Variant rs2200733 and rs10033464 on chromosome 4q25 are associated with increased risk of atrial fibrillation after catheter ablation: Evidence from a meta-analysis

Background: Common genetic polymorphisms at chromosome 4q25 were associated with increased susceptibility to atrial fibrillation (AF). However, it remained controversial whether these variants could be used as risk predictors for AF recurrence after catheter ablation. We therefore performed a metaanalysis to quantify the association between rs2200733 C>T/rs10033464 G>T and AF recurrence. Methods: Relevant studies were systematically retrieved from PubMed, Web of Science, Elsevier database and Cochrane library through November 2016. Data were abstracted and pooled using Stata 12.0 software. Results: A total of 2,145 patients undergoing catheter ablation were included. Patients with rs2200733 TT or TT+CT showed an overall increased susceptibility to AF recurrence (homozygous model [TT vs. CC]: odds ratio [OR] = 2.03, 95% confidence interval [CI] 1.49–2.76, p = 0.000; dominant model [TT+TC vs. CC]: OR = 1.48, 95% CI 1.17–1.87, p = 0.001; recessive model [TT vs. TC+CC]: OR = 1.88, 95% CI 1.12–3.15, p = 0.017). Subgroup analysis also identified a positive relation in Caucasians and late recurrence of AF in allelic, homozygous and dominant comparison. Moreover, a significant increased risk of AF recurrence was observed in patients with rs10033464 TG or TT+TG (heterozygous model [TG vs. GG]: OR = 1.46, 95% CI 1.01–2.12, p = 0.047; dominant model [TT+TG vs. GG]: OR = 1.51, 95% CI 1.04–2.17, p = 0.029). Conclusions: After catheter ablation, rs2200733 (TT or TT+TC) and rs10033464 (TT+TG or TG) were associated with increased risk of AF recurrence

Simultaneous extraction and determination of alkaloids and organic acids in Uncariae Ramulas Cum Unicis by vortex-assisted matrix solid phase dispersion extraction coupled with UHPLC-MS/MS

A simple and efficient vortex-assisted matrix solid phase dispersion with a ultra-high-performance liquid chromatography-triple quadrupole mass spectrometer (VA-MSPD-UHPLC-MS/MS) was applied for simultaneous extraction and determination of seven alkaloids and three organic acids from Uncariae Ramulas Cum Unicis. The optimal extraction conditions of the target components were obtained by Box-Behnken design (BBD) combined with response surface methodology (RSM). The results of the method validation showed that this analytical method displayed good linearity with a correlation coefficient (r) no lower than 0.9990. The recoveries of ten active ingredients from Uncariae Ramulas Cum Unicis ranged from 95.9% to 103% (RSD ≤ 2.77%). The RSDs of intra-day and inter-day precisions were all below 2.97%. The present method exhibited not only lower solvent and sample usage, but also shorter sample processing and analysis time. Consequently, the developed VA-MSPD-UHPLC-MS/MS method could be successfully and effectively used for the extraction and analysis of ten active components from Uncariae Ramulas Cum Unicis

Microstructural and Compositional Features of the Fibrous and Hyaline Cartilage on the Medial Tibial Plateau Imply a Unique Role for the Hopping Locomotion of Kangaroo

Hopping provides efficient and energy saving locomotion for kangaroos, but it results in great forces in the knee joints. A previous study has suggested that a unique fibrous cartilage in the central region of the tibial cartilage could serve to decrease the peak stresses generated within kangaroo tibiofemoral joints. However, the influences of the microstructure, composition and mechanical properties of the central fibrous and peripheral hyaline cartilage on the function of the knee joints are still to be defined. The present study showed that the fibrous cartilage was thicker and had a lower chondrocyte density than the hyaline cartilage. Despite having a higher PG content in the middle and deep zones, the fibrous cartilage had an inferior compressive strength compared to the peripheral hyaline cartilage. The fibrous cartilage had a complex three dimensional collagen meshwork with collagen bundles parallel to the surface in the superficial zone, and with collagen bundles both parallel and perpendicular to the surface in the middle and deep zones. The collagen in the hyaline cartilage displayed a typical Benninghoff structure, with collagen fibres parallel to the surface in the superficial zone and collagen fibres perpendicular to the surface in the deep zone. Elastin fibres were found throughout the entire tissue depth of the fibrous cartilage and displayed a similar alignment to the adjacent collagen bundles. In comparison, the elastin fibres in the hyaline cartilage were confined within the superficial zone.This study examined for the first time the fibrillary structure, PG content and compressive properties of the central fibrous cartilage pad and peripheral hyaline cartilage within the kangaroo medial tibial plateau. It provided insights into the microstructure and composition of the fibrous and peripheral hyaline cartilage in relation to the unique mechanical properties of the tissues to provide for the normal activities of kangaroos

