A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice.

Background: Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides.

A multitask deep learning model utilizing electrocardiograms for major cardiovascular adverse events prediction.

Deep learning analysis of electrocardiography (ECG) may predict cardiovascular outcomes. We present a novel multi-task deep learning model, the ECG-MACE, which predicts the one-year first-ever major adverse cardiovascular events (MACE) using 2,821,889 standard 12-lead ECGs, including training (n = 984,895), validation (n = 422,061), and test (n = 1,414,933) sets, from Chang Gung Memorial Hospital database in Taiwan. Data from another independent medical center (n = 113,224) was retrieved for external validation.

Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

Background: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia.

Methods: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention.

Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions.

Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-risk Settings: A Randomized Controlled Trial.

Background: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease.

Methods: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

Introduction: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions.

Methods: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

UB-612 pan-SARS-CoV-2 T cell immunity-promoting vaccine protects against COVID-19 moderate-severe disease.

UB-612 pan-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine targets the monomeric Spike S1-receptor binding domain (RBD) subunit protein along with five sequence-conserved T cell epitopes found on Spike S2 and non-Spike M and N proteins. UB-612 vaccination safely induces potent, broad, and long-lasting immunity against SARS-CoV-2. A phase-2 trial-extended observational study during the Omicron BA.

A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset.

Materials And Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016.

Missing methane emissions from urban sewer networks.

Methane emissions from sewer networks are an important source of anthropogenic greenhouse gases (GHGs) but are not currently reflected in the national GHG inventory. We found significant CH emissions of approximately 573 [395-831] CH t y from sewer networks in the old residential and commercial areas of Seoul (Gwanak district) using an electric vehicle-based atmospheric GHG monitoring platform. The majority of ethane-to-methane ratios (<0.

Kojic Acid Gene Clusters and the Transcriptional Activation Mechanism of KojR on Expression of Clustered Genes.

Kojic acid (KA) is a fungal metabolite and has a variety of applications in the cosmetics and food industries. is a well-known producer of KA, and its KA biosynthesis gene cluster has been identified. In this study, we showed that nearly all section aspergilli except for had complete KA gene clusters, and only one species, , contained a partial KA gene cluster.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

Background: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking.

Objective: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population.

Design: Multicenter randomized controlled study.

Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.

Background: The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome.

Methods: Forty-five paroxysmal AF patients (30 males, 57.

A Retrospective Study of the Safety and Immunogenicity of MVC-COV1901 Vaccine for People Living with HIV.

Background: This study aimed to assess the safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminum hydroxide, for people living with HIV (PWH).

Methods: A total of 57 PWH of ≥20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received two doses of MVC-COV1901 28 days apart.

Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial.

Background: Sodium-glucose cotransporter 2 inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. Although it has been theorized that sodium-glucose cotransporter 2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine whether sodium-glucose cotransporter 2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure.

Relationship of Plaque Features at Coronary CT to Coronary Hemodynamics and Cardiovascular Events.

Background Plaque assessments with coronary CT angiography (CCTA) and coronary flow indexes have prognostic implications. Purpose To investigate the association and additive prognostic value of plaque burden and characteristics at CCTA with coronary pressure and flow. Materials and Methods Data of patients with coronary artery disease who underwent CCTA within 90 days before physiologic assessments at tertiary cardiovascular centers between January 2011 and December 2018 were retrospectively analyzed, which included fractional flow reserve (FFR), resting distal coronary artery pressure (Pd)-to-aortic pressure (Pa) ratio (hereafter, Pd/Pa), coronary flow reserve (CFR), hyperemic flow (1/hyperemic mean transit time [Tmn]), resting flow (1/resting Tmn), and index of microcirculatory resistance (IMR).

A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook.

Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies.

Improving the Safety of Mesenchymal Stem Cell-Based Therapy Using Herpes Simplex Virus Thymidine Kinase.

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis.

Transmembrane Mucin 1 Blocks Fluorescein Ingress to Corneal Epithelium.

Purpose: To determine the role of transmembrane mucins in blocking fluorescein ingress to the corneal epithelium and its deficiency in contributing to corneal fluorescein punctate staining.

Methods: A dry eye model was established by extirpating lacrimal and Harderian glands in rabbits to correlate the expression of mucins with fluorescein-stained areas on the corneal button using immunofluorescence. Expression of transmembrane mucins was promoted in human corneal epithelial cells (HCECs) by culturing with the mucin-promoting medium (MPM) or diquafosol treatment.

Measurement of the Sixth-Order Cumulant of Net-Proton Multiplicity Distributions in Au+Au Collisions at sqrt[s_{NN}]=27, 54.4, and 200 GeV at RHIC.

According to first-principle lattice QCD calculations, the transition from quark-gluon plasma to hadronic matter is a smooth crossover in the region μ_{B}≤T_{c}. In this range the ratio, C_{6}/C_{2}, of net-baryon distributions are predicted to be negative. In this Letter, we report the first measurement of the midrapidity net-proton C_{6}/C_{2} from 27, 54.

Heat-Killed Lactobacilli Preparations Promote Healing in the Experimental Cutaneous Wounds.

Probiotics are defined as microorganisms with beneficial health effects when consumed by humans, being applied mainly to improve allergic or intestinal diseases. Due to the increasing resistance of pathogens to antibiotics, the abuse of antibiotics becomes inefficient in the skin and in systemic infections, and probiotics may also provide the protective effect for repairing the healing of infected cutaneous wounds. Here we selected two Lactobacillus strains, GMNL-6 and GMNL-653, in heat-killed format to examine the beneficial effect in skin wound repair through the selection by promoting collagen synthesis in Hs68 fibroblast cells.

A population-specific reference panel for improved genotype imputation in African Americans.

There is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals.