Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Antagonisation of Prokineticin Receptor-2 Attenuates Preeclampsia Symptoms.

Preeclampsia (PE) is the most threatening pathology of human pregnancy. Placenta from PE patients releases harmful factors that contribute to the exacerbation of the disease. Among these factors is the prokineticin1 (PROK1) and its receptor, PROKR2 that we identified as a mediators of PE.

The effect of sevelamer on serum calcification propensity in patients with chronic kidney disease: the results of a multicentre, double-blind, placebo-controlled, randomized clinical trial.

Background: The serum calcification propensity test (or T50 test) might become a standard tool for the assessment of vascular calcification risk and T50 might be a valuable biomarker in clinical trials of treatments intended to slow the progression of vascular calcification. Literature data suggest that non-calcium-containing phosphate binders can influence T50 in chronic dialysed patients. However, it is not clear whether similar interventions are effective in patients at earlier stages of chronic kidney disease (CKD).

PDE11A is a phenotype modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: results of a 334 patients' series.

Purpose: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing's syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal and morphological levels. ARMC5 inactivating pathogenic variants are causative of PBMAH and rare variants of PDE11A have been associated with PBMAH.

Methods: Leukocyte DNA of 354 PBMAH index cases was sequenced for ARMC5 and PDE11A genes by Next generation sequencing (NGS).

The effects of recent stressful life events on outcomes in individuals at clinical high risk for psychosis: results from the longitudinal EU-GEI high-risk study.

Background: Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.

Methods: The study used longitudinal data from the EU-GEI High Risk study.

CAR T-Cell Therapy for Rheumatic Diseases: What Does the Future Hold?

Chimeric antigen receptor (CAR) T-cell therapy, initially successful in treating hematological malignancies, is emerging as a potential treatment for autoimmune diseases, including rheumatic conditions. CAR T cells, engineered to target and eliminate autoreactive B cells, offer a novel approach to managing diseases like systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myopathies, where B cells play a pivotal role in disease pathology. Early case reports have demonstrated promising results, with patients achieving significant disease remission, normalization of serological markers, and the ability to discontinue traditional immunosuppressive therapies, which supported the initiation of several clinical trials.

Expression of Yes-associated protein in endothelial cells of human corneas before and after storage in organ culture.

The cornea, the anterior meniscus-shaped transparent and refractive structure of the eyeball, is the first mechanical barrier of the eye. Its functionality heavily relies on the health of its endothelium, its most posterior layer. The treatment of corneal endothelial cells (CECs) deficiency is allogeneic corneal graft using stored donor corneas.

Upregulation of haematopoetic cell kinase (Hck) activity by a secreted parasite effector protein (Ta9) drives proliferation of Theileria annulata-transformed leukocytes.

Reversible transformation of bovine leukocytes by the intracellular parasites Theileria annulata and Theileria parva is central to pathogenesis of the diseases they cause, tropical theileriosis and East Coast Fever, respectively. Parasite-dependent constitutive activation of major host transcription factors such as AP-1 (Activating Protein 1) and NF-κB (Nuclear Factor-Kappa B) sustains the transformed state. Although parasite interaction with host cell signaling pathways upstream of AP-1 have been studied, the precise contribution of Theileria encoded factors capable of modulating AP-1 transcriptional activity, and other infection-altered signaling pathways is not fully understood.

Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors.

Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.

Different disease activity trajectories in early axial spondyloarthritis lead to significantly different long-term outcomes: a trajectory-based analysis of the DESIR cohort over 10 years.

Introduction: The study aimed to identify and describe disease activity trajectories over 10 years in patients with recent-onset axial spondyloarthritis (axSpA) and determine their impact on long-term outcomes.

Methods: This prospective, multicentre study (Devenir des Spondylarthropathies Indifférenciées Récentes cohort, ClinicalTrials.gov NCT) followed patients with early axSpA for 10 years.

Emotional intelligence and the dark triad: a latent profile analysis to investigate the Jekyll and Hyde of the emotionally intelligent manager.

Managers sometimes have a bad reputation as they are often perceived as more manipulative than other employees. This study focuses on the Dark Triad (DT)-comprising psychopathy, Machiavellianism, and narcissism-and its connection with managers' "Ability" Emotional Intelligence (AEI). The link between DT (measured through the Dirty Dozen) and managers' AEI (measured through QEPro, an AEI performance test) was examined through a Latent Profile Analysis (LPA).

Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Knockout Mice.

Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of mutant phenotypes.

Nutritionally acquired immunodeficiency must be addressed with the same urgency as HIV to end tuberculosis.

Tuberculosis (TB) is the leading infectious killer worldwide, with 10.6 million cases and 1.6 million deaths in 2021 alone.

Vaccine policies in France and Europe.

This review outlines the outcome of the COVID-19 vaccination campaign in France and assesses the respective roles of information and coercion in its overall success. These data are then put into perspective of the evolution of vaccination acceptance in France.

The First Lugano Workshop on the role of adenomyosis in ART.

Adenomyosis is an important clinical condition with uncertain prevalence, and clinical focus on adenomyosis in patients undergoing assisted reproductive technology (ART) has increased during recent years. Recognizing the limited clinical knowledge on the impact of adenomyosis on ART outcomes, the First Lugano Adenomyosis Workshop was a symposium involving experts in the field of adenomyosis, covering basic research, imaging, surgery and infertility to highlight current advances and future research areas over a wide range of topics related to adenomyosis. Adenomyosis is characterized by altered oestrogen and progesterone signalling pathways.

How do we respond to the threat of multidrug-resistant bacteria? Comparison of antibiotic appraisals from 2016 to 2020 of the French, English, and German HTA agencies.

Antimicrobial resistance (AMR) has become a worldwide growing concern over the past decades. Thus, encouraging manufacturers to develop new antibiotics is needed. We hypothesised that transparency on the regulatory appraisals of antibiotics would provide an incentive to pharmaceutical development.

Fatherhood experiences: A qualitative approach of cisgender and transgender fathers in assisted reproductive technologies (ART) situation with sperm donation.

Assisted reproductive technologies have offered new ways and pathways to conceive a child. However, very few is known about insights into the complexities and challenges faced by trans fathers in contemporary parenthood journeys. This qualitative study explores the experiences of transgender and cisgender fathers who conceived children through donor sperm insemination (DSI) and natural conception (NC).

Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06).

Background: Current HIV prophylactic vaccines evaluate HIV Env as purified proteins. CD40.HIVRI.

Endoscopic papillectomy versus surgical ampullectomy for adenomas and early cancers of the papilla: a retrospective Pancreas2000/European Pancreatic Club analysis.

Objective: Ampullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study analysing EP and TSA.

Design: Of all patients in the database, lesions with prior interventions, benign histology advanced malignancy (T2 and more), patients with hereditary syndromes and those undergoing pancreatoduodenectomy were excluded.