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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.)

Germline BRCA1 mutation carriers face a high breast cancer risk; however, the underlying mechanisms for this risk are not completely understood. Using a new genetically engineered mouse model of germline Brca1 heterozygosity, we demonstrate that early tumor onset in a Brca1 heterozygous background cannot be fully explained by the conventional 'two-hit' hypothesis, suggesting the existence of inherent tumor-promoting alterations in the Brca1 heterozygous state. Single-cell RNA sequencing and assay for transposase-accessible chromatin with sequencing analyses uncover a unique set of differentially accessible chromatin regions in ostensibly normal Brca1 heterozygous mammary epithelial cells, distinct from wild-type cells and partially mimicking the chromatin and RNA-level changes in tumor cells. Transcription factor analyses identify loss of ELF5 and gain of AP-1 sites in these epigenetically primed regions; in vivo experiments further implicate AP-1 and Wnt10a as strong promoters of Brca1-related breast cancer. These findings reveal a previously unappreciated epigenetic effect of Brca1 haploinsufficiency in accelerating tumorigenesis, advancing our mechanistic understanding and informing potential therapeutic strategies., Competing Interests: Competing interests: A.R. is a cofounder of and equity holder in Celsius Therapeutics and an equity holder in Immunitas; she was a scientific advisory board member for Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until 31 July 2020. A.R. has been an employee of Genentech (a member of the Roche Group) since August 2020 and holds equity in Roche. None of these affiliations represent competing interests regarding the present study. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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.)

Background: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear., Methods: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed., Results: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively., Conclusions: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L., Trial Registration: ClinicalTrials.gov ID: NCT02633358., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. 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.

The Hubbard model is an iconic model in quantum many-body physics and has been intensely studied, especially since the discovery of high-temperature cuprate superconductors. Combining the complementary capabilities of two computational methods, we found superconductivity in both the electron- and hole-doped regimes of the two-dimensional Hubbard model with next-nearest-neighbor hopping. In the electron-doped regime, superconductivity was weaker and was accompanied by antiferromagnetic Néel correlations at low doping. The strong superconductivity on the hole-doped side coexisted with stripe order, which persisted into the overdoped region with weaker hole-density modulation. These stripe orders varied in fillings between 0.6 and 0.8. Our results suggest the applicability of the Hubbard model with next-nearest hopping for describing cuprate high-transition temperature ( T c ) superconductivity.

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.)

Background: Pacing-induced cardiomyopathy is an undesired outcome in patients with atrioventricular block (AVB), and our animal model showed lipotoxic cardiomyopathy after pacing., Objectives: The purpose of this study was to explore the mechanisms and clinical outcomes of statins in AVB patients receiving pacing., Methods: Rat ventricular cardiomyocytes were treated with atorvastatin, liver X receptor (LXR) agonist, and LXR antagonist during pacing. Pigs were divided into 3 groups: right ventricular pacing, pacing with concomitant atorvastatin treatment, and sham control. Clinically, we enrolled 1717 AVB patients who had received a permanent pacemaker from Chang Gung Memorial Hospital Medical database. The primary outcome (cardiovascular death or heart failure [HF] hospitalization) and individual outcome were compared between statin and nonstatin groups after inverse probability of treatment weighting., Results: Lipid accumulation in rat cardiomyocytes by pacing was significantly reduced by treatment with LXR agonist and atorvastatin, whereas LXR antagonist counteracted the atorvastatin effect on lipid expression. Left ventricular ejection fraction (LVEF) was significantly lower in the AVB pig pacing group compared to the group concomitantly treated with atorvastatin. Moreover, lipid accumulation and fibronectin expression were significantly ameliorated by concomitant treatment with atorvastatin. In the clinical study, the statin group had a significantly lower risk of the primary outcome event (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.56-0.84), less HF hospitalization (HR 0.45; 95% CI 0.30-0.67), and higher LVEF than the nonstatin group., Conclusion: In experimental models, atorvastatin ameliorated lipid accumulation in cardiomyocytes and fibrosis in left ventricular myocardium induced by pacing. Clinically, treatment with statins was associated with less HF hospitalization and cardiovascular death in AVB patients receiving pacemaker therapy., (Copyright © 2022 Heart Rhythm Society. Published by 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.

Little is known about whether venous thromboembolism (VTE) causes worse critical limb events in populations with atrial fibrillation (AF). A retrospective cohort study using claims data from Taiwan's National Health Insurance program between 2001 and 2013 compared AF patients with or without VTE. Outcomes were percutaneous transluminal angioplasty (PTA), amputation, systemic thromboembolism, all-cause mortality, cardiovascular death, ischemic stroke, and acute myocardial infarction. Patients ( n = 316,817) with newly diagnosed AF were analyzed; of those, 2514 (0.79%) had VTE history. After inverse probability of treatment weighting, a history of VTE was significantly associated with higher risks of PTA (3.3 vs 2.2%; subdistribution hazard ratio [SHR] 1.47; 95% confidence interval [CI] 1.17-1.84); above knee amputation (0.7 vs 0.3%; HR 2.15; 95% CI 1.10-4.21); systemic thromboembolism (5.8 vs 3.9%; SHR 1.48; 95% CI 1.21-1.80); all-cause mortality (53 vs 46.4%; HR 1.20, 95% CI 1.12-1.29); and cardiovascular death (34.8 vs 29.4%; HR 1.25, 95% CI 1.14-1.36). In conclusion, VTE might increase the risk of critical lower limb events (PTA and above-knee amputation), systemic thromboembolism, and mortality in the AF population. However, current data cannot confirm a causal relationship between VTE and clinical outcomes in this population.

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.)