Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.

Clustering of variants into functional classes correlates with cancer risk and identifies different phenotypes of Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a heterogeneous predisposition to an individually variable spectrum of cancers caused by pathogenic germline variants. We used a clustering method to assign TP53 missense variants to classes based on their functional activities in experimental assays assessing biological p53 functions. Correlations with LFS phenotypes were analyzed using the public germline mutation database and validated in three LFS clinical cohorts.

Secondary organizing pneumonia associated with protracted COVID: A case series.

Objectives: Immunocompromised B-cell-depleted patients are at risk of developing protracted COVID-19, a clinical syndrome characterized by prolonged viral shedding and respiratory symptoms that can lead to hypoxemic pneumonia. Our aim is to describe this unusual condition and its treatment.

Patients And Methods: This monocentric retrospective study reports six cases of severe organizing pneumonia that developed during the clinical course of protracted COVID-19.

Season-dependent physiological behavior of growing on heavy-metal contaminated areas in relation to soil properties.

is often considered as a suitable plant species for phytomanagement of heavy metal polluted sites. Nevertheless, its physiological behavior in response to the level of metal toxicity throughout the growing season remains poorly documented. was cultivated on three sites in Belgium (BSJ: non-polluted control; CAR: slightly contaminated; VM strongly polluted by Cd, Pb, Cu, Zn, Ni and As).

Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis.

Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis.

From cultivation to cancer: formation of -nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific -nitrosamines (TSNAs), such as '-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation.

Exploring the genetic and molecular basis of differences in multiple myeloma of individuals of African and European descent.

Multiple Myeloma is a typical example of a neoplasm that shows significant differences in incidence, age of onset, type, and frequency of genetic alterations between patients of African and European ancestry. This perspective explores the hypothesis that both genetic polymorphisms and spontaneous somatic mutations in the TP53 tumor suppressor gene are determinants of these differences. In the US, the rates of occurrence of MM are at least twice as high in African Americans (AA) as in Caucasian Americans (CA).

First Molecular Characterization of Chronic Hepatitis B Carriers in Timbuktu, Mali.

In Mali, hepatocellular carcinoma (HCC) is the third and sixth most common cancer in men and women, respectively. Mali comprises several distinct climato-ecological zones. Most studies to date have been conducted in the sub-Sahelian zone of southern Mali, including the capital city Bamako.

Comparison of analytical performances between clot waveform analysis and FibWave in edoxaban-treated patients and healthy controls.

Introduction: The activated partial thromboplastin time (aPTT) and the prothrombin time (PT) are widely available coagulation parameters which are however poor predictors of the anticoagulant effect of direct oral anticoagulants (DOACs). Some coagulometers use the clot waveform analysis (CWA) to assess the clotting time but mainly based on a unique parameter. The improvement of these methodologies and the evaluation of the other waveform parameters may increase the sensitivity to DOACs.

Decrease in liver cancer incidence rates in Bamako, Mali over 28 years of population-based cancer registration (1987-2015).

Background: Primary liver cancer is common in West Africa due to endemic risk factors. However, epidemiological studies of the global burden and trends of liver cancer are limited. We report changes in trends of the incidence of liver cancer over a period of 28 years using the population-based cancer registry of Bamako, Mali.

Heterozygous BRCA1 and BRCA2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents With Cancer.

Background: Genetic predisposition is has been identified as a cause of cancer, yet little is known about the role of adult cancer predisposition syndromes in childhood cancer. We examined the extent to which heterozygous pathogenic germline variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, MSH2, MSH6, MLH1, and PMS2 contribute to cancer risk in children and adolescents.

Methods: We conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer.

Genotype-phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition.

SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation Cross-talk.

Unlabelled: Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels.

The edoxaban-M4 metabolite and measurement of edoxaban by chromogenic assays in human plasma.

Introduction: Edoxaban is the only anti-Xa inhibitor metabolized in pharmacologically active moiety that could interfere with chromogenic anti-Xa assays, especially in case of drug-drug interactions or physiological disorders.

Materials And Methods: We evaluated the contribution of the main metabolite of edoxaban, edoxaban-M4 (M4), in 79 plasma samples from patients taking edoxaban. The total anti-Xa activity was evaluated on three different chromogenic factor Xa-based assays.

Liver Decompensation after Bariatric Surgery in the Absence of Cirrhosis.

Purpose: Metabolic dysfunction-associated fatty liver disease-related cirrhosis is possible at the time of bariatric surgery, complicated by further liver decompensation. Hepatic decompensation can also occur in the absence of cirrhosis but the presentation is less clear.

Methods: We analyze the clinical characteristics, histological findings, and management of patients without cirrhosis who developed hepatic decompensation after bariatric surgery in our single tertiary-care hospital.

[Clinical use and evolution of circulating biomarkers in the era of personalized oncology: From protein markers to bioclinical scores].

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments.