commun.YushengJiNational Institute of InformaticsTokumiYokohiraOkayama UniversityTutomuMuraseNagoya UniversityThis paper tackles a Virtual Machine (VM) migration control problem to maximize the progress (accuracy) of information processing tasks in multi-stage information processing systems. The conventional methods for this problem (e.g., VM sweeping method and VM number averaging method) are effective only for specific situations, such as when the system load is high. In this paper, in order to achieve high accuracy in various situations, we propose a VM migration method using a Deep Reinforcement Learning (DRL) algorithm. It is difficult to directly apply a DRL algorithm to the VM migration control problem because the size of the solution space of the problem dynamically changes according to the number of VMs staying in the system while the size of the agent’s action space is fixed in DRL algorithms. Therefore, the proposed method divides the VM migration control problem into two problems: the problem of determining only the VM distribution (i.e., the proportion of the number of VMs deployed on each edge server) and the problem of determining the locations of all the VMs so that it follows the determined VM distribution. The former problem is solved by a DRL algorithm, and the latter problem is solved by a heuristic method. The simulation results confirm that our proposed method can select quasi-optimal VM locations in various situations with different link delays.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2227-97171242024Pyrene-Modified Cyclic Peptides Detect Cu2+ Ions by Fluorescence in Water746ENYuhiMaekawaDepartment of Applied Chemistry, Faculty of Science and Engineering, Kindai UniversitySoraSakuraDepartment of Applied Chemistry, Faculty of Science and Engineering, Kindai UniversityYujiFurutaniDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRentoFujiharaDepartment of Applied Chemistry, Faculty of Science and Engineering, Kindai UniversityHisashiSugimeDepartment of Applied Chemistry, Faculty of Science and Engineering, Kindai UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMizukiKitamatsuDepartment of Applied Chemistry, Faculty of Science and Engineering, Kindai UniversityThe detection of metal ions is an option for maintaining water quality and diagnosing metal ion-related diseases. In this study, we successfully detected metal ions using fluorescent peptides in water. First, we prepared seven linear (L1-L7) and seven cyclic (C1-C7) peptides containing two pyrenyl (Pyr) units and assessed the response to various metal ions by fluorescence. The results indicated that C1, which contains a hexameric cyclic peptide moiety consisting of Pyr and Gly units, did not show a fluorescent response to metal ions, while the linear L1 corresponding to C1 showed a response to Cu2+, but its selectivity was found to be poor through a competition assay for each metal ion. We then assessed C2-C7 and L2-L7, in which Gly was replaced by His units at various positions in the same manner. The results showed that C2-C7 responded to Cu2+ in a manner dependent on the His position. Additionally, superior selectivity was observed in C7 through a competition assay. These results demonstrate that the structural restriction of peptides and the sequence affect the selective detection of Cu2+ and reveal that peptides with an appropriate structure can accomplish the fluorescent detection of Cu2+ specifically.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0946-271610142023Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells431447ENYumaGoharaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNahokoTomonobuDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineRieKinoshitaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityLénaAudebertDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYouyiChenDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineNi Luh Gede YoniKomalasariDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineFanJiangDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineChikakoYoshizawaDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHitoshiMurataDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKen-ichiYamamotoDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasamiWatanabeDepartment of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiromiKumonInnovation Center Okayama for Nanobio-Targeted Therapy, Okayama UniversityMasakiyoSakaguchiDepartment of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineThe adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3—namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama1865-03331642023Investigation of uncertainty in internal target volume definition for lung stereotactic body radiotherapy497505ENDaikiNakanishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJun-IchiFukunagaDivision of Radiology, Department of Medical Technology, Kyushu University HospitalTaka-AkiHiroseDivision of Radiology, Department of Medical Technology, Kyushu University HospitalTadamasaYoshitakeDepartment of Clinical Radiology, Graduate School of Medical Sciences, Kyushu UniversityMotoharuSasakiGraduate School of Biomedical Sciences, Tokushima UniversityThis study evaluated the validity of internal target volumes (ITVs) defined by three- (3DCT) and four-dimensional computed tomography (4DCT), and subsequently compared them with actual movements during treatment. Five patients with upper lobe lung tumors were treated with stereotactic body radiotherapy (SBRT) at 48 Gy in four fractions. Planning 3DCT images were acquired with peak-exhale and peak-inhale breath-holds, and 4DCT images were acquired in the cine mode under free breathing. Cine images were acquired using an electronic portal imaging device during irradiation. Tumor coverage was evaluated based on the manner in which the peak-to-peak breathing amplitude on the planning CT covered the range of tumor motion (± 3 SD) during irradiation in the left–right, anteroposterior, and cranio-caudal (CC) directions. The mean tumor coverage of the 4DCT-based ITV was better than that of the 3DCT-based ITV in the CC direction. The internal margin should be considered when setting the irradiation field for 4DCT. The proposed 4DCT-based ITV can be used as an efficient approach in free-breathing SBRT for upper-lobe tumors of the lung because its coverage is superior to that of 3DCT.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0920-90697532023GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation243253ENGhmkinHassanDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversitySaid M.AfifyDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversityMaram H.ZahraDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversityHend M.NawaraDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversityKazukiKumonDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversityYoshiakiIwasakiHealth Service Center, Okayama UniversityDavid S.SalomonCenter for Cancer Research, National Cancer InstituteAkimasaSenoDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversityMasaharuSenoDepartment of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama UniversityInduced pluripotent stem cells (iPSCs) are useful tools for modeling diseases and developing personalized medicine. We have been developing cancer stem cells (CSCs) from iPSCs with conditioned medium (CM) of cancer-derived cells as the mimicry of the microenvironment of tumor initiation. However, the conversion of human iPSCs has not always been efficient with only CM. In this study, human iPSCs reprogrammed from monocytes of healthy volunteers were cultured in a media containing 50% of the CM from human pancreatic cancer derived BxPC3 cells supplemented with a MEK inhibitor (AZD6244) and a GSK-3α/β inhibitor (CHIR99021). The survived cells were assessed for the characteristics of CSCs in vitro and in vivo. As a result, they exhibited CSC phenotypes of self-renewal, differentiation, and malignant tumorigenicity. Primary culture of the malignant tumors of the converted cells exhibited the elevated expression of CSC related genes CD44, CD24 and EPCAM maintaining the expression of stemness genes. In conclusion, the inhibition of GSK-3α/β and MEK and the microenvironment of tumor initiation mimicked by the CM can convert human normal stem cells into CSCs. This study could provide insights into establishing potentially novel personalized cancer models which could help investigate the tumor initiation and screening of personalized therapies on CSCs.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024裏表紙・英文目次ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024投稿規程・奥付ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-3227420242023年度次世代医療機器開発人材育成プログラム BIZENデバイスデザインコースの取り組み4149ENToshioKORENAGAOrganization for Research Strategy and Development, Okayama UniversityDaisukeUCHIDACenter for Innovative Clinical Medicine, Okayama University HospitalToshioKISHIMOTOOrganization for Research Strategy and Development, Okayama UniversityYoshinariSENGOKUCenter for Innovative Clinical Medicine, Okayama University HospitalHisaoOKACenter for Innovative Clinical Medicine, Okayama University HospitalTsuneakiTSUZUKICenter for Innovative Clinical Medicine, Okayama University HospitalYasuyukiYOSHIBAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunSAKURAIOrganization for Research Strategy and Development, Okayama University10.18926/interdisciplinary/66897No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-3227420242023年度における「先進病院実習」の取り組み3139ENMizukiMORITAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTomoakiMORIFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshiakiAIDAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToyohikoWATANABEFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityDaijiFUJIIFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNahokoHARADAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityReiHAKAMADAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYasuyukiYOSHIBAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/66896No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024ヘルスシステム統合科学研究科国際シンポジウム報告2729ENToshihikoKIWAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaokiKANAYAMAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNahokoHARADAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityReiHAKAMADAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/66895No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024医療における無益性に関する議論の変遷：レビュー1925ENShiroOHYAMAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/66894No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024アトピー性皮膚炎のある成人が経験するかゆみに関する記述研究918ENYukiHIRAMIFaculty of Health Sciences, Okayama UniversityKanakoFUJIMOTOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasahideKODAFaculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNahokoHARADAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/66893Background: Atopic Dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching, significantly impacting patients' psychosocial well-being worldwide. Objective: This study aimed to elucidate the multifaceted and multilayered burden of itch in adult AD patients, exploring strategies to capture the complexity of the disease and its symptoms comprehensively. Methods: The study utilized an array of Patient Reported Outcome (PRO) measures and conducted an exploratory analysis of patients' subjective descriptions of their itch experiences. Results: Twenty-three participants (female: n=16) were enrolled in the study. The Analyses revealed that none of the participants experienced in the same way about physical, emotional, and psychological burden of itch and limitation in social life. Additionally, it was found that PROs capture only partial aspects of itch and do not provide a comprehensive understanding. Discussion: The findings highlight the necessity of employing multiple PROs and conducting in-depth patient interviews to understand the daily life challenges associated with itch. The potential of interdisciplinary research to address the complex burden of itch in AD patients is also emphasized. Conclusion: A comprehensive understanding of the symptom of itch in AD patients requires the use of multiple PROs.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024⼈類社会の持続的発展に貢献する統合科学117ENAkioGOFUKUOkayama University10.18926/interdisciplinary/66892With the increase of the complexity of human society because of the globalization and the advancement of each scientific field, innovations by effective collaborations of experts in various fields become necessary to solve problems in human society and to increase the findings of each field. From the backgrounds, the interdisciplinary science b ecomes popular in recent y ears. This article p resents the approach of interdisciplinary science and its importance to the sustainable development of human society. As an example of studies by interdisciplinary science, this article introduces a virtual reality based mirror visual feedback therapy system that the author has been developed in collaboration with medical doctors, professors in engineering field and students of the author’s laboratory in Okayama University.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322742024表紙・目次ENNo potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221412024Development of a novel AAK1 inhibitor via Kinobeads-based screening6723ENAkariYoshidaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySatomiOhtsukaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityFumiyaMatsumotoDepartment of Science Education, Graduate School of Education, Okayama UniversityTomoyukiMiyagawaDepartment of Science Education, Graduate School of Education, Okayama UniversityReiOkinoDepartment of Science Education, Graduate School of Education, Okayama UniversityYumeyaIkedaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNatsumeTadaApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkiraGotohApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasakiMagariApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaoyaHatanoApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRyoMorishitaCellFree Sciences Co. LtdAyanoSatohOrganelle Systems Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYukinariSunatsukiGraduate School of Natural Science and Technology, Okayama UniversityUlf J.NilssonDepartment of Chemistry, Lund UniversityTeruhikoIshikawaDepartment of Science Education, Graduate School of Education, Okayama UniversityHiroshiTokumitsuApplied Cell Biology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityA chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor-immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKK alpha/1 and beta/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 mu M), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 mu M) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 mu M), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 mu M TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama2234-943X142024Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface1371342ENTettaTakahashiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-IchiYamamotoDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiMurataDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNi Luh Gede YoniKomalasariFaculty of Medicine, Udayana UniversityYouyiChenDepartment of Breast Surgery, The First Affiliated Hospital, Zhejiang University School of MedicineFanJiangDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaGoharaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshikiOchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesI. Made WinarsaRumaFaculty of Medicine, Udayana UniversityI. WayanSumardikaFaculty of Medicine, Udayana UniversityJinZhouMedical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of TechnologyTomokoHonjoDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshihikoSakaguchiDepartment of Microbiology, Tokushima Bunri UniversityAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolFutoshiKuribayashiDepartment of Biochemistry, Kawasaki Medical SchoolEisakuKondoDivision of Tumor Pathology, Near InfraRed Photo-Immuno-Therapy Research Institute, Kansai Medical UniversityYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshitoZamamiDepartment of Pharmacy, Okayama University HospitalMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-β1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain.<br>
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Methods: Cell invasion was assessed using a transwell-based assay, protein–protein interactions by an immunoprecipitation–Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography.<br>
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Results: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion.<br>
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Conclusion: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2077-03831362024Enhancing Diagnostic Precision: Evaluation of Preprocessing Filters in Simple Diffusion Kurtosis Imaging for Head and Neck Tumors1783ENYukiNakamitsuRadiological Technology, Graduate School of Health Sciences, Okayama UniversityMasahiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityYudaiShimizuDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKazuhiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityYuukiYoshimuraRadiological Technology, Graduate School of Health Sciences, Okayama UniversitySuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYoshihideNakamuraDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukaFukumuraDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityRyoKamizakiRadiological Technology, Graduate School of Health Sciences, Okayama UniversityWlla E.Al-HammadDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityYoshinoriTanabeRadiological Technology, Graduate School of Health Sciences, Okayama UniversityKoheiSugimotoRadiological Technology, Graduate School of Health Sciences, Okayama UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityMajdBarhamDepartment of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National UniversityNouhaTekikiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBackground: Our initial clinical study using simple diffusion kurtosis imaging (SDI), which simultaneously produces a diffusion kurtosis image (DKI) and an apparent diffusion coefficient map, confirmed the usefulness of SDI for tumor diagnosis. However, the obtained DKI had noticeable variability in the mean kurtosis (MK) values, which is inherent to SDI. We aimed to improve this variability in SDI by preprocessing with three different filters (Gaussian [G], median [M], and nonlocal mean) of the diffusion-weighted images used for SDI. Methods: The usefulness of filter parameters for diagnosis was examined in basic and clinical studies involving 13 patients with head and neck tumors. Results: The filter parameters, which did not change the median MK value, but reduced the variability and significantly homogenized the MK values in tumor and normal tissues in both basic and clinical studies, were identified. In the receiver operating characteristic curve analysis for distinguishing tumors from normal tissues using MK values, the area under curve values significantly improved from 0.627 without filters to 0.641 with G (sigma = 0.5) and 0.638 with M (radius = 0.5). Conclusions: Thus, image pretreatment with G and M for SDI was shown to be useful for improving tumor diagnosis in clinical practice.No potential conflict of interest relevant to this article was reported.Public Library of ScienceActa Medica Okayama1932-62031912024Aromatic oil from lavender as an atopic dermatitis suppressante0296408ENHarunaSatoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKosukeKatoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMayukoKoreishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityYoshioTsujinoGraduate School of Science, Technology, and Innovation, Kobe UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityIn atopic dermatitis (AD), nerves are abnormally stretched near the surface of the skin, making it sensitive to itching. Expression of neurotrophic factor Artemin (ARTN) involved in such nerve stretching is induced by the xenobiotic response (XRE) to air pollutants and UV radiation products. Therefore, AD can be monitored by the XRE response. Previously, we established a human keratinocyte cell line stably expressing a NanoLuc reporter gene downstream of XRE. We found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan metabolite and known inducer of the XRE, increased reporter and Artemin mRNA expression, indicating that FICZ-treated cells could be a model for AD. Lavender essential oil has been used in folk medicine to treat AD, but the scientific basis for its use is unclear. In the present study, we investigated the efficacy of lavender essential oil and its major components, linalyl acetate and linalool, to suppress AD and sensitize skin using the established AD model cell line, and keratinocyte and dendritic cell activation assays. Our results indicated that lavender essential oil from L. angustifolia and linalyl acetate exerted a strong AD inhibitory effect and almost no skin sensitization. Our model is useful in that it can circumvent the practice of using animal studies to evaluate AD medicines.No potential conflict of interest relevant to this article was reported.岡山大学農学部附属山陽圏フィールド科学センターActa Medica Okayama0910-8742422020序iiENNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0343-86518132024Mutational analysis of the transmembrane α4-helix of Bacillus thuringiensis mosquito-larvicidal Cry4Aa toxin80ENHirokazuTakahashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMamiAsakuraGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToruIdeGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTohruHayakawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityCry4Aa, produced by Bacillus thuringiensis subsp. israelensis, exhibits specific toxicity to larvae of medically important mosquito genera. Cry4Aa functions as a pore-forming toxin, and a helical hairpin (α4-loop-α5) of domain I is believed to be the transmembrane domain that forms toxin pores. Pore formation is considered to be a central mode of Cry4Aa action, but the relationship between pore formation and toxicity is poorly understood. In the present study, we constructed Cry4Aa mutants in which each polar amino acid residues within the transmembrane α4 helix was replaced with glutamic acid. Bioassays using Culex pipiens mosquito larvae and subsequent ion permeability measurements using symmetric KCl solution revealed an apparent correlation between toxicity and toxin pore conductance for most of the Cry4Aa mutants. In contrast, the Cry4Aa mutant H178E was a clear exception, almost losing its toxicity but still exhibiting a moderately high conductivity of about 60% of the wild-type. Furthermore, the conductance of the pore formed by the N190E mutant (about 50% of the wild-type) was close to that of H178E, but the toxicity was significantly higher than that of H178E. Ion selectivity measurements using asymmetric KCl solution revealed a significant decrease in cation selectivity of toxin pores formed by H178E compared to N190E. Our data suggest that the toxicity of Cry4Aa is primarily pore related. The formation of toxin pores that are highly ion-permeable and also highly cation-selective may enhance the influx of cations and water into the target cell, thereby facilitating the eventual death of mosquito larvae.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1424-82202422024Ultrathin Platinum Film Hydrogen Sensors with a Twin-T Type Notch Filter Circuit548ENShokiWakabayashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYukiOhGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHaruhitoNakayamaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihikoKiwaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityIn recent years, hydrogen energy has garnered attention as a potential solution for mitigating greenhouse gas emissions. However, concerns regarding the inherent risk of hydrogen gas leakage and potential explosions have necessitated the development of advanced sensors. Within our research group, we have innovated an ultrathin platinum (Pt) film hydrogen sensor that gauges resistance changes in Pt thin films when exposed to hydrogen gas. Notably, the sensitivity of each sensor is contingent upon the thickness of the Pt film. To address the challenge of detecting hydrogen using multiple sensors, we integrated the ultrathin Pt film as a resistance element within a twin-T type notch filter. This filter exhibits a distinctive reduction in output signals at a specific frequency. The frequency properties of the notch filter dynamically alter with changes in the resistance of the Pt film induced by hydrogen exposure. Consequently, the ultrathin Pt film hydrogen sensor monitors output signal variations around the notch frequency, responding to shifts in frequency properties. This innovative approach enables the electrical control of sensor sensitivity by adjusting the operating frequency in proximity to the notch frequency. Additionally, the simultaneous detection of hydrogen by multiple sensors was successfully achieved by interconnecting sensors with distinct notch frequencies in series.No potential conflict of interest relevant to this article was reported.岡山大学農学部Acta Medica Okayama2186-77551132024異なる施肥条件下における水稲品種の窒素利用効率 ―日本晴とタカナリの比較―3339ENKuniyukiSaitohThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYusukeDannoThe Graduate School of Natural Science and Technology, Okayama UniversityThe rice cultivar Nipponbare and the high-yielding cultivar Takanari were cultivated in field trials for three years from 2003, and in pot trials (1/2,000a) for two years from 2004. In the field trials, the following three levels of fertilizer were applied：“0N” without fertilizer, “1N” with the standard amount(8kgN 10a–1), and “2N” with twice the standard amount (16kgN 10a–1). In the pot trial, three levels of fertilizer were applied：“0N” without fertilizer, “1.5N” with 1.5times the standard amount (1.5gN pot–1), and “3N” with three times the standard amount (3gN pot–1). In the field trials, yields were higher in Takanari (538 to 843g m–2) than in Nihonbare (423 to 577g m–2), and the increase in yield with fertilizer application was also larger in Takanari. This was related to the larger sink capacity of Takanari and the smaller decrease in the percentage of filled grain with larger sink capacity. The dry matter weight and nitrogen uptake at the panicle initiation stage were higher in the plots with higher fertilizer application, but the differences between the cultivars were small. Dry matter weight and nitrogen uptake at harvest time were higher in Takanari, and nitrogen use efficiency and sink production efficiency were also higher in Takanari, but the differences in nitrogen use efficiency between cultivars became smaller with increasing fertilizer application. The nitrogen use efficiency for dry matter production also decreased with increasing fertilizer application, and was higher in 2005 in Takanari. The leaf photosynthetic rate of Takanari was higher than that of Nipponbare in the pot experiment. The difference in leaf photosynthetic rate was related to the nitrogen use efficiency (photosynthetic rate / leaf nitrogen content), and the difference in leaf nitrogen content between cultivars was small. The nitrogen use efficiency for dry matter was highest in the “0N” and decreased with increasing fertilizer application, and was higher in Takanari than in Nipponbare. This was presumably related to the higher nitrogen use efficiency of photosynthesis. It was found that fertilizer application decreased nitrogen use efficiency and sink production efficiency, but yield increased with increasing sink capacity, and that differences in nitrogen use efficiency among cultivars were related to the amount of nitrogen absorbed up to the panicle initiation stage and sink production efficiency. In order to improve the efficiency of fertilizer application, it is desirable to increase nitrogen absorption, which is expressed as multiplying the number of days to panicle initiation and the rate of nitrogen absorption, and to select cultivars with higher sink production efficiency.No potential conflict of interest relevant to this article was reported.