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Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.
Science
January 2025
Center for Pulmonary Vascular Biology and Medicine, Pittsburgh, Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.
View Article and Find Full Text PDFEnhanced Antibiotic Release and Mechanical Strength in UHMWPE Antibiotic Blends: The Role of Submicron Gentamicin Sulfate Particles.
J Bone Joint Surg Am
January 2025
Harris Orthopaedics Laboratory, Massachusetts General Hospital, Boston, Massachusetts.
Background: Periprosthetic joint infections (PJIs) are a major complication of total joint replacement surgeries. This study investigated the enhancement of mechanical properties and antibiotic release in ultra-high molecular weight polyethylene (UHMWPE) through the encapsulation of submicron gentamicin sulfate (GS) particles, addressing the critical need for improved implant materials in orthopaedic surgery, particularly in managing PJIs.
Methods: The present study involved embedding submicron GS particles into UHMWPE flakes at concentrations of 2% to 10% by weight.
Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).
Br J Dermatol
January 2025
Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA.
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.
View Article and Find Full Text PDFIdentifying the Minimal Clinically Important Difference in Emotion Regulation Among Youth Using the JoyPop App: Survey Study.
JMIR Form Res
January 2025
Department of Psychology, Lakehead University, Thunder Bay, ON, Canada.
Background: The minimal clinically important difference (MCID) is an important threshold to consider when evaluating the meaningfulness of improvement following an intervention. The JoyPop app is an evidence-based smartphone app designed to improve resilience and emotion regulation. Information is needed regarding the JoyPop app's MCID among culturally diverse youth.
View Article and Find Full Text PDFIntegrating RNA-seq and scRNA-seq to explore the prognostic features and immune landscape of exosome-related genes in breast cancer metastasis.
Ann Med
December 2025
Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, PR China.
Objective: This study aims to explore the role of exosome-related genes in breast cancer (BRCA) metastasis by integrating RNA-seq and single-cell RNA-seq (scRNA-seq) data from BRCA samples and to develop a reliable prognostic model.
Methods: Initially, a comprehensive analysis was conducted on exosome-related genes from the BRCA cohort in The Cancer Genome Atlas (TCGA) database. Three prognostic genes (JUP, CAPZA1 and ARVCF) were identified through univariate Cox regression and Lasso-Cox regression analyses, and a metastasis-related risk score model was established based on these genes.
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