Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention.

Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members.

Longitudinal evolution of the transdiagnostic prodrome to severe mental disorders: a dynamic temporal network analysis informed by natural language processing and electronic health records.

Modelling the prodrome to severe mental disorders (SMD), including unipolar mood disorders (UMD), bipolar mood disorders (BMD) and psychotic disorders (PSY), should consider both the evolution and interactions of symptoms and substance use (prodromal features) over time. Temporal network analysis can detect causal dependence between and within prodromal features by representing prodromal features as nodes, with their connections (edges) indicating the likelihood of one feature preceding the other. In SMD, node centrality could reveal insights into important prodromal features and potential intervention targets.

Increased Levels of Anti- Antibodies During Hospital Admission in Septic Patients.

Background/objectives: In a previous study, we described elevated anti- IgG levels in septic patients in relation to disease severity. In this study, our objective was to analyze the evolution of anti- immunoglobulins in septic patients during hospital admission and their association with αβ and γδ T cell subsets.

Methods: We recruited 80 subjects: 40 patients with sepsis and 40 controls.

Tranexamic acid for postpartum bleeding: a systematic review and individual patient data meta-analysis of randomised controlled trials.

Background: Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth.

Methods: In this systematic review and IPD meta-analysis, we searched the WHO International Clinical Trials Registry Platform from database inception to Aug 4, 2024 for randomised trials that assessed the effects of tranexamic acid in women giving birth.

Herpes Simplex Virus type 1 inhibits autophagy in glial cells but requires ATG5 for the success of viral replication.

Herpes Simplex Virus type 1 (HSV-1) 1 is a neurotropic virus that has been associated with neurodegenerative disorders. The dysregulation of autophagy by HSV-1 has been proposed as a potential cause of neurodegeneration. While studies have extensively tackled the interaction between autophagy and HSV-1 in neurons, research in glial cells is currently limited.