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Shu-Hui Lin,1,2,* Hsin-Kai Wang,3,4,* Kun-Tu Yeh,1,5 Hui-Chun Tai,1,6 Hui-Yi Wang,1 Lan-Ru Huang,2 Chun-Wen Chiu,7 Chia-Min Chung,8,9 Bharath Kumar Velmurugan101Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan; 3Public Health Bureau, Tainan City Government, Tainan, Taiwan; 4Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan; 5School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 6Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 7Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan; 8Graduate Institute of BioMedical Sciences, China Medical University, Taichung, Taiwan; 9Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; 10Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam*These authors contributed equally to this work Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma.Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters.Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan–Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270).Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).Keywords: T stage, c-MYC, OSCC, biomarker, survival

Bharath Kumar Velmurugan,1 Hsin-Kai Wang,2,3 Chia-Min Chung,4,5 Chien-Hsun Lee,6 Lan-Ru Huang,7 Kun-Tu Yeh,6,7* Shu-Hui Lin6,8*1Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam; 2Public Health Bureau, Tainan City Government, Tainan City, Taiwan; 3Jenteh Junior College of Medicine, Nursing and Management, Taiwan; 4Graduate Institute of BioMedical Sciences, China Medical University, Taichung, Taiwan; 5Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; 6Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan; 7School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan *These authors contributed equally to this workIntroduction: Oral cancer is a prevalent form of cancer worldwide, particularly in Taiwan, and mechanisms involved in oral squamous cell carcinoma (OSCC) progression remain relatively unknown. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncoprotein, is aberrantly expressed in many human malignant tumors including oral cancer. However, the expression and role played by CIP2A in oral cancer pathogenesis remain obscure.Methods: In this study, immunohistochemistry was used to analyze CIP2A expression between OSCC tissues and their adjacent noncancerous tissues. Furthermore, associations between CIP2A expression and histopathological parameters were investigated.Results: In this study, we showed that CIP2A was overexpressed in most of the OSCC tissues. High CIP2A expression was significantly associated with moderate/poor tumor differentiation (P=0.02). No significant association was found between CIP2A expression and other clinical parameters. Kaplan–Meier analysis revealed that high CIP2A expression showed poorer survival rates than those with low CIP2A expression (P=0.047). Multivariate Cox regression analysis indicated that CIP2A expression, N stage, American Joint Committee on Cancer stage and clinical therapy were independent prognostic factors for survival.Conclusion: Thus, our study suggests that CIP2A is an independent prognostic marker for OSCC and a novel target for OSCC treatment.Keywords: CIP2A, OSCC: prognosis, survival, Taiwan

Chang-Min Chung,1,2 Yu-Hsiang Tseng,3 Yu-Sheng Lin,3 Jen-Te Hsu,4 Po-Chang Wang31School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan County, 2Chang Gung University of Science and Technology, Chiayi County, 3Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, 4Department of Medicine, College of Medicine, Chang Gung University, Taoyuan County, TaiwanObjective: Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess risk of cardiovascular disease in Asia. We examined whether baPWV was associated with coronary atherosclerosis and presence and extent of coronary artery disease (CAD) in older patients with chest pain.Methods: This cross-sectional study enrolled 370 consecutive patients >65 years old who underwent baPWV measurement and elective coronary angiogram for suspected CAD at a single cardiovascular center, between June 2013 and July 2014.Results: In addition to diabetes mellitus and body mass index, baPWV was one of the statistically meaningful predictors of significant CAD (diameter of stenosis >50%) in a multivariate analysis. When the extent of CAD was classified as nonsignificant or significant CAD (ie, one-, two-, and three-vessel disease), there was a significant difference in baPWV between the significant and nonsignificant CAD groups, but not between the three significant CAD groups. Multivariate linear regression analyses showed that the number of diseased vessels and baPWV were both significantly associated with the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score. The cutoff value of baPWV at 1,874 cm/s had a sensitivity of 60.1%, specificity of 70.8%, and area under receiver operating characteristic curve of 0.639 in predicting CAD.Conclusion: Arterial stiffness determined by baPWV was associated independently with CAD severity, as assessed by angiography and the SYNTAX score in older patients with chest pain. As a result, increased arterial stiffness assessed by baPWV is associated with the severity and presence of CAD in older patients.Keywords: brachial-ankle pulse wave velocity, arterial stiffness, coronary artery disease, SYNTAX score

Chang-Min Chung,1,2 Hui-Wen Cheng,2 Jung-Jung Chang,2 Yu-Sheng Lin,2 Ju-Feng Hsiao,2 Shih-Tai Chang,1 Jen-Te Hsu2,31School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, 2Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, 3Department of Medicine, College of Medicine, Chang Gung University, Taoyuan County, TaiwanBackground: Resistant hypertension (RH) is a common clinical condition associated with increased cardiovascular mortality and morbidity in older patients. Several factors and conditions interfering with blood pressure (BP) control, such as excess sodium intake, obesity, diabetes, older age, kidney disease, and certain identifiable causes of hypertension are common in patients resistant to antihypertensive treatment. Arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV), is increasingly recognized as an important prognostic index and potential therapeutic target in hypertensive patients. The aim of this study was to determine whether there is an association between RH and arterial stiffness. Methods: This study included 1,620 patients aged ≥65 years who were referred or self-referred to the outpatient hypertension unit located at a single cardiovascular center. They were separated into normotensive, controlled BP, and resistant hypertension groups. Home BP, blood laboratory parameters, echocardiographic studies and baPWV all were measured. Results: The likelihood of diabetes mellitus was significantly greater in the RH group than in the group with controlled BP (odds ratio 2.114, 95% confidence interval [CI] 1.194–3.744, P=0.010). Systolic BP was correlated in the RH group significantly more than in the group with controlled BP (odds ratio 1.032, 95% CI 1.012–1.053, P=0.001). baPWV (odds ratio 1.084, 95% CI 1.016–1.156, P=0.015) was significantly correlated with the presence of RH. The other factors were negatively correlated with the existence of RH.Conclusion: In patients aged ≥65 years, the patients with RH have elevated vascular stiffness more than the well controlled hypertension group. baPWV increased with arterial stiffness and was correlated with BP levels. Strict BP control is necessary to prevent severe functional and structural vascular changes in the course of hypertensive disease.Keywords: arterial stiffness, brachial-ankle pulse wave velocity, resistant hypertension

Numerical results for ground-state and excited-state properties (energies, double occupancies, and Matsubara-axis self-energies) of the single-orbital Hubbard model on a two-dimensional square lattice are presented, in order to provide an assessment of our ability to compute accurate results in the thermodynamic limit. Many methods are employed, including auxiliary-field quantum Monte Carlo, bare and bold-line diagrammatic Monte Carlo, method of dual fermions, density matrix embedding theory, density matrix renormalization group, dynamical cluster approximation, diffusion Monte Carlo within a fixed-node approximation, unrestricted coupled cluster theory, and multireference projected Hartree-Fock methods. Comparison of results obtained by different methods allows for the identification of uncertainties and systematic errors. The importance of extrapolation to converged thermodynamic-limit values is emphasized. Cases where agreement between different methods is obtained establish benchmark results that may be useful in the validation of new approaches and the improvement of existing methods.

