High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH.

Comparison of Plasma p-tau217 and [F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia.

Background And Objectives: To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments.

Methods: We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications.

Cardiac compressed sensing real-time cine for the assessment of left ventricular function: a large sample size analysis.

Background: Segmented cine imaging using a balanced steady-state free precession sequence is the gold standard for accurately quantifying cardiac function and myocardial mass. However, this method suffers from inefficient K-space sampling, resulting in long scan times, and requires multiple breath holds that can be difficult for some patients. Real-time compressed sensing (CS) cine reduces image acquisition time through K-space undersampling and iterative reconstruction, enabling rapid magnetic resonance (MR) imaging.

Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer.

Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener. It has been proposed that fructose promotes the growth of some tumours directly by serving as a fuel. Here we show that fructose supplementation enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer without causing weight gain or insulin resistance.

A yeast-based oral therapeutic delivers immune checkpoint inhibitors to reduce intestinal tumor burden.

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var.

Evaluation of a Tailored Patient Navigation Program for Improving Multitarget Stool DNA Test Adherence.

Background: Multitarget stool DNA (mt-sDNA) is an increasingly utilized noninvasive option for colorectal cancer screening; however, its impact is limited by imperfect test adherence. Tailored patient navigation (TPN) improves adherence for other cancer screening tests, but its role in mt-sDNA is not known.

Aim: Determine whether TPN improves mt-sDNA completion and reduces sample could not be processed (SCNBP) result rates.

All-Suture Anchor Techniques for Biceps Tenodesis Are Noninferior in End-Cycle Stiffness to an Interference Screw Technique; However, Secondary Outcomes, Such as Ultimate Failure Load, Yield Load, Creep, and Load-to-Failure Stiffness, Are Inferior in an Ovine Model.

Purpose: To assess the biomechanical performance of 2 simplified loop-and-tack biceps tenodesis techniques, all-suture anchor and all-suture anchor with a button, compared with the interference screw technique in an ovine model.

Methods: Twenty-one biceps tenodesis procedures were executed on the humeri and flexor digitorum profundus tendons of skeletally mature, female sheep. Limbs were evenly randomized into 2 experimental groups (all-suture anchor with or without button) and 1 control group (interference screw).

Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.

The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples.

Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance.

Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the tumor microenvironment (TME).

Enhancing transcription-replication conflict targets ecDNA-positive cancers.

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival. At present, there are no ecDNA-specific treatments.

Navigating the changing landscape of BTK-targeted therapies for B cell lymphomas and chronic lymphocytic leukaemia.

The B cell receptor (BCR) signalling pathway has an integral role in the pathogenesis of many B cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma, diffuse large B cell lymphoma and Waldenström macroglobulinaemia. Bruton tyrosine kinase (BTK) is a key node mediating signal transduction downstream of the BCR. The advent of BTK inhibitors has revolutionized the treatment landscape of B cell malignancies, with these agents often replacing highly intensive and toxic chemoimmunotherapy regimens as the standard of care.

Endovascular thrombectomy for childhood stroke (Save ChildS Pro): an international, multicentre, prospective registry study.

Background: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke.

Methods: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular thrombectomy plus best medical practice or best medical treatment alone.

Cigarette Smoking and Observed Growth of Unruptured Intracranial Aneurysms: A Systematic Literature Review and Meta-Analysis.

Background: Smoking and observed growth of intracranial aneurysms are known risk factors for rupture. The mechanism by which smoking increases this risk is not completely elucidated. Furthermore, an association between smoking and aneurysm growth has not been clearly defined in the literature.