Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay.

Copy number variants (CNVs) are recognized as a crucial genetic cause of neurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA), the first-tier diagnostic test for individuals with NDDs, has been utilized to detect CNVs in clinical practice, but most reports are still from populations of European ancestry. To contribute more worldwide clinical genomics data, we investigated the genetic etiology of 410 Han Chinese patients with NDDs (151 with autism and 259 with unexplained intellectual disability (ID) and developmental delay (DD)) using CMA (Affymetrix) after G-banding karyotyping.

Repeatability and reproducibility of corneal higher-order aberrations measurements after small incision lenticule extraction using the Scheimpflug-Placido topographer.

Background: To evaluate the precision of corneal higher-order aberrations measurements after small incision lenticule extraction (SMILE) using the Sirius Scheimpflug-Placido topographer (CSO, Italy).

Methods: Seventy-five eyes from 75 postoperative subjects were included in this prospective study. Three consecutive corneal aberrometric measurements were obtained with the Scheimpflug-Placido topographer by two experienced operators to assess intra- and inter-observer reproducibility.

Effectiveness of a Workplace-Based, Multicomponent Hypertension Management Program in Real-World Practice: A Propensity-Matched Analysis.

Limited studies had investigated the potential benefits of workplace-based hypertension management programs on long-term blood pressure (BP) control and health outcomes. This study used the propensity score matching to examine the effectiveness of a workplace-based hypertension management program on BP control and risks of major adverse cardiovascular events and all-cause mortality. Within the Kailuan study, a workplace-based hypertension management program was initiated in 2009 among men with hypertension, which included regular BP measuring (twice a month), free antihypertensive medications, and individualized health consultation.

Whole-Tumor Histogram Analysis of Multiple Diffusion Metrics for Glioma Genotyping.

Background The isocitrate dehydrogenase genotype and codeletion status are key molecular markers included in glioma pathologic diagnosis. Advanced diffusion models provide additional microstructural information. Purpose To compare the diagnostic performance of histogram features of multiple diffusion metrics in predicting glioma and genotyping.

Impairment and Plasticity of Language-Related White Matter in Patients With Brain Arteriovenous Malformations.

Background: Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas.

Methods: Thirty-three patients with AVMs involving language areas were prospectively enrolled.

Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.

DNA methylation, a key epigenetic driver of transcriptional silencing, is universally dysregulated in cancer. Reversal of DNA methylation by hypomethylating agents, such as the cytidine analogs decitabine or azacytidine, has demonstrated clinical benefit in hematologic malignancies. These nucleoside analogs are incorporated into replicating DNA where they inhibit DNA cytosine methyltransferases DNMT1, DNMT3A and DNMT3B through irreversible covalent interactions.

Selective Antisite Defect Formation in WS Monolayers via Reactive Growth on Dilute W-Au Alloy Substrates.

Defects are ubiquitous in 2D materials and can affect the structure and properties of the materials and also introduce new functionalities. Methods to adjust the structure and density of defects during bottom-up synthesis are required to control the growth of 2D materials with tailored optical and electronic properties. Here, the authors present an Au-assisted chemical vapor deposition approach to selectively form S and S2 antisite defects, whereby one or two sulfur atoms substitute for a tungsten atom in WS monolayers.

Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing.

Background: Metastases are responsible for over 70% of deaths from lung adenocarcinomas. Previous large-scale studies of LUAD mainly focused on primary diseases. We aimed to comprehensively analyze the genomic landscape of metastatic LUADs and elucidate its clinical implications in the context of precision medicine.

Preparation of long single-strand DNA concatemers for high-level fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) is a powerful tool to visualize transcripts in fixed cells and tissues. Despite the recent advances in FISH detection methods, it remains challenging to achieve high-level FISH imaging with a simple workflow. Here, we introduce a method to prepare long single-strand DNA concatemers (lssDNAc) through a controllable rolling-circle amplification (CRCA).

