A virally encoded high-resolution screen of cytomegalovirus dependencies.

Genetic screens have transformed our ability to interrogate cellular factor requirements for viral infections, but most current approaches are limited in their sensitivity, biased towards early stages of infection and provide only simplistic phenotypic information that is often based on survival of infected cells. Here, by engineering human cytomegalovirus to express single guide RNA libraries directly from the viral genome, we developed virus-encoded CRISPR-based direct readout screening (VECOS), a sensitive, versatile, viral-centric approach that enables profiling of different stages of viral infection in a pooled format. Using this approach, we identified hundreds of host dependency and restriction factors and quantified their direct effects on viral genome replication, viral particle secretion and infectiousness of secreted particles, providing a multi-dimensional perspective on virus-host interactions.

Health-related quality of life after minimal-invasive treatment of aortic valve stenosis in the elderly.

Background: Although transfemoral transcatheter aortic valve implantation (TF-TAVI) offers superior early outcome over open surgical aortic valve replacement (SAVR) in the elderly, a comparison of TF-TAVI with surgery performed through partial upper mini sternotomy (PUMS) hasn't yet been validated. The aim of the present study is to evaluate the clinical outcome and quality of life of patients subjected to TF-TAVI and open surgical aortic valve replacement through partial upper mini sternotomy (PUMS-SAVR).

Methods: Baseline, procedural and post-treatment data of 197 consecutive patients: 137 TF-TAVI and 60 PUMS-SAVR treated at Philipps University of Marburg, were retrospectively collected.

Left ventricular free wall rupture caused by myocardial ischemia without treatable atherosclerotic coronary disease: a case series.

Background: The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure. Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation.

Sequential composite BIMA grafting for 3v-CAD: factors that predict successful outcome of the one-inflow and two-inflow revascularization techniques.

Objective: The effect of one-inflow and two-inflow coronary surgical revascularization techniques inclosing skeletonized double mammary artery (BIMA) as T-graft on outcome is studied.

Methods: Early ad mid-term outcome of complete BIMA revascularization (C-T-BIMA) versus left-sided BIMA with right-sided aorto-coronary bypass (L-T-BIMA + R-CABG) is quantified and analyzed by multivariate logistic regression, Cox-regression, and Kaplan-Meier analysis in a series of 204 consecutive patients treated for triple-vessel coronary disease (3v-CAD).

Results: The L-T-BIMA + R-CABG technique (n = 104) enables higher number of total (4.

A Group Randomized Controlled Trial of Relationships Under Construction Sexual Risk Avoidance Education.

Background: We analyzed data from a study to evaluate the effectiveness of the Relationships Under Construction (RUC) sexual risk avoidance education program promoting positive youth development and healthy relationships.

Methods: Twelve schools in the Midwestern region of the United States randomized to the intervention implemented RUC in health or science classes, while control schools collected study measures and implemented the standard curriculum.

Results: Post-randomization analyses revealed significant differences in grade, race/ethnicity, and prior relationship education at baseline between intervention and control students.

An analysis of physiological responses as indicators of driver takeover readiness in conditionally automated driving.

By the year 2045, it is projected that Autonomous Vehicles (AVs) will make up half of the new vehicle market. Successful adoption of AVs can reduce drivers' stress and fatigue, curb traffic congestion, and improve safety, mobility, and economic efficiency. Due to the limited intelligence in relevant technologies, human-in-the-loop modalities are still necessary to ensure the safety of AVs at current or near future stages, because the vehicles may not be able to handle all emergencies.

GNAQ/GNA11 Mosaicism Causes Aberrant Calcium Signaling Susceptible to Targeted Therapeutics.

Mosaic variants in genes GNAQ or GNA11 lead to a spectrum of vascular and pigmentary diseases including Sturge-Weber syndrome, in which progressive postnatal neurological deterioration led us to seek biologically targeted therapeutics. Using two cellular models, we find that disease-causing GNAQ/11 variants hyperactivate constitutive and G-protein coupled receptor ligand-induced intracellular calcium signaling in endothelial cells. We go on to show that the aberrant ligand-activated intracellular calcium signal is fueled by extracellular calcium influx through calcium-release-activated channels.

Development of the Palliative Care Law and Policy GPS to Assess National Policies in Palliative Care.

State policy-making to address disparities in access to and quality of palliative care is increasing. Yet, there is no mechanism to systematically assess palliative care policies nationally. We describe the development of the Palliative Care Law and Policy GPS by the Center to Advance Palliative Care and the Yale Solomon Center for Health Law and Policy.

Bilateral vocal fold paresis and glottal bridge synechia in COVID-19.

Key Clinical Message: Bilateral vocal fold paresis (BVFP) is a rare complication in COVID-19 and should be considered as differential diagnosis in COVID-19-patients presenting with dyspnea and stridor. High-dose intravenous corticosteroids can be useful treating COVID-19-related laryngeal edema and vocal fold paresis. This case shows the complexity of laryngeal complications in COVID-19 requiring surgeries and functional therapies.

Outcome of Surgery for Ischemic Mitral Regurgitation Depends on the Type and Timing of the Coronary Revascularization.

Objective: Long-term outcomes of mitral valve (MV) repair versus MV replacement for ischemic mitral regurgitation (IMR) in patients undergoing either prior (PCR) or concomitant coronary revascularization (CCR) by surgery (CABG) or intervention (PCI) are uncertain.

Methods And Results: Of 446 patients receiving MV surgery for IMR between July 2006 and December 2010, 125 patients-87 CCR (69.1%) and 38 PCR (30.

GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia.

Familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2) are due to loss- and gain-of-function mutations, respectively, of the GNA11 gene that encodes the G protein subunit Gα11, a signaling partner of the calcium-sensing receptor (CaSR). To date, four probands with FHH2-associated Gα11 mutations and eight probands with ADH2-associated Gα11 mutations have been reported. In a 10-year period, we identified 37 different germline GNA11 variants in >1200 probands referred for investigation of genetic causes for hypercalcemia or hypocalcemia, comprising 14 synonymous, 12 noncoding, and 11 nonsynonymous variants.

Sourcing UK COVID-19 News: An Analysis of Sourcing Patterns of 15 UK News Outlets Reporting on COVID-19 Across Facebook, Twitter, and Instagram.

How a health emergency is defined and presented through the news media matters for public understanding and health outcomes. Previous studies have endeavored to identify the patterns of news sourcing in crisis coverage, specifically the interplay between political sources and health expert sources, but yielded inconclusive results. This study analyses the types and roles of actors (those entities mentioned in a story) and sources cited in news coverage of COVID-19 by surveying social media posts published by 15 UK news outlets coverage across Facebook, Twitter, and Instagram between 1 January to December 31 2020.

Targeting Health-Related Social Risks in the Clinical Setting: New Policy Momentum and Practice Considerations.

The federal government is funding a sea change in health care by investing in interventions targeting social determinants of health, which are significant contributors to illness and health inequity. This funding power has encouraged states, professional and accreditation organizations, health care entities, and providers to focus heavily on social determinants. We examine how this shift in focus affects clinical practice in the fields of oncology and emergency medicine, and highlight potential areas of reform.

The Synergy of Legal and Medical Palliative Care: Challenges and Opportunities in Palliative MLP and the Yale Experience.

Palliative care and medical-legal partnership are complementary disciplines dedicated to integrating care to treat the whole patient and intervening before a legal or medical issue is at a crisis point. In this paper, we discuss the founding and operations of the Yale Palliative Medical Legal Partnership, give examples of typical cases, explain special considerations in this area of law, and propose areas for further research.

INTRODUCTION: Medical-Legal Partnerships: Equity, Evolution, and Evaluation.

The COVID-19 pandemic laid bare systemic inequities shaped by social determinants of health (SDoH). Public health agencies, legislators, health systems, and community organizations took notice, and there is currently unprecedented interest in identifying and implementing programs to address SDoH. This special issue focuses on the role of medical-legal partnerships (MLPs) in addressing SDoH and racial and social inequities, as well as the need to support these efforts with evidence-based research, data, and meaningful partnerships and funding.

Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19.

https://bit.ly/3pqM9Vv.

Differentiated impact of pulmonary hypertension on outcome after left ventricular assist device implantation and tricuspid valve repair.

The present study aimed to investigate the impact of pulmonary hypertension (PH) on short-term survival after LVAD implantation with or without tricuspid annuloplasty valve repair (TVr) performed to treat regurgitation and avoid RV-failure post-LVAD insertion. Data of 24 patients receiving LVAD-implantation are assessed and compared. The primary outcome is in-hospital survival.

Impact of the underlying aortic pathology on postimplantation syndrome after endovascular thoracic aortic repair.

Background: Thoracic endovascular aortic repair (TEVAR) is the treatment option of choice for almost all pathologies of the descending thoracic aorta. The aim of the present study was to determine the impact of aortic pathology on the occurrence of postimplantation syndrome (PIS) after TEVAR.

Methods: Seventy-four patients undergoing TEVAR for aortic dissection (TAD, 25), aortic aneurysm (TAA, 26), and aortic rupture or perforated ulcer (TAR/PAU, 23) were included in this retrospective study.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.