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Wei-Ting Hsu,* I-Wei Shang, Min Pan* Department of Physical Education and Kinesiology, National Dong Hwa University, Hualien, Taiwan*These authors contributed equally to this workCorrespondence: Min Pan, Email pan13min@gmail.comPurpose: This study aims to validate the Chinese version of the Novelty Need Satisfaction Scale (NNSS) within physical education (PE) contexts, incorporating three distinct studies to examine its reliability, validity, and measurement invariance across gender and different samples.Methods: Study 1 involved translating the original NNSS into Chinese and evaluating it through confirmatory factor analysis, item analysis, and assessments of internal consistency reliability among 390 students (53.8% male, 46.2% female), averaging 14.5 years in age. Study 2 assessed the discriminant validity of the Chinese NNSS by exploring correlations between novelty need satisfaction and three conventional basic psychological needs (BPNs) - autonomy, competence, and relatedness, in a larger cohort of 845 students (51.7% male, 48.3% female), with an average age of 14.8 years. This study also investigated the relationships between novelty need satisfaction, autonomous motivation, and enjoyment in PE. Study 3 examined the measurement invariance of the Chinese NNSS across gender and different samples, using a sample of 1235 students (52.6% male, 47.4% female), with an average age of 14.6 years.Results: The one-factor, five-item structure of the Chinese NNSS was confirmed in Study 1. Study 2 demonstrated the distinct yet covariant nature of novelty need satisfaction among BPNs and its predictive capability for enjoyment in PE through autonomous motivation. Study 3 confirmed the measurement invariance of the Chinese NNSS across gender and samples, validating its reliability and applicability.Conclusion: The validation of the Chinese NNSS within PE settings not only adds the need for novelty to the motivational sequence proposed by self-determination theory (SDT) but also emphasizes its significant role in enhancing autonomous motivation and enjoyment. This study suggests the scale’s utility for future research in exploring the dynamics among BPNs and provides deeper insights into the motivational processes in PE.Keywords: self-determination theory, basic psychological needs, cross-cultural validation, need for novelty

Hsin-I Cheng,1,* Wei-Ting Hsu,2,3,* Wei-Hsun Wang,4,5 Ren-Hau Li,6,7 Feng-Cheng Tang,3,4,8 Shu-Ling Huang6,7 1Department of Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 330, Taiwan; 2Department of Construction Engineering, Chaoyang University of Technology, Taichung, 413, Taiwan; 3Department of Leisure Services Management, Chaoyang University of Technology, Taichung, 413, Taiwan; 4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 402, Taiwan; 5Department of Orthopaedics, Changhua Christian Hospital, Changhua, 500, Taiwan; 6Department of Psychology, Chung Shan Medical University, Taichung, 402, Taiwan; 7Room of Clinical Psychology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan; 8Department of Occupational Medicine, Changhua Christian Hospital, Changhua, 500, Taiwan*These authors contributed equally to this workCorrespondence: Shu-Ling Huang, Department of Psychology, Chung Shan Medical University, 110, Section 1, Jianguo North Road, South District, Taichung, 402, Taiwan, Tel +886-4-24730022 ext. 12301, Fax +886-4-23248191, Email shuling@csmu.edu.tw Feng-Cheng Tang, Department Occupational Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan, Tel +886-4-7286929, Fax +886-4-727-0910, Email 106159@cch.org.twPurpose: The present study aims to examine the disparate effects of health behavior models, namely exercise self-efficacy (ESE), health belief model (HBM), and planned behavior theory (PBT), applied to clarify the degree of regular exercise among workers in Taiwan.Methods: A cross-sectional research design was adopted. A questionnaire was distributed to obtain information pertaining to regular exercise level, demographic characteristics, and the scores of ESE, HBM, and PBT. In total, 400 full-time workers voluntarily participated in this study.Results: The results showed that only 20.5% of the participants exercised regularly, 37.3% exercised irregularly, and 42.3% did not exercise currently. “Perceived benefits” and “perceived barriers” pertaining to HBM; “attitude” and “perceived behavioral control” pertaining to PBT; and ESE were associated with regular exercise level in the multiple linear regression analyses of each health behavior model. When all three models were considered simultaneously, ESE provided the greatest explanation of the variances for regular exercise levels. PBT total made a smaller contribution in the prediction of regular exercise level, while the effect of HBM did not show statistical significance. In order to explore the practicality of moving beyond theoretical models and focusing on the components across health behavior models to enhance workers’ exercise behavior, the components showing statistical significance in separate analysis were put into the multiple linear regression simultaneously. The results showed that ESE, perceived barriers of health behavior, attitude, and perceived behavioral control were significantly associated with regular exercise level.Conclusion: A low percentage of workers exercising regularly should be a notable issue for workplace health promotion. Neither utilizing cues to exercise nor advertising health threats of physical inactivity is sufficient to enable workers to exercise regularly. Enhancing workers’ ESE and behavior control and removing the exercise barriers would constitute efficient strategies for maintaining the exercise habit of workers.Keywords: exercise, self-efficacy, health belief model, planned behavior theory, worker

Wen-Tung Hsu,1 Deng-Ho Yang,1– 4 Chun-Cheng Liao,3,5 Jia -Wen Chen,6 Wen-Hsiu Hsu,3,7 Chia-Wen Kuo,3,8 Hung-Chang Hsu,9 Sheng-Huang Chang,10 Li-Mien Chen2,3 1Division of Laboratory, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 2Department of Internal Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 3School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, Republic of China; 5Department of Family Medicine, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 6Medicine Laboratory, Ministry of Health and Welfare Feng Yuan Hospital, Taichung, Taiwan, Republic of China; 7Division of Gastroenterology, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 8Division of Nephrology, Taichung Armed Force General Hospital, Taichung, Taiwan, Republic of China; 9Division of Laboratory, Ching Chyuan Hospital, Taichung, Taiwan, Republic of China; 10Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan, Republic of ChinaCorrespondence: Li-Mien ChenDepartment of Internal Medicine, Taichung Armed Force General Hospital, No. 348, Sec. 2, Chung-Shan Road, Taiping, Taichung, Taiwan, Republic of ChinaEmail c332860@ms65.hinet.netPurpose: To evaluate the blood glucose and renal function, determine the prevalence of hyperglycemia/diabetes mellitus (DM) and renal disease (nephropathy), and investigate the association between hyperglycemia/DM and renal disease in patients with viral hepatitis (VH).Patients and Methods: A total of 491 subjects were included in the study. Patients with VH were further divided into the hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV-HCV co-infection subgroups. Fasting blood glucose, glycated hemoglobin (HbA1c), glycated albumin (GA), glutamic oxaloacetic transaminase (GOT), creatinine (Cr), and cystatin C (Cys C) levels were measured. Urine microalbumin levels were also assessed. Formulas for estimated average glucose calculated using glycated albumin(eAG(GA)), estimated average glucose calculated using HbA1c (eAG(HbA1c)), and estimated glomerular filtration rate calculated using cystatin C (eGFRcys) were used to evaluate the average glucose and renal function.Results: The prevalence of hyperglycemia/DM and renal disease was significantly higher in the VH group, especially in the HCV subgroup. The prevalence of renal disease was significantly higher in patients with VH with eAG(GA) ≥ 200 mg/dL.Conclusion: Our study used multiple parameters to evaluate blood glucose and renal function in patients with VH and found that hyperglycemia/DM and renal disease are closely associated with VH, especially in subjects with HCV infection. Patients with VH, especially those with HCV infection and hyperglycemia/DM, were particularly vulnerable to renal disease.Keywords: viral hepatitis, hyperglycemia, diabetes mellitus, renal disease, nephropathy

Background: Sacubitril/valsartan (S/V) reduces mortality and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF), but low adherence remains a challenge. Early initiation of S/V is recommended, yet no practical tool currently exists to effectively communicate its benefits to outpatients or assess patient stability before S/V initiation during hospitalization., Methods: We collected data retrospectively from 527 HFrEF patients who started S/V between March 2017 and January 2020 at the National Taiwan University Hospital, with follow-up through September 2022. A modern stepwise variable selection approach was applied to fit the optimal Cox's proportional-hazards model to address nonlinear covariate effects and potential multicollinearity. Penalized smoothing splines were used to visualize nonlinear effects and identify cutoff values for continuous covariates. The model was then integrated into an interactive Streamlit dashboard for real-time simulation and risk prediction based on patient-specific covariates., Results: We identified 20 key variables - 12 associated with increased risk and 8 conferring protective effects. Some variables presented actionable cutoff values. The predictive model helped estimate individualized hazard ratios and covariate-adjusted survival curves, which serve as both a patient engagement platform in outpatient settings and a practical tool for physicians to assess inpatient stability before initiating S/V., Conclusion: Our interactive visualization dashboard can potentially improve medication adherence and clinical outcomes by involving patients in their treatment journey and facilitating more informed decision-making. A pragmatic clinical trial is currently underway to further evaluate the dashboard's clinical utility and effectiveness in both outpatient and inpatient environments., Competing Interests: Declaration of competing interest The authors affirm the absence of any known competing financial interests or personal relationships that might have been perceived to influence the work presented in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

An artificial intelligence (AI)-enabled electrocardiogram (ECG) model has been developed in a healthy adult population to predict ECG biological age (ECG-BA). This ECG-BA exhibited a robust correlation with chronological age (CA) in healthy adults and additionally significantly enhanced the prediction of aging-related diseases' onset in adults with subclinical diseases. The model showed particularly strong predictive power for cardiovascular and non-cardiovascular diseases such as stroke, coronary artery disease, peripheral arterial occlusive disease, myocardial infarction, Alzheimer's disease, osteoarthritis, and cancers. When combined with CA, ECG-BA improved diagnostic accuracy and risk classification by 21% over using CA alone, notably offering the greatest improvements in cancer prediction. The net reclassification improvement significantly reduced misclassification rates for disease onset predictions. This comprehensive study validates ECG-BA as an effective supplement to CA, advancing the precision of risk assessments for aging-related conditions and suggesting broad implications for enhancing preventive healthcare strategies, potentially leading to better patient outcomes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: The data on immune responses of individuals undergoing modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination are scarce. We aimed to compare Mpox virus-specific antibody and neutralizing antibody responses among people with and those without HIV receiving MVA-BN vaccines., Methods: This prospective study enrolled participants undergoing two-dose MVA-BN vaccination to investigate seroresponses after vaccination. Blood samples were collected before and after each dose of vaccination for determinations of anti-A29 and anti-H3 IgG. Neutralization tests were conducted for samples tested positive for both anti-A29 and anti-H3 IgG., Results: Overall, 441 participants undergoing two-dose MVA-BN vaccination were enrolled. Seroconversion for anti-A29 and anti-H3 IgG, respectively, after the second dose of vaccination was 18.2% and 61.2%, 10.9% and 65.0%, and 51.6% and 90.6% among people with HIV, people without HIV, and those who had had smallpox vaccination previously, respectively. About 20% of the participants with seroconversion lost seroresponses after a 7-month period of observation. None of the serum samples from vaccinated participants demonstrated neutralizing ability., Conclusions: Participants with previous smallpox vaccination had higher and more sustained antibody responses after receiving two doses of MVA-BN vaccines than those who had not undergone smallpox vaccination. More studies are warranted to assess the seroresponses to booster MVA-BN vaccination for vaccine nonresponders or those having lost seroresponses., Competing Interests: Declarations 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 article., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Relative free energy (RFE) calculations are now widely used in academia and the industry, but their accuracy is often limited by poor sampling of the complexes' conformational ensemble. To help address conformational sampling problems when simulating many relative binding free energies, we developed a novel method termed multiple topology replica exchange of expanded ensembles (MT-REXEE). This method enables parallel expanded ensemble calculations, facilitating iterative RFE computations while allowing conformational exchange between parallel transformations. These iterative transformations can be adaptable to any set of systems with a common backbone or central substructure. We demonstrate that the MT-REXEE method maintains thermodynamic cycle closure to the same extent as standard expanded ensemble calculations for both solvation free energy and relative binding free energy calculations. The transformations tested involve systems that incorporate diverse heavy atoms and multisite perturbations of a small molecule core resembling multisite λ dynamics, without necessitating modifications to the MD code. Our initial implementation is in GROMACS. We outline a systematic approach for the topology setup and provide instructions on how to perform inter-replica coordinate modifications. This work shows that MT-REXEE can be used to perform accurate and reproducible free energy estimates and prompts expansion to more complex test systems and other molecular dynamics simulation infrastructures.

Microplastics (MPs) are ubiquitous environmental pollutants extensively detected in atmospheric environments. Airborne MPs have raised concerns due to their transport and potential health risks of inhalation exposure. However, the factors influencing airborne MPs, particularly their concentrations and shapes suspended in urban air, remain unclear. We investigated MPs in total suspension particles with one-year measurements in Taipei City and identified their features using Nile Red staining combined with fluorescence microscopy and micro-Fourier transform infrared (μFTIR) spectroscopy. This study quantified the mean number concentration of total MPs as approximately 6.0 #/m³. We observed that MP abundance varied seasonally, with higher levels in the warm season than in the cold. A similar trend was noted for polymer types. Fragment-like MPs were the predominant shape, mainly found in polystyrene (PS), polyethylene (PE), and polypropylene (PP), while fibrous MPs, detected mostly as polyethylene terephthalate (PET) and polyamide (PA), were primarily observed at sizes greater than 300 μm. Both fiber and fragment-like MPs were positively associated with particle mass concentration, temperature, ultraviolet (UV) index, and wind speed, but negatively correlated with relative humidity and rainfall. Fibrous MPs were more affected by environmental factors than fragment-like MPs. Meteorological changes significantly influenced suspended MPs more than human activity within the city., 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: To pioneer the first artificial intelligence system integrating radiological and objective clinical data, simulating the clinical reasoning process, for the early prediction of high-risk influenza patients., Materials and Methods: Our system was developed using a cohort from National Taiwan University Hospital in Taiwan, with external validation data from ASST Grande Ospedale Metropolitano Niguarda in Italy. Convolutional neural networks pretrained on ImageNet were regressively trained using a 5-point scale to develop the influenza chest X-ray (CXR) severity scoring model, FluDeep-XR. Early, late, and joint fusion structures, incorporating varying weights of CXR severity with clinical data, were designed to predict 30-day mortality and compared with models using only CXR or clinical data. The best-performing model was designated as FluDeep. The explainability of FluDeep-XR and FluDeep was illustrated through activation maps and SHapley Additive exPlanations (SHAP)., Results: The Xception-based model, FluDeep-XR, achieved a mean square error of 0.738 in the external validation dataset. The Random Forest-based late fusion model, FluDeep, outperformed all the other models, achieving an area under the receiver operating curve of 0.818 and a sensitivity of 0.706 in the external dataset. Activation maps highlighted clear lung fields. Shapley additive explanations identified age, C-reactive protein, hematocrit, heart rate, and respiratory rate as the top 5 important clinical features., Discussion: The integration of medical imaging with objective clinical data outperformed single-modality models to predict 30-day mortality in influenza patients. We ensured the explainability of our models aligned with clinical knowledge and validated its applicability across foreign institutions., Conclusion: FluDeep highlights the potential of combining radiological and clinical information in late fusion design, enhancing diagnostic accuracy and offering an explainable, and generalizable decision support system., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dental anxiety and odontophobia are common issues, leading to challenges with oral hygiene and dental health. Music distraction offers an effective and side effect-free solution to alleviate pain and increase the acceptability of dental treatments. Our meta-analysis aimed to assess the efficacy of music distraction in reducing patient anxiety during invasive dental procedures in children and adults. Methods: The PubMed, Web of Science, and Embase databases were searched for clinically controlled trials, using the keywords "music" and "dental anxiety". The main outcome measured was the anxiety score. A meta-analysis was conducted using a random-effects model to estimate the standardized mean differences (SMDs). The subgroup analyses were conducted based on age groups, music preferences, and music styles. The research protocol has been registered with PROSPERO (Registration ID: CRD42022357961). Results: A total of 24 controlled clinical trials involving 1830 participants met the inclusion criteria for the meta-analysis. Music distraction significantly reduced dental anxiety during invasive procedures under local anesthesia (SMD, -0.50; 95% CI, -0.80 to -0.21; p = 0.0009; I 2 = 83%). Our subgroup analysis revealed that music distraction was more effective in adults (SMD, -0.51; p = 0.0007) than in children (SMD, -0.47; p = 0.13) in reducing dental anxiety. Regarding music selection, music chosen by the participant (SMD, -1.01; p = 0.008) demonstrated more anxiolytic effects than by the author (SMD, -0.24; p = 0.02). Regarding music styles, classical music (SMD, -0.69; p = 0.009) was associated with better anxiolytic effects in adults. Conclusions: Our meta-analysis supports the use of music to alleviate dental anxiety during invasive procedures. Listening to classical or customized music can serve as an effective adjunct to outpatient surgical care in dental clinics.

This study examined the relationships between job-related factors and overall physical activity (PA), including its subdivisions: leisure-time PA, transportation PA, and work-related PA. Additionally, this study investigated the associations between exercise intentions and different types of PA. A cross-sectional design was employed, utilizing a questionnaire to collect data on participants' demographics, job-related characteristics, exercise intentions, and levels of PA. A total of 400 full-time workers voluntarily participated in this study. The findings identified women, white-collar workers, those with longer working hours, and individuals with low exercise intentions as high-risk groups for insufficient overall PA in multiple linear regression analysis. After controlling for covariates, occupation was found to be associated with both overall PA (β = 0.146) and work-related PA (β = 0.236). Shift workers exhibited higher levels of work-related PA (β = 0.234). Furthermore, exercise intentions showed associations with overall PA (β = 0.243), leisure-time PA (β = 0.523), and transportation PA (β = 0.176) but did not demonstrate a significant relationship with work-related PA. This study highlights the importance of implementing comprehensive approaches in workplace health promotion programs aimed at enhancing various types of PA. Strategies should focus on improving exercise intentions to boost leisure-time and transportation PA, while work-related PA requires tailored interventions based on job-specific factors.

Introduction: Diabetes mellitus (DM) is a prevalent metabolic disorder associated with various postoperative complications. The association between DM and postoperative opioid use remains unclear, with conflicting evidence in the literature. This systematic review and meta-analysis comprehensively evaluated the association between DM and postoperative opioid consumption, pain sensation, and adverse effects in surgical patients., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of electronic databases identified studies investigating the relationship between DM and postoperative pain outcomes. Eligible studies, both prospective and retrospective, were included based on the predefined criteria. Data extraction and quality assessment were performed independently by the authors. Meta-analyses were performed using Review Manager 5., Results: Among 100 initially identified articles, five studies met the inclusion criteria. In the meta-analysis, 473 participants were included. The results indicated that patients with DM had significantly higher postoperative opioid consumption (standardized mean difference, 0.79; 95% confidence interval, 0.26-1.31; P = 0.003) than those in the control group, with substantial heterogeneity (I 2  = 83%). No significant differences in postoperative pain scale scores at rest or during movement were observed. Adverse effects, including nausea, vomiting, and pruritus, showed varied outcomes, whereas overall satisfaction did not differ between the two groups., Conclusions: This meta-analysis provides evidence that patients with DM undergoing surgery consume more opioids postoperatively. Understanding the association between DM and pain management is crucial for optimizing perioperative care in this patient population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The fault diagnosis on a transmission line based on the characteristics of the power spectral entropy is proposed in this article. The data preprocessing for the experimental measurement is also introduced using the EEMD. The EEMD is used to preprocess experimental measurements, which are nonlinear and non-stationary fault signals, to overcome the mode mixing. This study focuses on the fault location detection of transmission lines during faults. The proposed method is adopted for different fault types through simulation under the fault point by collecting current and voltage signals at a distance from the fault point. An analysis and comprehensive evaluation of three-phase measured current and voltage signals at distinct fault locations is conducted. The form and position of the fault are distinguished directly and effectively, thereby significantly improving the transmission line efficiency and accuracy of fault diagnosis.

Only a few researchers have shown how environmental factors and road features relate to Autonomous Vehicle (AV) crash severity levels, and none have focused on the data limitation problems, such as small sample sizes, imbalanced datasets, and high dimensional features. To address these problems, we analyzed an AV crash dataset (2019 to 2021) from the California Department of Motor Vehicles (CA DMV), which included 266 collision reports (51 of those causing injuries). We included external environmental variables by collecting various points of interest (POIs) and roadway features from Open Street Map (OSM) and Data San Francisco (SF). Random Over-Sampling Examples (ROSE) and the Synthetic Minority Over-Sampling Technique (SMOTE) methods were used to balance the dataset and increase the sample size. These two balancing methods were used to expand the dataset and solve the small sample size problem simultaneously. Mutual information, random forest, and XGboost were utilized to address the high dimensional feature and the selection problem caused by including a variety of types of POIs as predictive variables. Because existing studies do not use consistent procedures, we compared the effectiveness of using the feature-selection preprocessing method as the first process to employing the data-balance technique as the first process. Our results showed that AV crash severity levels are related to vehicle manufacturers, vehicle damage level, collision type, vehicle movement, the parties involved in the crash, speed limit, and some types of POIs (areas near transportation, entertainment venues, public places, schools, and medical facilities). Both resampling methods and three data preprocessing methods improved model performance, and the model that used SMOTE and data-balancing first was the best. The results suggest that over-sampling and the feature selection method can improve model prediction performance and define new factors related to AV crash severity levels., 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.)

Particle plasmon resonance (PPR), or localized surface plasmon resonance (LSPR), utilizes intrinsic resonance in metal nanoparticles for sensor fabrication. While diffraction grating waveguides monitor bioaffinity adsorption with out-of-plane illumination, integrating them with PPR for biomolecular detection schemes remains underexplored. This study introduces a label-free biosensing platform integrating PPR with a diffraction grating waveguide. Gold nanoparticles are immobilized on a glass slide in contact with a sample, while a UV-assisted embossed diffraction grating is positioned opposite. The setup utilizes diffraction in reflection to detect changes in the environment's refractive index, indicating biomolecular binding at the gold nanoparticle surface. The positional shift of the diffracted beam, measured with varying refractive indices of sucrose solutions, shows a sensitivity of 0.97 mm/RIU at 8 cm from a position-sensitive detector, highlighting enhanced sensitivity due to PPR-diffraction coupling near the gold nanoparticle surface. Furthermore, the sensor achieved a resolution of 3.1 × 10 -4 refractive index unit and a detection limit of 4.4 pM for detection of anti-DNP. The sensitivity of the diffracted spot was confirmed using finite element method (FEM) simulations in COMSOL Multiphysics. This study presents a significant advancement in biosensing technology, offering practical solutions for sensitive, rapid, and label-free biomolecule detection.

Background: Aging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics., Methods: A case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1-7 days and 181-187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths., Results: The study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70-4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47-5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15-26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82-66.64)., Conclusions: NSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Early identification of impending in-hospital cardiac arrest (IHCA) improves clinical outcomes but remains elusive for practicing clinicians., Objective: We aimed to develop a multimodal machine learning algorithm based on ensemble techniques to predict the occurrence of IHCA., Methods: Our model was developed by the Multiparameter Intelligent Monitoring of Intensive Care (MIMIC)-IV database and validated in the Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Baseline features consisting of patient demographics, presenting illness, and comorbidities were collected to train a random forest model. Next, vital signs were extracted to train a long short-term memory model. A support vector machine algorithm then stacked the results to form the final prediction model., Results: Of 23,909 patients in the MIMIC-IV database and 10,049 patients in the eICU-CRD database, 452 and 85 patients, respectively, had IHCA. At 13 hours in advance of an IHCA event, our algorithm had already demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI 0.815-0.885) in the MIMIC-IV database. External validation with the eICU-CRD and National Taiwan University Hospital databases also presented satisfactory results, showing area under the receiver operating characteristic curve values of 0.81 (95% CI 0.763-0.851) and 0.945 (95% CI 0.934-0.956), respectively., Conclusions: Using only vital signs and information available in the electronic medical record, our model demonstrates it is possible to detect a trajectory of clinical deterioration up to 13 hours in advance. This predictive tool, which has undergone external validation, could forewarn and help clinicians identify patients in need of assessment to improve their overall prognosis., (© Hsin-Ying Lee, Po-Chih Kuo, Frank Qian, Chien-Hung Li, Jiun-Ruey Hu, Wan-Ting Hsu, Hong-Jie Jhou, Po-Huang Chen, Cho-Hao Lee, Chin-Hua Su, Po-Chun Liao, I-Ju Wu, Chien-Chang Lee. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Generalized ensemble methods such as Hamiltonian replica exchange (HREX) and expanded ensemble (EE) have been shown effective in free energy calculations for various contexts, given their ability to circumvent free energy barriers via nonphysical pathways defined by states with different modified Hamiltonians. However, both HREX and EE methods come with drawbacks, such as limited flexibility in parameter specification or the lack of parallelizability for more complicated applications. To address this challenge, we present the method of replica exchange of expanded ensembles (REXEE), which integrates the principles of HREX and EE methods by periodically exchanging coordinates of EE replicas sampling different yet overlapping sets of alchemical states. With the solvation free energy calculation of anthracene and binding free energy calculation of the CB7-10 binding complex, we show that the REXEE method achieves the same level of accuracy in free energy calculations as the HREX and EE methods, while offering enhanced flexibility and parallelizability. Additionally, we examined REXEE simulations with various setups to understand how different exchange frequencies and replica configurations influence the sampling efficiency in the fixed-weight phase and the weight convergence in the weight-updating phase. The REXEE approach can be further extended to support asynchronous parallelization schemes, allowing looser communications between larger numbers of loosely coupled processors such as cloud computing and therefore promising much more scalable and adaptive executions of alchemical free energy calculations. All algorithms for the REXEE method are available in the Python package ensemble_md, which offers an interface for REXEE simulation management without modifying the source code in GROMACS.

The assembly and disassembly of biomolecular condensates are crucial for the subcellular compartmentalization of biomolecules in the control of cellular reactions. Recently, a correlation has been discovered between the phase transition of condensates and their maturation (aggregation) process in diseases. Therefore, modulating the phase of condensates to unravel the roles of condensation has become a matter of interest. Here, we create a peptide-based phase modulator, JSF1, which forms droplets in the dark and transforms into amyloid-like fibrils upon photoinitiation, as evidenced by their distinctive nanomechanical and dynamic properties. JSF1 is found to effectively enhance the condensation of purified fused in sarcoma (FUS) protein and, upon light exposure, induce its fibrilization. We also use JSF1 to modulate the biophysical states of FUS condensates in live cells and elucidate the relationship between FUS phase transition and FUS proteinopathy, thereby shedding light on the effect of protein phase transition on cellular function and malfunction., (© 2024. The Author(s).)

Ischemic stroke is a leading cause of mortality and disability. The relationships of heart rate variability (HRV) and stroke-related factors with mortality and functional outcome are complex and not fully understood. Understanding these relationships is crucial for providing better insights regarding ischemic stroke prognosis. The objective of this study is to examine the relationship between HRV, neurological function, and clinical factors with mortality and 3-month behavioral functional outcome in ischemic stroke. We prospectively collected the HRV data and monitored the behavioral functional outcome of patients with ischemic stroke. The behavioral functional outcome was represented by a modified Rankin Scale (mRS) score. This study population consisted of 58 ischemic stroke patients (56.9% male; mean age 70) with favorable (mRS score ≤ 2) and unfavorable (mRS score ≥ 3) outcome. The analysis indicated that the median of the mean RR interval (RR mean) showed no statistical difference between mortality groups. Conversely, the median of the RR mean had significant association with unfavorable outcome (OR = 0.989, p = 0.007). Lower hemoglobin levels had significant association with unfavorable outcome (OR = 0.411, p = 0.010). Higher National Institute of Health Stroke Scale (NIHSS) score at admission had significant association with unfavorable outcome (OR = 1.396, p = 0.002). In contrast, age, stroke history, NIHSS score at admission, and hemoglobin showed no significant association with mortality in ischemic stroke. These results imply that HRV, as indicated by the median of RR mean, alongside specific clinical factors and neurological function at admission (measured by NIHSS score), may serve as potential prognostic indicators for 3-month behavioral functional outcome in ischemic stroke.

Numerous previous studies have shown the effectiveness of music therapy in enhancing cognitive functions in patients with dementia. Despite this, robust evidence in this field, especially concerning the comparison of different music therapy types, is lacking. Therefore, randomized controlled trials (RCTs) focusing on music therapy and cognitive functions in dementia patients, termed by "music" AND "dementia" OR "Alzheimer's disease" AND "cognitive", were identified from primary electronic databases to conduct this network meta-analysis (NMA). The primary outcome focused on the impact on cognitive functions, and the secondary outcome was the comparison of dropout rates between the intervention groups and the usual care control groups. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed for effect evaluation. This study protocol has been registered in IPLASY (INPLASY202430082). A total of 14 RCTs with 1056 participants were enrolled, examining interventions including Active Music Therapy (AMT), Active Music Therapy with Singing (AMT + Sing), Rhythmic Music Therapy (RMT), Listening to Music (LtM), and Singing (Sing). The results indicated that RMT, AMT + Sing, and AMT all significantly improve cognitive functions in dementia patients, of which the SMD were 0.76 (95% CI = 0.32-1.21), 0.79 (95% CI = 0.03-1.49), and 0.57 (0.18-0.96), respectively. Compared with the control group (usual care), no music therapy type was associated with an increased dropout risk. In conclusion, music therapy can improve cognitive functions in patients with dementia without increasing the risk of dropout, particularly RMT, AMT + Sing, and AMT.

Background: Spiritual care plays a significant role in holistic patient care, addressing not only physical ailments but also attending to patients' emotional and spiritual well-being. While the importance of spiritual care in nursing is widely recognized, there is often a gap in understanding nurses' willingness to provide such care. This cross-sectional study aimed to explore the association between self-efficacy, spiritual well-being, and willingness to provide spiritual care among nursing staff., Methods: The study conducted a cross-sectional survey of full-time registered nurses at a hospital in Taiwan from January 2019 to December 2019. A sample comprising 168 nurses was selected for participation in the study through a random sampling method. In addition to collecting demographic variables, the assessment tools used in the study include the General Self-Efficacy Scale (GSES) for measuring self-efficacy, the Spiritual Index of Well-Being Chinese Version (SIWB-C) for evaluating spiritual well-being, and the Spiritual Care Needs Inventory (SCNI) to gauge willingness to provide spiritual care., Results: Most participants in the study were female, accounting for 98.2% (n = 165). The mean age of all 168 nurses was 37.1 ± 9.3 years. Additionally, most participants held a Bachelor's degree (79.2%, n = 133) and possessed clinical experience was 10.5 ± 9.3 years. Through logistic regression analysis, it was found that regardless of whether participants have received sufficient spiritual care training, both GSES and SIWB-C remain influential factors in determining the provision of spiritual care., Conclusions: Collaboration between healthcare management and nursing staff is essential for fostering a healthcare environment that not only appreciates the physical and spiritual dimensions of patient care but also prioritizes the enhancement of nurses ' self-efficacy and well-being., (© 2024. The Author(s).)

Transition metal dichalcogenide (TMD) heterobilayers have emerged as a promising platform for exploring solid-state quantum simulators and many-body quantum phenomena. Their type II band alignment, combined with the moiré superlattice, inevitably leads to nontrivial exciton interactions and dynamics. Here, we unveil the distinct Auger annihilation processes for delocalized interlayer excitons in WS 2 /WSe 2 moiré heterobilayers. By fitting the characteristic efficiency droop and bimolecular recombination rate, we quantitatively determine an ultralow Auger coefficient of 1.3 × 10 -5 cm 2 s -1 , which is >100-fold smaller than that of excitons in TMD monolayers. In addition, we reveal selective exciton upconversion into the WSe 2 layer, which highlights the significance of intralayer electron Coulomb interactions in dictating the microscopic scattering pathways. The distinct Auger processes arising from spatial electron-hole separation have important implications for TMD heterobilayers while endowing interlayer excitons and their strongly correlated states with unique layer degrees of freedom.

Sepsis patients have a high risk of developing in-hospital cardiac arrest (IHCA), which portends poor survival. However, little is known about whether the increased incidence of IHCA is due to sepsis itself or to comorbidities harbored by sepsis patients. We conducted a retrospective population-based cohort study comprising 20,022 patients admitted with sepsis to hospitals in Taiwan using the National Health Insurance Research Database (NHIRD). We constructed three non-sepsis comparison cohorts using risk set sampling and propensity score (PS) matching. We used univariate conditional logistic regression to evaluate the risk of IHCA and associated mortality. We identified 12,790 inpatients without infection (matched cohort 1), 12,789 inpatients with infection but without sepsis (matched cohort 2), and 10,536 inpatients with end-organ dysfunction but without sepsis (matched cohort 3). In the three PS-matched cohorts, the odds ratios (OR) for developing ICHA were 21.17 (95% CI 17.19, 26.06), 18.96 (95% CI: 15.56, 23.10), and 1.23 (95% CI: 1.13, 1.33), respectively (p < 0.001 for all ORs). In conclusion, in our study of inpatients across Taiwan, sepsis was independently associated with an increased risk of IHCA. Further studies should focus on identifying the proxy causes of IHCA using real-time monitoring data to further reduce the incidence of cardiopulmonary insufficiency in patients with sepsis., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

This study aimed to evaluate the efficacy of omega-3 fatty acid supplementation interventions in improving depression in patients with dementia. To achieve this objective, randomized controlled trials (RCTs) were identified from primary electronic databases, focusing on the relationship between omega-3 fatty acids and depression in patients with dementia. The primary outcome was the impact of omega-3 fatty acids on post-intervention depression in patients with dementia, with subgroup analyses conducted based on the type of intervention (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) combination), duration of intervention (3 months, 6 months, 12 months, ≥24 months), cognitive function (ranging from mild cognitive impairment (MCI) to severe dementia), and daily dosage (high, medium, low, applicable to both DHA and EPA). The study has been duly registered with PROSPERO (registration ID: CRD42023408744). A meta-analysis of five studies (n = 517) included in nine systematic reviews showed that omega-3 supplementation had a non-significant trend toward affecting depressive symptoms in patients with dementia (standardized mean difference (SMD): 0.147; 95% confidence interval (CI): -0.324 to 0.049; p = 0.141). Subgroup analyses revealed that DHA supplementation significantly reduced depressive symptoms (SMD: -0.247; p = 0.039). There was no significant effect for high (SMD: -0.169; 95% CI: -0.454 to 0.116; p = 0.246) or medium (SMD: -0.061; 95% CI: -0.228 to 0.105; p = 0.470) doses of EPA. However, low doses of EPA were significantly effective (SMD: -0.953; 95% CI: -1.534 to -0.373; p = 0.001), with notable improvements in patients with MCI (SMD: -0.934; p < 0.001). The study concludes that omega-3 fatty acids, particularly through DHA supplementation, may alleviate depressive symptoms in patients with MCI. Given the limited sample size, further long-term RCTs are recommended to better understand the efficacy and optimal management of omega-3 supplementation in this population using different dosages.

This study aimed to assess the efficacy of various music therapy interventions in ameliorating depressive symptoms in dementia patients, utilizing a network meta-analysis approach. We rigorously selected randomized controlled trials focused on music therapy for dementia with depressive symptoms from major electronic databases. The primary outcome measured was the impact on depressive symptoms, with the secondary outcome evaluating dropout rates across different intervention groups and standard care control groups. The research protocol has been duly registered with PROSPERO (Registration ID: CRD42023393059). Our network meta-analysis incorporated 14 randomized controlled trials involving a total of 1080 participants and examined a range of interventions, including active music therapy, listening to music, rhythmic music therapy, singing, and tailored music interventions. The analysis revealed that active music therapy combined with singing emerged as the most effective intervention, demonstrating a significant improvement in depressive symptoms in dementia patients (Standardized Mean Difference [SMD] = -0.89, 95% Confidence Interval [CI]: -1.48 to -0.30). In contrast, listening to music alone showed a smaller effect (SMD = -0.26, 95% CI: -0.71 to 0.20). This study was particularly noteworthy for not showing higher dropout rates compared to standard care, indicating its feasibility and acceptability in clinical settings. The findings of our study indicate that active music therapy combined with singing is an effective approach to reducing depressive symptoms in dementia patients, potentially due to enhanced social interaction. These results offer new perspectives for dementia care, suggesting a promising direction for further research and clinical application.

