Search

Background: Residential greenness has been linked to various health benefits, but evidence on its association with sperm quality remains limited., Methods: We enrolled 28,089 adult men from an infertility clinic in Hubei, China, from 2014 to 2020. Residential greenness was estimated using the Normalized Vegetation Index (NDVI) from satellite imagery, averaged within buffers of 250 m, 500 m and 1000 m around each participant's residential address. We employed multivariate linear regression analysis to evaluate the association between NDVI exposure and semen quality, while controlling for individual characteristics and semen collection season. Additionally, we performed subgroup analyses to investigate potential variations in the association based on individual characteristics., Results: An interquartile range increase of 0.243 in NDVI within the 1000 m buffer was associated with increases of 1.68 % (95 % CI: 0.31 %, 3.06 %) in sperm concentration, 0.43 % (95 % CI: 0.08 %, 0.79 %) in progressive motility, and 0.50 % (95 % CI: 0.14 %, 0.87 %) in total motility. These associations were consistent across different buffer sizes. The associations were more pronounced during the 70-90 lag days prior to semen collection (spermatogenesis stage) and among men aged ≥ 40 years or those with lower education levels., Conclusions: Our study demonstrated that exposure to residential greenness may act as an innovative protective factor for semen quality., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Corticobasal degeneration (CBD) is a clinically heterogeneous neurodegenerative disorder, for which pathological investigations are essential for a definitive diagnosis. This study explored the clinical characteristics of Japanese patients with pathologically confirmed CBD., Methods: We reviewed the data of Japanese patients with pathologically confirmed CBD who were consecutively autopsied at our institute. Clinical data were obtained from medical records and clinicopathological conferences., Results: Of the 34 patients initially reviewed, three were excluded because of a lack of detailed clinical data. Of the remaining 31 patients, 16 were men and 15 were women. The mean ages at onset and death were 63.3 ± 6.7 (51-79) years and 69.1 ± 6.9 (54-86), respectively. The median disease duration was 6.0 (2.5-12) years. The clinical phenotypes were as follows: progressive supranuclear palsy syndrome (PSPS; n = 20, 64.5 %), probable or possible corticobasal syndrome (n = 6, 19.4 %), frontal behavioral-spatial syndrome (n = 4, 12.9 %), nonfluent/agrammatic variant of primary progressive aphasia (n = 1, 3.2 %). Furthermore, 28 (90.3 %) patients exhibited dysphagia with a median latency of 3.5 (1.0-10.0) years, and 22 (71.0 %) patients who underwent tube feeding survived longer than those who did not (P = 0.013)., Conclusions: Compared with Western populations, a high prevalence of PSPS may be a clinical characteristic of Japanese patients with CBD. Additionally, dysphagia occurs in many patients with early latency and may shorten survival. Tube feeding contributes to the prolonged survival of patients with CBD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: With the recent advent of technology, it is important to confirm the health and safety of the youth. This study aimed to prospectively evaluate the relationship between Wi-Fi, cordless phones, and mobile phone usage patterns and behavioral problems., Methods: This study involved 2465 children aged 8-17 years from the Hokkaido Study on Environment and Children's Health from October 2020 to January 2021, with a follow-up from September 2021 to March 2022. The mother-child dyad provided information on the presence of residential Wi-Fi and cordless phones, cordless phone call duration, and mobile phone usage pattern (duration of calls using mobile network and internet, online audio streaming, online video streaming, and playing online games) via a baseline questionnaire. Based on the scores on Strength and Difficulties Questionnaire at baseline and follow-up, the children were categorized into four groups: normal, persistent, improved, and concurrent., Results: No significant association was found between Wi-Fi, mobile phone calls via mobile networks, and behavioral problems. Cordless phone at home had higher odds for improvement in total difficulty scores, and cordless phone for calling more than 4 min per week had lower odds of persistent problematic prosocial behavior. Longer duration of mobile phone calling via the internet (>40 min/week) had higher odds of concurrent total difficulties. Mobile phone calling via mobile network for <5 min per week had higher odds for improved total difficulty scores. Audio streaming via mobile phones for 60-120 min had lower odds of persistent total difficulties., Conclusion: Our results showed sporadic findings between residential RF-EMF indoor sources and mobile phone usage pattern. These observed findings could be affected by residual confounding and chance findings. Ongoing follow-up studies are necessary to further explore this association through detailed exposure assessment and addressing the potential limitations of our study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Reiko Kishi reports financial support was provided by Japanese Ministry of Internal Affairs and Communications. 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.)

Objective: Maternal environmental metal exposure is common, but long-term prospective epidemiological evidence of its impact on children's intellectual development is still insufficient., Methods: Data on maternal plasma metal levels and child intelligence were obtained for 211 3-6-year-old children from Guangxi Zhuang Birth Cohort. ICP-MS was employed to detect 17 metals, including 7 essential metals (Mn, Fe, Co, Ni, Cu, Zn, Mo) and 10 non-essential metals (As, Rb, Sr, Cd, Sb, Cs, Ba, W, Pb, U), in maternal plasma samples obtained before 13 weeks of gestation during the initial maternity checkup. Child intelligence was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. The GLM, RCS and mixture models were used to assess the associations of maternal plasma metal levels with child intelligence quotient (IQ) scores., Results: The GLM analysis revealed that U had a significant adverse effect on child IQ scores in high-dose exposure groups (-9.236 [-18.644, -4.936], p = 0.006) after adjusting for covariates, while Sb showed a linear adverse effect on children's intelligence in the adjusted model (-4.028 [-7.432, -0.626], p = 0.021). BKMR modeling indicated that overall IQ scores decreased as concentrations of non-essential metals mixtures increased after adjusting for essential metal mixtures, consistent with findings from the WQS (β [95% CI], -8.463 [-14.449, -2.476], p = 0.007) and Qgcomp models (-7.003 [-12.928, -1.078], p = 0.022). Among the non-essential metals, U had the highest negative weight at 37.96%, followed by Pb (23.35%) and Sb (16.91%). Furthermore, potential interactions were observed between metals (Pb and U) and Sb in the study findings., Conclusion: Reducing exposure to non-essential metal mixtures, especially U, Sb and Pb, during early pregnancy and ensuring adequate intake of specific essential metal elements could be a critical intervention in addressing childhood intellectual impairment., 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 Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women., 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 B.V. All rights reserved.)

Background: Increasing expectations that biologics can be used as disease-modifying agents have introduced the concept of clinical remission (CR) in managements of severe asthma. Given the clinical relevance of computed tomography (CT) and blood biomarkers, we hypothesized that further refinement of CR criteria as well as incorporation of CT and blood biomarkers as indicators for structural and biological remission (SR, BR) would enable predicting long-term disease stability in patients with severe asthma treated with biologics., Methods: This Japanese multicenter prospective observational cohort will enroll patients with severe asthma who will start a new biologic (including a change from another biologic). The enrolled patients will be longitudinally followed up for 3 years. At enrollment, patients will undergo postbronchodilator spirometry, blood tests, fractional exhaled nitric oxide, chest and sinus CT, and patient-reported outcome questionnaires. Follow-up examinations will be performed at 1, 3, 6, 12, 24, and 36 months. The rates of CR resulting from different criteria after 1 year of treatment with biologics will be compared, and factors associated with long-term disease stability after 3 years of biologic treatments will be identified., Discussion: This multicenter study in Japan will provide data that will help establish more appropriate criteria for CR, structural remission, and biological remission to predict long-term disease stability in patients with severe asthma who receive biologic therapy., Ethics and Dissemination: The study was approved by the Ethics Committee of Kyoto University (No. R4419, approval date June 11th, 2024)., Trial Registration: The University Hospital Medical Information Network (UMIN000053771)., Competing Interests: Declaration of competing interest N.T. received honoraria for lectures for AstraZeneca and research funding from Fujifilm, and Daiichi Sankyo. Y.H. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi, Boehringer Ingelheim JP. S.M. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi. J.M. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi and research funding from AstraZeneca, GlaxoSmithKline, Novartis. T.W. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi. K.O. received honoraria for lectures for AstraZeneca, Boehringer Ingelheim JP. M.Y. received honoraria for lectures for AstraZeneca, GlaxoSmithKline and research funding from Boehringer Ingelheim JP, GlaxoSmithKline, Clairvo technologies Inc. K.A. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim JP. Y.N. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim JP and research funding from Boehringer Ingelheim JP, GlaxoSmithKline, Clairvo technologies Inc. T. Hirano received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi. K. Matsunaga received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Kyorin Pharma, Novartis, Sanofi. T. Koya received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi, Novartis. H.M. received honoraria for lectures for AstraZeneca, Sanofi, GlaxoSmithKline, Novartis. K.F. received honoraria for lectures for AstraZeneca, GlaxoSmithKline, Sanofi, Novartis, Boehringer Ingelheim JP, Kyorin Pharma and research funding from AstraZeneca, GlaxoSmithKline, Novartis, Boehringer Ingelheim JP, Chugai Pharmaceutical. S. K. received honoraria for lectures for AstraZeneca, Boehringer Ingelheim JP and research funding from Novartis. T. Kaneko received honoraria for lectures for AstraZeneca, Kyorin Pharma, Novartis, Sanofi, Boehringer Ingelheim JP. T. Hirai. received research funding from Fujifilm and Daiichi Sankyo., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objective: We analyze the characteristics and related factors of human chorionic gonadotropin (hCG) of pituitary origin to establish the reference interval to resolve clinical confusion and avoid harmful therapy to Chinese postmenopausal women with "positive" hCG., Materials and Methods: This retrospective cohort study identified individuals who underwent hCG measurements at an academic hospital. Three gonadotropins (hCG, follicle stimulating hormone (FSH), and luteinizing hormone (LH)) was drawn from medical records. The age-stratified analyses were performed first. Then the correlations of hCG and FSH, LH as well as age were analysed. Finally, characteristics and associations of hCG, LH, and FSH were evaluated to identify pituitary hCG in postmenopausal women in clinical settings., Results: In total, 9796 cases from 11172 records met inclusion criteria and contributed 9796 hCG, 7541 FSH, and 7536 LH values. The upper reference interval for our cohorts was 5.3 IU/L. HCG, FSH, and LH concentration had no significant correlations with age. HCG moderately correlated with FSH (r = 0.47) and LH level (r = 0.53). However, it was FSH but not LH that manifested good clinical applicability., Conclusion: The prevalence of hCG≥5.0 IU/L and 5.3 IU/L in women ≥55 years is 2.8% and 2.3% in the study population from China. The level of hCG 5.3 IU/L was suggested to be the positive threshold for postmenopausal women. FSH≥40IU/L helps to distinguish the pituitary source of hCG in postmenopausal women whose serum hCG concentrations were between 5.3 and 16 IU/L., Competing Interests: Conflicts of interest None reported., (Copyright © 2024. Published by Elsevier B.V.)

Sodium Alginate has a high demand and is favored for food packaging; however, this film typically exhibits poor antimicrobial activity. In this study, sodium alginate film containing peppermint essential oil, Japanese rice vinegar, or a combination of both, is used to analyze antimicrobial, mechanical, structural, and optical properties. The scanning electron microscopy (SEM) technique is utilized to observe the film's surface and cross-section homogeneity. The addition of peppermint essential oil and Japanese rice vinegar to the alginate film solution improves fungal growth and spore germination prevention. Unlike the film containing vinegar, the film with peppermint essential oil shows the lowest transparency. It also has the lowest tensile strength and exhibits the highest elongation at break and water vapor permeability. Conclusively, the film containing a combination of vinegar and essential oil indicates moderate values. According to AFM topography, the film with a mix of essential oil and vinegar has a smoother, more homogeneous surface than other films. Our results prove that combining vinegar and oil with sodium alginate film is an ideal choice. This combination significantly improves the performance of food packaging., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hakka Huangjiu, a traditional Chinese rice wine, boasts a rich history and is known for its immunomodulatory, antibacterial, anti-aging and anti-fatigue effects. However, there is limited research on the primary active components and molecular mechanism of the bioactivity of Hakka Huangjiu. To address this gap, this study assessed the structural characteristics, antioxidant, and immunomodulatory activities of the polysaccharide-1 of Guangdong Hakka Huangjiu (HP1). Structural analysis revealed that HP1 had a low molecular weight polysaccharide of 5550 Da, primarily consisting of glucose (93.2 %), with smaller amounts of xylose, mannuronic acid and galactose. Methylation and NMR analysis suggested that the main glycosidic linkages present in HP1 are α-D-Glcp-(1→, →4)-α-D-Glcp-(1 → and →6) -α-D-Glcp-(1→. Furthermore, HP1 exhibited dose-dependent DPPH·, ABTS + and OH· scavenging activity. HP1 exhibited significant protection of HepG2 cells from H 2 O 2 damage. Additionally, HP1 induced the release of NO, TNF-α, IL-6 and iNOS in RAW264.7 cells. HP1 treatment significantly increased mRNA expression of TNF-α, IL-6, iNOS, COX-2, IL-1β and TGF-β1. These results suggested that polysaccharides HP1 may have potential as a novel natural antioxidant and immunomodulatory product for use in nutraceuticals and functional foods., 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 B.V. All rights reserved.)

Objective: In this study, we investigated the fear of disease progression in Chinese PBT patients and examined the correlation between sociodemographic, clinical, and psychological variables of patients with the fear of progression (FoP). Additionally, the study also evaluated the subjective experience of FoP in patients with primary brain tumors (PBT)., Methods: A mixed-methods study was conducted between March 2022 and December 2023, consisting of two phases: a quantitative approach in phase I, and a qualitative approach in phase II. In phase I, 305 patients with PBT filled in several questionnaires. An analysis was performed to identify potential predictors associated with FoP. In phase II, semi-structured interviews were conducted with 16 participants whose FoP scores were ≥ 34 in phase I to obtain information on their personal experiences with FoP., Results: The results of the quantitative study showed that 192 (63 %) patients experienced high levels of FoP. The mean score of fear of progression was (34.02±6.78). Young age, high disease uncertainty, low social support, high negative coping and low positive coping are important factors affecting FoP in PBT patients. Qualitative research focused on three themes: triggers, coping styles, and the help needed., Conclusion: Enhanced screening and assessment of FoP is essential to identify dysfunctionin PBT. Meanwhile, the implications of these predictors for enhanced healthcare professional education and patient self-management may help healthcare providers implement relevant interventions promptly and help patients reduce their FoP. However, due to limitations such as sample, reporting bias, and specific mechanisms between predictors and FOPs that have not yet been explored in depth, further exploration is needed in the future., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patients often experience multiple prolonged symptoms following acute coronavirus disease 2019 (COVID-19) recovery, defined as long coronavirus disease (COVID). Patients with long COVID may experience dyspnea during acute and post-acute phases. Therefore, this study aimed to identify specific risk factors for dyspnea in patients with long COVID., Methods: Hospitalized patients with COVID-19, aged ≥18 years, were enrolled in this multicenter cohort study conducted at 26 medical institutions across Japan. Clinical data during hospitalization and patient-reported outcomes after discharge at the 3, 6, and 12-month follow-ups were retrieved from medical records and paper-based or smartphone application-based questionnaires, respectively., Results: Generalized linear mixed model (GLMM) analysis of prolonged dyspnea at each time point during follow-up showed that this symptom was associated with chronic obstructive pulmonary disease (COPD) (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.31-5.74), asthma (OR, 2.21; 95%CI, 1.17-4.16), and ventilator management (OR, 3.10; 95%CI, 1.65-5.83). In addition, patients with COPD (44.4%) and ventilator management (25.0%) were more frequently associated with delayed dyspnea onset. The generalized estimating equations analysis results with multiple imputed datasets, conducted as a sensitivity analysis, confirmed the adjusted GLMM analysis results., Conclusions: Prolonged dyspnea was associated with COPD, asthma, and severe infection that required mechanical ventilation in the Japanese population with long COVID. Further investigation is needed to clarify its mechanism and develop prophylactic and therapeutic strategies for dyspnea in patients with long COVID., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Objective: Develop a time-dependent deep learning model to accurately predict the prognosis of pediatric glioma patients, which can assist clinicians in making precise treatment decisions and reducing patient risk., Study Design: The study involved pediatric glioma patients from the Surveillance, Epidemiology, and End Results (SEER) Registry (2000-2018) and Tangdu Hospital in China (2010-2018) within specific time frames. For training, we selected two neural network-based algorithms (DeepSurv, neural multi-task logistic regression [N-MTLR]) and one ensemble learning-based algorithm (random survival forest [RSF]). Additionally, a multivariable Cox proportional hazard (CoxPH) model was developed for comparison purposes. The SEER dataset was randomly divided into 80 % for training and 20 % for testing, while the Tangdu Hospital dataset served as an external validation cohort. Super-parameters were fine-tuned through 1000 repeated random searches and 5-fold cross-validation on the training cohort. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). Furthermore, the accuracy of predicting survival at 1, 3, and 5 years was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and the area under the ROC curves (AUC). The generalization ability of the model was assessed using the C-index of the Tangdu Hospital data, ROC curves for 1, 3, and 5 years, and AUC values. Lastly, decision curve analysis (DCA) curves for 1, 3, and 5-year time frames are provided to assess the net benefits across different models., Results: A total of 9532 patients with pediatric glioma were included in this study, comprising 9274 patients from the SEER database and 258 patients from Tangdu Hospital in China. The average age at diagnosis was 9.4 ± 6.2 years, and the average survival time was 96 ± 66 months. Through comprehensive performance comparison, the DeepSurv model demonstrated the highest effectiveness, with a C-index of 0.881 on the training cohort. Furthermore, it exhibited excellent accuracy in predicting the 1-year, 3-year, and 5-year survival rates (AUC: 0.903-0.939). Notably, the DeepSurv model also achieved remarkable performance and accuracy on the Chinese dataset (C-index: 0.782, AUC: 0.761-0.852). Comprehensive analysis of DeepSurv, N-MTLR, and RSF revealed that tumor stage, radiotherapy, histological type, tumor size, chemotherapy, age, and surgical method are all significant factors influencing the prognosis of pediatric glioma. Finally, an online version of the pediatric glioma survival predictor based on the DeepSurv model has been established and can be accessed through https://pediatricglioma-tangdu.streamlit.app., Conclusions: The DeepSurv model exhibits exceptional efficacy in predicting the survival of pediatric glioma patients, demonstrating strong performance in discrimination, calibration, stability, and generalization. By utilizing the online version of the pediatric glioma survival predictor, which is based on the DeepSurv model, clinicians can accurately predict patient survival and offer personalized treatment options., 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. Published by Elsevier Ltd.)

Background: Eyebrow transplant surgeries have become increasingly popular in recent years. Periauricular hair, with its slow growth rate and fine caliber similar to eyebrow hair, has been strategically used in eyebrow transplants to achieve enhanced and authentically natural aesthetic results., Objectives: This study aimed to assess the postoperative clinical outcomes of using periauricular hair for eyebrow transplantation., Methods: Data from 81 patients (72 women and 9 men) who underwent eyebrow transplantation with periauricular hair between October 2020 and September 2022 were analyzed. They were followed up for 15 months' post-surgery to evaluate recovery and complications. Patient satisfaction and quality of postoperative life were assessed using a 5-point Likert scale., Results: For female patients, the average total number of transplanted hair grafts and surgery duration were 402.33 ± 158.48 FU (follicular unit) and 193.86 ± 66.69 min, respectively. Contrastingly, male patients exhibited slightly higher values, with an average of 481.78 ± 126.43 FU and 229.00 ± 96.80 min, respectively. No significant complications were reported during the postoperative follow-up. Patients expressed general satisfaction with immediate and 15-month postoperative outcomes, reflected in a mean overall satisfaction score of 4.90. The overall satisfaction of the subjects at 15 months postoperative was significantly higher than the preoperative satisfaction (Z = -8.483, p < 0.001). The eyebrow/forehead surgery did not have a significant impact on postoperative satisfaction (H = 5.355, p = 0.374 > 0.05); however, patients without tattoos tended to report higher levels of postoperative satisfaction (Z = 8.056, p = 0.004 < 0.05). Patient satisfaction ratings for physical function, psychological function, social function, and quality of life post-operation were 5, 4.95, and 4.94, respectively., Conclusions: Eyebrow transplant using periauricular hair can improve cosmetic outcomes and is a viable option in clinical practice., Competing Interests: Declaration of competing interest None., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Periodontitis is a chronic multifactorial inflammatory disease which eventually lead to tooth loss (TL). Therefore, a retrospective study was conducted to evaluate the status of tooth survival within 11 years after non-surgical periodontal treatment (NSPT) and to analyze the risk factors especially crown-root ratio (CRR) that affected TL in Chinese with advanced periodontitis., Methods: 3481 teeth of 131 subjects who underwent NSPT were examined retrospectively within a mean follow-up period of 11.6 years. The association of risk factors including clinical and radiographic parameters with TL was assessed using univariate and multivariate Cox regression analyses. Smooth curve fitting and segmented regression model were conducted to show the nonlinear relationship and the threshold effect between CRR and the risk of TL., Results: 347 teeth were lost in 97 patients in this study. Male, diabetes mellitus, heavy-smoker, molar, probing depth (PD), attachment loss (AL), bleeding on probing (BOP), tooth mobility, and radiographic bone loss were significantly associated with tooth loss (P < 0.05). A nonlinear relationship between CRR and the risk of TL was found, with different turning point values between molars and non-molars (1.9 vs. 2.76)., Conclusions: The findings based on practice-based clinical and radiographic data do suggest a nonlinear relationship between CRR and the survival of teeth, and provide evidence to help clinicians to determine the prognosis of teeth for patients with advanced periodontitis., Clinical Significance: Based on clinical and radiographic data, this study provides an individualized basis for clinicians to judge the dental prognosis of patients with advanced periodontitis according to the different tooth sites., 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.)

Objectives: The objectives of the present study were to (i) re-evaluate and expand the psychometric properties of two weight stigma instruments-the Perceived Weight Stigma Scale (PWSS) and the Weight Self-Stigma Questionnaire (WSSQ) among a large sample of adolescents using advanced psychometric methods and (ii) examine how the different types of weight stigma (i.e., PWSS and WSSQ) are associated with psychological distress., Study Design: Cross-sectional study., Methods: In September 2023, a cross-sectional survey utilising convenience sampling was used to recruit 9995 adolescents (mean age = 16.36 years [standard deviation = 0.78]; 57.8% males). They completed the PWSS, WSSQ, and a measure on psychological distress. The data were analysed using Rasch analysis, confirmatory factor analysis (CFA), structural equation modelling (SEM), and network analysis., Results: The CFA and Rasch model results showed acceptable psychometric properties regarding factor structure, factor loading, difficulty, and infit and outfit mean squares (except Items 4 and 7 of the PWSS). There was no substantial differential item functioning for any tested items across the sex and weight categories. The CFA and SEM results showed promising validity indices with significant associations between both weight stigma scales and psychological distress (i.e., depression, anxiety, and stress). Network analysis showed inter-variable connectivity between nodes PWSS3 ("People act as if they are afraid of you") and WSSQF7 ("I feel insecure about others' opinions of me")., Conclusions: Both weight stigma scales had acceptable psychometric properties and were significantly associated with psychological distress, although each assessed different types of weight stigma. This suggests that researchers and clinicians can use these scales to reliably and validly assess weight stigmas among adolescents., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Study Design: Cross-sectional study., Objectives: Suboptimal health status (SHS) is a third state between health and disease. Long-term being SHS will be detrimental to one's ability development. Previous studies have demonstrated the associations of lifestyle behaviors or work stress with SHS, but few studies have comprehensively analyzed the underlying factors and mechanisms between the three. This study aimed to investigate whether lifestyle behaviors mediated the relationship between self-perceived work stress and SHS., Methods: A total of 4238 urban workers, who participated in a cross-sectional survey conducted from December 2018 to October 2019, were included. A general linear model was used to explore the associations between lifestyle behaviors and self-perceived work stress with SHS after adjusting for demographic variables. Structural equation modeling was performed to examine the mediation by lifestyle behaviors., Results: The mean transformed scores of physical, mental, and social SHS were 70.98, 67.17, and 61.72, respectively. Unhealthy lifestyle behaviors and high self-perceived work stress positively affected SHS (P < 0.001). Self-perceived work stress imposed negative effects on physical SHS (β = -0.228, P < 0.001), mental SHS (β = -0.237, P < 0.001), and social SHS (β = -0.092, P < 0.001). The indirect effects of self-perceived work stress on physical SHS (β = -0.139, 95% CI: -0.178 to -0.106), mental SHS (β = -0.106, 95% CI: -0.134 to -0.082), and social SHS (β = -0.121, 95% CI: -0.154 to -0.092) were statistically significant., Conclusions: Lifestyle behaviors and self-perceived work stress were significantly associated with SHS among Chinese urban workers. The mediating effects of unhealthy lifestyle behaviors were found in the relationship between high self-perceived work stress and SHS. Future longitudinal research may verify these associations and elucidate the underlying mechanisms., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Indolent natural killer cell lymphoproliferative disorder of the gastrointestinal tract (iNKLPD-GI) is an uncommon, recently recognized lymphoid proliferation of mature NK cells primarily manifesting in the GI tract. Unlike NK/T lymphoma, iNKLPD-GI exhibits a rather indolent clinical course, underscoring the need for cautious management to prevent unnecessary interventions. However, clinical and molecular features of this entity have not been thoroughly understood. This study aimed to add more information to the current knowledge of this disease. Seven patients with iNKLPD-GI were included in our study. Clinical data included initial symptoms, endoscopic manifestations, pathological features, and therapies. Besides, next-generation sequencing was arranged to explore the underlying genetic mechanism of this disease. In our study, iNKLPD-GI in the urinary bladder was first identified. Edema of extremities (3, 42.8 %) was the most prevalent onset symptom which was reported for the first time. Pathological and immunohistological features were found to display the phenotype of NK cells. Unlike extranodal NK/T cell lymphoma, Epstein-Barr virus-encoded small RNA (EBER) were negative in all patients. Moreover, we found that two patients harbored JAK3 mutation. Apart from JAK3 K563&#95;C565del previously reported in the literature, we discovered new JAK3 mutation sites. Other mutations including BRAF, KRAS, and SH2B3 were also identified. In conclusion, iNKLPD-GI was an indolent atypical NK-cell proliferation with diverse clinical characteristics. "Watch and wait" therapy was preferable to intense chemotherapy. Recurrent JAK3 mutation may be the underlying mechanism responsible for the neoplastic nature of the disease and may serve as a potential target for patients with severe symptoms., 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. Published by Elsevier Inc.)

Introduction: Surgery is often delayed in patients with proximal femoral fractures who receive oral anticoagulants, to avoid complications related to perioperative bleeding. However, surgery delay may increase the risk of postoperative mortality. Our primary goal was to understand whether anticoagulated patients benefit from early surgery in terms of survival and perioperative complications., Methods: This is a multicenter retrospective cohort study of 581,189 patients with proximal femoral fractures. About 2.0 % (n = 11,385) received direct oral anticoagulants (DOAC) and 1.5 % (n = 8,726) received warfarin. Surgery was performed within 48 h in 37.6 % of DOAC patients, 27.6 % of warfarin patients and in 41.9 % of nonanticoagulated patients. Survival analysis was applied to compare mortality rate, blood transfusions, systemic complications and surgical complications during hospitalization between the study groups., Results: Patients receiving anticoagulation were older and had more comorbidities than patients without anticoagulation. There were overall similar rates of mortality (0.8 %, 1.1 % and 1.2 %) and surgical complications (2.1 %, 2.1 % and 2.2 %) in non-anticoagulated, DOAC and warfarin patients. Blood transfusions and systemic complications were higher in all anticoagulated patients regardless of surgery timing. There were comparable rates of early surgery (41.9 %, 37.6 % and 27.6 %, respectively). When operated early, DOAC patients had more surgical complications (OR=1.24, p = 0.04). Warfarin patients operated early had higher mortality (OR=1.48, p = 0.08) and higher risk of blood transfusions (OR=1.24, p < 0.001)., Discussion: Age and comorbidities could explain higher rates of postoperative systemic complications in anticoagulated patients. Nevertheless, overall short-term mortality was similar between the groups. Early surgery was associated with higher rates of surgical complications in DOAC patients. When operated early, patients receiving warfarin were at an increased risk of mortality (p = 0.08) and perioperative blood transfusions., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to evaluate the associations between adherence to 24-Hour Movement Guidelines (24-HMG) with continuous metabolic syndrome score (cMetS) among Chinese children., Study Design: Cross-sectional study., Methods: We conducted a cross-sectional study among 4604 children aged 6-17 years from Shenzhen, China. The 24-HMG was constructed using the self-report information on moderate-to-vigorous physical activity (MVPA), screen time (ST), and sleep duration. The cMetS was calculated based on waist circumference, homoeostatic model assessment for insulin resistance, mean arterial blood pressure, high-density lipoprotein cholesterol, and triglyceride. Multivariate linear regression models were used to assess the associations between adherence to recommendations of 24-HMG and cMetS., Results: Among the participants, 563 (12.23%) students adhered to 3 recommendations of the 24-HMG. We found that adhering to more recommendations was negatively associated with cMetS (P for trend: <0.001). For specific combinations, meeting the ST + MVPA recommendations was negatively associated with cMetS (coefficients [β]: -0.686; 95% confidence interval [CI]: -1.148, -0.223). Individuals who adhered to all recommendations had a lower cMetS (β: -0.693; 95% CI: -1.147, -0.238) than those who met none of the recommendations., Conclusions: Our study showed that adherence to more recommendations of the 24-HMG was associated with lower levels of cMetS in Chinese children and adolescents., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Tranexamic acid is one component of a complex management algorithm for postpartum hemorrhage. In Japan, the 2010 obstetric hemorrhage management guidelines was revised in 2017, adding the recommendation for the administration of tranexamic acid for postpartum hemorrhage. This research aims to delineate the temporal trends in tranexamic acid administration in patients undergoing cesarean deliveries and to examine the impact of the obstetric hemorrhage management guidelines implementation., Methods: An interrupted time series analysis was conducted on data from patients who underwent cesarean deliveries from April 2012 to August 2021, sourced from Japan's nationwide health insurance claims database. We examined the trends of tranexamic acid usage and blood transfusion use before and after the implementation of the revised guidelines in 2017., Results: The study cohort comprised 91 166 cesarean deliveries. Prior to the guideline implementation, the rate of tranexamic acid usage decreased. Post-guidelines implementation, there was a statistically significant increase in the rate of tranexamic acid use, with a quarterly percentage change of 0.48% (95% confidence interval: 0.36 to 0.60; P < 0.001). The guidelines implementation in 2017 was not significantly associated with a change in the rate of transfusions., Conclusions: This interrupted time series analysis demonstrated a significant increase in the rate of tranexamic acid administration following the implementation of the revised guidelines, reversing the previously observed downward trend. Our findings could reflect the impact of the revised guideline on the use of tranexamic acid for postpartum hemorrhage, but this did not translate to fewer blood transfusions., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Japan's super-aged society presents significant challenges, particularly with regard to managing aspiration pneumonia among older adults. We aimed to investigate the link between anticholinergic drug use and the incidence of aspiration pneumonia, primarily utilizing data from the Japanese Adverse Drug Event Report (JADER) database., Methods: The primarily analysis included JADER data from the first quarter of 2004 through the third quarter of 2023, focusing on 2367 cases of aspiration pneumonia in individuals aged ≥60 years. The study examined the association of aspiration pneumonia with 49 drugs listed in the Anticholinergic Risk Scale, using the Reporting Odds Ratio for signal detection. A scoping review incorporating findings from MEDLINE and the Cochrane Library was conducted to validate these associations., Results: The primary analysis identified an increased risk of aspiration pneumonia associated with specific drugs, including clozapine, haloperidol, risperidone, quetiapine, and olanzapine. A total of 20 drugs were significantly associated with an increased risk of aspiration pneumonia. Our results emphasize the importance of considering the dopamine-blocking effects of these drugs, particularly in at-risk populations, such as older adults, and those with conditions, such as schizophrenia or Parkinson's disease., Conclusions: The study highlights the importance of careful monitoring of anticholinergic drugs with potent dopamine-blocking effects, such as clozapine, haloperidol, risperidone, quetiapine, and olanzapine, to reduce the risk of aspiration pneumonia. Future research should include observational and interventional studies to further investigate these findings., Ethics and Dissemination: As this study utilized pre-existing anonymized information, approval from an ethics committee was not required., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Respiratory syncytial virus (RSV) represents a global health concern, including in older adults. This study assessed the safety and immunogenicity of mRNA-1345, an investigational mRNA RSV vaccine, in adults aged ≥60 years of Japanese descent., Methods: In this phase 1, randomized, observer-blind, placebo-controlled study, participants were randomized to receive one injection of mRNA-1345 100 μg or placebo. Solicited local and systemic adverse reactions (ARs) were collected within 7 days following injection. Unsolicited adverse events (AEs) were collected up to 28 days after injection; AEs of special interest, medically attended AEs, and serious AEs were collected through end of study. Immunogenicity was assessed at baseline and months 1, 2, 3, and 6 following injection., Results: Twenty-five adults of Japanese descent aged ≥60 years received one injection of mRNA-1345 100 μg (n = 21) or placebo (n = 4). mRNA-1345 was well-tolerated; the most common local and systemic solicited ARs were injection site pain, and fatigue and myalgia, respectively, which were generally mild to moderate and transient. No serious AEs were reported. Neutralizing (nAb) and binding (bAb) antibodies were detectable at baseline, consistent with prior RSV exposure. mRNA-1345 boosted RSV nAb titers and preF bAb concentrations 1 month post-injection (geometric mean fold rise: RSV-A nAb, 11.2; RSV-B nAb, 6.6; preF bAb, 9.1). Titers among mRNA-1345 recipients remained above baseline through 6 months., Conclusions: mRNA-1345 100 μg was well-tolerated among older adults of Japanese descent and induced nAbs and bAbs which were durable through 6 months, supporting its continued development., Trial Registration: ClinicalTrials.gov, NCT04528719., Competing Interests: Declaration of competing interest Archana Kapoor, Alana K. Simorellis, Caroline Reuter, Catherine A. Panozzo, Christine A. Shaw, Eleanor Wilson, Grace L. Chen, Hanako Mihara, Jaya Goswami, Lauren Wilson, Rakesh Dhar, Ruiting Guo, Runa Mithani, and Sonia K. Stoszek are employees of Moderna, Inc., and hold stock/stock options in the company. Anthony Mills received research funding from Janssen Pharmaceuticals. Sonia K. Stoszek received travel fees, gifts, and others from Moderna, Inc. David Fitz-Patrick received research funding from Pfizer., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objectives: In this observational study, we