Sex Differences in Quality of Life and their Explanatory Variables in Patients with Non-Valvular Atrial Fibrillation

Background: Women with atrial fibrillation (AF) have poorer quality of life (QoL) than men; however, the factors contributing to the poorer QoL in women is unclear. Methods: We analyzed data for 3562 patients with non-valvular AF enrolled in the China Registry of Atrial Fibrillation. The Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) was used to evaluate QoL, which was compared between women and men. A multivariate logistic regression analysis model was used to explore factors potentially explaining the sex difference in QoL. Results: Overall, 43.3% of the cohort comprised women (n=1541) who were older than their male counterparts (72 ± 9.8 vs. 68 ± 11.9 years, P<0.001). Compared with men, women were more likely to have more symptoms, hypertension, diabetes mellitus, and heart failure. Women were less likely than men to receive catheter ablation (4.5% vs. 6.1%, P=0.044). Women also had lower physical component summary (PCS) scores (48 ± 9 vs. 51 ± 9, P<0.001) and mental component summary (MCS) scores (49 ± 10 vs. 51 ± 10, P<0.001) than men. In the multivariable analysis of the poorer PCS scores in women, patient age explained 32.9%, low socioeconomic status explained 20.0%, lifestyle explained 14.3%, cardiovascular comorbidities explained 15.7%, the presence of more symptoms explained 5.7%, and less catheter ablation explained 1.4%. These factors also explained similar proportions of the sex difference in MCS scores. Together, these factors explained 54.3% of the poorer physical function status and 46.8% of the poorer mental function status in women than men. Conclusions: Women with AF had poorer QoL than men. The following factors partly explained the poorer QoL in women: older age, low level of socioeconomic status, more cardiovascular comorbidities, less smoking and drinking, more symptoms, and less catheter ablation

Variation in the Glucose Transporter gene <i>SLC2A2 </i>is associated with glycaemic response to metformin

Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10−14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine

Thermal–Mechanical Coupling Behavior of Directional Polymethylmethacrylate under Tension and Compression

In this work, the quasi-static and dynamic mechanical behavior of directional polymethylmethacrylate is investigated under conditions of uniaxial compression and tension. The main purpose of this investigation is to discuss the effect of strain rate and temperature on the deformation characteristics and failure of such material. Research was carried out with the use of an electric universal testing machine and split Hopkinson bars, which were equipped with high- and low-temperature control systems. The experimental methods for studying the tensile and compressive response of polymer materials under different testing conditions were validated by one-dimensional stress wave theory and digital-image correlation technique. The finite deformation stress&#8315;strain behaviors of the samples under different loading condition were obtained with a constant temperature ranging from 218 to 373 K. The experimental results showed that the uniaxial tensile and compressive behaviors of directional polymethylmethacrylate under finite deformation are strongly dependent on temperature, decreased tensile and compressive stress of the material under different strain levels, and increased temperature. Meanwhile, the dynamic tensile and compressive stresses of the material are much higher than the quasi-static stresses, showing the strain-rate strengthening effect. Moreover, the tensile and compressive mechanical behavior of directional polymethylmethacrylate has significant asymmetry. Finally, a visco-hyperelastic model is established to predict the rate-dependence mechanical behavior of directional polymethylmethacrylate at different temperatures

Mobile Device Passive Localization Based on IEEE 802.11 Probe Request Frames

This paper presents a novel passive mobile device localization mode based on IEEE 802.11 Probe Request frames. In this approach, the listener can discover mobile devices by receiving the Probe Request frames and localize them on his walking path. The unique location of the mobile device is estimated on a geometric diagram and right-angled walking path. In model equations, site-related parameter, that is, path loss exponent, is eliminated to make the approach site-independent. To implement unique localization, the right-angled walking path is designed and the optimal location is estimated from the optional points. The performance of our method has been evaluated inside the room, outside the room, and in outdoor scenarios. Three kinds of walking paths, for example, horizontal, vertical, and slanted, are also tested

Metabolic disorders and risk of cardiovascular diseases: a two-sample mendelian randomization study

