Exploring the conformational space of ROS1 kinase domain and the impact of allosteric mutations.

Chromosomal rearrangements are common oncogenic events in Non-Small Cell Lung Cancer. An example is the fusion of the ROS1 kinase domain with extracellular receptors. Although the fusion leads to a target that is druggable with multi-kinase inhibitors, several reports indicate the emergence of point mutations leading to drug resistance.

Sexual dimorphism in pathogenic variant-harbouring individuals.

Background: Individuals harbouring pathogenic variants are at risk for aneurysms/dissections throughout the arterial tree. Based on prior reports of sex differences in thoracic aortic aneurysm/dissection, we investigated the sexual dimorphism for vascular events in variant-harbouring patients.

Methods: We analysed two large pedigrees comprising 84 individuals segregating pathogenic missense variants affecting the same p.

Artificial Intelligence-Enhanced Electrocardiography for Prediction of Incident Hypertension.

Importance: Hypertension underpins significant global morbidity and mortality. Early lifestyle intervention and treatment are effective in reducing adverse outcomes. Artificial intelligence-enhanced electrocardiography (AI-ECG) has been shown to identify a broad spectrum of subclinical disease and may be useful for predicting incident hypertension.

Transcriptomic analysis of + non-small cell lung cancer reveals an upregulation of nucleotide synthesis and cell adhesion pathways.

Introduction: The transcriptomic characteristics of + non-small cell lung cancer (NSCLC) represent a crucial aspect of its tumor biology. These features provide valuable insights into key dysregulated pathways, potentially leading to the discovery of novel targetable alterations or biomarkers.

Methods: From The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, all available + (n = 10), + (n = 5) and + (n = 5) NSCLC tumor and + cell line (n = 7) RNA-sequencing files were collected.

Cataract surgical training: Analysis of the results of the European Board of Ophthalmology survey in the Swiss cohort.

Introduction: This study, part of a series, analyses the Swiss cohort from an EBO survey on cataract surgery training in Europe, focusing on Switzerland's unique program. The survey identifies two models: training all residents in surgery, and a "high-volume surgeon" model where only some learn CS post-residency.

Methods: This study analyses the survey results of Swiss participants in the EBO examinations (2018-2022) and compared them with the most important cohorts (Germany, France and Spain).

Wound Healing in External Rhinoplasty-The Effect of Fibrin Glue on Dead Space Closure: A Retrospective Propensity Score-Matched Study.

Introduction: The presence of "dead space" in external rhinoplasty creates a welcoming environment for erratic soft tissue contraction. Poor redraping of the skin over the underlying osseocartilaginous framework at the end of the surgery may result in its creation. If surgeons can control and reliably predict skin contraction and wound healing, septorhinoplasty results would undoubtedly improve.

Exercise into Pain in Chronic Rotator Cuff-Related Shoulder Pain: A Randomized Controlled Trial with 6-Month Follow-Up.

Purpose: Exercise therapy is the first-line treatment in rotator cuff-related shoulder pain (RCRSP), and diverse types of exercise seem effective. However, it is not still clear if painful exercise should be allowed or avoided during exercises. The objective of this study was to investigate if exercise into pain is more effective than no pain in RCRSP.

Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients.

Background: Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.

Methods: COPERNIC is an international, multicenter clinical trial.

A Case-Control Study Supports Genetic Contribution of the Gene Family in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease.

The paraoxonase () gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare variants on both conditions was investigated. A total of 507 healthy weight individuals and 744 patients with obesity including 433 with histological liver assessment, were sequenced with single-molecule molecular inversion probes (smMIPs), allowing the identification of genetic contributions to obesity and MASLD-related liver features.

Clinicopathological and molecular differences between stage IV screen-detected and interval colorectal cancers in the Flemish screening program.

Introduction: Interval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC.

Simultaneous detection of eight cancer types using a multiplex droplet digital PCR assay.

DNA methylation biomarkers have emerged as promising tools for cancer detection. Common methylation patterns across tumor types allow multi-cancer detection. Droplet digital PCR (ddPCR) has gained considerable attention for methylation detection.

IMPRESS: Improved methylation profiling using restriction enzymes and smMIP sequencing, combined with a new biomarker panel, creating a multi-cancer detection assay.

Background: Despite the worldwide progress in cancer diagnostics, more sensitive diagnostic biomarkers are needed. The methylome has been extensively investigated in the last decades, but a low-cost, bisulfite-free detection method for multiplex analysis is still lacking.

Methods: We developed a methylation detection technique called IMPRESS, which combines methylation-sensitive restriction enzymes and single-molecule Molecular Inversion Probes.

Generation of four distinct isogenic cell lines with truncating variants in I-band or A-band titin.

Truncating variants in TTN (TTNtv) are present in 15-25 % of patients with idiopathic dilated cardiomyopathy. Interestingly, the pathogenicity of TTNtv seems to be linked to their location within the gene. More proximal I-band TTNtv (TTNtvI) harbour less pathogenic potential than distant A-band TTNtv (TTNtvA).

Cognitive deficits in human ApoE4 knock-in mice: A systematic review and meta-analysis.

Apolipoprotein-E4 (ApoE4) is an important genetic risk factor for Alzheimer's disease. The development of targeted-replacement human ApoE knock-in mice facilitates research into mechanisms by which ApoE4 affects the brain. We performed meta-analyses and meta-regression analyses to examine differences in cognitive performance between ApoE4 and ApoE3 mice.