aimed to evaluate the independent and overlapping effects of multiple frailty domains on long-term care insurance (LTCI) use., Design: Population-based cohort design., Setting and Participants: In total, 9804 community-dwelling older adults were recruited from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes., Methods: The physical domain of frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria. The cognitive domain of frailty was identified as impairment of memory, attention, executive function, or processing speed using standardized thresholds established for each domain in population-based cohorts. The social domain was operationalized using the National Center for Geriatrics and Gerontology-Social Frailty Scale. The use of LTCI was prospectively determined over 60 months using data extracted from the Japanese long-term care insurance system., Results: The data from 7745 participants were analyzed, of whom 793 (10.2%) required LTCI certification within 60 months (interquartile range: 60-60 months). The Kaplan-Meier curve analysis demonstrated that a high number of frailty domains was associated with incident LTCI use. The proportions of incident LTCI use were 6.0%, 12.4%, 30.1%, and 43.9% for non-frail participants and those with impairments in 1, 2, and 3 frailty domains, respectively. In the multivariate Cox regression model, physical, cognitive, and social domain impairments independently increased the risk of incident LTCI use [physical domain impairment, hazard ratio (HR), 1.67; 95% CI, 1.39-2.01; cognitive domain impairment, HR, 1.59; 95% CI, 1.37-1.84; social domain impairment, HR, 1.26; 95% CI, 1.05-1.50]., Conclusions and Implications: Overlapping frailty domains were strongly associated with incident LTCI use among community-dwelling older adults. These findings emphasize the importance of assessing multiple frailty domains and tailoring interventions according to the unique circumstances of older adults to prevent functional disabilities., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Physical exercise improves physical and psychological health. However, information on the quantitative impact of Traditional Chinese Exercise (TCE) on physical and psychological health remains limited. Therefore, this systematic review and meta-analysis aimed to quantitatively explore the effects of TCE on the physical and psychological health of patients with multiple sclerosis (MS)., Methods: A comprehensive search was conducted across seven electronic databases (PubMed, SCOPUS, CINAHL, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang) from their inception to March 7, 2024 using the terms, Taiji, Tai Chi, Tai Chi Chuan, Qigong, Baduanjin, Wuqinxi, Yijinjing, multiple sclerosis, and disseminated sclerosis. Randomized controlled trials (RCTs) and non-RCTs reporting the effects of TCE on physical function or psychological health outcomes in MS patients were included. A random-effects model and 95 % confidence intervals (95 % CI) were used to compute the effect sizes., Results: Eleven studies, including 461 subjects with MS, were included in this meta-analysis. TCE significantly increased balance (d = 0.88, 95 % CI [0.45, 1.31], p < 0.001, I 2  = 39.26 %), activities of daily living (d = 1.17, 95 % CI [0.30, 2.04], p < 0.001, I 2  = 89.15 %), Multiple Sclerosis Impact Scale (MSIS) scores (d = 0.53, 95 % CI [0.12, 0.93], p = 0.01, I 2  = 0 %), depression (d = 0.66, 95 % CI [0.003, 1.32], p = 0.049, I 2  = 62.97 %), and Activities-Specific Balance Confidence (ABC) scores (d = 1.30, 95 % CI [0.41, 2.18], p < 0.001, I 2  = 0 %) compared with control conditions., Conclusions: This meta-analysis suggests the efficacy of TCE in improving balance, activities of daily living, MSIS scores, depression, and ABC scores in MS patients. However, further high-quality research is warranted to investigate these findings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Dysfunctional breathing (DB) is a major asthma comorbidity; however, it is not well recognized in Japan. Moreover, it has rarely been reported in the asthma population, and its clinical characteristics are unclear. We aimed to clarify the clinical characteristics of DB as a comorbidity in patients with asthma in Japan. Questionnaire surveys were conducted among patients with asthma at medical facilities in three regions of Japan (Niigata, Kumamoto, and Tokyo)., Methods: This cross-sectional questionnaire survey targeting patients with asthma who had regularly visited medical institutions and their doctors was conducted from September to November 2021. The questionnaire addressed the control status and method of treatment. The diagnosis of DB was evaluated using the Nijmegen questionnaire (NQ)., Results: There were 2087 eligible participants. Based on their NQ scores, 217 patients were classified into the DB group (NQ ≥ 19). There were significant differences with respect to sex, disease duration, Asthma Control Test (ACT) scores, Patient Health Questionnaire-9 (PHQ-9) scores, type-2 biomarkers, pulmonary function indices, treatment methods, severity, and asthma exacerbations in the previous year between the DB and non-DB groups. In the multivariate analysis, there were significant differences in sex, disease duration (≥15 y), ACT scores (<20), and PHQ-9 scores (≥10). The cluster analysis of cases with DB classified the population into four clusters., Conclusions: The asthma population with DB exhibited several characteristics, including depression and poorly controlled asthma. Further large-scale interventional investigations with longer follow-up periods are necessary to verify these findings., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Objectives: Suicide is a serious mental health problem among university students. The current study aimed to examine the effectiveness of a novel intervention that targets suicide risk by enhancing self-esteem and self-compassion., Methods: Participants were recruited from the healthcare center at a Japanese University. Measurements of suicidal risk, self-compassion, self-esteem, and other psychological variables were collected at baseline, post-intervention, four-week follow-up, eight-week follow-up, and twelve-week follow-up. Participants also provided feedback on the program's acceptability., Results: A total of 17 participants consented to participate in the intervention, 14 completed post-treatment assessment, 10 completed the four-week follow-up assessment, and 8 completed the eight-week and twelve-week follow-up assessment. Following the intervention, the study observed moderate to large improvements in self-esteem, self-compassion, hopelessness, depression, and suicide risk. The participants also reported reliable changes in clinical outcomes and positive perceptions of the program., Conclusions: The psychoeducation program exhibited high acceptability and feasibility and promising early outcomes. Despite the small sample size and lack of a control group, these findings suggest potential benefits of the program. Further studies for examining the efficacy of the program are highly warranted., Competing Interests: Declaration of Competing Interest None of the authors have a conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Some studies reported a relationship between life-space mobility (LSM) and frailty assessed by physical aspects; however, a more comprehensive discussion of frailty is underdeveloped. In addition, previous studies have focused only on older Euro-American people. Therefore, we aimed to examine LSM-frailty relationships in community-dwelling older Japanese persons using physical and comprehensive frailty indices., Design: A cross-sectional study., Setting and Participants: We used the data of 8898 older adults from a baseline survey of the Kyoto-Kameoka Study in Japan., Methods: The validated life-space assessment (LSA) was used to evaluate LSM and categorized it into quartiles. Two validated indices were used to evaluate frailty: the Kihon Checklist (KCL) and the simple Frailty Screening Index (FSI). Multivariable logistic regression was used to determine the relationships between LSM scores and frailty., Results: The mean age (SD) of the participants was 73.4 (6.3) years, and 53.3% were women. The mean LSM score of the study participants was 53.0. The prevalence of frailty by KCL and FSI was 40.7% and 16.8%, respectively. Significant differences between LSM score and frailty prevalence were observed [KCL: Q1, reference; Q2, odds ratio (OR) 0.53, 95% CI 0.45-0.62; Q3, OR 0.30, 95% CI 0.25-0.35; Q4: OR 0.22, 95% CI 0.18-0.26, P for trend <.001; FSI: Q1, reference; Q2, OR 0.57, 95% CI 0.48-0.68; Q3: OR 0.38, 95% CI 0.31-0.46; Q4: OR 0.35, 95% CI 0.28-0.42, P for trend <.001]. Similar results were observed when LSM scores were examined at 10-point intervals, with LSM and frailty exhibiting an L-shaped relationship. The LSM score dose-response curve at which the OR for frailty plateaued among older individuals was approximately 81-90 score., Conclusions and Implications: LSM score and frailty prevalence exhibited L-shaped relationships in community-dwelling older persons. This study's findings provide useful data for setting LSM targets for preventing frailty in community-dwelling older persons., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: The INCREASE trial, conducted in the United States, showed that inhaled treprostinil improved exercise capacity in pulmonary hypertension associated with interstitial lung disease (PH-ILD). However, hemodynamic and pharmacokinetic measurements were not performed in the trial. The objective of this trial was to evaluate the efficacy on hemodynamics and exercise capacity, safety, and pharmacokinetics (PK) of inhaled treprostinil in Japanese patients with PH-ILD., Methods: This trial was a multicenter, non-randomized, open-label, single-arm trial of patients with PH-ILD. Inhaled treprostinil was administered at 3 breaths (18 μg)/session four times daily, and the dose was gradually increased to a maximum of 12 breaths (72 μg)/session. The primary endpoints were the change of pulmonary vascular resistance index (PVRI) and peak 6-min walking distance (6MWD) from baseline to week 16. Endpoints also included other efficacy parameters, safety, and PK., Results: Twenty patients received inhaled treprostinil. At week 16, PVRI decreased from baseline by -40.1% (95% CI, -53.1 to -27.2) and peak 6MWD increased by 13.0 m (95% CI, -15.0 to 49.0). The most frequently reported adverse events related with treprostinil were cough, malaise and blood pressure decreased. PK was similar to those in pulmonary arterial hypertension (PAH) patients., Conclusions: Treatment with inhaled treprostinil using the same dosing regimen as in the INCREASE trial resulted in improvements in hemodynamics and exercise capacity with a favorable tolerability and safety profile in Japanese patients with PH-ILD., Competing Interests: Declaration of competing interest Seiichiro Sakao received honoraria from Nippon Shinyaku. Co., Ltd.; Yasuhiro Kondoh received honoraria from Nippon Boehringer Ingelheim.; Hideyuki Kinoshita received honoraria from Nippon Shinyaku Co., Ltd.; Osamu; Nishiyama received honoraria from Janssen Pharmaceutical K.K, Nippon Boehringer Ingelheim, and Nippon Shinyaku Co., Ltd.; Takeshi Ogo received honoraria from Bayer Pharma Japan, Janssen Pharmaceutical K.K, and Nippon Shinyaku Co., Ltd.; Nobuhiro Tanabe received honoraria from Bayer Pharma Japan, Janssen Pharmaceutical K.K, and Nippon Shinyaku Co., Ltd.; Shun Minatsuki received research funding from Fukuda Denshi Co. Ltd. and Sumitomo Mitsui Trust Bank.; Kazuhiko Nakayama has no conflict of interest.; Yu Taniguchi received research grant from Janssen Pharmaceutical K.K.; Kenta Takahashi and Masahiro Takatsu are employees of Mochida Pharmaceutical. They have received remuneration and travel fees within the framework of their employment.; Takashi Ogura received honoraria from Nippon Boehringer Ingelheim., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population., Methods and Results: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001)., Conclusions: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: This study aims to investigate the association of Chinese visceral adiposity index (CVAI) with incident hyperuricemia (HUA)., Methods and Results: We included 5186 adults aged ≥45 years from China Health and Retirement Longitudinal Study. Modified Poisson regression model was used to estimate the relative risks (RRs) of incident HUA associated with baseline CVAI, and logistic model was used to estimate the odds ratios (ORs) of HUA for CVAI change. Restricted cubic splines analysis was adopted to model the dose-response associations. The area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the predictive value of CVAI. During 4-year follow-up, a total of 510 (9.8%) HUA cases were identified. The RRs (95%CIs) of incident HUA were 3.75 (2.85-4.93) for quartile 4 versus quartile 1 and 1.56 (1.45-1.69) for per-standard deviation increase in baseline CVAI. For the analyses of CVAI change, compared with stable group, participants in decreased group had 34% lower risk (OR 0.66, 95%CI 0.49-0.87) and those in increased group had 35% (1.35, 1.03-1.78) higher risk of HUA. Linear associations of baseline CVAI and its change with HUA were observed (P nonlinear >0.05). Besides, the AUC value for HUA was 0.654 (0.629-0.679), which was higher than other five obesity indices., Conclusions: Our study found linear associations between baseline CVAI and its change and risk of HUA. CVAI had the best predictive performance in predicting incident HUA. These findings suggest CVAI as a reliable obesity index to identify individuals with higher HUA risk., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: Lorlatinib, a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated robust overall and intracranial antitumor activity in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) previously treated with an ALK inhibitor in a global phase 1/2 study (NCT01970865) and a multicenter phase 2 study conducted in China (NCT03909971). We report updated 3-year follow-up data from the phase 2 study., Materials and Methods: Chinese patients with locally advanced or metastatic ALK-positive NSCLC that progressed after crizotinib as the only prior ALK inhibitor (cohort 1) or after 1 non-crizotinib ALK inhibitor (cohort 2), were enrolled in the study. All patients received lorlatinib 100 mg once daily., Results: At data cutoff, of 109 enrolled patients, the median duration of follow-up for progression-free survival (PFS) was 35.8 months in cohort 1 (n = 67) and 33.1 months in cohort 2 (n = 42). Median PFS (95% CI) per independent central review was 26.3 months (16.6-35.9) and 5.6 months (2.9-12.4), respectively. The median duration of follow-up for overall survival (OS) was 36.4 months and 37.5 months, respectively. Median OS (95% CI) was not reached (NR; NR-NR) and 21.9 months (11.9-NR), respectively. Median intracranial time to progression (95% CI) was NR (NR-NR) and NR (9.7 months-NR), respectively. No new safety signals emerged with long-term treatment., Conclusion: The long-term data confirm robust overall and intracranial clinical activity of lorlatinib, with no new safety signals emerging. These results support using lorlatinib in Chinese patients with previously treated ALK-positive NSCLC with or without brain metastases., Clinicaltrials: gov NCT03909971., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/μL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/μL in boys and 824 and 875 pmol/μL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity., 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 Inc. All rights reserved.)

Background and Aims: The relationship between vitamin D and cardiovascular health (CVH) in children remains unclear. We aimed to explore the association between vitamin D and CVH metrics using the latest Life's Essential 8 (LE8) among Chinese children and adolescents., Methods and Results: A cross-sectional study containing 2680 participants aged 7-18 years (1340 boys and 1340 girls) was performed in South China in 2013. Vitamin D levels were categorized as follows: ≥20 ng/mL (sufficiency), 12 - < 20 ng/mL (inadequacy), and <12 ng/mL (deficiency). The CVH metrics of LE8 was assessed by overall CVH score, health behavior score, health factor score and high CVH, among which the health behaviors included diet, physical activity, nicotine exposure, and sleep health, as well as the health factors contained body mass index, blood lipids, blood glucose, and blood pressure. Different regression models were used to assess the associations between vitamin D levels and CVH metrics of LE8. Results showed that the prevalence of vitamin D deficiency and inadequacy was 7.5% and 44.4%, respectively. Boys had lower levels in overall CVH score, health behavior score, and health factor score than girls. After adjusting for potential confounds, upward trends in diet score, health behavior score, and high CVH were observed with increasing vitamin D levels., Conclusion: Vitamin D levels were positively associated with high CVH based on LE8, and more attention should be paid on boys due to whose lower levels in CVH metrics., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: Improved understanding of metabolic obesity phenotypes holds great promise for personalized strategies to combat obesity and its co-morbidities. Such investigation is however lacking in Tibetans with unique living environments and lifestyle in the highlands. Effects of altitude on heterogeneous metabolic obesity phenotypes remain unexplored., Methods: We defined metabolic obesity phenotypes i.e., metabolically healthy/unhealthy and obesity/normal weight in Tibetans (n = 1204) living at 2800 m in the suburb or over 4000 m in pastoral areas. 129 lipoprotein parameters and 25 low-molecular-weight metabolites were quantified and their associations with each phenotype were assessed using logistic regression models adjusting for potential confounders. The metabolic BMI (mBMI) was generated using a machine learning strategy and its relationship with prevalence of obesity co-morbidities and dietary exposures were investigated., Results: Ultrahigh altitude positively associated with the metabolically healthy and non-obese phenotype and had a tendency towards a negative association with metabolically unhealthy phenotype. Phenotype-specific associations were found for 107 metabolites (e.g., lipoprotein subclasses, N-acetyl-glycoproteins, amino acids, fatty acids and lactate, p < 0.05), among which 55 were manipulated by altitude. The mBMI showed consistent yet more pronounced associations with cardiometabolic outcomes than BMI. The ORs for diabetes, prediabetes and hypertriglyceridemia were reduced in individuals residing at ultrahigh altitude compared to those residing at high altitude. The mBMI mediated the negative association between pastoral diet and prevalence of prediabetes, hypertension and hypertriglyceridemia, respectively., Conclusions: We found metabolite markers representing distinct obesity phenotypes associated with obesity co-morbidities and the modification effect of altitude, deciphering mechanisms underlying protective effect of ultrahigh altitude and the pastoral diet on metabolic health., 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 B.V. All rights reserved.)

