Assessment of NSCLC disease burden: A survival model-based meta-analysis study.

We present a meta-analytics approach to quantify NSCLC disease burden by integrative survival models. Aggregated survival data from public sources were used to parameterize the models for early as well as advanced NSCLC stages incorporating chemotherapies, targeted therapies, and immunotherapies. Overall survival (OS) was predicted in a heterogeneous patient cohort based on various stratifications and initial conditions.

Impact of Serotonin Transporter Absence on Brain Insulin Receptor Expression, Plasma Metabolome Changes, and ADHD-like Behavior in Mice fed a Western Diet.

The impaired function of the serotonin transporter (SERT) in humans has been linked to a higher risk of obesity and type 2 diabetes, especially as people age. Consuming a "Western diet" (WD), which is high in saturated fats, cholesterol, and sugars, can induce metabolic syndrome. Previous research indicated that mice carrying a targeted inactivation of the gene (knockout, KO) and fed a WD display significant metabolic disturbances and behaviors reminiscent of ADHD.

Optimization of the MACE endpoint composition to increase power in studies of lipid-lowering therapies-a model-based meta-analysis.

Aims: To develop a model-informed methodology for the optimization of the Major Adverse Cardiac Events (MACE) composite endpoint, based on a model-based meta-analysis across anti-hypercholesterolemia trials of statin and anti-PCSK9 drugs.

Methods And Results: Mixed-effects meta-regression modeling of stand-alone MACE outcomes was performed, with therapy type, population demographics, baseline and change over time in lipid biomarkers as predictors. Randomized clinical trials up to June 28, 2022, of either statins or anti-PCSK9 therapies were identified through a systematic review process in PubMed and ClinicalTrials.

Genotypes of the UCP1 gene polymorphisms and cardiometabolic diseases: A multifactorial study of association with disease probability.

Cardiometabolic diseases (CMDs) are complex disorders with a heterogenous phenotype, which are caused by multiple factors including genetic factors. Single nucleotide polymorphisms (SNPs) rs45539933 (p.Ala64Thr), rs10011540 (c.

Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis.

Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse events (AEs), which may be dependent on ICI dose. Applying a model-based meta-analysis to evaluate safety data from published clinical trials from 2005 to 2018, we analyzed the dose/exposure dependence of ICI treatment-related AE (trAE) and immune-mediated AE (imAE) rates. Unlike with PD-1 inhibitor monotherapy, CTLA-4 inhibitor monotherapy exhibited a dose/exposure dependence on most AE types evaluated.

PeTTSy: a computational tool for perturbation analysis of complex systems biology models.

Background: Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary.

Results: Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems).

A Generic Mechanism for Enhanced Cytokine Signaling via Cytokine-Neutralizing Antibodies.

Enhancement or inhibition of cytokine signaling and corresponding immune cells responses are critical factors in various disease treatments. Cytokine signaling may be inhibited by cytokine-neutralizing antibodies (CNAs), which prevents further activation of cytokine receptors. However, CNAs may result in enhanced-instead of inhibitory-cytokine signaling (an "agonistic effect") in various in vitro and in vivo experiments.