Electron ptychography has emerged as a popular technology for high-resolution imaging by combining the high coherence of electron sources with the ultra-fast scanning electron coil. However, the limitations of conventional pixelated detectors, including poor dynamic range and slow data readout speeds, have posed restrictions in the past on conducting electron ptychography experiments. We used the Gatan STELA pixelated detector to capture sequential diffraction data of monolayer two-dimensional (2D) materials for ptychographic reconstruction. By using the pixelated detector and electron ptychography, we demonstrate the observation of the radiation damage at atomic resolution in Transition Metal Dichalcogenides (TMDs)., (© 2024. The Author(s).)

Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases. When fine-scale population structure was explored using NETVIEW, cases were distributed throughout an extended pedigree. When genotyped cases ( n = 49) and dogs from the control group ( n = 281) were compared in a genome-wide association analysis of lymphoma risk, the most prominent associated regions were detected on CFA13 and CFA33. The top SNPs in a 5.4 Mb region on CFA13 were significant at a chromosome-wide level, and the region was fine-mapped to ~1.2 Mb (CFA13: 25.2-26.4 Mb; CanFam3.1) with four potential functional candidates, including the MYC proto-oncogene bHLH transcription factor (MYC) and a region syntenic with the human and mouse lncRNA Pvt1 oncogene ( PVT1) . A 380 Kb associated region at CFA33: 7.7-8.1 Mb contained the coding sequence for SUMO specific peptidase7 (SENP7) and NFK inhibitor zeta (NFKBIZ) genes. These genes have annotations related to cancer, amongst others, and both have functional links to MYC regulation. Genomic signatures identified in lymphoma cases suggest that increased risk contributed by the regions identified by GWAS may complement a complex predisposing genetic background.

Purpose: To better understand the role of novelty satisfaction in distance physical education (PE) during the COVID-19 pandemic, this study aimed to determine the relationships among students' novelty satisfaction, basic psychological needs satisfaction, autonomous motivation, effort, and enjoyment and to examine the mediating effects of autonomous motivation in the relationships between novelty satisfaction and effort and enjoyment., Methods: The participants were 332 undergraduate students from 10 PE classes. Structural equation modeling was used for data analysis., Results: Satisfaction of students' need for novelty and the three basic needs positively predicted autonomous motivation, which in turn positively predicted effort and enjoyment. The relationships between students' novelty satisfaction and their effort and enjoyment were mediated by autonomous motivation., Conclusion: This study provides important insights into needs satisfaction and motivational underpinnings of outcomes in distance PE during the COVID-19 pandemic. We suggest that future studies develop novelty support strategies based on our findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ectopic kidney and median arcuate ligament syndrome are both rare conditions. The clinical presentation and diagnosis of these conditions are not well studied. There are no reports on the combination of these two rare conditions., Case Presentation: We report a 24-year-old woman with fever, dysuria, urinary frequency and left flank pain for two days. The primary diagnoses in the clinic were left acute pyelonephritis and left hydronephrosis due to throbbing pain in the left costovertebral angle and pyuria. However, further computed tomography showed right ectopic pelvic kidney, left renal pelvis dilatation without definite ureteral lesion, good bilateral renal contrast enhancement, and compression of the celiac axis due to obstruction by the median arcuate ligament. Chronic abdominal symptoms were reported by the patient after repeat history taking. The patient's condition was fully explained and discussed with her and her family, but they refused further therapy. After the acute pyelonephritis began improving, the patient was discharged for follow-up at our outpatient clinic., Conclusion: We present an extremely rare case of a combination of two rare conditions: ectopic kidney and median arcuate ligament syndrome. No study to date has reported on the relationship between the two diseases. Given the rarity of the two conditions, no evidence or even a hypothesis exists to explain the possible etiology of their combination. More reports are required to enhance the understanding of these rare conditions., (© 2023. The Author(s).)

Music interventions (MIs) have been widely used to relieve anxiety in dementia in clinical settings. However, limited meta-analysis with randomized controlled trials (RCTs) on this topic has been conducted so far. A systematic search was conducted in four major databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for data provided by RCTs from the inception to February 2023. The search strategy employed the terms "anxiety AND music AND dementia OR Alzheimer's disease". Thirteen RCTs (827 participants) were included. The results showed MI reduced anxiety significantly (SMD = -0.67, p < 0.001), especially for Alzheimer's disease ( p = 0.007) and Mixed ( p < 0.001)-type dementia. Moreover, significant improvements in agitation ( p = 0.021) and depression ( p < 0.001) in dementia were observed. Additionally, several psychological mechanisms which may be associated with MI were reviewed comprehensively. In conclusion, our findings support the efficacy of MI in alleviating anxiety symptoms in dementia patients. PROSPERO Registration (ID: CRD42021276646).

Parkinson's disease (PD) is associated with a range of non-motor symptoms that lack effective treatments. Acupuncture is a popular alternative therapy for PD patients that has been shown to improve motor symptoms. However, the efficacy of acupuncture in treating non-motor symptoms has remained controversial. The goal of our study was to systematically assess the existing evidence for acupuncture's efficacy in treating PD non-motor symptoms of sleep disorders, depression, anxiety, and fatigue. We conducted a meta-analysis of clinical trials by searching Pubmed, Embase, CINAHL, and Web of Science as electronic databases to evaluate acupuncture treatment for PD non-motor symptoms. Thirteen clinical trials met our inclusion criteria, and their methodological quality was assessed using the modified Jadad scale, indicating a moderate overall quality. Our results showed that acupuncture improved PD-related sleep disorders and depression but had no effect on anxiety and fatigue. Our meta-analysis suggests that acupuncture can be used as a complementary treatment for sleep disturbances and depression in PD patients and may exhibit a dual therapeutic effect on motor and non-motor symptoms. However, further well-designed clinical trials with larger sample sizes are needed to confirm these findings. Overall, our study highlights the potential of acupuncture as a viable complementary therapy for the treatment of PD non-motor symptoms of sleep disorders and depression, which can improve the quality of life of PD patients.

Background: Both the Sport Education (SE) model and Teaching Games for Understanding (TGfU) have been connected to the theory of situated learning, which is a game-centered curricular model. TGfU emphasizes tactical awareness, decision making, and skill execution. The SE model provides a complete season during physical education (PE) lessons. Therefore, it is worth exploring the integration of TGfU with SE (TGfU-SE) model in PE courses, and whether the hybrid TGfU-SE model can achieve better learning effects for students than the TGfU model alone., Purpose: The purpose of the study was to compare the difference in learning effects between the TGfU-SE model and the TGfU model on students' learning motivation, sport enjoyment, responsibility, and game performance., Methods: This study used a quasi-experimental design to compare different learning effects between the experimental group (TGfU-SE) and the control group (TGfU). The participants lived in Taiwan, including two junior high school PE teachers and four PE classes with a total of 90 students (TGfU-SE group, n  = 46; TGfU group, n  = 44). Each teacher taught two PE classes, one with an experimental group and one with a control group. This study used four research instruments, including the Responsibility Scale in Physical Education (RSPE), Learning Motivation Scale in Physical Education (LMSPE), Sport Enjoyment Scale in Physical Education (SESPE), and Game Performance assessment instrument (GPAI). Analysis of covariance (ANCOVA) and the independent t -test were used to analyze the data., Results: The results of this study showed that the TGfU-SE model had more positive learning effects on students' learning motivation, sport enjoyment, responsibility, and game performance than the TGfU model., Conclusion: we concluded that the TGfU-SE model had a more positive influence on students' learning performance than the TGfU model. It is suggested that the hybrid TGfU-SE model could be implemented effectively in the PE curriculum., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pan, Huang and Hsu.)

Purpose: Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological treatments for acne., Methods: Randomized controlled trials comparing the efficacy of pharmacological therapies for acne vulgaris in patients of any age and sex and with a treatment duration of >2 weeks were included. PubMed and Embase databases were searched from inception until February 2022. Our prespecified primary end points were mean percentage reduction in total, inflammatory, and noninflammatory lesions. Treatment ranking was determined by P values., Results: There were 210 articles describing 221 trials and 37 interventions included in the analysis. Our primary analysis of percentage reduction in total lesion count had 65,601 patients enrolled. Across all trials, the mean age was 20.4 years. The median duration of treatment was 12 weeks. The median total, inflammatory, and noninflammatory lesion counts were 72, 27, and 44, respectively. The most effective treatment was oral isotretinoin (mean difference [MD] = 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (BPO) (MD = 38.15; P = .95) and by triple therapy containing an oral antibiotic, a topical retinoid, and BPO (MD = 34.83; P = .90). For monotherapies, oral or topical antibiotics or topical retinoids have comparable efficacy for inflammatory lesions, while oral or topical antibiotics have less effect on noninflammatory lesions., Conclusion: The most effective treatment for acne is oral isotretinoin, followed by triple therapies containing a topical retinoid, BPO, and an antibiotic. We present detailed comparisons of each intervention to serve as a practical database., (© 2023 Annals of Family Medicine, Inc.)

This paper studies containment policies for combating a pandemic in an open-economy context. It does so via quantitative analyses using a model that incorporates a standard epidemiological compartmental model in a general equilibrium multi-country, multi-sector Ricardian model of international trade with input-output linkages. We quantitatively evaluate the long-run welfare and real-income losses due to the short-run pandemic shocks, and we study the role of trade in these effects. We devise a novel approach to computing national optimal policies. We find that (1) the long-run welfare and real-income losses due to just two years of pandemic shocks are substantial; (2) international trade helps buffer both the welfare and real-income losses, and it also saves lives; (3) the computed optimal policies indicate that most countries should have tightened their containment measures relative to what was done; and (4) compared to the case of autarky, the optimal policy under trade is generally more stringent., (© 2023 The Author(s).)

Until recently, most genetic studies of headache have been conducted on participants with European ancestry. We therefore conducted a large-scale genome-wide association study of self-reported headache in individuals of East Asian ancestry (specifically those who were identified as Han Chinese). In this study, 108 855 participants were enrolled, including 12 026 headache cases from the Taiwan Biobank. For broadly defined headache phenotype, we identified a locus on Chromosome 17, with the lead single-nucleotide polymorphism rs8072917 (odds ratio 1.08, P = 4.49 × 10 -8 ), mapped to two protein-coding genes RNF213 and ENDOV . For severe headache phenotype, we found a strong association on Chromosome 8, with the lead single-nucleotide polymorphism rs13272202 (odds ratio 1.30, P = 1.02 × 10 -9 ), mapped to gene RP11-1101K5.1 . We then conducted a conditional analysis and a statistical fine-mapping of the broadly defined headache-associated loci and identified a single credible set of loci with rs8072917 supporting that this lead variant was the true causal variant on RNF213 gene region. RNF213 replicated the result of previous studies and played important roles in the biological mechanism of broadly defined headache. On the basis of the previous results found in the Taiwan Biobank, we conducted phenome-wide association studies for the lead variants using data from the UK Biobank and found that the causal variant (single-nucleotide polymorphism rs8072917) was associated with muscle symptoms, cellulitis and abscess of face and neck, and cardiogenic shock. Our findings foster the genetic architecture of headache in individuals of East Asian ancestry. Our study can be replicated using genomic data linked to electronic health records from a variety of countries, therefore affecting a wide range of ethnicities globally. Our genome-phenome association study may facilitate the development of new genetic tests and novel drug mechanisms., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Performing alchemical transformations, in which one molecular system is nonphysically changed to another system, is a popular approach adopted in performing free energy calculations associated with various biophysical processes, such as protein-ligand binding or the transfer of a molecule between environments. While the sampling of alchemical intermediate states in either parallel (e.g., Hamiltonian replica exchange) or serial manner (e.g., expanded ensemble) can bridge the high-probability regions in the configurational space between two end states of interest, alchemical methods can fail in scenarios where the most important slow degrees of freedom in the configurational space are, in large part, orthogonal to the alchemical variable, or if the system gets trapped in a deep basin extending in both the configurational and alchemical space. To alleviate these issues, we propose to use alchemical variables as an additional dimension in metadynamics, making it possible to both sample collective variables and to enhance sampling in free energy calculations simultaneously. In this study, we validate our implementation of "alchemical metadynamics" in PLUMED with test systems and alchemical processes with varying complexities and dimensionalities of collective variable space, including the interconversion between the torsional metastable states of a toy system and the methylation of a nucleoside both in the isolated form and in a duplex. We show that multidimensional alchemical metadynamics can address the challenges mentioned above and further accelerate sampling by introducing configurational collective variables. The method can trivially be combined with other metadynamics-based algorithms implemented in PLUMED. The necessary PLUMED code changes have already been released for general use in PLUMED 2.8.

Dog breeds represent canine sub-populations with distinctive phenotypic features and limited genetic diversity. We have established a resource to study breed-specific genetic diversity. Utilising genetic resources within our laboratory biobank, public domain genotype data and the phylogenetic framework of 23 breed clades, the primary objective for this study was to identify genomic regions that differentiate the Bullmastiff breed. Through application of a composite index analysis (CSS), genomic signatures were identified in Bullmastiffs when compared to the formative breeds, Mastiffs and Bulldogs, and to 22 other breed groups. Significant regions were identified on 15 chromosomes, with the most differentiated regions found on CFA1, CFA9, and CFA18. These regions may reflect genetic drift following establishment of the breed or the effects of selective breeding during development of the modern Bullmastiff. This was supported by analysis of genes from the identified genomic regions, including 458 genes from the multi-clade analysis, which revealed enriched pathways that may be related to characteristic traits and distinct morphology of the breed. The study demonstrates the utility of the CSS method in breed-specific genome analysis and advances our understanding of genetic diversity in Bullmastiff dogs.

A moiré superlattice formed in twisted van der Waals bilayers has emerged as a new tuning knob for creating new electronic states in two-dimensional materials. Excitonic properties can also be altered drastically due to the presence of moiré potential. However, quantifying the moiré potential for excitons is nontrivial. By creating a large ensemble of MoSe 2 /MoS 2 heterobilayers with a systematic variation of twist angles, we map out the minibands of interlayer and intralayer excitons as a function of twist angles, from which we determine the moiré potential for excitons. Surprisingly, the moiré potential depth for intralayer excitons is up to ∼130 meV, comparable to that for interlayer excitons. This result is markedly different from theoretical calculations based on density functional theory, which show an order of magnitude smaller moiré potential for intralayer excitons. The remarkably deep intralayer moiré potential is understood within the framework of structural reconstruction within the moiré unit cell.

