Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration.

Background: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease.

Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair.

Background: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated.

Support for pictorial health warning labels on cigarette packages in the United States among adults who currently smoke or quit smoking: Findings from the ITC US Smoking and Vaping Surveys.

Introduction: In March 2020, the US Food and Drug Administration (FDA) finalized new pictorial health warnings (PHWs), covering 50% of the front and back of the pack; however, legal challenges from cigarette manufacturers have prevented the new warnings from being implemented. About 70% of adults in the general US population support PHWs. This study assessed support for PHWs in 2016, 2018 and 2020 among US adults (aged ≥18 years) who currently smoke or formerly smoked cigarettes.

ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy.

The programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases regulating PD-1 stability have been reported, deubiquitinases governing PD-1 homeostasis to modulate tumor immunotherapy remain unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1.

Effects of Pelleted and Extruded Feed on Growth Performance, Intestinal Histology and Microbiota of Juvenile Red Swamp Crayfish ().

The study was conducted to evaluate the extruded and pelleting feed production on growth performance, intestinal histology and microbiome analysis of juvenile red swamp crayfish, Procambarus clarkii. Crayfish were fed either pelleted or extruded feeds that were made using the same formula. Crayfish fed extruded feed had a lower feed conversion ratio, as well as significantly higher levels of trypsin and amylase (p < 0.

A novel animal model of primary blast lung injury and its pathological changes in mice.

Background: Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study.

Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.

Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab.

missense mutations in Xia-Gibbs syndrome.

Xia-Gibbs syndrome (XGS; MIM: 615829) is a phenotypically heterogeneous neurodevelopmental disorder (NDD) caused by newly arising mutations in the AT-Hook DNA-Binding Motif-Containing 1 () gene that are predicted to lead to truncated AHDC1 protein synthesis. More than 270 individuals have been diagnosed with XGS worldwide. Despite the absence of an independent assay for AHDC1 protein function to corroborate potential functional consequences of rare variant genetic findings, there are also reports of individuals with XGS-like trait manifestations who have missense mutations and who have been provided a molecular diagnosis of the disorder.

Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.

Background: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).

Methods: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age.

Awareness of Marketing of Heated Tobacco Products and Cigarettes and Support for Tobacco Marketing Restrictions in Japan: Findings from the 2018 International Tobacco Control (ITC) Japan Survey.

Japan is one of the world's largest cigarette markets and the top heated tobacco product (HTP) market. No forms of tobacco advertising, promotion, and sponsorship (TAPS) are banned under national law, although the industry has some voluntary TAPS restrictions. This study examines Japanese tobacco users' self-reported exposure to cigarette and HTP marketing through eight channels, as well as their support for TAPS bans.

Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters.

COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple systems, including the human embryonic stem cell-derived cardiomyocytes and lung cultures.

CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas.

Natural killer (NK) cells are a promising cellular immunotherapy for cancer. Cytokine-induced memory-like (ML) NK cells differentiate after activation with interleukin-12 (IL-12), IL-15, and IL-18, exhibit potent antitumor responses, and safely induce complete remissions in patients with leukemia. However, many cancers are not fully recognized via NK cell receptors.

MK-8719, a Novel and Selective -GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy.

Deposition of hyperphosphorylated and aggregated tau protein in the central nervous system is characteristic of Alzheimer disease and other tauopathies. Tau is subject to -linked -acetylglucosamine (-GlcNAc) modification, and -GlcNAcylation of tau has been shown to influence tau phosphorylation and aggregation. Inhibition of -GlcNAcase (OGA), the enzyme that removes -GlcNAc moieties, is a novel strategy to attenuate the formation of pathologic tau.

Lymphocyte counts and infection rates: Long-term fingolimod treatment in primary progressive MS.

Objective: To evaluate lymphocyte counts and incidences of infections in patients with primary progressive MS (PPMS) receiving fingolimod 0.5 mg/d or placebo over 5 years during the INFORMS study, to assess infection rates with longer-term treatment.

Methods: INFORMS was a randomized, multicenter, double-blind, placebo-controlled, parallel-group, phase 3 study of the sphingosine 1-phosphate receptor modulator fingolimod in patients with PPMS.

Novel Susceptibility Loci for Moyamoya Disease Revealed by a Genome-Wide Association Study.

Background And Purpose: Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by bilateral internal carotid artery stenosis and often leads to stroke in children or young adults. Although familial inheritance is well recognized, the genetic basis of MMD remains poorly understood.

Methods: A 2-stage genome-wide association study was conducted involving 1492 cases and 5084 controls.

Geometric Parameter Analysis of Ruptured and Unruptured Aneurysms in Patients with Symmetric Bilateral Intracranial Aneurysms: A Multicenter CT Angiography Study.

Background And Purpose: Previous studies of geometric and morphologic parameters of intracranial aneurysms have been conducted to determine rupture risk, which remains incompletely defined due to patient-specific risk factors, such as sex, hypertension, and age. To this end, we compared characteristics of ruptured and unruptured aneurysms in the same patients with symmetric bilateral intracranial aneurysms.

Materials And Methods: Between January 2008 and March 2014, 2361 patients with 2674 aneurysms were diagnosed by CT angiography or surgical findings at 4 medical centers.

Effect of clopidogrel with aspirin on functional outcome in TIA or minor stroke: CHANCE substudy.

Objective: We compared the effect of clopidogrel plus aspirin vs aspirin alone on functional outcome and quality of life in the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial of aspirin-clopidogrel vs aspirin alone after acute minor stroke or TIA.

Methods: Participants were assessed at 90 days for functional outcome using the modified Rankin Scale (mRS) and quality of life using the EuroQol-5 Dimension (EQ-5D). Poor functional outcome was defined as mRS score of 2-6 at 90 days and poor quality of life as EQ-5D index score of 0.

VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells.

Background: Malignant glioma is a common and lethal primary brain tumor in adults. Here we identified a novel oncoprotein, vesicle-associated membrane protein 8 (VAMP8), and investigated its roles in tumorigenisis and chemoresistance in glioma.

Methods: The expression of gene and protein were determined by quantitative PCR and Western blot, respectively.