Background: Long COVID affects millions of people and results in a substantial decrease in quality of life. Previous primary studies and reviews attempted to study the effect of vaccination against long COVID, but these studies varied in the cut-off time of long COVID. We adhered to the WHO's definition of long COVID and conducted a systematic review and meta-analysis on the effect of pre-COVID and post-COVID vaccination on long COVID., Methods: We obtained data from 13 databases up to 18 February 2024, including peer reviewed and preprint studies. Our inclusion criteria were: (1) long COVID definition as 3 months or beyond, (2) comparing long COVID symptoms between vaccinated and unvaccinated groups, (3) subjects received vaccinations either before or after infected with COVID, (4) the number of doses received by participants was specified. We extracted study characteristics and data and computed the summary odds ratio (OR) with the DerSimonian and Laird random effects model. We then performed subgroup analyses based on the main vaccine brand and long COVID assessment method. ROBINS-I framework was used for assessment of risk of bias and the GRADE approach was used for evaluating the certainty of evidence., Findings: We included data from 25 observational studies (n = 14,128,260) with no randomised controlled trials. One-dose pre-COVID vaccination did not have an effect on long COVID (number of studies = 10, summary OR = 1.01, 95% CI = 0.88-1.15, p-value = 0.896). Two-dose pre-COVID vaccination was associated with a 24% reduced odds of long COVID (number of studies = 15, summary OR = 0.76, 95% CI = 0.65-0.89, p-value = 0.001) and 4 symptoms (fatigue, headache, loss of smell, muscle pain) out of 10 symptoms analysed. The OR of three-dose pre-COVID vaccination against overall long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.31, 95% CI = 0.05-1.84, p-value = 0.198). One-dose post-COVID vaccination was associated with a 15% reduced odds of long COVID (number of studies = 5, summary OR = 0.85, 95% CI = 0.73-0.98, p-value = 0.024). The OR of two-dose post-COVID vaccination against long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.63, 95% CI = 0.38-1.03, p-value = 0.066)., Interpretation: Our study suggests that 2-dose pre-COVID vaccination and 1-dose post-COVID vaccination are associated with a lower risk of long COVID. Since long COVID reduces quality of life substantially, vaccination could be a possible measure to maintain quality of life by partially protecting against long COVID., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Sarcopenia is a common age-related disease, defined as a decrease in muscle strength and function owing to reduced skeletal muscle. One way to diagnose sarcopenia is through gait analysis and foot-pressure imaging., Motivation and Research Gap: We collected our own multimodal dataset from 100 subjects, consisting of both foot-pressure and skeleton data with real patients, which provides a unique resource for future studies aimed at more comprehensive analyses. While artificial intelligence has been employed for sarcopenia detection, previous studies have predominantly focused on skeleton-based datasets without exploring the combined potential of skeleton and foot pressure dataset. This study conducts separate experiments for foot-pressure and skeleton datasets, it demonstrates the potential of each data type in sarcopenia classification., Methods: This study had two components. First, we collected skeleton and foot-pressure datasets and classified them into sarcopenia and non-sarcopenia groups based on grip strength, gait performance, and appendicular skeletal muscle mass. Second, we performed experiments on the foot-pressure dataset using the ResNet-18 and spatiotemporal graph convolutional network (ST-GCN) models on the skeleton dataset to classify normal and abnormal gaits due to sarcopenia. For an accurate diagnosis, real-time walking of 100 participants was recorded at 30 fps as RGB + D images. The skeleton dataset was constructed by extracting 3D skeleton information comprising 25 feature points from the image, whereas the foot-pressure dataset was constructed by exerting pressure on the foot-pressure plates., Results: As a baseline evaluation, the accuracies of sarcopenia classification performance from foot-pressure image using Resnet-18 and skeleton sequences using ST-GCN were identified as 77.16 and 78.63%, respectively., Discussion: The experimental results demonstrated the potential applications of sarcopenia and non-sarcopenia classifications based on foot-pressure images and skeleton sequences., 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 © 2024 Naseem, Kim, Seo, Lee, Chung, Shin and Lee.)

Background/Objectives : Major depressive disorder (MDD) frequently co-occurs with substance use disorders such as alcohol and nicotine use disorders. Comorbid substance use disorders worsen the clinical symptoms of MDD and exacerbate addictive behaviors and presentations. However, the relationship between MDD and betel quid use disorder (BUD) in Taiwan has not been extensively investigated. Methods : We performed this cross-sectional study investigated associations between betel quid use, BUD, and MDD specifically in the Taiwanese population. Long-term betel quid use is a major public health concern, contributing significantly to the high incidence of oral cancers, which rank fifth among the top ten most common cancers in Taiwan. Results : Among patients with MDD, the current BUD prevalence rate was 7.32%, and the lifetime BUD prevalence rate was 15.45%. Patients with comorbid BUD were more likely to have severe alcohol and nicotine dependence disorders and required longer antidepressant treatment. Conclusions : Notably, 16.98% of patients with comorbid BUD who received selective serotonin reuptake inhibitor treatment achieved abstinence. BUD has a detrimental effect on health outcomes in patients with MDD, and selective serotonin reuptake inhibitor treatment may be required to be prolonged for betel quid abstinence therapy to be effective. Additional studies should investigate medication therapies for betel quid addiction disorders.

This study attempted to establish a viscosity-based prediction of membrane fouling. Various factors, including pH, temperature, MLSS concentration, and the addition of NaOCl and citric acid were identified, and their effect on sludge properties such as EPS concentration and wastewater viscosity were estimated. There was a very good correlation between these parameters with EPS concentration and viscosity. The increase in EPS concentration and viscosity significantly affected the membrane flux and filtration time for all the different experimental conditions. However, there were fluctuations in results obtained from experiments related to change in pH, including the addition of antifouling agents NaOCl and citric acid. Such variations accompanied by low correlation in these experiments indicated the influence of pH that may pose difficulty in a viscosity-based estimation of membrane fouling. However, if such large variations in operating conditions could be avoided and the reactor could be operated under optimal conditions, a much better correlation could be obtained between viscosity and membrane fouling. Data from continuously operated MBR systems support this observation, where even a linear equation defining relation between viscosity and transmembrane pressure (TMP) could be obtained. Overall, findings from this study provide a great insight into membrane fouling prediction using viscosity-based methods., Competing Interests: Declaration of competing interest There is no conflict of interest between the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 ( p = 0.0194), 4 ( p = 0.0078), 6 ( p = 0.0277), and 8 ( p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 ( p = 0.0313), 4 ( p = 0.0134), 6 ( p = 0.0061), and 8 ( p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score ( p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.

This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed the best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium-to-fluoride ratio of 0.6 within the first 40 days of continuous operation. The resulting particle size increased by more than double during this time, along with a 36% increase in the seed bed height, indicating the deposition of CaF 2 onto the silica seed. The SEM-EDX analysis showed the size and shape of the crystals formed, along with the presence of a high amount of Ca-F ions. The purity of the CaF 2 crystals was determined to be 91.1% though ICP-OES analysis. Following the continuous experiment, different process improvement strategies were explored. The addition of an excess amount of calcium resulted in the removal of an additional 6% of the fluoride; however, compared to this single-stage process, a two-stage approach was found to be a better strategy to achieve a low effluent concentration of fluoride. The fluoride removal reached 94% with this two-stage approach under the optimum conditions of 4 + 1 h HRT combinations and a [Ca 2+ ]/[F - ] ratio of 0.55 and 0.7 for the two reactors, respectively. CFD simulation showed the impact of the inlet diameter, bottom-angle shape, and width-to-height ratio of the reactor on the mixing inside the reactor and the possibility of further improvement in the reactor performance by optimizing the FBR configuration.

This study utilized a fluidized bed reactor (FBR) for fluoride removal from high-concentration fluoride-ion-containing simulated semiconductor industry wastewater and recovered high-purity CaF 2 crystals. The effects of hydraulic retention time (HRT), pH, Ca 2+ to F - ratio, upflow velocity, seed size and seed bed height were investigated by performing lab-scale batch experiments. Considering fluoride removal and CaF 2 crystallization efficiency, 5 h HRT, pH 6, seed height of 50 cm and [Ca 2+ ]/[F - ] ratio of 0.55 (mol/mol) were found to be optimum. The effect of the interaction between the important process parameters on fluoride removal was further analyzed using response surface methodology (RSM) experimental design. The results showed that all the individual parameters have a significant impact ( p = 0.0001) on fluoride removal. SEM-EDX and FTIR analysis showed the composition of the crystals formed inside FBR. HR-XRD analysis confirmed that the crystalline structure of samples was mainly CaF 2 . The results clearly demonstrated the feasibility of silica seed material containing FBR for efficient removal and recovery of fluoride as high-purity calcium fluoride crystals.

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study., Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years)., Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p  = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p  < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p  = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients., Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Background  Congenital muscular torticollis (CMT) is a common musculoskeletal disorder in children. Secondary scoliosis can occur in patients with CMT; however, the extent of inclination and improvement of scoliosis after surgical correction of CMT have not been adequately studied. In this study, we aimed to evaluate and measure the improvement in vertebral tilting after surgical correction according to age at the time of surgery. Methods  Between June 2007 and January 2020, 831 patients with CMT underwent sternocleidomastoid release. Among them, 426 patients were enrolled, and their medical records were retrospectively reviewed. Ultimately, 210 patients available for radiological evaluation and analysis were enrolled in this study. The patients were divided into four groups according to age at the time of surgery to determine the relationship between age and changes in scoliosis. Results  Our findings showed an improvement in scoliosis in all age groups after surgery. The results for follow-up after 1 year confirmed long-term improvement in vertebral tilting. The degree of improvement in scoliosis was significantly higher in the younger age group than in patients aged 18 years or older. Conclusion  The effect of surgical release on scoliosis was significant in all age groups. The findings of this study suggest that CMT should be corrected before the age of 3 years to ensure an optimal surgical mitigation of scoliosis. Furthermore, in cases of neglected CMT, surgical release should be actively attempted because there is significant improvement., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Betel quid (BQ) is the fourth most popular psychoactive substance in the world, and BQ use disorder (BUD) is prevalent in Asian countries. Although the mechanisms underlying BUD remain unclear, studies have reported influences from monoamine oxidase inhibitor. We enrolled 50 patients with BUD and assessed their BQ consumption habits, emotional conditions, and the clinical severity of addiction-assessed using the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] ( DSM-5 ) criteria, Substance Use Severity Rating Scale, and Yale-Brown Obsessive Compulsive Disorder Rating Scale for BQ. Patients were categorized into the severe group when showing six or more symptoms defined by DSM-5 . A genome-wide association study was conducted for single nucleotide polymorphisms in BRCA1 , COL9A1 , NOTCH1 , HSPA13 , FAT1 , and MAOA by using patients' blood samples. More severe BUD symptoms were associated with younger age of using BQ and poor oral hygiene and with severe craving for and more anxiety toward BQ use. The MAOA rs5953210 polymorphism was significantly associated with severe BUD (odds ratio, 6.43; 95% confidence interval, 5.12-7.74; p < 0.01) and might contribute to BQ-associated cancer risk. Further studies are required to investigate the addictive properties of BQ and the development of novel diagnostic tools and pharmacotherapeutic alternatives to BUD treatment.

Background: Little research has been done on ischemic outcomes related to left ventricular ejection fraction (EF) in acute decompensated heart failure (ADHF)., Methods: A retrospective cohort study was conducted between 2001 and 2021 using the Chang Gung Research Database. ADHF Patients discharged from hospitals between January 1, 2005, and December 31, 2019. Cardiovascular (CV) mortality and heart failure (HF) rehospitalization are the primary outcome components, along with all-cause mortality, acute myocardial infarction (AMI) and stroke., Results: A total of 12,852 ADHF patients were identified, of whom 2,222 (17.3%) had HFmrEF, the mean (SD) age was 68.5 (14.6) years, and 1,327 (59.7%) were males. In comparison with HFrEF and HFpEF patients, HFmrEF patients had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease. Patients with HFmrEF were more likely to experience renal failure, dialysis, and replacement. Both HFmrEF and HFrEF had similar rates of cardioversion and coronary interventions. There was an intermediate clinical outcome between HFpEF and HFrEF, but HFmrEF had the highest rate of AMI (HFpEF, 9.3%; HFmrEF, 13.6%; HFrEF, 9.9%). The AMI rates in HFmrEF were higher than those in HFpEF (AHR, 1.15; 95% Confidence Interval, 0.99 to 1.32) but not in HFrEF (AHR, 0.99; 95% Confidence Interval, 0.87 to 1.13)., Conclusion: Acute decompression in patients with HFmrEF increases the risk of myocardial infarction. The relationship between HFmrEF and ischemic cardiomyopathy, as well as optimal anti-ischemic treatment, requires further research on a large scale., (© 2023. The Author(s).)

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to inadequate insulin secretion, resistance, or both. The cardiovascular complications of DM are the leading cause of morbidity and mortality in diabetic patients. There are three major types of pathophysiologic cardiac remodeling including coronary artery atherosclerosis, cardiac autonomic neuropathy, and DM cardiomyopathy in patients with DM. DM cardiomyopathy is a distinct cardiomyopathy characterized by myocardial dysfunction in the absence of coronary artery disease, hypertension, and valvular heart disease. Cardiac fibrosis, defined as the excessive deposition of extracellular matrix (ECM) proteins, is a hallmark of DM cardiomyopathy. The pathophysiology of cardiac fibrosis in DM cardiomyopathy is complex and involves multiple cellular and molecular mechanisms. Cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction (HFpEF), which increases mortality and the incidence of hospitalizations. As medical technology advances, the severity of cardiac fibrosis in DM cardiomyopathy can be evaluated by non-invasive imaging modalities such as echocardiography, heart computed tomography (CT), cardiac magnetic resonance imaging (MRI), and nuclear imaging. In this review article, we will discuss the pathophysiology of cardiac fibrosis in DM cardiomyopathy, non-invasive imaging modalities to evaluate the severity of cardiac fibrosis, and therapeutic strategies for DM cardiomyopathy.

Background: Little is known about the effect that different time sequences for coronary ligation and reperfusion have on ischemic-reperfusion (IR) injury., Objective: To investigate the relationship between the extent of IR injury and the timeframe for coronary ligation/reperfusion in three animal models., Methods: Three rat models were used: normal Sprague-Dawley rats, diabetes mellitus (DM) rats, and fat rats. The rats in each model were divided into four groups based on the coronary ligation period (L): 30, 60, 120, and 180 min, and then divided into seven sub-groups based on the reperfusion period (R): 0, 30, 60, 120, 180, 270, and 360 min. R0 was the IR injury baseline for each sub-group. The hearts were harvested and stained with Evans blue and 2,3,5-triphenyl tetrazolium chloride dye to distinguish the different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The difference between each subgroup and baseline (R0) for the necrotic area/AAR was calculated., Results: In the normal rats, the highest IR injury differences compared with the baseline group occurred at L120, with a reperfusion time of > 180 min. The highest IR injury difference compared to the baseline group occurred at L30, with a reperfusion time of > 180 min in the DM rats and at L60R270, L120R180 in the fat rats., Conclusions: IR injury, as induced by different coronary ligation and reperfusion time intervals, had diverse expression profiles in the different animal models. Optimal animal models with optimal coronary ligation/reperfusion protocols to achieve maximal IR injury will affect the results and interpretation of future studies.