Identification of Human Norovirus GII.3 Blockade Antibody Epitopes.

Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population.

Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome.

Background: Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

Purpose: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China.

Design: Retrospective cohort study.

Methods: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data.

Exploring Cell Surface-Nanopillar Interactions with 3D Super-Resolution Microscopy.

Plasma membrane topography has been shown to strongly influence the behavior of many cellular processes such as clathrin-mediated endocytosis, actin rearrangements, and others. Recent studies have used three-dimensional (3D) nanostructures such as nanopillars to imprint well-defined membrane curvatures (the "nano-bio interface"). In these studies, proteins and their interactions were probed by two-dimensional fluorescence microscopy.

The Precision of a New Anterior Segment Optical Coherence Tomographer and Its Comparison With a Swept-Source OCT-Based Optical Biometer in Patients With Cataract.

Purpose: To assess the precision of a new spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39; CSO) and its comparison with a swept-source OCT (SS-OCT) biometer (Argos; Movu, Inc) in patients with cataract.

Methods: Fifty-three right eyes from 53 patients were examined by two experienced operators three times using both devices randomly. Employing the within-subject standard deviation (S), test-retest variability, coefficient of variation, and intraclass correlation coefficient to evaluate intraoperator repeatability and interoperator reproducibility; the double-angle plots to analyze astigmatism; and Bland-Altman plots and 95% limits of agreement to verify the agreement between devices.

Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

Background: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear.

Methods: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes.

Changes of psychotic-like experiences and their association with anxiety/depression among young adolescents before COVID-19 and after the lockdown in China.

Objective: Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study.

EPAS1 (Endothelial PAS Domain Protein 1) Orchestrates Transactivation of Endothelial ICAM1 (Intercellular Adhesion Molecule 1) by Small Nucleolar RNA Host Gene 5 (SNHG5) to Promote Hypoxic Pulmonary Hypertension.

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Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum.

Background And Objectives: To investigate the association of age and the presence of contrast-enhancing lesions (CELs) on cranial MRI scans in different disease courses of multiple sclerosis (MS), we describe the frequency of CELs as a function of age in 4 large randomized controlled trial (RCT) datasets.

Methods: Using original trial data from CombiRx (Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis; clinicaltrials.gov identifier NCT00211887), a trial in relapsing-remitting MS; ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis; clinicaltrials.

Defining Age-specific Relationships of Respiratory Syncytial Virus and Rhinovirus Species in Hospitalized Children With Acute Wheeze.

Background: Acute wheezing is one of the most common hospital presentations for young children. Respiratory syncytial virus (RSV) and rhinovirus (RV) species A, B and the more recently described species C are implicated in the majority of these presentations. However, the relative importance and age-specificities of these viruses have not been defined.

Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV.

The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread social and economic disruption. Effective interventions are urgently needed for the prevention and treatment of COVID-19. Neutralizing monoclonal antibodies (mAbs) have demonstrated their prophylactic and therapeutic efficacy against SARS-CoV-2, and several have been granted authorization for emergency use.

Development of an Androgen Receptor Inhibitor Targeting the N-Terminal Domain of Androgen Receptor for Treatment of Castration Resistant Prostate Cancer.

Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance can occur when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or through the expression of constitutively active splice variants lacking the androgen binding domain entirely (e.g.

Population pharmacokinetic analysis of rivaroxaban in children and comparison to prospective physiologically-based pharmacokinetic predictions.

Rivaroxaban has been investigated in the EINSTEIN-Jr program for the treatment of acute venous thromboembolism (VTE) in children aged 0 to 18 years and in the UNIVERSE program for thromboprophylaxis in children aged 2 to 8 years with congenital heart disease after Fontan-procedure. Physiologically-based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modeling were used throughout the pediatric development of rivaroxaban according to the learn-and-confirm paradigm. The development strategy was to match pediatric drug exposures to adult exposure proven to be safe and efficacious.

Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.

DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP.