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Two-dimensional transition metal dichalcogenides (2D TMDs) have shown exceptional electrochemical catalytic activity for the efficient generation of hydrogen through electrochemical water splitting. In the case of molybdenum disulfide (MoS2), a prominent member of 2D TMDs, the electrochemically active sites primarily reside at the edges, while the basal plane, which constitutes the majority of the MoS2 structure, remains relatively inactive. In this study, we aimed to activate the inert sites of the basal plane with some defective structure for hydrogen evolution reaction (HER) by employing an electrochemical-probe in combination with voltage sweeping. The initiation of HER at these previously inactive sites was visualized and confirmed using scanning electrochemical cell microscopy (SECCM). Our findings reveal that the enhanced HER activity originates from surface defects induced by the probing process.

Aim: Spouses experience conflicting emotions when caring for partners with severe mental illnesses. They can have negative emotions while also regarding caregiving as positive and may develop a better marital relationship through the caregiving process. This study investigated factors affecting the negative and positive emotions of husbands and wives acting as caregivers of their spouses with severe mental illnesses., Methods: An online nationwide survey of 166 spouses caring for partners diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder was conducted. Caregivers' negative and positive emotions, personal and role strains in the care burden, sense of coherence, and patients' disabilities in family communication were assessed. We conducted a series of hierarchical multiple regression analyses to evaluate the effects of these factors on the emotions of husbands and wives separately., Results: Among the 166 spouses, 112 (67%) were husbands and 54 (33%) were wives. Husbands were caregivers to 1.4 times as many individuals diagnosed with psychotic disorder as were wives. The negative emotions of husbands were linked to personal strain, whereas those of wives were associated with patient disability in family communication. Sense of coherence was the only factor predicting positive emotions for both sexes., Conclusion: Support for spousal caregivers should be adjusted according to sex. A reduction in husbands' personal strain can alleviate their negative emotions, whereas wives' negative emotions can be relieved by improving communication within their families. Regardless of sex, a higher sense of coherence level has the potential to suppress negative emotions and enhance positive emotions., Competing Interests: Nao Shiraishi has received lecture fees from Mochida Pharma and Sumitomo Pharma. Tatsuo Akechi has received lecture fees from AstraZeneca, Chugai, Daiichi‐Sankyo, EISAI, Janssen, Kowa, Kyowa Kirin, Lundbeck, MSD, Meiji‐Seika Pharma, Mochida, Nipro, Otsuka, Pfizer, Sumitomo Pharma, Takeda, Tsumura, and Viatris and royalties from Igaku‐Shoin. Tatsuo Akechi was the inventor of pending patents (2020‐135195, 2022‐069057) (Institute) and has patents (7313617) (Institute). The remaining authors declare no conflict of interest., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background and Objectives: Weight loss is a critical health issue among the older population. This study aimed to explore the association between weight loss and oral health in older adults., Methods: We used cross-sectional data from the Uonuma Chronic Kidney Disease Cohort Study. The binary logistic regression models were fitted to estimate the relationship between weight loss and independent variables including the number of teeth present., Results: The participants included 1656 females and 1625 males. There were 1217 females (73.4%) and 1236 males (76.0%) with normal BMI (18.5 ≤ BMI < 25) in the previous year. Weight loss was determined over a 12-month period. Individuals with normal BMI in previous year, and those with weight loss (≥ 5%) or those whom maintained a stable weight were further analysed. The regression analysis (model 3, fully adjusted) showed that females with 0 and 1-10 teeth present had a higher likelihood of losing weight (OR = 4.07; 95% CI = 1.85-8.93, OR = 2.33; 95% CI = 1.24-4.39) compared with those with 20 or more teeth. Current smokers had a higher likelihood of losing weight (OR = 3.15; 95% CI = 1.01-9.76) than lifelong abstainers. Among males, both current and previous smokers showed a higher likelihood of losing weight (OR = 4.94; 95%CI = 1.76-13.8, OR = 3.35; 95% CI = 1.29-8.68) than those who never smoked., Conclusions: This study indicates that the number of teeth and smoking are both linked to weight loss in females. However, in males, the association between the number of teeth and weight loss may be compromised due to the high prevalence of smoking in this group., (© 2024 John Wiley & Sons Ltd.)

Photosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophyll a / c -binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatom Thalassiosira pseudonana CCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein-protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs from T. pseudonana and the diatom Chaetoceros gracilis , underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms., Competing Interests: KK, YN, JX, MK, HO, JS, KI, RN No competing interests declared, (© 2024, Kato, Nakajima, Xing et al.)

This study aims to investigate and compare the psychosocial and oral health factors among Myanmar older adults with and without a history of COVID-19 infection and assess the association between psychological factors and oral health outcomes among those with a history of COVID-19 infection. A cross-sectional study was conducted among 203 participants in Yangon from 2023 to 2024 using face-to-face interviews and clinical oral examinations. Participants with a history of COVID-19 infection experienced greater psychological distress and poorer oral health outcomes than those without such a history. In those who contracted COVID-19, depression positively associated with decayed teeth; decayed, missing, and filled permanent teeth (DMFT); and oral health impact profile-14 (OHIP-14), whereas negatively associated with present teeth. Anxiety positively related to decayed teeth, DMFT, and periodontal pockets. Stress negatively associated with decayed teeth, but positively with OHIP-14. Implementing oral health promotion programs and providing mental support for this vulnerable population are essential to improve their oral health and well-being., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A locomotor system that can function across different environmental conditions and produce a range of performances is one of the most critical abilities needed for extant and extinct animals in order to survive and maximise their competitive fitness. Recent engineering-inspired paleontological studies have reconstructed feasible locomotor patterns in extinct animals. However, it is still challenging to describe how extinct animals successfully adjust their locomotor patterns to new situations (e.g., changes in locomotor speed and morphology). In this study, we develop a novel reconstruction method based on a bio-inspired control system. We focus on plesiosaurs, an extinct aquatic reptile group which has two pairs of flipper-shaped limbs, and demonstrate that a highly optimised, flexible locomotor pattern for all four flippers can be reconstructed based on a decentralized control scheme formulated from extant animals' locomotion. The results of our robotic experiments show that a simple, local sensory feedback mechanism allows the plesiosaur-like robot to exploit the fluid flow between the flippers and generate efficient swimming patterns in response to changes in locomotor conditions. Our new method provides further evidence how decentralized control systems can produce a pathway between extinct and extant animals in order to understand the how extinct animals moved and how these movement patterns may have evolved., (© 2024. The Author(s).)