Insulated gate bipolar transistor (IGBT) is an important power device for the conversion, control, and transmission of semiconductor power, and is used in various industrial fields. The IGBT module currently uses silicone gel as an insulating layer. Since higher power density and more severe temperature applications have become the trend according to the development of electronic device industry, insulating materials with improved heat resistance and insulation performances should be developed. In this study, we intended to synthesize a new insulating material with enhanced thermal stability and reduced thermal conductivity. Poly(imide-siloxane) (PIS) was prepared and crosslinked through a hydrosilylation reaction to obtain a semi-solid Crosslinked PIS. Thermal decomposition temperature, thermal conductivity, optical transparency, dielectric constant, and rheological property of the Crosslinked PIS were investigated and compared to those of a commercial silicone gel. The Crosslinked PIS showed high thermal stability and low thermal conductivity, along with other desirable properties, and so could be useful as an IGBT-insulating material.

Background: Heart rate (HR) control is important in heart failure (HF) patients with reduced ejection fraction, and ivabradine is indicated for patients with chronic HF and sinus rhythm. However, ivabradine is limited in initiation of ivabradine at acute stage of HF., Materials and Methods: This multi-institutional retrospective study enrolled 30,639 patients who were admitted for HF from January 01, 2013 to December 31, 2018 at Chang Gung Memorial Hospitals. After applying selection criteria, the eligible patients were divided into ivabradine and non-ivabradine groups according to the initiation of ivabradine at the index hospitalization. HR, clinical outcomes including HF hospitalization, all-cause hospitalization, mortality, the composite of cardiovascular (CV) death or HF hospitalization and newly developed atrial fibrillation, and left ventricular ejection fraction (LVEF) and left atrium size were compared between the ivabradine and non-ivabradine groups after inverse probability of treatment weighting (IPTW) analysis after 12 months., Results: The HR at admission in the ivabradine group ( n = 433) was 99.04 ± 20.69/min, compared to 86.99 ± 20.34/min in the non-ivabradine group ( n = 9,601). After IPTW, HR was lower in the ivabradine group than that in the non-ivabradine group after 12 months (74.14 ± 8.53 vs. 81.23 ± 16.79 bpm, p = 0.079). However, there were no significant differences in HF hospitalization (HR = 1.02; 95% CI, 0.38-2.79), all-cause hospitalization (HR = 0.95; 95% CI, 0.54-1.68), mortality (HR = 0.87; 95% CI, 0.69-1.08), the composite of CV death or HF hospitalization (HR = 0.87; 95% CI, 0.69-1.08) and newly developed AF between the two groups. In addition, LVEF increased with time in both groups, but there were no significant differences during the observation period., Conclusion: Ivabradine was beneficial in controlling HR when initiated in patients with acute stage of HF, but it did not seem to provide any benefits in reducing HF hospitalization, all-cause hospitalization, and mortality in 1 year after discharge., 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 © 2022 Yang, Tsai, Jan, Chang, Chung, Lin, Chen and Lin.)

Various groups of antihypertensive drugs targeting different pathways have been developed; however, the pharmacometabolic responses to these drugs have rarely been compared to elucidate the common pathway of blood pressure regulation. Here, we performed a comparative multi-dimensional pharmacometabolic study on the four major lines of antihypertensive drugs, namely angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics (DIURs), through ultra-performance liquid chromatography coupled to quantum time-of-flight mass spectrometry. Two hundred fifty patients with young-onset hypertension, who were equally divided among five study groups: non-medicated, ACEi, ARB, CCB, and DIUR groups, were recruited. In a metabolome-wide association study conducted through analysis of covariance, 37 molecular features significantly associated with pharmacometabolic responses to antihypertensive drugs were identified. One-third of these features were shared by multiple medications. ACEis, ARBs, and DIURs shared more features than CCB, partially reflecting that ACEis, ARBs, and DIURs affect the renin-angiotensin-aldosterone system. Thirteen molecular features were consistently identified by all four models of the analysis of covariance. A tandem mass spectrometry (or MS/MS) experiment was performed to decipher the chemical structure of these 13 molecular features, including ARB-associated lysophosphatidylcholine (P4135), CCB-associated diacylglycerol(15:0/18:2) (P1175), and DIUR-associated oleamide (P1516). In addition, diacylglycerol(15:0/14:2) (P408) was significantly associated with the pharmacometabolic response to all four antihypertensive drugs. The identified metabolites provide insights into the mechanisms of blood pressure regulation and potential predictive markers of pharmacometabolic responses to antihypertensive drugs., Competing Interests: 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., (© 2022 The Author(s).)

Background and Objectives: Previous studies have revealed that independent variables (lower extremity strength, postural control ability, and body composition) influence gait performance and variability, but the difference in the relative influence between these variables is unclear. Hence, this study determines the variable that is the most influential predictor of gait performance and variability among potential independent variables in the elderly. Materials and Methods: Seventy-eight subjects aged ≥60 years participated. For each subject, the gait variables and lower extremity muscle strength were measured using an accelerometer worn on both feet during a 6-minute walk and a manual force sensor, respectively. The static balance ability was measured through two force plates, and the body composition was measured by applying bioelectrical impedance analysis. Linear regression analyses were performed stepwise to determine whether these variables affect gait performance and variability. Results: After adjusting for sex and gait performance, the ankle strength, body fat mass, mean velocity in the medial-lateral direction, ankle plantar flexion strength, and girth were predictors of gait speed dorsiflexion, gait performance, swing width of the gait performance, walking speed, and gait variability, respectively. Conclusions: Overall, gait performance in the elderly is related to muscle strength, postural control, and body composition in a complex manner, but gait variability appears to be more closely related to ankle muscle strength. This study provides further evidence that muscle strength is important in motor function and stability.

Emergency department visits (EDV) are common among older adults with and without dementia. The risk factors and demands of EDVs for people with dementia have been well studied; however, the association between EDVs and conversion to dementia among people with predementia has not been thoroughly explored. To study the predictive value of EDVs in predementia's progression to dementia. The baseline predementia cohort registered from September 2015 to August 2017, with longitudinal follow-up in the History-based Artificial Intelligent Clinical Dementia Diagnostic System database, was retrospectively analyzed. The rates of conversion among the different EDVs were compared. Multivariate logistic regression and Cox proportional hazards analyses were applied to study the influence of EDVs on progression. Age, education, sex, neuropsychological tests, activities of daily living, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors were adjusted for. A total of 512 participants were analyzed, including 339 (66.2%) non-converters and 173 (33.8%) converters with a mean follow-up of 3.3 (range 0.4-6.1) and 2.8 (range 0.5-5.9) years, respectively. Compared to people without EDV (EDV 0), the hazard ratios for conversion to dementia were 3.6, 5.9, and 6.9 in those with EDV once (EDV 1), twice (EDV 2), and more than twice (EDV >2), respectively. In addition, older age, lower education, poorer cognition, poorer ADL performance, and longer follow-up periods also increased the conversion rates. EDVs in the predementia stages highly predict progression to dementia. Therefore, a sound public health as well as primary healthcare system that provide strategies for better management of mental and physical condition might help prevention of EDVs among older people in the predementia stages., Competing Interests: The authors have declared that no competing interests exist.

Objective: SLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension., Methods: Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3 . Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR)., Results: In cohort 1, SLC12A3 rs16963397 C/C or C/G ( P = 0.005), rs13334864 C/C or C/T ( P = 0.020), and rs7187932 A/A or A/G polymorphisms ( P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158-9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529-227.005, P = 0.022) than their counterparts., Conclusion: SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension., 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 © 2022 Huang, Chung, Yang, Leu, Huang, Lin, Wu, Lin, Pan and Chen.)

The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation. Of particular interest is a subset of alveolar cells termed basal-luminal (BL) cells, which exhibit poor transcriptional lineage fidelity, accumulate with age, and carry a gene signature associated with basal-like breast cancer. We further utilize a medium-depletion approach to identify molecular factors regulating cell-subtype proportion in organoids. Together, these data are a rich resource to elucidate diverse mammary cell states., Competing Interests: Declaration of interests J.S.B. is a scientific advisory board (SAB) member of Frontier Medicines and eFFECTOR Therapeutics and was an Agios Pharmaceuticals SAB member until January 2022. D.A.D. is on the SAB for Oncology Analytics, Inc., has consulted for Novartis, and receives research support from Canon, Inc. J.E.G. is a paid consultant for Helix and an uncompensated consultant for Konica Minolta and Earli. K.L.N. is a Nest Genomics SAB member. R.C.J.S. and W.L.G. are current employees of Genmab B.V. and Carcell Therapeutics, respectively. There are no conflicts of interest with this work. P.K.S. is an SAB or Board of Directors member of Applied Biomath, Nanostring, RareCyte Inc., and Glencoe Software, which distributes a commercial version of OMERO. In the last five years, P.K.S. has received research funding from Novartis and Merck. S.S. is a consultant for RareCyte Inc. A.R. is a co-founder and equity holder of Celsius Therapeutics and an equity holder in Immunitas. She was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov until July 31, 2020. She has been an employee of Genentech since August 1, 2020 and has equity in Roche. P.K.S., S.S., and A.R. declare that these relationships have not influenced this manuscript’s content. G.K.G. is of no relation to the Gray Foundation leadership. J.S.B. is on the Advisory Board of Developmental Cell., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Generally, microcapsule-based self-healing materials have the limitation of single local self-healing. A few studies have reported repeatable self-healing in these microcapsular materials, but there is a challenge to develop multi-cycle self-healing materials that have the advantages of easier preparation and a more efficient operation. In this work, a mixture of two vegetable oils, soybean and olive oil, was used as a healing agent. The atmospheric oxygen-induced reaction behavior (in the presence of a catalyst) was investigated for various compositions of the vegetable oil mixtures; infrared spectroscopy, recovery testing, and viscoelasticity measurement were performed to find an optimum composition of the healing agent. Microcapsules loaded with soybean oil and catalyst-containing olive oil were separately prepared and used to prepare a dual-capsule self-healing coating. It was demonstrated through optical and scanning electron microscopy that, upon scribing the self-healing coating, the vegetable oils flowed out from microcapsules to self-heal the damaged area. When the healed area of the self-healing coating was re-scribed, self-healing was repeated, which was confirmed by scanning electron microscopy (SEM) and anticorrosion and electrochemical testing. Our new repeatable self-healing coating provides the merits of easy preparation, no need for external intervention such as light irradiation, and an environmentally-friendly nature.

Graphene oxide-cysteamine-silver nanoparticle (GCA)/silver nanowire (AgNW)/GCA/colorless poly(amide-imide) (cPAI) structures based on cPAI substrates with polyimide and polyamide syntheses were fabricated to study their characteristics. A layer of electrodes was constructed using a sandwich structure-such as GCA/AgNW/GCA-with cPAI used as a substrate to increase the heat resistance and improve their mechanical properties. Furthermore, to overcome the disadvantages of AgNWs-such as their high surface roughness and weak adhesion between the substrate and electrode layers-electrodes with embedded structures were fabricated using a peel-off process. Through bending, tapping, and durability tests, it was confirmed that these multilayer electrodes exhibited better mechanical durability than conventional AgNW electrodes. Resistive random-access memory based on GCA/AgNW/GCA/cPAI electrodes was fabricated, and its applicability to nonvolatile memory was confirmed. The memory device had an ON/OFF current ratio of ~10 4 @0.5 V, exhibiting write-once-read-many time characteristics, maintaining these memory characteristics for up to 300 sweep cycles. These findings suggest that GCA/AgNW/GCA/cPAI electrodes could be used as flexible and transparent electrodes for next-generation flexible nonvolatile memories.

Objective: To investigate which types of β-blockers have better efficacy and safety profiles in patients with concomitant chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI) to address concerns about use of β-blockers in COPD., Methods: We identified 65,699 patients with COPD prescribed β-blockers after first MI in the Taiwan National Health Insurance Research Database between January 1, 2001, and December 31, 2013. Comparisons were performed using the inverse probability of treatment weighting method. The primary outcome was all-cause mortality; secondary outcomes were heart failure hospitalization, major adverse cardiac and cerebrovascular event (MACCE), and major adverse pulmonary event (MAPE)., Results: A total of 14,789 patients prescribed β-blockers were enrolled, of whom 7247 (49.0%) used cardioselective β-blockers and 7542 (51.0%) used nonselective β-blockers. The cardioselective group had lower incidence rates of mortality (hazard ratio [HR], 0.93; 95% CI, 0.89 to 0.96), MACCE (HR, 0.96; 95% CI, 0.93 to 0.998), heart failure hospitalization (subdistribution HR, 0.84; 95% CI, 0.78 to 0.91), and MAPE (HR, 0.94; 95% CI, 0.90 to 0.98) at the end of follow-up after weighting. Similar results were also found in subgroup analysis between those prescribed bisoprolol and those prescribed carvedilol., Conclusion: Patients prescribed a cardioselective β-blocker may have a lower incidence of all-cause mortality, MACCE, heart failure hospitalization, and MAPE than those prescribed a nonselective β-blocker. Cardioselective β-blocker treatment during hospitalization and continuing after discharge appears to be superior to nonselective β-blocker treatment in patients with COPD after MI., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We herein report transparent self-cleaning coatings based on polyimide-fluorinated silica sol (PIFSS) nanocomposite. Polyamic acid-silica sol (PASS) suspensions were synthesized by adding four different amounts of a silica sol suspension to each end-capped polyamic acid solution. The PASS suspensions were spin-coated on glass slides, thermally imidized and treated with triethoxy-1 H ,1 H ,2 H ,2 H -perfluorodecylsilane (TEFDS) to prepare PIFSS coatings. The PIFSS coatings showed high resistance to separation from glass substrates and thermal stability. Furthermore, the PIFSS coatings on the glass substrate could be cleanly removed using polar aprotic solvents and repeated coating was possible. As the amount of silica sol particles in the PIFSS coating was increased, the hydrophobic contact angle increased. Among them, PIFSS-10 and PIFSS-15 coatings showed nearly superhydrophobic contact angles (144° and 148°, respectively) and good self-cleaning property. It was confirmed by SEM and AFM studies that their hydrophobic and self-cleaning properties are due to uniform particle distribution and relatively high surface roughness. PIFSS-10 coating showed a high transmittance value (88%) at 550 nm and good self-cleaning property, therefore suitable as a transparent self-cleaning coating. The advantages of the coating are that the fabrication process is simple, and the substrate is reusable. The PIFSS coating is expected to be applied in solar cell panels, windows, lenses and safety goggles.

