Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint.

Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear.

T cell malignancies after CAR T cell therapy in the DESCAR-T registry.

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.

Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

High-efficiency base editing in the retina in primates and human tissues.

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.

One-quarter of freshwater fauna threatened with extinction.

Freshwater ecosystems are highly biodiverse and important for livelihoods and economic development, but are under substantial stress. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods are used to guide environmental policy and conservation prioritization, whereas recent proposals for target setting in freshwaters use abiotic factors.

Saturation genome editing-based clinical classification of BRCA2 variants.

Sequencing-based genetic tests have uncovered a vast array of BRCA2 sequence variants. Owing to limited clinical, familial and epidemiological data, thousands of variants are considered to be variants of uncertain significance (VUS). Here we have utilized CRISPR-Cas9-based saturation genome editing in a humanized mouse embryonic stem cell line to determine the functional effect of VUS.

New Silurian aculiferan fossils reveal complex early history of Mollusca.

Mollusca is the second most species-rich animal phylum, but the pathways of early molluscan evolution have long been controversial. Modern faunas retain only a fraction of the past forms in this hyperdiverse and long-lived group. Recent analyses have consistently recovered a fundamental split into two sister clades, Conchifera (including gastropods, bivalves and cephalopods) and Aculifera, comprising Polyplacophora ('chitons') and Aplacophora.

A distinct hypothalamus-habenula circuit governs risk preference.

Appropriate risk evaluation is essential for survival in complex, uncertain environments. Confronted with choosing between certain (safe) and uncertain (risky) options, animals show strong preference for either option consistently across extended time periods. How such risk preference is encoded in the brain remains elusive.

Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson's disease model triggered by α-synuclein overexpression.

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia.

Investigating Parkinson's disease risk across farming activities using data mining and large-scale administrative health data.

The risk of Parkinson's disease (PD) associated with farming has received considerable attention, in particular for pesticide exposure. However, data on PD risk associated with specific farming activities is lacking. We aimed to explore whether specific farming activities exhibited a higher risk of PD than others among the entire French farm manager (FM) population.

Diet-wide analyses for risk of colorectal cancer: prospective study of 12,251 incident cases among 542,778 women in the UK.

Uncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

Improvement in genomic prediction of maize with prior gene ontology information depends on traits and environmental conditions.

Classical genomic prediction approaches rely on statistical associations between traits and markers rather than their biological significance. Biologically informed selection of genomic regions can help prioritize polymorphisms by considering underlying biological processes, making prediction models robust and accurate. Gene ontology (GO) terms can be used for this purpose, and the information can be integrated into genomic prediction models through marker categorization.

Minimally invasive management of cervical spondylodiscitis. A multicenter experience.

The urgent etiological diagnosis represents the main management objective of cervical spondylodiscitis (CSD) to start as soon as possible antibiotic treatment to prevent neurological deterioration. The present study aimed to evaluate a multicenter experience implementing a minimally invasive surgical approach (MISA) to manage CSD such pathology vs the most complex and aggressive surgical strategies currently used.This retrospective multicenter study used a database of 70 patients from five European neurosurgical centers.

SLC10A7 regulates O-GalNAc glycosylation and Ca homeostasis in the secretory pathway: insights into SLC10A7-CDG.

Glycans are known to be fundamental for many cellular and physiological functions. Congenital disorders of glycosylation (CDG) currently encompassing over 160 subtypes, are characterized by glycan synthesis and/or processing defects. Despite the increasing number of CDG patients, therapeutic options remain very limited as our knowledge on glycan synthesis is fragmented.

The influence of time and implants in high-dose rate image-guided adaptive brachytherapy for locally advanced cervical cancer.

