Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.

Objectives: The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration.

Phase I/II study of trifluridine/tipiracil plus XB2001 versus trifluridine/tipiracil in metastatic colorectal cancer.

Trifluridine/tipiracil-bevacizumab is a standard of care in metastatic colorectal cancer (mCRC) after chemotherapy failure. We aim to assess the addition of XB2001 (anti-IL-1 alpha monoclonal antibody) plus trifluridine/tipiracil-bevacizumab in mCRC refractory to standard chemotherapy. This multicenter, randomized, double blind, non-comparative Phase I-II study (ClinicalTrials.

Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French pharmacovigilance database.

Background: Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung diseases (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through Adverse Drug Reaction (ADR) reports to pharmacovigilance centres.

Clinical outcomes in patients in any phase of CML treated with ponatinib in France-Data from the TOPASE observational study.

The TOPASE study was set up to evaluate the outcomes of chronic myeloid leukaemia [CML] patients treated with ponatinib (PON) in a real-world setting in France. One hundred and twenty CML patients, 105 in chronic phase (CP), 8 in accelerated phase (AP) and 7 in blastic phase (BP) were included. Fifty-one (49%) of the CP-CML patients were in third line of treatment.

Influence of Defense Mechanisms on Sport Burnout: A Multiple Mediation Analysis Effects of Resilience, Stress and Recovery.

The aims of this study were: (a) to explore the relationships between adaptive defense mechanisms (ADMs), maladaptive defense mechanisms (MADMs), stress, recovery, resilience, and sport burnout; and (b) to examine resilience, stress, and recovery as mediators of the relationship between defense mechanisms and burnout. One hundred and seventy-five athletes ( = 20.30 years, = 3.

Valorization of the Invasive Blue Crabs () in the Mediterranean: Nutritional Value, Bioactive Compounds and Sustainable By-Products Utilization.

The blue crab (), originally from the western Atlantic Ocean, has recently spread to the Mediterranean and is now considered one of the one hundred most invasive species in that region. This opportunistic species, known for its adaptability to different temperatures and salinities, negatively impacts biodiversity and human activities such as fishing and tourism in the Mediterranean. However, the blue crab is gaining interest as a potential food resource due to its high nutritional value and delicate, sweet flavor.

Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing (WES) for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care.

Methods: Exome sequencing data and clinical characteristics from 132 patients with advanced or metastatic NSCLC were analyzed.

Longitudinal trajectories of intensity and direction of emotions among athletes in sports competitions: do defense mechanisms matter?

Objectives: This study explored whether several subgroups of athletes representing distinct trajectories of intensity and direction of pleasant and unpleasant emotions (anger, anxiety, dejection, excitement, and happiness) could be shown to exist within the latent growth analysis (LCGA). A secondary objective was to examine whether athletes belonging to distinct trajectories of intensity and direction of emotions reported distinct scores of adaptive defense mechanisms (ADM) and maladaptive defense mechanisms (MDM).

Design: A longitudinal four-wave measurement design was used in the present study.

Deep Learning Artificial Intelligence Predicts Homologous Recombination Deficiency and Platinum Response From Histologic Slides.

Purpose: Cancers with homologous recombination deficiency (HRD) can benefit from platinum salts and poly(ADP-ribose) polymerase inhibitors. Standard diagnostic tests for detecting HRD require molecular profiling, which is not universally available.

Methods: We trained DeepHRD, a deep learning platform for predicting HRD from hematoxylin and eosin (H&E)-stained histopathological slides, using primary breast (n = 1,008) and ovarian (n = 459) cancers from The Cancer Genome Atlas (TCGA).

HER2-Low Luminal Breast Carcinoma Is Not a Homogenous Clinicopathological and Molecular Entity.

Background: With the development of some new antibody-drug conjugates, the HER2 classification of breast carcinomas now includes the HER2-low (H2L) category: IHC 1+, 2+ non-amplified by ISH, and double-equivocal carcinomas, mostly luminal, expressing hormone receptors (HR+).

Methods: We analyzed mutational status and transcriptomic activities of three HER2 effector pathways: PI3K-AKT, MAPK, and JAK-STAT, in association with clinicopathologic features, in 62 H2L carcinomas compared to 43 HER2-positive and 20 HER2-negative carcinomas, all HR+.

Results: H2L carcinomas had significantly lower histoprognostic grades and mitotic and Ki67 proliferation indexes than HER2-positive carcinomas.

Machine learning evaluation of immune infiltrate through digital tumour score allows prediction of survival outcome in a pooled analysis of three international stage III colon cancer cohorts.

Background: T-cell immune infiltrates are robust prognostic variables in localised colon cancer. Evaluation of prognosis using artificial intelligence is an emerging field. We evaluated whether machine learning analysis improved prediction of patient outcome in comparison with analysis of T cell infiltrate only or in association with clinical variables.

Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.

Background And Objective: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa.

Rationale and design of the FRENch CoHort of myocardial Infarction Evaluation (FRENCHIE) study.

Background: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important.

Aims: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period.

Expectations, needs and mid-term outcomes in people accessing to secondary findings from ES: 1st French mixed study (FIND Study).

Generation and subsequently accessibility of secondary findings (SF) in diagnostic practice is a subject of debate around the world and particularly in Europe. The French FIND study has been set up to assess patient/parent expectations regarding SF from exome sequencing (ES) and to collect their real-life experience until 1 year after the delivery of results. 340 patients who had ES for undiagnosed developmental disorders were included in this multicenter mixed study (quantitative N = 340; qualitative N = 26).

Glycemic and lipid control in patients with diabetes at time of myocardial infarction.

Objective: Cardiovascular risk is increased in patients with diabetes. Little is known about glycemic and lipid control in patients with diabetes. We aimed to assess glycemic and lipid controls in patients with diabetes at time of their myocardial infarction.

Oral anticancer medicine interventions: A cross-sectional study in French community pharmacies.

Introduction: The increasing number of oral anticancer medicines (OAMs) dispensed in community pharmacies and the associated challenges (misuse, management of side effects) give the community pharmacist (CP) a major role in the pharmacotherapeutic management of cancer patients. In France, as a response to these challenges, cancer outpatients can schedule a meeting with their CP to ensure the safe and effective use of OAMs. The objectives of this study were to evaluate the perspectives of these interventions regarding their implementation and the opinion of French CPs.

Impact of breast surgical procedure on survival in BRCA mutated patients with invasive breast cancer: Mastectomy versus conservative treatment.

Introduction: Patients with BRCA1/2 mutations have a higher risk of developing breast cancer compared to the wild-type population. For patients with a BRCA mutation, there are no specific recommendations for surgical management. The aim of this study was therefore to retrospectively investigate overall survival (OS) and recurrence-free survival (RFS) of BRCA mutated patients with localized invasive breast cancer, by comparing conservative surgery versus mastectomy.