Background: This study investigated whether intensive lipid-lowering therapy with pitavastatin and ezetimibe lowers the incidence of heart failure (HF) events in patients with acute coronary syndrome (ACS)., Methods and Results: In the HIJ-PROPER study, 1,734 patients with ACS were randomly assigned to either pitavastatin plus ezetimibe therapy (n=864) or pitavastatin monotherapy (n=857). We examined the incidence of HF between these 2 groups over a 3.9-year period after ACS. The primary endpoint of the study was hospitalization for HF. The mean low-density lipoprotein cholesterol levels during the follow-up period were 65.1 mg/dL in the pitavastatin plus ezetimibe group and 84.6 mg/dL in the pitavastatin monotherapy group. The incidence of HF hospitalization was significantly lower in the pitavastatin plus ezetimibe group than in the pitavastatin monotherapy group (19 [2.2%] vs. 40 [4.7%] patients; hazard ratio 0.47, 95% confidence interval 0.27-0.81; P<0.005). This trend was consistent after multivariable analysis using multiple models., Conclusions: Intensive lipid-lowering therapy with pitavastatin and ezetimibe is associated with a lower incidence of hospitalization for HF in patients with ACS.

Yokoi A, Miyasaka H, Ogawa H, Itoh S, Okazaki H, Sonoda S. Effect of combining an upper limb rehabilitation support robot with task-oriented training on severe upper limb paralysis after spinal cord infarction: A case report. Jpn J Compr Rehabil Sci 2024; 15: 42-48., Objective: This study examined the effect of an upper limb rehabilitation support robot and task-oriented training on treating a patient with severe upper limb paralysis after spinal cord infarction who required total assistance with self-care., Case: A 60-year-old man was diagnosed with watershed infarction in the C5-7 spinal cord region. He was admitted to our hospital 18 days after onset of the disease. The patient had severe paralysis of both upper limbs, and the total score for the Functional Independence Measure (FIM) motor items was 25 points. Regarding the Canadian Occupational Performance Measure (COPM), three goals were listed: "eating," "going to the toilet," and "raising one's hand in a meeting." The performance of "going to the toilet" was rated three points, and the performance and satisfaction of other items were one point. The intervention was practiced for 1 h/day, mainly items selected from COPM. The training using an upper limb rehabilitation support robot was added for 1 h/day. The upper limb rehabilitation support robot adjusted the range of motion and dosage according to the patient's motor function level and recovery status. About three months after admission, he improved until his upper limbs could be held in space on activities of daily living (ADL), and the total score for the FIM motor items improved to 81 points. The satisfaction and performance of all items listed as goals in COPM at the time of admission improved to ten points, and the patient was discharged 108 days after admission., Conclusions: The upper limb rehabilitation support robot training that matched the level of motor function improved the motor function and active range of motion (ROM). ADL generalization through task-oriented training helped improve self-care. The use of COPM for the training to enable the patient to acquire the ability to perform meaningful activities led to improved COPM performance and satisfaction., Competing Interests: Conflict of Interests: The authors have no conflict of interest directly relevant to the content of this article., (©2024 Kaifukuki Rehabilitation Ward Association.)

We report the development of a novel synthetic approach for the highly strained atrop-Tyr C-6-to-Trp N-1' linkage, which can be executed on a decagram scale using a modular strategy involving palladium-catalyzed C-H arylation followed by Larock macrocyclization. The first total synthesis of lapparbin (1) was achieved by applying this synthetic strategy. Furthermore, the modular synthesis utilizing C-H arylation and Larock macrocyclization, discovered in the total synthesis of lapparbin (1), was demonstrated to be applicable to various arbitrary biaryl linkages, including non-natural types., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP., Materials and Methods: We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0., Results: Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively)., Conclusion: The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients., Methods: We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy., Results: Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094)., Conclusions: Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dental caries is a widespread oral health issue in Asia, affecting an estimated 30% to 90% of children and adults. Many caries cases remain untreated, resulting in pain and infection. In response, the Asian Academy of Preventive Dentistry (AAPD) emphasises comprehensive caries management and organised a fluoride workshop at the 15th International Conference of the AAPD in 2023. The AAPD invited a group of experts to form a fluoride working group to review existing literature and develop fluoride recommendations for stakeholders across Asian countries and regions. The working group assessed caries risk and identified commonly used topical fluoride products for home care, professional, and community settings in Asia. The working group concluded that fluoride is a safe and highly effective strategy to reduce caries prevalence and incidence. The working group provided key recommendations based on successful regional caries management practices: (1) use topical fluoride for prevention and control of dental caries; (2) encourage the use of fluoride toothpaste with a concentration of at least 1,000 ppm for effective caries reduction; (3) advise a 0.05% fluoride mouth rinse as soon as children can spit it out to prevent early childhood caries; (4) deliver professionally administered fluoride, such as 5% sodium fluoride varnish, 2% fluoride gel, or 1.23% acidulated phosphate fluoride preparations, to decrease dental caries in at-risk individuals; and (5) apply 38% silver diamine fluoride to arrest cavitated caries. These recommendations aim to help practitioners, health care providers, and parents/caregivers make informed decisions about fluoride use as part of comprehensive oral health care in the region., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A set of arylazopyrazole-based inhibitors targeting the mitotic motor protein CENP-E was discovered through the chemical platform using the quantitative cyclization of 1,3-diketone intermediate with various hydrazines under mild conditions. Through this efficient platform, the structure-activity relationship pertaining to the pyrazole photoswitch in photoswitchable CENP-E inhibitors not only in vitro but also in cells was successfully clarified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The β2-adrenergic receptor (β2-AR) is a therapeutic target for circulatory agonists and exhibits oncogenic activity in several cancers. However, its role in advanced colorectal cancer (CRC) treated using chemotherapy remains unclear. We investigated the potential of β2-AR as a novel chemosensitivity marker and therapeutic target in inoperable CRC., Methods: β2-AR expression was evaluated immunohistochemically in 80 advanced or recurrent CRC cases for which untreated resected specimens were available before systemic chemotherapy implementation. We assessed the relationship among β2-AR protein expression, clinicopathological factors, therapeutic response, and prognosis. Furthermore, we evaluated the significance of β2-AR as an in vitro and in vivo therapeutic target using CRC cell lines and a CRC xenograft model treated with the β-blocker, propranolol, and other anticancer agents., Results: High tumoral β2-AR expression was associated with shorter progression-free survival and chemotherapeutic resistance in patients treated with oxaliplatin-based regimens and bevacizumab-based regimens. We found no synergistic effect between propranolol and oxaliplatin. However, combined administration of propranolol and bevacizumab induced significant tumor shrinkage in the CRC xenograft model., Conclusions: β2-AR is a possible biomarker for chemosensitivity and prognosis in advanced CRC. Repositioning existing β-blockers could be beneficial for treating CRC resistant to existing treatment regimens., (© 2024. Society of Surgical Oncology.)

Background: Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients., Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a post hoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years., Results: Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p < 0.0001). The increased risk in the aspirin group was prominent within 3 years, and the hazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3 years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p = 0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group., Conclusion: The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Medical interviewing is a critical skill in clinical practice, yet opportunities for practical training are limited in Japanese medical schools, necessitating urgent measures. Given advancements in artificial intelligence (AI) technology, its application in the medical field is expanding. However, reports on its application in medical interviews in medical education are scarce., Objective: This study aimed to investigate whether medical students' interview skills could be improved by engaging with AI-simulated patients using large language models, including the provision of feedback., Methods: This nonrandomized controlled trial was conducted with fourth-year medical students in Japan. A simulation program using large language models was provided to 35 students in the intervention group in 2023, while 110 students from 2022 who did not participate in the intervention were selected as the control group. The primary outcome was the score on the Pre-Clinical Clerkship Objective Structured Clinical Examination (pre-CC OSCE), a national standardized clinical skills examination, in medical interviewing. Secondary outcomes included surveys such as the Simulation-Based Training Quality Assurance Tool (SBT-QA10), administered at the start and end of the study., Results: The AI intervention group showed significantly higher scores on medical interviews than the control group (AI group vs control group: mean 28.1, SD 1.6 vs 27.1, SD 2.2; P=.01). There was a trend of inverse correlation between the SBT-QA10 and pre-CC OSCE scores (regression coefficient -2.0 to -2.1). No significant safety concerns were observed., Conclusions: Education through medical interviews using AI-simulated patients has demonstrated safety and a certain level of educational effectiveness. However, at present, the educational effects of this platform on nonverbal communication skills are limited, suggesting that it should be used as a supplementary tool to traditional simulation education., (©Akira Yamamoto, Masahide Koda, Hiroko Ogawa, Tomoko Miyoshi, Yoshinobu Maeda, Fumio Otsuka, Hideo Ino. Originally published in JMIR Medical Education (https://mededu.jmir.org), 23.09.2024.)

Background: An automated measurement system for the placement angles of acetabular cup in total hip arthroplasty prostheses was developed utilizing artificial intelligence (AI) algorithms. The AI-powered system enables immediate measurement by capturing an anteroposterior pelvic X-ray through a smartphone camera., Methods: While developing the AI-powered measurement system, we trained AI utilizing 100 labeled anteroposterior pelvic X-rays to recognize the hip joint and 483 labeled anteroposterior pelvic X-rays to identify anatomical landmarks and the acetabular cup. To validate the AI-powered system, we measured the acetabular cup placement angles of 126 unlabeled post-total hip arthroplasty anteroposterior pelvic X-rays with both the AI-powered system and conventional measurement methods and assessed the correlation between the 2 methods., Results: The Pearson's correlation coefficients for the acetabular cup placement angles measured using the AI-powered system and conventional method were 0.88 (95% confidence interval, 0.84-0.92, P < .001) in inclination angle and 0.76 (95% confidence interval, 0.67-0.83, P < .001) in anteversion angle, respectively., Conclusions: Both inclination and anteversion angles measured using the AI-powered system showed a strong correlation with angles obtained through conventional methods., (© 2024 The Authors.)

The type 1 ryanodine receptor (RyR1) is a Ca 2+ release channel in the sarcoplasmic reticulum that is essential for skeletal muscle contraction. RyR1 forms a channel with six transmembrane segments, in which S5 is the fifth segment and is thought to contribute to pore formation. However, its role in channel gating remains unclear. Here, we performed a functional analysis of several disease-associated mutations in S5 and interpreted the results with respect to the published RyR1 structures to identify potential interactions associated with the mutant phenotypes. We demonstrate that S5 plays a dual role in channel gating: the cytoplasmic side interacts with S6 to reduce the channel activity, whereas the luminal side forms a rigid structural base necessary for S6 displacement in channel opening. These results deepen our understanding of the molecular mechanisms of RyR1 channel gating and provide insight into the divergent disease phenotypes caused by mutations in S5., (© 2024. The Author(s).)