Abstract Background Metabolic disorders are increasing worldwide and are characterized by various risk factors such as abdominal obesity, insulin resistance, impaired glucose metabolism, and dyslipidemia. Observational studies suggested a bidirectional association between cardiovascular diseases and metabolic disorders and its components. However, the causal associations between them remained unclear. This study aims to investigate the causal relationship between metabolic disorders and cardiovascular disease through Mendelian randomization (MR) analysis. Methods A two-sample MR analysis based on publicly available genome-wide association studies were used to infer the causality. The single-nucleotide polymorphisms with potential pleiotropy were excluded by MR-PRESSO. The effect estimates were constructed using the random-effects inverse-variance-weighted method as the primary estimate. Furthermore, MR-Egger and weighted median were also performed to detect heterogeneity and pleiotropy. Results Genetically predicted metabolic disorders increased the risk for coronary heart disease (OR = 1.77, 95% CI: 1.55–2.03, p < 0.001), myocardial infarction (OR = 1.75, 95% CI: 1.52–2.03, p < 0.001), heart failure (OR = 1.26, 95% CI: 1.14–1.39, p < 0.001), hypertension (OR = 1.01, 95% CI: 1.00-1.02, p = 0.002), and stroke (OR = 1.19, 95% CI: 1.08–1.32, p < 0.001). The concordance of the results of various complementary sensitivity MR methods reinforces the causal relationship further. Conclusion This study provides evidence of a causal relationship between metabolic disorders and increased risk of coronary heart disease, myocardial infarction, heart failure, hypertension, and stroke. Special attention should be paid to improving metabolic disorders to reduce the development of cardiovascular diseases

Identification and Prediction of Wetland Ecological Risk in Key Cities of the Yangtze River Economic Belt: From the Perspective of Land Development

Rapid urbanization aggravates the degradation of wetland function. However, few studies have quantitatively analyzed and predicted the comprehensive impacts of different scenarios and types of human activities on wetland ecosystems from the perspective of land development. Combined with the Habitat Risk Assessment (HRA) model and the Cellular Automata (Ca)-Markov model, this study quantitatively measured the impact intensity and spatial distribution of different types of human activities on the wetland ecosystem in 2015, simulated and predicted the ecological pressure on the wetland in 2030, and identified the ecological risk hotspots of the Yangtze River waterfront along the upper, middle, and lower reaches of the Yangtze River Economic Belt. The results showed that the ecological risk of wetlands in the study area was low in the urban core and high in the suburbs. Construction activities posed a greater risk to wetlands. The intensity of human activities in the ecological protection scenario will be significantly lower than that in the natural development scenario in 2030. The waterfront in the middle and lower reaches of the Yangtze River will face more ecological risks. The results of the study can provide theoretical and technical support for wetland conservation policy formulation and waterfront development in the Yangtze River Economic Belt

MDR1 overexpression combined with ERG11 mutations induce high-level fluconazole resistance in Candida tropicalis clinical isolates

Abstract Background Marked increases in fluconazole resistance in Candida tropicalis have been recently reported. In this study, the molecular mechanisms behind fluconazole resistance were investigated. Methods Twenty-two C. tropicalis clinical isolates, including 12 fluconazole-resistant isolates and 10 fluconazole-susceptible isolates, were collected from a tertiary care teaching hospital in Beijing between 2013 and 2017. Antifungal susceptibility testing, multilocus sequence typing, ERG11 amplification and sequencing, quantitative real-time reverse transcription-polymerase chain reaction (ERG11, UPC2, MDR1, and CDR1), and clinical data collection were performed for all C. tropicalis isolates. Results Multilocus sequence typing revealed that the 10 fluconazole-susceptible isolates and 12 fluconazole-resistant isolates were divided into nine and seven diploid sequence types, respectively. Of the 12 patients with fluconazole-resistant isolates, six had been previously exposed to azole and four had a fatal outcome. Y132F and S154F amino acid substitutions in Erg11p were found in all fluconazole-resistant isolates except one. MDR1 gene overexpression was identified in fluconazole-resistant isolates. In particular, seven high-level fluconazole resistant isolates (minimum inhibitory concentration ≥ 128 mg/L) and three pan-azole resistant isolates were identified. CDR1, ERG11, and UPC2 gene expression levels in fluconazole-resistant isolates were not significantly different from the control isolates (P = 0.262, P = 0.598, P = 0.114, respectively). Conclusions This study provides evidence that the combination of MDR1 gene overexpression and ERG11 missense mutations is responsible for high-level fluconazole resistance and pan-azole resistance in C. tropicalis clinical isolates. To the best of our knowledge, this is the first study investigating the relationship between MDR1 gene overexpression and increased fluconazole resistance

Simultaneously improved strength and ductility in aluminum matrix composite with heterogeneous structures under impact loadings

Heterostructured composites with the coexistence of hard and soft phases can achieve a superior strength-ductility synergy. However, the deformation and fracture mechanisms of these composites under impact loading has not been comprehensively understood. In this work, an in-situ TiB2/2024 Al composite was adopted to investigate the role of heterogeneous structures on the tensile mechanical responses at different strain rates and temperatures. Surprisingly, a simultaneously enhancement of strength and ductility was found in the composite under impact loading. To explore the underlying mechanisms responsible for the observed mechanical behavior, microstructural analyses were performed on the samples before and after deformation. Results reveal that the composite has obvious heterogeneous structure consist of particle-rich regions (regard as hard phase) and particle-lean regions (soft phase). The interaction between the two phases can affect the strain hardening behavior of the composites at different plastic deformation stages. Compared with the strain rate insensitive matrix, the particle-induced constraint makes the flow stress of the composite increases substantially with an increase in strain rate. Meanwhile, the tortuous crack propagation paths induced by the cooperation of hard and soft phases contribute to the improved ductility at high strain rates

Lymphovascular or perineural invasion is associated with lymph node metastasis and survival outcomes in patients with gastric cancer

Abstract Background Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC. Methods Records of 1488 patients with stage I‐–III GC and 3327 patients with stage I–III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC. Results Patients with stage I–III GC had a significantly higher incidence of LVI/PNI than patients with stage I–III CRC (50.54% vs. 21.91%, p  < 0.001). LVI/PNI was significantly associated with higher CEA, higher CA199, deeper tumor invasion, more lymph node metastasis, and advanced TNM stage in GC ( p  < 0.05). Multivariate logistic regression analysis identified LVI/PNI (OR = 2.64, 95%CI: 2.05–3.40, p  < 0.001) as an independent risk factor for LNM in GC. The OS rate was significantly lower in the LVI/PNI‐positive GC group than that in the LVI/PNI‐negative GC group ( p  < 0.001). On multivariate Cox regression analysis, LVI/PNI (HR = 1.34, 95%CI: 1.04–1.71, p  = 0.023) was an independent prognostic factor for OS in GC. Conclusion GC has a high incidence of LVI/PNI, which was closely associated with disease progression. LVI/PNI could serve as an independent risk factor for LNM and the prognosis of patients with curative resected GC. These findings will be helpful in predicting survival outcomes more accurately and establishing individualized treatment plans

Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma

Abstract Myosin heavy chain 9 (MYH9) plays an important role in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The present research aimed to investigate the role of MYH9 in glioma and determine whether MYH9 is involved in the temozolomide chemoresistance of glioma cells. Our results showed that MYH9 increased the proliferation and temozolomide resistance of glioma cells. The mechanistic experiments showed that the binding of MYH9 to NAP1L1, a potential promoter of tumor proliferation, inhibited the ubiquitination and degradation of NAP1L1 by recruiting USP14. Upregulation of NAP1L1 increased its binding with c-Myc and activated c-Myc, which induced the expression of CCND1/CDK4, promoting glioma cell temozolomide resistance and proliferation. Additionally, we found that MYH9 upregulation was strongly related to patient survival and is therefore a negative factor for patients with glioma. Altogether, our results show that MYH9 plays a role in glioma progression by regulating NAP1L1 deubiquitination. Thus, targeting MYH9 is a potential therapeutic strategy for the clinical treatment of glioma in the future