岡山大学農学部Acta Medica Okayama2186-77551132024Analytical studies on high-yielding characteristics of US soybean cv. ‘UA4805’ in comparison with Japanese cv. ‘Akimaro’2532ENSultanzada MohammadMaroufGraduate School of Environmental and Life ScienceYuHasegawaSchool of AgricultureRyutaManabeSchool of AgricultureKuniyukiSaitohGraduate School of Environmental and Life ScienceField experiments were conducted in 2020 and 2021 at the Field Science Center of Okayama Univ. (34°41’ N, 133°55’ E). Two Soybean cultivars ‘UA4805’ and ‘Akimaro’ were sown with two planting densities, 12.5plants m−2 (sparse, 80×10cm) and 25plants m−2 (dense, 80×5cm)on May 25 (early), June 29 (normal), and Aug. 3 (late) in 2020, and 80 and 30cm row-width, and 12.5 and 25 plant m−2 in 2021 on June 23. Seed yield was higher in ‘UA4805’ than in ‘Akimaro’ in 2020 and 2021. The later the sowing time, the higher the seeds/stem ratio. Both cultivars showed higher dry matter in dense planting. Dry matter was higher in ‘Akimaro’, while seed yield was lower than ‘UA4805’. In contrast, ‘UA4805’ showed lower dry matter with higher seed yield. The numbers of nodes, pods, and seeds were higher in ‘UA4805’ resulting in the higher seed yield. Lodging score is larger in ‘Akimaro’ especially in dense planting. The seeds/stem ratio is much higher in ‘UA4805’ than ‘Akimaro’ across 2 densities, 3 sowing times and 2 row width. Pods setting ratio was nearly two times higher in ‘UA4805’ compared to ‘Akimaro’. The greater seed yield of ‘UA4805’ compared to ‘Akimaro’ was due to the higher pod setting ratio, seeds/stem ratio, and lower lodging score, nevertheless the dry matter was larger in ‘Akimaro’. If late sowing is applied, higher planting density is recommended for better seed yield. Narrow row is an effective way to improve seed yield in soybean.No potential conflict of interest relevant to this article was reported.岡山大学農学部Acta Medica Okayama2186-77551132024水稲における窒素利用効率の品種間差異1724ENKuniyukiSaitohThe Graduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityYoshifumiIwameThe Graduate School of Natural Science and Technology, Okayama UniversityMasahikoMaekawaInstitute of Plant Science and Resources （IPSR）, Okayama UniversityKazuyoshiTakedaInstitute of Plant Science and Resources（IPSR）, Okayama UniversityWe investigated the effects of fertilizer-free and fertilizer-applied cultivation on growth, yield and nitrogen (N) utilization of rice cultivars in our Kurashiki paddy fields (Institute of Plant Science and Resources, Okayama Univ.), which have been cultivated without fertilizer since 1970, and also in our Okayama paddy fields, which are conventionally cultivated. In 2001, the cultivars Nipponbare (NIP) and Nourin 18 (N18) were cultivated in the Kurashiki fields, with a “0N plot” (no fertilizer application), a “1N plot” (standard fertilizer application), and a “2N plot” (double fertilizer application). In 2002, five cultivars were grown without fertilizer in the Kurashiki fields, and 51cultivars were tested in 0N and 1N plots in the Okayama fields. Yield (2001) in the Kurashiki fields was higher in the 0N plot for N18 (379g m–2), which had a higher number of spikelets per m2, than NIP (300 g m–2), while in the 1N and 2N plots it was higher for NIP, which had a higher percentage of ripening, and N18 had high yield potential even without fertilizer application, but low fertilizer tolerance. The differences in yield were related to N-uptake (NU), and the differences in N use efficiency (NUE, yield/NU) between cultivars were small. The pot experiment showed that the yield of 0N plot was higher for N18 than NIP grown in Kurashiki soil because of the higher number of spikelets per hill, and the yield in the Okayama soil was higher than that in the Kurashiki soil. Long-term non-fertilized soils are of poor soil fertility, which also decreases the NUE, and the NUE of N18 is higher than that of NIP under isolated conditions. The difference in yields is closely related to sink capacity (SC). In 2002, yields in the Kurashiki fields were highest in Takanari (TAK, 494g m–2) and lowest in NIP (350g m–2), and differences in yields were closely related to SC. NUE was highest in TAK (68.6) and lowest in Akebono (48.1). TAK had high NUE and high sink production efficiency (SPE, SC/NU), while N18 had low NUE but high SC due to higher NU, ensuring high yield even under unfertilized cultivation. Yields in the 0N and 1N plots cultivated in 2002 varied between 244–631g m–2 and 199–769g m–2, respectively. A close positive correlation was observed between yield and SC, and between NU and SC, suggesting that the SC through NU is involved in determining yield. A positive correlation was also observed between NUE and yield. It was found that yield increased with an increase in NUE, and that NUE decreased although yield increased with fertilizer application. Through selection of cultivars with high SPE, it is expected that it will be possible to breed low-input, high-yielding cultivars with high NUE in the future.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-082512112023Development of Hexagonal Pyramid-Shaped Flexible Actuator with Anisotropic Stiffness for Upper-Limb Rehabilitation Device424ENSoShimookaFaculty of Environmental, Life, Natural Science and Technology, Okayama UniversityHirokiHimuroFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkioGofukuFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRehabilitation devices for passive exercise have been actively researched and developed in accordance with Japan's aging society. A previous study proposed and tested an extension-type flexible pneumatic actuator (EFPA) with reinforced stiffness that could achieve passive exercise in patients. In addition, a rehabilitation device for shoulder joints with an embedded controller and small valves was proposed and tested. Joints such as the shoulder and scapula were subjected to passive exercise utilizing the tested device. However, it is difficult for patients with contractions to perform the same exercise because the reinforced EFPA can buckle. Here, to realize an EFPA with a higher stiffness, a flexible actuator in the shape of a hexagonal pyramid is proposed and tested. The hexagonal pyramid shape of a flexible actuator has a high stiffness in the direction of motion and flexibility in other directions; hereafter, this characteristic is called anisotropic stiffness. The characteristics of the hexagonal pyramid shape of the EFPA are described and compared with those of a previously reinforced EFPA. An analytical model was proposed to predict and design the shape of the hexagonal pyramid EFPA. The validity of the model is also described.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2079-773712122023Random Mutational Analysis Targeting Residue K155 within the Transmembrane β-Hairpin of the Mosquitocidal Mpp46Ab Toxin1481ENMidokaMiyazakiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMamiAsakuraGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToruIdeGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTohruHayakawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMpp46Ab is a mosquito-larvicidal pore-forming toxin derived from Bacillus thuringiensis TK-E6. Pore formation is believed to be a central mode of Mpp46Ab action, and the cation selectivity of the channel pores, in particular, is closely related to its mosquito-larvicidal activity. In the present study, we constructed a mutant library in which residue K155 within the transmembrane β-hairpin was randomly replaced with other amino acid residues. Upon mutagenesis and following primary screening using Culex pipiens mosquito larvae, we obtained 15 mutants in addition to the wild-type toxin. Bioassays using purified proteins revealed that two mutants, K155E and K155I, exhibited toxicity significantly higher than that of the wild-type toxin. Although increased cation selectivity was previously reported for K155E channel pores, we demonstrated in the present study that the cation selectivity of K155I channel pores was also significantly increased. Considering the characteristics of the amino acids, the charge of residue 155 may not directly affect the cation selectivity of Mpp46Ab channel pores. Replacement of K155 with glutamic acid or isoleucine may induce a similar conformational change in the region associated with the ion selectivity of the Mpp46Ab channel pores. Mutagenesis targeting the transmembrane β-hairpin may be an effective strategy for enhancing the ion permeability of the channel pores and the resulting mosquito-larvicidal activity of Mpp46Ab.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813532023網膜色素変性症147151ENToshihikoMatsuoFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Department of Ophthalmology, Okayama University HospitalNo potential conflict of interest relevant to this article was reported.American Physiological SocietyActa Medica Okayama0022-307712752022Tactile angle discriminability improvement: contributions of working memory training and continuous attended sensory input13981406ENWuWangSchool of Psychological and Cognitive Sciences, Peking UniversityJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHuazhiLiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYulongLiuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYiyangYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiabinYuCollege of Information Engineering, China Jiliang UniversityXiaoyuTangSchool of Psychology, Liaoning Collaborative Innovation Center of Children and Adolescents Healthy Personality Assessment and Cultivation, Liaoning Normal UniversityJingjingYangSchool of Computer Science and Technology, Changchun University of Science and TechnologySatoshiTakahashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimichiEjimaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinglongWuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPerceptual learning is commonly assumed to enhance perception through continuous attended sensory input. However, learning is generalizable to performance in untrained stimuli and tasks. Although previous studies have observed a possible generalization effect across tasks as a result of working memory (WM) training, comparisons of the contributions of WM training and continuous attended sensory input to perceptual learning generalization are still rare. Therefore, we compared which factors contributed most to perceptual generalization and investigated which skills acquired during WM training led to tactile generalization across tasks. Here, a Braille-like dot pattern matching n-back WM task was used as the WM training task, with four workload levels (0, 1, 2, and 3-back levels). A tactile angle discrimination (TAD) task was used as a pre- and posttest to assess improvements in tactile perception. Between tests, four subject groups were randomly assigned to four different workload n-back tasks to consecutively complete three sessions of training. The results showed that tactile n-back WM training could enhance TAD performance, with the 3-back training group having the highest TAD threshold improvement rate. Furthermore, the rate of WM capacity improvement on the 3-back level across training sessions was correlated with the rate of TAD threshold improvement. These findings suggest that continuous attended sensory input and enhanced WM capacity can lead to improvements in TAD ability, and that greater improvements in WM capacity can predict greater improvements in TAD performance.<br>
NEW & NOTEWORTHY Perceptual learning is not always specific to the trained task and stimuli. We demonstrate that both continuous attended sensory input and improved WM capacity can be used to enhance tactile angle discrimination (TAD) ability. Moreover, WM capacity improvement is important in generalizing the training effect to the TAD ability. These findings contribute to understanding the mechanism of perceptual learning generalization across tasks.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231842023赴日モンゴル人留学生史研究序説― 戦前期善隣高等商業学校蒙古留学生特設予科を中心に ―18ENKazuakiKAJIIFaculty of Education, Okayama UniversityXuefengBAODoctor’s Course, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/bgeou/66127 善隣協会は1934 年から東アジアの政治，経済，文化の指導を図り，中国，蒙古，回教圏民族に対して教育事業を展開した。大東亜共栄圏構想に向け，同協会は善隣高等商業学校を創設し，満州国，中国，蒙彊政権地域で活躍する日本人青年の育成を行った。それとともに，善隣協会は蒙彊政権から日本に派遣される内モンゴル人留学生の受け入れを進めた。善隣高等商業学校はこの留学生のための教育を担った。同校は蒙古留学生特設予科と善隣学寮を設置し，留学生が日本の高等教育機関へ進学する際に必要となる語学や教養の予備教育を担う機関とした。本稿は，先行研究をふまえ，新たな史料を用いつつ，この特設予科と善隣学寮がモンゴル人留学生教育に果たした役割について検討を加えるものである。No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023ベイズ統計を用いた頭部CT検査における検査実施者の造影効果に与える影響に関する研究ENKoheiSUGIMOTOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023悪性神経膠腫に対する強度変調陽子線治療と強度変調回転放射線治療の線量分布比較に関する研究ENJunyaMIYATAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Study on audiovisual integration and cross-modal working memory training in young and older adults ENAoGuoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Development of novel probe for detecting two mutations on one RNA ENMYAT THUGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama0014-481924032022Global surface features contribute to human haptic roughness estimations773789ENHuazhiLiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJiajiaYangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYinghuaYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWuWangSchool of Psychological and Cognitive Sciences, Peking UniversityYulongLiuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMengniZhouGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityQingqingLiDepartment of Teacher Education, Wenzhou UniversityJingjingYangSchool of Computer Science and Technology, Changchun University of Science and TechnologyShipingShaoSchool of Social Welfare, Yonsei UniversitySatoshiTakahashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimichiEjimaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinglongWuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPrevious studies have paid special attention to the relationship between local features (e.g., raised dots) and human roughness perception. However, the relationship between global features (e.g., curved surface) and haptic roughness perception is still unclear. In the present study, a series of roughness estimation experiments was performed to investigate how global features affect human roughness perception. In each experiment, participants were asked to estimate the roughness of a series of haptic stimuli that combined local features (raised dots) and global features (sinusoidal-like curves). Experiments were designed to reveal whether global features changed their haptic roughness estimation. Furthermore, the present study tested whether the exploration method (direct, indirect, and static) changed haptic roughness estimations and examined the contribution of global features to roughness estimations. The results showed that sinusoidal-like curved surfaces with small periods were perceived to be rougher than those with large periods, while the direction of finger movement and indirect exploration did not change this phenomenon. Furthermore, the influence of global features on roughness was modulated by local features, regardless of whether raised-dot surfaces or smooth surfaces were used. Taken together, these findings suggested that an object’s global features contribute to haptic roughness perceptions, while local features change the weight of the contribution that global features make to haptic roughness perceptions.No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama2433-41465522023地方公共サービス革新プロセスの視座の構築114ENDaijiFujiiHiroshiKanaji10.18926/OER/66033 When local governments develop public services, they often experience innovation processes. More often, the innovation processes referred to here seem to be the perceived needs for transformation faced with external pressures and the purposive responses to them. This article tries to depict this discourse from a different viewpoint. One of the perspectives that has been proposed so far is that the external environments are made up of multiple actors, and that the historical backgrounds and the relationships between these actors affect the structure of administrative organizations and the methods of providing public services. The transformation processes could be one-time events no matter how long the processes may take, but this article tries to argue they may connote a circular mechanism where both of the administrative organizations and the external actors feedback to each other. In order to elaborate this direction of theorizing, three steps are employed by applying existent literature of various types developed in rather a broader context of social sciences. First, if one of the goals of postmodern theorization is liberating the psychological energies of actors from the cramped social reality that structuralists postulated, then Actor-Network-Theory may be useful. Second, according to Sarasbathy’s research on entrepreneurial behaviors, the view that we effectuate our future through what we can do now is attractive in order to create a new discourse of social innovations, where we appreciate them as not springing out of nowhere all of sudden. Third, once this article accepts polyphonic views on social realities where congested discourses interact during abovementioned process, the role of civic entrepreneurs on the frontline can never be overstated enough. This is because such civic entrepreneurs could cooperate with minority opinions and raise them into broader contexts of dialogues within societies.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama1792-09812652023Evaluation of the accuracy of heart dose prediction by machine learning for selecting patients not requiring deep inspiration breath‑hold radiotherapy after breast cancer surgery536ENRyoKamizakiDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMasahiroKurodaDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityWllaAl‑HammadDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNouhaTekikiDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHinataIshizakaDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityKazuhiroKurodaDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityKoheiSugimotoDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityYoshinoriTanabeDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMajdBarhamDepartment of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An‑Najah National UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityYukiNakamitsuDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMasakiHiranoDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityYukiMutoDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityHirokiIharaDepartment of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySoichiSugiyamaDepartment of Proton Beam Therapy, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIncreased heart dose during postoperative radiotherapy (RT) for left‑sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath‑hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left‑sided BC. However, treatment planning and DIBH for RT are laborious, time‑consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre‑select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right‑left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve‑receiver operating characteristic of 0.88, for a cut‑off value of 300 cGy. The present study suggested that ML can be used to pre‑select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC.No potential conflict of interest relevant to this article was reported.nature portfolioActa Medica Okayama2045-23221312023Photo-dependent cytosolic delivery of shRNA into a single blastomere in a mouse embryo13050ENYukaIkawaDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakuyaWakaiDepartment of Animal Science, Graduate of Environmental and Life Science, Okayama UniversityHiroakiFunahashiDepartment of Animal Science, Graduate of Environmental and Life Science, Okayama UniversityTet HtutSoeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySingle-cell-specific delivery of small RNAs, such as short hairpin RNA (shRNA) and small noncoding RNAs, allows us to elucidate the roles of specific upregulation of RNA expression and RNAi-mediated gene suppression in early embryo development. The photoinduced cytosolic dispersion of RNA (PCDR) method that we previously reported can introduce small RNAs into the cytosol of photoirradiated cells and enable RNA delivery into a single-cell in a spatiotemporally specific manner. However, the PCDR method has only been applied to planer cultured cells and not to embryos. This study demonstrated that the PCDR method can be utilized for photo-dependent cytosolic shRNA delivery into a single blastomere and for single blastomere-specific RNA interference in mouse embryos. Our results indicate that PCDR is a promising approach for studying the developmental process of early embryogenesis.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama2049-94341612021Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells3ENTaichiNagahataGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshioTsujinoGraduate School of Science, Technology and Innovation, Kobe UniversityEijiTakayamaDepartment of Oral Biochemistry, Asahi University School of DentistryHarukaHikasaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySkin sensitization is an allergic reaction caused by certain chemical substances, and is an important factor to be taken into consideration when evaluating the safety of numerous types of products. Although animal testing has long been used to evaluate skin sensitization, the recent trend to regulate such testing has led to the development and use of alternative methods. Skin sensitization reactions are summarized in the form of an adverse outcome pathway consisting of four key events (KE), including covalent binding to skin proteins (KE1), keratinocyte activation (KE2), and dendritic cell activation (KE3). Equivalent alternative methods have been developed for KE1 to KE3, but no valid alternative has yet been developed for the evaluation of KE4 and T‑cell activation. Current alternative methods rely on data from KE1 to KE3 to predict the effect of chemicals on skin sensitization. The addition of KE4 data is expected to improve the accuracy and reproducibility of such predictions. The aim of this study was to establish an assay to evaluate KE4 T‑cell activation to supplement data on skin sensitization related to KE4. To evaluate T‑cell activation, the Jurkat T‑cell line stably expressing luciferase downstream of the pro‑inflammatory cytokine interleukin‑2 promoter was used. After exposure to known skin sensitizing agents and control substances, luciferase activity measurements revealed that this assay was valid for evaluating skin sensitization. However, two skin sensitizers known to have immunosuppressive effects on T‑cells reacted negatively in this assay. The results revealed that this assay simultaneously allows for monitoring of the skin sensitization and immuno‑suppressiveness of chemical substances and supplements KE4 T‑cell activation data, and may thus contribute to reducing the use of animal experiments.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0924-42473612023A soft rotary actuator with a flexible shaft using flexible pneumatic actuators114603ENSoShimookaFaculty of Natural Science and Technology, Okayama UniversityMikuKawanakaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkioGofukuFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThis paper proposes a soft rotary actuator that can rotate even when its shaft is bent. The tested rotary actuator consists of three Extension-type Flexible Pneumatic Actuators (EFPA), flexible plates for restraining the EFPAs geometrically, and a polyurethane tube as a shaft. The EFPA consists of a silicone rubber tube covered with a sleeve that can expand significantly in the axial direction when the tube is pressurized. By restraining the EFPA to a helical shape using plates, the proposed rotary actuator can rotate when the three EFPAs are extended in the rotational direction upon the application of pressure. It is confirmed that the tested actuator could rotate even if the shaft is bent, because the shaft and EFPAs consist of flexible materials. The maximum rotation angle and torque are approximately 400° and 0.5 Nm, respectively, for an input pressure of 500 kPa. An analytical model of the tested actuator is proposed to predict the relationship between the rotation angle and the input pressure. A comparison between the calculated and experimental rotation angles reveals that the experimental results can be accurately predicted using the proposed analytical model, which considers the effects of EFPA friction and restraining.No potential conflict of interest relevant to this article was reported.Cell PressActa Medica Okayama2405-8440982023Bayesian statistical modeling to predict observer-specific optimal windowing parameters in magnetic resonance imaginge19038ENKoheiSugimotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasatakaOitaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasahiroKurodaDepartment of Radiological Technology, Faculty of Health Sciences, Okayama UniversityMagnetic resonance (MR) images require a process known as windowing for optimizing the display conditions. However, the conventional windowing process often fails to achieve the preferred display conditions for observers due to various factors. This study proposes a novel framework for predicting the preferred windowing parameters for each observer using Bayesian statistical modeling. MR images obtained from 1000 patients were divided into training and test sets at a 7:3 ratio. The image intensity and windowing parameters were standardized using previously reported methods. Bayesian statistical modeling was utilized to predict the windowing parameters preferred by three MR imaging (MRI) operators. The performance of the proposed framework was evaluated by assessing the mean relative error (MRE), mean absolute error (MAE), and Pearson's correlation coefficient (ρ) of the test set. In addition, the naive method, which presumes that the average value of the windowing parameters for each acquisition sequence and body region in the training set is optimal, was also used for comparison. Three MRI operators and three radiologists conducted visual assessments. The mean MRE, MAE, and ρ values for the window level and width (WL/WW) in the proposed framework were 12.6 and 13.9, 42.9 and 85.4, and 0.98 and 0.98, respectively. These results outperformed those obtained using the naive method. The visual assessments revealed no significant differences between the original and predicted display conditions, indicating that the proposed framework accurately predicts individualized windowing parameters with the additional advantages of robustness and ease of use. Thus, the proposed framework can effectively predict the windowing parameters preferred by each observer.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1198-00523082023Mean Heart Dose Prediction Using Parameters of Single-Slice Computed Tomography and Body Mass Index: Machine Learning Approach for Radiotherapy of Left-Sided Breast Cancer of Asian Patients74127424ENWlla E.Al-HammadDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityRyoKamizakiRadiological Technology, Graduate School of Health Sciences, Okayama UniversityNouhaTekikiDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHinataIshizakaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityKazuhiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityKoheiSugimotoRadiological Technology, Graduate School of Health Sciences, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityYoshinoriTanabeRadiological Technology, Graduate School of Health Sciences, Okayama UniversityMajdBarhamDepartment of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityYudaiShimizuDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiNakamitsuRadiological Technology, Graduate School of Health Sciences, Okayama UniversityJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDeep inspiration breath-hold (DIBH) is an excellent technique to reduce the incidental radiation received by the heart during radiotherapy in patients with breast cancer. However, DIBH is costly and time-consuming for patients and radiotherapy staff. In Asian countries, the use of DIBH is restricted due to the limited number of patients with a high mean heart dose (MHD) and the shortage of radiotherapy personnel and equipment compared to that in the USA. This study aimed to develop, evaluate, and compare the performance of ten machine learning algorithms for predicting MHD using a patient's body mass index and single-slice CT parameters to identify patients who may not require DIBH. Machine learning models were built and tested using a dataset containing 207 patients with left-sided breast cancer who were treated with field-in-field radiotherapy with free breathing. The average MHD was 251 cGy. Stratified repeated four-fold cross-validation was used to build models using 165 training data. The models were compared internally using their average performance metrics: F2 score, AUC, recall, accuracy, Cohen's kappa, and Matthews correlation coefficient. The final performance evaluation for each model was further externally analyzed using 42 unseen test data. The performance of each model was evaluated as a binary classifier by setting the cut-off value of MHD & GE; 300 cGy. The deep neural network (DNN) achieved the highest F2 score (78.9%). Most models successfully classified all patients with high MHD as true positive. This study indicates that the ten models, especially the DNN, might have the potential to identify patients who may not require DIBH.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2076-34251372023Audiovisual n-Back Training Alters the Neural Processes of Working Memory and Audiovisual Integration: Evidence of Changes in ERPs992ENAoGuoCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWeipingYangDepartment of Psychology, Faculty of Education, Hubei UniversityXiangfuYangDepartment of Psychology, Faculty of Education, Hubei UniversityJinfeiLinDepartment of Psychology, Faculty of Education, Hubei UniversityZimoLiCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYannaRenDepartment of Psychology, College of Humanities and Management, Guizhou University of Traditional Chinese MedicineJiajiaYangCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinglongWuCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University(1) Background: This study investigates whether audiovisual n-back training leads to training effects on working memory and transfer effects on perceptual processing. (2) Methods: Before and after training, the participants were tested using the audiovisual n-back task (1-, 2-, or 3-back), to detect training effects, and the audiovisual discrimination task, to detect transfer effects. (3) Results: For the training effect, the behavioral results show that training leads to greater accuracy and faster response times. Stronger training gains in accuracy and response time using 3- and 2-back tasks, compared to 1-back, were observed in the training group. Event-related potentials (ERPs) data revealed an enhancement of P300 in the frontal and central regions across all working memory levels after training. Training also led to the enhancement of N200 in the central region in the 3-back condition. For the transfer effect, greater audiovisual integration in the frontal and central regions during the post-test rather than pre-test was observed at an early stage (80-120 ms) in the training group. (4) Conclusion: Our findings provide evidence that audiovisual n-back training enhances neural processes underlying a working memory and demonstrate a positive influence of higher cognitive functions on lower cognitive functions.No potential conflict of interest relevant to this article was reported.岡山大学経済学会Acta Medica Okayama2433-41465512023小田なら著『〈伝統医学〉が創られるとき：ベトナム医療政策史』（京都大学学術出版会，2022年）7787ENHiroshiKinoshitaDaijiFujii10.18926/OER/65686No potential conflict of interest relevant to this article was reported.Royal Society of Chemistry (RSC)Acta Medica Okayama0003-2654148112023FRET probe for detecting two mutations in one EGFR mRNA26262632ENMyatThuDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKoutaYanaiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHajimeShigetoHealth and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)ShoheiYamamuraHealth and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)KazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTechnologies for visualizing and tracking RNA are essential in molecular biology, including in disease-related fields. In this study, we propose a novel probe set (DAt-probe and T-probe) that simultaneously detects two mutations in the same RNA using fluorescence resonance energy transfer (FRET). The DAt-probe carrying the fluorophore Atto488 and the quencher Dabcyl were used to detect a cancer mutation (exon19del), and the T-probe carrying the fluorophore Tamra was used to detect drug resistance mutations (T790M) in epidermal growth factor receptor (EGFR) mRNA. These probes were designed to induce FRET when both mutations were present in the mRNA. Gel electrophoresis confirmed that the two probes could efficiently bind to the mutant mRNA. We measured the FRET ratios using wild-type and double-mutant RNAs and found a significant difference between them. Even in living cells, the FRET probe could visualize mutant RNA. As a result, we conclude that this probe set provides a method for detecting two mutations in the single EGFR mRNA via FRET.No potential conflict of interest relevant to this article was reported.nature portfolioActa Medica Okayama2399-3642612023NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism596ENNobuhiroOkadaGraduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama UniversityChihiroUekiGraduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama UniversityMasahiroShimazakiLaboratory for Malignancy Control Research, Medical Innovation Center, Kyoto UniversityGokiTsujimotoGraduate School of Interdisciplinary Science & Engineering in Health Systems, Okayama UniversitySusumuKohnoDivision of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa UniversityHayatoMuranakaDivision of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa UniversityKiyotsuguYoshikawaFaculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal ArtsChiakiTakahashiDivision of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa UniversityTwo splicing variants exist in NFYA that exhibit high expression in many human tumour types. The balance in their expression correlates with prognosis in breast cancer, but functional differences remain unclear. Here, we demonstrate that NFYAv1, a long-form variant, upregulates the transcription of essential lipogenic enzymes ACACA and FASN to enhance the malignant behavior of triple-negative breast cancer (TNBC). Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior in vitro and in vivo, indicating that the NFYAv1-lipogenesis axis is essential for TNBC malignant behavior and that the axis might be a potential therapeutic target for TNBC. Furthermore, mice deficient in lipogenic enzymes, such as Acly, Acaca, and Fasn, exhibit embryonic lethality; however, Nfyav1-deficient mice exhibited no apparent developmental abnormalities. Our results indicate that the NFYAv1-lipogenesis axis has tumour-promoting effects and that NFYAv1 may be a safe therapeutic target for TNBC.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7732023Usefulness of Simple Diffusion Kurtosis Imaging for Head and Neck Tumors: An Early Clinical Study273280ENYudaiShimizuDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityYukiNakamitsuRadiological Technology, Graduate School of Health Sciences, Okayama UniversityWlla E.Al-HammadDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSuzukaYoshidaDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukaFukumuraDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihideNakamuraDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroKurodaRadiological Technology, Graduate School of Health Sciences, Okayama UniversityRyoKamizakiRadiological Technology, Graduate School of Health Sciences, Okayama UniversitySatoshiImajohRadiological Technology, Graduate School of Health Sciences, Okayama UniversityYoshinoriTanabeRadiological Technology, Graduate School of Health Sciences, Okayama UniversityKoheiSugimotoGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityBabatunde O.BamgboseDepartment of Oral Diagnostic Sciences, Faculty of Dentistry, Bayero UniversityYoshinobuYanagiDepartment of Dental Informatics, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJunichiAsaumiDepartment of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOriginal Article10.18926/AMO/65492Diffusion kurtosis (DK) imaging (DKI), a type of restricted diffusion-weighted imaging, has been reported to be useful for tumor diagnoses in clinical studies. We developed a software program to simultaneously create DK images with apparent diffusion coefficient (ADC) maps and conducted an initial clinical study. Multi-shot echo-planar diffusion-weighted images were obtained at b-values of 0, 400, and 800 sec/mm2 for simple DKI, and DK images were created simultaneously with the ADC map. The usefulness of the DK image and ADC map was evaluated using a pixel analysis of all pixels and a median analysis of the pixels of each case. Tumor and normal tissues differed significantly in both pixel and median analyses. In the pixel analysis, the area under the curve was 0.64 for the mean kurtosis (MK) value and 0.77 for the ADC value. In the median analysis, the MK value was 0.74, and the ADC value was 0.75. The MK and ADC values correlated moderately in the pixel analysis and strongly in the median analysis. Our simple DKI system created DK images simultaneously with ADC maps, and the obtained MK and ADC values were useful for differentiating head and neck tumors from normal tissue.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023裏表紙・英文目次ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023投稿規程・奥付ENNo potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-3227320232022 年度における「先進病院実習」の取り組み7582ENMizukiMORITAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNaokiKANAYAMAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshiakiAIDAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToyohikoWATANABEGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNoboruYAMASHITAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityReiHAKAMADAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYasuyukiYOSHIBAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65468No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023留学生受入れ促進のための英語講義開催7374ENToshihikoKIWAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65467No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023岡山大学中央図書館・個人文庫「杏村文庫」の調査：哲学思想を中心に6771ENRyozoSUZUKIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65466No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-32273202320世紀前半における赴日モンゴル人留学生史：内モンゴル医療衛生の近代化におけるホルチンビリクら留学生の位置付けについて6166ENXuefengBAOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65465No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023中国における医療用人工知能発展の歴史的分析：中医学エキスパートシステムを中心に5160ENLingQINGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65464This study is based on a historical analysis of the technological development and introduction of artificial intelligence for medical use in China, based on the progress of application of artificial intelligence technology development to the medical field of traditional Chinese medicine and the experience of many experts in clinical practice. Through the application history of Traditional Chinese Medicine（TCM）expert systems technology, we will review its historical characteristics and the necessity of TCM expert system technology. By examining the application cases of TCM expert systems, we can find that Traditional Chinese Medicine（TCM）expert systems play an important role as an auxiliary means of diagnosis and treatment for doctors. This paper finds that the development of Traditional Chinese Medicine（TCM）expert systems is directly related to the change of Chinese government's science and technology policy through the investigation of the application history of Traditional Chinese Medicine（TCM）expert systems. At the same time, because the science and technology policy directly related to the traditional Chinese Medicine（TCM）expert systems appeared late, so the implementation technology of the traditional Chinese Medicine（TCM）expert systems is still insufficient. The technical level adopted in the implementation of the existing traditional Chinese Medicine（TCM）expert systems is still in a relatively low state. Therefore, whether in hardware or software, we should develop a new integrated traditional Chinese Medicine（TCM）expert systems based on the treatment theory of many Traditional Chinese Medicine（TCM）expert systems, so as to meet the needs of modern Traditional Chinese Medicine（TCM）expert systems diagnosis, people's need for healthy life, and medical care. Finally, when studying the historical issues of Traditional Chinese Medicine （TCM）expert systems, the Chinese government's science and technology policy changes are also an integral part.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023〈迷惑〉意識の類型：『おだやかな死』における〈迷惑〉の用例分析を通じて3949ENNatsumiTANAKAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65463In contemporary Japan, the elderly often say that they do not wish to be a burden on anyone, and they make important decisions with this motivation (here called feelings of "Meiwaku/Burden"). This paper seeks to categorize feelings of "Meiwaku/Burden" according to its relationship to the type of motivation they express. For this purpose, we focused on feelings of "Meiwaku/Burden" of elderly people in France. As there is no easily corresponding phrase in French for our word "Meiwaku/Burden", the French use several different words to express this sense "Meiwaku/Burden". Here we draw examples from Une mort très douce by Simone de Beauvoir, as well as her La Ceremonie des adieux.<br>
The analysis of examples given in these books indicates that "Meiwaku/Burden" of the elderly is motivated by three factors: relationships (déranger), emotions (ennuyer), and body/physical (gêner). In this paper, according to these three motivations we categorize feelings of "Meiwaku/Burden" three types: the feelings of "Meiwaku/Burden" about relationships, the feelings of "Meiwaku/Burden" about emotions, and the feelings of "Meiwaku/Burden" about bodily/physical things.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023〈迷惑〉意識と自律：スピリチュアルペインとSPBの議論を手がかりに2938ENHarukaHIKASAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65462This study aimed to clarify the meaning of feelings of “Meiwaku/Burden” in Japan, which is expressed as “I do not want to bother others” or “I do not want to be a burden.” This is examined specifically in the context of medical care for the terminally and chronically ill. The first section of this paper reviews the core meaning of autonomy and the situations in which feelings of “Meiwaku/Burden” is focused in Japan. Section 2 examines the meaning of “Meiwaku” and “burden,” which is understood in regards to “autonomy,” particularly in the context of patients’ terminal suffering and spiritual pain in palliative care in Japan. Section 3 verifies that “Meiwaku” and “burden” in Japan are sometimes understood as “self-perceived burden (SPB).” Section 4 examines the meaning of “burden” in the discussion of SPB. Section 5 attempts to clarify the meaning of feelings of “Meiwaku/Burden” in medical care, specifically in the context of “autonomy.”No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023相互行為としての〈迷惑〉意識：贈与論的アプローチからの考察1527ENRyozoSUZUKIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University10.18926/interdisciplinary/65461This paper examines elderly people’s Feelings of "Meiwaku / Burden" from the perspective of the act of gift-giving. In Japanese, the word "Morau" is used not only in receiving a concrete object, but also in having something done by someone. Both acts lead to the human relationship and the reciprocity. Both cases can cause a burden on receivers and others. We use then “Sumimasen”. This is not as the same as English words “Thank You”. But this usage of Japanese can be explained from a Gift-giving-theoretic point of view. Because, in terms of the outcome, they are the same thing from this theory. Therefore, we will examine the meaning of the word "receive" based on discussions by Kunio Yanagida, Michizo Toida, Ruth Benedict, Marcel Mauss, and others. We hope to clarify what is elderly people’s Feelings of "Meiwaku / Burden" by analyzing the meaning of human relationships brought about by the act of gift-giving in general.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023特集にあたって1113ENMasafumiMOTOMURAFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThis special feature is based on the symposium ,"Feelings of "Meiwaku/Burden" in Modern Japan’s Super-aging Society,” which was held on Monday, September 19, 2022. This symposium was sponsored by JSPS KAKENHI Grant Number JP20A00007. This project focuses on the fact that when people think about aging, end-of-life care, and death in modern Japan, many feel that “they do not want to be a burden to others.” The project is divided into three research groups: historic studies, studies of contemporary Japan, and field research. The symposium reported the results of the contemporary Japan research group, which is halfway through its research. The symposium consisted of two sessions, and this special feature is based on the three participants in the session titled “Feelings of"Meiwaku/Burden" : A Comparison with Other Countries.” Ryozo Suzuki’s study focuses on “the giving of gifts as being mutual actions of giving and receiving” to understand the elderly’s feelings of meiwaku and analyzes the significance and complex structures of the feeling of “being a burden to others” at the end of one’s life. Haruka Hikasa’s study considers the feelings of meiwaku in relation to the subject’s autonomy in the context of medical care provided to people with terminal or chronic illnesses. Natsumi Tanaka’s study examines the feelings of meiwaku among the elderly in France and is based on the work of Simone de Beauvoir. She determines the motivations behind the elderly’s feelings of meiwaku and categorizes them. The abovementioned studies present important research results and facilitate future comparative research on the feelings of meiwaku between Japan and other countries.No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023大学院ヘルスシステム統合科学研究科：設置の構想と経緯19ENMasaharuSENOFaculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University10.18926/interdisciplinary/65459No potential conflict of interest relevant to this article was reported.岡山大学大学院ヘルスシステム統合科学研究科Acta Medica Okayama2436-322732023表紙・目次ENNo potential conflict of interest relevant to this article was reported.Frontiers in PsychologyActa Medica Okayama1664-1078142023Auditory affective content facilitates time-to-contact estimation of visual affective targets1105824ENFeifeiLuDepartment of Psychology, Research Center for Psychology and Behavioral Sciences, Soochow UniversityYouLiCollege of Chinese Language and Culture, Jinan UniversityJiajiaYangApplied Brain Science Lab, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAijunWangDepartment of Psychology, Research Center for Psychology and Behavioral Sciences, Soochow UniversityMingZhangCognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityReacting to a moving object requires an ability to estimate when a moving object reaches its destination, also referred to as the time-to-contact (TTC) estimation. Although the TTC estimation of threatening visually moving objects is known to be underestimated, the effect of the affective content of auditory information on visual TTC estimation remains unclear. We manipulated the velocity and presentation time to investigate the TTC of a threat or non-threat target with the addition of auditory information. In the task, a visual or an audiovisual target moved from right to left and disappeared behind an occluder. Participants' task was to estimate the TTC of the target, they needed to press a button when they thought that the target contacted a destination behind the occluder. Behaviorally, the additional auditory affective content facilitated TTC estimation; velocity was a more critical factor than presentation time in determining the audiovisual threat facilitation effect. Overall, the results indicate that exposure to auditory affective content can influence TTC estimation and that the effect of velocity on TTC estimation will provide more information than presentation time.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Study on the signaling pathway in tumor initiation and the efficacy of signaling inhibitors for cancer stem cell targeting therapyENYanningXuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023プロスタグランジンE2の慢性的暴露による人工多能性幹細胞のがん幹細胞化の研究ENHidekiMINEMATSUGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023多葉コリメータを使用したペンシルビームスキャニング陽子線治療の線量検証に関する研究ENYukiTOMINAGAGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Study on the effect of facial feature and expression in visual cuteness perceptionENLichangYAOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Study on the effect of subliminal stimulus in human choice processingENQIDAIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Motion planning of a snake robot in crowded pipe environmentsENYongdongWANGGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023工学PBLにおける分野横断型チーム実践効果の統計的分析ENMasayaMIKAMIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2023Practice research of comprehensive and quantitative autoantibody assay systemsENAiMIYAMOTOGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2075-44181382023Deep Active Learning for Automatic Mitotic Cell Detection on HEp-2 Specimen Medical Images1416ENAsaadAnaamGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMugahed A.Al-antariDepartment of Artificial Intelligence, College of Software & Convergence Technology, Daeyang AI Center, Sejong UniversityJamilHussainDepartment of Data Science, College of Software & Convergence Technology, Daeyang AI Center, Sejong UniversityNagwanAbdel SameeDepartment of Information Technology, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman UniversityMaaliAlabdulhafithDepartment of Information Technology, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman UniversityAkioGofukuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityIdentifying Human Epithelial Type 2 (HEp-2) mitotic cells is a crucial procedure in anti-nuclear antibodies (ANAs) testing, which is the standard protocol for detecting connective tissue diseases (CTD). Due to the low throughput and labor-subjectivity of the ANAs' manual screening test, there is a need to develop a reliable HEp-2 computer-aided diagnosis (CAD) system. The automatic detection of mitotic cells from the microscopic HEp-2 specimen images is an essential step to support the diagnosis process and enhance the throughput of this test. This work proposes a deep active learning (DAL) approach to overcoming the cell labeling challenge. Moreover, deep learning detectors are tailored to automatically identify the mitotic cells directly in the entire microscopic HEp-2 specimen images, avoiding the segmentation step. The proposed framework is validated using the I3A Task-2 dataset over 5-fold cross-validation trials. Using the YOLO predictor, promising mitotic cell prediction results are achieved with an average of 90.011% recall, 88.307% precision, and 81.531% mAP. Whereas, average scores of 86.986% recall, 85.282% precision, and 78.506% mAP are obtained using the Faster R-CNN predictor. Employing the DAL method over four labeling rounds effectively enhances the accuracy of the data annotation, and hence, improves the prediction performance. The proposed framework could be practically applicable to support medical personnel in making rapid and accurate decisions about the mitotic cells' existence.No potential conflict of interest relevant to this article was reported.Humana New YorkActa Medica Okayama2022An Electron Tomographic Analysis of Giantin-Deficient Golgi Proposes a New Function of the Golgin Protein Family235246ENAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMitsukoHayashi-NishinoInstitute of Scientific and Industrial Research, Osaka UniversityKunihikoNishinoInstitute of Scientific and Industrial Research, Osaka UniversityThe Golgi apparatus is an organelle that mediates modifications, sorting, and transport of proteins and lipids. Golgins are a group of proteins with coiled-coil structures that localize to the Golgi and are thought to function as tethers to facilitate the docking of vesicles, Rab GTPases, and cytoskeleton components to the Golgi stack. Giantin is the longest golgin and has been thought to function as a tether for COPI vesicles along with other golgins, such as p115 and GM130. Contrary to our expectation that the loss of the tether will result in an increase in untethered COPI vesicles in the cytoplasm, our electron microscopy observations showed that the fenestrae normally present in Golgi cisternae were reduced upon Giantin knockdown. We also found that this structural change is accompanied by altered secretion of cargo proteins and cell surface glycosylation. These results indicate that there exists a correlation between Golgi structural changes caused by the loss of Giantin and Golgi function. Here, we describe electron tomography methods for the detection of structural changes in the Golgi.No potential conflict of interest relevant to this article was reported.Frontiers MediaActa Medica Okayama2296-9144102023Parameter search of a CPG network using a genetic algorithm for a snake robot with tactile sensors moving on a soft floor1138019ENHajimeTamuraGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTetsushiKamegawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityWhen a snake robot explores a collapsed house as a rescue robot, it needs to move through various obstacles, some of which may be made of soft materials, such as mattresses. In this study, we call mattress-like environment as a soft floor, which deforms when some force is added to it. We focused on the central pattern generator (CPG) network as a control for the snake robot to propel itself on the soft floor and constructed a CPG network that feeds back contact information between the robot and the floor. A genetic algorithm was used to determine the parameters of the CPG network suitable for the soft floor. To verify the obtained parameters, comparative simulations were conducted using the parameters obtained