Objectives: Atrial fibrillation (AF) is linked to an increased risk of stroke and dementia. Atrial flutter (AFL) is also linked to an increased risk of stroke but at a different level of risk as compared to AF. Little is known about the difference in the risk of dementia between AF and AFL. This study aims to investigate whether the risk of dementia is different between AF and AFL. Methods: Patients with newly diagnosed AF and AFL during 2001-2013 were retrieved from Taiwan's National Health Insurance Research Database. Patients with incomplete demographic data, aged <20 years, history of valvular surgery, rheumatic heart disease, hyperthyroidism, and history of dementia were excluded. The incidence of new-onset dementia was set as the primary outcome and analyzed in patients with AF and AFL after propensity score matching (PSM). Results: A total of 232,425 and 7,569 patients with AF and AFL, respectively, were eligible for analysis. After 4:1 PSM, we included 30,276 and 7,569 patients with AF and AFL, respectively, for analysis. Additionally, patients with AF ( n = 29,187) and AFL ( n = 451) who received oral anticoagulants were enrolled for comparison. The risk of dementia was higher in patients with AF compared with patients with AFL (subdistribution hazard ratio (SHR) = 1.52, 95% CI 1.39-1.66; p < 0.0001) before PSM and remained higher in patients with AF (SHR = 1.14, 95% CI 1.04-1.25; p = 0.0064) after PSM. The risk of dementia was higher in patients with AF without previous history of stroke after PSM but the risk did not differ between patients with AF and AFL with previous history of stroke. Among patients who received oral anticoagulants, the cumulative incidences of dementia were significantly higher in patients with AF than in patients with AFL before and after PSM (all P < 0.05). Conclusions: This study found that, among patients without history of stroke, the risk of dementia was higher in patients with AF than in patients with AFL, and CHA 2 DS 2 -VASc score might be useful for risk stratification of dementia between patients with AF and AFL., 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 © 2021 Wang, Chen, Lin, Chen, Chong, Hsueh, Chung and Chen.)

The purpose of this study was to develop a microcapsule-type self-healing coating system that could self-heal cracks and then maintain the healed state even upon crack expansion. Mixtures consisting of a photoinitiator and two methacrylate components, bismethacryloxypropyl-terminated polydimethylsiloxane (BMT-PDMS) and monomethacryloxypropyl-terminated PDMS (MMT-PDMS), were transformed into viscoelastic semi-solids through photoreaction. The viscoelasticity of the reacted mixtures could be controlled by varying the mass ratio of the two methacrylates. Through a stretchability test, the optimal composition mixture was chosen as a healing agent. Microcapsules loaded with the healing agent were prepared and dispersed in a commercial undercoating to obtain a self-healing coating formulation. The formulation was applied onto mortar specimens, and then cracks were generated in the coating by using a universal testing machine (UTM). Cracks with around a 150-μm mean width were generated and were allowed to self-heal under UV light. Then, the cracks were expanded up to 650 μm in width. By conducting a water sorptivity test at each expanded crack width, the self-healing efficiency and capability of maintaining the healed state were evaluated. The B-M-1.5-1-based coating showed a healing efficiency of 90% at a 150-μm crack width and maintained its healing efficiency (about 80%) up to a 350-μm crack width. This self-healing coating system is promising for the protection of structural materials that can undergo crack formation and expansion.

Objective: This study assesses the mortality outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF)., Methods: Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer-related death. Secondary outcomes were all-cause mortality, major bleeding, and gastrointestinal (GI) bleeding., Results: Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer-related death at one year (HR = 0.71, 95% CI = 0.54-0.93) and at the end of follow-ups (HR = 0.79, 95% CI = 0.64-0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all-cause mortality (HR = 0.81, 95% CI = 0.67-0.97), major bleeding (HR = 0.64, 95% CI = 0.47-0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39-0.84) at the end of follow-ups compared with rivaroxaban., Conclusion: Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer-related death and all-cause mortality., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Alternative forms of cigarettes, such as electronic cigarettes (e-cigarettes), are becoming increasingly common among adolescents. Many high schools now provide smoking-prevention education in an attempt to minimize the potential negative health effects and illness burdens e-cigarettes may induce in adolescents. However, it is often difficult to motivate young students to engage with traditional education regarding the harmful effects of tobacco; thus, the development of alternative approaches may be required., Objective: In this study, we aimed to conduct an acceptability evaluation of educational virtual reality games designed to support smoking-prevention measures. We based the acceptability evaluation on the following two experience types: game-playing and content-learning experiences. The paths by which these experience types affect the intention to abstain from smoking were also examined., Methods: We applied a prospective observational study design. We developed educational games based on three-dimensional virtual reality technology, in which participants operated joysticks to complete challenge tasks. To increase the possibility of the games fostering motivation to abstain from smoking, the ARCS motivational model (comprising attention, relevance, confidence, and satisfaction) was used as a framework during the games' design. We measured the participants' game-playing experiences by inquiring about the strength of the ARCS elements; content-learning experiences were measured using overall knowledge improvement and the perceived persuasiveness of the content. A total of 130 students participated in the program. Study hypotheses for this evaluation were derived from a literature review. We used partial least squares structural equation modeling to examine the proposed hypotheses., Results: Based on the responses of the students to questionnaire items concerning attention, relevance, confidence, and satisfaction in the context of the games, most students agreed or strongly agreed that the educational games were motivational, and that their game-playing experiences were positive. Regarding content-learning experiences, there was a significant improvement in knowledge (t 129 =25.67, P<.001), and most students perceived themselves as being persuaded to abstain from smoking. Attention, relevance, and satisfaction significantly influenced perceived persuasiveness (t=3.19, P<.001; t=4.28, P<.001; and t=3.49, P<.001, respectively); however, confidence did not (t=0.42, P=.67). Perceived persuasiveness, relevance, and satisfaction significantly influenced the intention to abstain from smoking (t=3.57, P<.001). In addition to directly affecting the intention to abstain from smoking, indirect effects were observed from both relevance and satisfaction to intention via perceived persuasiveness (t=2.87, P=.004 and t=2.11, P=.04, respectively). However, intention was not significantly influenced by knowledge improvement., Conclusions: Our findings revealed that the educational games were positively accepted by the participating students. This indicates that the integration of the ARCS framework and persuasive strategies is applicable for smoking-prevention education. We recommend that the games be included as teaching materials for smoking-prevention education., (©Jong-Long Guo, Hsiao-Pei Hsu, Tzu-Ming Lai, Mei-Ling Lin, Chih-Ming Chung, Chiu-Mieh Huang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.09.2021.)

Areca nut (AN) was identified as carcinogenic to humans. Around 600 million people globally use AN in some form, yet no effective therapeutic drug is available to overcome AN addiction. This preclinical study examines the effects of antidepressants on AN use with animal models. We produced AN powder and dissolved it into drinking water, training 55 C57BL/6 mice in free self-selection to drink AN water or normal water. Then, the mice were randomly divided into four groups. Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs) were given as three treatment groups and one placebo group for four weeks. In the follow-up period, the preference and amount of free selection of AN and normal water, and oral pathological change were evaluated. There was a significant decrease in preference for AN drinking during the first four weeks, and the 36th week after drug withdrawal in the MAOI and SSRI groups (all p < 0.05). The drug-reducing effect of AN water in the 1-4-week period was significant in the MAOI group ( p < 0.0001) and was also significant in the 3-4-week period in the SSRI group ( p = 0.03). The TCA group did not show a decrease effect. At the endpoint (60 weeks), oral mucosal fibrosis (OSF) levels and risk in the SSRI ( p = 0.0081) and MAOI ( p = 0.01) groups were significantly lower than those in the control group. Antidepressant drugs MAOIs and SSRIs could reduce the amount of AN use and decrease the early stage of oral fibrosis in mice, but SSRIs may need to be boosted again.

Atrial fibrillation (AF) is one of the risk factors for dementia. Female sex is an inconsistent risk factor for dementia after adjusting for age in the general population, and there lacks research on its impact in developing dementia in patients with AF. This paper aims to investigate whether female sex is a risk factor for dementia in AF patients. Data of patients with newly diagnosed AF between 2001-2013 were retrieved from Taiwan's National Health Insurance Research Database. Exclusion criteria were: patients with incomplete demographic data, age < 20 years, rheumatic heart disease, hyperthyroidism, past valvular heart surgery, and a history of dementia. Propensity score matching (PSM) between sexes was performed, including comorbidities, medications and index date stratified by age. The primary outcome was a new diagnosis of dementia at follow-up. A total of 117,517 men and 156,705 women were eligible for analysis. After 1:1 PSM, both 100,065 men and women (aged 72.5 ± 12.5 years) were included for analysis. Dementia risk varied with age in women compared with men. The difference was negligible for ≤55 years (sub distribution HR (SHR) = 0.89, 95% CI 0.73-1.07), but increased between 56-65 years (SHR = 1.13, 95% CI 1.02-1.25), 66-75 years (SHR = 1.14, 95% CI 1.09-1.20), 75-85 years (SHR = 1.11, 95% CI 1.07-1.15) and >85 years (SHR 1.10, 95% CI 1.04-1.16) for females. This study establishes that female sex increases the risk of developing dementia compared to male sex in AF patients aged >56 years. However, the impact of female sex on dementia in AF patients differs between dementia types.

Little is known about the association between deep vein thrombosis (DVT) and arterial complications in patients with type 2 diabetes (T2DM). The aim of this retrospective cohort study was to assess the influence of prior DVT on major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) in T2DM. A total of 1,628,675 patients with T2DM with or without a history of DVT from 2001 to 2013 were identified in the National Health Insurance Research Database of Taiwan. Before matching, the patients in the DVT group (n = 2020) were older than the control group (66.3 vs. 58.3 years). Patients in the DVT group were more likely to be female than the control group (54.3% vs. 47.5%). Before matching, the DVT group had higher prevalence of most comorbidities, more prescription of antiplatelet, antihypertensive agents and insulins, but less prescription of metformin and sulfonylurea. During a mean follow-up of 5.2 years (standard deviation: 3.9 years), the matched DVT group (n = 2017) have a significantly increased risk of MALE (8.4% vs. 5.2%; subdistribution hazard ratio [SHR] 1.60, 95% CI 1.34-1.90), foot ulcer (5.2% vs. 2.6%, SHR 1.96, 95% CI 1.57-2.45), gangrene (3.4% vs. 2.3%, SHR 1.44, 95% CI 1.10-1.90) and amputation (2.5% vs. 1.7%; SHR 1.42, 95% CI 1.03-1.95) than the 10,085 matched controls without DVT. They also tended to have a greater risk of all-cause mortality (38.1% vs. 33.1%; hazard ratio [HR] 1.18, 95% CI 1.09-1.27) and systemic thromboembolism (4.2% vs. 2.6%; SHR 1.56, 95% CI 1.22-1.99), respectively. We showed the presence of DVT may be associated with an increased risk of MALEs, major amputation, and thromboembolism, contributing to a higher mortality rate in T2DM.

Addiction is characterized by drug-craving, compulsive drug-taking, and relapse, and results from the interaction between multiple genetic and environmental factors. Reward pathways play an important role in mediating drug-seeking and drug-taking behaviors, and relapse. The objective of this study was to identify heroin addicts who carry specific genetic variants in their dopaminergic reward systems. A total of 326 heroin-dependent patients undergoing methadone maintenance therapy (MMT) were recruited from the Addiction Center of the China Medical University Hospital. A heroin-use and craving questionnaire was used to evaluate the urge for heroin, the daily or weekly frequency of heroin usage, daily life disturbance, anxiety, and the ability to overcome heroin use. A general linear regression model was used to assess the associations of genetic polymorphisms in one's dopaminergic reward system with heroin-use and craving scores. Results: The most significant results were obtained for rs2240158 in GRIN3B ( p = 0.021), rs3983721 in GRIN3A ( p = 0.00326), rs2129575 in TPH2 ( p = 0.033), rs6583954 in CYP2C19 ( p = 0.033), and rs174699 in COMT ( p = 0.036). These were all associated with heroin-using and craving scores with and without adjustments for age, sex, and body mass index. We combined five variants, and the ensuing dose-response effect indicated that heroin-craving scores increased with the numbers of risk alleles ( p for trend = 0.0008). These findings will likely help us to understand the genetic mechanism of craving, which will help in predicting the risk of relapse in clinical practice and the potential for therapies to target craving in heroin addiction.

Anti-drug antibody (ADAb) development is associated with secondary therapeutic failure in biologic-treated rheumatoid arthritis (RA) patients. With a treat-to-target goal, we aimed to identify biomarkers for predicting ADAb development and therapeutic response in adalimumab-treated patients. Three independent cohorts were enrolled. In Cohort-1, 24 plasma samples (6 ADAb-positive and 6 ADAb-negative patients at baseline and week 24 of adalimumab therapy, respectively) were assayed with immune-related microarray containing 1,636 correctly folded functional proteins. Next, we executed statistically powered autoantibody profiling analysis of 50 samples in Cohort-2 (24 ADAb-positive and 26 ADAb-negative patients). Subsequently, immunofluorescence assay was performed on 48 samples in Cohort-3 to correlate with ADAb titers and drug levels. The biomarkers were identified for predicting ADAb development and therapeutic response using the immune-related microarray and machine learning approach. ADAb-positive patients had lower drug levels at week 24 (median = 0.024  μ g/ml) compared with ADAb-negative patients (median = 6.38  μ g/ml, p < 0.001). ROC analysis based on the ADAb status revealed the top 20 autoantibodies with AUC ≥ 0.7 in differentiating both groups in Cohort-1. Analysis of Cohort-2 dataset identified a panel of 8 biomarkers (TROVE2, SSB, NDE1, ZHX2, SH3GL1, CARD9, PTPN20, and KLHL12) with 80.6% specificity, 77.4% sensitivity, and 79.0% accuracy in discriminating poor from EULAR responders. Immunofluorescence assay validated that anti-TROVE2 antibody could highly predict ADAb development and poor EULAR response (AUC 0.79 and 0.89, respectively). Multivariate regression analysis proved anti-TROVE2 antibody to be an independent predictor for developing ADAb. Immune-related protein microarray and replication analysis identified anti-TROVE2 antibody as a useful biomarker for predicting ADAb development and therapeutic response in adalimumab-treated patients., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Po-Ku Chen et al.)