The chemical constituents of Saxifraga stolonifera, S. fortunei, S. nipponica, S. cortusifolia, and S. rebunshirensis were investigated for structure and virucidal activity. In addition to the Saxifraga species-derived tannins, 30 compounds (1-30) were isolated from the five species. 5-Hydroxy-4-methoxy-3-O-(6-O-caffeoyl)-β-D-glucopyranosyl benzoic acid (1) and kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-β-D-xylopyranoside (2) were identified as undescribed compounds. Although 1 was isolated as the (E)-isomer of its caffeoyl moiety, under light it became over time a mixture of the (Z)-isomer (1a) and (E)-isomer (1). Kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-β-D-glucopyranoside (3) was an analog of 2 and a known compound, whose NMR assignment was reconsidered and described. 6-Isopropyl-5,5-dimethyldihydropyrimidine-2,4(1H,3H)-dione (30) was expected to be a racemic mixture based on its optical rotation and X-ray crystallography data. The virucidal activities of the isolated compounds (1-30) against influenza A virus, severe acute respiratory syndrome coronavirus 2, feline calicivirus, and murine norovirus were evaluated to identify the presence of compounds other than the Saxifraga species-derived tannins, which exhibited virucidal activities. Although the isolated compound activities were relatively weak compared to those of Saxifraga species-derived tannins, the potential virucidal activity of the compounds with galloyl groups was confirmed., Competing Interests: Declaration of competing interest The authors indicate that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index, and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment., Results: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease/progressive disease group significantly increased (p = 0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased., Conclusion: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy., (© 2024 S. Karger AG, Basel.)

Objective: This study aimed to understand the effectiveness of regular care in reducing the incidence of severe peristomal skin disorders, as well as to identify their risk factors., Summary Background Data: Peristomal skin disorders occur frequently in outpatient settings and require appropriate intervention. It remains, however, to be demonstrated when the need to follow up these patients decreases and whether assessing severity of peristomal skin disorders is useful., Methods: This prospective, multicenter, observational cohort study was conducted in six regional high-volume Japanese hospitals. The primary endpoint of the study was the effectiveness of regular follow-up in reducing the incidence of severe peristomal skin disorders via a scoring system at a defined regular outpatient visit. Propensity score matching was performed to compare a control group and patients with severe peristomal skin disorders., Results: In total, 217 patients between December 2019 and December 2021 were enrolled, and 191 patients were analyzed. Multivariate analysis showed that loop stoma (odds ratio [OR], 5.017; 95% confidence interval [CI], 1.350-18.639; P=0.016) and stoma height of <10 mm (OR, 7.831; 95% CI, 1.760-34.838; P=0.007) were independent risk factors for all peristomal skin disorders. After propensity score matching, the incidence of the disorders was not significantly different between the specified evaluation timing and historical control groups (75.7% vs. 77.2%, P=0.775), and the incidence of the severe disorders based on the ABCD and DET scores (5.9% vs. 19.1%, P<0.001 and 1.5% vs. 29.4%, P<0.001, respectively) was significantly lower in the specified evaluation timing group than in the historical control group., Conclusion: Regular peristomal skin disease follow-up and scoring, as well as appropriate stoma care at the stoma outpatient visit did not change the frequency of peristomal skin disease, but severe peristomal skin disorders were prevented. Additionally, risk factors for peristomal skin disorders were found to be height <10 mm and loop stoma., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: An increasing number of patients with complicated systemic comorbidity can undergo colorectal cancer (CRC) surgery. Such patients have a high risk of developing poor postoperative outcomes. This study aimed to identify preoperative factors, including nutritional and sarcopenia statuses, leading to poor postoperative outcomes in patients with severe systemic comorbidities., Patients and Methods: This study included 114 patients who underwent radical CRC resections and had American Society of Anesthesiologists Physical Statuses ≥3. We retrospectively analyzed the relationships between clinical factors, postoperative complications (within 28 days postoperatively and Clavien-Dindo classification grade ≥2), length of hospital stay, discharge destination, and overall survival (OS)., Results: The median patient age was 74.5 years (range=41.0-93.0 years). Thirty-six patients had postoperative complications (31.6%), and the risk factors in the multivariate analyses were rectal cancer and preoperative nutritional disorders with Prognostic Nutritional Index ≤40. In patients with nutritional disorders, the postoperative hospital stay was longer, and a higher (but not statistically significant) percentage were not discharged home. Moreover, the independent factors for OS identified in the multivariate analyses were body mass index (BMI) and hemodialysis., Conclusion: In patients with CRC and severe systemic comorbidities, those with Prognostic Nutritional Index ≤40 have a high risk of developing postoperative complications, leading to a prolonged postoperative hospital stay and possibly preventing discharge home. Additionally, among these patients, OS was poor in those with low BMI or preoperative hemodialysis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI., Methods: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups., Results: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000)., Conclusions: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE., Competing Interests: Declaration of competing interest Dr. Yasuda reports remuneration for lectures from Takeda, Daiichi Sankyo, and Bristol-Myers Squibb and trust research/joint research funds from Takeda and Daiichi Sankyo; Dr. Takayama reports lecture fees from Daiichi Sankyo; and Dr. Ogawa reports lecture fees and research grants from Abbot Medical Japan, Bayer, Daiichi Sankyo, Eisai, Kowa, Takeda Pharmaceutical, and Teijin. Other authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Acaryochloris species belong to a special category of cyanobacteria possessing chlorophyll (Chl) d. One of the photosynthetic characteristics of Acaryochloris marina MBIC11017 is that the absorption spectra of photosystem I (PSI) showed almost no bands and shoulders of low-energy Chls d over 740 nm. In contrast, the absorption spectra of other Acaryochloris species showed a shoulder around 740 nm, suggesting that low-energy Chls d within PSI are diversified among Acaryochloris species. In this study, we purified PSI trimer and monomer cores from Acaryochloris sp. NBRC 102871 and examined their protein and pigment compositions and spectral properties. The protein bands and pigment compositions of the PSI trimer and monomer of NBRC102871 were virtually identical to those of MBIC11017. The absorption spectra of the NBRC102871 PSIs exhibited a shoulder around 740 nm, whereas the fluorescence spectra of PSI trimer and monomer displayed maximum peaks at 754 and 767 nm, respectively. These spectral properties were different from those of MBIC11017, indicating the presence of low-energy Chls d within the NBRC102871 PSIs. Moreover, we analyzed the NBRC102871 genome to identify amino acid sequences of PSI proteins and compared them with those of the A. marina MBIC11017 and MBIC10699 strains whose genomes are available. The results showed that some of the sequences in NBRC102871 were distinct from those in MBIC11017 and MBIC10699. These findings provide insights into the variety of low-energy Chls d with respect to the protein environments of PSI cores among the three Acaryochloris strains., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system., Methods: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort., Results: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test)., Conclusions: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria., (© 2024. The Author(s).)

A concise synthetic strategy utilizing a Zr catalyst for the construction of cyctetryptomycin A and B is reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers with a Zr catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr-catalyzed radical coupling. The radical dimerization reaction mediated by the Zr catalyst required 1,2-bis(diphenylphosphino)ethane (dppe) as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr-catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations., (© 2024 Wiley-VCH GmbH.)

Objectives: To describe the oral health-related quality of life (OHRQoL) and its potential influencing factors within the Myanmar population., Methods: Data were from the first national oral health survey, involving 3,513 participants aged 15-18 years, 35-44 years, and 60-74 years from 21 selected townships in Myanmar. Self-administered questionnaire-based surveys, conducted from December 2016 to January 2017, included socio-demographics, behavioral factors, self-reported oral conditions (number of teeth present, teeth and gingival conditions), and inquiries regarding OHRQoL (a set of 12 questions with 5 response options) using the recommended questions from WHO Oral Health Surveys., Results: The most prevalent oral health issues were difficulties in chewing (32.2%) and biting foods (30.8%). In bivariate analysis, older individuals, rural residents, and participants with higher educational levels were associated with OHRQoL. In multiple regression analysis, self-reported number of teeth, teeth and gingival conditions were strong predictors of OHRQoL in all age groups., Conclusion: Self-rated oral health conditions predicted quality of life due to oral problems. The development of national oral health policies and strategies is imperative to facilitate early detection of oral health problems and promote the awareness of oral health importance., (Copyright© 2024 Dennis Barber Ltd.)

Pulse oximetry is used to screen for respiratory failure in dyspnea patients. However, pulse oximetry can yield false-positive results in certain situations. Unstable hemoglobinopathy is a disease in which mutations in the globin-encoding gene result in abnormal globin chain production, causing low percutaneous oxygen saturation (SpO 2 ) levels due to changes in hemoglobin absorbance and oxygen affinity. We identified a new family lineage of Hb Hirosaki in an adult patient with chronic obstructive pulmonary disease, dyspnea, and low SpO 2 . According to our literature review, only a few cases of unstable hemoglobinopathy have been reported in adults. Most patients with unstable hemoglobinopathy are asymptomatic, and those with dyspnea often have respiratory diseases or severe anemia. To differentiate unstable hemoglobinopathy, an appropriate assessment of the discrepancy between SpO 2 values and arterial blood gas analysis results is important.

Cathepsin C (CatC) is an enzyme which regulates the maturation of neutrophil serine proteases (NSPs) essential for neutrophil activation. Activated neutrophils are key players in the innate immune system, and are also implicated in the etiology of various inflammatory diseases. This study aims to demonstrate a therapeutic potential for CatC inhibitors against disorders in which activated neutrophil-derived neutrophil extracellular traps (NETs) play a significant role. We demonstrate that a CatC inhibitor, MOD06051, dose-dependently suppresses the cellular activity of NSPs, including neutrophil elastase (NE), in vitro. Neutrophils derived from MOD06051-administered rats exhibit significantly lower NE activity and NET-forming ability than controls. Furthermore, MOD06051 dose-dependently ameliorates vasculitis and significantly decreases NETs when administered to a rat model of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody-associated vasculitis (AAV). These findings suggest that CatC inhibition is a promising strategy to reduce neutrophil activation and improve activated neutrophil-mediated diseases such as MPO-AAV., (© 2024. The Author(s).)

This study investigates novel short-lived long noncoding RNAs (lncRNAs) in mice with altered expression in metabolic dysfunction-associated steatotic liver (MASH) and liver fibrosis. LncRNAs share similarities with mRNAs in their transcription by RNA polymerase II, possession of a 5' cap structure, and presence of a polyA tail. We identified two lncRNAs, Kcnq1ot1 and Rmst, significantly decreased in both conditions. These lncRNAs showed dramatic expression changes in MASH livers induced by Western diets and CCl 4 , and in fibrotic livers induced by CCl 4 alone. The decrease was more pronounced in liver fibrosis, suggesting their potential as biomarkers for disease progression. Our findings are consistent across different fibrosis models, indicating a crucial role for these lncRNAs in MASH and liver fibrosis in mice. With MASH becoming a global health issue and its progression to fibrosis associated with hepatocarcinogenesis and poor prognosis, understanding the underlying mechanisms is critical. This research contributes to elucidating lncRNA functions in murine liver diseases and provides a foundation for developing novel therapeutic strategies targeting lncRNAs in MASH and liver fibrosis, offering new avenues for potential therapeutic interventions.

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.

Background: Stereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment., Methods: We collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT., Results: A total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P < 0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Median OS for patients with scores of 0-2, 3, and 4-5 were 9.0, 3.5 and 1.7 months, respectively (P < 0.001)., Conclusions: Male sex, KPS ≤ 60, presence of ECM, NLR ≥ 5, and LDH ≥ ULN were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT., (© 2024. The Author(s).)

Objectives: This study aimed to assess the intricate relationship between salivary IgA antibody levels to PAc (361-386) (PPA), mutans streptococci colonization, and root caries development in older adults., Materials and Methods: This study included 307 participants aged 76 years residing in Niigata city, Japan. Clinical oral examinations were performed at baseline in 2004 and 1 year later, during which the total number of untreated and treated root caries was assessed using the root decayed, filled tooth (DFT) index. The stimulated saliva samples were collected using the spitting method during the baseline survey. Salivary IgA antibody levels to amino acid residues 361-386 of Streptococcus mutans PAc were quantified using an enzyme-linked immunosorbent assay. Statistical analyses, including the χ 2 test, Mann-Whitney U test, and logistic regressions, were performed to examine the association of increased root DFT with the independent variables., Results: Among the 307 participants (53.1% men), the mean root DFT at baseline was 3.77 ± 3.66, and 36.5% of the study sample exhibited increased root DFT after 1 year with a mean increment of 0.36 ± 0.48. Participants with increase in root DFT after 1 year had significantly higher rates of low PPA levels (≤ 25th percentile) than those without increased root DFT (p = 0.020). Low PPA levels (≤ 25th percentile) were significantly more likely to have an increased risk of root caries development compared with PPA levels > 25th percentile (adjusted OR: 1.88, 95% CI: 1.09-3.25)., Conclusion: Low PPA levels and root caries incidence correlated significantly, suggesting that low levels of salivary IgA antibody to PAc (361-386) may serve as a risk factor for increased root caries in older adults., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Patient-derived xenografts (PDXs) are increasingly utilized in preclinical drug efficacy studies due to their ability to retain the molecular, histological, and drug response characteristics of patient tumors. This study aimed to investigate the factors influencing the successful engraftment of PDXs. Lung adenocarcinoma PDXs were established using freshly resected tumor tissues obtained through surgery. Radiological data of pulmonary nodules from this PDX cohort were analyzed, categorizing them into solid tumors and tumors with ground-glass opacity (GGO) based on preoperative CT images. Gene mutation status was obtained from next generation sequencing data and MassARRAY panel. A total of 254 resected primary lung adenocarcinomas were utilized for PDX establishment, with successful initial engraftment in 58 cases (22.8 %); stable engraftment defined as at least three serial passages was observed in 43 cases (16.9 %). The stable engraftment rates of PDXs from solid tumors and tumors with GGO were 22.1 % (42 of 190 cases) and 1.6 % (1 of 64 cases), respectively (P < 0.001). Adenocarcinomas with advanced stage, poor differentiation, solid histologic subtype, and KRAS or TP53 gene mutations were associated with stable PDX engraftment. Avoiding tumors with GGO features could enhance the cost-effectiveness of establishing PDX models from early-stage resected lung adenocarcinomas., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KY is a consultant for Olympus Medical Systems Corporation, Johnson & Johnson Enterprise Innovation, Inc., and Medtronic. KY also has collaborations with Johnson & Johnson Enterprise Innovation, Inc, Olympus Corporation, and ODS Medical Inc., Siemens, and OKF Technologies. No conflicts for remaining authors., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission., Methods and Results: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m 2 , a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004)., Conclusions: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study aimed to clarify differences in clinical features and prognostic outcomes between IC and CLTI, and prognostic factors in patients undergoing endovascular therapy (EVT)., Materials and Methods: A total of 692 patients with 808 limbs were enrolled from 20 institutions in Japan. The primary measurements were the 3-year rates of major adverse cardiovascular event (MACE) and reintervention., Results: Among patients, 79.0% had IC and 21.0% had CLTI. Patients with CLTI were more frequently women and more likely to have impaired functional status, undernutrition, comorbidities, hypercoagulation, hyperinflammation, distal artery disease, short single antiplatelet and long anticoagulation therapies, and late cilostazol than patients with IC. Aortoiliac and femoropopliteal diseases were dominant in patients with IC and infrapopliteal disease was dominant in patients with CLTI. Patients with CLTI underwent less frequently aortoiliac intervention and more frequently infrapopliteal intervention than patients with IC. Longitudinal change of ankle-brachial index (ABI) exhibited different patterns between IC and CLTI (pinteraction=0.002), but ABI improved after EVT both in IC and in CLTI (p<0.001), which was sustained over time. Dorsal and plantar skin perfusion pressure in CLTI showed a similar improvement pattern (pinteraction=0.181). Distribution of Rutherford category improved both in IC and in CLTI (each p<0.001). Three-year MACE rates were 20.4% and 42.3% and 3-year reintervention rates were 22.1% and 46.8% for patients with IC and CLTI, respectively (log-rank p<0.001). Elevated D-dimer (p=0.001), age (p=0.043), impaired functional status (p=0.018), and end-stage renal disease (p=0.019) were independently associated with MACE. After considering competing risks of death and major amputation for reintervention, elevated erythrocyte sedimentation rate (p=0.003) and infrainguinal intervention (p=0.002) were independently associated with reintervention. Patients with CLTI merely showed borderline significance for MACE (adjusted hazard ratio 1.700, 95% confidence interval 0.950-3.042, p=0.074) and reintervention (adjusted hazard ratio 1.976, 95% confidence interval 0.999-3.909, p=0.05)., Conclusions: The CLTI is characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared with IC. Also, CLTI has approximately twice MACE and reintervention rates than IC, and the underlying inflammatory coagulation disorder per se is associated with these outcomes., Clinical Impact: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study, JPASSION study found that CLTI was characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared to IC. Also, CLTI had approximately twice major adverse cardiovascular event (MACE) and reintervention rates than IC. Intriguingly, the underlying inflammatory coagulation disorder per se was independently associated with MACE and reintervention. Further studies to clarify the role of anticoagulation and anti-inflammatory therapies will contribute to the development of post-interventional therapeutics in the context of peripheral artery disease., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: O.K. has received a research grant and consulting fees from Terumo and has received lecture fees from Medicon, Otsuka Pharmaceutical, and Kowa Pharmaceutical. H.O. has received lecture fees from Bayer Pharmaceutical, Bristol-Meyers Squibb, Eisai, Novartis Pharma, Pfizer, Towa Pharmaceutical, and Toa Eiyo. S.Y. has received remuneration for lecture from Bristol-Meyers, Bayer, and Daiichi-Sankyo; has received trust research/joint research funds from Takeda, NEC, Daiichi-Sankyo, Bayer, and Abbott; and is affiliated with endowed department sponsored by Abbott, Terumo, Nihon-Kohden, Medtronic, Japan Lifeline, Otsuka, Ono, Boehringer Ingelheim, Takeda, Kowa, Zeon, Shionogi, Nippon-Shinyaku, Mochida, and Tesco. The remaining authors have nothing to disclose.

Purpose: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost., Materials and Methods: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival., Results: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases., Conclusion: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer., Study Registration: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845)., (© 2024. The Author(s).)

Aims: This study aims to evaluate the periodontal status and its changes among Japanese older adults over a 10-year period., Methods and Results: A total of 206 dentate older adults aged 70 years who completely participated in 10 years of oral examination were included. The community periodontal index (CPI) was used to assess the gingival and periodontal pocket status, while the loss of attachment (LA) scoring system was used to report the extensive LA. A higher score in CPI (Code 3 and Code 4) and more extensive attachment loss were found in a majority of participants. During follow-up evaluation, mean number of sextants with CPI code 4 remained stable, while CPI code 3 significantly decreased particularly in male participants. Whereas, sextants without attachment loss significantly decreased on average. The mean number of missing sextants significantly increased from 1.1 to 1.9, and 5.8% of subjects had all sextants excluded in the follow-up., Conclusion: This study indicated that majority of the older people experienced severe periodontal disease and this condition remained stable during 10-year period. Additionally, the incidence of tooth loss increased as individuals aged. Regular oral care and maintenance are highly recommended for older population., (© 2024 Special Care Dentistry Association and Wiley Periodicals LLC.)

We have investigated the vortex dynamics in a thin film of an iron-based superconductor FeSe&#95;{0.5}Te&#95;{0.5} by observing second-harmonic generation (SHG) in the terahertz frequency range. We visualized the picosecond trajectory of two-dimensional vortex motion in a pinning potential tilted by Meissner shielding current. The SHG perpendicular to the driving field is observed, corresponding to the nonreciprocal nonlinear Hall effect under the current-induced inversion symmetry breaking, whereas the linear Hall effect is negligible. The estimated vortex mass, as light as a bare electron, suggests that the vortex core moves independently from quasiparticles at such a high frequency and large velocity ≈300  km/s.

Background and Aims: Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events partly due to measurement methods that cannot distinguish between uncleaved and furin-cleaved forms of PCSK9., Methods: This is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The primary endpoint was major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In this case-cohort study, serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among 426 participants who developed MACCE (cases) and 1,478 randomly selected participants (sub-cohort)., Results: From 1,478 patients in sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of the primary endpoint in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile (hazard ration [HR] 0.809; 95% confidence intervals [CI], 0.541-1.209). Similarly, the HR for the highest to lowest quartiles of furin-cleaved PCSK9 was 0.948 [95% CI, 0.645-1.392] (P = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE., Conclusions: In a large-scale secondary prevention cohort, serum mature and furin-cleaved PCSK9 levels did not provide useful information for predicting future cardiovascular events in statin-treated patients with stable CAD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kiyoshi Hibi reports financial support was provided by the Public Health Research Foundation. Kiyoshi Hibi reports financial support was provided by Kowa. Kiyoshi Hibi reports a relationship with Abbott Medical that includes: speaking and lecture fees. Kiyoshi Hibi reports a relationship with Daiichi Sankyo that includes: speaking and lecture fees. Kiyoshi Hibi reports a relationship with Medtronic that includes: speaking and lecture fees. Kiyoshi Hibi reports a relationship with the Research Institute for Production Development that includes: funding grants. Kiyoshi Hibi reports a relationship with Japan Medical Device Corporation that includes: funding grants. Kiyoshi Hibi reports a relationship with Abbott Medical that includes: funding grants. Kiyoshi Hibi reports a relationship with NIPRO that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) is used to evaluate surgical skills essential for laparoscopic surgery, but whether surgeons with this certification as operators improve the short-term outcomes and prognosis after rectal cancer surgery is unclear. This cohort study was designed to compare the short-term and long-term outcomes of laparoscopic surgery for advanced rectal cancer performed by an ESSQS-certified surgeon versus a surgeon without ESSQS certification., Methods: The outcomes of cStage II and III rectal cancer surgery cases performed at 56 Japanese hospitals between 2014 and 2016 were retrospectively reviewed. To examine the impact of ESSQS-certified surgeons as surgeons, the outcomes of cases with only ESSQS-certified surgeons as operators were compared with those without involvement of ESSQS-certified surgeons., Results: A total of 3197 cases were enrolled, with 1015 in which surgery was performed by ESSQS-certified surgeons, and 544 in which there was no involvement of ESSQS-certified surgeons. After propensity score matching, the ESSQS group had significantly shorter operative time ( p  < 0.001), a lower conversion rate to open surgery ( p  < 0.001), and more dissected lymph nodes ( p  = 0.002)., Conclusion: Laparoscopic rectal surgery performed by ESSQS-certified surgeons was significantly associated with improved short-term outcomes. This demonstrates the utility of the ESSQS certification system., Competing Interests: The authors declare no conflicts of interest for this article., (© 2024 The Author(s). Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: This study aimed to evaluate bone union of the tibial tuberosity in patients undergoing medial opening wedge distal tibial tuberosity osteotomy (OWDTO). It was hypothesized that bone union of the tibial tuberosity could be associated with lateral hinge fractures (LHFs), but not thickness of the tibial tuberosity osteotomy., Methods: Data of 61 consecutive patients who underwent OWDTO were retrospectively reviewed. Radiographic parameters of the lower limb and LHFs were evaluated. Thickness of the tibial tuberosity osteotomy and bone union of the tibial tuberosity were assessed at 1, 2, 3, 4, and 5 cm distal to the most proximal part of the tibial tuberosity on computed tomography. Bone union was assessed. Factors related to bone union of the tibial tuberosity were analyzed., Results: There were 13 postoperative onset LHFs: all healed with conservative treatments within 6 months after surgery. The total score of bone union of the tibial tuberosity was 8.4 ± 2.1 points, which correlated with age, postoperative medial proximal tibial angle (MPTA), correction angle, and postoperative onset LHF (r = 0.307, 0.388, 0.275, and -0.624, respectively; p  = 0.016, 0.002, 0.033, and <0.001, respectively). Regression coefficient for postoperative onset LHF, postoperative MPTA, and body mass index were -0.619 ( p  < 0.001), 0.285 ( p  = 0.003), and -0.227 ( p  = 0.021), respectively., Conclusion: Postoperative onset LHFs, but not thickness of the tibial tuberosity osteotomy, were a risk factor for delayed union of the tibial tuberosity following OWDTO. Furthermore, to prevent delayed union of the tibial tuberosity, postoperative onset LHFs should be prevented., Level of Evidence: LEVEL III, Case-control study., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Background/aim: Adjuvant capecitabine and oxaliplatin (CAPOX) therapy is standard strategy for colorectal cancer with risk of recurrence. Early dose reduction (EDR) of CAPOX therapy is commonly used in real-world practice. However, there is limited evidence regarding the effectiveness of CAPOX for patients who had EDR. Therefore, this study aimed to clarify the risks of EDR and its effect on long-term outcomes and body composition factors., Patients and Methods: Patients who received CAPOX therapy after radical surgery for colorectal cancer between June 2013 and December 2021 were included. EDR was defined as dose reduction within four courses of CAPOX therapy. Body composition factors were measured for 1 year following surgery to determine the EDR effects., Results: Eighty-four patients were included; 35 (42%) of them had EDR. The multivariate analysis revealed that underweight [odds ratio (OR)=4.95, 95% confidence interval (CI)=1.13-21.7, p=0.03] was a risk factor for EDR. Relapse-free survival (RFS) was significantly better in the non-EDR group (p=0.01). The 5-year RFS rates for the non-EDR and EDR groups were 88.7% and 65.4%, respectively. The multivariate analysis revealed that age >65 years [hazard ratio (HR)=3.97; 95% CI=1.16-13.62, p=0.03] and EDR (HR=7.62; 95% CI=1.71-33.91, p=0.005) were associated with poorer RFS. The 1-year body composition analysis revealed decreases in all factors in the EDR group., Conclusion: Preoperative underweight status was associated with EDR, which resulted in decreased RFS and body composition factors when compared with the non-EDR group. Therefore, avoiding EDR and early nutritional intervention after EDR may improve outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Phase angle (PhA), which is measured using bioelectrical impedance analysis, is an indicator of muscle quality and malnutrition. PhA has been shown to be correlated with sarcopenia and malnutrition; however, studies on patients with chronic obstructive pulmonary disease (COPD) are limited. In this study, we investigated the correlation between PhA and sarcopenia and malnutrition and determined the cutoff values of PhA for those in patients with COPD., Methods: This study included 105 male patients with COPD (mean age 75.7 ± 7.7 years, mean forced expiratory volume in 1s % predicted [%FEV 1 ] 57.0 ± 20.1%) and 12 male controls (mean age 74.1 ± 3.8 years) who were outpatients between December 2019 and March 2024. PhA was measured using the InBody S10, and its correlation with sarcopenia and malnutrition was assessed. The cutoff PhA values for sarcopenia and malnutrition were determined using receiver operating characteristic curves., Results: The prevalence rates of sarcopenia and malnutrition were 31% and 22%, respectively, in patients with COPD. PhA significantly correlated with sarcopenia- and malnutrition-related indicators. Multivariate logistic regression analysis independently correlated PhA with sarcopenia and malnutrition. The cutoff values of the PhA for sarcopenia and malnutrition were 4.75° (AUC = 0.78, 95% CI = 0.68-0.88) and 4.25° (AUC = 0.75, 95% CI = 0.63-0.86), respectively., Conclusions: PhA was significantly correlated with sarcopenia and malnutrition in Japanese patients with COPD and may be a useful diagnostic indicator., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Although much progress has been made in diagnosis of carcinomas, no established methods have been confirmed to elucidate their morphological features., Methods: Three-dimensional structure of esophageal carcinomas was assessed using transparency-enhancing technology. Endoscopically resected esophageal squamous cell carcinoma was fluorescently stained, optically cleared using a transparency-enhancing reagent called LUCID, and visualized using laser scanning microscopy. The resulting microscope images were converted to virtual HE images for observation using ImageJ software., Results: Microscopic observation and image editing enabled three-dimensional image reconstruction and conversion to virtual HE images. The structure of abnormal blood vessels in esophageal carcinoma recognized by endoscopy could be observed in the 3 dimensions. Squamous cell carcinoma and normal squamous epithelium could be distinguished in the virtual HE images., Conclusions: The results suggested that transparency-enhancing technology and virtual HE images may be feasible for clinical application and represent a novel histopathological method for evaluating endoscopically resected specimens., (© 2024. The Author(s).)

Pneumonia caused by Legionella longbeachae, transmitted through contaminated soil, is very rare in Japan. A 70-year-old man with severe respiratory failure was admitted to our hospital and underwent multidisciplinary procedures. Although a urinary antigen test was negative for Legionella, he was clinically diagnosed with legionellosis and administered levofloxacin. His condition subsequently improved. Thereafter, sputum culture detected L. longbeachae. Because the DNA of L. longbeachae was detected in the gardening soil, it is suspected source of infection. Therefore, it is important to suspect legionellosis based on clinical information, even if a urine antigen test is negative.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS)., Methods: Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples., Results: At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off., Conclusions: CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer., (© 2024. The Author(s).)