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Three-Stream and Double Attention-Based DenseNet-BiLSTM for Fine Land Cover Classification of Complex Mining Landscapes

The fine classification of land cover around complex mining areas is important for environmental protection and sustainable development. Although some advances have been made in the utilization of high-resolution remote sensing imagery and classification algorithms, the following issues still remain: (1) how the multimodal spectral–spatial and topographic features can be learned for complex mining areas; (2) how the key features can be extracted; and (3) how the contextual information can be captured among different features. In this study, we proposed a novel model comprising the following three main strategies: (1) design comprising a three-stream multimodal feature learning and post-fusion method; (2) integration of deep separable asymmetric convolution blocks and parallel channel and spatial attention mechanisms into the DenseNet architecture; and (3) use of a bidirectional long short-term memory (BiLSTM) network to further learn cross-channel context features. The experiments were carried out in Wuhan City, China using ZiYuan-3 imagery. The proposed model was found to exhibit a better performance than other models, with an overall accuracy of 98.65% ± 0.05% and an improvement of 4.03% over the basic model. In addition, the proposed model yielded an obviously better visual prediction map for the entire study area. Overall, the proposed model is beneficial for multimodal feature learning and complex landscape applications

Expression Profiles and Ontology Analysis of Circular RNAs in a Mouse Model of Myocardial Ischemia/Reperfusion Injury

Circular RNAs (circRNAs) play important roles in cellular physiology. The association between circRNAs and myocardial ischemia/reperfusion (I/R) injury remains largely unknown. The aim of this study was to test the effects of myocardial I/R circRNA expression and explore the potential roles of these circRNAs. CircRNAs were screened by high-throughput sequencing, and the expression of dysregulated circRNAs was further validated using quantitative real-time polymerase chain reaction. Nineteen upregulated and 20 downregulated circRNAs were identified. Gene Ontology analysis indicated that the dysregulated transcripts were associated with fundamental pathophysiologic processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed significant changes in adherens junction, the HIF-1 signaling pathway, the cell cycle, and the FoxO signaling pathway which have a close relationship with myocardial I/R injury. The circRNA-miRNA analysis demonstrated the broad potential of the differentially expressed circRNAs to regulate target genes by acting on the miRNAs. This study provides a foundation for understanding the roles and mechanisms of circRNAs in myocardial I/R injury

Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study

Abstract Background Thyroid hormones deeply influence the cardiovascular system; however, the association between the fT3/fT4 ratio and the clinical outcome in euthyroid patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) is not well defined. Therefore, the present study aimed to assess the prognostic performance of the fT3/fT4 ratio in predicting the long-term prognosis in euthyroid patients with AMI undergoing PCI. Methods In a prospective cohort study with a 1-year follow-up, according to the clinical end point, 953 euthyroid individuals (61.0 ± 11.6; female, 25.8%) were divided into two groups: (1) the survival group (n = 915) and (2) the death group (n = 38). Results According to Cox regression multivariate analysis, fT4 (HR: 1.249, 95% CI: 1.053–1.480, p = 0.010) and the fT3/fT4 ratio (HR: 3.546, 95% CI: 1.705–7.377, p = 0.001) were associated with an increased risk of 1-year all-cause mortality. The prognostic performance of the fT3/fT4 ratio was similar to the Global Registry of Acute Coronary Events (GRACE) score in predicting 1-year all-cause mortality (C-statistic: z = 0.261, p = 0.794; IDI: -0.017, p = 0.452; NRI: -0.049, p = 0.766), but better than fT4 (C-statistic: z = 2.438, p = 0.015; IDI: 0.053, p = 0.002; NRI: 0.656, p < 0.001). The fT3/fT4 ratio also significantly improved the prognostic performance of the GRACE score (GRACE score vs GRACE score + fT3/fT4 ratio: C-statistic: z = 2.116, p = 0.034; IDI: 0.0415, p = 0.007; NRI: 0.614, p < 0.001). Conclusions In euthyroid patients with AMI undergoing PCI, the fT3/fT4 ratio was an independent predictor of 1-year all-cause mortality. Its prognostic performance was similar to the GRACE score, and also improved its prognostic performance (GRACE score vs GRACE score + fT3/fT4 ratio)