Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Integrative Analysis of Histone Acetylation Regulated CYP4F12 in Esophageal Cancer Development.

Current therapeutic strategies for esophageal cancer (EC) patients have yielded limited improvements in survival rates. Recent research has highlighted the influence of drug metabolism enzymes on both drug response and EC development. Our study aims to identify specific drug metabolism enzymes regulated by histone acetylation and to elucidate its molecular and clinical features.

SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.

Background: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown.

Methods: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production.

Endoplasmic Reticulum Protein 72 Regulates Integrin Mac-1 Activity to Influence Neutrophil Recruitment.

Background: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement.

Simultaneous Comparisons of 25 Acute Migraine Medications Based on 10 Million Users' Self-Reported Records From a Smartphone Application.

Background And Objectives: Many acute treatment options exist for migraine. However, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking.

Methods: This is a retrospective analysis of 10,842,795 migraine attack records extracted from an e-diary smartphone application between June 30, 2014, and July 2, 2020.

USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart.

Background: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy.

Methods: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice.

Association of Neighborhood Deprivation With Thrombolysis and Thrombectomy for Acute Stroke in a Health System With Universal Access.

Background And Objectives: The association between socioeconomic status and acute ischemic stroke treatments remain uncertain, particularly in countries with universal health care systems. This study aimed to investigate the association between neighborhood-level material deprivation and the odds of receiving IV thrombolysis or thrombectomy for acute ischemic stroke within a single-payer, government-funded health care system.

Methods: We conducted a population-based cohort study using linked administrative data from Ontario, Canada.

An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern.

First-principles study on the structure and electronic properties of MCS (M = Sc, Ti, Y, Zr and Hf, = 1, 2).

Two-dimensional (2D) transition metal carbides/nitrides, known as MXenes, have attracted extensive attention due to their rich elemental composition and diverse surface chemistry. In this study, the crystal structure, electronic, mechanical, and electronic transport properties of MCS (M = Sc, Ti, Y, Zr, and Hf, = 1, 2) were investigated by density functional theory (DFT). Our results showed that the studied MCS except YCS are thermodynamically, dynamically, thermally, and mechanically stable.

Automatic screening of patients with atrial fibrillation from 24-h Holter recording using deep learning.

Aims: As the demand for atrial fibrillation (AF) screening increases, clinicians spend a significant amount of time identifying AF signals from massive amounts of data obtained during long-term dynamic electrocardiogram (ECG) monitoring. The identification of AF signals is subjective and depends on the experience of clinicians. However, experienced cardiologists are scarce.

The impact of rare protein coding genetic variation on adult cognitive function.

Compelling evidence suggests that human cognitive function is strongly influenced by genetics. Here, we conduct a large-scale exome study to examine whether rare protein-coding variants impact cognitive function in the adult population (n = 485,930). We identify eight genes (ADGRB2, KDM5B, GIGYF1, ANKRD12, SLC8A1, RC3H2, CACNA1A and BCAS3) that are associated with adult cognitive function through rare coding variants with large effects.

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations.

Association of Cardiovascular Health Score Trajectory With Incident Myocardial Infarction in Hypertensive Patients.

Background: The association between changes in cardiovascular health score (CHS) over time and myocardial infarction (MI) risk in hypertensive patients remains unclear.

Method: This was a prospective study comprising 17 374 hypertensive patients from the Kailuan study cohort who underwent 3 surveys and were identified to be free of MI, stroke, or cancer from 2006 to 2010. CHS consisted of 7 cardiovascular health metrics (plasma glucose, total cholesterol, blood pressure, smoking, body mass index, physical activity, salt intake), ranging from 0 (worst) to 13 (best) in the study.

Distinct mutational features across preinvasive and invasive subtypes identified through comprehensive profiling of surgically resected lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a heterogeneous disease. Our study aimed to understand the unique molecular features of preinvasive to invasive LUAD subtypes. We retrospectively analyzed the clinical, histopathological, and molecular data of 3,254 Chinese patients with preinvasive lesions (n = 252), minimally invasive adenocarcinomas (n = 479), and invasive LUAD (n = 2,523).

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic.

Remnant Cholesterol Variability and Incident Ischemic Stroke in the General Population.

Background: Studies have demonstrated that remnant cholesterol is correlated with the risk of ischemic stroke. However, it is unknown whether visit-to-visit variability in remnant cholesterol concentration affects ischemic stroke. We sought to examine the role of remnant cholesterol variability in the subsequent development of ischemic stroke in the general population.

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination.

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time.

Hourly Air Pollutants and Acute Coronary Syndrome Onset in 1.29 Million Patients.

Background: Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality from acute coronary syndrome (ACS); however, the associations of subdaily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated.

Methods: We conducted a time-stratified case-crossover study among 1 292 880 patients with ACS from 2239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM), coarse particulate matter (PM), nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO), and ozone (O) were collected.

Association of Chronic Liver Disease and Mortality in Patients With Aneurysmal Subarachnoid Hemorrhage.

Background And Purpose: Chronic liver disease (CLD) is a risk factor for increased morbidity and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between CLD and mortality remains unknown.

Methods: In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2009 and 2019.

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Objective: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes.

Methods: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.