Background and Aims: Current evidence of the association between egg consumption and cardiovascular diseases (CVD) is controversial. We aim to investigate the longitudinal association between egg consumption and the risk of CVD among Chinese adults., Methods and Results: A total of 16,030 adults who attended China Health and Nutrition Survey 1991-2015 were included in this study. Egg consumption was collected with 3-day 24-h recall method supplemented by household inventory record. Cumulative mean egg intake during 1991-2011 were calculated as the habitual intake. CVD incidence was self-reported as being diagnosed by physicians following study entry. The association between egg consumption and incident CVD was examined using Cox regression. The mean age (SD) of the study population was 43.7 (14.8) years and 51% were women. During a 9.9-year (median 9.0) follow up, 663 CVD incidents were reported. The corresponding incident rate (per 1000 person-year) by egg consumption level of none, 1-20, 21-50, and 50+gram/day was 2.6, 4.8, 4.2, 5.5 (P < 0.001) with the unadjusted HR (95% CI) of 1.0, 1.42 (1.12-1.80), 1.31 (1.02-1.67), 2.01 (1.53-2.64). After adjusted for demo socioeconomic, and behaviour factors, egg consumption>50 g/day increased the CVD incident by 43% (HR 1.43, 95% CI 1.02-2.00. BMI, hypertension, and diabetes mediated the association between egg consumption and CVD., Conclusion: Higher egg intake, as part of the modern dietary pattern high in sugars, fat, and animal-source foods, increased the risk of CVD. The effect of egg on CVD incident was partly mediated by overweight/obesity, hypertension, and diabetes., Competing Interests: Conflict of interest None., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to assess the prevalence of lumbopelvic pain (LPP), including low back pain (LBP) and/or pelvic girdle pain (PGP), consultation rate, and desire for treatment of postnatal Japanese women., Methods: We performed a cross-sectional study of 98 postnatal Japanese women within 1 year of childbirth. We retrospectively evaluated the prevalence of LBP before and during pregnancy and the prevalence of LPP after childbirth using a self-administered questionnaire. We used the distribution of pain to differentiate LBP and/or PGP after childbirth and its intensity was assessed using a visual analogue scale. The effects of LPP on daily life were assessed using the Oswestry disability index (ODI). In addition, we assessed the consultation rate for LPP and the desire to consult a healthcare professional, using self-administered questionnaires., Results: The prevalence of LPP after childbirth was 66%. Women with a history of LBP before and during pregnancy were more likely to have LPP following childbirth (both P < 0.001). The consultation rate among the postnatal women with LPP was 9%, but 56% of the women wished to consult a healthcare professional. The ODI score was significantly higher in postnatal women who wanted to consult a healthcare professional than in those who did not (P < 0.01)., Conclusions: Two thirds of the postnatal Japanese women who participated in this study had LPP, but the consultation rate was low. However, more than half of these women had the desire to consult a healthcare professional., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The associations between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [β (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; β (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [β (95% CI): 0.97 (0.61, 1.34) in males; β (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) μmol/L for males and 3.81 (95% CI: 1.60, 6.03) μmol/L for females. The association between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption., 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 Inc. All rights reserved.)

Background: In reconstructive surgery for large bone defects, the demand for bone allografts has increased over the years; however, it is unclear how the supply and demand in Japanese regional bone banks have evolved over time. This study investigated the 15-year supply and demand of bone allografts stored in a regional bone bank, along with assessing the screening process's effectiveness., Methods: The target period was 15 years from April 2005 to March 2020. The period was subdivided into three 5-year periods: first, second, and third. The study items included the number of bone allografts donated, the number of bone allografts used, donor and user facilities, surgical methods using bone allografts, and the number of bone allografts discarded. We used the Cochran-Armitage test for statistical analysis., Results: A total of 1852 bone allografts were donated to the bone bank, and a total of 1721 were used. A total of 677 bone allografts grafts were provided in the first period, 738 in the second period, and 525 in the third period, indicating a decreasing trend. The average number of allografts per surgery was 2.8 in the first, 3.1 in the second, and 1.7 in the third, showing a decreasing trend. Concerning the percentage of each surgery using bone allografts, spine fusion decreased in the third period but not significantly, whereas primary hip arthroplasty increased significantly in the third period. The total number of discarded bone allografts was 4.8% of the total number of donated bone allografts, largely because of a lack of screening tests., Conclusion: Although the number of allogeneic bone surgeries has been increasing over time, the number of allogeneic bone donations has shown a decreasing trend, and there is a need to develop a system that can provide surgeons with sufficient bone allografts., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Objective: This study explores the impact of leisure activity and the association between childhood starvation and the risk of diabetes in older Chinese adults., Design: Prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort study in China., Setting and Participants: A total of 4637 older adults aged ≥65 years, all with documented diabetes history, experiences of childhood starvation, and participation in leisure activities were recruited., Methods: Childhood starvation exposure was assessed via self-reported responses from a structured questionnaire. The leisure activities were measured by 9 distinctive components and categorized into 3 distinct categories: productive activity, recreational activity, and sedentary activity. Diabetes status was determined by self-reported, physician-diagnosed cases during the follow-up period. Nonparametric survival models were employed for analysis., Results: Over an average follow-up period of 4.3 years, 215 of 4637 participants (4.6%) reported a confirmed diagnosis of diabetes. Nonparametric survival models showed that those reporting childhood starvation had a higher risk of late-life diabetes [hazard ratio (HR) 1.72, 95% CI 1.21-2.44]. Engaging in productive activity (HR 0.90, 95% CI 0.83-0.99) and recreational activity (HR 0.88, 95% CI 0.77-1.00) was linked with a reduced risk of late-life diabetes. Sedentary activity did not show a significant effect. Further analysis highlighted the interactions effects of leisure activities on diabetes risk across different demographic and historical exposure subgroups., Conclusions and Implications: Engaging in productive and recreational leisure activities was inversely associated with the risk of diabetes in older adults who experienced childhood starvation. Promoting such activities could be beneficial in mitigating long-term diabetes risk related to early-life nutritional deficiencies., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) is a nontyphoidal Salmonella pathogen that causes swine paratyphoids. S. Choleraesuis is a zoonotic pathogen transmitted to humans via contaminated food and causes sepsis. Here, we report a rare case of pyelonephritis caused by S. Choleraesuis in a Japanese patient with a carcinoma of unknown primary origin. On the day of admission, the patient was diagnosed with pyelonephritis associated with ureteral stent obstruction. He had no history of raw pork consumption or gastrointestinal symptoms. Gram-negative rods were isolated from urine and blood cultures, identified as Salmonella enterica subsp. enterica using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The serological typing results were O7: -: 1 and 5; however, the serotypes could not be determined. The isolate was identified as S. Choleraesuis using multilocus sequence typing, nucleotide sequence analysis of the fliC gene, and biochemical examination. Four days after a 14-day course of intravenous piperacillin-tazobactam (9 g/day), the patient showed relapse of the condition. Subsequently, the patient was treated with intravenous ceftriaxone (2 g/day) and oral amoxicillin (1000 mg/day) for 14 days each; recurrence was not observed. This novel case of pyelonephritis with bacteremia was caused by S. Choleraesuis in Japan. Conventional testing methods could not identify the serotypes; however, the case highlights the importance of adopting advanced diagnostic techniques based on molecular biology to ensure accurate pathogen identification., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism., Methods: Plasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model., Results: Single-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDL-C). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that Se-Fe exhibited synergistic effects on LDL-C and non-HDL-C, and Se-Sn showed a synergistic effect on HDL-C., Conclusions: Our study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects., 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 B.V. All rights reserved.)

Background: The purpose of this study was to investigate the vessel density (VD) of the macular superficial capillary plexus (SCP) and its associated factors in healthy subjects., Methods: This prospective, cross-sectional study enrolled healthy Chinese volunteers. The optical coherence tomography angiography (OCTA) was used to measure the superficial VD in macula. A generalized estimation equation (GEE) model was used to analyze the ocular and systemic associated factors., Results: A total of 516 eyes of 262 healthy subjects were included (mean age 38.59 ± 21.03 years). The total VD of macular SCP was 16.85 ± 2.28 mm -1 . The VD in the inner ring and outer ring were significantly higher than that in the central ring, with the density being highest in nasal quadrant and lowest in the superior quadrant. After adjusting the ocular and systemic factors, age (β=-0.0085, P = 0.0122) and SSI (β=1.3261, P < 0.001) were significantly associated with total VD of the macular SCP., Conclusions: Among the healthy Chinese subjects included in the study, the mean total VD of macular SCP was 16.85 ± 2.28mm -1 . The macular superficial capillary density was positively associated with age and SSI. Further studies are still required to better understand the change of macular VD in aging and other pathological conditions., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yufei Dai reports was provided by National Natural Science Foundation of China. Yuxin Zheng reports was provided by National Key Research and Development Program of China. Yuanyuan Chen reports financial support was provided by National Natural Science Foundation of China. 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Hypertension is a risk factor for developing chronic kidney disease (CKD). Studies of adult participants in the USA reported that hypertension increased the risk of developing CKD even in the non-diabetic population. However, studies in non-diabetic populations are limited and additional studies in other races are required. This study aimed to examine the relationship between hypertension and the development of CKD in non-diabetic Asian adults., Methods and Results: In this longitudinal study, non-diabetic Japanese adults who took annual checkups from 1998 to 2023 were included. CKD was defined as <60 mL/min/1.73 m 2 , and hypertension was classified into four levels according to the guidelines of the American College of Cardiology/American Heart Association. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. Of the 7363 (men: 40.3%) people in the final cohort, 2498 (men: 40.1%) developed CKD after a mean follow-up of 7.99 years. Elevated blood pressure (BP) and hypertension stage 2 had a 9% (95% confidence interval [CI]: 1%-16%) and 11% (95% CI: 5%-17%) shorter survival time to CKD onset, respectively, than normal BP. Hypertension stage 1 also had a shorter survival to CKD onset by point estimate, but all 95% CIs crossed 1 in all models., Conclusions: In a relatively healthy Asian population without diabetes, controlling BP to an appropriate range reduces the risk of developing CKD., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Yukari Okawa declares a relationship with Zentsuji City that includes employment. Toshiharu Mitsuhashi declares no potential conflict of interest associated with this manuscript., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Breast cancer mortality varies in urban and rural areas in China. Studies have reported urban-rural difference across time period, however, the evaluation on urban-rural differences in age and birth cohort effects is limited. Our aim was to quantitatively assess urban-rural disparities in age, period and cohort effects in breast cancer mortality in China., Methods: We collected age-specific breast cancer mortality rates for urban and rural females aged 20-84 years from 1987 to 2021. Hierarchical age-period-cohort (HAPC) models were used to evaluate the effect of area (urban, rural) on breast cancer mortality and investigate urban-rural differences in age, time period and birth cohort effects., Results: We found a significant area (urban, rural) effect on breast cancer mortality in that rural females had a lower mortality risk than urban females [-0.25 (95 % confidence interval (CI): -0.32, -0.17)]. Age trajectories of mortality based on the HAPC model showed nonlinear trends with adjustment for area variable. The urban-rural difference in age effect appeared to be divergent with age, and urban women had higher mortality risk in the senior age group. The urban-rural difference in birth cohort effect indicated a reversal around the birth cohort group of 1962-1966, after which rural females had a higher mortality risk than urban females., Conclusion: The area (urban, rural) could affect breast cancer mortality among women, and the effect of urban-rural difference varies with age and birth cohort. To promote the health of urban and rural females, the gap between urban and rural areas should be shorten., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies., Methods: In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35])., Results: At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was -39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: -33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified., Conclusions: Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Spot urine collection offers a convenient alternative to the more cumbersome 24-h urine collection. However, the widely recognized estimation models, such as Tanaka and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT), have not been adequately adapted for widespread use in the general Chinese population., Objectives: This study was designed to evaluate the precision of the Tanaka and INTERSALT calibration models, alongside a locally Zhejiang Province-formulated model, in predicting 24-h urinary sodium (24-hUNa) excretion among the Chinese population., Methods: The study comprised 1424 participants, aged 18-69 y, who provided both comprehensive 24-h urine and fasting morning urine samples. The researchers assessed the accuracy of the measured 24-hUNa against the estimates obtained from the Tanaka, INTERSALT, and Zhejiang models. This evaluation was conducted at both population and individual levels, employing a range of statistical techniques, including bias analysis, correlation coefficients, intraclass correlation coefficients, receiver operating characteristic curves, Bland-Altman plots, as well as relative and absolute difference calculations, and misclassification rates., Results: The measured average 24-hUNa excretion was found to be 165.7 ± 71.5 mmol/24-h. Notably, there was a significant deviation between the estimated and measured values for the Tanaka-adjusted model [-11.7 mmol, 95% confidence interval (CI): -16.7, -6.7 mmol/24-h], indicating a statistically significant difference. In contrast, the deviations for the INTERSALT-adjusted model (0.6 mmol, 95% CI: -4.2, 5.4 mmol/24-h) and the Zhejiang model (0.2 mmol, 95% CI: -4.6, 5.0 mmol/24-h) were nonsignificant. The correlation coefficients for the models were 0.303, 0.398, and 0.391, respectively, with the INTERSALT-adjusted and Zhejiang models showing superior performance at the population level., Conclusions: The 3 evaluation models may serve as effective, low-burden alternatives for assessing urinary sodium levels in the population. However, to enhance the accuracy and reliability of predictions at the individual level, further repeated measurements are necessary to minimize measurement errors and augment the validity of the estimations., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study investigated Cantonese and Hong Kong Sign Language (HKSL) phonological activation patterns in Hong Kong deaf readers using the ERP technique. Two experiments employing the error disruption paradigm were conducted while recording participants' EEGs. Experiment 1 focused on orthographic and speech-based phonological processing, while Experiment 2 examined sign-phonological processing. ERP analyses focused on the P200 (180-220 ms) and N400 (300-500 ms) components. The results of Experiment 1 showed that hearing readers exhibited both orthographic and phonological effects in the P200 and N400 windows, consistent with previous studies on Chinese reading. In deaf readers, significant speech-based phonological effects were observed in the P200 window, and orthographic effects spanned both the P200 and N400 windows. Comparative analysis between the two groups revealed distinct spatial distributions for orthographic and speech-based phonological ERP effects, which may indicate the engagement of different neural networks during early processing stages. Experiment 2 found evidence of sign-phonological activation in both the P200 and N400 windows among deaf readers, which may reflect the involvement of sign-phonological representations in early lexical access and later semantic integration. Furthermore, exploratory analysis revealed that higher reading fluency in deaf readers correlated with stronger orthographic effects in the P200 window and diminished effects in the N400 window, indicating that efficient orthographic processing during early lexical access is a distinguishing feature of proficient deaf readers., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population., Methods: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19. The exposure variable was BMI measured at the time of admission, and the study outcomes were progression to critical illness and death. Analyses were performed for each age group., Results: Overall, 58,944 patients met the inclusion criteria. The risk of critical illness increased monotonically with higher BMI. In contrast, the relationship between BMI and mortality follows a J-shaped curve; being underweight and obese are risk factors for mortality. When stratified by age, similar trends were observed for both critical illness and mortality., Conclusion: A higher BMI is a risk factor for the progression of COVID-19 severity, whereas both lower and higher BMIs are risk factors for mortality in the Japanese population., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)