No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials.

Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively.

Pitavastatin to Prevent Cardiovascular Disease in HIV Infection.

Background: The risk of cardiovascular disease is increased among persons with human immunodeficiency virus (HIV) infection, so data regarding primary prevention strategies in this population are needed.

Methods: In this phase 3 trial, we randomly assigned 7769 participants with HIV infection with a low-to-moderate risk of cardiovascular disease who were receiving antiretroviral therapy to receive daily pitavastatin calcium (at a dose of 4 mg) or placebo. The primary outcome was the occurrence of a major adverse cardiovascular event, which was defined as a composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause.

Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model.

The development of an effective and durable vaccine remains a central goal in the fight against malaria. Circumsporozoite protein (CSP) is the major surface protein of sporozoites and the target of the only licensed Plasmodium falciparum (Pf) malaria vaccine, RTS,S/AS01. However, vaccine efficacy is low and short-lived, highlighting the need for a second-generation vaccine with superior efficacy and durability.

Efficacy, Tolerability, and Retention of Antiseizure Medications in -Associated Infantile Epilepsy.

Background And Objectives: Pathogenic variants in , encoding for the proline-rich transmembrane protein 2, were identified as the main cause of self-limiting sporadic and familial infantile epilepsy. Reported data on treatment response to antiseizure medications (ASMs) in defined monogenic epilepsies are limited. The aim of this study was to evaluate the treatment response of ASMs in children with monogenic -associated infantile epilepsy.

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

Background: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU).

Methods: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization.

Presenting Symptoms in Patients Undergoing Coronary Artery Disease Evaluation: Association With Noninvasive Test Results and Clinical Outcomes in the PROMISE Trial.

Background: Patients evaluated for coronary artery disease have a range of symptoms and underlying risk. The relationships between patient-described symptoms, clinician conclusions, and subsequent clinical management and outcomes remain incompletely described.

Methods: In this secondary analysis, we examined the association between 4 types of presenting symptoms (substernal/left-sided chest pain, other chest/neck/arm pain, dyspnea, and other symptoms) and patient risk, noninvasive test results, clinical management, and outcomes for stable outpatients randomized in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial.

Robotic Setup Promises Consistent Effects of Multilocular Gastrointestinal Electrical Stimulation: First Results of a Porcine Study.

Background: Electrical stimulation (ES) of several gastrointestinal (GI) segments is a promising therapeutic option for multilocular GI dysmotility, but conventional surgical access by laparotomy involves a high degree of tissue trauma. We evaluated a minimally invasive surgical approach using a robotic surgical system to perform electromyographic (EMG) recordings and ES of several porcine GI segments, comparing these data to an open surgical approach by laparotomy.

Materials And Methods: In 5 acute porcine experiments, we placed multiple electrodes on the stomach, duodenum, jejunum, ileum, and colon.

Highly Active N,O Zinc Guanidine Catalysts for the Ring-Opening Polymerization of Lactide.

New zinc guanidine complexes with N,O donor functionalities were prepared, characterized by X-Ray crystallography, and examined for their catalytic activity in the solvent-free ring-opening polymerization (ROP) of technical-grade rac-lactide at 150 °C. All complexes showed a high activity. The fastest complex [ZnCl (DMEGasme)] (C1) produced colorless poly(lactide) (PLA) after 90 min with a conversion of 52 % and high molar masses (M =69 100, polydispersity=1.

Bispecific digoxigenin-binding antibodies for targeted payload delivery.

Bispecific antibodies that bind cell-surface targets as well as digoxigenin (Dig) were generated for targeted payload delivery. Targeting moieties are IgGs that bind the tumor antigens Her2, IGF1R, CD22, or LeY. A Dig-binding single-chain Fv was attached in disulfide-stabilized form to C termini of CH3 domains of targeting antibodies.

Multistrange baryon production in Au-Au collisions at sqrt[s(NN)]=130 GeV.

The transverse mass spectra and midrapidity yields for Xis and Omegas are presented. For the 10% most central collisions, the (-)Xi(+)/h(-) ratio increases from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies while the Xi(-)/h(-) stays approximately constant. A hydrodynamically inspired model fit to the Xi spectra, which assumes a thermalized source, seems to indicate that these multistrange particles experience a significant transverse flow effect, but are emitted when the system is hotter and the flow is smaller than values obtained from a combined fit to pi, K, p, and Lambdas.

A cell shrinkage-induced non-selective cation conductance with a novel pharmacology in Ehrlich-Lettre-ascites tumour cells.

In whole-cell recordings on Ehrlich-Lettre-ascites tumour (ELA) cells, the shrinkage-induced activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(choline):P(NMDG) of 1.00:0.97:0.