Clinical efficacy of sacubitril/valsartan combined with cardiac rehabilitation in patients with heart failure after acute myocardial infarction: a single-center randomized trial.

Objective: To investigate the effect of sacubitril/valsartan (ARNI) combined with cardiac rehabilitation (CR) in patients with heart failure (HF) after acute myocardial infarction (AMI).

Methods: A total of 118 patients with HF after AMI were screened and randomly divided into an experimental group and a control group. The control group was given ARNI.

A cross-species proteomic map reveals neoteny of human synapse development.

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways.

Cardiopulmonary exercise test-based assessment of the effects of sacubitril/valsartan on the blood pressure response to exercise in patients with acute myocardial infarction during hospitalization.

Objective: To investigate the effects of sacubitril/valsartan (S/V) on cardiopulmonary function and blood pressure response to exercise during hospitalization in patients with acute myocardial infarction (AMI) based on the cardiopulmonary exercise test (CPET).

Methods: A total of 265 AMI patients were treated with either perindopril or S/V within 24 hours of admission. CPET was completed for all patients before discharge.

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms.

miR760 regulates ATXN1 levels via interaction with its 5' untranslated region.

Identifying modifiers of dosage-sensitive genes involved in neurodegenerative disorders is imperative to discover novel genetic risk factors and potential therapeutic entry points. In this study, we focus on Ataxin-1 (), a dosage-sensitive gene involved in the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1). While the precise maintenance of ATXN1 levels is essential to prevent disease, the mechanisms that regulate expression remain largely unknown.

Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders.

A large number of genes have been implicated in neurodevelopmental disorders (NDDs), but their contributions to NDD pathology are difficult to decipher without understanding their diverse roles in different brain cell types. Here, we integrated NDD genetics with single-cell RNA sequencing data to assess coexpression enrichment patterns of various NDD gene sets. We identified midfetal cortical neural progenitor cell development-more specifically, the ventricular radial glia-to-intermediate progenitor cell transition at gestational week 10-as a key point of convergence in autism spectrum disorder (ASD) and epilepsy.

BAZ2B haploinsufficiency as a cause of developmental delay, intellectual disability, and autism spectrum disorder.

The bromodomain adjacent to zinc finger 2B gene (BAZ2B) encodes a protein involved in chromatin remodeling. Loss of BAZ2B function has been postulated to cause neurodevelopmental disorders. To determine whether BAZ2B deficiency is likely to contribute to the pathogenesis of these disorders, we performed bioinformatics analyses that demonstrated a high level of functional convergence during fetal cortical development between BAZ2B and genes known to cause autism spectrum disorder (ASD) and neurodevelopmental disorder.

A kinome-wide RNAi screen identifies ERK2 as a druggable regulator of Shank3 stability.

Neurons are sensitive to changes in the dosage of many genes, especially those regulating synaptic functions. Haploinsufficiency of SHANK3 causes Phelan-McDermid syndrome and autism, whereas duplication of the same gene leads to SHANK3 duplication syndrome, a disorder characterized by neuropsychiatric phenotypes including hyperactivity and bipolar disorder as well as epilepsy. We recently demonstrated the functional modularity of Shank3, which suggests that normalizing levels of Shank3 itself might be more fruitful than correcting pathways that function downstream of it for treatment of disorders caused by alterations in SHANK3 dosage.

An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function.

Genome sequencing has revealed an increasing number of genetic variations that are associated with neuropsychiatric disorders. Frequently, studies limit their focus to likely gene-disrupting mutations because they are relatively easy to interpret. Missense variants, instead, have often been undervalued.

High-Throughput Functional Analysis Distinguishes Pathogenic, Nonpathogenic, and Compensatory Transcriptional Changes in Neurodegeneration.

Discriminating transcriptional changes that drive disease pathogenesis from nonpathogenic and compensatory responses is a daunting challenge. This is particularly true for neurodegenerative diseases, which affect the expression of thousands of genes in different brain regions at different disease stages. Here we integrate functional testing and network approaches to analyze previously reported transcriptional alterations in the brains of Huntington disease (HD) patients.

Otud7a Knockout Mice Recapitulate Many Neurological Features of 15q13.3 Microdeletion Syndrome.

15q13.3 microdeletion syndrome is characterized by a wide spectrum of neurodevelopmental disorders, including developmental delay, intellectual disability, epilepsy, language impairment, abnormal behaviors, neuropsychiatric disorders, and hypotonia. This syndrome is caused by a deletion on chromosome 15q, which typically encompasses six genes.

Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses.

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD.

FOXG1 expression shows correlation with neuronal differentiation in cerebellar development, aggressive phenotype in medulloblastomas, and survival in a xenograft model of medulloblastoma.

FOXG1 is a transcription factor that interacts with multiple signaling pathways and modulates neuronal differentiation in the telencephalon. Dysregulation of FOXG1 expression has been previously reported in medulloblastoma. In this study, we demonstrate a regional specific expression of FOXG1 and its colocalization with Nestin expression in the premigratory mitotically active (outer) layer of the external granular layer of the cerebellum.

Molecular pathway identification using biological network-regularized logistic models.

Background: Selecting genes and pathways indicative of disease is a central problem in computational biology. This problem is especially challenging when parsing multi-dimensional genomic data. A number of tools, such as L1-norm based regularization and its extensions elastic net and fused lasso, have been introduced to deal with this challenge.

Combinatorial therapy discovery using mixed integer linear programming.

Motivation: Combinatorial therapies play increasingly important roles in combating complex diseases. Owing to the huge cost associated with experimental methods in identifying optimal drug combinations, computational approaches can provide a guide to limit the search space and reduce cost. However, few computational approaches have been developed for this purpose, and thus there is a great need of new algorithms for drug combination prediction.

Digital sorting of complex tissues for cell type-specific gene expression profiles.

Background: Cellular heterogeneity is present in almost all gene expression profiles. However, transcriptome analysis of tissue specimens often ignores the cellular heterogeneity present in these samples. Standard deconvolution algorithms require prior knowledge of the cell type frequencies within a tissue or their in vitro expression profiles.

Understanding gene essentiality by finely characterizing hubs in the yeast protein interaction network.

The centrality-lethality rule, i.e., high-degree proteins or hubs tend to be more essential than low-degree proteins in the yeast protein interaction network, reveals that a protein's central position indicates its important function, but whether and why hubs tend to be more essential have been heavily debated.