Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.

Prognostic value of extracellular volume fraction in myocardial infarction and myocardial infarction with nonobstructive coronary arteries: A multicenter study.

Rationale And Objectives: The aim of the present retrospective study was to evaluate the prognostic role of the extracellular volume fraction (ECV) in patients with myocardial infarction (MI) and myocardial infarction with nonobstructive coronary arteries (MINOCA). The present study hypothesized that ECV is associated with major adverse cardiovascular events (MACEs) in MI and MINOCA patients.

Materials And Methods: Cardiac magnetic resonance (CMR) imaging was performed on 351 consecutive patients (mean age: 58 ± 12 years; 252 [71.

Spectral CT-based nomogram for preoperative prediction of Lauren classification in locally advanced gastric cancer: a prospective study.

Objectives: To develop a nomogram based on clinical features and spectral quantitative parameters to preoperatively predict the Lauren classification for locally advanced gastric cancer (LAGC).

Methods: Patients diagnosed with LAGC by postoperative pathology who underwent abdominal triple-phase enhanced spectral computed tomography (CT) were prospectively enrolled in this study between June 2023 and December 2023. All the patients were categorized into intestinal- and diffuse-type groups according to the Lauren classification.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

Background: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear.

Methods: A total of 2395 participants (41.

Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension.

Background: Despite endothelial dysfunction being an initial step in the development of hypertension and associated cardiovascular/renal injuries, effective therapeutic strategies to prevent endothelial dysfunction are still lacking. GPR183 (G protein-coupled receptor 183), a recently identified G protein-coupled receptor for oxysterols and hydroxylated metabolites of cholesterol, has pleiotropic roles in lipid metabolism and immune responses. However, the role of GPR183 in the regulation of endothelial function remains unknown.

Utility of Chimeric Mice with Humanized Livers for Predicting Hepatic Organic Anion-Transporting Polypeptide 1B-Mediated Clinical Drug-Drug Interactions.

The influence of transporters on the pharmacokinetics of drugs is being increasingly recognized, and drug-drug interactions (DDIs) via modulation of transporters could lead to clinical adverse events. Organic anion-transporting polypeptide 1B (OATP1B) is a liver-specific uptake transporter in humans that can transport a broad range of substrates, including statins. It is a challenge to predict OATP1B-mediated DDIs using preclinical animal models because of species differences in substrate specificity and abundance levels of transporters.

Impact of Heat Treatment on the Mechanical Properties and Fracture Morphology of Ti555211 Alloy.

Heat treatment is important for optimizing the strength performance and improving the toughness of titanium alloys. In this study, we investigated the impact of three heat treatment methods (β-annealing, double annealing, and solid-solution and aging treatment) on the mechanical properties and fracture morphology of Ti555211 titanium alloy. The results show that after β-annealing treatment, the alloy retains a high strength, while showing almost no ductility, and no yield strength.

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

Increased vascular stiffness in children exposed in utero but not children exposed postnatally to emissions from a coal mine fire.

Background: Chronic, low-intensity air pollution exposure has been consistently associated with increased atherosclerosis in adults. However, there was limited research regarding the implications of acute, high-intensity air pollution exposure during childhood. We aimed to determine whether there were any associations between early-life exposure to such an episode and early-life vascular function changes.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention.

Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore.

Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: a randomized double-blind placebo-controlled clinical trial.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies.

Objectives: To explore the effects of spesolimab treatment in patients with HS.

BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension.

Background: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-β (transforming growth factor-β) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-β family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-βR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination.

Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: a bidirectional two-sample Mendelian randomization analysis.

Purpose: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis, whether a causal relationship exists, and provides some evidence of causality.

Methods: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS).

Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle.

Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously.

Human naïve pluripotent stem cells (hnPSCs) can generate integrated models of blastocysts termed blastoids upon switch to inductive medium. However, the underlying mechanisms remain obscure. Here we report that self-renewing hnPSCs spontaneously and efficiently give rise to blastoids upon three dimensional (3D) suspension culture.

SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19.

T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4 and CD8 T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

Introduction: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment.

Semi-mechanistic population pharmacokinetic/pharmacodynamic modeling of a elongation factor 2 inhibitor cabamiquine for prevention and cure of malaria.

Cabamiquine is a novel antimalarial agent that demonstrates the potential for chemoprevention and treatment of malaria. In this article, the dose-exposure-response relationship of cabamiquine was characterized using a population pharmacokinetic (PK)/pharmacodynamic (PD) model, incorporating the effects of cabamiquine on parasite dynamics at the liver and blood stages of malaria infection. Modeling was performed sequentially.

Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration.

Background: The importance of mitochondria in normal heart function are well recognized and recent studies have implicated changes in mitochondrial metabolism with some forms of heart disease. Previous studies demonstrated that knockdown of the mitochondrial ribosomal protein S5 (MRPS5) by small interfering RNA (siRNA) inhibits mitochondrial translation and thereby causes a mitonuclear protein imbalance. Therefore, we decided to examine the effects of MRPS5 loss and the role of these processes on cardiomyocyte proliferation.