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.

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.

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.

Aortic valve replacement vs. conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial.

Background And Aims: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, ClinicalTrials.gov).

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.

Postpartum Oxytocin Treatment via the Mother Reprograms Long-Term Behavioral Disorders Induced by Early Life Stress on the Plasma and Brain Metabolome in the Rat.

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the "metabolic syndrome". We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conducted in the plasma and frontal cortex.

Rational design of a genomically humanized mouse model for dominantly inherited hearing loss, DFNA9.

DFNA9 is a dominantly inherited form of adult-onset progressive hearing impairment caused by mutations in the COCH gene. COCH encodes cochlin, a crucial extracellular matrix protein. We established a genomically humanized mouse model for the Dutch/Belgian c.

Singlet oxygen-based photoelectrochemical detection of single-point mutations in the KRAS oncogene.

Single nucleotide point mutations in the KRAS oncogene occur frequently in human cancers, rendering them intriguing targets for diagnosis, early detection and personalized treatment. Current detection methods are based on polymerase chain reaction, sometimes combined with next-generation sequencing, which can be expensive, complex and have limited availability. Here, we propose a novel singlet oxygen (O)-based photoelectrochemical detection methodology for single-point mutations, using KRAS mutations as a case study.

The effects of summarization and factual retrieval practice on text comprehension and text retention in elementary education.

When reading a text in school, the goal is both text comprehension and text retention. We examined the effects of the learning strategies summarization and factual retrieval practice on third- and fourth-grade pupils' text comprehension and retention of factual knowledge from a text, using restudy as a control condition. The experiment was conducted in an authentic classroom setting, with teachers executing the experiment using original course materials.

Widely Split P Waves After Pharmacologic Cardioversion in a Patient With Atrial Fibrillation.

We report a case of a clinically asymptomatic patient with extreme P-wave separation on the electrocardiogram mimicking atrial tachycardia with atrioventricular block. The accurate examination of the patient, analysis of the electrocardiogram, and echocardiographic findings led to proper diagnosis, management, and treatment. ().

The Quest for Circulating Biomarkers in Neuroendocrine Neoplasms: a Clinical Perspective.

Given the considerable heterogeneity in neuroendocrine neoplasms (NENs), it appears unlikely that a sole biomarker exists capable of fully capturing all useful clinical aspects of these tumors. This is reflected in the abundant number of biomarkers presently available for the diagnosis, prognosis, and monitoring of NEN patients. Although assessment of immunohistochemical and radiological markers remains paramount and often obligatory, there has been a notable surge of interest in circulating biomarkers over the years given the numerous benefits associated with liquid biopsies.

Combined Cardiac Damage Staging by Echocardiography and Cardiac Catheterization in Patients With Clinically Significant Aortic Stenosis.

Background: Cardiac damage (CD) staging enhances risk stratification in patients with clinically significant aortic stenosis (AS). We aimed to assess the prognostic value and reclassification rate of right heart catheterization (RHC) compared with transthoracic echocardiography (TTE) in characterising CD staging at 3-year follow-up in patients with clinically significant AS, to identify patients that would benefit from RHC for prognostic stratification, and to test the prognostic value of combined CD staging.

Methods: An observational cohort study of 432 AS patients undergoing TTE and RHC were divided into moderate or asymptomatic severe (m/asAS) and symptomatic severe (ssAS) AS.

Association of Mild-to-Moderate Aortic Regurgitation With Outcomes in Heart Failure With Preserved Ejection Fraction.

Objective: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF).

Methods: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded.

Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs.

Background: Biomarker discovery in colorectal cancer has mostly focused on methylation patterns in normal and colorectal tumor tissue, but adenomas remain understudied. Therefore, we performed the first epigenome-wide study to profile methylation of all three tissue types combined and to identify discriminatory biomarkers.

Results: Public methylation array data (Illumina EPIC and 450K) were collected from a total of 1 892 colorectal samples.

New Developments in Treating RAS-Mutated Metastatic Colorectal Cancer.

One of the great challenges in digestive oncology is choosing the optimal therapy for RAS-mutated metastatic colorectal cancer (mCRC). Even though the RAS genes and accompanying pathway were identified decades ago and extensive knowledge exists on their role in carcinogenesis, it has proven challenging to translate these insights into new therapies and clinical benefit for patients. However, recently, new drugs targeting this pathway (for example, KRAS inhibitors) have shown promising results in clinical trials, as monotherapy or in combination regimens.