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We studied leukemic stem cells (LSCs) in a Smad4(-/-) mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. While HOXA9-SMAD4 complexes accumulate in the cytoplasm of normal hematopoietic stem- and progenitor cells (HSPCs) transduced with these oncogenes, there is no cytoplasmic accumulation of HOXA9 in Smad4(-/-) HSPCs and as a con

Background Von Willebrand factor (VWF) and coagulation factor VIII (FVIII) plasma levels are associated with increased risk for venous thromboembolism (VTE). Objectives This study aimed to determine the thrombotic risk of rare and common variants of 27 genes linked to VWF or FVIII plasma levels in genome-wide association studies. Methods Exon sequences of 27 genes linked to plasma levels of VWF or

Background. The estimation of glomerular filtration rate (GFR) is one tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea ) equation is the most validated in Europe. More recently, cystatin C has been proposed as a biomarker. We studied the performances of the EKFC equations in a large cohort of subjects according to

Objectives: To evaluate the feasibility of AI-assisted reading of prostate magnetic resonance imaging (MRI) in Organized Prostate cancer Testing (OPT). Methods: Retrospective cohort study including 57 men with elevated prostate-specific antigen (PSA) levels ≥3 µg/L that performed bi-parametric MRI in OPT. The results of a CE-marked deep learning (DL) algorithm for prostate MRI lesion detection wer

Objectives: There are several breast cancer (BC) risk factors—many related to body composition, hormonal status, and fertility patterns. However, it is not known if risk factors in healthy women are associated with specific mammographic features at the time of BC diagnosis. Our aim was to assess the potential association between pre-diagnostic body composition and mammographic features in the diag

Osteoarthritis is one of the most common musculoskeletal diseases and increases the risk of severe cardiovascular disease, like heart attack and stroke. In some individuals, osteoarthritis and cardiovascular disease will co-occur. This co-occurrence might be due to shared risk factors, for example high age, lifestyle factors and/or a shared genetic liability for the two diseases. Here, we show tha

BACKGROUND: Systemic lupus erythematosus (SLE) patients, with or without neuropsychiatric SLE (NPSLE), exhibit greater neuronal impairment compared to healthy individuals in terms of neuronal damage, magnet resonance imaging (MRI) changes and cognitive dysfunction. Interferon (IFN)-α is a key immunopathogenic driver of SLE, being persistently overexpressed in the majority of patients. This longitu

The manipulation and focusing of submicron/nanometre-scale objects are becoming increasingly important in the fields of biology, chemistry, and materials science. Acoustofluidics provides for the high throughput and precise manipulation of cells and particles with simple equipment. However, application to submicron/nanoparticles is challenging due to the particle volume dependence of the acoustic

There is a long history of avian studies investigating the impacts of urbanization. While differences in several life-history traits have been documented, either between urban and rural populations or across generalized urbanization gradients, a detailed understanding of which specific environmental variables cause these phenotypic differences is still lacking. Here, we quantified several local en

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index)

Conventional dendritic cells (cDCs) are potent antigen-presenting cells (APCs) that integrate signals from their environment allowing them to direct situation-adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross-species transcriptomics to show that RORγt+ DCs are a co

BACKGROUND: Numerous studies report that education and exercise interventions can shift people's willingness to undergo joint replacement surgery for osteoarthritis. We aimed to investigate whether becoming unwilling to undergo surgery following an education and exercise intervention for hip and knee osteoarthritis is associated with lower probability of receiving actual surgery.METHODS AND FINDIN

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer lacking effective drugs and therefore new treatment targets are needed. In this study, we define the role of homeobox protein B6 (HOXB6) and HOXB8 in controlling pancreatic cancer tumorigenesis and immune response. Transcriptomic analysis comparing human embryonic and PDAC tissue identified a large overlap of expression profiles suggesting

Automated detection of cell nuclei in fluorescence microscopy images is a key task in bioimage analysis. It is essential for most types of microscopy-based high-throughput drug and genomic screening and is often required in smaller scale experiments as well. To develop and evaluate algorithms and neural networks that perform instance or semantic segmentation for detecting nuclei, high quality anno

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adoptin

Ambient pressure x-ray photoelectron spectroscopy (APXPS) can provide a compelling platform for studying an analyte's oxidation and reduction reactions in solutions. This paper presents proof-of-principle operando measurements of a model organometallic complex, iron hexacyanide, in an aqueous solution using the dip-and-pull technique. The data demonstrates that the electrochemically active liquid

Mutated Nucleophosmin 1 (NPM1) is the most common genetic alteration in acute myeloid leukemia (AML), found in approximately 30% of cases. Although mutations in this gene are considered favorable according to current risk stratification guidelines, a large fraction of patients will suffer from relapse, demonstrating the urgent need for new treatment options. Therefore, we aimed to identify cell su

Objective: To determine the relation between concentrations of prostate specific antigen at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population to evaluate whether screening for prostate cancer and chemoprevention could be stratified by risk. Design: Case-control study with 1:3 matching nested within a highly representative population based cohort stu

Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, MITF and SOX10, important in melanoma development and progression hav

People appear to vary in their susceptibility to lifestyle risk factors for cardiometabolic disease; determining a priori who is most sensitive may help optimize the timing, design, and delivery of preventative interventions. We aimed to ascertain a person's degree of resilience or sensitivity to adverse lifestyle exposures and determine whether these classifications help predict cardiometabolic d