Blood pressure (BP) is characterized by spontaneous oscillation over time, which is described as BP variability (BPV). The current study aimed to investigate whether short-term BPV was correlated with hypertensive nephropathy in Han Chinese individuals with hypertension. A single-center prospective cohort study of 300 Han Chinese participants with hypertension was conducted in Taiwan. Five different BPV parameters were derived from ambulatory BP monitoring (ABPM), including standard deviation (SD), weighted SD (wSD), coefficient of variation (CoV), successive variation (SV), and average real variability (ARV). Renal event was defined as > 50% reduction in baseline estimated glomerular filtration rate (eGFR). The average age of the participants was 63.5 years. The baseline eGFR was 84.5 mL/min/1.73 m 2 . The participants were divided into two groups according to the wSD of systolic BP (SBP). Survival was assessed via a Kaplan-Meier analysis. During the 4.2-year follow-up, the participants with the highest SBP wSD tertile had a greater number of renal events (6.0%) than their counterparts (0.5%) (log-rank test, p = .007). The Cox proportional hazard regression model was used to assess the independent effects of BPV, and results showed that 24-h SBP (HR = 1.105; 95% CI = 1.020-1.197, p = .015) and 24-h DBP (HR = 1.162; 95% CI = 1.004-1.344, p = .044) were independently associated with renal events. However, BPV parameters were only associated with renal events univariately, but not after adjusting for baseline characteristics, 24-h mean BP, and office BP. Therefore, the risk of hypertensive nephropathy was independently associated with 24-h mean BP, but not with ambulatory BPV, in Han Chinese participants with hypertension., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Aims: The clinical outcome and threshold of oral anticoagulation differs between patients with solitary atrial flutter (AFL) and those with AFL developing atrial fibrillation (AF) (AFL-DAF). We therefore investigated previously unevaluated predictors of AF development in patients with AFL, and also the predictive values of risk scores in predicting the occurrence of AF and ischaemic stroke., Methods and Results: Participants were those diagnosed with AFL between 1 January 2001 and 31 December 2013. Patients were classified into solitary AFL and AFL-DAF groups during follow-up. Finally, 4101 patients with solitary AFL and 4101 patients with AFL-DAF were included after 1:1 propensity score matching with CHA 2 DS 2 -VASc scores and their components, AFL diagnosis year and other comorbidities. The group difference in the prevalence of ischaemic stroke/transient ischaemic attack (TIA) and congestive heart failure (CHF) was substantial, that of vascular disease was moderate, and that of diabetes and hypertension was negligible. Therefore, we reweighted the component of heart failure as 2 (the same with stroke/TIA) and vascular disease as 1 in the proposed A 2 C 2 S 2 -VASc score. The proposed A 2 C 2 S 2 -VASc and CHA 2 DS 2 -VAS C scores showed patients with AFL who had higher delta scores and follow-up scores had higher risk of AF development. The delta score outperformed the follow-up score in both scoring systems in predicting ischaemic stroke., Conclusion: This study showed that new-onset CHF, stroke/TIA and vascular disease were predictors of AF development in patients with AFL. The dynamic score and changes in both CHA 2 DS 2 -VAS C and the proposed A 2 C 2 S 2 -VASc score could predict the development of AF and ischaemic stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non-diabetic hypertensive patients aged 20-50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24-h ambulatory BP monitoring, and 24-h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24-h ambulatory BP, and 24-h urine catecholamine excretion. In men, 24-h urine total catecholamine levels were correlated with 24-h SBP (r = 0.103, p = .008) and 24-h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24-h urine total catecholamine levels and 24-h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01-3.29, p = .048) and 24-h urine total catecholamine (β = 5.03, 95% CI 0.62-9.44, p = .025) were both independently associated with 24-h SBP; being male was independently associated with 24-h DBP (β = 3.55, 95% CI 2.26-4.85, p < .001). In conclusion, Chinese men with hypertension had higher SNS activity than women, and SNS activity was independently associated with 24-h ambulatory BP in men rather than in women. These findings suggest that different hypertensive treatment strategies should be considered according to patient sex., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Purpose: The aim is to determine whether serial post-systolic shortening (PSS) using speckle tracking echocardiography (STE) could predict major adverse cardiovascular events (MACE), especially symptom-driven infarct-related artery (IRA) revascularization and improvement in segmental function in post-myocardial infarction patients., Methods/results: Ninety-four patients (average age 61.1 ± 12.5 y, 84 [84.9%] male) with new-onset acute myocardial infarction were enrolled. Serial echocardiography was performed during the initial presentation, and at 3, 6 and 12 months after admission. PSS, strain and systolic strain rate were calculated using STE. Improvement in segmental function was defined as a decrease of ≧1 grade in wall motion score. During the follow-up (29.4 ± 12.7months), 22 patients (23.4%) had MACE and 17 patients had symptom-driven IRA revascularization. In multivariate model, PSS at 3 months was independently predictive for symptom-driven IRA revascularization (Hazard ratio (HR) = 0.5, 95% CI = 0.26-0.97) and for MACE (HR = 0.4, 95% CI = 0.24-0.67) (p < 0.05). Segmental function improvements were found in 255 segments (66.1%) and ROC curve analyses showed that AUC (95% CI) of the initial PSS was 0.7(0.65-0.77) (cut-off values = -1.08, sensitivity = 58%, specificity = 73% specificity)., Conclusions: Post-systolic shortening at 3 months is an independent predictor for symptom-driven IRA revascularization and MACE. Regional wall motion recovery also could be predicted by initial PSS. Serial assessment of two-dimensional STE should be investigated in post-myocardial infarction patients in the future., Competing Interests: The authors have declared that no competing interests exist.

Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing to generate a detailed transcriptomic atlas of young and aged murine mammary tissues. By analyzing epithelial, stromal, and immune cells, we identify age-dependent alterations in cell proportions and gene expression, providing evidence that suggests alveolar maturation and physiological decline. The analysis also uncovers potential pro-tumorigenic mechanisms coupled to the age-associated loss of tumor suppressor function and change in microenvironment. In addition, we identify a rare, age-dependent luminal population co-expressing hormone-sensing and secretory-alveolar lineage markers, as well as two macrophage populations expressing distinct gene signatures, underscoring the complex heterogeneity of the mammary epithelia and stroma. Collectively, this rich single-cell atlas reveals the effects of aging on mammary physiology and can serve as a useful resource for understanding aging-associated cancer risk., Competing Interests: Declaration of Interests J.L.G. is a consultant for Glaxo-Smith Kline (GSK), Codagenix, Verseau, Kymera, and Array BioPharma and receives sponsored research support from GSK, Array BioPharma, and Eli Lilly. A.R. is a founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics, and until August 31, 2020, was on the science advisory boards (SABs) of Syros Pharmaceuticals, Neogene Therapeutics, Asimov, and ThermoFisher Scientific. From August 1, 2020, A.R. is an employee of Genentech, a member of the Roche Group. J.S.B. is on the SAB of Agios Pharmaceuticals, eFFECTOR Therapeutics, and Frontier Medicines., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Graphene oxide (GO)-cysteamine-Ag nanoparticles (GCA)-silver nanowire (AgNW) fabricated by depositing GCA over sprayed AgNWs on PET films were proposed for transparent and flexible electrodes, and their optical, electrical, and mechanical properties were analyzed by energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, atomic force microscopy, scanning electron microscopy, transmission electron microscopy, current-voltage measurements, and bending test. GCA-AgNW electrodes show optical transmittance of >80% at 550 nm and exhibit a high figure-of-merit value of up to 116.13 in the samples with sheet resistances of 20-40 Ω/◻. It was observed that the detrimental oxidation of bare AgNWs over time was considerably decreased, and the mechanical robustness was improved. To apply the layer as an actual electrode in working devices, a Pt/GO/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate/GCA-AgNW/polyethylene terephthalate structure was fabricated, and resistive switching memory was demonstrated. On the basis of these results, we confirm that the proposed GCA-AgNW layer can be used as transparent and flexible electrode.

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers ( p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers.