Comment on van Gemert et al. Child Abuse, Misdiagnosed by an Expertise Center-Part II-Misuse of Bayes' Theorem. 2023, , 843.

Recently, part I and part II of a series of three papers were published, namely the papers by Vlaming et al [...

Genome sequencing reveals the impact of non-canonical exon inclusions in rare genetic disease.

Introduction: Advancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging sequencing technologies are now being deployed in the clinical setting to address the remaining diagnostic gap.

Methods: We tested whether short-read genome sequencing could increase diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive clinical genetic testing.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.

Genetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using rare variant aggregation testing based on whole-exome sequencing data to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene-metabolite associations, many previously unreported. Complementary approaches (genetic, computational (in silico gene knockouts in whole-body models of human metabolism) and one experimental proof of principle) provided orthogonal evidence that studies of rare, damaging variants in the heterozygous state permit inferences concordant with those from inborn errors of metabolism.

Clinical characteristics and serological profiles of Lyme disease in children: a 15-year retrospective cohort study in Switzerland.

Background: Lyme disease (LD) is caused by and is the most common tickborne disease in the northern hemisphere. Although classical characteristics of LD are well-known, the diagnosis and treatment are often delayed. Laboratory diagnosis by serological testing is recommended for most LD manifestations.

Antiplatelet therapy is not associated with increased risk of complications after lumbar puncture.

Background: Lumbar puncture (LP) is a critical diagnostic procedure in the evaluation of neurological diseases. Although considered safe, complications such as post-dural puncture headache (PDPH), back pain, subdural hematoma or venous sinus thrombosis may still occur. Whether the use of antiplatelet therapy (APT) increases the risk of complications after LP, remains unclear.

Real-Time Neurophysiological and Subjective Indices of Cognitive Engagement in High-Speed Flight.

Introduction: Managing cognitive demand is critical for aviation safety. Yet, accurately assessing pilot workload during complex flight maneuvers remains challenging. This study evaluated an integrated methodology combining real-time cognitive engagement indicators to provide a comprehensive assessment and assess the reliability of physiological and subjective measures for monitoring operator state.

Effects of a Digital Intervention to Improve DASH and Blood Pressure Among US Adults.

Background: Dietary Approaches to Stop Hypertension (DASH) is a recommended first-line treatment for adults with hypertension, yet adherence to DASH is low.

Purpose: To evaluate the efficacy of a digital health intervention (DHI), compared with attention control, on changes in DASH adherence and blood pressure among adults with hypertension.

Methods: Nourish was a 12-month, parallel, 2-arm, randomized controlled trial of a virtually delivered DHI.

Examining the potential of an internet-based emotion regulation intervention added to acute psychiatric inpatient care: results from a randomized controlled pilot trial.

The feasibility and the preliminary effectiveness of an internet-based emotion regulation intervention added to acute psychiatric inpatient care were assessed with a randomized controlled pilot trial. Sixty patients were allocated in a 1:1 ratio to the intervention group or treatment as usual (TAU). Feasibility was evaluated via patient satisfaction, system usability, and program usage.

Thermoresponsive gel embedding extracellular vesicles from adipose stromal cells improves the healing of colonic anastomoses following irradiation in rats.

Anastomotic leak occurrence is a severe complication after colorectal surgery. Considering the difficulty of treating these leaks and their impact on patient care, there is a strong need for an efficient prevention strategy. We evaluated a combination of extracellular vesicles (EVs) from rat adipose-derived stromal cells with a thermoresponsive gel, Pluronic® F127 (PF-127) to prevent anastomotic leaks.

Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer.

The canonical model of tumor suppressor gene (TSG)-mediated oncogenesis posits that loss of both alleles is necessary for inactivation. Here, through allele-specific analysis of sequencing data from 48,179 cancer patients, we define the prevalence, selective pressure for, and functional consequences of biallelic inactivation across TSGs. TSGs largely assort into distinct classes associated with either pan-cancer (Class 1) or lineage-specific (Class 2) patterns of selection for biallelic loss, although some TSGs are predominantly monoallelically inactivated (Class 3/4).

ATAC and SAGA histone acetyltransferase modules facilitate transcription factor binding to nucleosomes independent of their acetylation activity.

Transcription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recruit transcription coactivators to open chromatin and enable binding of general transcription factors and RNA polymerase II to promoters. Two key human transcriptional coactivator complexes, ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5 acetyltransferase), containing histone acetyltransferase (HAT) activity, target genomic loci to increase promoter accessibility. To better understand the function of ATAC and SAGA HAT complexes, we used in vitro biochemical and biophysical assays to characterize human ATAC and SAGA HAT module interactions with nucleosomes and how a transcription factor (TF) coordinates these interactions.

Applying a polysaccharide lyase from to disrupt alginate exopolysaccharide produced by clinical isolates.

Unlabelled: is considered one of the most challenging, drug-resistant, opportunistic pathogens partly due to its ability to synthesize robust biofilms. Biofilm is a mixture of extracellular polymeric substances (EPS) that encapsulates microbial cells, leading to immune evasion, antibiotic resistance, and thus higher risk of infection. In the cystic fibrosis lung environment, undergoes a mucoid transition, defined by overproduction of the exopolysaccharide alginate.

Clinical results of autologous fat transfer for basal thumb arthritis with a minimum of three years' follow-up.

Aims: In the treatment of basal thumb osteoarthritis (OA), intra-articular autologous fat transplantation has become of great interest within recent years as a minimally invasive and effective alternative to surgical intervention with regard to pain reduction. This study aims to assess its long-term effectiveness.

Methods: Patients diagnosed with stage one to three OA received a single intra-articular autologous fat transplantation.

Arthroscopic Autologous Minced Cartilage Implantation of Cartilage Defects in the Knee: A 2-Year Follow-up of 62 Patients.

Background: Symptomatic cartilage defects of the knee joint are frequently diagnosed and can be treated with different available surgical methods. Nevertheless, there is currently no gold standard treatment for all indications. Minced cartilage implantation is increasingly coming into focus as a refined surgical technique.

Age- and sex-specific reference percentile curves for accelerometry-measured physical activity in healthy European children and adolescents.

Unlabelled: Physical activity measured by accelerometry (PA-accelerometry) is used as an indicator of physical capacity in chronic diseases. Currently, only fragmented age ranges of reference percentile curves are available for European children and adolescents. This study aimed to provide age- and sex-specific percentiles for physical activity measured by hip-worn accelerometry derived throughout the full age range of European children and adolescents.

Differences in Ancestry and Presence of Gastric Precursor Lesions in Individuals With Young- and Average-Onset Gastric Cancer.

Background: There has been a paradoxical rise in young-onset gastric cancer (YOGC), defined as gastric cancer (GC) diagnosed before age 50. Precursor lesions may contribute to pathogenesis, though their role in progression to different histologic subtypes is unclear. The impact of self-reported race is also poorly characterized and may be unreliable as a proxy for genetic differences.

Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis: The Phase IIIb ENSEMBLE 4-Year, Single-Arm, Open-Label Trial.

Background And Objectives: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS).

Association between education level and access to disease-modifying treatment in patients with multiple sclerosis in France.

Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS).

Objective: This study aimed to analyze the association between education level and DMT use in France.

Methods: All patients from OFSEP network with MS onset over 1996-2014 and aged ⩾ 25 years at onset were included.