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Risk prediction of recurrent venous thromboembolism : a multiple genetic risk model

A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including establis

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate

Incidence of Nocturia in Men with Lower Urinary Tract Symptoms Associated with Benign Prostatic Enlargement and Outcomes After Medical Treatment : Results from the Evolution European Association of Urology Research Foundation Prospective Multinational Registry

Background Nocturia is one of the most prevalent and bothersome lower urinary tract symptoms (LUTS) in men, leading to increased morbidity and mortality and a considerable economic burden on healthcare systems. Understanding its natural history, effect of pharmacotherapy, and predictors of failure of pharmacotherapy would allow optimised patient management. Objective To evaluate the prevalence an

Predicting the deposition spot radius and the nanoparticle concentration distribution in an electrostatic precipitator

Deposition of aerosol nanoparticles using an electrostatic precipitator is widely used in the aerosol community. Despite this, basic knowledge regarding what governs the deposition has been missing. This concerns the prediction of the size of the particle collection zone, but also, perhaps more importantly, prediction of the nanoparticle concentration distribution on the substrate, both of which a

Prevalence of serious bacterial infections and management of febrile infants ≤60 days in Swedish Pediatric Emergency Departments

BACKGROUND. The reported prevalence of serious bacterial infections (SBI: urinary tract infection (UTI), bacteremia, and meningitis) among febrile infants ≤60 days of age varies from 8% to 23%. There are indications that the prevalence of infections differs between the sexes. Infants with fever at home but afebrile at the pediatric emergency department (PED) might have a lower risk of SBIs. Furthe

Meningioma microstructure assessed by diffusion MRI : An investigation of the source of mean diffusivity and fractional anisotropy by quantitative histology

BACKGROUND: Mean diffusivity (MD) and fractional anisotropy (FA) from diffusion MRI (dMRI) have been associated with cell density and tissue anisotropy across tumors, but it is unknown whether these associations persist at the microscopic level.PURPOSE: To quantify the degree to which cell density and anisotropy, as determined from histology, account for the intra-tumor variability of MD and FA in

Warming reshapes the invertebrate predation pressure on the plankton community

Climate change stressors, including warming and heatwaves, can alter plankton composition and dominance patterns in temperate shallow lakes, which can disrupt ecosystem function and curtail ecosystem services. Understanding how these alterations could take place under future climates is therefore important. To understand such changes, we performed a year-long mesocosm experiment with controls refl

Proteomic Workflows for High-Quality Quantitative Proteome and Post-Translational Modification Analysis of Clinically Relevant Samples from Formalin-Fixed Paraffin-Embedded Archives

Well-characterized archival formalin-fixed paraffin-embedded (FFPE) tissues are of much value for prospective biomarker discovery studies, and protocols that offer high throughput and good reproducibility are essential in proteomics. Therefore, we implemented efficient paraffin removal and protein extraction from FFPE tissues followed by an optimized two-enzyme digestion using suspension trapping

Sunbed Use Increases Cutaneous Squamous Cell Carcinoma Risk in Women : A Large-scale, Prospective Study in Sweden

The incidence of cutaneous squamous cell carcinoma has increased rapidly in Sweden in the past decades. Here, we present a prospective study of the Melanoma in Southern Sweden (MISS)-cohort, with 29,460 participating women in southern Sweden that investigates the risk factors for cutaneous squamous cell carcinoma. Data on the host and skin cancer risk factors were collected through questionnaires

Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer

Background: The main objectives of this study were to evaluate the concordance between self-reported and registry-reported information regarding family history of breast cancer (BC), ovarian cancer (OvC) and other types of cancer in first-degree relatives of patients with early onset BC, and to determine the frequency of mutation carriers and non-mutation carriers. The secondary objective was to d

A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network

Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantita

Medical therapy versus transurethral resection of the prostate (TURP) for the treatment of symptomatic benign prostatic enlargement (BPE) : a cost minimisation analysis

Purpose: A cost minimisation analysis compares the costs of different interventions’ to ascertain the least expensive over time. We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement (BPE). Methods: The Evolution registry is a prospective, multicentre registry, conducted by th

Global, regional, and national burden of neurological disorders, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.METHODS: We estimated prevalence, incidence, d

Quality of Life After Open Radical Prostatectomy Compared with Robot-assisted Radical Prostatectomy

Background: Surgery for prostate cancer has a large impact on quality of life (QoL). Objective: To evaluate predictors for the level of self-assessed QoL at 3 mo, 12 mo, and 24 mo after robot-assisted laparoscopic (RALP) and open radical prostatectomy (ORP). Design, setting, and participants: The LAParoscopic Prostatectomy Robot Open study, a prospective, controlled, nonrandomised trial of more th

The role of SRC family kinases in FLT3 signaling

The receptor tyrosine kinase FLT3 is expressed almost exclusively in the hematopoietic compartment. Binding of its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. This leads to autophosphorylation of FLT3 on several tyrosine residues which constitute high affinity binding sites for signal transduction molecules. Recruitment of these signal t

A prospective study to evaluate the intra-individual reproducibility of bone scans for quantitative assessment in patients with metastatic prostate cancer

Background: The Bone Scan Index (BSI) is used to quantitatively assess the total tumour burden in bone scans of patients with metastatic prostate cancer. The clinical utility of BSI has recently been validated as a prognostic imaging biomarker. However, the clinical utility of the on-treatment change in BSI is dependent on the reproducibility of bone scans. The objective of this prospective study

Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer

Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-

Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI) : a prespecified interim analysis of a prospective, multicentre, non-randomised, trial

Background: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. Methods: In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres i

A1M/α1-Microglobulin Protects from Heme-Induced Placental and Renal Damage in a Pregnant Sheep Model of Preeclampsia.

Preeclampsia (PE) is a serious pregnancy complication that manifests as hypertension and proteinuria after the 20(th) gestation week. Previously, fetal hemoglobin (HbF) has been identified as a plausible causative factor. Cell-free Hb and its degradation products are known to cause oxidative stress and tissue damage, typical of the PE placenta. A1M (α1-microglobulin) is an endogenous scavenger of