MDPI Acta Medica Okayama 2227-7080 13 4 2025 An Implementation of Creep Test Assisting System with Dial Gauge Needle Reading and Smart Lighting Function for Laboratory Automation 139 EN Dezheng Kong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shihao Fang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Noprianto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuhiro Okayasu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pradini Puspitaningayu Department of Electrical Engineering, Universitas Negeri Surabaya For decades, analog dial gauges have been essential for measuring and monitoring data at various industrial instruments including production machines and laboratory equipment. Among them, we focus on the instrument for creep test in a mechanical engineering laboratory, which evaluates material strength under sustained stress. Manual reading of gauges imposes significant labor demands, especially in long-duration tests. This burden further increases under low-lighting environments, where poor visibility can lead to misreading data points, potentially compromising the accuracy of test results. In this paper, to address the challenges, we implement a creep test assisting system that possesses the following features: (1) to save the installation cost, a web camera and Raspberry Pi are employed to capture images of the dial gauge and automate the needle reading by image processing in real time, (2) to ensure reliability under low-lighting environments, a smart lighting mechanism is integrated to turn on a supplementary light when the dial gauge is not clearly visible, and (3) to allow a user to stay in a distant place from the instrument during a creep test, material break is detected and the corresponding message is notified to a laboratory staff using LINE automatically. For evaluations, we install the implemented system into a material strength measuring instrument at Okayama University, Japan, and confirm the effectiveness and accuracy through conducting experiments under various lighting conditions. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 26 14 2025 Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells 6927 EN Yoshihiko Itoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenichi Inagaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Terasaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eisaku Morimoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Ishii Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimitomo Yamaoka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Fujisawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 17 9 2025 Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma 1559 EN Anqi Chang Department of Oral Pathology and Medicine, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Okayama University Tianyan Piao Department of Oral Pathology and Medicine, Okayama University Takuma Arashima Department of Oral Pathology and Medicine, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Okayama University Yamin Soe Department of Oral Pathology and Medicine, Okayama University Zin Zin Min Department of Oral Pathology and Medicine, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Okayama University Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor-bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 18 9 2025 Initial Bonding Performance to CAD/CAM Restorative Materials: The Impact of Stepwise Concentration Variation in 8-Methacryloxyoctyl Trimethoxy Silane and 3-Methacryloxypropyl Trimethoxy Silane on Feldspathic Ceramic, Lithium Disilicate Glass-Ceramic, and Polymer-Infiltrated Ceramic 1983 EN Yukinori Maruo Department of Prosthodontics, Okayama University Miho Kuwahara Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Matsumoto Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences This study investigated the effects of varying concentrations of two distinct silane agents, 8-methacryloxyoctyl trimethoxy silane (8-MOTS) and 3-methacryloxypropyl trimethoxy silane (γ-MPTS), on their initial bonding efficacy to feldspathic ceramic (FC), lithium disilicate glass-ceramic (LD) and polymer-infiltrated ceramic (PIC) specimens, in 10% increments for concentrations ranging from 10% to 40%. Shear bond strengths between the ceramic substrates and the luting material were assessed following 24 h incubation in distilled water. For FC, the median value of shear bond strength peaked at 20% of γ-MPTS (7.4 MPa), while 8-MOTS exhibited a concentration-dependent increase, reaching its highest value at 40% (13.1 MPa). For LD, γ-MPTS above 10% yielded similar strength median values (10.2 MPa), whereas 8-MOTS at 30% (15.8 MPa) and 40% (13.4 MPa) yielded higher strength values than at 10% (2.9 MPa) and 20% (4.1 MPa), with the highest median value exhibited at 30%. For PIC, both γ-MPTS and 8-MOTS demonstrated similarly low bond strength values which were not significantly different from the non-silane-treated specimens. When applied on silica-based FC and LD, silane revealed a concentration-dependent bonding effect, with 8-MOTS exhibiting superior bond strength to γ-MPTS. However, PIC, characterized by a high inorganic filler content, demonstrated limited bondability with both silanes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-7080 13 4 2025 An Implementation of Creep Test Assisting System with Dial Gauge Needle Reading and Smart Lighting Function for Laboratory Automation 139 EN Dezheng Kong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shihao Fang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuhiro Noprianto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuhiro Okayasu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pradini Puspitaningayu Department of Electrical Engineering, Universitas Negeri Surabaya For decades, analog dial gauges have been essential for measuring and monitoring data at various industrial instruments including production machines and laboratory equipment. Among them, we focus on the instrument for creep test in a mechanical engineering laboratory, which evaluates material strength under sustained stress. Manual reading of gauges imposes significant labor demands, especially in long-duration tests. This burden further increases under low-lighting environments, where poor visibility can lead to misreading data points, potentially compromising the accuracy of test results. In this paper, to address the challenges, we implement a creep test assisting system that possesses the following features: (1) to save the installation cost, a web camera and Raspberry Pi are employed to capture images of the dial gauge and automate the needle reading by image processing in real time, (2) to ensure reliability under low-lighting environments, a smart lighting mechanism is integrated to turn on a supplementary light when the dial gauge is not clearly visible, and (3) to allow a user to stay in a distant place from the instrument during a creep test, material break is detected and the corresponding message is notified to a laboratory staff using LINE automatically. For evaluations, we install the implemented system into a material strength measuring instrument at Okayama University, Japan, and confirm the effectiveness and accuracy through conducting experiments under various lighting conditions. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 7 2 2025 Molecular Iodine-Catalyzed Synthesis of 3,3-Disubstituted Isatins: Total Synthesis of Indole Alkaloid, 3,3-Dimethoxy-2-oxindole 43 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shota Asai School of Pharmacy, Shujitsu University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 3,3-Dialkoxy-2-oxindoles are prevalent in natural products and exhibit unique biological activities. Among them, acyclic alkoxy analogues show instability in acidic conditions, making access to acyclic isatin ketals highly challenging. Conventional methods for the synthesis of 3,3-dialkoxy-2-oxindoles usually require strongly acidic and harsh reaction conditions, resulting in a low overall efficiency. Herein, we report on an acid- and metal-free protocol for the synthesis of 3,3-dialkoxy-2-oxindoles from isatins through an iodine-catalyzed ketalization. This photochemical protocol does not require the use of any specific reagents such as metal catalysts. Furthermore, the total synthesis of an unprecedented 2-oxindole alkaloid bearing 3,3-dimethoxy moiety is achieved. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 25 7 2025 Length Estimation of Pneumatic Artificial Muscle with Optical Fiber Sensor Using Machine Learning 2221 EN Yilei Ni Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shuichi Wakimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Weihang Tian Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuichiro Toda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takefumi Kanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Daisuke Yamaguchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University A McKibben artificial muscle is a soft actuator driven by air pressure, characterized by its flexibility, lightweight design, and high power-to-weight ratio. We have developed a smart artificial muscle that is capable of sensing its motion. To enable this sensing function, an optical fiber was integrated into the sleeve consisting of multiple fibers and serving as a component of the McKibben artificial muscle. By measuring the macrobending loss of the optical fiber, the length of the smart artificial muscle is expected to be estimated. However, experimental results indicated that the sensor's characteristics depend not only on the length but also on the load and the applied air pressure. This dependency arises because the stress applied to the optical fiber increases, causing microbending loss. In this study, we employed a machine learning model, primarily composed of Long Short-Term Memory (LSTM) neural networks, to estimate the length of the smart artificial muscle. The experimental results demonstrate that the length estimation obtained through machine learning exhibits a smaller error. This suggests that machine learning is a feasible approach to enhancing the length measurement accuracy of the smart artificial muscle. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 7 2025 Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis 2287 EN Yuki Fujii Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuyuki Matsumoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Akihiro Matsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shigeru Horiguchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Koichiro Tsutsumi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 7 2025 Impact of Lifestyle Changes on Body Weight Gain During Nationwide Lockdown Due to COVID-19 Pandemic 2242 EN Chisa Nishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: During the coronavirus disease 2019 (COVID-19) pandemic, people in Japan were urged to stay at home as much as possible, and this resulted in significant changes in lifestyle behavior. The new lifestyle included factors affecting both energy intake and energy consumption, and it is now thought that weight gain during the lockdown was the result of complex effects. The aim of this study was to determine the relationships among lifestyle habits, laboratory data, and body weight gain during the lockdown using medical check-up data. Methods: A total of 3789 individuals who had undergone consecutive medical check-ups during the period from 2018 to 2020 were included in this study. Participants whose body weight had increased by 5% or more were divided into two groups: a before-lockdown group (participants who had gained weight between 2018 and 2019) and an after-lockdown group (participants who had gained weight between 2019 and 2020). Physical measurements, laboratory data, and answers to six questions about lifestyle habits, for which information was obtained from the records from medical check-ups, were compared in the two groups. Results: There was no significant difference between the distribution of weight changes in 2018-2019 before the lockdown and the distribution of weight changes in 2019-2020 after the lockdown. The before-lockdown and after-lockdown groups both included about 7% of the total participants (279 and 273 participants, respectively). Diastolic blood pressure and levels of AST, ALT, and LDL-C were significantly higher in the after-lockdown group than in the before-lockdown group. The percentages of participants with alcohol consumption and exercise habits were significantly higher in the after-lockdown group than in the before-lockdown group, and an analysis by gender showed that the differences were significant for women but not for men. Conclusions: The distributions of weight changes before and during the COVID-19 pandemic were similar. Exercise habits and alcohol consumption might have been unique factors causing weight gain during the COVID-19 pandemic, particularly in women. Our findings suggest that the impact of behavioral restrictions and lifestyle changes during a pandemic may be different in men and women. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-4893 18 3 2025 A Hair Drawing Evaluation Algorithm for Exactness Assessment Method in Portrait Drawing Learning Assistant System 143 EN Yue Zhang Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Erita Cicilia Febrianti Department of Electrical Engineering, Politeknik Elektronika Negeri Surabaya Amang Sudarsono Department of Electrical Engineering, Politeknik Elektronika Negeri Surabaya Chenchien Hsu Department of Electrical Engineering, National Taiwan Normal University Nowadays, portrait drawing has become increasingly popular as a means of developing artistic skills and nurturing emotional expression. However, it is challenging for novices to start learning it, as they usually lack a solid grasp of proportions and structural foundations of the five senses. To address this problem, we have studied Portrait Drawing Learning Assistant System (PDLAS) for guiding novices by providing auxiliary lines of facial features, generated by utilizing OpenPose and OpenCV libraries. For PDLAS, we have also presented the exactness assessment method to evaluate drawing accuracy using the Normalized Cross-Correlation (NCC) algorithm. It calculates the similarity score between the drawing result and the initial portrait photo. Unfortunately, the current method does not assess the hair drawing, although it occupies a large part of a portrait and often determines its quality. In this paper, we present a hair drawing evaluation algorithm for the exactness assessment method to offer comprehensive feedback to users in PDLAS. To emphasize hair lines, this algorithm extracts the texture of the hair region by computing the eigenvalues and eigenvectors of the hair image. For evaluations, we applied the proposal to drawing results by seven students from Okayama University, Japan and confirmed the validity. In addition, we observed the NCC score improvement in PDLAS by modifying the face parts with low similarity scores from the exactness assessment method. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 6 2025 Vesicular Glutamate Transporter 3 Is Involved in Glutamatergic Signalling in Podocytes 2485 EN Naoko Nishii Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Kawai Department of Cell Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Yasuoka Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Abe Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Tatsumi Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuika Harada Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Takaaki Miyaji Department of Genomics and Proteomics, Advanced Science Research Center, Okayama University Shunai Li Center for Innovative Clinical Medicine, Okayama University Hospital Moemi Tsukano Central Research Laboratory, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Center for Innovative Clinical Medicine, Okayama University Hospital Daisuke Ogawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohji Takei Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Yamada Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Glomerular podocytes act as a part of the filtration barrier in the kidney. The activity of this filter is regulated by ionotropic and metabotropic glutamate receptors. Adjacent podocytes can potentially release glutamate into the intercellular space; however, little is known about how podocytes release glutamate. Here, we demonstrated vesicular glutamate transporter 3 (VGLUT3)-dependent glutamate release from podocytes. Immunofluorescence analysis revealed that rat glomerular podocytes and an immortal mouse podocyte cell line (MPC) express VGLUT1 and VGLUT3. Consistent with this finding, quantitative RT-PCR revealed the expression of VGLUT1 and VGLUT3 mRNA in undifferentiated and differentiated MPCs. In addition, the exocytotic proteins vesicle-associated membrane protein 2, synapsin 1, and synaptophysin 1 were present in punctate patterns and colocalized with VGLUT3 in MPCs. Interestingly, approximately 30% of VGLUT3 colocalized with VGLUT1. By immunoelectron microscopy, VGLUT3 was often observed around clear vesicle-like structures in differentiated MPCs. Differentiated MPCs released glutamate following depolarization with high potassium levels and after stimulation with the muscarinic agonist pilocarpine. The depletion of VGLUT3 in MPCs by RNA interference reduced depolarization-dependent glutamate release. These results strongly suggest that VGLUT3 is involved in glutamatergic signalling in podocytes and may be a new drug target for various kidney diseases. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1999-5903 17 3 2025 Facial Privacy Protection with Dynamic Multi-User Access Control for Online Photo Platforms 124 EN Andri Santoso Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Green Innovation Center, Okayama University Yuta Kodera Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University In the digital age, sharing moments through photos has become a daily habit. However, every face captured in these photos is vulnerable to unauthorized identification and potential misuse through AI-powered synthetic content generation. Previously, we introduced SnapSafe, a secure system for enabling selective image privacy focusing on facial regions for single-party scenarios. Recognizing that group photos with multiple subjects are a more common scenario, we extend SnapSafe to support multi-user facial privacy protection with dynamic access control designed for online photo platforms. Our approach introduces key splitting for access control, an owner-centric permission system for granting and revoking access to facial regions, and a request-based mechanism allowing subjects to initiate access permissions. These features ensure that facial regions remain protected while maintaining the visibility of non-facial content for general viewing. To ensure reproducibility and isolation, we implemented our solution using Docker containers. Our experimental assessment covered diverse scenarios, categorized as "Single", "Small", "Medium", and "Large", based on the number of faces in the photos. The results demonstrate the system's effectiveness across all test scenarios, consistently performing face encryption operations in under 350 ms and achieving average face decryption times below 286 ms across various group sizes. The key-splitting operations maintained a 100% success rate across all group configurations, while revocation operations were executed efficiently with server processing times remaining under 16 ms. These results validate the system's capability in managing facial privacy while maintaining practical usability in online photo sharing contexts. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 6 2025 Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis 2713 EN Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Marina Kawaguchi Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Oguni Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Yasuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Nahoko Iwata Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 15 6 2025 Robustness of Machine Learning Predictions for Determining Whether Deep Inspiration Breath-Hold Is Required in Breast Cancer Radiation Therapy 668 EN Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Jamal, Ghaida Al Jamal Department of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology Mamiko Fujikura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/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.

MDPI Acta Medica Okayama 2075-4418 15 6 2025 Improving Diagnostic Performance for Head and Neck Tumors with Simple Diffusion Kurtosis Imaging and Machine Learning Bi-Parameter Analysis 790 EN Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuka Fukumura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nurul N. Kamaruddin Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Yanagi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/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.

MDPI Acta Medica Okayama 2227-9032 13 6 2025 Effects of Trehalose on Halitosis: A Randomized Cross-Over Clinical Trial 619 EN Hisataka Miyai Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takaaki Tomofuji Department of Community Oral Health, School of Dentistry, Asahi University Hirofumi Mizuno Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Momoko Nakahara Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Kota Kataoka Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Ichiro Sumita Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Yurika Uchida Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Naoki Toyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reiko Yamanaka-Kohno Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Halitosis is a condition characterized by an unpleasant malodor. Intra-oral halitosis is caused by volatile sulfur compounds (VSCs) and can be associated with oral dryness. Trehalose is one of the materials used to relieve oral dryness. The aim of the present study was to investigate the effect of trehalose on halitosis. Methods: This prospective, double-blinded, placebo-controlled, cross-over study enrolled volunteers from Okayama University Hospital. The participants were randomly divided into two groups, with one group receiving trehalose (a 10% trehalose solution) and the other receiving a placebo (distilled water) in a 1:1 allocation. The primary study outcome was the subjective organoleptic test. The secondary outcomes were the concentrations of the VSCs, which were measured using a portable gas chromatography device, and the oral moisture status, which was measured using an oral moisture meter. The planned sample size was 10 participants based on the previous study. Results: The final intention-to-treat analysis was performed using the data from 9 participants. After applying 10% trehalose as an oral spray, the organoleptic score decreased in a time-dependent manner. However, no significant differences were seen between the trehalose and placebo groups. In terms of secondary outcomes, the oral moisture levels increased immediately after the trehalose spray application, and significant differences in the amount of change from the baseline were seen between the trehalose and placebo groups (p = 0.047). No significant differences were seen in any of the other variables (p > 0.05). Conclusions: We could not identify any positive effects on halitosis from a one-time 10% trehalose application as an oral spray in this prospective, double-blinded, placebo-controlled, cross-over study. However, the trehalose application immediately improved the oral moisture levels and was useful for treating oral dryness. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 13 5 2025 Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial 577 EN Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Takayama Department of Oral Biochemistry, Asahi University School of Dentistry Shinichi Tokuno Graduate School of Health Innovation, Kanagawa University of Human Services Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann–Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3417 15 5 2025 Deep Reinforcement Learning for Dynamic Pricing and Ordering Policies in Perishable Inventory Management 2421 EN Yusuke Nomura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ziang Liu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tatsushi Nishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Perishable goods have a limited shelf life, and inventory should be discarded once it exceeds its shelf life. Finding optimal inventory management policies is essential since inefficient policies can lead to increased waste and higher costs. While many previous studies assume the perishable inventory is processed following the First In, First Out rule, it does not reflect customer purchasing behavior. In practice, customers' preferences are influenced by the shelf life and price of products. This study optimizes inventory and pricing policies for a perishable inventory management problem considering age-dependent probabilistic demand. However, introducing dynamic pricing significantly increases the complexity of the problem. To tackle this challenge, we propose eliminating irrational actions in dynamic programming without sacrificing optimality. To solve this problem more efficiently, we also implement a deep reinforcement learning algorithm, proximal policy optimization, to solve this problem. The results show that dynamic programming with action reduction achieved an average of 63.1% reduction in computation time compared to vanilla dynamic programming. In most cases, proximal policy optimization achieved an optimality gap of less than 10%. Sensitivity analysis of the demand model revealed a negative correlation between customer sensitivity to shelf lives or prices and total profits. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2304-6767 13 2 2025 Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress 61 EN Takenori Kanai Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University Kyoko Osawa Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University Koichiro Kajiwara Department of Oral Growth & Development, Hokkaido University Yoshiaki Sato Department of Orthodontics, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University Yoshihiko Sawa Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: We investigated morphological differences in osteocyte processes between aged mice and our original podoplanin-conditional knockout (cKO) mice in which the floxed exon 3 of podoplanin was deleted by Dmp-1-driven Cre (Dmp1-Cre;PdpnΔ/Δ). Methods: SEM observation on osteocyte cell process, histochemistry for bone remodeling with mechanostress, and RT-PCR for RANKL and M-CSF in podoplanin cKO mouse bone with mechanostress was investigated. Results: SEM observations showed fewer and thinner osteocyte processes in femurs from 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than from 23-week-old wild-type mice, while the numbers of osteocyte processes in femurs and calvarias were similar in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice and 48-week-old wild-type mice. Furthermore, cell process numbers in femurs and calvarias were significantly smaller in 23-week-old Dmp1-Cre;PdpnΔ/Δ mice than in 48-week-old wild-type mice. In the test for differences in alveolar bone resorption under mechanical stress between Dmp1-Cre;PdpnΔ/Δ and wild-type mice, the area of TRAP-positive resorption pits was larger in wild-type mice than in Dmp1-Cre;PdpnΔ/Δ mice. In a quantitative tissue PCR analysis, the mRNA expression levels of RANKL and M-CSF in alveolar bone under mechanical stress were significantly lower in Dmp1-Cre;PdpnΔ/Δ mice than in wild-type mice. These results suggest that a reduction in cell process formation in osteocytes with podoplanin cKO affected the absorption of alveolar bone under mechanical stress in Dmp1-Cre;PdpnΔ/Δ mice. Conclusions: In podoplanin-deficient bone, the deformation of osteocyte processes by mechanical stimuli is not recognized as a stress due to the lower number of cell processes with podoplanin deficiency; therefore, the production of osteoclast migration/differentiation factors by activated osteocytes is not fully induced and macrophage migration to alveolar bone with mechanical stress appeared to be suppressed. These results indicate that podoplanin-dependent osteocyte process formation indirectly plays a key role in sensing mechanical stress in bone. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 4 2025 Natural Course and Long-Term Outcomes of Gastric Subepithelial Lesions: A Systematic Review 1055 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Gastric subepithelial lesions (SELs) are often incidentally detected during endoscopic examinations, with most patients being asymptomatic and lesions measuring <20 mm. Despite their generally indolent nature, certain SELs, such as gastrointestinal stromal tumors, require resection. Current guidelines recommend periodic surveillance; however, the natural course and long-term outcomes of gastric SELs have not been sufficiently investigated. This systematic review aimed to synthesize evidence on the progression, growth rate, and risk factors associated with gastric SELs to inform clinical management strategies. Methods: A comprehensive search of PubMed was conducted for peer-reviewed studies published between January 2000 and November 2024. Eligible studies included original studies on the follow-up and progression of gastric SELs. Non-English articles, reviews, case reports, and unrelated topics were excluded. In total, 277 articles were screened, with 15 additional articles identified through manual screening. Ultimately, 41 articles were included in the analysis. The study protocol is registered in PROSPERO (CRD42024614865). Results: Large-scale studies reported low growth rates of 2.0-8.5% over 2.0-5.0 years, while smaller studies reported a broader range of growth rates of 5.4-28.4%. The factors contributing to these discrepancies include patient selection, follow-up duration, and growth criteria. Risk factors for lesion size increase include larger initial lesion size, irregular margins, heterogeneous echo patterns, and certain tumor locations. Conclusions: These findings underscore the need for individualized management strategies based on lesion size, imaging characteristics, and risk factors. The close monitoring of high-risk lesions is crucial for timely intervention. Standardized growth criteria and optimized follow-up protocols are essential for improving clinical decision making and patient outcomes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 4 2025 Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study 1391 EN Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nobuyoshi Matsuki Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoko Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Keigo Ueda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yui Matsuda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Takase Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Omura Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 13 2 2025 The Abnormal Expression of Tubular SGLT2 and GULT2 in Diabetes Model Mice with Malocclusion-Induced Hyperglycemia 267 EN Koichiro Kajiwara Department of Oral Growth & Development, Fukuoka Dental College Sachio Tamaoki Department of Oral Growth & Development, Fukuoka Dental College Yoshihiko Sawa Department of Oral Function & Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: A relationship between malocclusion and the promotion of diabetes has been suggested. In hyperglycemia, the expression of sodium-glucose cotransporter 2 (SGLT2) and the facilitative glucose transporter 2 (GLUT2) is upregulated in proximal tubular cells, leading to an increase in renal glucose reabsorption. The present study aimed to investigate whether malocclusion contributes to diabetic exacerbation. Methods: Streptozotocin (STZ)-induced diabetic mice with malocclusion due to cutting molars were investigated based on increased blood glucose levels. PCR and immunohistochemical analyses were performed on diabetic mice kidneys to investigate the expression of SGLT2 and GLUT2. Results: Animal experiments were performed using 32 mice for 21 days. The time to reach a diabetic condition in STZ-administered mice was shorter with malocclusion than without malocclusion. The increase and mean blood glucose levels in STZ-administered mice were steeper and higher with malocclusion than without malocclusion. Urea albumin, BUN, and CRE levels were higher in diabetic mice with malocclusion than in diabetic mice without. Immunoreaction with anti-SGLT2 and anti-GLUT2 in the renal tissue of STZ-administered mice was stronger with malocclusion than without malocclusion. The amounts of SGLT2 and GLUT2 mRNA in the renal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. The amounts of TNF-a and IL-6 mRNA in the large intestinal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. Conclusions: Our results indicate that malocclusion accelerates the tubular expression of SGLT2 and GLUT2 under hyperglycemia. Malocclusion may be a diabetes-exacerbating factor with increased poor glycemic control due to shortened occlusion time resulting from swallowing food without chewing. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-445X 14 2 2025 Interchangeability of Cross-Platform Orthophotographic and LiDAR Data in DeepLabV3+-Based Land Cover Classification Method 217 EN Shijun Pan Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University Takashi Kojima TOKEN C. E. E. Consultants Co., Ltd. Yutaro Hashimoto Graduate School of Environmental and Life Science, Okayama University Riverine environmental information includes important data to collect, and the data collection still requires personnel's field surveys. These on-site tasks still face significant limitations (i.e., hard or danger to entry). In recent years, as one of the efficient approaches for data collection, air-vehicle-based Light Detection and Ranging technologies have already been applied in global environmental research, i.e., land cover classification (LCC) or environmental monitoring. For this study, the authors specifically focused on seven types of LCC (i.e., bamboo, tree, grass, bare ground, water, road, and clutter) that can be parameterized for flood simulation. A validated airborne LiDAR bathymetry system (ALB) and a UAV-borne green LiDAR System (GLS) were applied in this study for cross-platform analysis of LCC. Furthermore, LiDAR data were visualized using high-contrast color scales to improve the accuracy of land cover classification methods through image fusion techniques. If high-resolution aerial imagery is available, then it must be downscaled to match the resolution of low-resolution point clouds. Cross-platform data interchangeability was assessed by comparing the interchangeability, which measures the absolute difference in overall accuracy (OA) or macro-F1 by comparing the cross-platform interchangeability. It is noteworthy that relying solely on aerial photographs is inadequate for achieving precise labeling, particularly under limited sunlight conditions that can lead to misclassification. In such cases, LiDAR plays a crucial role in facilitating target recognition. All the approaches (i.e., low-resolution digital imagery, LiDAR-derived imagery and image fusion) present results of over 0.65 OA and of around 0.6 macro-F1. The authors found that the vegetation (bamboo, tree, grass) and road species have comparatively better performance compared with clutter and bare ground species. Given the stated conditions, differences in the species derived from different years (ALB from year 2017 and GLS from year 2020) are the main reason. Because the identification of clutter species includes all the items except for the relative species in this research, RGB-based features of the clutter species cannot be substituted easily because of the 3-year gap compared with other species. Derived from on-site reconstruction, the bare ground species also has a further color change between ALB and GLS that leads to decreased interchangeability. In the case of individual species, without considering seasons and platforms, image fusion can classify bamboo and trees with higher F1 scores compared to low-resolution digital imagery and LiDAR-derived imagery, which has especially proved the cross-platform interchangeability in the high vegetation types. In recent years, high-resolution photography (UAV), high-precision LiDAR measurement (ALB, GLS), and satellite imagery have been used. LiDAR measurement equipment is expensive, and measurement opportunities are limited. Based on this, it would be desirable if ALB and GLS could be continuously classified by Artificial Intelligence, and in this study, the authors investigated such data interchangeability. A unique and crucial aspect of this study is exploring the interchangeability of land cover classification models across different LiDAR platforms. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-1729 15 2 2025 Distinct Infection Mechanisms of Rhizoctonia solani AG-1 IA and AG-4 HG-I+II in Brachypodium distachyon and Barley 235 EN Niranjan Mahadevan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rozi Fernanda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yusuke Kouzai Crop Stress Management Group, Division of Plant Molecular Regulation Research, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO) Natsuka Kohno Faculty of Agriculture, Okayama University Reiko Nagao Faculty of Agriculture, Okayama University Khin Thida Nyein Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Megumi Watanabe Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nanami Sakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hidenori Matsui Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuhiro Toyoda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuki Ichinose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Keiichi Mochida RIKEN Center for Sustainable Resource Science Hiroshi Hisano Institute of Plant Science and Resources, Okayama University Yoshiteru Noutoshi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Rhizoctonia solani is a basidiomycete phytopathogenic fungus that causes rapid necrosis in a wide range of crop species, leading to substantial agricultural losses worldwide. The species complex is divided into 13 anastomosis groups (AGs) based on hyphal fusion compatibility and further subdivided by culture morphology. While R. solani classifications were shown to be independent of host specificity, it remains unclear whether different R. solani isolates share similar virulence mechanisms. Here, we investigated the infectivity of Japanese R. solani isolates on Brachypodium distachyon and barley. Two isolates, AG-1 IA (from rice) and AG-4 HG-I+II (from cauliflower), infected leaves of both plants, but only AG-4 HG-I+II infected roots. B. distachyon accessions Bd3-1 and Gaz-4 and barley cultivar 'Morex' exhibited enhanced resistance to both isolates compared to B. distachyon Bd21 and barley cultivars 'Haruna Nijo' and 'Golden Promise'. During AG-1 IA infection, but not AG-4 HG-I+II infection, resistant Bd3-1 and Morex induced genes for salicylic acid (SA) and N-hydroxypipecolic acid (NHP) biosynthesis. Pretreatment with SA or NHP conferred resistance to AG-1 IA, but not AG-4 HG-I+II, in susceptible B. distachyon Bd21 and barley Haruna Nijo. On the leaves of susceptible Bd21 and Haruna Nijo, AG-1 IA developed extensive mycelial networks with numerous infection cushions, which are specialized infection structures well-characterized in rice sheath blight. In contrast, AG-4 HG-I+II formed dispersed mycelial masses associated with underlying necrosis. We propose that the R. solani species complex encompasses at least two distinct infection strategies: AG-1 IA exhibits a hemibiotrophic lifestyle, while AG-4 HG-I+II follows a predominantly necrotrophic strategy. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2308-3425 12 2 2025 Clinical Significance of Serum Omega-3 Fatty Acids on Endothelial Function in Patients with Coronary Artery Disease Under Statin Therapy 60 EN Kei Yunoki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Hiroaki Matsumi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Motoki Kubo Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Yoshiki Hata Minamino Cardiovascular Hospital Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Vascular endothelial function plays an important role in the pathogenesis of atherosclerosis. The reduction in low-density lipoprotein cholesterol (LDL-C) is a key therapy for preventing coronary artery disease (CAD), but the role of omega-3 fatty acids as residual risk factors of CAD remains controversial. We studied the correlation between serum omega-3 fatty acid levels and endothelial function in patients with CAD receiving statin therapy and examined the effect of eicosapentaenoic acid (EPA) therapy on endothelial function. Methods: A total of 150 consecutive patients with CAD receiving statin therapy (LDL-C levels < 100 mg/dL) were enrolled. Serum omega-3 fatty acid levels were measured, and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery. Subsequently, 65 patients with impaired FMD (<6%) and low EPA/arachidonic acid (AA) (<0.3) were administered EPA, and FMD was reassessed after 3 months. Results: A multivariate linear regression analysis demonstrated that serum docosahexaenoic acid (DHA) and EPA plus DHA levels were independent determinants of %FMD (β = 0.214 and 0.163, p < 0.05, respectively). The EPA therapy significantly improved %FMD (from 3.7 ± 1.0% to 4.1 ± 1.0%, p < 0.05) in patients with low EPA/AA, and especially in patients with low EPA/AA and high triglyceride levels (from 3.4 ± 1.0% to 4.0 ± 1.1%, p < 0.01). Conclusions: Serum omega-3 fatty acid levels were associated with endothelial dysfunction in patients with CAD receiving statin therapy. EPA therapy improves endothelial function in patients with low EPA/AA, especially those with low EPA/AA and high triglycerides. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2313-7673 10 2 2025 Radiographic and Clinical Assessment of Unidirectional Porous Beta-Tricalcium Phosphate to Treat Benign Bone Tumors 101 EN Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Haruyoshi Katayama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuto Itano Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takanao Kurozumi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Teruhiko Ando Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences The purpose of this study was to evaluate radiographic changes, clinical outcomes, and complications following unidirectional porous beta-tricalcium phosphate (UDPTCP) implantation for the treatment of benign bone tumors. We retrospectively analyzed 46 patients who underwent intralesional resection. The patients were divided into two cohorts: Cohort 1 (n = 32), which included all bones except the phalanges and metacarpal/tarsal bones, and Cohort 2 (n = 14), which included the phalanges and metacarpal/tarsal bones. Radiographic changes were assessed at each reading based on resorption of the implanted UDPTCP and bone trabeculation through the defect. UDPTCP resorption and bone trabeculation were observed on radiographs within 3 months of surgery in all patients. Bone remodeling in the cavity progressed steadily for up to 3 years postoperatively. In Cohort 1, resorption and trabeculation progressed significantly in young patients, and trabeculation developed significantly in small lesions. The rates of resorption and trabeculation at 3 months postoperatively correlated statistically with their increased rates at one year. There was no statistical difference in resorption and trabeculation rates between Cohort 1 and Cohort 2. There were no cases of postoperative deep infections or allergic reactions related to the implant. UDPTCP is a useful bone-filling substitute for the treatment of benign bone tumors and has a low complication rate. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 16 2 2025 Implementation of Sensor Input Setup Assistance Service Using Generative AI for SEMAR IoT Application Server Platform 108 EN I. Nyoman Darma Kotama Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University Anak Agung Surya Pradhana Graduate School of Natural Science and Technology, Okayama University Noprianto Graduate School of Natural Science and Technology, Okayama University I. Gusti Made Ngurah Desnanjaya Department of Computer System Engineering, Institute of Business and Technology Indonesia For rapid deployments of various IoT application systems, we have developed Smart Environmental Monitoring and Analytical in Real-Time (SEMAR) as an integrated server platform. It is equipped with rich functions for collecting, analyzing, and visualizing various data. Unfortunately, the proper configuration of SEMAR with a variety of IoT devices can be complex and challenging for novice users, since it often requires technical expertise. The assistance of Generative AI can be helpful to solve this drawback. In this paper, we present an implementation of a sensor input setup assistance service for SEMAR using prompt engineering techniques and Generative AI. A user needs to define the requirement specifications and environments of the IoT application system for sensor inputs, and give them to the service. Then, the service provides step-by-step guidance on sensor connections, communicating board configurations, network connections, and communication protocols to the user, which can help the user easily set up the configuration to connect the relevant devices to SEMAR. For evaluations, we applied the proposal to the input sensor setup processes of three practical IoT application systems with SEMAR, namely, a smart light, water heater, and room temperature monitoring system. In addition, we applied it to the setup process of an IoT application system for a course for undergraduate students at the Insitut Bisnis dan Teknologi (INSTIKI), Indonesia. The results demonstrate the effectiveness of the proposed service for SEMAR. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 16 2 2025 An Application of SEMAR IoT Application Server Platform to Drone-Based Wall Inspection System Using AI Model 91 EN Yohanes Yohanie Fridelin Panduman Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Radhiatul Husna Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Noprianto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shunya Sakamaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sritrusta Sukaridhoto Department of Informatics and Computer, Politeknik Elektronika Negeri Surabaya Yan Watequlis Syaifudin Department of Information Technology, State Polytechnic of Malang Alfiandi Aulia Rahmadani Department of Electrical Engineering, State Polytechnic of Malang Recently, artificial intelligence (AI) has been adopted in a number of Internet of Things (IoT) application systems to enhance intelligence. We have developed a ready-made server with rich built-in functions to collect, process, display, analyze, and store data from various IoT devices, the SEMAR (Smart Environmental Monitoring and Analytics in Real-Time) IoT application server platform, in which various AI techniques have been implemented to enhance its capabilities. In this paper, we present an application of SEMAR to a drone-based wall inspection system using an object detection AI model called You Only Look Once (YOLO). This system aims to detect wall cracks at high places using images taken via a camera on a flying drone. An edge computing device is installed to control the drone, sending the taken images through the Kafka system, storing them with the drone flight data, and sending the data to SEMAR. The images are analyzed via YOLO through SEMAR. For evaluations, we implemented the system using Ryze Tello for the drone and Raspberry Pi for the edge, and we evaluated the detection accuracy. The preliminary experiment results confirmed the effectiveness of the proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2224-2708 14 1 2024 Enhancing Campus Environment: Real-Time Air Quality Monitoring Through IoT and Web Technologies 2 EN Alfiandi Aulia Rahmadani Department of Electrical Engineering, State Polytechnic of Malang Yan Watequlis Syaifudin Department of Information Technology, State Polytechnic of Malang Budhy Setiawan Department of Electrical Engineering, State Polytechnic of Malang Yohanes Yohanie Fridelin Panduman Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Nowadays, enhancing campus environments through mitigations of air pollutions is an essential endeavor to support academic achievements, health, and safety of students and staffs in higher educational institutes. In laboratories, pollutants from welding, auto repairs, or chemical experiments can drastically degrade the air quality in the campus, endangering the respiratory and cognitive health of students and staffs. Besides, in universities in Indonesia, automobile emissions of harmful substances such as carbon monoxide (CO), nitrogen dioxide (NO2), and hydrocarbon (HC) have been a serious problem for a long time. Almost everybody is using a motorbike or a car every day in daily life, while the number of students is continuously increasing. However, people in many campuses including managements do not be aware these problems, since air quality is not monitored. In this paper, we present a real-time air quality monitoring system utilizing Internet of Things (IoT) integrated sensors capable of detecting pollutants and measuring environmental conditions to visualize them. By transmitting data to the SEMAR IoT application server platform via an ESP32 microcontroller, this system provides instant alerts through a web application and Telegram notifications when pollutant levels exceed safe thresholds. For evaluations of the proposed system, we adopted three sensors to measure the levels of CO, NO2, and HC and conducted experiments in three sites, namely, Mechatronics Laboratory, Power and Emission Laboratory, and Parking Lot, at the State Polytechnic of Malang, Indonesia. Then, the results reveal Good, Unhealthy, and Dangerous for them, respectively, among the five categories defined by the Indonesian government. The system highlighted its ability to monitor air quality fluctuations, trigger warnings of hazardous conditions, and inform the campus community. The correlation of the sensor levels can identify the relationship of each pollutant, which provides insight into the characteristics of pollutants in a particular scenario. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 14 3 2025 Interrelationships Between Plasma Levels of Brain Natriuretic Peptide and Prolonged Symptoms Due to Long COVID 817 EN Yohei Masuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, <= 18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 3 2025 LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes 1007 EN Shuichi Naniwa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Aki Yoshida Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yoshihisa Nasu Locomotive Pain Center, Okayama University Hospital Ryuichi Nakahara Locomotive Pain Center, Okayama University Hospital Takashi Ohtsuki Department of Medical Technology, Graduate School of Health Sciences, Okayama University Yoshifumi Hotta Department of Orthopaedic Surgery, Sayo Central Hospital Noriyuki Shimizu Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Chinatsu Ichikawa Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Deting Lin Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Noriaki Otsuka Department of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Toshifumi Ozaki Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We 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.

MDPI Acta Medica Okayama 2076-328X 15 1 2025 The Impact of Task Context on Pleasantness and Softness Estimations: A Study Based on Three Touch Strategies 63 EN Binyue Gao Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshimichi Ejima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jinglong Wu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University This 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.

MDPI Acta Medica Okayama 2079-6374 15 1 2025 Mapping Surface Potential in DNA Aptamer-Neurochemical and Membrane-Ion Interactions on the SOS Substrate Using Terahertz Microscopy 46 EN Kosei Morita Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuta Mitsuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sota Yoshida Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In 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.

MDPI Acta Medica Okayama 1661-6596 26 2 2025 Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia 835 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Kuroda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Katanosaka Department of Pharmacy, Kinjo Gakuin University Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1 alpha and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-431X 14 1 2025 An Investigation of Hand Gestures for Controlling Video Games in a Rehabilitation Exergame System 25 EN Radhiatul Husna Department of Information and Communication Systems, Okayama University Komang Candra Brata Department of Information and Communication Systems, Okayama University Irin Tri Anggraini Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Alfiandi Aulia Rahmadani Department of Electrical Engineering, State Polytechnic of Malang Chih-Peng Fan Department of Electrical Engineering, National Chung Hsing University Musculoskeletal disorders (MSDs) can significantly impact individuals' quality of life (QoL), often requiring effective rehabilitation strategies to promote recovery. However, traditional rehabilitation methods can be expensive and may lack engagement, leading to poor adherence to therapy exercise routines. An exergame system can be a solution to this problem. In this paper, we investigate appropriate hand gestures for controlling video games in a rehabilitation exergame system. The Mediapipe Python library is adopted for the real-time recognition of gestures. We choose 10 easy gestures among 32 possible simple gestures. Then, we specify and compare the best and the second-best groups used to control the game. Comprehensive experiments are conducted with 16 students at Andalas University, Indonesia, to find appropriate gestures and evaluate user experiences of the system using the System Usability Scale (SUS) and User Experience Questionnaire (UEQ). The results show that the hand gestures in the best group are more accessible than in the second-best group. The results suggest appropriate hand gestures for game controls and confirm the proposal's validity. In future work, we plan to enhance the exergame system by integrating a diverse set of video games, while expanding its application to a broader and more diverse sample. We will also study other practical applications of the hand gesture control function. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 15 1 2024 The Gut-Kidney Axis in Chronic Kidney Diseases 21 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 14 1 2025 Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy 60 EN Abdul Basith Fithroni Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Haruki Inoue Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shengli Zhou Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Taufik Fatwa Nur Hakim Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Tada Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Minoru Suzuki Institute for Integrated Radiation and Nuclear Science, Kyoto University Yoshinori Sakurai Institute for Integrated Radiation and Nuclear Science, Kyoto University Manabu Ishimoto J-BEAM, Inc. Naoyuki Yamada Nihon Fukushi Fuiin Holding, Co., Ltd. Rani Sauriasari Faculty of Pharmacy, Universitas Indonesia Wolfgang A. G. Sauerwein Deutsche Gesellschaft für Bor-Neutroneneinfangtherapie DGBNCT e.V., University Hospital Essen, Klinik für Strahlentherapie Kazunori Watanabe Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Matsuura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Boron (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.

MDPI Acta Medica Okayama 2072-6694 17 1 2024 The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis 29 EN Joe Hasei Department of Medical Information and Assistive Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichi Nakahara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yujiro Otsuka Department of Radiology, Juntendo University School of Medicine Yusuke Nakamura Plusman LCC Kunihiro Ikuta Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University Shuhei Osaki Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Tamiya Hironari Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute Shinji Miwa Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences Shusa Ohshika Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine Shunji Nishimura Department of Orthopaedic Surgery, Kindai University Hospital Naoaki Kahara Department of Orthopedic Surgery, Mizushima Central Hospital Aki Yoshida Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Nakata Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kunisada Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-9292 13 24 2024 An Implementation of Web-Based Answer Platform in the Flutter Programming Learning Assistant System Using Docker Compose 4878 EN Lynn Htet Aung Department of Information and Communication Systems, Okayama University Soe Thandar Aung Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Htoo Htoo Sandi Kyaw Department of Computer and Information Science, Tokyo University of Agriculture and Technology Wen-Chung Kao Department of Electrical Engineering, National Taiwan Normal University Programming has gained significant importance worldwide as societies increasingly rely on computer application systems. To support novices in learning various programming languages, we have developed the Programming Learning Assistant System (PLAS). It offers several types of exercise problems with different learning goals and levels for step-by-step self-study. As a personal answer platform in PLAS, we have implemented a web application using Node.js and EJS for Java and Python programming. Recently, the Flutter framework with Dart programming has become popular, enabling developers to build applications for mobile, web, and desktop environments from a single codebase. Thus, we have extended PLAS by implementing the Flutter environment with Visual Studio Code to support it. Additionally, we have developed an image-based user interface (UI) testing tool to verify student source code by comparing its generated UI image with the standard one using the ORB and SIFT algorithms in OpenCV. For efficient distribution to students, we have generated Docker images of the answer platform, Flutter environment, and image-based UI testing tool. In this paper, we present the implementation of a web-based answer platform for the Flutter Programming Learning Assistant System (FPLAS) by integrating three Docker images using Docker Compose. Additionally, to capture UI images automatically, an Nginx web application server is adopted with its Docker image. For evaluations, we asked 10 graduate students at Okayama University, Japan, to install the answer platform on their PCs and solve five exercise problems. All the students successfully completed the problems, which confirms the validity and effectiveness of the proposed system. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3425 14 12 2024 The Impact of Selective Spatial Attention on Auditory-Tactile Integration: An Event-Related Potential Study 1258 EN Weichao An Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Nan Zhang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Shengnan Li Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jinglong Wu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Background: 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.

MDPI Acta Medica Okayama 2076-3425 14 12 2024 Contributions of the Primary Sensorimotor Cortex and Posterior Parietal Cortex to Motor Learning and Transfer 1184 EN Chenyu Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Background: 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.

MDPI Acta Medica Okayama 2072-6643 16 24 2024 Association Between Change in Prognostic Nutritional Index During Neoadjuvant Therapy and Dental Occlusal Support in Patients with Esophageal Cancer Under Neoadjuvant Therapy: A Retrospective Longitudinal Pilot Study 4383 EN Reiko Yamanaka-Kohno Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mami Inoue-Minakuchi Department of Oral Rehabilitation and Regenerative Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Morita Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: A high prognostic nutritional index (PNI) is associated with good prognosis in patients with esophageal cancer. However, nutritional status often decreases during neoadjuvant therapy. Functional tooth units (FTUs) provide an index for the status of posterior occlusal support. We have previously reported that low PNI is related to low FTUs. Objectives: The purpose of this study was to retrospectively examine whether the status of occlusal support relates to changes in PNI during neoadjuvant therapy in patients with esophageal cancer. Methods: This study included 34 patients who underwent neoadjuvant therapy before esophagectomy (32 men, 2 women; age, 36-82 years) in 2012 at Okayama University Hospital. Patients were divided into the good occlusal support group (FTUs >= 11, n = 18) or poor occlusal support group (FTUs < 11, n = 16), and changes in PNI during neoadjuvant therapy were investigated. Results: PNI decreased significantly after neoadjuvant therapy, particularly in the good occlusal support group, and became more dispersed after neoadjuvant therapy. Decreases in PNI after neoadjuvant therapy showed a significant positive correlation with good occlusal support by multiple regression analysis (p = 0.03). The proportions of patients provided with nutritional intervention (p = 0.02) or early dental intervention (p = 0.04) were lower in the good occlusal support group than in the poor occlusal support group. Conclusions: Even in patients with esophageal cancer with good occlusal support experienced significant declines in PNI during neoadjuvant therapy, potentially due to delayed nutritional and dental interventions. Early multidisciplinary interventions are thus recommended for all patients, regardless of preoperative dental or nutritional status. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 23 2024 Clinical Characteristics of Persistent Hypophosphatasemia Uncovered in Adult Patients: A Retrospective Study at a Japanese Tertiary Hospital 7078 EN Shintaro Fujiwara Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Furukawa Department of Laboratory Medicine, Okayama University Hospital Akihito Higashikage Department of Laboratory Medicine, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Hypophosphatasemia is often overlooked despite its potential to indicate underlying pathologies. The aim of this study was to determine the prevalence of persistent hypophosphatasemia in a large, urban, multi-specialty hospital population and characterize the clinical and laboratory findings in adult patients with this condition. Methods: In this retrospective observational study, the results of 424,434 alkaline phosphatase (ALP) tests in 50,136 patients aged >= 18 years that were performed at Okayama University Hospital between July 2020 and October 2023 were analyzed. Persistent hypophosphatasemia was defined as consistently low ALP levels (<= 40 IU/L) for 28 days with a minimum recorded level of <= 35 IU/L. Results: Persistent hypophosphatasemia was detected in 273 patients (0.54% of the tested patients), and the patients with persistent hypophosphatasemia included a higher proportion of females (72.5% vs. 52.9% in the people without persistent hypophosphatasemia; chi-squared test, p < 0.01) and had a younger median age (51 years vs. 63 years; Mann-Whitney U test, p < 0.01) than those in the overall tested population. The common causes of persistent hypophosphatasemia were cancer (30%), glucocorticoid use (21%), and immunosuppressants (16%). Notably, 38 patients (14%) had no apparent cause for low ALP values. These patients were categorized on the basis of their clinical characteristics, with some patients presenting symptoms potentially related to adult hypophosphatasia. Conclusions: This study provides prevalence and insights into the causes and characteristics of persistent hypophosphatasemia in a Japanese tertiary care setting. While most cases were associated with known causes, patients with unexplained hypophosphatasemia and symptoms such as chronic pain, muscle weakness, and general fatigue could have adult hypophosphatasia. In such cases, comprehensive evaluation and further investigation for hypophosphatasia should be considered. Persistent hypophosphatasemia of undetermined etiology could be a crucial initial step in diagnostic algorithms for this condition. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 13 24 2024 iPSC-Derived Biological Pacemaker-From Bench to Bedside 2045 EN Quan Duy Vo Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Toshihiro Iida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naofumi Amioka Department of Cardiovascular Medicine, Okayama University Hospital Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 15 12 2024 A Yoga Pose Difficulty Level Estimation Method Using OpenPose for Self-Practice System to Yoga Beginners 789 EN Cheng-Liang Shih Department of Electrical Engineering, National Chung Hsing University Jun-You Liu Department of Electrical Engineering, National Chung Hsing University Irin Tri Anggraini Department of Electrical and Communication Engineering, Okayama University Yanqi Xiao Department of Electrical and Communication Engineering, Okayama University Nobuo Funabiki Department of Electrical and Communication Engineering, Okayama University Chih-Peng Fan Department of Electrical Engineering, National Chung Hsing University Yoga is an exercise preferable for various users at different ages to enhance physical and mental health. To help beginner yoga self-practitioners avoid getting injured by selecting difficult yoga poses, the information of the difficulty level of yoga poses is very important to provide an objective metric to assist yoga self-practitioners in selecting appropriate exercises on the basis of their skill level by using the yoga self-practice system. To enhance the developed yoga self-practice system, the yoga difficulty level estimation function will enable users to clearly understand whether the selected yoga poses are suitable for them. In this paper, the newest difficulty level estimation method of yoga poses is proposed by using and analyzing OpenPose two-dimensional (2D) human body keypoints. The proposed method effectively uses the selected six keypoints areas of the upper and lower body, body support types, center of gravity calculations, and body tilt angles and slopes to produce estimations. Firstly, the method calculates the weighted centers of the upper and lower human body for each pose by using keypoints. Secondly, it refers the slope of the centroid line between the two centers and infers the body's balance state. Lastly, the system estimates the difficulty level by additionally considering the keypoints of the body to contact the ground. For evaluations of the proposal, more than one hundred yoga poses are collected from the Internet and applied to classify them into five difficulty levels. Through comparisons with subjective levels from one instructor and 10 users, the validity of the estimation results is confirmed, a comparison is performed with existing designs, and it is implemented in embedded systems. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 23 2024 The Design and Implementation of Kerberos-Blockchain Vehicular Ad-Hoc Networks Authentication Across Diverse Network Scenarios 7428 EN Maya Rahayu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Biplob Hossain Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Green Innovation Center, Okayama University Yuta Kodera Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Arshad Ali Faculty of CSE, Hajee Mohammad Danesh Science and Technology University Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Vehicular Ad-Hoc Networks (VANETs) play an essential role in the intelligent transportation era, furnishing users with essential roadway data to facilitate optimal route selection and mitigate the risk of accidents. However, the network exposure makes VANETs susceptible to cyber threats, making authentication crucial for ensuring security and integrity. Therefore, joining entity verification is essential to ensure the integrity and security of communication in VANETs. However, to authenticate the entities, authentication time should be minimized to guarantee fast and secure authentication procedures. We propose an authentication system for VANETs using blockchain and Kerberos for storing authentication messages in a blockchain ledger accessible to Trusted Authentication Servers (TASs) and Roadside Units (RSUs). We evaluate the system in three diverse network scenarios: suburban, urban with 1 TAS, and urban with 2 TASs. The findings reveal that this proposal is applicable in diverse network scenarios to fulfill the network requirements, including authentication, handover, and end-to-end delay, considering an additional TAS for an increasing number of vehicles. The system is also practicable in storing the authentication message in blockchain considering the gas values and memory size for all scenarios. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2071-1050 16 23 2024 Assessing CO2 Reduction Effects Through Decarbonization Scenarios in the Residential and Transportation Sectors: Challenges and Solutions for Japan's Hilly and Mountainous Areas 10342 EN Xiyue Hao Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chuyue Yan Department of Socio-Environmental Energy Science, Graduate School of Energy Science, Kyoto University Daisuke Narumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Depopulation, aging, and regional decline are becoming increasingly serious issues in Japan's hilly and mountainous areas. Focusing on mitigating environmental damage and envisioning a sustainable future for these regions, this study examines the potential for reducing CO2 emissions in the residential and transportation sectors by 2050. Bottom-up simulations were used to estimate CO2 emissions. Subsequently, six decarbonization scenarios were formulated, considering various measures from the perspectives of population distribution and technological progress. Based on these scenarios, this study analyzes changes in future population, energy consumption, and CO2 emissions by 2050. The results of this study show the following. (1) Depopulation and aging problems in these regions are expected to become more severe in the future. It is necessary to take action to promote sustainable regional development. (2) Pursuing decarbonization has a positive impact on enhancing regional sustainability; however, maintaining the intensity of measures at the current level could lead to a reduction of only 40% in CO2 emissions per capita by 2050 compared with 2020. (3) Scenarios that strengthen decarbonization measures could achieve a reduction of over 95% by 2050, indicating that carbon neutrality is attainable. However, this will require implementing measures at a higher intensity, especially in the transportation sector. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2076-3417 14 23 2024 Preparation of Nano- and Microparticles Obtained from Polymerization Reaction and Their Application to Surface Coating of Woody Materials 11326 EN Toshinori Shimanouchi Department of Environmental Chemistry and Materials, Okayama University, Daichi Hirota Department of Environmental Chemistry and Materials, Okayama University, Masafumi Yoshida Department of Environmental Chemistry and Materials, Okayama University, Kazuma Yasuhara Division of Materials Science, Nara Institute of Science and Technology (NAIST) Yukitaka Kimura Department of Environmental Chemistry and Materials, Okayama University, A surface coating of polymer particles of different hydrophobicity and wide-ranged size is helpful for the surface modification of materials such as woody thin board (WTB) derived from biomass. A preparation method for polymer particles was, in this study, proposed using a capillary-type flow system. Under hydrothermal conditions, the refinement of dispersed oil droplets in water (O/W emulsions) and the polymerization reaction could be simultaneously advanced, and polymer particles of polystyrene (PS), polyvinyl alcohol (PVA), polymethyl methacrylate (PMMA), and poly-L-lactic acid (PLLA) with a particle size of about 100 nm could be synthesized. The coating of polymer particles gave an improved effect on the water repellency of WTBs due to the hydrophobicity of polymer particles and an alteration of surface roughness, and it also provided long-term stability (more than 6 years). No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2077-0383 13 22 2024 The Clinical Significance of Interstitial Pneumonia with Autoimmune Features in Cryptogenic Organizing Pneumonia: A Prospective Multicenter Observational Study 6870 EN Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Hirohisa Ichikawa Department of Respiratory Medicine, KKR Takamatsu Hospital Yukako Arakawa Department of Respiratory Medicine, KKR Takamatsu Hospital Yoshihiro Mori Department of Respiratory Medicine, KKR Takamatsu Hospital Tomoki Tamura Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Shoichi Kuyama Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center Chiaki Matsumoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Keisuke Sugimoto Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital Noboru Hamada Department of Respiratory Medicine, Okayama City Hospital Toshimitsu Suwaki Department of Respiratory Medicine, Okayama City Hospital Junko Itano Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Satoru Senoo Department of Respiratory Medicine, Fukuyama Medical Center Akihiko Taniguchi Department of Respiratory Medicine, Fukuyama Medical Center Yumi Inukai Department of Allergy and Respiratory Medicine, Okayama University Hospital Machiko Arita Department of Respiratory Medicine, Kurashiki Central Hospital Satoko Makimoto Department of Radiology, Okayama University Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Takashi Matsushita Department of Dermatology, Kanazawa University Graduate School of Medical Science Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Background: There are cases of idiopathic interstitial pneumonias (IIPs) that do not meet the diagnostic criteria for connective tissue disease but have clinical features suggestive of autoimmune process. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept for these patients. Although several prospective studies on IPAF have been conducted, its clinical significance in cryptogenic organizing pneumonia (COP) remains unclear. Methods: Patients aged >= 20 years with suspected COP were prospectively enrolled between June 2018 and December 2022. Among the enrolled patients, those diagnosed with COP based on computed tomography (CT) and bronchoalveolar lavage (BAL) findings were compared between the IPAF and non-IPAF groups. Results: A total of 56 patients were enrolled in this study. Of these, 30 were diagnosed with COP and included in the analysis. Clinical and serological features were positive in two and six patients, respectively. Each feature was exclusive, and eight patients (26.7%) were diagnosed with IPAF. There were no differences between the IPAF and non-IPAF groups in terms of clinical features, including BAL findings, laboratory data, CT findings, and clinical course. During the one-year follow-up period, the frequency of COP exacerbation did not differ between the IPAF and non-IPAF groups, and no cases of systemic autoimmune disease or death occurred in either group. Conclusions: The COP characteristics of the IPAF and non-IPAF groups are similar in all aspects, and distinguishing between the two groups may be of little significance. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 22 2024 Distribution and Incorporation of Extracellular Vesicles into Chondrocytes and Synoviocytes 11942 EN Takashi Ohtsuki Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ren Takashita Department of Medical Technology, Graduate School of Health Sciences, Okayama University Shintaro Kodama Department of Medical Technology, Graduate School of Health Sciences, Okayama University Kentaro Ikemura Department of Medical Technology, Graduate School of Health Sciences, Okayama University Gabriel Opoku Department of Medical Technology, Graduate School of Health Sciences, Okayama University Shogo Watanabe Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takayuki Furumatsu Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Yamada Department of Neuroscience, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Mitsuru Ando Laboratory of Biomaterials, Institute for Life and Medical Sciences, Kyoto University Kazunari Akiyoshi Department of Immunology, Graduate School of Medicine, Kyoto University Keiichiro Nishida Department of Orthopedic Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Osteoarthritis (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.

MDPI Acta Medica Okayama 1661-6596 25 22 2024 Efficient Production of Chondrocyte Particles from Human iPSC-Derived Chondroprogenitors Using a Plate-Based Cell Self-Aggregation Technique 12063 EN Shojiro Hanaki Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Daisuke Yamada Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tomoka Takao Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ryosuke Iwai Institute of Frontier Science and Technology, Okayama University of Science Takeshi Takarada Department of Regenerative Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine The limited capacity of articular cartilage for self-repair is a critical challenge in orthopedic medicine. Here, we aimed to develop a simplified method of generating chondrocyte particles from human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells (ExpLBM) using a cell self-aggregation technique (CAT). ExpLBM cells were induced to form chondrocyte particles through a stepwise differentiation protocol performed on a CAT plate (prevelex-CAT (R)), which enables efficient and consistent production of an arbitrary number of uniformly sized particles. Histological and immunohistochemical analyses confirmed that the generated chondrocyte particles expressed key cartilage markers, such as type II collagen and aggrecan, but not hypertrophic markers, such as type X collagen. Additionally, when these particles were transplanted into osteochondral defects in rats with X-linked severe combined immunodeficiency, they demonstrated successful engraftment and extracellular matrix production, as evidenced by Safranin O and Toluidine Blue staining. These data suggest that the plate-based CAT system offers a robust and scalable approach to produce a large number of chondrocyte particles in a simplified and efficient manner, with potential application to cartilage regeneration. Future studies will focus on refining the system and exploring its clinical applications to the treatment of cartilage defects. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-9721 12 11 2024 The Change in Public Perception and Knowledge Acquisition Methods of Chronic Kidney Disease Among General Population in Okayama Prefecture, Japan 268 EN Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Okayama University Naoki Kashihara Kawasaki Geriatric Medical Center Hirofumi Makino Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences CKD public education plays a very important role in effective chronic kidney disease (CKD) countermeasure. We have been conducting CKD public education programs in Okayama Prefecture since 2007. Here, we aimed to examine the actual status of CKD perceptance and changes in CKD perceptance due to these education programs. The study was conducted on individuals who underwent health checkups at 12 medical institutions across five medical regions in Okayama Prefecture between 1 October and 30 November in 2015, 2019, and 2023. The results showed that overall CKD perceptance has improved over time (perceptance of "CKD" 4% to 7%, "chronic kidney disease" 27% to 34%, 2015 vs. 2023). "Chronic kidney disease" was more commonly recognized than "CKD", and the elderly were more aware of the disease than younger people. The CKD perceptance improved across all age groups. However, the rate of CKD perceptance is still low, especially among young people. Previously, newspapers were the second most common resource of information about CKD after television. However, the Internet has recently replaced newspapers as the second most common source of information, especially among younger people. Understanding of the exact diagnosis of CKD also remains insufficient. It is necessary to continue more effective CKD public education programs through more intelligible terminology and information sources that match the demographics of target population. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2673-6284 12 2 2023 Development of the Follow-Up Human 3D Oral Cancer Model in Cancer Treatment 35 EN Kazuyo Igawa Neutron Therapy Research Center, Okayama University Kenji Izumi Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University Yoshinori Sakurai Institute for Integrated Radiation and Nuclear Science, Kyoto University As function preservation cancer therapy, targeted radiation therapies have been developed for the quality of life of cancer patients. However, preclinical animal studies evaluating the safety and efficacy of targeted radiation therapy is challenging from the viewpoints of animal welfare and animal protection, as well as the management of animal in radiation-controlled areas under the regulations. We fabricated the human 3D oral cancer model that considers the time axis of the follow up in cancer treatment. Therefore, in this study, the 3D model with human oral cancer cells and normal oral fibroblasts was treated based on clinical protocol. After cancer treatment, the histological findings of the 3D oral cancer model indicated the clinical correlation between tumor response and surrounding normal tissue. This 3D model has potential as a tool for preclinical studies alternative to animal studies. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 21 2024 Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition 11592 EN Tomoki Tsuchida Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Kubota Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shizuki Kamiuezono Department of Medicinal Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University Nobumasa Takasugi Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Ito School of Life Sciences, Tokyo University of Pharmacy and Life Sciences Yoshito Kumagai Graduate School of Pharmaceutical Sciences, Kyushu University Takashi Uehara Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses. A total of 45 environmental electrophiles were screened for inhibitory effects on the activity of DNA methyltransferase 3B (DNMT3B), a key enzyme in DNA methylation, and four compounds were identified. We focused on 1,2-naphthoquinone (1,2-NQ), an air pollutant whose toxicity has been reported previously. Interestingly, we found that 1,2-NQ modified multiple lysine and histidine residues in DNMT3B, one of which was near the active site in DNMT3B. It was found that 1,2-NQ altered gene expression and evoked inflammatory responses in lung adenocarcinoma cell lines. Furthermore, we found that 1,2-NQ upregulated CXCL8 expression through DNA demethylation of the distal enhancer and promoted cancer cell growth. Our study reveals novel mechanisms of epigenetic regulation by environmental electrophiles through the inhibition of DNMT3B activity and suggests their physiological impact. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-4991 14 20 2024 Colossal Dielectric Constant of Nanocrystalline/Amorphous Homo-Composite BaTiO3 Films Deposited via Pulsed Laser Deposition Technique 1677 EN Shinya Kondo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taichi Murakami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Loick Pichon Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications Joel Leblanc-Lavoie Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications Takashi Teranishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Akira Kishimoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khakani, My Ali El Khakani Institut National de la Recherche Scientifique (INRS), Centre Énergie, Matériaux et Télécommunications We report the pulsed laser deposition (PLD) of nanocrystalline/amorphous homo-composite BaTiO3 (BTO) films exhibiting an unprecedented combination of a colossal dielectric constant (epsilon(r)) and extremely low dielectric loss (tan delta). By varying the substrate deposition temperature (T-d) over a wide range (300-800 degrees C), we identified T-d = 550 degrees C as the optimal temperature for growing BTO films with an epsilon(r) as high as similar to 3060 and a tan delta as low as 0.04 (at 20 kHz). High-resolution transmission electron microscopy revealed that the PLD-BTO films consist of BTO nanocrystals (similar to 20-30 nm size) embedded within an otherwise amorphous BTO matrix. The impressive dielectric behavior is attributed to the combination of highly crystallized small BTO nanograins, which amplify interfacial polarization, and the surrounding amorphous matrix, which effectively isolates the nanograins from charge carrier transport. Our findings could facilitate the development of next-generation integrated dielectric devices. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2078-2489 15 10 2024 A Study of Exergame System Using Hand Gestures for Wrist Flexibility Improvement for Tenosynovitis Prevention 622 EN Yanqi Xiao Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Irin Tri Anggraini Department of Information and Communication Systems, Okayama University Cheng-Liang Shih Department of Information and Communication Systems, Okayama University Chih-Peng Fan Department of Information and Communication Systems, Okayama University Currently, as an increasing number of people have been addicted to using cellular phones, smartphone tenosynovitis has become common from long-term use of fingers for their operations. Hand exercise while playing video games, which is called exergame, can be a good solution to provide enjoyable daily exercise opportunities for its prevention, particularly, for young people. In this paper, we implemented a simple exergame system with a hand gesture recognition program made in Python using the Mediapipe library. We designed three sets of hand gestures to control the key operations to play the games as different exercises useful for tenosynovitis prevention. For evaluations, we prepared five video games running on a web browser and asked 10 students from Okayama and Hiroshima Universities, Japan, to play them and answer 10 questions in the questionnaire. Their playing results and System Usability Scale (SUS) scores confirmed the usability of the proposal, although we improved one gesture set to reduce its complexity. Moreover, by measuring the angles for maximum wrist movements, we found that the wrist flexibility was improved by playing the games, which verifies the effectiveness of the proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 15 10 2024 An Independent Learning System for Flutter Cross-Platform Mobile Programming with Code Modification Problems 614 EN Safira Adine Kinari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Soe Thandar Aung Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Khaing Hsu Wai Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mustika Mentari Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Pradini Puspitaningayu Department of Electrical Engineering, Universitas Negeri Surabaya Nowadays, with the common use of smartphones in daily lives, mobile applications have become popular around the world, which will lead to a rise in Flutter framework. Developed by Google, Flutter with Dart programming provides a cross-platform development environment to create visually appealing and responsive user interfaces across mobile, web, and desktop platforms using a single codebase. However, due to time and staff limitations, the Flutter/Dart programming course is not included in curricula, even in IT departments in universities. Therefore, independent learning environments for students are essential to meet this growing popularity. Previously, we have developed programming learning assistant system (PLAS) as a web-browser-based self-learning platform for novice students. PLAS offers various types of exercise problems designed to cultivate programming skills step-by-step through a lot of code reading and code writing practices. Among them, one particular type is the code modification problem (CMP), which asks to modify the given source code to satisfy the new specifications. CMP is expected to be solved by novices with little effort if they have knowledge of other programming languages. Thus, PLAS with CMP will be an excellent platform for independent learning. In this paper, we present PLAS with CMP for the independent learning of Flutter/Dart programming. To improve the readability of the source code by students, we provided rich comments on grammar or behaviors. Besides, the code can be downloaded so that students can check and run it on an IDE. For evaluations, we generated 38 CMP instances for basic and multimedia/storage topics in Flutter/Dart programming and assigned them to 21 master students at Okayama University, Japan, who have never studied it. The results confirm the validity of the proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 19 2024 The Liver Transection Area Is a Novel Predictor for Surgical Difficulty in Laparoscopic Liver Resection 5686 EN Motohiko Yamada Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomokazu Fuji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Yasui Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Jiro Kimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takeyoshi Nishiyama Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Kanehira Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: A difficulty scoring system was developed to estimate the surgical outcomes of laparoscopic liver surgery (LLS); however, the effect of the liver transection area (LTA) on LLS outcomes have not been previously examined. Therefore, this study investigated the predictive significance of the LTA for LLS. Methods: This retrospective study included 106 patients who underwent LLS in our hospital between January 2012 and December 2023. The association of the LTA with the surgical difficulty level and operative time was investigated. Multivariate analyses were performed to identify factors predicting surgical difficulty in LLS. Results: The median LTA and operative time were 62.5 (IQR, 36.0–91.8) cm2 and 250 (IQR, 195–310) minutes, respectively. The LTA was significantly associated with surgical difficulty as evaluated using the IWATE Criteria. Moreover, the LTA significantly correlated with operative time (r2 = 0.19, p < 0.001). The multivariable analyses found that the LTA (≥59 cm2) (odds ratio [OR], 6.07; 95% confidence interval [CI], 2.38–16.6; p < 0.001) and the type of LLS (≥segmentectomy) (OR, 3.79; 95% CI, 1.35–11.4; p = 0.01) were significant factors associated with surgical difficulty. Conclusions: The LTA is a useful parameter that reflects the difficulty of LLS. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2673-8732 4 3 2024 A User Location Reset Method through Object Recognition in Indoor Navigation System Using Unity and a Smartphone (INSUS) 295 312 EN Evianita Dewi Fajrianti Graduate School of Natural Science and Technology, Okayama University Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Amma Liesvarastranta Haz Graduate School of Natural Science and Technology, Okayama University Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University Sritrusta Sukaridhoto Department of Informatic and Computer, Politeknik Elektronika Negeri Surabaya To enhance user experiences of reaching destinations in large, complex buildings, we have developed a indoor navigation system using Unity and a smartphone called INSUS. It can reset the user location using a quick response (QR) code to reduce the loss of direction of the user during navigation. However, this approach needs a number of QR code sheets to be prepared in the field, causing extra loads at implementation. In this paper, we propose another reset method to reduce loads by recognizing information of naturally installed signs in the field using object detection and Optical Character Recognition (OCR) technologies. A lot of signs exist in a building, containing texts such as room numbers, room names, and floor numbers. In the proposal, the Sign Image is taken with a smartphone, the sign is detected by YOLOv8, the text inside the sign is recognized by PaddleOCR, and it is compared with each record in the Room Database using Levenshtein distance. For evaluations, we applied the proposal in two buildings in Okayama University, Japan. The results show that YOLOv8 achieved mAP@0.5 0.995 and mAP@0.5:0.95 0.978, and PaddleOCR could extract text in the sign image accurately with an averaged CER% lower than 10%. The combination of both YOLOv8 and PaddleOCR decreases the execution time by 6.71s compared to the previous method. The results confirmed the effectiveness of the proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-2607 12 9 2024 A Novel C-Terminal Truncated Bacteriocin Found by Comparison between Leuconostoc mesenteroides 406 and 213M0 Isolated from Mongolian Traditional Fermented Milk, Airag 1781 EN Chihiro Hasiqimuge Graduate School of Environmental and Life Science, Okayama University Chihiro Hano Graduate School of Environmental and Life Science, Okayama University Kensuke Arakawa Graduate School of Environmental and Life Science, Okayama University Saki Yoshida Graduate School of Environmental and Life Science, Okayama University Junliang Zhao Graduate School of Environmental and Life Science, Okayama University Hidehiro Toh Advanced Genomics Center, National Institute of Genetics Hidetoshi Morita Graduate School of Environmental and Life Science, Okayama University Taku Miyamoto Graduate School of Environmental and Life Science, Okayama University Bacteriocins produced by lactic acid bacteria are known to be useful tools for food biopreservation and fermentation control. Leuconostoc mesenteroides subsp. mesenteroides 406 and 213M0 isolated from different samples of Mongolian traditional fermented milk, airag, had been reported to produce listericidal bacteriocin-like inhibitory substances with similar but slightly different properties. In this study, the antibacterial properties and the related gene sequences of both strains were compared, and then their bacteriocins were purified and identified. Strain 406 was superior to strain 213M0 in cell growth and antibacterial activity against many strains. However, the activity of 213M0 was stronger than that of 406 against a few strains. DNA sequencing revealed two and three plasmids in 406 and 213M0, respectively, and each one of them harbored an almost identical mesentericin Y105-B105 gene cluster. Removal of these plasmids resulted in a complete loss of activity, indicating that the antibacterial activity of both strains was generated by bacteriocins encoded on the plasmids. Mesentericins Y105 and B105 were purified from both cultures, and another novel bacteriocin, named mesentericin M, was identified from the 213M0 culture only. Its structural gene was coded on a 213M0 plasmid and, surprisingly, its C-terminal three amino acid residues were post-translationally cleaved. To our knowledge, this is the first report of a C-terminal truncated bacteriocin. In conclusion, the novel bacteriocin should be mainly responsible for the difference in antibacterial properties between the two strains. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-431X 13 9 2024 A Study of a Drawing Exactness Assessment Method Using Localized Normalized Cross-Correlations in a Portrait Drawing Learning Assistant System 215 EN Yue Zhang Graduate School of Environmental, Life, Natural Sciences and Technology, Okayama University Zitong Kong Graduate School of Environmental, Life, Natural Sciences and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Sciences and Technology, Okayama University Chen-Chien Hsu Department of Electrical Engineering, National Taiwan Normal University Nowadays, portrait drawing has gained significance in cultivating painting skills and human sentiments. In practice, novices often struggle with this art form without proper guidance from professionals, since they lack understanding of the proportions and structures of facial features. To solve this limitation, we have developed a Portrait Drawing Learning Assistant System (PDLAS) to assist novices in learning portrait drawing. The PDLAS provides auxiliary lines as references for facial features that are extracted by applying OpenPose and OpenCV libraries to a face photo image of the target. A learner can draw a portrait on an iPad using drawing software where the auxiliary lines appear on a different layer to the portrait. However, in the current implementation, the PDLAS does not offer a function to assess the exactness of the drawing result for feedback to the learner. In this paper, we present a drawing exactness assessment method using a Localized Normalized Cross-Correlation (NCC) algorithm in the PDLAS. NCC gives a similarity score between the original face photo and drawing result images by calculating the correlation of the brightness distributions. For precise feedback, the method calculates the NCC for each face component by extracting the bounding box. In addition, in this paper, we improve the auxiliary lines for the nose. For evaluations, we asked students at Okayama University, Japan, to draw portraits using the PDLAS, and applied the proposed method to their drawing results, where the application results validated the effectiveness by suggesting improvements in drawing components. The system usability was also confirmed through a questionnaire with a SUS score. The main finding of this research is that the implementation of the NCC algorithm within the PDLAS significantly enhances the accuracy of novice portrait drawings by providing detailed feedback on specific facial features, proving the system's efficacy in art education and training. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2504-446X 8 9 2024 Generating 3D Models for UAV-Based Detection of Riparian PET Plastic Bottle Waste: Integrating Local Social Media and InstantMesh 471 EN Shijun Pan Graduate School of Environmental and Life Science, Okayama University Keisuke Yoshida Graduate School of Environmental and Life Science, Okayama University Daichi Shimoe Graduate School of Environmental and Life Science, Okayama University Takashi Kojima TOKEN C.E.E. Consultants Co., Ltd. Satoshi Nishiyama Graduate School of Environmental and Life Science, Okayama University In recent years, waste pollution has become a severe threat to riparian environments worldwide. Along with the advancement of deep learning (DL) algorithms (i.e., object detection models), related techniques have become useful for practical applications. This work attempts to develop a data generation approach to generate datasets for small target recognition, especially for recognition in remote sensing images. A relevant point is that similarity between data used for model training and data used for testing is crucially important for object detection model performance. Therefore, obtaining training data with high similarity to the monitored objects is a key objective of this study. Currently, Artificial Intelligence Generated Content (AIGC), such as single target objects generated by Luma AI, is a promising data source for DL-based object detection models. However, most of the training data supporting the generated results are not from Japan. Consequently, the generated data are less similar to monitored objects in Japan, having, for example, different label colors, shapes, and designs. For this study, the authors developed a data generation approach by combining social media (Clean-Up Okayama) and single-image-based 3D model generation algorithms (e.g., InstantMesh) to provide a reliable reference for future generations of localized data. The trained YOLOv8 model in this research, obtained from the S2PS (Similar to Practical Situation) AIGC dataset, produced encouraging results (high F1 scores, approximately 0.9) in scenario-controlled UAV-based riparian PET bottle waste identification tasks. The results of this study show the potential of AIGC to supplement or replace real-world data collection and reduce the on-site work load. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 16 17 2024 Cyclic Oligosaccharide-Induced Modulation of Immunoglobulin A Reactivity to Gut Bacteria Contributes to Alterations in the Bacterial Community Structure 2824 EN Taisei Miyamoto Graduate School of Environmental and Life Science, Okayama University Takeshi Tsuruta Graduate School of Environmental and Life Science, Okayama University Mao Teraoka Graduate School of Environmental and Life Science, Okayama University Tianyang Wang Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Graduate School of Environmental and Life Science, Okayama University Immunoglobulin A (IgA) is a major gut antibody that coats commensal gut bacteria and contributes to shaping a stable gut bacterial composition. Although previous studies have shown that cyclic oligosaccharides, including cyclic nigerosyl-1,6-nigerose (CNN) and cyclodextrins (CDs, including alpha CD, beta CD, and gamma CD), alter the gut bacterial composition, it remains unclear whether cyclic oligosaccharides modify the IgA coating of gut bacteria, which relates to cyclic oligosaccharide-induced alteration of the gut bacterial composition. To address this issue, mice were maintained for 12 weeks on diets containing CNN, alpha CD, beta CD, or gamma CD; the animals' feces were evaluated for their bacterial composition and the IgA coating index (ICI), a measure of the degree of IgA coating of bacteria. We observed that the intake of each cyclic oligosaccharide altered the gut bacterial composition, with changes in the ICI found at both the phylum and genus levels. The ICI for Bacillota, Lachnospiraceae NK4A136 group, UC Lachnospiraceae, and Tuzzerella were significantly and positively correlated with the relative abundance (RA) in total bacteria for these bacteria; in contrast, significant correlations were not seen for other phyla and genera. Our observations suggest that cyclic oligosaccharide-induced modulation of the IgA coating of gut bacteria may partly relate to changes in the community structure of the gut bacteria. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 17 17 2024 Antibacterial Dental Adhesive Containing Cetylpyridinium Chloride Montmorillonite 4368 EN Yohei Okazaki Department of Oral Health Sciences, BIOMAT, KU Leuven Kiichi Nakamori Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University Chenmin Yao Department of Oral Health Sciences, BIOMAT, KU Leuven Mohammed H. Ahmed Department of Oral Health Sciences, BIOMAT, KU Leuven Benjamin Mercelis Department of Oral Health Sciences, BIOMAT, KU Leuven Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Science, Okayama University Dental School Yukinori Maruo Department of Prosthodontics, Okayama University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Yasuhiko Abe Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University Meerbeek, Bart Van Meerbeek Department of Oral Health Sciences, BIOMAT, KU Leuven Kumiko Yoshihara Department of Pathology & Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Oral bacteria cause tooth caries and periodontal disease. Much research is being conducted to prevent both major oral diseases by rendering dental materials' antimicrobial potential. However, such antimicrobial materials are regarded as 'combination' products and face high hurdles for regulatory approval. We loaded inorganic montmorillonite with the antimicrobial agent cetylpyridinium chloride, referred to below as 'CPC-Mont'. CPC-Mont particles in a 1, 3 and 5 wt% concentration were added to the considered gold-standard self-etch adhesive Clearfil SE Bond 2 ('CSE2'; Kuraray Noritake) to render its antibacterial potential (CSE2 without CPC-Mont served as control). Besides measuring (immediate) bonding effectiveness and (aged) bond durability to dentin, the antibacterial activity against S. mutans and the polymerization-conversion rate was assessed. Immediate and aged bond strength was not affected by 1 and 3 wt% CPC-Mont addition, while 5 wt% CPC-Mont significantly lowered bond strength and bond durability. The higher the concentration of the antimicrobial material added, the stronger the antimicrobial activity. Polymerization conversion was not affected by the CPC-Mont addition in any of the three concentrations. Hence, adding 3 wt% CPC-Mont to the two-step self-etch adhesive rendered additional antimicrobial potential on top of its primary bonding function. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2073-4360 16 16 2024 Long-Term Bonding Performance of One-Bottle vs. Two-Bottle Bonding Agents to Lithium Disilicate Ceramics 2266 EN Masao Irie Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Okada Department of Dental Biomaterials, Tohoku University Graduate School of Dentistry Yukinori Maruo Department of Prosthodontics, Okayama University Hospital Goro Nishigawa Department of Prosthodontics, Okayama University Hospital Takuya Matsumoto Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The aim of this study was to compare the long-term bonding performance to lithium disilicate (LDS) ceramic between one-bottle and two-bottle bonding agents. Bonding performance was investigated under these LDS pretreatment conditions: with hydrofluoric acid (HF) only, without HF, with a two-bottle bonding agent (Tokuyama Universal Bond II) only. Shear bond strengths between LDS and nine resin cements (both self-adhesive and conventional adhesive types) were measured at three time periods: after one-day water storage (Base), and after 5000 and 20,000 thermocycles (TC 5k and TC 20k respectively). Difference in degradation between one- and two-bottle bonding agents containing the silane coupling agent was compared by high-performance liquid chromatography. With HF pretreatment, bond strengths were not significantly different among the three time periods for each resin cement. Without HF, ESTECEM II and Super-Bond Universal showed significantly higher values than others at TC 5k and TC 20k when treated with the recommended bonding agents, especially at TC 20k. Difference in degradation between one- and two-bottle bonding agents containing the silane coupling agent was compared by high-performance liquid chromatography (HPLC). For both cements, these values at TC 20k were also not significantly different from pretreatment with only Tokuyama Universal Bond II. For LDS, long-term bond durability could be maintained by pretreatment with Tokuyama Universal Bond II instead of the hazardous HF. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-8994 16 8 2024 An Enhanced Active Access-Point Configuration Algorithm Using the Throughput Request Satisfaction Method for an Energy-Efficient Wireless Local-Area Network 1005 EN Bin Wu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Dezheng Kong Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Xuan Wang Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taishiro Seto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yu-Cheng Fan Department of Electronic Engineering, National Taipei University of Technology Wireless Local-Area Networks (WLANs), as a popular internet access solution, are widely used in numerous places, including enterprises, campuses, and public venues. As the number of devices increases, large-scale deployments will cause the problem of dense wireless networks, including a lot of energy consumption. Thus, the optimization of energy-efficient wireless AP devices has become a focal point of attention. To reduce energy consumption, we have proposed the active access-point (AP) configuration algorithm for WLANs using APs with a dual interface. This uses the greedy algorithm combined with the local search optimization method to find the minimum number of activated APs while satisfying the minimum throughput constraint. However, the previous algorithm basically satisfies only the average throughput among the multiple hosts associated with one AP, wherein some hosts may not reach the required one. In this paper, to overcome this limitation, we propose an enhanced active AP configuration algorithm by incorporating the throughput request satisfaction method that controls the actual throughput at the target value (target throughput) for every host by applying traffic shaping. The target throughput is calculated from the single and concurrent communicating throughput of each host based on channel occupancy time. The minimum throughput constraint will be iteratively adjusted to obtain the required target throughput and achieve the fair throughput allocation. For evaluations, we conducted simulations using the WIMNET simulator and experiments using the testbed system with a Raspberry Pi 4B for APs in four topology cases with five APs and ten hosts. The results show that the proposed method always achieved the required minimum throughput in simulations as well as in experiments, while minimizing the number of active APs. Thus, the validity and effectiveness of our proposal were confirmed. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 16 2024 Development of Antimicrobial Surfaces Using Diamond-like Carbon or Diamond-like Carbon-Based Coatings 8593 EN Yasuhiro Fujii Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama University Tatsuyuki Nakatani Institute of Frontier Science and Technology, Okayama University of Science Daiki Ousaka Department of Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Susumu Oozawa Division of Medical Safety Management, Safety Management Facility, Okayama University Hospital, Okayama University Yasushi Sasai Department of Pharmacy, Gifu University of Medical Science Shingo Kasahara Department of Cardiovascular Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The medical device market is a high-growth sector expected to sustain an annual growth rate of over 5%, even in developed countries. Daily, numerous patients have medical devices implanted or inserted within their bodies. While medical devices have significantly improved patient outcomes, as foreign objects, their wider use can lead to an increase in device-related infections, thereby imposing a burden on healthcare systems. Multiple materials with significant societal impact have evolved over time: the 19th century was the age of iron, the 20th century was dominated by silicon, and the 21st century is often referred to as the era of carbon. In particular, the development of nanocarbon materials and their potential applications in medicine are being explored, although the scope of these applications remains limited. Technological innovations in carbon materials are remarkable, and their application in medicine is expected to advance greatly. For example, diamond-like carbon (DLC) has garnered considerable attention for the development of antimicrobial surfaces. Both DLC itself and its derivatives have been reported to exhibit anti-microbial properties. This review discusses the current state of DLC-based antimicrobial surface development. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 15 8 2024 An Image-Based User Interface Testing Method for Flutter Programming Learning Assistant System 464 EN Soe Thandar Aung Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Lynn Htet Aung Department of Information and Communication Systems, Okayama University Safira Adine Kinari Department of Information and Communication Systems, Okayama University Khaing Hsu Wai Department of Information and Communication Systems, Okayama University Mustika Mentari Department of Information and Communication Systems, Okayama University Flutter has become popular for providing a uniform development environment for user interfaces (UIs) on smart phones, web browsers, and desktop applications. We have developed the Flutter programming learning assistant system (FPLAS) to assist its novice students' self-study. We implemented the Docker-based Flutter environment with Visual Studio Code and three introductory exercise projects. However, the correctness of students' answers is manually checked, although automatic checking is necessary to reduce teachers' workload and provide quick responses to students. This paper presents an image-based user interface (UI) testing method to automate UI testing by the answer code using the Flask framework. This method produces the UI image by running the answer code and compares it with the image made by the model code for the assignment using ORB and SIFT algorithms in the OpenCV library. One notable aspect is the necessity to capture multiple UI screenshots through page transitions by user input actions for the accurate detection of changes in UI elements. For evaluations, we assigned five Flutter exercise projects to fourth-year bachelor and first-year master engineering students at Okayama University, Japan, and applied the proposed method to their answers. The results confirm the effectiveness of the proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 6 4 2024 Azidoindolines—From Synthesis to Application: A Review 556 580 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Azide-containing compounds, organic azides, showcases a variety of reactivities, making them highly convenient and chameleonic intermediates. An indoline derivative has been proven to be of great significance in drug discovery due to its sp3-rich property. In this context, it is interesting to perform such vigorous azidation on medicinal-relevant indoles/indolines, resulting in the production of sp3-rich azidoindolines. The potential biological activity, in combination with the sp3-rich indoline bearing the azido moiety, makes azidoindolines an attractive synthetic target for medicinal and synthetic chemists. This review describes recent advances in the synthesis and application of azidoindolines: (1) iodine-mediated azidations, (2) metal-catalyzed azidations, (3) electrochemical azidations, (4) photochemical azidations, (5) azidation using a combination of an oxidant and an azide source, and (6) nucleophilic azidation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 12 16 2024 Postgraduate Year Two Medical Residents' Awareness of Personal Development as a Physician during the Management of Inpatients: A Qualitative Study 1621 EN Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruo Obara Department of General Internal Medicine, Okinawa Chubu Hospital Takanobu Hirosawa Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hiroko Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Clinical experiences, helping relationships, and reflection are key factors for personal development for physicians. However, few studies have shown which experiences are important for personal growth and how medical residents specifically use their experiences for personal growth. The aim of this study was to identify from the medical residents' perspective which clinical experiences contribute to their personal development. We employed a qualitative design, conducting semi-structured interviews with ten postgraduate year two medical residents at a Japanese teaching hospital. The interviews were transcribed in interview memos, anonymized, and subjected to reflective thematic analysis to generate themes relevant to personal and professional development. Successful clinical experiences with autonomy and responsibility in clinical management were shown to be essential points for personal development as a physician. Autonomy in this study was the attitude of making one's own choices when managing patients. Responsibility was the obligation of the resident to take charge of a patient. Instructing junior trainees, appreciation received from patients, and approval granted by attending physicians reinforced their feelings of personal growth. The realization of what experiences and concepts influence medical residents' personal growth and development will make their professional development more effective. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 13 16 2024 Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes 1373 EN Hiroshi Yamada Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirona Osaka Graduate School of Science, Nagoya University Nanami Tatsumi Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miu Araki Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Abe Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiko Kaihara Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ken Takahashi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eizo Takashima Division of Malaria Research, Proteo-Science Center, Ehime University Takayuki Uchihashi Graduate School of Science, Nagoya University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takei Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of alpha-actinin and enhanced the alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 16 2024 Quercetin Attenuates Acetaldehyde-Induced Cytotoxicity via the Heme Oxygenase-1-Dependent Antioxidant Mechanism in Hepatocytes 9038 EN Kexin Li Graduate School of Environmental and Life Science, Okayama University Minori Kidawara Graduate School of Environmental and Life Science, Okayama University Qiguang Chen Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University It is still unclear whether or how quercetin influences the toxic events induced by acetaldehyde in hepatocytes, though quercetin has been reported to mitigate alcohol-induced mouse liver injury. In this study, we evaluated the modulating effect of quercetin on the cytotoxicity induced by acetaldehyde in mouse hepatoma Hepa1c1c7 cells, the frequently used cellular hepatocyte model. The pretreatment with quercetin significantly inhibited the cytotoxicity induced by acetaldehyde. The treatment with quercetin itself had an ability to enhance the total ALDH activity, as well as the ALDH1A1 and ALDH3A1 gene expressions. The acetaldehyde treatment significantly enhanced the intracellular reactive oxygen species (ROS) level, whereas the quercetin pretreatment dose-dependently inhibited it. Accordingly, the treatment with quercetin itself significantly up-regulated the representative intracellular antioxidant-related gene expressions, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase, catalytic subunit (GCLC), and cystine/glutamate exchanger (xCT), that coincided with the enhancement of the total intracellular glutathione (GSH) level. Tin protoporphyrin IX (SNPP), a typical HO-1 inhibitor, restored the quercetin-induced reduction in the intracellular ROS level, whereas buthionine sulphoximine, a representative GSH biosynthesis inhibitor, did not. SNPP also cancelled the quercetin-induced cytoprotection against acetaldehyde. These results suggest that the low-molecular-weight antioxidants produced by the HO-1 enzymatic reaction are mainly attributable to quercetin-induced cytoprotection. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 17 16 2024 Effect of Scaffold Geometrical Structure on Macrophage Polarization during Bone Regeneration Using Honeycomb Tricalcium Phosphate 4108 EN Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetsugu Tsujigiwa Department of Life Science, Faculty of Science, Okayama University of Science Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anqi Chang Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tianyan Piao Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasunori Inada Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuma Arashima Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayumi Morimatsu Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ayumi Tanaka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The polarization balance of M1/M2 macrophages with different functions is important in osteogenesis and bone repair processes. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which is a cylindrical scaffold with a honeycomb arrangement of straight pores, and we demonstrated that TCP with 300 and 500 mu m pore diameters (300TCP and 500TCP) induced bone formation within the pores. However, the details of the influence of macrophage polarization on bone formation using engineered biomaterials, especially with respect to the geometric structure of the artificial biomaterials, are unknown. In this study, we examined whether differences in bone tissue formation due to differences in TCP geometry were due to the polarity of the assembling macrophages. Immunohistochemistry for IBA-1, iNOS, and CD163 single staining was performed. The 300TCP showed a marked infiltration of iNOS-positive cells, which are thought to be M1 macrophages, during the osteogenesis process, while no involvement of CD163-positive cells, which are thought to be M2 macrophages, was observed in the TCP pores. In addition, 500TCP showed a clustering of iNOS-positive cells and CD163-positive cells at 2 weeks, suggesting the involvement of M2 macrophages in the formation of bone tissue in the TCP pores. In conclusion, we demonstrated for the first time that the geometrical structure of the artificial biomaterial, i.e., the pore size of honeycomb TCP, affects the polarization of M1/2 macrophages and bone tissue formation in TCP pores. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2673-7078 3 4 2023 Estimation of the Effects of Achilles Tendon Geometry on the Magnitude and Distribution of Local Strain: A Finite Element Analysis 583 595 EN Shota Enomoto Institute for Promotion of Education and Campus Life, Okayama University Toshiaki Oda Graduate School of Education, Hyogo University of Teacher Education We investigated the influence of Achilles tendon (AT) geometry on local-strain magnitude and distribution during loading, using finite element analysis. We calculated the following eight AT parameters for 18 healthy men: thickness and width of the most distal part, minimum cross-sectional area (mCSA), and most proximal part; length; and position of the mCSA. To investigate the effect of AT geometry on the magnitude and distribution of local strain, we created three-dimensional numerical models by changing the AT parameter values for every one standard deviation (SD) in the range of ±2 SD. A 4000 N lengthening force was applied to the proximal surface of all the models. The mean first principal strain (FPS) was determined every 3% of the length. The highest FPS in each model was mainly observed in the proximal regions; the 86–89% site (the most proximal site was set at 100%) had the highest number of models with the highest FPS (nine models). The highest FPS was observed in the model with a distal thickness of −2 SD, which was 27.1% higher than that of the standard model observed in the 2–5% site. Therefore, the AT geometry influences local-strain magnitude and distribution during loading. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 15 2024 Evolution and Effects of Ad Hoc Multidisciplinary Team Meetings in the Emergency Intensive Care Unit: A Five-Year Analysis 4324 EN Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Ageta Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Tsukahara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Multidisciplinary team meetings (MDTMs) are crucial in the ICU. However, daily rounds may not address all sensitive issues due to time constraints and the complexity of cases. This study aimed to describe detailed information and characteristics of ad hoc MDTMs in the ICU. Methods: This single-center, retrospective study analyzed adult emergency ICU admissions at Okayama University Hospital from 1 January 2019 to 31 December 2023. During this period, weekly regular multidisciplinary team ICU rounds were introduced in June 2020, and regular weekday morning MDTMs began in April 2022. A multiple logistic regression analysis was applied to determine the impact of these changes on the frequency of ad hoc MDTMs, adjusting for variables including annual changes. Results: The study analyzed 2487 adult EICU patients, with a median age of 66, and 63.3% of them male. MDTMs were held for 168 patients (6.8%), typically those with severe conditions, including higher COVID-19 prevalence and APACHE II scores, and longer ICU stays. Despite a constant total number of MDTMs, the likelihood of conducting ad hoc MDTMs increased annually (adjusted OR 1.19; 95% CI, 1.04-1.35). Of the 329 MDTMs conducted for these patients, 59.0% addressed end-of-life care, involving an average of 11 participants, mainly nurses and emergency and critical-care physicians. Conclusions: Changes in ICU round and meeting structures might be associated with a higher frequency of conducting ad hoc MDTMs, highlighting their evolving role and importance in patient care management. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 15 2024 Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients 8370 EN Mitsuru Tsuge Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Kou Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenichiro Kudo Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kazuhiro Nouso Department of Gastroenterology, Okayama City Hospital Naohiro Oda Department of Internal Medicine, Fukuyama City Hospital Sho Mitsumune Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Goro Kimura Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Haruto Yamada Department of Infectious Disease, Okayama City Hospital Ichiro Takata Department of Internal Medicine, Fukuyama City Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Kohei Tsukahara Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrine Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirokazu Tsukahara Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 15 2024 Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure 4384 EN Keiichiro Iwasaki Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Chikara Urabe Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Satoru Sakuragi Department of Cardiovascular Medicine, Iwakuni Clinical Center Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Takefumi Oka Department of Cardiology, Tsuyama Chuo Hospital Naoto Tokunaga Department of Cardiology, Ibara City Hospital Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2223-7747 13 15 2024 Light-Driven H2 Production in Chlamydomonas reinhardtii: Lessons from Engineering of Photosynthesis 2114 EN Michael Hippler Institute of Plant Science and Resources, Okayama University Fatemeh Khosravitabar Department of Biological and Environmental Sciences, University of Gothenburg In the green alga Chlamydomonas reinhardtii, hydrogen production is catalyzed via the [FeFe]-hydrogenases HydA1 and HydA2. The electrons required for the catalysis are transferred from ferredoxin (FDX) towards the hydrogenases. In the light, ferredoxin receives its electrons from photosystem I (PSI) so that H-2 production becomes a fully light-driven process. HydA1 and HydA2 are highly O-2 sensitive; consequently, the formation of H-2 occurs mainly under anoxic conditions. Yet, photo-H-2 production is tightly coupled to the efficiency of photosynthetic electron transport and linked to the photosynthetic control via the Cyt b(6)f complex, the control of electron transfer at the level of photosystem II (PSII) and the structural remodeling of photosystem I (PSI). These processes also determine the efficiency of linear (LEF) and cyclic electron flow (CEF). The latter is competitive with H-2 photoproduction. Additionally, the CBB cycle competes with H-2 photoproduction. Consequently, an in-depth understanding of light-driven H-2 production via photosynthetic electron transfer and its competition with CO2 fixation is essential for improving photo-H-2 production. At the same time, the smart design of photo-H-2 production schemes and photo-H-2 bioreactors are challenges for efficient up-scaling of light-driven photo-H-2 production. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 16 15 2024 Utilizing the Metaverse to Provide Innovative Psychosocial Support for Pediatric, Adolescent, and Young Adult Patients with Rare Cancer 2617 EN Joe Hasei Department of Medical Information and Assistive Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hisashi Ishida Department of Pediatrics, Okayama University Hospital Hideki Katayama Department of Palliative and Supportive Care, Okayama University Hospital Naoko Maeda Department of Pediatrics, NHO National Hospital Organization Nagoya Medical Center Akihito Nagano Department of Orthopedic Surgery, Graduate School of Medicine, Gifu University Motoharu Ochi Department of Pediatrics, Okayama University Hospital Masako Okamura Division of Survivorship, Institute for Cancer Control, National Cancer Center Shintaro Iwata Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Kunihiro Ikuta Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University Shinichirou Yoshida Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University Tomohiro Fujiwara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Nakata Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichi Nakahara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kunisada Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing’s sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-9292 13 15 2024 Performance Investigations of VSLAM and Google Street View Integration in Outdoor Location-Based Augmented Reality under Various Lighting Conditions 2930 EN Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Prismahardi Aji Riyantoko Graduate School of Natural Science and Technology, Okayama University Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Mustika Mentari Graduate School of Natural Science and Technology, Okayama University The growing demand for Location-based Augmented Reality (LAR) experiences has driven the integration of Visual Simultaneous Localization And Mapping (VSLAM) with Google Street View (GSV) to enhance the accuracy. However, the impact of the ambient light intensity on the accuracy and reliability is underexplored, posing significant challenges in outdoor LAR implementations. This paper investigates the impact of light conditions on the accuracy and reliability of the VSLAM/GSV integration approach in outdoor LAR implementations. This study fills a gap in the current literature and offers valuable insights into vision-based approach implementation under different light conditions. Extensive experiments were conducted at five Point of Interest (POI) locations under various light conditions with a total of 100 datasets. Descriptive statistic methods were employed to analyze the data and assess the performance variation. Additionally, the Analysis of Variance (ANOVA) analysis was utilized to assess the impact of different light conditions on the accuracy metric and horizontal tracking time, determining whether there are significant differences in performance across varying levels of light intensity. The experimental results revealed that a significant correlation (p < 0.05) exists between the ambient light intensity and the accuracy of the VSLAM/GSV integration approach. Through the confidence interval estimation, the minimum illuminance 434 lx is needed to provide a feasible and consistent accuracy. Variations in visual references, such as wet surfaces in the rainy season, also impact the horizontal tracking time and accuracy. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 14 2024 Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID: A Retrospective Study in Japan 4099 EN Sho Yokoyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masayuki Kishida Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients' backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m(2); p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 14 2024 New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review 4199 EN Lutfun Nahar Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Md Asaduzzaman Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-9292 13 14 2024 A Reference Paper Collection System Using Web Scraping 2700 EN Inzali Naing Department of Information and Communication Systems, Okayama University Soe Thandar Aung Department of Information and Communication Systems, Okayama University Khaing Hsu Wai Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Collecting reference papers from the Internet is one of the most important activities for progressing research and writing papers about their results. Unfortunately, the current process using Google Scholar may not be efficient, since a lot of paper files cannot be accessed directly by the user. Even if they are accessible, their effectiveness needs to be checked manually. In this paper, we propose a reference paper collection system using web scraping to automate paper collections from websites. This system can collect or monitor data from the Internet, which is considered as the environment, using Selenium, a popular web scraping software, as the sensor; this examines the similarity against the search target by comparing the keywords using the Bert model. The Bert model is a deep learning model for natural language processing (NLP) that can understand context by analyzing the relationships between words in a sentence bidirectionally. The Python Flask is adopted at the web application server, where Angular is used for data presentations. For the evaluation, we measured the performance, investigated the accuracy, and asked members of our laboratory to use the proposed method and provide their feedback. Their results confirm the method’s effectiveness. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 13 2024 Changes in Working Situations of Employed Long COVID Patients: Retrospective Study in Japanese Outpatient Clinic 3809 EN Yui Matsuda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Sunada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Hasegawa Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Takase Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Omura Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keigo Ueda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: The present study aimed to uncover the impact of long COVID on the working situations of Japanese patients. Methods: Changes in the working situations of the patients who visited our long COVID clinic were evaluated from medical records for the aspects of physical status, quality of life (QOL), and mental conditions. <br> Results: Of 846 long COVID patients who visited our clinic from February 2021 to December 2023, 545 employed patients aged between 18 and 65 years were included in this study. A total of 295 patients (54.1%) with long COVID (median age: 43 years, female: 55.6%) experienced changes in their working status. Those patients included 220 patients (40.4%) who took a leave of absence, 53 patients (9.7%) who retired, and 22 patients (4%) with reduced working hours. Most of the patients (93.2%) with changes in working conditions had mild disease severity in the acute phase of COVID-19. The majority of those patients with mild disease severity (58.8%) were infected in the Omicron-variant phase and included 65.3% of the female patients. The major symptoms in long COVID patients who had changes in their working situations were fatigue, insomnia, headache, and dyspnea. Scores indicating fatigue and QOL were worsened in long COVID patients who had changes in their working situations. In addition, 63.7% of the long COVID patients with changes in their working situations had decreases in their incomes. <br> Conclusions: Changes in the working situation of long COVID patients who were employed had a negative impact on the maintenance of their QOL. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 13 2024 Mechanisms and Functions of Sweet Reception in Oral and Extraoral Organs 7398 EN Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuzo Ninomiya Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The oral detection of sugars relies on two types of receptor systems. The first is the G-protein-coupled receptor TAS1R2/TAS1R3. When activated, this receptor triggers a downstream signaling cascade involving gustducin, phospholipase C beta 2 (PLC beta 2), and transient receptor potential channel M5 (TRPM5). The second type of receptor is the glucose transporter. When glucose enters the cell via this transporter, it is metabolized to produce ATP. This ATP inhibits the opening of KATP channels, leading to cell depolarization. Beside these receptor systems, sweet-sensitive taste cells have mechanisms to regulate their sensitivity to sweet substances based on internal and external states of the body. Sweet taste receptors are not limited to the oral cavity; they are also present in extraoral organs such as the gastrointestinal tract, pancreas, and brain. These extraoral sweet receptors are involved in various functions, including glucose absorption, insulin release, sugar preference, and food intake, contributing to the maintenance of energy homeostasis. Additionally, sweet receptors may have unique roles in certain organs like the trachea and bone. This review summarizes past and recent studies on sweet receptor systems, exploring the molecular mechanisms and physiological functions of sweet (sugar) detection in both oral and extraoral organs. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 13 2024 Optimizing IoT Intrusion Detection Using Balanced Class Distribution, Feature Selection, and Ensemble Machine Learning Techniques 4293 EN Muhammad Bisri Musthafa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Samsul Huda Green Innovation Center, Okayama University Yuta Kodera Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Arshad Ali Faculty of CSE, Hajee Mohammad Danesh Science and Technology University Shunsuke Araki Graduate School of Computer Science and Systems Engineering, Kyushu Institute of Technology Jedidah Mwaura Graduate School of Computer Science and Systems Engineering, Kyushu Institute of Technology Yasuyuki Nogami Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Internet of Things (IoT) devices are leading to advancements in innovation, efficiency, and sustainability across various industries. However, as the number of connected IoT devices increases, the risk of intrusion becomes a major concern in IoT security. To prevent intrusions, it is crucial to implement intrusion detection systems (IDSs) that can detect and prevent such attacks. IDSs are a critical component of cybersecurity infrastructure. They are designed to detect and respond to malicious activities within a network or system. Traditional IDS methods rely on predefined signatures or rules to identify known threats, but these techniques may struggle to detect novel or sophisticated attacks. The implementation of IDSs with machine learning (ML) and deep learning (DL) techniques has been proposed to improve IDSs' ability to detect attacks. This will enhance overall cybersecurity posture and resilience. However, ML and DL techniques face several issues that may impact the models' performance and effectiveness, such as overfitting and the effects of unimportant features on finding meaningful patterns. To ensure better performance and reliability of machine learning models in IDSs when dealing with new and unseen threats, the models need to be optimized. This can be done by addressing overfitting and implementing feature selection. In this paper, we propose a scheme to optimize IoT intrusion detection by using class balancing and feature selection for preprocessing. We evaluated the experiment on the UNSW-NB15 dataset and the NSL-KD dataset by implementing two different ensemble models: one using a support vector machine (SVM) with bagging and another using long short-term memory (LSTM) with stacking. The results of the performance and the confusion matrix show that the LSTM stacking with analysis of variance (ANOVA) feature selection model is a superior model for classifying network attacks. It has remarkable accuracies of 96.92% and 99.77% and overfitting values of 0.33% and 0.04% on the two datasets, respectively. The model's ROC is also shaped with a sharp bend, with AUC values of 0.9665 and 0.9971 for the UNSW-NB15 dataset and the NSL-KD dataset, respectively. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 16 13 2024 Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer 2326 EN Saori Yoshida Preliminary Examination Room, Okayama University Hospital Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yamin Soe Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Htoo Shwe Eain Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sho Sanou Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yohei Takeshita Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miki Hisatomi Department of Oral and Maxillofacial Radiology, Okayama University Hospital Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Yanagi Preliminary Examination Room, Okayama University Hospital Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin–AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2221-3759 12 2 2024 Harderian Gland Development and Degeneration in the Fgf10-Deficient Heterozygous Mouse 16 EN Shiori Ikeda Department of Cytology and Histology, Medical School, Okayama University Keita Sato Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hirofumi Fujita Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitomi Ono-Minagi Department of Cytology and Histology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Miyaishi Department of Legal Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tsutomu Nohno Department of Cytology and Histology, Medical School, Okayama University Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The mouse Harderian gland (HG) is a secretory gland that covers the posterior portion of the eyeball, opening at the base of the nictitating membrane. The HG serves to protect the eye surface from infection with its secretions. Mice open their eyelids at about 2 weeks of age, and the development of the HG primordium mechanically opens the eye by pushing the eyeball from its rear. Therefore, when HG formation is disturbed, the eye exhibits enophthalmos (the slit-eye phenotype), and a line of Fgf10(+/-) heterozygous loss-of-function mice exhibits slit-eye due to the HG atrophy. However, it has not been clarified how and when HGs degenerate and atrophy in Fgf10(+/-) mice. In this study, we observed the HGs in embryonic (E13.5 to E19), postnatal (P0.5 to P18) and 74-week-old Fgf10(+/-) mice. We found that more than half of the Fgf10(+/-) mice had markedly degenerated HGs, often unilaterally. The degenerated HG tissue had a melanized appearance and was replaced by connective tissue, which was observed by P10. The development of HGs was delayed or disrupted in the similar proportion of Fgf10(+/-) embryos, as revealed via histology and the loss of HG-marker expression. In situ hybridization showed Fgf10 expression was observed in the Harderian mesenchyme in wild-type as well as in the HG-lacking heterozygote at E19. These results show that the Fgf10 haploinsufficiency causes delayed or defective HG development, often unilaterally from the unexpectedly early neonatal period. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 12 2024 Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model 6648 EN Anh Tuan Dang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikue Tosa Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emilio Satoshi Hara Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Mikai Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wakana Kitagawa Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Yonezawa Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/beta-Tricalcium phosphate (E-rhBMP-2/beta-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/beta-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/beta-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/beta-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 16 12 2024 Prognostic Implications of Insulin Resistance in Heart Failure in Japan 1888 EN Keiichiro Iwasaki Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazufumi Nakamura Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Akagi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoichi Takaya Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hironobu Toda Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index >= 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59-77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4-37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39-2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28-2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28-2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 25 13 2024 Genome-Wide Association Study with Three Control Cohorts of Japanese Patients with Esotropia and Exotropia of Comitant Strabismus and Idiopathic Superior Oblique Muscle Palsy 6986 EN Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ichiro Hamasaki Department of Ophthalmology, Okayama University Hospital Yoichiro Kamatani Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo Takahisa Kawaguchi Center for Genomic Medicine, Graduate School of Medicine, Kyoto University Izumi Yamaguchi Center for Genomic Medicine, Graduate School of Medicine, Kyoto University Fumihiko Matsuda Center for Genomic Medicine, Graduate School of Medicine, Kyoto University Akira Saito StaGen Co., Ltd. Kazuyuki Nakazono StaGen Co., Ltd. Shigeo Kamitsuji StaGen Co., Ltd. Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p < 5 × 10−8, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10−6. In comparison with BBJ (180K), RARB (retinoic acid receptor-β) was detected as a candidate at a significant level of p < 5 × 10−8 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1420-3049 29 11 2024 In Vitro Study of Tumor-Homing Peptide-Modified Magnetic Nanoparticles for Magnetic Hyperthermia 2632 EN Shengli Zhou Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kaname Tsutsumiuchi College of Bioscience and Biotechnology, Chubu University Ritsuko Imai College of Bioscience and Biotechnology, Chubu University Yukiko Miki College of Bioscience and Biotechnology, Chubu University Anna Kondo College of Bioscience and Biotechnology, Chubu University Hiroshi Nakagawa College of Bioscience and Biotechnology, Chubu University Kazunori Watanabe Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Cancer 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.

MDPI Acta Medica Okayama 1661-6596 25 11 2024 Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury 5889 EN Shangze Gao Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Dengli Wang Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keyue Liu Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuko Tomono Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Li Fu Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuan Gao Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Takahashi Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Yata Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Nishibori Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components—thrombin, heme, and ferrous ion— prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 11 2024 SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes 6269 EN Tianyi Wang Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tong Gao Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masakiyo Sakaguchi Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Teizo Yoshimura Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihiro Matsukawa Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3425 14 5 2024 Go/No-Go Ratios Modulate Inhibition-Related Brain Activity: An Event-Related Potential Study 414 EN Nan Zhang Graduate of Interdisciplinary Science and Engineering in Health Systems, Okayama University Weichao An Graduate of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yinghua Yu Graduate of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jinglong Wu Graduate of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jiajia Yang Graduate 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.

MDPI Acta Medica Okayama 1420-3049 29 10 2024 Recognition of 8-Oxo-2′-deoxyguanosine in DNA Using the Triphosphate of 2′-Deoxycytidine Connecting the 1,3-Diazaphenoxazine Unit, dCdapTP 2270 EN Takato Sakurada Graduate School of Pharmaceutical Sciences, Kyushu University Yuta Chikada Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Miyahara Graduate School of Pharmaceutical Sciences, Kyushu University Yosuke Taniguchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University DNA is constantly damaged by various external and internal factors. In particular, oxidative damage occurs in a steady state, and 8-oxo-2 '-deoxyguanosine (oxodG) is known as the main oxidative damage. OxodG is a strong genotoxic nucleoside and is thought to be involved in the pathogenesis of cancer and neurological diseases. However, a breakthrough method to detect the position of oxodG in DNA has not yet been developed. Therefore, we attempted to develop a novel method to detect oxodG in DNA using artificial nucleosides. Recently, we have succeeded in the recognition of oxodG in DNA by a single nucleotide elongation reaction using nucleoside derivatives based on a purine skeleton with a 1,3-diazaphenoxazine unit. In this study, we developed a new nucleoside derivative with a pyrimidine skeleton in order to further improve the recognition ability and enzymatic reaction efficiency. We, therefore, designed and synthesized 2 '-deoxycytidine-1,3-diazaphenoxazine (Cdap) and its triphosphate derivatives. The results showed that it was incorporated into the primer strand relative to the dG template because of its cytidine skeleton, but it was more effective at the complementary position of the oxodG template. These results indicate that the new nucleoside derivative can be considered as one of the new candidates for the detection of oxodG in DNA. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 16 10 2024 Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors 1811 EN Masahiko Sue Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuto Takeuchi Department of Gastroenterology and Hepatology, Okayama University Hospital Shoichiro Hirata Department of Gastroenterology and Hepatology, Okayama University Hospital Akinobu Takaki Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 13 10 2024 Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa 807 EN Xindi Mu Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ha Thi Thu Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kun Zhao Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taishi Komori Tomoko Yonezawa Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Implantology, Okayama University Hospital Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-2607 12 5 2024 Isolation of Vibrio cholerae and Vibrio vulnificus from Estuarine Waters, and Genotyping of V. vulnificus Isolates Using Loop-Mediated Isothermal Amplification 877 EN Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Megumi Kurata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Riho Hirose Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaya Yoshikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Liang Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Yamagishi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tamaki Mizuno Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bacteria in the genus Vibrio are ubiquitous in estuarine and coastal waters. Some species (including Vibrio cholerae and Vibrio vulnificus) are known human pathogens causing ailments like cholera, diarrhea, or septicemia. Notably, V. vulnificus can also cause a severe systemic infection (known as vibriosis) in eels raised in aquaculture facilities. Water samples were periodically collected from the estuary of the Asahi River, located in the southern part of Okayama City, Japan. These samples were directly plated onto CHROMagar Vibrio plates, and colonies displaying turquoise-blue coloration were selected. Thereafter, polymerase chain reaction was used to identify V. cholerae and V. vulnificus. A total of 30 V. cholerae strains and 194 V. vulnificus strains were isolated during the warm season when the water temperature (WT) was higher than 20 degrees C. Concurrently, an increase in coliforms was observed during this period. Notably, V. vulnificus has two genotypes, designated as genotype 1 and genotype 2. Genotype 1 is pathogenic to humans, while genotype 2 is pathogenic to both humans and eels. The loop-mediated isothermal amplification method was developed to rapidly determine genotypes at a low cost. Of the 194 strains isolated, 80 (41.2%) were identified as genotype 1 strains. Among the 41 strains isolated when the WTs were higher than 28 degrees C, 25 strains (61.0%) belonged to genotype 1. In contrast, of the 32 strains isolated when the WTs were lower than 24 degrees C, 27 strains (84.4%) belonged to genotype 2. These results suggest that the distribution of the two genotypes was influenced by WT. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 12 10 2024 Effect of Antimicrobial Photodynamic Therapy on the Tongue Dorsum on Reducing Halitosis and the Duration of the Effect: A Randomized Clinical Trial 980 EN Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichiro Nagasaki Okayama University Dental School Nanami Sawada Department of Preventive Dentistry, Okayama University Hospital Manabu Morita Department of Oral Health Sciences, Takarazuka University of Medical and Health Care Antimicrobial photodynamic therapy (PDT) is a treatment that is gaining popularity in modern clinical medicine. However, little is known about the effect of PDT alone on reducing oral halitosis and the duration of the effect. This trial examined the effect of PDT on the tongue dorsum on reducing oral halitosis and the duration of the effect. This study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and Okayama University Hospital (CRB20-015), and it was registered in the Japan Registry of Clinical Trials (jRCTs061200060). Twenty-two participants were randomly assigned to two groups: an intervention group and control group. PDT was performed in the intervention group using red laser emission and methylene blue gel on the middle and posterior area of the tongue dorsum. The concentration of volatile sulfur compounds, bacterial count on the tongue dorsum, probing pocket depth, bleeding on probing, and simplified oral debris index score were determined before and 1 week after PDT. The Mann-Whitney U test was used to assess the significance of the differences in each parameter between the two groups. We found that the hydrogen sulfide concentration and bacterial count on the tongue dorsum were decreased in the intervention group, but there was no statistically significant difference between the two groups. These results indicated that performing only PDT on the tongue dorsum may not contribute to reducing halitosis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2313-7673 9 5 2024 Clinical Application of Unidirectional Porous Hydroxyapatite to Bone Tumor Surgery and Other Orthopedic Surgery 294 EN Toshiyuki Kunisada Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Nakata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Hata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kohei Sato Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Haruyoshi Katayama Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ayana Kondo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-163X 14 5 2024 Measurements of Thermodynamic Data of Water in Ca-Bentonite by Relative Humidity Method 477 EN Kosuke Ichikawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruo Sato Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Buffer material (compacted bentonite), one of the engineered barrier elements in the geological disposal of a high-level radioactive waste, develops swelling stress due to groundwater penetration from the surrounding rock mass. Montmorillonite is the major clay mineral component of bentonite. Even previous studies provide few mechanical and thermodynamic data on Ca-montmorillonite. In this study, thermodynamic data on Ca-montmorillonite were obtained as a function of water content by measuring relative humidity (RH) and temperature. The activities of water and the relative partial molar Gibbs free energies of water were determined from the experimental results, and the swelling stress of Ca-bentonite was calculated using the thermodynamic model and compared with measured data. The activities of water and the relative partial molar Gibbs free energies obtained in the experiments decreased with decreasing water content in water contents lower than about 25%. This trend was similar to that of Na-montmorillonite. The swelling stress calculated based on the thermodynamic model was approximately 200 MPa at a montmorillonite partial density of 2.0 Mg/m3 and approximately 10 MPa at a montmorillonite partial density of 1.4 Mg/m3. The swelling stresses in the high-density region (around 2.0 Mg/m3) were higher than that of Na-montmorillonite and were similar levels in the low-density region (around 1.5 Mg/m3). Comparison with measured data showed the practicality of the thermodynamic model. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 15 4 2024 A Study of Learning Environment for Initiating Flutter App Development Using Docker 191 EN Soe Thandar Aung Department of Information and Communication Systems, Okayama University Nobuo Funabiki Department of Information and Communication Systems, Okayama University Lynn Htet Aung Department of Information and Communication Systems, Okayama University Safira Adine Kinari Department of Information and Communication Systems, Okayama University Mustika Mentari Department of Information and Communication Systems, Okayama University Khaing Hsu Wai Department of Information and Communication Systems, Okayama University The Flutter framework with Dart programming allows developers to effortlessly build applications for both web and mobile from a single codebase. It enables efficient conversions to native codes for mobile apps and optimized JavaScript for web browsers. Since utilizing a wide range of widgets in Flutter ensures consistent experiences on various devices for users, it becomes crucial in programming education by providing a unified environment for learning app development while reducing the need for platform-specific knowledge. However, the setup of the Flutter environment is challenging for novice students due to its multiple steps, such as installing dependencies and configuring environments. To support independent learning for these students, it is essential to simplify the setup by providing user-friendly instructions and automated tools. In this paper, we present a Docker-based environment for Flutter app developments across Windows, Linux, and Mac through Visual Studio Code, ensuring a unified learning experience. This paper aims to simplify complex configurations and address the obstacles encountered by students when initiating Flutter projects. For the evaluation, we prepared three simple Flutter projects along with the setup environment in a Docker container. Then, we asked 24 Master's students at Okayama University, Japan, to install the environment and modify the source codes in the projects independently by following the given instructions. The results show that all the students successfully completed the assignments, which confirms the efficiency and validity of our proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9717 12 4 2024 Pyrene-Modified Cyclic Peptides Detect Cu2+ Ions by Fluorescence in Water 746 EN Yuhi Maekawa Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University Sora Sakura Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University Yuji Furutani Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rento Fujihara Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University Hisashi Sugime Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University Takashi Ohtsuki Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mizuki Kitamatsu Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University The 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.

MDPI Acta Medica Okayama 2075-163X 14 4 2024 Swelling Stress of Bentonite: Thermodynamics of Interlayer Water in K-Montmorillonite in Consideration of Alteration 430 EN Misato Endo Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruo Sato Institute of Academic and Research, Okayama University The buffer material that makes up the geological disposal system of high-level waste swells by contact with groundwater and seals space with rock mass and fractures in rock mass. The buffer material has a function of mechanical buffer with rock pressure, and swelling stress is important in this case. The alteration of bentonite may occur due to the initial replacement of cations (Na+ ions) in the interlayer with K+ ions upon contact with groundwater, but there are no studies on the swelling stress of K-bentonite. In this study, the author prepared K-montmorillonite samples and obtained thermodynamic data on interlayer water as a function of water content using a relative humidity method. The swelling stress was analyzed based on a thermodynamic model developed in earlier studies and compared with measured data. The activity and the relative partial molar Gibbs free energy of porewater decreased with decreasing water content in the region, below approximately 15%. This behavior significantly differs from that of other ions, such as Na. The swelling stress calculated based on the thermodynamic model and date occurred in the region of high density of 1.9 Mg/m3 with montmorillonite partial density. It was indicated for the first time that K-bentonite scarcely swells under realistic design conditions. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-163X 14 4 2024 Changes of Temperature and Moisture Distribution over Time by Thermo-Hydro-Chemical (T-H-C)-Coupled Analysis in Buffer Material Focusing on Montmorillonite Content 394 EN Kohei Ouchi Graduate School of Natural Science and Technology, Okayama University Haruo Sato Graduate School of Natural Science and Technology, Okayama University Bentonite is used as a buffer material in engineered barriers for the geological disposal of high-level radioactive waste. The buffer material will be made of bentonite, a natural clay, mixed with silica sand. The buffer material is affected by decay heat from high-level radioactive waste, infiltration of groundwater, and swelling of the buffer material. The analysis of these factors requires coupled analysis of heat transfer, moisture transfer, and groundwater chemistry. The purpose of this study is to develop a model to evaluate bentonite types and silica sand content in a unified manner for thermo-hydro-chemical (T-H-C)-coupled analysis in buffer materials. We focused on the content of the clay mineral montmorillonite, which is the main component of bentonite, and developed a model to derive the moisture diffusion coefficient of liquid water and water vapor based on Philip and de Vries, and Kozeny-Carman. The evolutions of the temperature and moisture distribution in the buffer material were analyzed, and the validity of each distribution was confirmed by comparison with the measured data obtained from an in situ experiment at 350 m in depth at the Horonobe Underground Research Center, Hokkaido, Japan. No potential conflict of interest relevant to this article was reported.

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

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

MDPI Acta Medica Okayama 1424-8220 24 7 2024 An Application of Throughput Request Satisfaction Method for Maximizing Concurrent Throughput in WLAN for IoT Application System 2173 EN Bin Wu Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Sujan Chandra Roy Graduate School of Natural Science and Technology, Okayama University Md. Mahbubur Rahman Graduate School of Natural Science and Technology, Okayama University Dezheng Kong Graduate School of Natural Science and Technology, Okayama University Shihao Fang Graduate School of Natural Science and Technology, Okayama University With the wide applications of the Internet of Things (IoT) in smart home systems, IEEE 802.11n Wireless Local Area Networks (WLANs) have become a frequently chosen communication technology due to their adaptability and affordability. In a high-density network of devices such as the smart home scenerio, a host often meets interferences from other devices and unequal Received Signal Strength (RSS) from Access Points (APs). This results in throughput unfairness/insufficiency problems between hosts communicating concurrently in WLAN. Previously, we have studied the throughput request satisfaction method to address this problem. It calculates the target throughput from measured single and concurrent throughputs of hosts and controls the actual throughput at this target one by applying traffic shaping at the AP. However, the insufficiency problem of maximizing the throughput is not solved due to interferences from other hosts. In this paper, we present an extension of the throughput request satisfaction method to maximize the throughput of a high-priority host under concurrent communications. It recalculates the target throughput to increase the actual throughput as much as possible while the other hosts satisfy the least throughput. For evaluations, we conduct experiments using the test-bed system with Raspberry Pi as the AP devices in several topologies in indoor environments. The results confirm the effectiveness of our proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 6 2024 Enhancing Diagnostic Precision: Evaluation of Preprocessing Filters in Simple Diffusion Kurtosis Imaging for Head and Neck Tumors 1783 EN Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Yuuki Yoshimura Radiological Technology, Graduate School of Health Sciences, Okayama University Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuka Fukumura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: 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.

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

MDPI Acta Medica Okayama 2076-0825 13 3 2024 A Microchannel Device for Droplet Classification by Manipulation Using Piezoelectric Vibrator 95 EN Ao Fujioka Graduate School of Natural Science and Technology, Okayama University Shoko Seo Graduate School of Natural Science and Technology, Okayama University Takefumi Kanda Graduate School of Natural Science and Technology, Okayama University Shuichi Wakimoto Graduate School of Natural Science and Technology, Okayama University Daisuke Yamaguchi Graduate School of Natural Science and Technology, Okayama University Emulsion formulations should be monodispersed in terms of their stability. Therefore, there is a need for a device that can classify droplets of the desired size from polydispersed emulsions in a fluidized bed manufacturing system. In the previous study, we evaluated the fabrication of a droplet manipulation device using acoustic radiation forces through simulation using the finite element method. In this study, particle manipulation experiments using 1, 6, and 10 mu m polystyrene particles were first estimated and evaluated in comparison with their theoretical particle behavior. Based on the results we obtained, the driving conditions and droplet behavior were derived, and the droplet manipulation device using ultrasonic waves to shrink monodisperse emulsions was evaluated. As a result, the droplet classification effect in the microchannel was confirmed to be consistent with the droplet behavior prediction, and the microchannel structure with a constriction component improved its classification effect. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2036-7414 15 1 2024 Differential Diagnoses and Management Approaches for Gastric Polyposis 122 144 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual's lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 15 3 2024 A Survey of AI Techniques in IoT Applications with Use Case Investigations in the Smart Environmental Monitoring and Analytics in Real-Time IoT Platform 153 EN Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Evianita Dewi Fajrianti Graduate School of Natural Science and Technology, Okayama University Shihao Fang Graduate School of Natural Science and Technology, Okayama University Sritrusta Sukaridhoto Department of Informatic and Computer, Politeknik Elektronika Negeri Surabaya In this paper, we have developed the SEMAR (Smart Environmental Monitoring and Analytics in Real-Time) IoT application server platform for fast deployments of IoT application systems. It provides various integration capabilities for the collection, display, and analysis of sensor data on a single platform. Recently, Artificial Intelligence (AI) has become very popular and widely used in various applications including IoT. To support this growth, the integration of AI into SEMAR is essential to enhance its capabilities after identifying the current trends of applicable AI technologies in IoT applications. In this paper, we first provide a comprehensive review of IoT applications using AI techniques in the literature. They cover predictive analytics, image classification, object detection, text spotting, auditory perception, Natural Language Processing (NLP), and collaborative AI. Next, we identify the characteristics of each technique by considering the key parameters, such as software requirements, input/output (I/O) data types, processing methods, and computations. Third, we design the integration of AI techniques into SEMAR based on the findings. Finally, we discuss use cases of SEMAR for IoT applications with AI techniques. The implementation of the proposed design in SEMAR and its use to IoT applications will be in future works. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 6 2024 Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression 3252 EN Jiewen Zhang Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Akiyama Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aung Ye Mun Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuji Tagashira Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tingling Zou Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Matsunaga Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teisaku Kohno Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs' endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2223-7747 13 5 2024 The Impact of Phenological Gaps on Leaf Characteristics and Foliage Dynamics of an Understory Dwarf Bamboo, Sasa kurilensis 719 EN Chongyang Wu Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration Ryota Tanaka Faculty of Agriculture, Okayama University Kyohei Fujiyoshi Faculty of Agriculture, Okayama University Yasuaki Akaji Biodiversity Division, National Institute for Environmental Studies Muneto Hirobe Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University Naoko Miki Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University Juan Li Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration Keiji Sakamoto Department of Environmental Ecology, Graduate School of Environmental and Life Science, Okayama University Jian Gao Beijing for Bamboo & Rattan Science and Technology/International Centre for Bamboo and Rattan, Key Laboratory of National Forestry and Grassland Administration Phenological gaps exert a significant influence on the growth of dwarf bamboos. However, how dwarf bamboos respond to and exploit these phenological gaps remain enigmatic. The light environment, soil nutrients, leaf morphology, maximum photosynthetic rate, foliage dynamics, and branching characteristics of Sasa kurilensis were examined under the canopies of Fagus crenata and Magnolia obovata. The goal was to elucidate the adaptive responses of S. kurilensis to phenological gaps in the forest understory. The findings suggest that phenological gaps under an M. obovata canopy augment the available biomass of S. kurilensis, enhancing leaf area, leaf thickness, and carbon content per unit area. However, these gaps do not appreciably influence the maximum photosynthetic rate, total leaf number, leaf lifespan, branch number, and average branch length. These findings underscore the significant impact of annually recurring phenological gaps on various aspects of S. kurilensis growth, such as its aboveground biomass, leaf morphology, and leaf biochemical characteristics. It appears that leaf morphology is a pivotal trait in the response of S. kurilensis to phenological gaps. Given the potential ubiquity of the influence of phenological gaps on dwarf bamboos across most deciduous broadleaf forests, this canopy phenomenon should not be overlooked. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 4 2024 An Enhancement of Outdoor Location-Based Augmented Reality Anchor Precision through VSLAM and Google Street View 1161 EN Komang Candra Brata Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Evianita Dewi Fajrianti Graduate School of Natural Science and Technology, Okayama University Outdoor Location-Based Augmented Reality (LAR) applications require precise positioning for seamless integrations of virtual content into immersive experiences. However, common solutions in outdoor LAR applications rely on traditional smartphone sensor fusion methods, such as the Global Positioning System (GPS) and compasses, which often lack the accuracy needed for precise AR content alignments. In this paper, we introduce an innovative approach to enhance LAR anchor precision in outdoor environments. We leveraged Visual Simultaneous Localization and Mapping (VSLAM) technology, in combination with innovative cloud-based methodologies, and harnessed the extensive visual reference database of Google Street View (GSV), to address the accuracy limitation problems. For the evaluation, 10 Point of Interest (POI) locations were used as anchor point coordinates in the experiments. We compared the accuracies between our approach and the common sensor fusion LAR solution comprehensively involving accuracy benchmarking and running load performance testing. The results demonstrate substantial enhancements in overall positioning accuracies compared to conventional GPS-based approaches for aligning AR anchor content in the real world. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-6120 4 2 2023 A Study of the Active Access-Point Configuration Algorithm under Channel Bonding to Dual IEEE 802.11n and 11ac Interfaces in an Elastic WLAN System for IoT Applications 274 296 EN Sujan Chandra Roy Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Md. Mahbubur Rahman Department Electrical and Electronic Engineering, Jatiya Kabi Kazi Nazrul Islam University Bin Wu Graduate School of Natural Science and Technology, Okayama University Minoru Kuribayashi Graduate School of Natural Science and Technology, Okayama University Wen-Chung Kao Department of Electrical Engineering, National Taiwan Normal University Currently, Internet of Things (IoT) has become common in various applications, including smart factories, smart cities, and smart homes. In them, wireless local-area networks (WLANs) are widely used due to their high-speed data transfer, flexible coverage ranges, and low costs. To enhance the performance, the WLAN configuration should be optimized in dense WLAN environments where multiple access points (APs) and hosts exist. Previously, we have studied the active AP configuration algorithm for dual interfaces using IEEE802.11n and 11ac protocols at each AP under non-channel bonding (non-CB). In this paper, we study the algorithm considering the channel bonding (CB) to enhance its capacity by bonding two channels together. To improve the throughput estimation accuracy of the algorithm, the reduction factor is introduced at contending hosts for the same AP. For evaluations, we conducted extensive experiments using the WIMENT simulator and the testbed system using Raspberry Pi 4B APs. The results show that the estimated throughput is well matched with the measured one, and the proposal achieves the higher throughput with a smaller number of active APs than the previous configurations. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 3 2024 Characteristics of Functional Hyperthermia Detected in an Outpatient Clinic for Fever of Unknown Origin 889 EN Kosuke Oka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index >= 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 22 2023 Epidemiology and Reporting Characteristics of Systematic Reviews in Orthopedic Journals: A Meta-Epidemiological Study 7031 EN Norio Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunsuke Taito Scientific Research WorkS Peer Support Group (SRWS-PSG) Takanori Miura Scientific Research WorkS Peer Support Group (SRWS-PSG) Takashi Ariie Scientific Research WorkS Peer Support Group (SRWS-PSG) Yosuke Tomita Department of Physical Therapy, Faculty of Health Care, Takasaki University of Health and Welfare Hirofumi Ogihara Scientific Research WorkS Peer Support Group (SRWS-PSG) Daijo Shiratsuchi Graduate School of Health Sciences, Kagoshima University Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasushi Tsujimoto Scientific Research WorkS Peer Support Group (SRWS-PSG) Systematic reviews (SRs) with complete reporting or rigorous methods can lead to less biased recommendations and decisions. A comprehensive analysis of the epidemiological and reporting characteristics of SRs in orthopedics is lacking. We evaluated 360 SRs, including 165 and 195 published in orthopedic journals in 2012 and 2022. According to the established reporting guidelines, we examined these SRs for key epidemiological characteristics, including focus areas, type of meta-analysis (MA), and reporting characteristics. Most SRs (71%) were therapy-related, with a significant proportion originating from authors in the USA, UK, and China. Pairwise MA was performed on half of the SRs. The proportion of protocol registrations improved by 2022 but remained low (33%). Despite a formal declaration of adherence to the reporting guidelines (68%), they were often not used and reported enough. Only 10% of the studies used full search strategies, including trial registries. Publication bias assessments, subgroup analyses, and sensitivity analyses were not even planned. The risk of bias assessment improved in 2022; however, the certainty of the evidence remained largely unassessed (8%). The use and reporting of standard methods in orthopedic SRs have remained suboptimal. Thus, authors, peer reviewers, journal editors, and readers should criticize the results more. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 3 2024 Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes 1443 EN Yoshifumi Hotta Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Hospital Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Hospital Shuichi Naniwa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Shimizu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chinatsu Ichikawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Deting Lin Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 3 2024 Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells 1585 EN Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Iwata Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine beta-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 2 2024 Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis 987 EN Quan Duy Vo Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Iida Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived-cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy's promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-2615 14 2 2024 A System for Monitoring Animals Based on Behavioral Information and Internal State Information 281 EN Taro Shibanoki Department of Intelligent Mechanical Systems, Faculty of Environmental, Life, Natural Science and Technology, Okayama University Yuugo Yamazaki Major in Computer and Information Sciences, Graduate School of Science and Engineering, Ibaraki University Hideyuki Tonooka Major in Computer and Information Sciences, Graduate School of Science and Engineering, Ibaraki University Managing the risk of injury or illness is an important consideration when keeping pets. This risk can be minimized if pets are monitored on a regular basis, but this can be difficult and time-consuming. However, because only the external behavior of the animal can be observed and the internal condition cannot be assessed, the animal’s state can easily be misjudged. Additionally, although some systems use heartbeat measurement to determine a state of tension, or use rest to assess the internal state, because an increase in heart rate can also occur as a result of exercise, it is desirable to use this measurement in combination with behavioral information. In the current study, we proposed a monitoring system for animals using video image analysis. The proposed system first extracts features related to behavioral information and the animal’s internal state via mask R-CNN using video images taken from the top of the cage. These features are used to detect typical daily activities and anomalous activities. This method produces an alert when the hamster behaves in an unusual way. In our experiment, the daily behavior of a hamster was measured and analyzed using the proposed system. The results showed that the features of the hamster’s behavior were successfully detected. When loud sounds were presented from outside the cage, the system was able to discriminate between the behavioral and internal changes of the hamster. In future research, we plan to improve the accuracy of the measurement of small movements and develop a more accurate system. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 2 2024 Ultrathin Platinum Film Hydrogen Sensors with a Twin-T Type Notch Filter Circuit 548 EN Shoki Wakabayashi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuki Oh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Haruhito Nakayama Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In 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.

MDPI Acta Medica Okayama 2227-9059 12 2 2024 Morphometric Analysis of the Eye by Magnetic Resonance Imaging in MGST2-Gene-Deficient Mice 370 EN Chaomulige Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kohei Sugimoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mary Miyaji Department of Medical Neurobiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Osamu Hosoya Department of Medical Neurobiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masashi Ueda Department of Biofunctional Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Ryosuke Kobayashi Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University Takuro Horii Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University Izuho Hatada Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University Strabismus, a neuro-ophthalmological condition characterized by misalignment of the eyes, is a common ophthalmic disorder affecting both children and adults. In our previous study, we identified the microsomal glutathione S-transferase 2 (MGST2) gene as one of the potential candidates for comitant strabismus susceptibility in a Japanese population. The MGST2 gene belongs to the membrane-associated protein involved in the generation of pro-inflammatory mediators, and it is also found in the protection against oxidative stress by decreasing the reactivity of oxidized lipids. To look for the roles of the MGST2 gene in the development, eye alignment, and overall morphology of the eye as the possible background of strabismus, MGST2 gene knockout (KO) mice were generated by CRISPR/Cas9-mediated gene editing with guide RNAs targeting the MGST2 exon 2. The ocular morphology of the KO mice was analyzed through high-resolution images obtained by a magnetic resonance imaging (MRI) machine for small animals. The morphometric analyses showed that the height, width, and volume of the eyeballs in MGST2 KO homozygous mice were significantly greater than those of wild-type mice, indicating that the eyes of MGST2 KO homozygous mice were significantly enlarged. There were no significant differences in the axis length and axis angle. These morphological changes may potentially contribute to the development of a subgroup of strabismus. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 12 1 2024 Hydrogen in Transplantation: Potential Applications and Therapeutic Implications 118 EN Takafumi Obara Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hiromichi Naito Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tsuyoshi Nojima Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Hirayama Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takashi Hongo Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kohei Ageta Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Toshiyuki Aokage Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Masaki Hisamura Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Tetsuya Yumoto Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Atsunori Nakao Department of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 18 2023 Advanced Techniques Using In Vivo Electroporation to Study the Molecular Mechanisms of Cerebral Development Disorders 14128 EN Chen Yang Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Atsunori Shitamukai Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Shucai Yang Human Anatomy and Histology and Embryology, School of Basic Medicine, Harbin Medical University Ayano Kawaguchi Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences The mammalian cerebral cortex undergoes a strictly regulated developmental process. Detailed in situ visualizations, imaging of these dynamic processes, and in vivo functional gene studies significantly enhance our understanding of brain development and related disorders. This review introduces basic techniques and recent advancements in in vivo electroporation for investigating the molecular mechanisms underlying cerebral diseases. In utero electroporation (IUE) is extensively used to visualize and modify these processes, including the forced expression of pathological mutants in human diseases; thus, this method can be used to establish animal disease models. The advent of advanced techniques, such as genome editing, including de novo knockout, knock-in, epigenetic editing, and spatiotemporal gene regulation, has further expanded our list of investigative tools. These tools include the iON expression switch for the precise control of timing and copy numbers of exogenous genes and TEMPO for investigating the temporal effects of genes. We also introduce the iGONAD method, an improved genome editing via oviductal nucleic acid delivery approach, as a novel genome-editing technique that has accelerated brain development exploration. These advanced in vivo electroporation methods are expected to provide valuable insights into pathological conditions associated with human brain disorders. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 5 4 2023 Total Synthesis of the Proposed Structure of Indolyl 1,2-Propanediol Alkaloid, 1-(1H-Indol-3-yloxy)propan-2-ol 2772 2784 EN Momoko Kimata Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The first total synthesis of the proposed structure of unprecedented indolyl derivative bearing 1,2-propanediol moiety is described. Isomerization of 3-alkoxyindolines through indolenium intermediates was the key step in the total synthesis. H-1, C-13-NMR, IR, and HRMS spectra of the synthetic compound drastically differed to those of the originally reported structure, which suggests the natural product requires revision. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 13 24 2023 Characteristic Mean Kurtosis Values in Simple Diffusion Kurtosis Imaging of Dentigerous Cysts 3619 EN Yuka Fukumura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Suzuka Yoshida Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihide Nakamura Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Wlla Al-Hammad Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nurul Kamaruddin Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Yanagi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We evaluated the usefulness of simple diffusion kurtosis (SD) imaging, which was developed to generate diffusion kurtosis images simultaneously with an apparent diffusion coefficient (ADC) map for 27 cystic disease lesions in the head and neck region. The mean kurtosis (MK) and ADC values were calculated for the cystic space. The MK values were dentigerous cyst (DC): 0.74, odontogenic keratocyst (OKC): 0.86, ranula (R): 0.13, and mucous cyst (M): 0, and the ADC values were DC: 1364 × 10−6 mm2/s, OKC: 925 × 10−6 mm2/s, R: 2718 × 10−6 mm2/s, and M: 2686 × 10−6 mm2/s. The MK values of DC and OKC were significantly higher than those of R and M, whereas their ADC values were significantly lower. One reason for the characteristic signal values in diffusion-weighted images of DC may be related to content components such as fibrous tissue and exudate cells. When imaging cystic disease in the head and neck region using SD imaging, the maximum b-value setting at the time of imaging should be limited to approximately 1200 s/mm2 for accurate MK value calculation. This study is the first to show that the MK values of DC are characteristically higher than those of other cysts. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-0825 12 11 2023 Development of Hexagonal Pyramid-Shaped Flexible Actuator with Anisotropic Stiffness for Upper-Limb Rehabilitation Device 424 EN So Shimooka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hiroki Himuro Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akio Gofuku Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Rehabilitation 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.

MDPI Acta Medica Okayama 2077-0383 12 22 2023 The Effectiveness of Rehabilitation after Open Surgical Release for Trigger Finger: A Prospective, Randomized, Controlled Study 7187 EN Taichi Saito Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Nakamichi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: It is not clear whether rehabilitation after surgery for trigger finger is effective. The aim of this study was to reveal its effectiveness for trigger finger. Methods: This study was a randomized, controlled trial that included patients who underwent operations for trigger fingers. The patients in the rehabilitation group had postoperative occupational therapy (OT) for 3 months, while the patients in the control group were not referred for rehabilitation but received advice for a range of motion exercises. We evaluated the severity of trigger finger, Disability of Arm-Shoulder-Hand (DASH) score, pain-visual analogue scale (VAS), grip strength, whether they gained a full range of motion (ROM), and complications before and after surgery. Results: Finally, 29 and 28 patients were included in the control and rehabilitation groups, respectively. At final follow-up, the DASH score, grip strength, and ROM were significantly improved in the rehabilitation group compared to that preoperatively. At final follow-up, pain was significantly improved in both groups from that preoperatively. There were no significant differences in the results, including the DASH score, grip strength, ROM and pain-VAS between the control and rehabilitation groups at the final follow-up. Subgroup analysis showed that there is a significant difference in the DASH score of patients doing housework or light work and those with a duration of symptoms >12 months between the control and rehabilitation groups at the final follow-up. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2079-7737 12 12 2023 Random Mutational Analysis Targeting Residue K155 within the Transmembrane β-Hairpin of the Mosquitocidal Mpp46Ab Toxin 1481 EN Midoka Miyazaki Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mami Asakura Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toru Ide Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tohru Hayakawa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mpp46Ab 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.

MDPI Acta Medica Okayama 2072-6694 15 24 2023 The Diagnosis and Treatment Approach for Oligo-Recurrent and Oligo-Progressive Renal Cell Carcinoma 5873 EN Kensuke Bekku Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tatsushi Kawada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sekito Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Maruyama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoaki Yamanoi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Tominaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Katayama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Iwata Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohei Edamura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoko Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuzuru Niibe Department of Public Health, School of Medicine, Kurume University One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed “oligo-recurrent” disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as “oligo-progression”, can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 24 2023 Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors 17294 EN Loc Dinh Hoang Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Eriko Aoyama Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miki Hiasa Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Omote Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kubota Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaharu Takigawa Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 13 18 2023 MicroRNAs as Biomarkers and Therapeutic Targets for Acute Kidney Injury 2893 EN Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-393X 11 11 2023 Characteristics of Persistent Symptoms Manifested after SARS-CoV-2 Vaccination: An Observational Retrospective Study in a Specialized Clinic for Vaccination-Related Adverse Events 1661 EN Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manami Fujita-Yamashita Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31-64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-6382 12 11 2023 Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans 1562 EN Yuki Shinoda-Ito Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Masaaki Nakayama Department of Oral Microbiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ikeda Department of Periodontics & Endodontics, Division of Dentistry, Okayama University Hospital Masahiro Ito Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiaki Ohara Department of Pathology and Experimental Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 20 2023 Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review 15450 EN Mitsuru Tsuge Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Uda Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Takahiro Eitoku Department of Pediatrics, Kawasaki Medical School Naomi Matsumoto Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Takashi Yorifuji Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4360 15 20 2023 Fabrication of a Fish-Bone-Inspired Inorganic-Organic Composite Membrane 4190 EN Yuyang Jiao Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Masahiro Okada Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Bhingaradiya Nutan Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ahmad Bikharudin Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Randa Musa Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Biological materials have properties like great strength and flexibility that are not present in synthetic materials. Using the ribs of crucian carp as a reference, we investigated the mechanisms behind the high mechanical properties of this rib bone, and found highly oriented layers of calcium phosphate (CaP) and collagen fibers. To fabricate a fish-rib-bone-mimicking membrane with similar structure and mechanical properties, this study involves (1) the rapid synthesis of plate-like CaP crystals, (2) the layering of CaP-gelatin hydrogels by gradual drying, and (3) controlling the shape of composite membranes using porous gypsum molds. Finally, as a result of optimizing the compositional ratio of CaP filler and gelatin hydrogel, a CaP filler content of 40% provided the optimal mechanical properties of toughness and stiffness similar to fish bone. Due to the rigidity, flexibility, and ease of shape control of the composite membrane materials, this membrane could be applied as a guided bone regeneration (GBR) membrane. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4433 14 10 2023 Numerical Analysis of Various Heat Countermeasures: Effects on Energy Consumption and Indoor Thermal Comfort in Densely Built Wooden House Area 1566 EN Shanshan Liu Department of Architecture and Building Engineering, Tokyo Institute of Technology Ronnen Levinson Heat Island Group, Lawrence Berkeley National Laboratory Daisuke Narumi Graduate School of Environmental and Life Science, Okayama University Densely built areas with poor thermal insulation suffer from high thermal environmental risks and generally consume high energy in summer. Determining the relationship between density and energy consumption is necessary, particularly when implementing urban heat island (UHI) countermeasures. This study evaluated the effects of density and UHI countermeasures on the energy consumption and indoor thermal comfort of a detached house in a typical densely built wooden house area in Yokohama City, Japan. Three densities and six countermeasures were considered. Annual hourly simulations based on the SCIENCE-Vent thermal environment simulation model yielded the following results: in densely built wooden house areas, the energy consumption and thermal discomfort increased with density. The green roof yielded the largest energy savings in the cooling and heating seasons, demonstrating the highest annual energy savings with 5.7%. Density had little impact on rooftop countermeasures, but the effect of the high-reflectance walls increased with density, and the reduction in annual energy consumption (air conditioning and lighting) is 2.6%, 3.0%, 3.6% in 37%, 47%, and 59% density cases, respectively. The impact of thermal countermeasures on indoor thermal comfort varied according to the thermal control mechanism. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2227-9059 11 10 2023 Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke 2773 EN Takayuki Nagase Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyohei Kin Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takao Yasuhara Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences The interruption of cerebral blood flow leads to ischemic cell death and results in ischemic stroke. Although ischemic stroke is one of the most important causes of long-term disability and mortality, limited treatments are available for functional recovery. Therefore, extensive research has been conducted to identify novel treatments. Neurogenesis is regarded as a fundamental mechanism of neural plasticity. Therefore, therapeutic strategies targeting neurogenesis are thought to be promising. Basic research has found that therapeutic intervention including cell therapy, rehabilitation, and pharmacotherapy increased neurogenesis and was accompanied by functional recovery after ischemic stroke. In this review, we consolidated the current knowledge of the relationship between neurogenesis and treatment for ischemic stroke. It revealed that many treatments for ischemic stroke, including clinical and preclinical ones, have enhanced brain repair and functional recovery post-stroke along with neurogenesis. However, the intricate mechanisms of neurogenesis and its impact on stroke recovery remain areas of extensive research, with numerous factors and pathways involved. Understanding neurogenesis will lead to more effective stroke treatments, benefiting not only stroke patients but also those with other neurological disorders. Further research is essential to bridge the gap between preclinical discoveries and clinical implementation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 13 19 2023 Role of Semaphorin 3A in Kidney Development and Diseases 3038 EN Yizhen Sang Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2071-1050 15 18 2023 The Relationship between the Evaluation of Public Transport Services and Travel-Based CO2 Emissions from Private Transport Modes in Regional and Metropolitan Areas in Japan 13296 EN Shreyas Pradhan Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takehito Ujihara Faculty of Environmental, Life, Natural Science and Technology, Okayama University Seiji Hashimoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Promoting public transport use is expected to contribute to reducing CO2 emissions in the transport sector. Using Okayama City and Central Tokyo as representative case studies of regional and metropolitan areas in Japan, this study examines the impact of the evaluation of the 'hard' and 'soft' attributes of rail and bus services on the overall evaluation. This study then explores the relationship between the overall evaluation and usage frequency of rail and bus services, as well as the relationship between the usage frequency and travel-based CO2 emissions from private transport modes. Furthermore, this study investigates whether the emissions cause differences in the evaluation of the 'hard' and 'soft' attributes of public transport services. The findings suggest prioritising an improvement in 'hard' rather than 'soft' attributes in order to reduce emissions through the use of public transport in regional areas. However, in metropolitan areas, no relationship was found between the evaluation of public transport services and emissions, presumably because of the lower ownership rate of private cars that residents can use freely and the markedly higher level of rail and bus services. This study provides a methodological reference for analysing the potential to reduce travel-based emissions from private transport modes by enhancing public transport service contents. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 18 2023 The Germinal Origin of Salivary and Lacrimal Glands and the Contributions of Neural Crest Cell-Derived Epithelium to Tissue Regeneration 13692 EN Hitomi Ono-Minagi Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsutomu Nohno Department of Cytology and Histology, Okayama University Medical School Takashi Serizawa Department of Physiology, Keio University School of Medicine Yu Usami Department of Oral and Maxillofacial Pathology, Osaka University Graduate School of Dentistry Takayoshi Sakai Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry Hideyuki Okano Department of Physiology, Keio University School of Medicine Hideyo Ohuchi Department of Cytology and Histology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences The vertebrate body comprises four distinct cell populations: cells derived from (1) ectoderm, (2) mesoderm, (3) endoderm, and (4) neural crest cells, often referred to as the fourth germ layer. Neural crest cells arise when the neural plate edges fuse to form a neural tube, which eventually develops into the brain and spinal cord. To date, the embryonic origin of exocrine glands located in the head and neck remains under debate. In this study, transgenic TRiCK mice were used to investigate the germinal origin of the salivary and lacrimal glands. TRiCK mice express fluorescent proteins under the regulatory control of Sox1, T/Brachyury, and Sox17 gene expressions. These genes are representative marker genes for neuroectoderm (Sox1), mesoderm (T), and endoderm (Sox17). Using this approach, the cellular lineages of the salivary and lacrimal glands were examined. We demonstrate that the salivary and lacrimal glands contain cells derived from all three germ layers. Notably, a subset of Sox1-driven fluorescent cells differentiated into epithelial cells, implying their neural crest origin. Also, these Sox1-driven fluorescent cells expressed high levels of stem cell markers. These cells were particularly pronounced in duct ligation and wound damage models, suggesting the involvement of neural crest-derived epithelial cells in regenerative processes following tissue injury. This study provides compelling evidence clarifying the germinal origin of exocrine glands and the contribution of neural crest-derived cells within the glandular epithelium to the regenerative response following tissue damage. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 23 14 2023 An Interface Setup Optimization Method Using a Throughput Estimation Model for Concurrently Communicating Access Points in a Wireless Local Area Network 6367 EN Fatema Akhter Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Ei Ei Htet Graduate School of Natural Science and Technology, Okayama University Bin Wu Graduate School of Natural Science and Technology, Okayama University Dezheng Kong Graduate School of Natural Science and Technology, Okayama University Shihao Fang Graduate School of Natural Science and Technology, Okayama University The IEEE 802.11 wireless local-area network (WLAN) has been deployed around the globe as a major Internet access medium due to its low cost and high flexibility and capacity. Unfortunately, dense wireless networks can suffer from poor performance due to high levels of radio interference resulting from adjoining access points (APs). To address this problem, we studied the AP transmission power optimization method, which selects the maximum or minimum power supplied to each AP so that the average signal-to-interference ratio (SIR) among the concurrently communicating APs is maximized.However, this method requires measurements of receiving signal strength (RSS) under all the possible combinations of powers. It may need intolerable loads and time as the number of APs increases. It also only considers the use of channel bonding (CB), although non-CB sometimes achieves higher performance under high levels of interference. In this paper, we present an AP interface setup optimization method using the throughput estimation model for concurrently communicating APs. The proposed method selects CB or non-CB in addition to the maximum or minimum power for each AP. This model approach avoids expensive costs of RSS measurements under a number of combinations. To estimate the RSS at an AP from another AP or a host, the model needs the distance and the obstacles between them, such as walls. Then, by calculating the estimated RSS with the model and calculating the SIR from them, the AP interface setups for a lot of APs in a large-scale wireless network can be optimized on a computer in a very short time. For evaluation, we conducted extensive experiments using Raspberry Pi for APs and Linux PCs for hosts under 12 network topologies in three buildings at Okayama University, Japan, and Jatiya Kabi Kazi Nazrul Islam University, Bangladesh. The results confirm that the proposed method selects the best AP interface setup with the highest total throughput in any topology. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 16 2023 Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study 5174 EN Hisao Higo Department of Allergy and Respiratory Medicine, Okayama University Hospital Hirohisa Ichikawa Department of Respiratory Medicine, KKR Takamatsu Hospital Yukako Arakawa Department of Respiratory Medicine, KKR Takamatsu Hospital Yoshihiro Mori Department of Respiratory Medicine, KKR Takamatsu Hospital Junko Itano Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Akihiko Taniguchi Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Senoo Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Goro Kimura Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Yasushi Tanimoto Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center Kohei Miyake Department of Respiratory Medicine, National Hospital Organization Himeji Medical Center Tomoya Katsuta Department of Respiratory Medicine, Ehime Prefectural Central Hospital Mikio Kataoka Department of Respiratory Medicine, Onomichi Municipal Hospital Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Nobuaki Miyahara Department of Allergy and Respiratory Medicine, Okayama University Hospital Okayama Respiratory Disease Study Group (ORDSG) Background: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. Methods: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. Results: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/ mu L), but all were asymptomatic and able to continue dupilumab therapy. Conclusions: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4701 13 8 2023 Microstructural Control and Alloy Design for Improving the Resistance to Delayed Fracture of Ultrahigh-Strength Automotive Steel Sheets 1368 EN Takehide Senuma Department of Mechanical and Systems Engineering, Okayama University Mitsuhiro Okayasu Department of Mechanical and Systems Engineering, Okayama University Hardy Mohrbacher NiobelCon BV The demand for higher-strength automotive steel sheets has increased significantly for lightweight and safe body concepts. However, the increment of the steel strength is often limited by the potential occurrence of delayed fracture. This paper discusses proper microstructure control and alloy design to improve the resistance against the delayed fracture of ultrahigh-strength automotive steel sheets in order to increase the usable upper limit of their strength and provides basic data serving as a practical guide for solving the problem of delayed fracture in ultrahigh-strength automotive steel sheets. It is confirmed that grain refinement, the appropriate dual-phase structure of martensite with ferrite or retained austenite, and surface decarburization, increase the resistance to delayed fracture. In terms of alloy design, the effects of Nb, Mo, and B on the delayed fracture resistance of hot-stamped steels have been investigated. The results suggest that there are other reasons for Nb to improve delayed fracture resistance in addition to grain refinement and the ability to trap hydrogen by its precipitates, as has been conventionally believed. Regarding Mo, it was clearly demonstrated that the segregation of this element at the grain boundary plays a main role in improving the delayed fracture resistance. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 16 2023 Interaction of Orexin and Bone Morphogenetic Proteins in Steroidogenesis by Human Adrenocortical Cells 12559 EN Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Iwata Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ran Nishioka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mako Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Orexins are neuropeptides that play important roles in sleep-wake regulation and food intake in the central nervous system, but their receptors are also expressed in peripheral tissues, including the endocrine system. In the present study, we investigated the functions of orexin in adrenal steroidogenesis using human adrenocortical H295R cells by focusing on its interaction with adrenocortical bone morphogenetic proteins (BMPs) that induce adrenocortical steroidogenesis. Treatment with orexin A increased the mRNA levels of steroidogenic enzymes including StAR, CYP11B2, CYP17, and HSD3B1, and these effects of orexin A were further enhanced in the presence of forskolin. Interestingly, orexin A treatment suppressed the BMP-receptor signaling detected by Smad1/5/9 phosphorylation and Id-1 expression through upregulation of inhibitory Smad7. Orexin A also suppressed endogenous BMP-6 expression but increased the expression of the type-II receptor of ActRII in H295R cells. Moreover, treatment with BMP-6 downregulated the mRNA level of OX1R, but not that of OX2R, expressed in H295R cells. In conclusion, the results indicate that both orexin and BMP-6 accelerate adrenocortical steroidogenesis in human adrenocortical cells; both pathways mutually inhibit each other, thereby leading to a fine-tuning of adrenocortical steroidogenesis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1198-0052 30 8 2023 Mean 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 Patients 7412 7424 EN Wlla E. Al-Hammad Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Ryo Kamizaki Radiological Technology, Graduate School of Health Sciences, Okayama University Nouha Tekiki Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hinata Ishizaka Radiological Technology, Graduate School of Health Sciences, Okayama University Kazuhiro Kuroda Radiological Technology, Graduate School of Health Sciences, Okayama University Kohei Sugimoto Radiological Technology, Graduate School of Health Sciences, Okayama University Masataka Oita Graduate School of Interdisciplinary Sciences and Engineering in Health Systems, Okayama University Yoshinori Tanabe Radiological Technology, Graduate School of Health Sciences, Okayama University Majd Barham Department of Dentistry and Dental Surgery, College of Medicine and Health Sciences, An-Najah National University Irfan Sugianto Department of Oral Radiology, Faculty of Dentistry, Hasanuddin University Yudai Shimizu Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Nakamitsu Radiological Technology, Graduate School of Health Sciences, Okayama University Junichi Asaumi Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Deep 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.

MDPI Acta Medica Okayama 2072-6694 15 15 2023 Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis 3786 EN Tsukasa Higashionna Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Keisaku Harada Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Akinari Maruo Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Niimura Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School Elizabeth Tan Graduate School, Centro Escolar University Manila Quynh Thi Vu Faculty of Pharmacy, Haiphong University of Medicine and Pharmacy Takayoshi Kawabata Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Hirofumi Hamano Department of Pharmacy, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Yoshito Zamami Department of Pharmacy, Kitakyushu City Yahata Hospital Keisuke Ishizawa Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School Ko Harada Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Shiro Hinotsu Department of Biostatistics and Data Management, Sapporo Medical University Mitsunobu R. Kano Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshihiro Koyama Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Simple Summary The number of cases of head and neck cancer (HNC) and related deaths has recently increased worldwide. To the best of our knowledge, few studies have examined crude or age-adjusted HNC mortality rates in Japan. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. In Japan, the number of HNC-related deaths increased 1.48-fold. Age-adjusted mortality rates for HNC were four times higher in men than in women, and the rates for both men and women decreased over the 21-year period. This study clarifies the changes in age-adjusted mortality rates of HNC in Japan over time and will aid in developing targeted screening and prevention programs for HNC. Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1073 16 15 2023 Features and Evolution of Global Energy Trade Patterns from the Perspective of Complex Networks 5677 EN Yingnan Cong Business School, China University of Political Science and Law Yufei Hou Business School, China University of Political Science and Law Jiaming Jiang Center for Artificial Intelligence and Mathematical Data Science, Okayama University Shuangzi Chen School of Economics, Hebei University Xiaojing Cai Graduate School of Humanities and Social Sciences, Okayama University As an integral part of economic trade, energy trade is crucial to international dynamics and national interests. In this study, an international energy trade network is constructed by abstracting countries as nodes and representing energy trade relations as edges. A variety of indicators are designed in terms of networks, nodes, bilaterals, and communities to analyze the temporal and spatial evolution of the global energy trade network from 2001 to 2020. The results indicate that network density and strength have been steadily increasing since the beginning of the 21st century. It is observed that the position of the United States as the core of the international energy market is being impacted by emerging developing countries, thus affecting the existing trade balance based on topological analysis. The weighted analysis of bilateral relations demonstrates that emerging countries such as China, Brazil, and Saudi Arabia are pursuing closer cooperation. The community analysis reveals that an increasing number of countries possess strong energy trade capabilities, resulting in a corresponding increase in energy trade volumes. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 15 2023 Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension 5028 EN Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazufumi Nakamura Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Megumi Kondo Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Heiichiro Udono Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Mikako Nishida Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yukihiro Saito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Yoshida Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroshi Ito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 14 7 2023 INSUS: Indoor Navigation System Using Unity and Smartphone for User Ambulation Assistance 359 EN Evianita Dewi Fajrianti Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Sritrusta Sukaridhoto Department of Informatic and Computer, Politeknik Elektronika Negeri Surabaya Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Kong Dezheng Graduate School of Natural Science and Technology, Okayama University Fang Shihao Graduate School of Natural Science and Technology, Okayama University Anak Agung Surya Pradhana Indonesian Institute of Business and Technology (INSTIKI) Currently, outdoor navigation systems have widely been used around the world on smartphones. They rely on GPS (Global Positioning System). However, indoor navigation systems are still under development due to the complex structure of indoor environments, including multiple floors, many rooms, steps, and elevators. In this paper, we present the design and implementation of the Indoor Navigation System using Unity and Smartphone (INSUS). INSUS shows the arrow of the moving direction on the camera view based on a smartphone's augmented reality (AR) technology. To trace the user location, it utilizes the Simultaneous Localization and Mapping (SLAM) technique with a gyroscope and a camera in a smartphone to track users' movements inside a building after initializing the current location by the QR code. Unity is introduced to obtain the 3D information of the target indoor environment for Visual SLAM. The data are stored in the IoT application server called SEMAR for visualizations. We implement a prototype system of INSUS inside buildings in two universities. We found that scanning QR codes with the smartphone perpendicular in angle between 60 degrees and 100 degrees achieves the highest QR code detection accuracy. We also found that the phone's tilt angles influence the navigation success rate, with 90 degrees to 100 degrees tilt angles giving better navigation success compared to lower tilt angles. INSUS also proved to be a robust navigation system, evidenced by near identical navigation success rate results in navigation scenarios with or without disturbance. Furthermore, based on the questionnaire responses from the respondents, it was generally found that INSUS received positive feedback and there is support to improve the system. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 24 14 2023 Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers 11768 EN Keisuke Tsuchiya Division of Organic Chemistry, National Institute of Health Sciences Kanako Horikoshi Division of Organic Chemistry, National Institute of Health Sciences Minami Fujita Division of Organic Chemistry, National Institute of Health Sciences Motoharu Hirano Division of Organic Chemistry, National Institute of Health Sciences Maho Miyamoto Division of Organic Chemistry, National Institute of Health Sciences Hidetomo Yokoo Division of Organic Chemistry, National Institute of Health Sciences Yosuke Demizu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10. This side chain maintained the hydrophobicity of TP10 and enhanced the helicity and cell penetrating efficiency. We evaluated the preferred secondary structures, and the ability to deliver 5(6)-carboxyfluorescein (CF) as a model small molecule and plasmid DNA (pDNA) as a model nucleotide. The stapled peptide F-3 with CF, in which the stapling structure was introduced at Gly residues, formed a stable & alpha;-helical structure and the highest cell-membrane permeability via an endocytosis process. Meanwhile, peptide F-4 demonstrated remarkable stability when forming a complex with pDNA, making it the optimal choice for the efficient intracellular delivery of pDNA. The results showed that stapled hydrophobic CPPs were able to deliver small molecules and pDNA into cells, and that different stapling positions in hydrophobic CPPs can control the efficiency of the cargo delivery. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 15 14 2023 Image-Guided Ablation Therapies for Extrahepatic Metastases from Hepatocellular Carcinoma: A Review 3665 EN Noriyuki Umakoshi Department of Radiology, Okayama University Hospital Yusuke Matsui Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Tomita Department of Radiology, Okayama University Hospital Mayu Uka Department of Radiology, Okayama University Hospital Takahiro Kawabata Department of Radiology, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Okayama University Graduate School of Health Science Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Simple Summary Although systemic therapies are a common treatment for patients with extrahepatic metastases from hepatocellular carcinoma (HCC), local ablative therapies, such as radiofrequency ablation, microwave ablation, and cryoablation, can be used in select patients who have metastases to the lung, bone, and other sites with curative or palliative intent. This review summarizes the currently available evidence on image-guided thermal ablation therapies for extrahepatic metastases from HCC. The most common sites of extrahepatic metastases from hepatocellular carcinoma (HCC) are the lungs, intra-abdominal lymph nodes, bones, and adrenal glands, in that order. Although systemic therapies are a common treatment for patients with extrahepatic metastases, local ablative therapies for the extrahepatic metastatic lesions can be performed in selected patients. In this article, the literature on image-guided thermal ablation for metastasis to each organ was reviewed to summarize the current evidence. Radiofrequency ablation was the most commonly evaluated technique, and microwave ablation, cryoablation, and percutaneous ethanol injection were also utilized. The local control rate of thermal ablation therapy was relatively favorable, at approximately 70-90% in various organs. The survival outcomes varied among the studies, and several studies reported that the absence of viable intrahepatic lesions was associated with improved survival rates. Since only retrospective data from relatively small studies has been available thus far, more robust studies with prospective designs and larger cohorts are desired to prove the usefulness of thermal ablation for extrahepatic metastases from HCC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1467-3037 45 7 2023 Update in Molecular Aspects and Diagnosis of Autoimmune Gastritis 5263 5275 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Recent studies have advanced our understanding of the pathophysiology of autoimmune gastritis, particularly its molecular aspects. The most noteworthy recent advancement lies in the identification of several candidate genes implicated in the pathogenesis of pernicious anemia through genome-wide association studies. These genes include PTPN22, PNPT1, HLA-DQB1, and IL2RA. Recent studies have also directed attention towards other genes such as ATP4A, ATP4B, AIRE, SLC26A7, SLC26A9, and BACH2 polymorphism. In-depth investigations have been conducted on lymphocytes and cytokines, including T helper 17 cells, interleukin (IL)-17A, IL-17E, IL-17F, IL-21, IL-19, tumor necrosis factor-α, IL-15, transforming growth factor-β1, IL-13, and diminished levels of IL-27. Animal studies have explored the involvement of roseolovirus and H. pylori in relation to the onset of the disease and the process of carcinogenesis, respectively. Recent studies have comprehensively examined the involvement of autoantibodies, serum pepsinogen, and esophagogastroduodenoscopy in the diagnosis of autoimmune gastritis. The current focus lies on individuals demonstrating atypical presentations of the disease, including those diagnosed in childhood, those yielding negative results for autoantibodies, and those lacking the typical endoscopic characteristics of mucosal atrophy. Here, we discuss the recent developments in this field, focusing on genetic predisposition, epigenetic modifications, lymphocytes, cytokines, oxidative stress, infectious agents, proteins, microRNAs, autoantibodies, serum pepsinogen, gastrin, esophagogastroduodenoscopy and microscopic findings, and the risk of gastric neoplasm. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3921 12 7 2023 Combined Effect of Salicylic Acid and Proline Mitigates Drought Stress in Rice (Oryza sativa L.) through the Modulation of Physiological Attributes and Antioxidant Enzymes 1438 EN Tahmina Akter Urmi Department of Soil Science, Faculty of Agriculture, Bangladesh Agricultural University Md. Moshiul Islam Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kamrun Naher Zumur Department of Agronomy, Faculty of Agriculture, Bangabandhu Sheikh Mujibur Rahman Agricultural University Md. Anwarul Abedin Department of Soil Science, Faculty of Agriculture, Bangladesh Agricultural University M. Moynul Haque Department of Agronomy, Faculty of Agriculture, Bangabandhu Sheikh Mujibur Rahman Agricultural University Manzer H. Siddiqui Department of Botany and Microbiology, College of Science, King Saud University Yoshiyuki Murata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Md. Anamul Hoque Department of Soil Science, Faculty of Agriculture, Bangladesh Agricultural University Salicylic acid (SA) and proline exhibit protective effects against a wide range of stresses. However, the combined impact of SA and proline on rice under drought stress is still unknown. Therefore, we investigated the protective roles of SA and/or proline in conferring drought tolerance in rice. There were eight treatments comprising the control (T1; 95-100% FC), 1.5 mM SA (T2), 2 mM proline (T3), 0.75 mM SA + 1 mM proline (T4), 45-50% FC (T5, drought stress), T5 + 1.5 mM SA (T6), T5 + 2 mM proline (T7), and T5 + 0.75 mM SA + 1 mM proline (T8), and two rice varieties: BRRI dhan66 and BRRI dhan75. Drought stress significantly decreased the plant growth, biomass, yield attributes, photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (Tr), photosynthetic pigments (chlorophyll and carotenoids content), relative water content (RWC), membrane stability index (MSI), soluble sugar and starch content, and uptake of N, P and K+ in roots and shoots. Drought-induced oxidative stress in the form of increased hydrogen peroxide (H2O2) production and lipid peroxidation (MDA) was observed. The combined application of SA (0.75 mM) + proline (1 mM) was found to be more effective than the single application of either for drought stress mitigation in rice. A combined dose of SA + proline alleviated oxidative stress through boosting antioxidant enzymatic activity in contrast to their separate application. The application of SA + proline also enhanced proline, soluble sugar and starch content, which resulted in the amelioration of osmotic stress. Consequently, the combined application of SA and proline significantly increased the gas exchange characteristics, photosynthetic pigments, RWC, MSI, nutrient uptake, plant growth, biomass and yield of rice. Therefore, the combined application of SA and proline alleviated the detrimental impacts of drought stress more pronouncedly than their separate application did by increasing osmoprotectants, improving nutrient transport, up-regulating antioxidant enzyme activity and inhibiting oxidative stress. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2223-7747 12 14 2023 Low-Oxygen Responses of Cut Carnation Flowers Associated with Modified Atmosphere Packaging 2738 EN Misaki Nakayama School of Education, Okayama University Nao Harada School of Education, Okayama University Ai Murai School of Education, Okayama University Sayaka Ueyama School of Education, Okayama University Taro Harada Faculty of Education, Okayama University Gaseous factors affect post-harvest physiological processes in horticultural crops, including ornamental flowers. However, the molecular responses of cut flowers to the low-oxygen conditions associated with modified atmosphere packaging (MAP) have not yet been elucidated. Here, we show that storage of cut carnation flowers in a sealed polypropylene bag decreased the oxygen concentration in the bag to 3-5% and slowed flower opening. The vase life of carnation flowers after storage for seven days under MAP conditions was comparable to that without storage and was improved by the application of a commercial-quality preservative. The adenylate energy charge (AEC) was maintained at high levels in petals from florets stored under MAP conditions. This was accompanied by the upregulation of four hypoxia-related genes, among which the HYPOXIA-RESPONSIVE ETHYLENE RESPONSE FACTOR and PHYTOGLOBIN genes (DcERF19 and DcPGB1) were newly identified. These results suggest that hypoxia-responsive genes contribute to the maintenance of the energy status in carnation flowers stored under MAP conditions, making this gas-controlling technique potentially effective for maintaining cut flower quality without cooling. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 14 2023 Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID 4737 EN Yukichika Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objective: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. Methods: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. Results: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients’ backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8–353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4–251.5) and no-fatigue group (86.7 μg/L, 37.5–209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = −0.328, p < 0.05). Conclusions: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 15 13 2023 Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway 2941 EN Shusuke Iwata Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Takai Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Keisuke Sanematsu Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Noriatsu Shigemura Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University Yuzo Ninomiya Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the K-ATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3425 13 7 2023 Audiovisual n-Back Training Alters the Neural Processes of Working Memory and Audiovisual Integration: Evidence of Changes in ERPs 992 EN Ao Guo Cognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Weiping Yang Department of Psychology, Faculty of Education, Hubei University Xiangfu Yang Department of Psychology, Faculty of Education, Hubei University Jinfei Lin Department of Psychology, Faculty of Education, Hubei University Zimo Li Cognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yanna Ren Department of Psychology, College of Humanities and Management, Guizhou University of Traditional Chinese Medicine Jiajia Yang Cognitive Neuroscience Laboratory, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jinglong Wu Cognitive 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.

MDPI Acta Medica Okayama 2313-433X 9 6 2023 White Box Watermarking for Convolution Layers in Fine-Tuning Model Using the Constant Weight Code 117 EN Minoru Kuribayashi Graduate School of Natural Science and Technology, Okayama University Tatsuya Yasui Graduate School of Natural Science and Technology, Okayama University Asad Malik Department of Computer Science, Aligarh Muslim University Deep neural network (DNN) watermarking is a potential approach for protecting the intellectual property rights of DNN models. Similar to classical watermarking techniques for multimedia content, the requirements for DNN watermarking include capacity, robustness, transparency, and other factors. Studies have focused on robustness against retraining and fine-tuning. However, less important neurons in the DNN model may be pruned. Moreover, although the encoding approach renders DNN watermarking robust against pruning attacks, the watermark is assumed to be embedded only into the fully connected layer in the fine-tuning model. In this study, we extended the method such that the model can be applied to any convolution layer of the DNN model and designed a watermark detector based on a statistical analysis of the extracted weight parameters to evaluate whether the model is watermarked. Using a nonfungible token mitigates the overwriting of the watermark and enables checking when the DNN model with the watermark was created. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3417 13 12 2023 Hydrothermal Preparation of Faceted Vesicles Made of Span 40 and Tween 40 and Their Characterization 6893 EN Toshinori Shimanouchi Department of Environmental Chemistry and Materials, Okayama University Yui Komori Department of Environmental Chemistry and Materials, Okayama University Kazuki Toramoto Department of Environmental Chemistry and Materials, Okayama University Keita Hayashi National Institute of Technology, Nara College Kazuma Yasuhara Division of Materials Science, Nara Institute of Science and Technology (NAIST) Ho-Sup Jung Center for Food and Bioconvergence, Department of Food Science and Biotechnology, Seoul National University Yukitaka Kimura Department of Environmental Chemistry and Materials, Okayama University The Span 40 (sorbitan monooleate)/Tween 40 (polyoxyethylene sorbitan monolaurate) system gives faceted vesicles with angular surfaces, rather than spherical vesicles. Herein, a continuous and facile preparation method, based on the subcritical water-assisted emulsification and solvent diffusion, was presented to yield faceted vesicles with two major and minor axes (Type A) and vesicles closer to a polyhedron (Type B). Type A, rather than Type B, vesicles were likely to be formed. From the measurements concerning & zeta;-potential, membrane fluidity, and the polarization environment of the membranes, faceted vesicles could be obtained at 0.25 wt% of the surfactant concentration. The phase-separated behavior of Span 40 and Tween 40 within vesicle membranes could explain the structural feature of faceted vesicles and calcein leakage behavior. The significant advantage is that Type A vesicles would be utilized as alternative drug carriers for others with low encapsulation efficiency, although the present technical limitations cause difficulty in the selective formation of Type A and B vesicles and the selection of adequate solvent to accelerate the solvent diffusion step. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 14 6 2023 An Edge Device Framework in SEMAR IoT Application Server Platform 312 EN Yohanes Yohanie Fridelin Panduman Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Sho Ito Graduate School of Natural Science and Technology, Okayama University Radhiatul Husna Graduate School of Natural Science and Technology, Okayama University Minoru Kuribayashi Graduate School of Natural Science and Technology, Okayama University Mitsuhiro Okayasu Graduate School of Natural Science and Technology, Okayama University Junya Shimazu Graduate School of Natural Science and Technology, Okayama University Sritrusta Sukaridhoto Department of Informatic and Computer, Politeknik Elektronika Negeri Surabaya Nowadays, the Internet of Things (IoT) has become widely used at various places and for various applications. To facilitate this trend, we have developed the IoT application server platform called SEMAR (Smart Environmental Monitoring and Analytical in Real-Time), which offers standard features for collecting, displaying, and analyzing sensor data. An edge device is usually installed to connect sensors with the server, where the interface configuration, the data processing, the communication protocol, and the transmission interval need to be defined by the user. In this paper, we proposed an edge device framework for SEMAR to remotely optimize the edge device utilization with three phases. In the initialization phase, it automatically downloads the configuration file to the device through HTTP communications. In the service phase, it converts data from various sensors into the standard data format and sends it to the server periodically. In the update phase, it remotely updates the configuration through MQTT communications. For evaluations, we applied the proposal to the fingerprint-based indoor localization system (FILS15.4) and the data logging system. The results confirm the effectiveness in utilizing SEMAR to develop IoT application systems. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2078-2489 14 6 2023 A Web-Based Docker Image Assistant Generation Tool for User-PC Computing System 300 EN Lynn Htet Aung Graduate School of Natural Science and Technology, Okayama University Nobuo Funabiki Graduate School of Natural Science and Technology, Okayama University Soe Thandar Aung Graduate School of Natural Science and Technology, Okayama University Xudong Zhou Graduate School of Natural Science and Technology, Okayama University Xu Xiang Graduate School of Natural Science and Technology, Okayama University Wen-Chung Kao Department of Electrical Engineering, National Taiwan Normal University Currently, we are developing the user-PC computing (UPC) system based on the master-worker model as a scalable, low-cost, and high-performance computing platform. To run various application programs on personal computers (PCs) with different environments for workers, it adopts Docker technology to bundle every necessary software as one image file. Unfortunately, the Docker file/image are manually generated through multiple steps by a user, which can be the bottleneck. In this paper, we present a web-based Docker image assistant generation (DIAG) tool in the UPC system to assist or reduce these process steps. It adopts Angular JavaScript for offering user interfaces, PHP Laravel for handling logic using RestAPI, MySQL database for storing data, and Shell scripting for speedily running the whole program. In addition, the worker-side code modification function is implemented so that a user can modify the source code of the running job and update the Docker image at a worker to speed up them. For evaluations, we collected 30 Docker files and 10 OpenFOAM jobs through reverse processing from Docker images in Github and generated the Docker images using the tool. Moreover, we modified source codes for network simulations and generated the Docker images in a worker five times. The results confirmed the validity of the proposal. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-2607 11 5 2023 Modulatory Effects of A1 Milk, A2 Milk, Soy, and Egg Proteins on Gut Microbiota and Fermentation 1194 EN Nuomin Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Riyang Baek Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Takeshi Tsuruta Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Milk can be divided into A1 and A2 types according to fi-casein variants, and there is a debate about whether A1 milk consumption exacerbates gut environments. This study examined the cecum microbiota and fermentation in mice fed A1 casein, A2 casein, mixed casein (commercial casein), soy protein isolate, and egg white. The cecum acetic acid concentration was higher, and the relative abundances of Muribaculaceae and Desulfovibrionaceae were greater in mice fed A1 versus A2 casein. The other parameters of cecum fermentation and microbiota composition were similar among the mice fed A1, A2, and mixed caseins. The differences were more distinctive among the three caseins, soy, and egg feedings. Chao 1 and Shannon indices of the cecum microbiota were lowered in egg white-fed mice, and the microbiota of mice fed milk, soy, and egg proteins were separately grouped by principal coordinate analysis. Mice fed the three caseins were characterized by a high abundance of Lactobacillaceae and Clostridiaceae, those fed soy were characterized by Corynebacteriaceae, Muribaculaceae, and Ruminococcaceae, and those fed egg white were characterized by Eggerthellaceae, Rikenellaceae, and Erysipelatoclostridiaceae. Thus, although several differences can arise between A1 and A2 caseins in terms of their modulatory effects on gut environments, the differences between milk, soy, and egg proteins can be more distinctive and are worth further consideration. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 15 11 2023 Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models 2971 EN Satoshi Komoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Teruki Kobayashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Noriyuki Nishiwaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toru Narusaka Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroaki Sato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuki Katsura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 10 2023 Manifestation of Headache Affecting Quality of Life in Long COVID Patients 3533 EN Kana Fujita Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naruhiko Sunada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Honda Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuki Tokumasu Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Nakano Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasue Sakurada Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mikako Obika Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideharu Hagiya Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fumio Otsuka Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3425 13 5 2023 Semantic Bimodal Presentation Differentially Slows Working Memory Retrieval 811 EN Jia Cheng Department of Psychology, Research Center for Psychology and Behavioral Sciences, Soochow University Jingjing Li Department of Psychology, Research Center for Psychology and Behavioral Sciences, Soochow University Aijun Wang Department of Psychology, Research Center for Psychology and Behavioral Sciences, Soochow University Ming Zhang Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Although evidence has shown that working memory (WM) can be differentially affected by the multisensory congruency of different visual and auditory stimuli, it remains unclear whether different multisensory congruency about concrete and abstract words could impact further WM retrieval. By manipulating the attention focus toward different matching conditions of visual and auditory word characteristics in a 2-back paradigm, the present study revealed that for the characteristically incongruent condition under the auditory retrieval condition, the response to abstract words was faster than that to concrete words, indicating that auditory abstract words are not affected by visual representation, while auditory concrete words are. Alternatively, for concrete words under the visual retrieval condition, WM retrieval was faster in the characteristically incongruent condition than in the characteristically congruent condition, indicating that visual representation formed by auditory concrete words may interfere with WM retrieval of visual concrete words. The present findings demonstrated that concrete words in multisensory conditions may be too aggressively encoded with other visual representations, which would inadvertently slow WM retrieval. However, abstract words seem to suppress interference better, showing better WM performance than concrete words in the multisensory condition. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2308-3425 10 5 2023 Diagnostic Performance of Cardiac Computed Tomography for Detecting Patent Foramen Ovale: Evaluation Using Transesophageal Echocardiography and Catheterization as Reference Standards 193 EN Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teiji Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Background: Patent foramen ovale (PFO) is associated with various diseases such as cryptogenic stroke, migraine, and platypnea-orthodeoxia syndrome. This study aimed to evaluate the diagnostic performance of cardiac computed tomography (CT) for PFO detection. Materials and Methods: Consecutive patients diagnosed with atrial fibrillation and who underwent catheter ablation with pre-procedural cardiac CT and transesophageal echocardiography (TEE) were enrolled in this study. The presence of PFO was defined as (1) the confirmation of PFO using TEE and/or (2) the catheter crossing the interatrial septum (IAS) into the left atrium during ablation. CT findings indicative of PFO included (1) the presence of a channel-like appearance (CLA) on the IAS and (2) a CLA with a contrast jet flow from the left atrium to the right atrium. The diagnostic performance of both a CLA alone and a CLA with a jet flow was evaluated for PFO detection. Results: Altogether, 151 patients were analyzed in the study (mean age, 68 years; men, 62%). Twenty-nine patients (19%) had PFO confirmed by TEE and/or catheterization. The diagnostic performance of a CLA alone was as follows: sensitivity, 72.4%; specificity, 79.5%; positive predictive value (PPV), 45.7%; negative predictive value (NPV), 92.4%. The diagnostic performance of a CLA with a jet flow was as follows: sensitivity, 65.5%; specificity, 98.4%; PPV, 90.5%; NPV, 92.3%. The diagnostic performance of a CLA with a jet flow was statistically superior to that of a CLA alone (p = 0.045), and the C-statistics were 0.76 and 0.82, respectively. Conclusion: A CLA with a contrast jet flow in cardiac CT has a high PPV for PFO detection, and its diagnostic performance is superior to that of a CLA alone. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-4991 13 9 2023 Long-Term Antibacterial Efficacy of Cetylpyridinium Chloride-Montmorillonite Containing PMMA Resin Cement 1495 EN Kumiko Yoshihara Department of Pathology & Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Science, Okayama University Dental School Yoji Makita National Institute of Advanced Industrial Science and Technology (AIST), Health and Medical Research Institute Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Bart Van Meerbeek Department of Oral Health Sciences, BIOMAT & UZ Leuven (University Hospitals Leuven), Dentistry, KU Leuven (University of Leuven) Despite being able to adhesively restore teeth, adhesives and cement do not possess any anticariogenic protection potential, by which caries recurrence may still occur and reduce the clinical lifetime of adhesive restorations. Several antibacterial agents have been incorporated into dental adhesives and cement to render them anticariogenic. Due to an additional therapeutic effect, such materials are classified as 'dental combination products' with more strict market regulations. We incorporated cetylpyridinium chloride (CPC), often used for oral hygiene applications, into montmorillonite (CPC-Mont), the latter to serve as a carrier for controlled CPC release. CPC-Mont incorporated into tissue conditioner has been approved by the Pharmaceuticals and Medical Devices Agency (PmontMDA) in Japan. To produce a clinically effective dental cement with the antibacterial potential to prevent secondary caries, we incorporated CPC-Mont into PMMA resin cement. We measured the flexural strength, shear bond strength onto dentin, CPC release, and the biofilm-inhibition potential of the experimental CPC-Mont-containing PMMA cement. An 8 and 10 wt% CPC-Mont concentration revealed the antibacterial potential without reducing the mechanical properties of the PMMA cement. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2071-1050 15 9 2023 Integrating Perspectives from Education for Sustainable Development to Foster Plant Awareness among Trainee Science Teachers: A Mixed Methods Study 7395 EN Khalifatulloh Fiel'ardh Graduate School of Education, Okayama University Indra Fardhani Faculty of Mathematics and Natural Science, Universitas Negeri Malang Hiroki Fujii Graduate School of Education, Okayama University This mixed-method study aimed to investigate the efficacy of an intervention unit that integrates perspectives from Education for Sustainable Development (ESD) to foster plant awareness, within the context of botanical lessons for trainee science teachers. Third-year undergraduate students (n = 91) studying to become lower secondary school (grade 7-9) science teachers from a public university in East Java, Indonesia, participated in this study. Data were collected through a self-reported questionnaire, reflective journal entries, and focus group interviews. The findings revealed a statistically significant increase in the participants' attention and attitude towards plants, relative interest in plants, and self-efficacy in teaching plant-related topics. The triangulation of the analysis results from the reflective journals and focus group interviews demonstrated that through transformative learning, the participants' experiences, perceptions, and learning evolved throughout the intervention unit, leading to their more comprehensive understanding of plant-related issues and their connection to broader sustainability concerns. These findings imply that the integration of ESD perspectives into botanical education positively affects plant awareness. Future research could further investigate the long-term impact of integrating ESD perspectives on teacher training programs. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 10 2 2022 Association between Overall Survival and Activities of Daily Living in Patients with Spinal Bone Metastases 350 EN Yoshiteru Akezaki Division of Physical Therapy, Kochi Professional University of Rehabilitation Eiji Nakata Department of Orthopaedic Surgery, Okayama University Hospital Masato Kikuuchi Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Shinsuke Sugihara Department of Rehabilitation Medicine, National Hospital Organization Shikoku Cancer Center Yoshimi Katayama Department of Rehabilitation Medicine, Okayama University Hospital Haruyoshi Katayama Department of Orthopaedic Surgery, Okayama University Hospital Masanori Hamada Department of Rehabilitation Medicine, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Objective: This study aimed to investigate the association between overall survival (OS) and activities of daily living (ADL) in patients with skeletal-related events. In this study, 265 patients whose clinical parameters were available before radiotherapy were investigated. Methods: Age, sex, ADL, pain, the primary site, spinal level of bone metastases, spinal instability, treatment strategy, including chemotherapy or palliative treatment, and OS were investigated. ADL patients with a Barthel index of >= 90 were classified as the high ADL group, while those with a score < 90 were classified as the low ADL group. For OS, patients surviving >= 160 days were classified as the non-poor prognosis group, and those who survived <160 days were classified as the poor prognosis group. Results: Age, sex, ADL, pain, the primary site, and treatment strategy for OS were different between the two groups (p < 0.1). Logistic regression analysis revealed that ADL, the primary site, and treatment strategy were significant predictors of OS (p < 0.05). High ADL, breast cancer, and chemotherapy had a positive effect on OS. Conclusions: It is suggested that improvements may be obtained by performing rehabilitation interventions to maintain and improve ADL, by constructing a system for monitoring spinal bone metastases with images before ADL decreases, and by performing interventions such as changes in treatment methods such as RT or surgery at appropriate times. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 13 8 2023 Deep Active Learning for Automatic Mitotic Cell Detection on HEp-2 Specimen Medical Images 1416 EN Asaad Anaam Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mugahed A. Al-antari Department of Artificial Intelligence, College of Software & Convergence Technology, Daeyang AI Center, Sejong University Jamil Hussain Department of Data Science, College of Software & Convergence Technology, Daeyang AI Center, Sejong University Nagwan Abdel Samee Department of Information Technology, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman University Maali Alabdulhafith Department of Information Technology, College of Computer and Information Sciences, Princess Nourah bint Abdulrahman University Akio Gofuku Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Identifying 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.

