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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.

Stem cell culture conditions and stability : a joint workshop of the PluriMes Consortium and Pluripotent Stem Cell Platform

Human stem cells have the potential to transform medicine. However, hurdles remain to ensure that manufacturing processes produce safe and effective products. A thorough understanding of the biological processes occurring during manufacture is fundamental to assuring these qualities and thus, their acceptability to regulators and clinicians. Leaders in both human pluripotent and somatic stem cells

Testing and Modelling of Electrical Traction Machines : Performance Characterisation with Measurements from Transient Operation

This thesis presents methods to derive and model the performance characteristics of interior permanent magnet machines – a machine type which is commonly used for propulsion of electrical vehicles. The thesis divides the performance characteristics into three subcategories: The electromagnetic properties, the loss profile and the thermal behaviour of the machines. One separate characterisation met

LINE-2 transposable elements are a source of functional human microRNAs and target sites

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) e

New approaches for brain repair-from rescue to reprogramming

The ability to repair or promote regeneration within the adult human brain has been envisioned for decades. Until recently, such efforts mainly involved delivery of growth factors and cell transplants designed to rescue or replace a specific population of neurons, and the results have largely been disappointing. New approaches using stem-cell-derived cell products and direct cell reprogramming hav

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

Repairing the brain : Cell replacement using stem cell-based technologies

Current approaches to cell replacement therapy in Parkinson's disease are strongly focused on the dopamine system, with the view that restoring dopaminergic inputs in a localized and physiologic manner will provide superior benefits in terms of effect and longevity compared with oral medication. Experience using transplants of fetal tissue containing dopaminergic cell precursors has provided valua

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

Long non-coding RNA in stem cell pluripotency and lineage commitment : functions and evolutionary conservation

LncRNAs have recently emerged as new and fundamental transcriptional and post-transcriptional regulators acting at multiple levels of gene expression. Indeed, lncRNAs participate in a wide variety of stem cell and developmental processes, acting in cis and/or in trans in the nuclear and/or in the cytoplasmic compartments, and generating an intricate network of interactions with RNAs, enhancers, an

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

Generation of Human 3D Lung Tissue Cultures (3D-LTCs) for Disease Modeling

Translation of novel discoveries to human disease is limited by the availability of human tissue-based models of disease. Precision-cut lung slices (PCLS) used as 3D lung tissue cultures (3D-LTCs) represent an elegant and biologically highly relevant 3D cell culture model, which highly resemble in situ tissue due to their complexity, biomechanics and molecular composition. Tissue slicing is widely

The Preparation of Decellularized Mouse Lung Matrix Scaffolds for Analysis of Lung Regenerative Cell Potential

Lung transplantation is the only option for patients with end-stage lung disease, but there is a shortage of available lung donors. Furthermore, efficiency of lung transplantation has been limited due to primary graft dysfunction. Recent mouse models mimicking lung disease in humans have allowed for deepening our understanding of disease pathomechanisms. Moreover, new techniques such as decellular