25-Hydroxycholecalciferol Improves Cardiac Metabolic Adaption, Mitochondrial Biogenetics, and Redox Status to Ameliorate Pathological Remodeling and Functional Failure in Obese Chickens.

Broiler breeder hens allowed ad libitum (Ad) feed intake developed obesity and cardiac pathogenesis and thereby were susceptible to sudden death. A supplement of 69 µg 25-hydroxycholecalciferol (25-OH-D3)/kg feed rescued the livability of feed-restricted (R) and Ad-hens (mortality; 6.7% vs.

Leadership Lingo: Developing a Shared Language of Leadership Behaviors to Enrich Debriefing Conversations.

Introduction: Leadership in medical emergencies is variable and frequently suboptimal, contributing to poor patient care and outcomes. Simulation training can improve leadership in both simulated practice and real clinical emergencies. Thoughtful debriefing is essential.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

Introduction: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness.

Methods: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]).

Staphylococcus aureus induces drug resistance in cancer T cells in Sézary syndrome.

Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), are prone to Staphylococcus aureus infections and have a poor prognosis due to treatment resistance. Here, we report that S aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S aureus and recombinant SE significantly inhibit cell death induced by histone deacetylase (HDAC) inhibitor romidepsin in primary malignant T cells from patients with SS.

Functional assessments of SARS-CoV-2 single-round infectious particles with variant-specific spike proteins on infectivity, drug sensitivity, and antibody neutralization.

Working with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is restricted to biosafety level III (BSL-3) laboratory. The study used a trans-complementation system consisting of virus-like particles (VLPs) and DNA-launched replicons to generate SARS-CoV-2 single-round infectious particles (SRIPs) with variant-specific spike (S) proteins. S gene of Wuhan-Hu-1 strain (S) or Omicron BA.

First Experimental Study of the Purely Leptonic Decay D_{s}^{*+}→e^{+}ν_{e}.

Using 7.33  fb^{-1} of e^{+}e^{-} collision data taken with the BESIII detector at the BEPCII collider, we report the first experimental study of the purely leptonic decay D_{s}^{*+}→e^{+}ν_{e}. Our data contain a signal of this decay with a statistical significance of 2.

Association between Glyphosate Exposure and Erythrograms in a Representative Sample of US Adults: NHANES 2013-2014.

Glyphosate is the most commonly utilized herbicide globally, and a growing body of experimental research has linked its exposure to red blood cell damage. However, the potential toxicity of glyphosate exposure on erythrocytes in the general population remains poorly understood. Therefore, we analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) of 1466 adults (≥ 18 years) to explore the potential relationship between glyphosate exposure and erythrocyte profiles.

Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.

Background: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.

Methods: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT.

Blink rate and facial orientation reveal distinctive patterns of attentional engagement in autistic toddlers: a digital phenotyping approach.

Differences in social attention are well-documented in autistic individuals, representing one of the earliest signs of autism. Spontaneous blink rate has been used to index attentional engagement, with lower blink rates reflecting increased engagement. We evaluated novel methods using computer vision analysis (CVA) for automatically quantifying patterns of attentional engagement in young autistic children, based on facial orientation and blink rate, which were captured via mobile devices.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

De novo design of modular peptide-binding proteins by superhelical matching.

General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, designing peptide-binding proteins is challenging, as most peptides do not have defined structures in isolation, and hydrogen bonds must be made to the buried polar groups in the peptide backbone. Here, inspired by natural and re-engineered protein-peptide systems, we set out to design proteins made out of repeating units that bind peptides with repeating sequences, with a one-to-one correspondence between the repeat units of the protein and those of the peptide.

Futibatinib for -Rearranged Intrahepatic Cholangiocarcinoma.

Background: Alterations in fibroblast growth factor receptor 2 () have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with -altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.

Methods: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic fusion-positive or rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors).

Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the pandemic that began late December 2019. The co-expression of SARS-CoV-2 structural proteins in cells could assemble into several types of virus-like particles (VLPs) without a viral RNA genome. VLPs containing S proteins with the structural and functional properties of authentic virions are safe materials to exploit for virus-cell entry and vaccine development.

De novo design of obligate ABC-type heterotrimeric proteins.

The de novo design of three protein chains that associate to form a heterotrimer (but not any of the possible two-chain heterodimers) and that can drive the assembly of higher-order branching structures is an important challenge for protein design. We designed helical heterotrimers with specificity conferred by buried hydrogen bond networks and large aromatic residues to enhance shape complementary packing. We obtained ten designs for which all three chains cooperatively assembled into heterotrimers with few or no other species present.

Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

Background: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection.

Methods: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery.

APA-Scan: detection and visualization of 3'-UTR alternative polyadenylation with RNA-seq and 3'-end-seq data.

Background: The eukaryotic genome is capable of producing multiple isoforms from a gene by alternative polyadenylation (APA) during pre-mRNA processing. APA in the 3'-untranslated region (3'-UTR) of mRNA produces transcripts with shorter or longer 3'-UTR. Often, 3'-UTR serves as a binding platform for microRNAs and RNA-binding proteins, which affect the fate of the mRNA transcript.

Impact of Native Language, English Proficiency, and Language Concordance on Interpersonal Care During Evaluation of Acute Coronary Syndrome.

Background: High-quality interpersonal interactions between clinicians and patients can improve communication and reduce health disparities among patients with novice English proficiency (NEP). Yet, little is known about the impact of native language, NEP, and native language concordance on patient on perceptions of interpersonal care in the emergency department (ED).

Objective: To determine the associations of native language, NEP, and native language concordance with patient perceptions of interpersonal care among patients undergoing evaluation for suspected acute coronary syndrome (ACS) in the ED.

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study.

Background And Objective: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There are limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors.

Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies.

Many people with hemophilia A (PwHA) undergo surgery in their lifetime, often because of complications of their disease. Emicizumab is the first bispecific monoclonal antibody prophylactic therapy for PwHA, and its efficacy and safety have been previously demonstrated; however, there is a need to build an evidence base on the management of PwHA on emicizumab undergoing surgery. Data from the HAVEN 1-4 phase 3 clinical trials were pooled to provide a summary of all minor and major surgeries in PwHA with or without factor VIII (FVIII) inhibitors who were receiving emicizumab prophylaxis.

Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

Background: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.

Methods: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia.

High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I.

Objective: We investigated the prevalence of preexisting M184V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

Design: Participant data were pooled from six clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed people with HIV.

Methods: Preexisting drug resistance was assessed by historical genotypes and/or baseline proviral DNA genotyping.