Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

Coffee and tea consumption and the risk of head and neck cancer: An updated pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Introduction: The relations between coffee and tea consumption and head and neck cancer (HNC) incidence are unclear. With increasing global HNC burden, this study aims to examine the association between coffee, tea, and HNC.

Methods: A pooled analysis of 9548 HNC cases and 15,783 controls from 14 individual-level case-control studies was conducted from the International Head and Neck Cancer Epidemiology consortium.

Preclinical and Clinical Pharmacokinetics of JNJ-75220795, an siRNA Therapeutic Targeting PNPLA3, for Metabolic Dysfunction-Associated Steatohepatitis.

JNJ-75220795 or ARO-PNPLA3 is an investigational small interfering ribonucleic acid agent conjugated with N-acetyl-d-galactosamine that targets the PNPLA3 gene, currently being developed for metabolic dysfunction-associated steatohepatitis (MASH). This study evaluated the pharmacokinetics (PK) profile of single subcutaneous doses of JNJ-75220795 in preclinical species as well as in human subjects with homozygous or heterozygous PNPLA3 I148M mutation in two phase 1 studies-a first-in-human study in the United States and a first-in-Japanese study in Japan. Preclinical PK in rats and non-human primates (NHP) showed a rapid systemic absorption and elimination following single subcutaneous doses.

A multi-domain computational framework investigating the short- and long-term viability of bioabsorbable magnesium fixation for tibial fractures.

This study presents a multi-domain computational framework to investigate the long-term performance of permanent and bioabsorbable magnesium fixation devices in orthopaedic fracture applications. The framework integrates a coupled model for bone fracture healing and remodeling, with an enhanced surface-based corrosion model to predict the performance of bioabsorbable magnesium devices. It was found that plated fracture fixation enabled fracture healing outcomes compare to non-plated models by facilitating direct fracture healing.

EpiFusion: Joint inference of the effective reproduction number by integrating phylodynamic and epidemiological modelling with particle filtering.

Accurately estimating the effective reproduction number (Rt) of a circulating pathogen is a fundamental challenge in the study of infectious disease. The fields of epidemiology and pathogen phylodynamics both share this goal, but to date, methodologies and data employed by each remain largely distinct. Here we present EpiFusion: a joint approach that can be used to harness the complementary strengths of each field to improve estimation of outbreak dynamics for large and poorly sampled epidemics, such as arboviral or respiratory virus outbreaks, and validate it for retrospective analysis.