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Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity

Essentials Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited. We performed a genome-wide analysis of variants influencing FSAP activity in Scandinavian cohorts. We replicated an association for Marburg-1 and identified an association for a HABP2 stop variant. We identified a novel locus near ADCY2 as a potential additional regulator of FSAP activity.

The co-predictive value of a cardiovascular score for CV outcomes in diabetic patients with no atrial fibrillation

Background Risk factors included in the cardiovascular (CHA2DS2‐VASc) score, currently used for atrial fibrillation (AF), may predispose to cardiovascular events whether or not AF is present. The aim was to explore the predictive role of CHA2DS2‐VASc score on cardiovascular outcomes in diabetic patients without AF. Methods We accessed individual data from 610 diabetic patients without AF at baseli

Social constraints and psychological well-being after prostate cancer : A follow-up at 12 and 24 months after surgery

Objective: Studies indicate that social constraints (barriers to emotional expression) may be a risk factor for psychological morbidity. We aimed to investigate the association between prostate cancer–related social constraints and psychological well-being following prostate cancer surgery. Methods: In a group of 3478 partnered patients, participating in the Laparoscopic Prostatectomy Robot Open t

Probing the Virtual Proteome to Identify Novel Disease Biomarkers

BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a "virtual proteomic" approach, linking genetically predi

Prostate cancer risk-associated single-nucleotide polymorphism affects prostate-specific antigen glycosylation and its function

BACKGROUND: Genetic association studies have reported single-nucleotide polymorphisms (SNPs) at chromosome 19q13.3 to be associated with prostate cancer (PCa) risk. Recently, the rs61752561 SNP (Asp84Asn substitution) in exon 3 of the kallikrein-related peptidase 3 (KLK3) gene encoding prostate-specific antigen (PSA) was reported to be strongly associated with PCa risk (P 2.3 108). However, the bi

Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer

Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood. Experimental Design: We applied mass spectrometry–based proteomics to a unique set of 17 prostate cancer patient–derived xenografts (PDX) to characterize the effects of castration in vivo, a

Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model : An Individual Patient Data Meta-Analysis

Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional ma

90-Day readmission after radical prostatectomy—a prospective comparison between robot-assisted and open surgery

Purpose: All types of surgery are associated with complications. The debate is ongoing whether robot-assisted radical prostatectomy can lower this risk compared to open surgery. The objective of the present study was to evaluate post-operative adverse events leading to readmissions, using clinical records to classify these adverse events systematically. Materials and methods: A prospective control

Integrator of stress responses calmodulin binding transcription activator 1 (Camta1) Regulates miR-212/miR-132 Expression and insulin secretion

Altered microRNA profiles have been demonstrated in experimental models of type 2 diabetes, including in islets of the diabetic Goto-Kakizaki (GK) rat. Our bioinformatic analysis of conserved sequences in promoters of microRNAs, previously observed to be up-regulated in GK rat islets, revealed putative CGCG-core motifs on the promoter of the miR-212/miR-132 cluster, overexpression of which has bee

Modifiable causes of premature death in middle-age in Western Europe : Results from the EPIC cohort study

Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. Methods: We analysed data from 264,906 European adults from the EPIC prospective

Sorting cells by their dynamical properties

Recent advances in cell sorting aim at the development of novel methods that are sensitive to various mechanical properties of cells. Microfluidic technologies have a great potential for cell sorting; however, the design of many micro-devices is based on theories developed for rigid spherical particles with size as a separation parameter. Clearly, most bioparticles are non-spherical and deformable

DNA sample cleanup using deterministic lateral displacement

Optical mapping relies on the preparation of fluorescent DNA. DNA must be imaged with good signal to noise and therefore the background of unwanted DNA fragments, fluorescent dyes and other reagents need to be removed. We use deterministic lateral displacement to separate 48.5 kbp DNA from < 10 kbp DNA. We also show the removal of 48.5 kbp DNA fragments from a background of fluorescent ATTO647N mo

Expression of STAT3 in Prostate Cancer Metastases

STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were posi

Origin of B-cell neoplasms in autoimmune disease

Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimm

Accurate prediction tools in prostate cancer require consistent assessment of included variables

Objective: The aim of this study was to create a preoperative prediction model predicting extraprostatic tumour growth in men with clinically organ-confined disease from a prospectively collected Swedish cohort. Materials and methods: The study used data from 3386 men in the prospective multi-centre Laparoscopic Prostatectomy Robot Open (LAPPRO) trial, with 14 participating urological departments.

Pollinators and Insect Pollination in Changing Agricultural Landscapes

Svensk sammanfattningKraftiga förluster av pollinerare är oroande och det har talats om risken för att en pollineringskris ska uppstå, med konsekvenser för både människor och miljö. De flesta blommande växter och tre av fyra odlade grödor är nämligen insektspollinerade (Box 1). Minskningarna hänger ihop med det moderna jordbrukets utveckling. Många gamla hagmarker och ängsmarker där bin och fjärilAgricultural intensification and associated loss of semi-natural grasslands, has resulted in reduced landscape heterogeneity. A concomitant loss of forage and nest sites for pollinating insects has driven declines across several pollinator taxa. Because 75% of the cultivated crops and more than 85% of the flowering plant species are insectpollinated, concerns have been raised that the pollinator d

Erectile Function and Oncologic Outcomes Following Open Retropubic and Robot-assisted Radical Prostatectomy : Results from the LAParoscopic Prostatectomy Robot Open Trial

Background: Whether surgeons perform better utilising a robot-assisted laparoscopic technique compared with an open approach during prostate cancer surgery is debatable. Objective: To report erectile function and early oncologic outcomes for both surgical modalities, stratified by prostate cancer risk grouping. Design, setting, and participants: In a prospective nonrandomised trial, we recruited 2