Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

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.

Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by α-syn preformed fibrils (PFF).

Protocol for identifying metabolite biomarkers in patient uterine fluid for early ovarian cancer detection.

High mortality of ovarian cancer (OC) is primarily attributed to the lack of effective early detection methods. Uterine fluid, pooling molecules from neighboring ovaries, presents an organ-specific advantage over conventional blood samples. Here, we present a protocol for identifying metabolite biomarkers in uterine fluid for early OC detection.

Safety and Efficacy of Reteplase Versus Alteplase for Acute Ischemic Stroke: A Phase 2 Randomized Controlled Trial.

Background: Reteplase is a more affordable new-generation thrombolytic with a prolonged half-life. We aimed to determine the safety dose range of reteplase for patients with acute ischemic stroke within 4.5 hours of onset.

Assessing the Assisted Six-Minute Cycling Test as a Measure of Endurance in Non-Ambulatory Patients with Spinal Muscular Atrophy (SMA).

Assessing endurance in non-ambulatory individuals with Spinal Muscular Atrophy (SMA) has been challenging due to limited evaluation tools. The Assisted 6-Minute Cycling Test (A6MCT) is an upper limb ergometer assessment used in other neurologic disorders to measure endurance. To study the performance of the A6MCT in the non-ambulatory SMA population, prospective data was collected on 38 individuals with SMA (13 sitters; 25 non-sitters), aged 5 to 74 years (mean = 30.

Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect.

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP-SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM).

A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity.

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913).

Diagnostic Performance and Safety of a Novel Ferumoxytol-Enhanced Coronary Magnetic Resonance Angiography.

Background: Currently, noninvasive arteriography for the diagnosis of coronary artery disease is clinically limited to the computed tomography scanning, where patients have to be exposed to the radiation and risks associated with iodinated contrast. We aimed to investigate the diagnostic performance and safety of a novel ferumoxytol-enhanced coronary magnetic resonance angiography (CMRA) in patients with suspected coronary artery disease.

Methods: Thirty patients, 19 males, with a median age of 63 years old, and 17 with renal insufficiency, who were scheduled for invasive coronary angiography, were enrolled.

Improvement of Precision in Recombinant Adeno-Associated Virus Infectious Titer Assay with Droplet Digital PCR as an Endpoint Measurement.

Recombinant adeno-associated virus (rAAV) has been utilized successfully for gene delivery for treatment of a variety of human diseases. To sustain the growth of recombinant AAV gene therapy products, there is a critical need for the development of accurate and robust analytical methods. Fifty percent tissue culture infectious dose (TCID) assay is an cell-based method widely used to determine AAV infectivity, and this assay is historically viewed as a challenge due to its high variability.

Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis.

Background: Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown.

Purpose: To compare the effectiveness of drugs for EDS in OSA using network meta-analysis.

A Phase 1 Study of Oral Vitamin D in Boys and Young Men With X-Linked Adrenoleukodystrophy.

Background And Objectives: There are no therapies for preventing cerebral demyelination in X-linked adrenoleukodystrophy (ALD). Higher plasma vitamin D levels have been linked to lower risk of inflammatory brain lesions. We assessed the safety and pharmacokinetics of oral vitamin D dosing regimens in boys and young men with ALD.

RNA Sensing and Innate Immunity Constitutes a Barrier for Interspecies Chimerism.

Interspecies chimera formation with human pluripotent stem cells (PSCs) holds great promise to generate humanized animal models and provide donor organs for transplant. However, the approach is currently limited by low levels of human cells ultimately represented in chimeric embryos. Different strategies have been developed to improve chimerism by genetically editing donor human PSCs.

Integrated multimodality microscope for accurate and efficient target-guided cryo-lamellae preparation.

Cryo-electron tomography (cryo-ET) is a revolutionary technique for resolving the structure of subcellular organelles and macromolecular complexes in their cellular context. However, the application of the cryo-ET is hampered by the sample preparation step. Performing cryo-focused ion beam milling at an arbitrary position on the sample is inefficient, and the target of interest is not guaranteed to be preserved when thinning the cell from several micrometers to less than 300 nm thick.

Elevated Placental microRNA-155 Is a Biomarker of a Preeclamptic Subtype.

Background: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation.

Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear.

Methods: VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 () and mice with conditional endothelial deletion of after chronic hypoxia exposure.

The Novel Lysosomal Autophagy Inhibitor (ROC-325) Ameliorates Experimental Pulmonary Hypertension.

Background: Autophagy plays an important role in the pathogenesis of pulmonary hypertension (PH). ROC-325 is a novel small molecule lysosomal autophagy inhibitor that has more potent anticancer activity than the antimalarial drug hydroxychloroquine, the latter has been prevalently used to inhibit autophagy. Here, we sought to determine the therapeutic benefit and mechanism of action of ROC-325 in experimental PH models.