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A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism

Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screen

Profiling of lincRNAs in human pluripotent stem cell derived forebrain neural progenitor cells

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be differentiated into many different cell types of the central nervous system. One challenge when using pluripotent stem cells is to develop robust and efficient differentiation protocols that result in homogenous cultures of the desired cell type. Here, we have utilized the SMAD-inhibitors SB431542 and Noggin in a

Patients' and physicians' disagreement on patients' understanding of clinical cancer trial information : A pairwise pilot study of mirroring subjective assessments compared with objective measurements

Background: Informed consent is a prerequisite for patients included in clinical trials. Trial design, inclusion criteria and legal requirements are increasingly complex. This complexity challenges design and delivery of written and oral trial information to ensure understandable information. To evaluate the level of concordance between patients' and informing physicians' assessments regarding pat

Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin

Objective: Little is known about midlife risk factors of future cardiac arrest. Our objective was to evaluate cardiovascular risk factors in midlife in relation to the risk of cardiac arrest (CA) of cardiac and non-cardiac origin later in life. Methods: We cross-matched individuals of the population based Malmö Diet and Cancer study (n = 30,447) with the local CA registry of the city of Malmö. Bas

Habits and self-assessed quality of life, negative intrusive thoughts and depressed mood in patients with prostate cancer : a longitudinal study

Objective: The aim of this study was to evaluate the association of self-assessed preoperative physical activity, alcohol consumption and smoking with self-assessed quality of life, negative intrusive thoughts and depressed mood after radical prostatectomy. Materials and methods: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, controlled, non-randomized longitudinal tri

Associations between macrophage colony-stimulating factor and monocyte chemotactic protein 1 in plasma and first-time coronary events : A Nested case-control Study

Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first-time acute coronary events in middle-aged persons. Methods and Results-We measured baseline plasma levels of macrophage colony-stimulating factor monocyte chemotactic protein 1; C-

Family history of diabetes and its relationship with insulin secretion and insulin sensitivity in Iraqi immigrants and native Swedes : a population-based cohort study

Aims: Middle Eastern immigrants to western countries are at high risk of developing type 2 diabetes. However, the heritability and impact of first-degree family history (FH) of type 2 diabetes on insulin secretion and action have not been adequately described. Methods: Citizens of Malmö, Sweden, aged 30–75 years born in Iraq or Sweden were invited to participate in this population-based study. Ins

Exploring the role of extracellular matrix proteins to develop biomarkers of plaque vulnerability and outcome

Cardiovascular disease (CVD) is the most common cause of death in industrialized countries. One underlying cause is atherosclerosis, which is a systemic disease characterized by plaques of retained lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins in the arterial wall. The biologic composition of an atherosclerotic plaque determines whether the plaque is

The effect of aged garlic extract on the atherosclerotic process-A randomized double-blind placebo-controlled trial

Background: One of the most serious secondary manifestations of Cardiovascular Disease (CVD) is coronary atherosclerosis. This study aimed to evaluate whether aged garlic extract (AGE) can influence coronary artery calcification (CAC) and to predict the individual effect of AGE using a standard process for data mining (CRISP-DM). Method: This was a single-center parallel randomized controlled stud

Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations

The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequenc

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19

Projecting Lifetime Risk of Symptomatic Knee Osteoarthritis and Total Knee Replacement in Individuals Sustaining a Complete Anterior Cruciate Ligament Tear in Early Adulthood

Objective: To estimate the lifetime risk of knee osteoarthritis (OA) and total knee replacement (TKR) in persons sustaining anterior cruciate ligament (ACL) tear by age 25 years. Methods: We used the Osteoarthritis Policy Model to project the cumulative incidence of symptomatic knee OA requiring TKR in varying situations: no prevalent or incident injury; isolated ACL tear, surgically treated; isol

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations

The interplay between the surface and bottom water environment within the Benguela Upwelling System over the last 70 ka

The Benguela Upwelling System (BUS), located between 30 and 20°S, is one of the fundamental high-productivity systems of the world ocean. The BUS has previously been studied in terms of primary productivity and ecology over glacial-interglacial timescales; however, the response and coupling with the benthic environment have received little attention. Here, for the first time, we present a high-res

Validation of the good outcome following attempted resuscitation score on in-hospital cardiac arrest in southern Sweden

Background There is a great need for a simple and clinically useful instrument to help physicians estimate the probability of survival to discharge with a good neurological outcome (cerebral performance category, CPC = 1) in cases of in-hospital cardiac arrest (IHCA). Our aim was to validate the “Good Outcome Following Attempted Resuscitation” (GO-FAR) score in a different country with different d

Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE-/- mice

Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovar