Hypomethylating agents for patients with VEXAS without myelodysplastic syndrome: Clinical outcome and longitudinal follow-up of vacuolization and UBA1 clonal dynamics.

VEXAS syndrome is a haemato-inflammatory disease caused by somatic UBA1 mutations and characterized by cytoplasmic vacuoles in myeloid and erythroid precursor cells. Although there is currently no standard treatment algorithm for VEXAS, patients are generally treated with anti-inflammatory therapies focused on symptom management, with only partial effectiveness. Hypomethylating agents (HMA) have shown promise in VEXAS patients with concomitant myelodysplastic syndrome (MDS), while the efficacy of HMA in VEXAS patients without MDS is largely unknown.

Sustainable Multi-Cycle Physical Recycling of Expanded Polystyrene Waste for Direct Ink Write 3D Printing and Casting: Analysis of Mechanical Properties.

This work investigates the sustainable reuse of expanded polystyrene (EPS) waste through a multi-cycle physical recycling process involving dissolution in acetone and subsequent manufacturing via Direct Ink Write (DIW) 3D printing and casting. Morphology and mechanical properties were evaluated as a function of the manufacturing technique and number of dissolution cycles. Morphological analysis revealed that casted specimens better replicated the target geometry, while voids in 3D-printed specimens aligned with the printing direction due to rapid solvent evaporation.

Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease.

Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (F) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans.

In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson's disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174).

Small-cohort GWAS discovery with AI over massive functional genomics knowledge graph.

Genome-wide association studies (GWASs) have identified tens of thousands of disease associated variants and provided critical insights into developing effective treatments. However, limited sample sizes have hindered the discovery of variants for uncommon and rare diseases. Here, we introduce KGWAS, a novel geometric deep learning method that leverages a massive functional knowledge graph across variants and genes to improve detection power in small-cohort GWASs significantly.