Analytical Validation and Performance of a Blood-Based P-tau217 Diagnostic Test for Alzheimer Disease.

Background: Blood-based biomarkers, especially P-tau217, have been gaining interest as diagnostic tools to measure Alzheimer disease (AD) pathology.

Methods: We developed a plasma P-tau217 chemiluminescent immunoassay using 4G10E2 and IBA493 as antibodies, a synthetic tau peptide as calibrator, and the Quanterix SP-X imager. Analytical validation performed in a College of American Pathologists-accredited CLIA laboratory involved multiple kit lots, operators, timepoints, and imagers.

Long-read epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.

AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, responses are typically short lived. Thus, there is an urgent need to develop more effective treatments.

Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers.

Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.

An Assessment of Open Fracture Management in Hospitals in Malawi Before and Immediately After Implementing Open Fracture Guidelines.

Background: Open fractures, a common consequence of road traffic collisions, are associated with a high risk of complications. The introduction of standard guidelines has been shown to improve patient care and reduce the risk of complications in several countries. In September 2021, the Malawi Orthopaedic Association/Arbeitsgemeinschaft für Osteosynthesefragen Alliance (MOA/AOA) guidelines and standards for open fracture management were introduced in Malawi.