Purpose: To compare the clinical outcomes of two different schedules of modern image-guided adaptive brachytherapy (IGABT) in patients underwent chemoradiotherapy (CCRT) and high-dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer treated (LACC) METHODS AND MATERIALS: Data from medical records of all consecutive patients with histologically proven cervical cancer (FIGO 2018 stage IB-IVA) treated by HDR-BT after CCRT at our institution between 2016 and 2021 were reviewed.

Results: Two hundred and 8 patients with LACC FIGO 2018 stages (IB 20.7%; II 26.

[Extramedullary hematopoiesis, a rare complication of sickle cell disease: A six-case series and literature review].

Introduction: Extramedullary hematopoiesis (EMH) is very rarely described during sickle cell disease (SCD). Our aim was to describe six cases of EMH occurring in adult SCD patients and to conduct a literature review.

Methods: Retrospective, descriptive, and monocentric study, identifying all cases of EMH recorded in our cohort of adult SCD patients, up to April 2024.

Benefit and Harms of Radical Nephroureterectomy as Part of a Multimodal Treatment Strategy for Upper Tract Urothelial Carcinoma Patients Presenting with Clinical Evidence of Regional Lymph Node Metastasis: A Systematic Review and Meta-analysis by the European Association of Urology Guidelines.

Background And Objective: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate.

genomic rearrangements in a 391 French bilateral periventricular nodular heterotopia cohort: prevalence and phenotypic correlations.

Background: loss of function manifests across a broad spectrum of phenotypes, ranging from severe prenatal onset to asymptomatic cases. Bilateral periventricular nodular heterotopia (BPNH) consistently occurs in affected individuals. This retrospective study involving French patients with BPNH evaluates the prevalence of gene dosage anomalies and investigates genotype-phenotype correlations in a large cohort of French patients with BPNH.

Impact of vaginoplasty on sexual health and satisfaction in transgender women.

Background: Demand for gender-affirming surgery (GAS) is rising. The main objective of this surgery is the creation of a perineo-genital complex that appears and functions as femininely as possible, with a sensitive clitoris and a vagina capable of receptive intercourse. Penile skin inversion is currently regarded as the gold standard technique.

A new quantitative reverse transcription PCR assay to improve the routine diagnosis of paracoccidioidomycosis.

Paracoccidioides are dimorphic fungal pathogens and the etiological agents of paracoccidioidomycosis (PCM). This severe systemic mycosis is restricted to Latin America, where it has been historically endemic. Currently, PCM presents the fewest diagnostic tools available when compared to other endemic mycoses.

Study protocol for an international registry observational study evaluating clinical outcomes of transcatheter versus standard surgical mitral valve operation for secondary mitral regurgitation: the TEERMISO study.

Background: Secondary mitral regurgitation (SMR) is a condition affecting the left ventricle (LV) rather than the mitral valve (MV). If the MV remains structurally unchanged, enlargement of the LV or impairment of the papillary muscles can occur. Several mechanical interventions are available to dictate the resolution of MR.

Do continuous glucose monitoring (CGM) metrics predict macrovascular and microvascular complications in diabetes? The FACULTY protocol of a retrospective real-world cohort study.

Introduction: Glycated haemoglobin (HbA1c) is currently the gold standard for assessing glycaemic control in diabetes, given the established relationship with microvascular and macrovascular complications in this condition. However, HbA1c is affected by non-glycaemic factors, while also failing to provide data on hypoglycaemic exposure and glucose variability, which are associated with adverse vascular outcomes. Continuous glucose monitoring (CGM)-derived glucose metrics provide a more comprehensive assessment of glycaemia, but their role in predicting future vascular complications remains unclear.

Description of Borderline Personality Disorder Hospitalizations for Adolescents and Adults in France Between 2013 and 2022: A Nationwide Retrospective Study.

Borderline personality disorder (BPD) is a frequent disorder with high mental health care utilization. This study aims to describe BPD hospitalization in France: using the French national hospitals database from 2013 to 2022, regarding sociodemographic factors and hospitalization characteristics. In total, this study included 121,235 patients.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.