Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

Explainable deep learning and virtual evolution identifies antimicrobial peptides with activity against multidrug-resistant human pathogens.

Artificial intelligence (AI) is a promising approach to identify new antimicrobial compounds in diverse microbial species. Here we developed an AI-based, explainable deep learning model, EvoGradient, that predicts the potency of antimicrobial peptides (AMPs) and virtually modifies peptide sequences to produce more potent AMPs, akin to in silico directed evolution. We applied this model to peptides encoded in low-abundance human oral bacteria, resulting in the virtual evolution of 32 peptides into potent AMPs.

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.

Neuroprotective Effects of Rapid Local Ischemic Postconditioning in Successful Endovascular Thrombectomy Patients.

Background: We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy.

Methods: We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery.

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.

Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.

Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC.

Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified.

Product Enhanced Reverse Transcriptase for assessing replication competent virus in vectors retroviral vectors pseudotyped with GALV and VSV-G envelopes.

We evaluated the use of the Product Enhanced Reverse Transcriptase (PERT) assay as a means of detecting virus in retroviral vectors products pseudotyped with Gibbon Ape Leukemia Virus (GALV) and Vesicular Stomatitis Virus G (VSVG) envelopes. PERT provides greater standardization than the S+/L- assay which has been used extensively in virus detection. A challenge is that PERT will also detect residual retroviral vectors as vector particles contain reverse transcriptase.

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.

Tai Chi and Aerobic Exercise on Cancer-Related Dyspnea in Advanced Lung Cancer Patients: A Randomized Clinical Trial.

Context: Dyspnea, a prevalent and debilitating symptom in patients with advanced lung cancer, negatively affects symptom burden and prognosis. Physical activity has emerged as a promising non-pharmacological intervention for managing dyspnea.

Objectives: This study compared the effectiveness of two widely-recognized physical activity modalities, namely Tai Chi (TC) and aerobic exercise (AE) for treating dyspnea in patients with advanced lung cancer.

Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

Background: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO.

Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations.

Purpose: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients.

Design: Cross-sectional study.

Methods: A total of 20 NCP patients and 20 age-matched controls were recruited.

Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score.

Efficacy of Probiotic Supplements on Brain-Derived Neurotrophic Factor, Inflammatory Biomarkers, Oxidative Stress and Cognitive Function in Patients with Alzheimer's Dementia: A 12-Week Randomized, Double-Blind Active-Controlled Study.

The role of neurotrophic factors, oxidative stress, and inflammation in the pathogenesis of Alzheimer's disease (AD) has been explored. Animal studies have reported the positive effects of probiotics on these factors. Some clinical studies also support the potential role of probiotics in improving cognitive function via the gut-brain axis in older adults.

Intermediate-Term Outcomes of Hip Arthroscopy for Femoroacetabular Impingement Syndrome in Patients With Global Versus Isolated Lateral Acetabular Overcoverage.

Background: Previous studies evaluating the outcomes of hip arthroscopy for patients with global acetabular overcoverage and focal superolateral acetabular overcoverage suffer from short-term follow-up and inconsistent radiographic criteria when defining these subpopulations of patients with femoroacetabular impingement syndrome (FAIS).

Purpose: To evaluate the intermediate-term postoperative outcomes for patients with FAIS in the setting of global acetabular overcoverage, lateral acetabular overcoverage, and normal acetabular coverage.

Study Design: Cohort study; Level of evidence, 3.

Decreased Hip Labral Width Measured on Preoperative Magnetic Resonance Imaging Is Associated With Greater Revision Rate After Primary Arthroscopic Labral Repair for Femoroacetabular Impingement Syndrome at 5-Year Follow-Up.

Purpose: To examine the associations between hip labral width and patient-reported outcomes, clinical threshold achievement rates, and rate of reoperation among patients with femoroacetabular impingement syndrome (FAIS) who underwent hip arthroscopy and labral repair at minimum 5-year follow-up.

Methods: Patients were identified from a prospective database who underwent primary hip arthroscopy for treatment of labral tears and FAIS. Modified Harris Hip Score (mHHS) and Nonarthritic Hip Score (NAHS) were recorded preoperatively and at 5-year follow-up.

Resident Memory-like CD8 T Cells Are Involved in Chronic Inflammatory and Neurodegenerative Diseases in the CNS.

Background And Objectives: Resident memory T (Trm) cells are a unique population that can survive and function in a compartmentalized tissue with inflammatory potential. We aim to investigate the alteration of Trm population in acute/chronic inflammatory and neurodegenerative diseases in the CNS.

Methods: The frequencies of CD4 and CD8 T cells expressing both CD69 and CD103, the markers for Trm cells, were quantified in the peripheral blood and CSF (n = 80 and 44, respectively) in a cross-sectional manner.

Application of a Deep Learning System to Detect Papilledema on Nonmydriatic Ocular Fundus Photographs in an Emergency Department.

Purpose: The Fundus photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) studies showed that ED providers poorly recognized funduscopic findings in patients in the ED. We tested a modified version of the Brain and Optic Nerve Study Artificial Intelligence (BONSAI) deep learning system on nonmydriatic fundus photographs from the FOTO-ED studies to determine if the deep learning system could have improved the detection of papilledema had it been available to ED providers as a real-time diagnostic aid.

Design: Retrospective secondary analysis of a cohort of patients included in the FOTO-ED studies.

Interactions of optic radiation lesions with retinal and brain atrophy in early multiple sclerosis.

Objective: Retrograde trans-synaptic neuroaxonal degeneration is considered a key pathological factor of subclinical retinal neuroaxonal damage in multiple sclerosis (MS). We aim to evaluate the longitudinal association of optic radiation (OR) lesion activity with retinal neuroaxonal damage and its role in correlations between retinal and brain atrophy in people with clinically isolated syndrome and early MS (pweMS).

Methods: Eighty-five pweMS were retrospectively screened from a prospective cohort (Berlin CIS cohort).

Dialysis Modality and Incident Stroke Among Patients With End-Stage Kidney Disease: A Registry-Based Cohort Study.

Background: Patients with end-stage kidney disease undergoing dialysis are at significant risk of stroke. Whether dialysis modality is associated with cerebrovascular disease is unclear. This study compared the risk of incident stroke in patients undergoing peritoneal dialysis or hemodialysis.