Prevalence of germline pathogenic variants in 779 patients with metastatic prostate cancer.

Objective: To assess the prevalence of germline pathogenic variants (gPVs) in genes associated with female breast cancer in Dutch patients with metastatic prostate cancer (mPCa).

Patients And Methods: In this prospective multicentre cohort study (n = 15 centres), germline genetic testing of the genes BRCA1, BRCA2, ATM, CHEK2 and PALB2 was offered to patients with mPCa. We assessed the prevalence of gPVs and compared it to a reference population of 16 823 individuals who underwent genetic testing for non-oncological conditions.

Novel BEST1 Variant Characterization in a Large French Cohort in Light of Updated Bestrophin-1 Structure-Function Correlation.

Purpose: To update knowledge on bestrophin-1 structure and function with the aim of assessing the pathogenicity of variants reported in the Leiden Open Variation Database (LOVD) and in a large French cohort of bestrophinopathies.

Methods: All unique variants reported in the latest version (October 2024) of the BEST1-LOVD database were uploaded and curated. We described all BEST1 variants identified in French patients analyzed at Lille University Hospital, between 2008 and 2024.

Migraine stigma and general knowledge of migraine: A cross-sectional European survey.

BackgroundThe stigma associated with migraine impacts patients' quality of life, mental health and their willingness to seek treatment. The present study aimed to gain insights into the stigma from the patient's perspective and to assess migraine knowledge among people without the condition.MethodsThis cross-sectional descriptive, quantitative study used two surveys (survey 1, open April 2023 to July 2023; survey 2, September 2023 to November 2023).

Associations between genetic predisposition to mental health problems and academic achievement: a developmental perspective using two population-based cohorts.

Background: Children's cognitive abilities play an important role throughout their academic career, but recent studies highlight the negative impacts of aggression, inattention, and impulsivity on academic success. These behaviors and traits are central to most externalizing (EXT) and neurodevelopmental (NDD) problems, which are substantially genetically influenced. We examined the mechanisms by which high levels of genetic predispositions to EXT and NDD problems associate with elevated mental health symptoms and subsequently lead to lower levels of academic achievement in two developmental periods (i.

Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study.

Systemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity.

Anti-thrombotic therapy in patients with cancer at the end of life and associated clinical outcomes: A cohort study using population-linked routinely collected data.

Anti-thrombotic therapy (ATT) in cancer patients approaching the end of life presents significant clinical challenges, balancing thrombotic and bleeding risks. This study analysed ATT prescribing patterns and associated outcomes in patients diagnosed with poor prognosis cancer, defined as cancer diagnoses associated with a 1-year life expectancy, using the Welsh national Secure Anonymised Information Linkage Databank. Retrospective cohort study of adults in Wales diagnosed with poor prognosis cancer between 2013 and 2021, following up patients from cancer diagnosis until death, end of follow-up or study end (31 December 2021).

Interstitial lung disease epidemiology and etiology in patients with solid malignant tumors: a systematic literature review.

Background: Interstitial lung disease (ILD) can occur in patients with cancer. ILD can be caused by anti-cancer treatments (drug-induced [DI] ILD), but also by opportunistic infection, and non-drug-related etiologies. This systematic literature review (SLR) investigated the epidemiology and etiology of non-DI ILD and DI ILD management and outcomes in patients with solid cancers.

Identifying resolution of clinically suspect arthralgia: a step towards understanding spontaneous reversal of an at-risk stage of rheumatoid arthritis.

Objective: Symptoms in the at-risk stage of clinically suspect arthralgia (CSA) can progress to Rheumatoid Arthritis (RA) or disappear spontaneously. The area of reversal of an at-risk stage is yet unexplored. Therefore, we aimed to determine its definition by evaluating patient-reported and rheumatologist-reported measures, and examine characteristics at baseline and over time of at-risk individuals with reversal.

Evidence-based implementation of lifestyle medicine in healthcare practice: a research agenda.

In recent years, significant insights have been gathered into the effectiveness of lifestyle interventions in the treatment of chronic non-communicable diseases (NCD). To speed up the implementation of evidence-based lifestyle medicine, we developed a research agenda in collaboration with Dutch experts in treating NCD, using a hybrid Delphi approach. The research agenda focuses on four key themes: (1) promoting sustainable behavioural change at patient, healthcare professional and organisational levels; (2) optimising research designs, methodology and outcomes for the evaluation of effectiveness and implementation of lifestyle medicine modalities in healthcare practice; (3) elucidating biological mechanisms underlying successful lifestyle interventions and (4) advancing data infrastructure to ensure accessible data for citizens, healthcare professionals, researchers and health insurers for monitoring and evaluation of health and lifestyle outcomes.

Metabolome informs about the chemical exposome and links to brain health.

The metabolome is an intermediate phenotype, summarizing the profile of all small molecules (<1.5 kDa) in biospecimens. The metabolome provides a readout for the net influence of the chemical exposome, diet, gut microbiome, and genome on human health.

SMAD3 and p300 complex scaffolding by long non-coding RNA LIMD1-AS1 promotes TGF-β-induced breast cancer cell plasticity.

Transforming growth factor (TGF)-β signaling enhances cancer cell plasticity by inducing epithelial-to-mesenchymal transition (EMT). Here, we identified a TGF-β-induced long non-coding RNA, LIMD1 Antisense RNA 1 (LIMD1-AS1) that strengthens the SMAD-mediated transcriptional response to TGF-β. LIMD1-AS1 expression is upregulated in breast cancer tissues compared to normal breast tissues, and high LIMD1-AS1 expression is associated with poor prognosis in breast cancer patients.

PyVADesign: a Python-based cloning tool for one-step generation of large mutant libraries.

Motivation: The generation and analysis of diverse mutants of a protein is a powerful tool for understanding protein function. However, generating such mutants can be time-consuming, while the commercial option of buying a series of mutant plasmids can be expensive. In contrast, the insertion of a synthesized double stranded DNA (dsDNA) fragment into a plasmid is a fast and low-cost method to generate a large library of mutants with one or more point mutations, insertions, or deletions.

Competing risks models with two time scales.

Competing risks models can involve more than one time scale. A relevant example is the study of mortality after a cancer diagnosis, where time since diagnosis but also age may jointly determine the hazards of death due to different causes. Multiple time scales have rarely been explored in the context of competing events.

Preoperative Staging in Oral Cavity Cancer: Nationwide Practice and Concordance With Pathology.

Objectives: The clarity of TNM-classification for oral cancer has a direct impact on healthcare resource allocation, treatment decisions, morbidity, and clinical outcomes. However, possible TNM ambiguity between hospitals exists due to the broad range of available diagnostics. Therefore, this study aims to assess current practice variation in preoperative staging for oral cavity cancer.

A Systematic Review of Modelling Approaches in Economic Evaluations of Treatments for Inherited Bleeding Disorders.

Objective: The aim of this review is to identify and assess modelling approaches in published model-based economic evaluations of treatments for individuals with inherited bleeding disorders.

Methods: A literature search was performed on seven electronic databases, from database inception until 30 May, 2024. Inclusion criteria were cost-effectiveness or cost-utility analyses using decision-analytic models.

Heart failure in patients with recently diagnosed atrial fibrillation: findings from the GLORIA-AF Registry Phase III.

Aims: Congestive heart failure (CHF) is often coexisting in patients with atrial fibrillation (AF), but the clinical epidemiology of this association is still uncertain. We aimed to analyse characteristics, management, and outcomes of patients with and without CHF, in a real-world cohort of patients with AF.

Methods And Results: From the GLORIA-AF Registry Phase III, which enrolled adults with a recent diagnosis of AF and a CHA2DS2-VASc ≥ 1, we analysed factors associated with CHF at baseline, the association of CHF with use of oral anticoagulants (OAC) and other treatments, and the risk of adverse outcomes during a 3-year follow-up.

Grade 2 central chondrosarcoma treated by intralesional curettage: observation or surgery? : a multicentre retrospective study.

Aims: The most appropriate management of patients who have undergone curettage for a suspected low-grade chondrosarcoma (CS), which has subsequently been found to be of grade 2, remains unknown. We aimed to assess whether these patients have an increased risk of local recurrence and distant metastasis if followed up over time, compared to those who undergo further treatment soon after the diagnosis has been established.

Methods: A retrospective study was undertaken which included 71 patients treated between January 2010 and December 2022 by intralesional curettage for a supposed low-grade CS, but who subsequently proved to have a histological grade 2 CS.

Protocol of a randomized controlled multicenter trial investigating process and effectiveness of a participatory organizational approach for preventing work-related mental health problems among employees: vital@work.

Background: Evidence links psychosocial work factors to work-related mental health problems, which affect productivity and highlight the need for workplace interventions. In order to establish sustainable change, a participatory strategy that considers the behavioral, organizational, and contextual (BOC) determinants when selecting and implementing interventions is needed. The objective of the current study, Vital@Work, is to prevent and reduce work-related mental health problems by using an evidence based Participatory Approach (PA) as strategy to compose a set of intervention activities tailored to BOC determinants.

Ex vivo 3D micro-tumour testing platform for predicting clinical response to platinum-based therapy in patients with high-grade serous ovarian cancer.

Around 20% of patients with primary high-grade ovarian cancer do not respond to chemotherapy, but predictive biomarkers are lacking. The purpose of the current study is to establish and clinically validate an ex vivo 3D micro-tumour testing platform that predicts patient-specific response to standard of care chemotherapy. 104 ovarian cancer patients with malignant ascites were included in the study.

High-throughput competitive binding assay for targeting RNA tertiary structures with small molecules: application to pseudoknots and G-quadruplexes.

There is an indisputable need for new screening methodologies to identify small molecules that target RNA tertiary structures, such as pseudoknots or G-quadruplexes. Here, we present a high-throughput competitive binding antisense assay designed to identify ligands for complex RNA tertiary structures. In this assay, initially customized for the bacterial PreQ1-I riboswitch pseudoknot, ligands compete with a rationally designed quencher-labelled antisense oligonucleotide for binding to a fluorophore-labelled riboswitch.

Right Ventricular Apical Pacing in Patients With Preserved LVEF: Adverse Effects and Mechanisms.

Background: Long-term adverse cardiac effects of right ventricular (RV) pacing in patients with normal left ventricular (LV) ejection fraction (EF) are not well studied.

Objectives: The purpose of this study was to evaluate adverse effects of RV apical pacing in patients with normal LVEF.

Methods: Medical records of patients who had undergone RV apical pacemaker implantation for pacing indications and had an LVEF ≥50% were reviewed to determine the effect of RV pacing burden on LV systolic and diastolic function, mechanical dyssynchrony, heart failure hospitalization (HFH), and all-cause mortality.