for the soft and hard floor, and the parameters were confirmed to be appropriate for each environment. By observing the difference in snake robot's propulsion depending on the presence or absence of the tactile sensor feedback signal, we confirmed the effectiveness of the tactile sensor considered in the parameter search.No potential conflict of interest relevant to this article was reported.Public Library of ScienceActa Medica Okayama1932-62031822023Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress responsee0281516ENYukiKyunaiDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityMikaSakamotoNational Institute of Genetics, ROISMayukoKoreishiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshioTsujinoGraduate School of Science, Technology, and Innovation, Kobe UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityGlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidant response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response.No potential conflict of interest relevant to this article was reported.Spandidos PublicationsActa Medica Okayama1792-09812532023Quantitative evaluation of the reduction of distortion and metallic artifacts in magnetic resonance images using the multiacquisition variable‑resonance image combination selective sequence109ENMasakiHiranoDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityYukiMutoDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityMasahiroKurodaDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityYutaFujiwaraDivision of Clinical Radiology Service, Okayama Central HospitalTomoakiSasakiDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityKazuhiroKurodaDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityRyoKamizakiDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversitySatoshiImajohDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityYoshinoriTanabeDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama UniversityWllaE. Al-HammadDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukiNakamitsuDepartment of Radiological Technology, Graduate School of Health Sciences, Okayama University, Okayama 700‑8558, JapanYudaiShimizuDepartment of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKoheiSugimotoGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University, Okayama, 770‑8558, JapanMasatakaOitaGraduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama UniversityIrfanSugiantoDepartment of Oral Radiology, Faculty of Dentistry, Hasanuddin UniversityBabatundeO. BamgboseDepartment of Oral Diagnostic Sciences, Faculty of Dentistry, Bayero UniversityMagnetic resonance imaging (MRI) is superior to computed tomography (CT) in determining changes in tissue structure, such as those observed following inflammation and infection. However, when metal implants or other metal objects are present, MRI exhibits more distortion and artifacts compared with CT, which hinders the accurate measurement of the implants. A limited number of reports have examined whether the novel MRI sequence, multiacquisition variable-resonance image combination selective (MAVRIC SL), can accurately measure metal implants without distortion. Therefore, the present study aimed to demonstrate whether MAVRIC SL could accurately measure metal implants without distortion and whether the area around the metal implants could be well delineated without artifacts. An agar phantom containing a titanium alloy lumbar implant was used for the present study and was imaged using a 3.0 T MRI machine. A total of three imaging sequences, namely MAVRIC SL, CUBE and magnetic image compilation (MAGiC), were applied and the results were compared. Distortion was evaluated by measuring the screw diameter and distance between the screws multiple times in the phase and frequency directions by two different investigators. The artifact region around the implant was examined using a quantitative method following standardization of the phantom signal values. It was revealed that MAVRIC SL was a superior sequence compared with CUBE and MAGiC, as there was significantly less distortion, a lack of bias between the two different investigators and significantly reduced artifact regions. These results suggested the possibility of utilizing MAVRIC SL for follow-up to observe metal implant insertions.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1424-82202312022Thickness Measurement at High Lift-Off for Underwater Corroded Iron-Steel Structures Using a Magnetic Sensor Probe380ENShoyaAdachiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMinoruHayashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTaiseiKawakamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYutoAndoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJinWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKenjiSakaiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihikoKiwaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshiyukiIshikawaDepartment of Civil, Environmental and Applied System Engineering, Faculty of Environmental and Urban Engineering, Kansai UniversityKeijiTsukadaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityInfrastructure facilities that were built approximately half a century ago have rapidly aged. Steel sheet piles, the inspection object in this study, are severely corroded, resulting in cave-in damages at wharfs. To solve such a problem, non-destructive inspection techniques are required. We previously demonstrated plate thickness measurement using extremely low-frequency eddy current testing. However, when the steel sheet piles are located in water, shellfish adhere to their surface, causing a lift-off of several tens of millimeters. Therefore, this large lift-off hinders the thickness measurement owing to fluctuations of magnetic signals. In this study, sensor probes with different coil diameters were prototyped and the optimum size for measuring steel sheet piles at high lift-off was investigated. Using the probes, the magnetic field was applied with a lift-off range from 0 to 80 mm, and the intensity and phase of the detected magnetic field were analyzed. Subsequently, by increasing the probe diameter, a good sensitivity was obtained for the thickness estimation with a lift-off of up to 60 mm. Moreover, these probes were used to measure the thickness of actual steel sheet piles, and measurements were successfully obtained at a high lift-off.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama1664-1078132022Subliminal meaning-contingent attentional orienting: The role of attentional control setting based on displaywide features1035690ENHuiyuanWangDepartment of Psychology, Jilin UniversityJiajiaYangFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYulinGaoDepartment of Psychology, Jilin UniversityMingZhangFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPeople's subjective factors can affect the spatial allocation of attention, and objects that are more in line with people's expectations are easier to attract attention. In the current study, we wanted to know whether the meaning-contingent spatial attentional orienting could occur at the subliminal level, that is, whether conscious awareness was needed, and which attentional control settings worked. The current study employed a modified spatial cueing paradigm and the cues were made imperceptible by backward masking. The results showed that the capture effects of the left and the right positions stemmed from the meaning-contingent attentional control setting based on displaywide features, while the inhibition effect of the lower position and the capture effect of the upper position stemmed from the abrupt onset of subliminal cues and their masks. It is concluded that the attentional orienting of meaning contingency could occur at the subliminal level, which was not restricted by conscious perception. In particular, the attentional control setting based on displaywide features played an important role in spatial attentional orienting, which was manifested in the consistent capture effects on the horizontal sides. This study refined and separated the spatial attentional orienting effects, supported the contingent involuntary attentional orienting hypothesis, and expanded its scope of application.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1424-822022222022Realization of Crowded Pipes Climbing Locomotion of Snake Robot Using Hybrid Force-Position Control Method9016ENYongdongWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTetsushiKamegawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThe movement capabilities of snake robots allow them to be applied in a variety of applications. We realized a snake robot climbing in crowded pipes. In this paper, we implement a sinusoidal curve control method that allows the snake robot to move faster. The control method is composed of a hybrid force-position controller that allows the snake robot to move more stably. We conducted experiments to confirm the effectiveness of the proposed method. The experimental results show that the proposed method is stable and effective compared to the previous control method that we had implemented in the snake robot.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama1526-9914232022Validation of pencil beam scanning proton therapy with multi-leaf collimator calculated by a commercial Monte Carlo dose enginee13817ENYukiTominagaDivision of Radiological Technology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYusukeSakuraiDepartment of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy ClinicJunyaMiyataDivision of Radiological Technology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShuichiHaradaHyogo Ion Beam Medical SupportTakashiAkagiHyogo Ion Beam Medical SupportMasatakaOitaDivision of Radiological Technology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityThis study aimed to evaluate the clinical beam commissioning results and lateral penumbra characteristics of our new pencil beam scanning (PBS) proton therapy using a multi-leaf collimator (MLC) calculated by use of a commercial Monte Carlo dose engine. Eighteen collimated uniform dose plans for cubic targets were optimized by the RayStation 9A treatment planning system (TPS), varying scan area, modulation widths, measurement depths, and collimator angles. To test the patient-specific measurements, we also created and verified five clinically realistic PBS plans with the MLC, such as the liver, prostate, base-of-skull, C-shape, and head-and-neck. The verification measurements consist of the depth dose (DD), lateral profile (LP), and absolute dose (AD). We compared the LPs and ADs between the calculation and measurements. For the cubic plans, the gamma index pass rates (gamma-passing) were on average 96.5% +/- 4.0% at 3%/3 mm for the DD and 95.2% +/- 7.6% at 2%/2 mm for the LP. In several LP measurements less than 75 mm depths, the gamma-passing deteriorated (increased the measured doses) by less than 90% with the scattering such as the MLC edge and range shifter. The deteriorated gamma-passing was satisfied by more than 90% at 2%/2 mm using uncollimated beams instead of collimated beams except for three planes. The AD differences and the lateral penumbra width (80%-20% distance) were within +/- 1.9% and +/- 1.1 mm, respectively. For the clinical plan measurements, the gamma-passing of LP at 2%/2 mm and the AD differences were 97.7% +/- 4.2% on average and within +/- 1.8%, respectively. The measurements were in good agreement with the calculations of both the cubic and clinical plans inserted in the MLC except for LPs less than 75 mm regions of some cubic and clinical plans. The calculation errors in collimated beams can be mitigated by substituting uncollimated beams.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022Study on the role of spatial frequency components in cuteness perception of infant facesENMENGNIZHOUGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022Study on the contribution of stimuli spatiotemporal features on human haptic object perceptionENHUAZHILIGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022Advanced Deep Learning Techniques for Efficient HEp-2 Computer-Aided Diagnosis SystemsENASAAD MUSAED AHMED ANAAMGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022A Study of Continuous Heartbeat Monitoring System Using the Internet of Things ApproachENEKO SAKTI RAMUKANTOROGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022A Study of Audio Scene Classification in Concept Drift SituationENIBNU DAQIQIL IDGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2073-440911202022Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect3307ENAbdul BasithFithroniDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKazukoKobayashiCollaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHirotakaUjiDepartment of Material Chemistry, Graduate School of Engineering, Kyoto UniversityManabuIshimotoFukushima SiC Applied Engineering Inc.MasaruAkehiCollaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityEijiMatsuuraDepartment of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityBNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006723192022Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model11035ENTsukasaShigehiroResearch Institute for Biomedical Sciences, Tokyo University of ScienceMahoUenoDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityMayumiKijihiraDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityRyotaroTakahashiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityChihoUmemuraDivision of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityEman A.TahaDivision of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversityChisakiKurosakaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityMegumiAsayamaDepartment of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama UniversityHiroshiMurakamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityYoshimasaNakamuraGraduate School of Environmental and Life Science, Okayama UniversityJunichiroFutamiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityJunkoMasudaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversitySecondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-gamma production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-gamma expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103(+)CD11b(+) dendritic cells (DCs) into the mLN, along with increased (1 -> 3)-beta-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103(+)CD11b(+) DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis15628ENHidekiMinematsuLaboratory of Nao‑Biotechnology, Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama UniversitySaid M.AfifyDivision of Biochemistry, Chemistry Department, Faculty of Science, Menoufa UniversityYukiSugiharaR&D Center, Katayama Chemicals Ind., Co. Ltd, Ina, MinohGhmkinHassanDepartment of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMaram H.ZahraDepartment of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkimasaSenoDepartment of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityMasakiAdachiR&D Center, Katayama Chemicals Ind., Co. Ltd, Ina, MinohMasaharuSenoDepartment of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPreviously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006723182022Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells10300ENNahokoTomonobuDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieKinoshitaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHidenoriWakeDepartment of Pharmacology, Kindai University Faculty of MedicineYusukeInoueFaculty of Science and Technology, Division of Molecular Science, Gunma UniversityI. Made WinarsaRumaFaculty of Medicine, Udayana UniversityKenSuzawaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumaGoharaDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNi Luh Gede YoniKomalasariDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFanJiangDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHitoshiMurataDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKen-IchiYamamotoDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesI. WayanSumardikaFaculty of Medicine, Udayana UniversityYouyiChenDepartment of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical UniversityJunichiroFutamiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkiraYamauchiDepartment of Biochemistry, Kawasaki Medical SchoolFutoshiKuribayashiDepartment of Biochemistry, Kawasaki Medical SchoolEisakuKondoDivision of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental SciencesShinichiToyookaDepartment of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasahiroNishiboriDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2296-634X102022NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression983599ENGokiTsujimotoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityRinItoGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKeiYoshikawaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityChihiroUekiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNobuhiroOkadaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityReprogramming of glucose metabolism occurs in many human tumor types, and one of these, gluconeogenesis, is known to exhibit anti-tumor effects in hepatocellular carcinoma (HCC). The transcription factor NFYA regulates gluconeogenesis in the normal liver tissue, but the function of the NFYA-gluconeogenesis axis in cancer and the functional differences of NFYA splicing variants in the regulation of gluconeogenesis is still unclear. Here, we demonstrate that NFYAv2, the short-form variant, upregulates the transcription of a gluconeogenic enzyme PCK1. We further reveal that its regulation induces high ROS levels and energy crisis in HCC and promotes cell death. These indicate that the NFYAv2-gluconeogenesis axis has enhanced anti-tumor effects in HCC, suggesting that the axis may be a potential therapeutic target for HCC. Furthermore, Nfyav1-deficient mice, spontaneously overexpressing Nfyav2, had no increasing gluconeogenesis in the liver. Taken together, our results reveal NFYAv2-gluconeogenesis axis has anti-tumor effects and the potential for NFYAv2 to be a safer therapeutic target for HCC.No potential conflict of interest relevant to this article was reported.岡山大学大学院教育学研究科Acta Medica Okayama1883-24231802022モンゴル伝統医学とその現代的意義18ENKazuakiKajiiXuefengBAOChaomuligeToshihikoMatsuoGraduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityWurihanBAIHospital of Inner Mongolia University for Nationalities10.18926/bgeou/63917In recent years, many countries including Japan have been advancing into super-aging society. This trend raises people̓s interest in health and longevity. In order to promote healthy longevity, it is recognized as useful measures to pay attention to “traditional medicine and complementary/alternative medicine” that cover not only illness treatment but also illness prevention, mental care, health maintenance, and human natural healing power.<br>
In this paper, we summarize the history and development of the theory of Mongolian traditional medicine in the Inner Mongolia to examine how it plays a role in clinical practice regarding health and longevity, and how it contributes to integrative medicine. In this context, patient-centered integrative medicine does not mean simple fusion of Mongolian traditional medicine with modern medicine. The characteristics of Mongolian traditional medicine would be combined with the characteristics of modern medicine, and altogether, the definition of each other̓s contribution may lead to the development of integrative medicine.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2072-666X1382022Optimization of Microchannels and Application of Basic Activation Functions of Deep Neural Network for Accuracy Analysis of Microfluidic Parameter Data1352ENFerozAhmedGraduate School of Interdisciplinary Science and Engineering in Health Systems, Department of Medical Bioengineering, Okayama UniversityMasashiShimizuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Department of Medical Bioengineering, Okayama UniversityJinWangGraduate School of Interdisciplinary Science and Engineering in Health Systems, Department of Medical Bioengineering, Okayama UniversityKenjiSakaiGraduate School of Interdisciplinary Science and Engineering in Health Systems, Department of Medical Bioengineering, Okayama UniversityToshihikoKiwaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Department of Medical Bioengineering, Okayama UniversityThe fabrication of microflow channels with high accuracy in terms of the optimization of the proposed designs, minimization of surface roughness, and flow control of microfluidic parameters is challenging when evaluating the performance of microfluidic systems. The use of conventional input devices, such as peristaltic pumps and digital pressure pumps, to evaluate the flow control of such parameters cannot confirm a wide range of data analysis with higher accuracy because of their operational drawbacks. In this study, we optimized the circular and rectangular-shaped microflow channels of a 100 mu m microfluidic chip using a three-dimensional simulation tool, and analyzed concentration profiles of different regions of the microflow channels. Then, we applied a deep learning (DL) algorithm for the dense layers of the rectified linear unit (ReLU), Leaky ReLU, and Swish activation functions to train and test 1600 experimental and interpolation of data samples which obtained from the microfluidic chip. Moreover, using the same DL algorithm, we configured three models for each of these three functions by changing the internal middle layers of these models. As a result, we obtained a total of 9 average accuracy values of ReLU, Leaky ReLU, and Swish functions for a defined threshold value of 6 x 10(-5) using the trial-and-error method. We applied single-to-five-fold cross-validation technique of deep neural network to avoid overfitting and reduce noises from data-set to evaluate better average accuracy of data of microfluidic parameters.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1424-822022142022A Heartbeat Classifier for Continuous Prediction Using a Wearable Device5080ENEko SaktiPramukantoroGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityAkioGofukuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityHeartbeat monitoring may play an essential role in the early detection of cardiovascular disease. When using a traditional monitoring system, an abnormal heartbeat may not appear during a recording in a healthcare facility due to the limited time. Thus, continuous and long-term monitoring is needed. Moreover, the conventional equipment may not be portable and cannot be used at arbitrary times and locations. A wearable sensor device such as Polar H10 offers the same capability as an alternative. It has gold-standard heartbeat recording and communication ability but still lacks analytical processing of the recorded data. An automatic heartbeat classification system can play as an analyzer and is still an open problem in the development stage. This paper proposes a heartbeat classifier based on RR interval data for real-time and continuous heartbeat monitoring using the Polar H10 wearable device. Several machine learning and deep learning methods were used to train the classifier. In the training process, we also compare intra-patient and inter-patient paradigms on the original and oversampling datasets to achieve higher classification accuracy and the fastest computation speed. As a result, with a constrain in RR interval data as the feature, the random forest-based classifier implemented in the system achieved up to 99.67% for accuracy, precision, recall, and F1-score. We are also conducting experiments involving healthy people to evaluate the classifier in a real-time monitoring system.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1420-304927122022Rational Design of Peptides Derived from Odorant-Binding Proteins for SARS-CoV-2-Related Volatile Organic Compounds Recognition3917ENJinWangFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityKenjiSakaiFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityToshihikoKiwaFaculty of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityPeptides are promising molecular-binding elements and have attracted great interest in novel biosensor development. In this study, a series of peptides derived from odorant-binding proteins (OBPs) were rationally designed for recognition of SARS-CoV-2-related volatile organic compounds (VOCs). Ethanol, nonanal, benzaldehyde, acetic acid, and acetone were selected as representative VOCs in the exhaled breath during the COVID-19 infection. Computational docking and prediction tools were utilized for OBPs peptide characterization and analysis. Multiple parameters, including the docking model, binding affinity, sequence specification, and structural folding, were investigated. The results demonstrated a rational, rapid, and efficient approach for designing breath-borne VOC-recognition peptides, which could further improve the biosensor performance for pioneering COVID-19 screening and many other applications.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0960-894X682022Ultrasound-dependent RNAi using TatU1A-rose bengal conjugate128767ENNanakoSumiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityShotaNagahiroDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityEijiNakataInstitute of Advanced Energy, Kyoto UniversityKazunoriWatanabeDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTakashiOhtsukiDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityTat-U1A-rose bengal conjugate (TatU1A-RB) was prepared as an ultrasound-sensitive RNA carrier molecule. This molecule consists of Tat cell-penetrating peptide, U1A RNA-binding protein, and rose bengal as a sonosensitizer. We demonstrated that TatU1A-RB delivered RNA via the endocytosis pathway, which was followed by ultrasound-dependent endosomal escape and cytosolic dispersion of the RNA. A short hairpin RNA (shRNA) delivered by TatU1A-RB mediated RNA interference (RNAi) ultrasound-dependently. Even by ultrasound irradiation through blood cells, RNAi could be induced with TatU1A-RB and the shRNA. This ultrasound-dependent cytosolic RNA delivery method will serve as the basis for a new approach to nucleic acid therapeutics.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0947-653928372022Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cellse202201253ENYutaMakiDepartment of Chemistry, Graduate School of Science, Osaka UniversityKazukiKawataDepartment of Chemistry, Graduate School of Science, Osaka UniversityYanboLiuDepartment of Chemistry, Graduate School of Science, Osaka UniversityKang‐YingGooDepartment of Chemistry, Graduate School of Science, Osaka UniversityRyoOkamotoDepartment of Chemistry, Graduate School of Science, Osaka UniversityYasuhiroKajiharaDepartment of Chemistry, Graduate School of Science, Osaka UniversityAyanoSatohGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityGlycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine-linked (N-) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B-subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex-type N-glycans, was introduced to the CTB. The synthesized monomeric glycosyl-CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N-glycans in specific organelles of living cells.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022Study on Benefits of Semantically Audiovisual Interaction on Unisensory Working MemoryENHongtaoYuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Acta Medica Okayama2022Research on Haptic Angle Discriminability and Development of Angle Magnitude Sorting SystemENYulongLiuGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama UniversityNo potential conflict of interest relevant to this article was reported.