Background: Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma. We aimed to also enhance the previously established Trauma-Related Injury Severity Score (TRISS) and Mechanism, GCS, Age, and Arterial Pressure (MGAP) score with the additional consideration of copeptin levels., Methods: This single-center prospective cohort study enrolled patients who presented to the emergency department with potential major injuries. The serum levels of copeptin were measured, and the correlation to clinical severity in terms of 30-day mortality and requirement of intensive care management was analyzed. By combining copeptin levels with TRISS or MGAP, comparison between performance of the original models with the copeptin-enhanced models was performed via discrimination, calibration, and reclassification analyses., Results: There was a significant increase in copeptin levels in patients who died within 30 days (median 644.4 pg/L, interquartile range [472.5, 785.9]) or were admitted to intensive care units (233.8 pg/L, [105.7, 366.4]), compared with those who survived (37.49 pg/L, [17.88, 77.68]). Adding the natural log of copeptin levels to the established TRISS and MGAP models improved the AUC of TRISS from 0.89 to 0.96, and that of MGAP from 0.82 to 0.95. Both calibrations as measured by Brier's scores and reclassification as measured by net reclassification improvement or integrated discrimination improvement demonstrated significant improvements. A Web-based calculator was built to generate predicted mortality rates of various models for convenient clinical use., Conclusion: Admission serum copeptin levels were correlated with clinical severity in multiple trauma. Coupling copeptin with preexisting trauma severity scores improved prediction accuracy. Copeptin shows promise as a novel biomarker for the prediction of trauma outcome., Level of Evidence: Prognostic and Epidemiologic; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

During breed development, domestic dogs have undergone genetic bottlenecks and sustained selective pressures, as a result distinctive genomic diversity occurs to varying degrees within and between breed groups. This diversity can be identified using standard methods or combinations of these methods. This study explored the application of a combined selection index, composite selection signals (CSS), derived from multiple methods to an existing genotype dataset from three breed groups developed in distinct regions of Asia: Qinghai-Tibet plateau dogs (adapted to living at altitude), Xi dogs (with superior running ability) and Mountain hounds (used for hunting ability). The CSS analysis confirmed top ranked genomic regions on CFA10 and CFA21 in Qinghai-Tibet plateau dogs, CFA1 in Xi dogs and CFA5 in Mountain hounds. CSS analysis identified additional significant genomic regions in each group, defined by a total of 1,397, 1,475 and 1,675 significant SNPs in the Qinghai-Tibetan Plateau dogs, Xi dogs and Mountain hounds, respectively. Chitinase 3 Like 1 (CHI3L1) and Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6) genes were located in the top ranked region on CFA7 (0.02-1 Mb) in the Qinghai-Tibetan Plateau dogs. Both genes have been associated with hypoxia responses or altitude adaptation in humans. For the Xi dogs, the top ranked region on CFA25 contained the Transient Receptor Potential Cation Channel Subfamily C Member 4 (TRPC4) gene. This calcium channel is important for optimal muscle performance during exercise. The outstanding signals in the Mountain dogs were on CFA5 with 213 significant SNPs that spanned genes involved in cardiac development, sight and generation of biochemical energy. These findings support the use of the combined index approach for identifying novel regions of genome diversity in dogs. As with other methods, the results do not prove causal links between these regions and phenotypes, but they may assist in focusing future studies that seek to identify functional pathways that contribute to breed diversity., (© 2023. The Author(s).)

Indirect measurements through a combination of microenvironment concentrations and personal activity diaries provide a potentially useful alternative for PM 2.5 exposure estimates. This study was to optimize a personal exposure model based on spatiotemporal model predictions for PM 2.5 exposure in a sub-cohort study. Personal, home indoor, home outdoor, and ambient monitoring data of PM 2.5 were conducted for an elderly population in the Taipei city of Taiwan. The proposed microenvironment exposure (ME) models incorporate PM 2.5 measurements and individual time-activity information with a generalized estimating equation (GEE) analysis. We evaluated model performance with daily personal PM 2.5 exposure based on the coefficient of determination, accuracy, and mean bias error. Ambient and home outdoor measures as exposure surrogates are likely to under- and overestimate personal exposure to PM 2.5 in our study population, respectively. Measured and predicted indoor exposures were highly correlated with personal PM 2.5 exposure. The awareness of peculiar smells is an important factor that significantly increases personal PM 2.5 exposure by 46-70%. The model incorporating home indoor PM 2.5 can achieve the highest agreement (R 2  = 0.790) with personal exposure and the lowest measurement error. The ME model with the GEE analysis combining home outdoor PM 2.5 determined by LUR model with a machine learning technique can improve the prediction (R 2  = 0.592) of personal PM 2.5 exposure, compared with the prediction of the traditional LUR model (R 2  = 0.385)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu-Cheng Chen reports financial support was provided by Ministry of Science and Technology., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Sacubitril/valsartan (S/V) reduces all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), but it may decline their estimated glomerular filtration rates (eGFR). In addition to eGFR, this clinical study aimed to develop a blood urea nitrogen (BUN)-based index to evaluate the status of renal perfusion and then identify predictors of all-cause death or heart transplant in patients with HFrEF receiving S/V., Methods: From the recruited 291 patients with HFrEF who were prescribed S/V from March 2017 to March 2019, we collected demographic, drug history, laboratory, echocardiographic, and clinical data from 1 year before S/V initiation until December 2020. Regression analysis was conducted by fitting Cox's models with time-dependent covariates for the survival time and applying the modern stepwise variable selection procedure. The smoothing spline method was used to detect nonlinearity in effect and yield optimal cut-off values for continuous covariates., Results: In the Cox's model, decreased hemoglobin level, decreased mean left ventricular ejection fraction, declined daily dose of S/V, decreased eGFR within 3 months, and increased BUN levels within 1 month and 9 months over time were significantly associated with an increased risk of all-cause death or heart transplant in patients with HFrEF., Conclusions: Adequate maintenance of renal perfusion is crucial for the continuous use of S/V and to avoid worsening renal function in patients with HFrEF. We defined the maximum increase in BUN levels within a specified period as the Worsening Renal Perfusion Index (WRPSV Index) to capture the prognostic effect of renal hypoperfusion in patients with HFrEF., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Co-infection of Helicobacter pylori and Fusobacterium nucleatum is a microbial biomarker for poor prognosis of gastric cancer patients. Fusobacterium nucleatum is associated with microsatellite instability and the accumulation of mutations in colorectal cancer. Here, we investigated the mutation landscape of Fusobacterium nucleatum -positive resected gastric cancer tissues using Illumina TruSight Oncology 500 comprehensive panel. Sequencing data were processed to identify the small nucleotide variants, small insertions and deletions, and unstable microsatellite sites. The bioinformatic algorithm also calculated copy number gains of preselected genes and tumor mutation burden. The recurrent genetic aberrations were identified in this study cohort. For gene amplification events, ERBB2, cell cycle regulators, and specific FGF ligands and receptors were the most frequently amplified genes. Pathogenic activation mutations of ERBB2, ERBB3, and PIK3CA, as well as loss-of-function of TP53, were identified in multiple patients. Furthermore, Fusobacterium nucleatum infection is positively correlated with a higher tumor mutation burden. Survival analysis showed that the combination of Fusobacterium nucleatum infection and high tumor mutation burden formed an extremely effective biomarker to predict poor prognosis. Our results indicated that the ERBB2-PIK3-AKT-mTOR pathway is frequently activated in gastric cancer and that Fusobacterium nucleatum and high mutation burden are strong biomarkers of poor prognosis for gastric cancer patients., Competing Interests: The authors declare no conflict of interest.