MDPI Acta Medica Okayama 2076-0760 12 4 2023 Impoverishment Persistence in Hydropower Dam-Induced Resettled Communities: A Sociological Investigation on Livelihood and Food Security in Vietnam 222 EN Pham Huu Ty Faculty of Land Resources and Agricultural Environment, University of Agriculture and Forestry, Hue University Baas Laura MAEX Platform, Mayor of Karnebeeklaan Tran Thi Phuong Faculty of Land Resources and Agricultural Environment, University of Agriculture and Forestry, Hue University Nguyen Quang Tan Graduate School of Environmental and Life Science, Okayama University The widespread development of hydropower dams has led to involuntary displacement, which has become a significant global issue. In Vietnam, around 70,000 households were displaced in 2020, causing uncertainty and social disruption. The aim of this study is to analyze the effects of resettlement on the livelihood and food security of displaced households, explore the underlying challenges and causes of these effects, and recommend policy implications for sustainable livelihood development and poverty alleviation. This study conducted a decade-long sociological examination of three displaced communities in Thua Thien Hue province, Vietnam. Our research reveals that resettled households are unable to regain their former standard of living due to the loss of cultivated land and restricted access to public property, which exacerbates food insecurity. Unemployment, illiteracy, and low income further perpetuate poverty. These findings highlight the deficiencies in current policies and planning approaches and call for implementing socially responsible resettlement processes guided by principles of equity. Addressing the inequalities arising from displacement and enabling affected communities to participate in growth is economically justified and morally imperative. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 8 2023 Neuropilin 1 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells 7394 EN Yaqiong Yu Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases Yoko Uchida-Fukuhara Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yao Weng Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuhan He Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases Mika Ikegame Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaya Yoshida Department of Oral Healthcare Education, Institute of Biomedical Sciences, Tokushima University Graduate School Hirohiko Okamura Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lihong Qiu Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for several ligands, is highly expressed in many kinds of mesenchymal stem cells (MSCs), but its function is poorly understood. In this study, we explored the roles of full-length NRP1 and glycosaminoglycan (GAG)-modifiable NRP1 in adipogenesis in C3H10T1/2 cells. The expression of full-length NRP1 and GAG-modifiable NRP1 increased during adipogenic differentiation in C3H10T1/2 cells. NRP1 knockdown repressed adipogenesis while decreasing the levels of Akt and ERK1/2 phosphorylation. Moreover, the scaffold protein JIP4 was involved in adipogenesis in C3H10T1/2 cells by interacting with NRP1. Furthermore, overexpression of non-GAG-modifiable NRP1 mutant (S612A) greatly promoted adipogenic differentiation, accompanied by upregulation of the phosphorylated Akt and ERK1/2. Taken together, these results indicate that NRP1 is a key regulator that promotes adipogenesis in C3H10T1/2 cells by interacting with JIP4 and activating the Akt and ERK1/2 pathway. Non-GAG-modifiable NRP1 mutant (S612A) accelerates the process of adipogenic differentiation, suggesting that GAG glycosylation is a negative post-translational modification of NRP1 in adipogenic differentiation. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-3921 12 4 2023 Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson's Disease 894 EN Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Parkinson's disease (PD) is characterized by motor symptoms based on a loss of nigrostriatal dopaminergic neurons and by non-motor symptoms which precede motor symptoms. Neurodegeneration accompanied by an accumulation of alpha-synuclein is thought to propagate from the enteric nervous system to the central nervous system. The pathogenesis in sporadic PD remains unknown. However, many reports indicate various etiological factors, such as oxidative stress, inflammation, alpha-synuclein toxicity and mitochondrial impairment, drive neurodegeneration. Exposure to heavy metals contributes to these etiopathogenesis and increases the risk of developing PD. Metallothioneins (MTs) are cysteine-rich metal-binding proteins; MTs chelate metals and inhibit metal-induced oxidative stress, inflammation and mitochondrial dysfunction. In addition, MTs possess antioxidative properties by scavenging free radicals and exert anti-inflammatory effects by suppression of microglial activation. Furthermore, MTs recently received attention as a potential target for attenuating metal-induced alpha-synuclein aggregation. In this article, we summarize MTs expression in the central and enteric nervous system, and review protective functions of MTs against etiopathogenesis in PD. We also discuss neuroprotective strategies for the prevention of central dopaminergic and enteric neurodegeneration by targeting MTs. This review highlights multifunctional MTs as a target for the development of disease-modifying drugs for PD. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 2075-4426 13 4 2023 The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study 582 EN Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yohei Maeshima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yuka Okuyama Japanese Red Cross Society Himeji Hospital Nozomu Otaka Kagawa Prefectural Central Hospital Haruyo Ujike Kagawa Prefectural Central Hospital Keiko Tanaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masashi Kitagawa National Hospital Organization Okayama Medical Center Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Masaru Kinomura Okayama Saiseikai General Hospital Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kosuke Ota National Hospital Organization Okayama Medical Center Keisuke Maruyama Okayama Saiseikai General Hospital Makoto Hiramatsu Okayama Saiseikai General Hospital, Yoshiyuki Oshiro Kawasaki Medical School General Medical Center Shigeru Morioka Okayama Central Hospital Keiichi Takiue Okayama City Hospital Kazuyoshi Omori Shigei Medical Research Hospital Masaki Fukushima Shigei Medical Research Hospital Naoyuki Gamou Japanese Red Cross Okayama Hospital Hiroshi Hirata Akebono Clinic Ryosuke Sato Sato Clinic Hirofumi Makino Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Introduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2306-5354 10 4 2023 Recent Advances in Apical Periodontitis Treatment: A Narrative Review 488 EN Zulema Arias Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mohammed Zahedul Islam Nizami Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital Xiaoting Chen Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinyi Chai Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bin Xu Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Canyan Kuang Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Apical periodontitis is an inflammatory response caused by pulp infection. It induces bone resorption in the apical and periapical regions of the tooth. The most conservative approach to treat this condition is nonsurgical endodontic treatment. However, clinical failure has been reported with this approach; thus, alternative procedures are required. This review highlights recent literature regarding advanced approaches for the treatment of apical periodontitis. Various therapies, including biological medications, antioxidants, specialized pro-resolving lipid mediators, and stem cell therapy, have been tested to increase the success rate of treatment for apical periodontitis. Some of these approaches remain in the in vivo phase of research, while others have just entered the translational research phase to validate clinical application. However, a detailed understanding of the molecular mechanisms that occur during development of the immunoinflammatory reaction in apical periodontitis remains unclear. The aim of this review was to summarize advanced approaches for the treatment of apical periodontitis. Further research can confirm the potential of these alternative nonsurgical endodontic treatment approaches. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 7 2023 Nutrients Associated with Sleep Bruxism 2623 EN Naoki Toyama Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Department of Preventive Dentistry, Okayama University Hospital Nanami Sawada Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miho Yamashita Department of Foods and Human Nutrition, Notre Dame Seishin University Momoe Komiyama Department of Foods and Human Nutrition, Notre Dame Seishin University Takahiko Nagahama Department of Foods and Human Nutrition, Notre Dame Seishin University Manabu Morita Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: The purpose of the present research was to identify nutrients related to sleep bruxism and to establish a hypothesis regarding the relationship between sleep bruxism and nutrients. Methods: We recruited 143 Japanese university students in 2021 and assigned them to sleep bruxism (n = 58) and non-sleep bruxism groups (n = 85), using an identical single-channel wearable electromyography device. To investigate nutrient intakes, participants answered a food frequency questionnaire based on food groups. We assessed differences in nutrient intakes between the sleep bruxism and non-sleep bruxism groups. Results: Logistic regression modeling showed that sleep bruxism tended to be associated with dietary fiber (odds ratio, 0.91; 95% confidence interval, 0.83-1.00; p = 0.059). In addition, a subgroup analysis selecting students in the top and bottom quartiles of dietary fiber intake showed that students with sleep bruxism had a significantly lower dietary fiber intake (10.4 +/- 4.6 g) than those without sleep bruxism (13.4 +/- 6.1 g; p = 0.022). Conclusion: The present research showed that dietary fiber intake may be related to sleep bruxism. Therefore, we hypothesized that dietary fiber would improve sleep bruxism in young adults. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2624-8549 5 1 2023 Aluminum-Catalyzed Cross Selective C3-N1′ Coupling Reactions of N-Methoxyindoles with Indoles 452 462 EN Keisuke Tokushige Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiki Yamashiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiya Hirao Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University C3–N1′ bond formation of bisindoles has been a great challenge due to the intrinsic reactivity of indoles as both C3 and N1-nucleophilic character. Herein, we demonstrate an C3–N1′ cross-coupling reaction of indoles using N-methoxyindoles as N-electrophilic indole reagents in the presence of Lewis acid. The bisindoles generated in this transformation are latent C3-nucleophile, allowing them to be used as strategic intermediates in sequential C3–N1′–C3′–N1″ triindole formations. The potential synthetic usefulness of this sequential transformation was highlighted upon application to the construction of C3–N1 looped polyindoles. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2309-608X 9 3 2023 The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model 314 EN Hidefumi Sako Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kazuhiro Omori Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaaki Nakayama Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Mandai Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science Hidetaka Ideguchi Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Saki Yoshimura-Nakagawa Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Kyosuke Sakaida Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Chiaki Nagata-Kamei Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroya Kobayashi Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoki Ishii Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Mitsuaki Ono Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery and Biopathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Suga Division of Applied Chemistry, Graduate School of Natural Sciences and Technology, Okayama University Shogo Takashiba Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p < 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p < 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2306-7381 10 3 2023 Monitoring the Milk Composition, Milk Microbiota, and Blood Metabolites of Jersey Cows throughout a Lactation Period 226 EN Peter Kiiru Gathinji Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Zabiallah Yousofi Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Karin Akada Animal Products Research Group, Institute of Livestock and Grassland Science, National Agriculture and Research Organization Ajmal Wali Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Department of Animal Science, Graduate School of Environmental and Life Science, Okayama University This study aimed to determine how milk composition, milk microbiota, and blood metabolites may change during the lactation period in Jersey cows. Milk and jugular blood samples were collected from eight healthy cows every other month from the beginning to the end of their lactation period. Samples of airborne dust were also collected to determine whether the cowshed microbiota could affect milk microbiota. Milk yield peaked in the first two months and gradually decreased as the lactation period progressed. Milk fat, protein, and solids-not-fat contents were low in the first month, and then increased during the middle and late lactation periods. In the first month, plasma non-esterified fatty acids (NEFA), haptoglobin (Hp), and aspartate transaminase (AST) levels were elevated, and high abundances of Burkholderiaceae and Oxalobacteraceae were observed in milk and airborne dust microbiota. The finding that contamination of the environmental microbiota in milk was coupled with elevated plasma NEFA, Hp, and AST levels indicated that impaired metabolic function during the early lactation period may increase the invasion of opportunistic bacteria. This study can affirm the importance of feeding and cowshed management and should provide a helpful addition to improving Jersey cow farming. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2076-0817 12 3 2023 Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model 398 EN Nagwa S. M. Aly Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Matsumori Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Thi Quyen Dinh Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Sato Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Department of Sanitary Microbiology, Faculty of Pharmaceutical Sciences, Okayama University Kyung-Soo Chang Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan Hak Sun Yu Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University Duc Tuan Cao Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, Hai Phong University of Medicine and Pharmacy Hye-Sook Kim Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2304-8158 12 6 2023 Taste Responses and Ingestive Behaviors to Ingredients of Fermented Milk in Mice 1150 EN Yuko Yamase Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hai Huang Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Mitoh Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiko Egusa Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryusuke Yoshida Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fermented milk is consumed worldwide because of its nutritious and healthful qualities. Although it is somewhat sour, causing some to dislike it, few studies have examined taste aspects of its ingredients. Wild-type mice and T1R3-GFP-KO mice lacking sweet/umami receptors were tested with various taste components (sucrose, galactose, lactose, galacto-oligosaccharides, fructo-oligosaccharides, l- and d-lactic acid) using 48 h two-bottle tests and short-term lick tests. d-lactic acid levels were measured after the ingestion of d- or; l-lactic acid or water to evaluate d-lactic acidosis. In wild-type mice, for the sweet ingredients the number of licks increased in a concentration-dependent manner, but avoidance was observed at higher concentrations in 48 h two-bottle tests; the sour ingredients d- and l-lactic acid showed concentration-dependent decreases in preference in both short- and long-term tests. In 48 h two-bottle tests comparing d- and l-lactic acid, wild-type but not T1R3-GFP-KO mice showed higher drinking rates for l-lactic acid. d-lactic acidosis did not occur and thus did not contribute to this preference. These results suggest that intake in short-term lick tests varied by preference for each ingredient, whereas intake variation in long-term lick tests reflects postingestive effects. l-lactic acid may have some palatable taste in addition to sour taste. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 24 6 2023 Stress-Inducible SCAND Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers 5168 EN Mona Sheta Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kunihiro Yoshida Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hideka Kanemoto Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Stuart K. Calderwood Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School Takanori Eguchi Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The cell stress response is an essential system present in every cell for responding and adapting to environmental stimulations. A major program for stress response is the heat shock factor (HSF)-heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain (SCAND)-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAND-only proteins that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of SCAND1, SCAND2, and MZF1 bound to HSP90 gene promoter regions in prostate cancer cells. Moreover, heat stress switched the transcript variants' expression from long noncoding RNA (lncRNA-SCAND2P) to protein-coding mRNA of SCAND2, potentially by regulating alternative splicing. High expression of HSP90AA1 correlated with poorer prognoses in several cancer types, although SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90AA1 in prostate cancer cells. Consistent with this, gene expression of SCAND2, SCAND1, and MZF1 was negatively correlated with HSP90 gene expression in prostate adenocarcinoma. By searching databases of patient-derived tumor samples, we found that MZF1 and SCAND2 RNA were more highly expressed in normal tissues than in tumor tissues in several cancer types. Of note, high RNA expression of SCAND2, SCAND1, and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 RNA was correlated with better prognoses of lung adenocarcinoma and sarcoma. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 16 4 2023 Novel Artificial Scaffold for Bone Marrow Regeneration: Honeycomb Tricalcium Phosphate 1393 EN Yasunori Inada Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidetsugu Tsujigiwa Department of Life Science, Faculty of Science, Okayama University of Science Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Qiusheng Shan Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tianyan Piao Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anqi Chang Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Bone marrow is complex structure containing heterogenetic cells, making it difficult to regenerate using artificial scaffolds. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which is a cylindrical scaffold with a honeycomb arrangement of straight pores, and we demonstrated that TCP with 300 and 500 mu m pore diameters (300TCP and 500TCP) induced bone marrow structure within the pores. In this study, we examined the optimal scaffold structure for bone marrow with homeostatic bone metabolism using honeycomb TCP. 300TCP and 500TCP were transplanted into rat muscle, and bone marrow formation was histologically assessed. Immunohistochemistry for CD45, CD34, Runt-related transcription factor 2 (Runx2), c-kit single staining, Runx2/N-cadherin, and c-kit/Tie-2 double staining was performed. The area of bone marrow structure, which includes CD45(+) round-shaped hematopoietic cells and CD34(+) sinusoidal vessels, was larger in 300TCP than in 500TCP. Additionally, Runx2(+) osteoblasts and c-kit(+) hematopoietic stem cells were observed on the surface of bone tissue formed within TCP. Among Runx2(+) osteoblasts, spindle-shaped N-cadherin(+) cells existed in association with c-kit(+)Tie-2(+) hematopoietic stem cells on the bone tissue formed within TCP, which formed a hematopoietic stem cell niche similar to as in vivo. Therefore, honeycomb TCP with 300 mu m pore diameters may be an artificial scaffold with an optimal geometric structure as a scaffold for bone marrow formation. No potential conflict of interest relevant to this article was reported.

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

MDPI Acta Medica Okayama 1999-4923 15 2 2023 Rationalizing the Binding Modes of PET Radiotracers Targeting the Norepinephrine Transporter 690 EN Anna Tutov Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Rudolf A. Werner Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital Würzburg Saskia Muehlig Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital Würzburg Thomas Zimmermann Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Koshino Department of Systems and Informatics, Hokkaido Information University Constantin Lapa Nuclear Medicine, Faculty of Medicine, University of Augsburg Michael Decker Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Purpose: A new PET radiotracer F-18-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure-activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of F-18-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 mu M, respectively), with meta-OH being the least active (22.67 mu M). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer-NET interaction, whereby a T-shaped pi-pi stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 12 5 2023 Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients 2062 EN Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Hasegawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikako Obika Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. Methods: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 mu g/dL (10.7 mu mol/L) were compared with characteristics of patients with normozincemia. Results: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = -0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 mu g/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. Conclusions: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1073 16 5 2023 Technology Trend Analysis of Japanese Green Vehicle Powertrains Technology Using Patent Citation Data 2221 EN Jiaming Jiang Center for Artificial Intelligence and Mathematical Data Science, Okayama University Yu Zhao School of Management, Department of Management, Tokyo University of Science As automobiles are major contributors to greenhouse gas emissions, the technological shift towards vehicle powertrain systems is an attempt to lower problems such as emissions of carbon dioxide and nitrogen oxides. Patent data are the most reliable measure of business performance for applied research and development activities when investigating knowledge domains or technology evolution. This is the first study on Japanese patent citation data of the green vehicle powertrains technology industry, using the social network analysis method, which emphasizes centrality estimates and community detection. This study not only elucidates the knowledge by visualizing flow patterns but also provides a precious and congregative method for verifying important patents under the International Patent Classification system and grasping the trend of the new technology industry. This study detects leading companies, not only in terms of the number of patents but also the importance of the patents. The empirical result shows that the International Patent Classification (IPC) class that starts with "B60K", which includes hybrid electric vehicle (HEV) and battery electric vehicle (BEV), is more likely to be the technology trend in the green vehicle powertrains industry. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4360 15 5 2023 Shear Bond Strength of Resin Luting Materials to Lithium Disilicate Ceramic: Correlation between Flexural Strength and Modulus of Elasticity 1128 EN Masao Irie Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masahiro Okada Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Yukinori Maruo Department of Prosthodontics, Division of Dentistry, Okayama University Goro Nishigawa Department of Prosthodontics, Division of Dentistry, Okayama University Takuya Matsumoto Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science This study investigates the effect of the curing mode (dual-cure vs. self-cure) of resin cements (four self-adhesive and seven conventional cements) on their flexural strength and flexural modulus of elasticity, alongside their shear bond strength to lithium disilicate ceramics (LDS). The study aims to determine the relationship between the bond strength and LDS, and the flexural strength and flexural modulus of elasticity of resin cements. Twelve conventional or adhesive and self-adhesive resin cements were tested. The manufacturer's recommended pretreating agents were used where indicated. The shear bond strengths to LDS and the flexural strength and flexural modulus of elasticity of the cement were measured immediately after setting, after one day of storage in distilled water at 37 degrees C, and after 20,000 thermocycles (TC 20k). The relationship between the bond strength to LDS, flexural strength, and flexural modulus of elasticity of resin cements was investigated using a multiple linear regression analysis. For all resin cements, the shear bond strength, flexural strength, and flexural modulus of elasticity were lowest immediately after setting. A clear and significant difference between dual-curing and self-curing modes was observed in all resin cements immediately after setting, except for ResiCem EX. Regardless of the difference of the core-mode condition of all resin cements, flexural strengths were correlated with the LDS surface upon shear bond strengths (R-2 = 0.24, n = 69, p < 0.001) and the flexural modulus of elasticity was correlated with them (R-2 = 0.14, n = 69, p < 0.001). Multiple linear regression analyses revealed that the shear bond strength was 17.877 + 0.166, the flexural strength was 0.643, and the flexural modulus was (R-2 = 0.51, n = 69, p < 0.001). The flexural strength or flexural modulus of elasticity may be used to predict the bond strength of resin cements to LDS. No potential conflict of interest relevant to this article was reported.