Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.

Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively.

Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID.

Results: The ES diagnostic yield was 42 of 74 (57%).

Integration of EpiSign, facial phenotyping, and likelihood ratio interpretation of clinical abnormalities in the re-classification of an ARID1B missense variant.

Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants.

Analysis of risk factors and short-term prognostic factors of arrhythmia in patients infected with mild/moderate SARS-CoV-2 Omicron variant.

Background: Complications, including arrhythmia, following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continue to be of concern. Omicron is the mainstream SARS-CoV-2 mutant circulating in mainland China. At present, there are few epidemiological studies concerning the relationship between arrhythmia and Omicron variant infection in mainland China.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

Aim: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP).

Methods: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs).

Results: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE.

Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function.

The main focus of this study was to compare the predictive value of coagulation, fibrinolysis, thromboelastography, stress response, and immune function in predicting the incidence of deep venous thrombosis (DVT) in lung cancer (LC) patients undergoing thoracoscopic LC resection vs thoracotomy LC resection. To do that, a prospective, single-center, case-control study involving 460 LC patients was conducted. The risk indicators affecting patients with DVT after LC resection in the testing cohort were determined using logistic regression and receiver operator characteristic (ROC) analyses.

Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review.

Autosomal recessive microcephaly and chorioretinopathy-1 (MCCRP1) is a rare Mendelian disorder resulting from biallelic loss of function variants in Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053). Clinical features of this disorder include microcephaly, cognitive impairment, dysmorphic features, and variable ophthalmological anomalies including chorioretinopathy. Microcephaly can be recognized prenatally and visual impairment becomes evident during the first year of life.

Efficacy of catheter ablation for atrial fibrillation in patients with significant functional mitral regurgitation.

Background: Catheter ablation has been established to be an effective therapy for paroxysmal atrial fibrillation (AF) and is recommended as the treatment of choice for many patients, including those with clinically significant functional mitral regurgitation (MR). However, there is little information available about the clinical efficacy of catheter ablation for paroxysmal AF in patients with significant functional MR.

Methods: We performed a retrospective study of 247 patients with paroxysmal AF who underwent AF ablation.

Genetic control of RNA splicing and its distinct role in complex trait variation.

Most genetic variants identified from genome-wide association studies (GWAS) in humans are noncoding, indicating their role in gene regulation. Previous studies have shown considerable links of GWAS signals to expression quantitative trait loci (eQTLs) but the links to other genetic regulatory mechanisms, such as splicing QTLs (sQTLs), are underexplored. Here, we introduce an sQTL mapping method, testing for heterogeneity between isoform-eQTL effects (THISTLE), with improved power over competing methods.

Parsimonious model for mass-univariate vertexwise analysis.

Covariance between gray-matter measurements can reflect structural or functional brain networks though it has also been shown to be influenced by confounding factors (e.g., age, head size, and scanner), which could lead to lower mapping precision (increased size of associated clusters) and create distal false positives associations in mass-univariate vertexwise analyses.

Association between complete right bundle branch block and atrial fibrillation development.

Background: Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear.

Methods: We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years).

Responses of soil mineral-associated and particulate organic carbon to carbon input: A meta-analysis.

A minor change of soil organic carbon (SOC) greatly influences atmospheric carbon dioxide concentration and climate change. Exogenous carbon (C) input into soils can induce SOC decomposition or sequestration. The response of SOC to C input can be better understood when SOC is separated into mineral-associated (MAOC) and particulate (POC) organic carbon.

Effect of catheter ablation on clinical outcomes in patients with atrial fibrillation and significant functional mitral regurgitation.

Background: In patients with atrial fibrillation (AF) and functional mitral regurgitation (MR), catheter ablation reduces the severity of MR and improves cardiac remodeling. However, its effects on prognosis are uncertain.

Methods: This retrospective study included 151 consecutive patients with AF and functional MR, 82 (54.

Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues.

miR-141-3p Reduces Cell Migration and Proliferation in an Modelof Atherosclerosis by Targeting Wnt5a.

Background: Atherosclerosis (AS) is a type of chronic vascular disease that is also a leading cause of numerous cardiovascular diseases in humans. The biomolecules responsible for the roles of microRNA (miR)-141-3p during AS development are less understood.

Methods: The relation between Wnt5a and miR-141-3p was predicted using bioinformatics software TargetScan 7.

Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.

Background: People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.

Antithrombotic Agents for tPA-Induced Cerebral Hemorrhage: A Systematic Review and Meta-Analysis of Preclinical Studies.

Background tPA (tissue-type plasminogen activator) remains the only approved drug for acute ischemic stroke, with a potentially serious adverse effect: hemorrhagic transformation. The effects of antithrombotic agents on tPA-induced hemorrhagic transformation after ischemic stroke are not clearly defined. We performed a systematic review and meta-analysis in preclinical studies aiming to evaluate the efficacy of antithrombotic agents on tPA-induced hemorrhagic transformation after ischemic stroke.

A unified framework for association and prediction from vertex-wise grey-matter structure.

The recent availability of large-scale neuroimaging cohorts facilitates deeper characterisation of the relationship between phenotypic and brain architecture variation in humans. Here, we investigate the association (previously coined morphometricity) of a phenotype with all 652,283 vertex-wise measures of cortical and subcortical morphology in a large data set from the UK Biobank (UKB; N = 9,497 for discovery, N = 4,323 for replication) and the Human Connectome Project (N = 1,110). We used a linear mixed model with the brain measures of individuals fitted as random effects with covariance relationships estimated from the imaging data.

Promoter-anchored chromatin interactions predicted from genetic analysis of epigenomic data.

Promoter-anchored chromatin interactions (PAIs) play a pivotal role in transcriptional regulation. Current high-throughput technologies for detecting PAIs, such as promoter capture Hi-C, are not scalable to large cohorts. Here, we present an analytical approach that uses summary-level data from cohort-based DNA methylation (DNAm) quantitative trait locus (mQTL) studies to predict PAIs.

Analysis of DNA methylation associates the cystine-glutamate antiporter SLC7A11 with risk of Parkinson's disease.

An improved understanding of etiological mechanisms in Parkinson's disease (PD) is urgently needed because the number of affected individuals is projected to increase rapidly as populations age. We present results from a blood-based methylome-wide association study of PD involving meta-analysis of 229 K CpG probes in 1,132 cases and 999 controls from two independent cohorts. We identify two previously unreported epigenome-wide significant associations with PD, including cg06690548 on chromosome 4.

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis.

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case-control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls).

An epigenome-wide association study of sex-specific chronological ageing.

Background: Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex.