Ferroptosis plays a role in tumorigenesis by affecting lipid peroxidation and metabolic pathways; however, its prognostic or therapeutic relevance in pancreatic adenocarcinoma (PAAD) remains poorly understood. In this study, we developed a prognostic ferroptosis-related gene (FRG)-based risk model using cohorts of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), proposing plausible therapeutics. Differentially expressed FRGs between tumors from TCGA-PAAD and normal pancreatic tissues from Genotype-Tissue Expression were analyzed to construct a prognostic risk model using univariate and multivariate Cox regression and LASSO analyses. A model incorporating AURKA, CAV1, and PML gene expression effectively distinguished survival differences between high- and low-risk groups among TCGA-PAAD patients, with validation in two ICGC cohorts. The high-risk group was enriched in gene sets involving mTOR, MAPK, and E2F signaling. The immune and stromal cells infiltration score did not differ between the groups. Analysis of PRISM datasets using our risk model to classify pancreatic cell lines suggested the dasatinib's efficacy in the high-risk group, which was experimentally confirmed in four cell lines with a high- or low-risk signature. In conclusion, this study proposed a robust FRG-based prognostic model that may help stratify PAAD patients with poor prognoses and select potential therapeutic avenues.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695983 | PMC |
Am J Sports Med
January 2025
Department of Pharmacology and Biostatistics, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Background: Patellar instability is frequently encountered by orthopaedic surgeons. One of the major risk factors of this condition is underlying trochlear dysplasia (TD). Recent trends have indicated the use of multiple procedures to correct patellar instability under these conditions.
View Article and Find Full Text PDFHGG Adv
January 2025
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).
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January 2025
Cosmetics Europe, Brussels, Belgium.
Grouping of chemicals has been proposed as a strategy to speed up the screening and identification of potential substances of concern among the broad chemical universe under REACH. Such grouping is usually based on shared structural features and should only be used for the prioritization objectives. However, additional considerations (as well as structural similarity) are needed, e.
View Article and Find Full Text PDFEnviron Sci Pollut Res Int
January 2025
Department of Environmental Health Engineering, School of Public Health, Mazandaran University of Medical Sciences, Sari, Iran.
Climate change significantly impacts the risk of eutrophication and, consequently, chlorophyll-a (Chl-a) concentrations. Understanding the impact of water flows is a crucial first step in developing insights into future patterns of change and associated risks. In this study, the Statistical DownScaling Model (SDSM)-a widely used daily downscaling method-is implemented to produce downscaled local climate variables, which serve as input for simulating future hydro-climate conditions using a hydrological model.
View Article and Find Full Text PDFSci Rep
January 2025
State Key Laboratory of Geohazard Prevention and GeoEnvironment Protection, Chengdu University of Technology, Chengdu, 610059, Sichuan, China.
Pakistan's geographic location makes it an important land hub between Central Asia, Middle East-North Africa, and China. However, the railways, roads, farmland, riverways, and residential quarters in the Piedmont plains of Baluchistan province in northwestern Pakistan are under serious threat of flooding in the summer of 2022. The urgency and severity of climate change's impact on humanity are underscored by the significant threats posed to human life and property in Piedmont Plains environments through extreme flood events, which has garnered widespread concerns.
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