Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

Understanding the Prevalence of Medial Arterial Calcification Among Complex Reconstructive Patients: Insights from a Decade of Experience at a Tertiary Limb Salvage Center.

: Medial arterial calcification (MAC), a distinct form of vascular pathology frequently coexisting with peripheral arterial disease (PAD), poses unique challenges in limb salvage among patients with diabetes, chronic kidney disease, and end-stage renal disease. This study examines the incidence of MAC and its impact on limb salvage outcomes over a decade of experience at a tertiary limb salvage center. : A retrospective review of all complex lower extremity (LE) reconstructions using local flap (LF) or free tissue transfer (FTT), performed from July 2011 to September 2022, was conducted.

Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia.

Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.

Qualitative and Quantitative Analysis of Tire Wear Particles (TWPs) in Road Dust Using a Novel Mode of Operation of TGA-GC/MS.

Detecting and quantifying tire wear particles (TWPs) in the environment pose a unique environmental challenge due to their chemical complexity. There are emerging concerns around TWPs due to their potential high numbers of particles released, outnumbering microplastics, as well as the leaching of toxic additives such as 6-PPD which has been linked to the death of salmon even when present at very low levels (<0.1 μg/L).

The CD123 antibody-drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia.

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models ( = 39).