Variation in Antithrombotic Therapy and Clinical Outcomes in Patients With Preexisting Atrial Fibrillation Undergoing Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

Background: Optimal antithrombotic management of patients with preexisting atrial fibrillation undergoing transcatheter aortic valve replacement is challenging given the need to balance the risk of bleeding and thromboembolism. We aimed to examine variation in care and association of antithrombotic therapies with 1-year outcomes of stroke, bleeding, and mortality in patients undergoing transcatheter aortic valve replacement with concomitant atrial fibrillation in the United States.

Methods: Patients who underwent transcatheter aortic valve replacement with preexisting atrial fibrillation from November 2011 through September 2015 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry linked to the Medicare database were examined according to receipt of oral anticoagulants (OACs) or antiplatelet therapies (APTs) or a combination of these (OAC+APT) at discharge.

Forward osmosis membranes for high-efficiency desalination with Nano-MoS composite substrates.

Attractive membranes are critical for improving efficiencies of forward osmosis (FO) desalination process. In this study, a novel FO-PES-MoS thin film composite (TFC) membrane was assembled using the phase transfer method through merging MoS nanosheets into substrate casting solution. A sequence of characterization techniques was applied to test microstructures and physicochemical properties of the membranes and modification mechanisms based on MoS concentrations.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Molecular cytogenetic characterization and fusarium head blight resistance of five wheat-Thinopyrum intermedium partial amphiploids.

Background: Partial amphiploids created by crossing octoploid tritelytrigia(2n = 8× = 56, AABBDDEE) and Thinopyrum intermedium (2n = 6× = 42, StStJJJJ) are important intermediates in wheat breeding because of their resistance to major wheat diseases. We examined the chromosome compositions of five wheat-Th. intermedium partial amphiploids using GISH and multicolor-FISH.

Characterization of chromosome constitution in three wheat - Thinopyrum intermedium amphiploids revealed frequent rearrangement of alien and wheat chromosomes.

Background: Thinopyrum intermedium (2n = 6x = 42) is an important wild perennial Triticeae species exhibiting many potentially favorable traits for wheat improvement. Wheat-Th. intermedium partial amphiploids serve as a bridge to transfer desirable genes from Th.

Distinct Body Mass Index Trajectories to Young-Adulthood Obesity and Their Different Cardiometabolic Consequences.

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A catalog of associations between rare coding variants and COVID-19 outcomes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential.

Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies.

Background: The optimal intake levels of fruit and vegetables for maintaining long-term health are uncertain.

Methods: We followed 66 719 women from the Nurses' Health Study (1984-2014) and 42 016 men from the Health Professionals Follow-up Study (1986-2014) who were free from cardiovascular disease (CVD), cancer, and diabetes at baseline. Diet was assessed using a validated semiquantitative food frequency questionnaire at baseline and updated every 2 to 4 years.

Genome-wide analysis in 756,646 individuals provides first genetic evidence that expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease.

SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.

Proteome-wide and matrisome-specific alterations during human pancreas development and maturation.

The extracellular matrix (ECM) is unique to each tissue and capable of guiding cell differentiation, migration, morphology, and function. The ECM proteome of different developmental stages has not been systematically studied in the human pancreas. In this study, we apply mass spectrometry-based quantitative proteomics strategies using N,N-dimethyl leucine isobaric tags to delineate proteome-wide and ECM-specific alterations in four age groups: fetal (18-20 weeks gestation), juvenile (5-16 years old), young adults (21-29 years old) and older adults (50-61 years old).

Titin Circular RNAs Create a Back-Splice Motif Essential for SRSF10 Splicing.

Background: TTN (Titin), the largest protein in humans, forms the molecular spring that spans half of the sarcomere to provide passive elasticity to the cardiomyocyte. Mutations that disrupt the transcript are the most frequent cause of hereditary heart failure. We showed before that produces a class of circular RNAs (circRNAs) that depend on RBM20 to be formed.

Astaxanthin Prevents Atrophy in Slow Muscle Fibers by Inhibiting Mitochondrial Reactive Oxygen Species via a Mitochondria-Mediated Apoptosis Pathway.

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle-atrophy-mediated disturbance of mitochondria, which have a lipid bilayer. Tail suspension was used to establish a muscle-atrophied mouse model.

Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma.

Personal neoantigen vaccines have been envisioned as an effective approach to induce, amplify and diversify antitumor T cell responses. To define the long-term effects of such a vaccine, we evaluated the clinical outcome and circulating immune responses of eight patients with surgically resected stage IIIB/C or IVM1a/b melanoma, at a median of almost 4 years after treatment with NeoVax, a long-peptide vaccine targeting up to 20 personal neoantigens per patient ( NCT01970358 ). All patients were alive and six were without evidence of active disease.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis.

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database.

Physical mapping of chromosome 7J and a purple coleoptile gene from Thinopyrum intermedium in the common wheat background.

A physical map of Thinopyrum intermedium chromosome 7J was constructed using translocation mapping, and a new seedling purple coleoptile gene was mapped to the bin of FL 0.35-0.63 of 7JS.

Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.

Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models.

Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing.

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.

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner. , MGD019 mediates the combinatorial blockade of PD-1 and CTLA-4, confirming dual inhibition via a single molecule.

Novel Dual Reporter Mouse Model Provides Definitive Labeling and Identification of Smooth Muscle Cells-Brief Report.

Objective: encodes a myosin heavy chain protein that is specifically expressed in smooth muscle cells (SMCs) and is important for maintaining vascular wall stability. The goal of this study is to generate a dual reporter mouse line for definitive visualization of MYH11 SMCs in vivo. Approach and Results: We generated a knock-in mouse model by inserting reporter cassette into the gene locus.

Invasive Coronary Angiography after Chest Pain Presentations to Emergency Departments.

We investigated patients presenting to emergency departments (EDs) with chest pain to identify factors that influence the use of invasive coronary angiography (ICA). Using linked ED, hospitalisations, death and cardiac biomarker data, we identified people aged 20 years and over who presented with chest pain to tertiary public hospital EDs in Western Australia from 1 January 2016 to 31 March 2017 (ED chest pain cohort). We report patient characteristics, ED discharge diagnosis, pathways to ICA, ICA within 90 days, troponin test results, and gender differences.

Prospective Evaluation of the Transparent, Elastomeric, Adaptable, Long-Lasting (TEAL) Respirator.

N95 filtering facepiece respirators (FFR) and surgical masks are essential in reducing airborne disease transmission, particularly during the COVID-19 pandemic. However, currently available FFR's and masks have major limitations, including masking facial features, waste, and integrity after decontamination. In a multi-institutional trial, we evaluated a transparent, elastomeric, adaptable, long-lasting (TEAL) respirator to evaluate success of qualitative fit test with user experience and biometric evaluation of temperature, respiratory rate, and fit of respirator using a novel sensor.

Direct quantification of in vivo mutagenesis and carcinogenesis using duplex sequencing.

The ability to accurately measure mutations is critical for basic research and identifying potential drug and chemical carcinogens. Current methods for in vivo quantification of mutagenesis are limited because they rely on transgenic rodent systems that are low-throughput, expensive, prolonged, and do not fully represent other species such as humans. Next-generation sequencing (NGS) is a conceptually attractive alternative for detecting mutations in the DNA of any organism; however, the limit of resolution for standard NGS is poor.

Chromosome-scale, haplotype-resolved assembly of human genomes.

Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day.