Mapping the developing human cardiac endothelium at single cell resolution identifies MECOM as a regulator of arteriovenous gene expression

AIMS: Coronary vasculature formation is a critical event during cardiac development, essential for heart function throughout perinatal and adult life. However, current understanding of coronary vascular development has largely been derived from transgenic mouse models. The aim of this study was to characterize the transcriptome of the human foetal cardiac endothelium using single-cell RNA sequencing (scRNA-seq) to provide critical new insights into the cellular heterogeneity and transcriptional dynamics that underpin endothelial specification within the vasculature of the developing heart. METHODS AND RESULTS: We acquired scRNA-seq data of over 10 000 foetal cardiac endothelial cells (ECs), revealing divergent EC subtypes including endocardial, capillary, venous, arterial, and lymphatic populations. Gene regulatory network analyses predicted roles for SMAD1 and MECOM in determining the identity of capillary and arterial populations, respectively. Trajectory inference analysis suggested an endocardial contribution to the coronary vasculature and subsequent arterialization of capillary endothelium accompanied by increasing MECOM expression. Comparative analysis of equivalent data from murine cardiac development demonstrated that transcriptional signatures defining endothelial subpopulations are largely conserved between human and mouse. Comprehensive characterization of the transcriptional response to MECOM knockdown in human embryonic stem cell-derived EC (hESC-EC) demonstrated an increase in the expression of non-arterial markers, including those enriched in venous EC. CONCLUSIONS: scRNA-seq of the human foetal cardiac endothelium identified distinct EC populations. A predicted endocardial contribution to the developing coronary vasculature was identified, as well as subsequent arterial specification of capillary EC. Loss of MECOM in hESC-EC increased expression of non-arterial markers, suggesting a role in maintaining arterial EC identity

The Next Generation Virgo Cluster Survey - Infrared (NGVS-IR): I. A new Near-UV/Optical/Near-IR Globular Cluster selection tool

The NGVS-IR project (Next Generation Virgo Survey - Infrared) is a contiguous near-infrared imaging survey of the Virgo cluster of galaxies. It complements the optical wide-field survey of Virgo (NGVS). The current state of NGVS-IR consists of Ks-band imaging of 4 deg^2 centered on M87, and J and Ks-band imaging of 16 deg^2 covering the region between M49 and M87. In this paper, we present the observations of the central 4 deg^2 centered on Virgo's core region. The data were acquired with WIRCam on the Canada-France-Hawaii Telescope and the total integration time was 41 hours distributed in 34 contiguous tiles. A survey-specific strategy was designed to account for extended galaxies while still measuring accurate sky brightness within the survey area. The average 5\sigma limiting magnitude is Ks=24.4 AB mag and the 50% completeness limit is Ks=23.75 AB mag for point source detections, when using only images with better than 0.7" seeing (median seeing 0.54"). Star clusters are marginally resolved in these image stacks, and Virgo galaxies with \mu_Ks=24.4 AB mag arcsec^-2 are detected. Combining the Ks data with optical and ultraviolet data, we build the uiK color-color diagram which allows a very clean color-based selection of globular clusters in Virgo. This diagnostic plot will provide reliable globular cluster candidates for spectroscopic follow-up campaigns needed to continue the exploration of Virgo's photometric and kinematic sub-structures, and will help the design of future searches for globular clusters in extragalactic systems. Equipped with this powerful new tool, future NGVS-IR investigations based on the uiK diagram will address the mapping and analysis of extended structures and compact stellar systems in and around Virgo galaxies.Comment: 23 pages, 18 figures. Accepted for publication in ApJ

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta‐analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta‐analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First‐degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Euclid preparation. XXV. The Euclid Morphology Challenge -- Towards model-fitting photometry for billions of galaxies

The ESA Euclid mission will provide high-quality imaging for about 1.5 billion galaxies. A software pipeline to automatically process and analyse such a huge amount of data in real time is being developed by the Science Ground Segment of the Euclid Consortium; this pipeline will include a model-fitting algorithm, which will provide photometric and morphological estimates of paramount importance for the core science goals of the mission and for legacy science. The Euclid Morphology Challenge is a comparative investigation of the performance of five model-fitting software packages on simulated Euclid data, aimed at providing the baseline to identify the best suited algorithm to be implemented in the pipeline. In this paper we describe the simulated data set, and we discuss the photometry results. A companion paper (Euclid Collaboration: Bretonni\`ere et al. 2022) is focused on the structural and morphological estimates. We created mock Euclid images simulating five fields of view of 0.48 deg2 each in the $I_E$ band of the VIS instrument, each with three realisations of galaxy profiles (single and double S\'ersic, and 'realistic' profiles obtained with a neural network); for one of the fields in the double S\'ersic realisation, we also simulated images for the three near-infrared $Y_E$, $J_E$ and $H_E$ bands of the NISP-P instrument, and five Rubin/LSST optical complementary bands ($u$, $g$, $r$, $i$, and $z$). To analyse the results we created diagnostic plots and defined ad-hoc metrics. Five model-fitting software packages (DeepLeGATo, Galapagos-2, Morfometryka, ProFit, and SourceXtractor++) were compared, all typically providing good results. (cut)Comment: 29 pages, 33 figures. Euclid pre-launch key paper. Companion paper: Bretonniere et al. 202

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707