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Expression of tSTAT3, pSTAT3 727 , and pSTAT3 705 in the epithelial cells of hormone-naïve prostate cancer

Background: The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3 727 and pSTAT3 705 ) in tissue microarrays (TMA) of two cohorts of localized horm

One-hour glucose value as a long-term predictor of cardiovascular morbidity and mortality : the Malmö Preventive Project

OBJECTIVE: To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality.DESIGN: Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974-1992.RESULTS: Median age was 48 (25th-75th percentile: 48-49) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascu

Genome-wide analysis yields new loci associating with aortic valve stenosis

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and

Neighborhoods and mortality in Sweden : Is deprivation best assessed nationally or regionally?

BACKGROUND The association between neighborhood deprivation and mortality is well established, but knowledge about whether deprivation is best assessed regionally or nationally is scarce. OBJECTIVE The present study aims to examine whether there is a difference in results when using national and county-specific neighborhood deprivation indices and whether the level of urbanization modifies the ass

Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from ge

Organ Specific Killing af a Dispensable Organ or a Cell Population in an Organ - a Successful Design for Cancer Therapy - a Hypothesis

Purpose: This article hypothesizes that designing cancer therapies based on the organ specific toxicity of the normal tissue of the organ from which the tumors originated could be worthwhile. A prerequisite for successful therapy is that the individual can recover from damage done to the organ or cells.Results: Therapeutic examples are given for lymphoma, kidney cancer, melanoma and leukemia.Concl

A novel rare CUBN variant and three additional genes identified in Europeans with and without diabetes : results from an exome-wide association study of albuminuria

Aims/hypothesis: Identifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants. Methods: We performed an

A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm

A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdom

Rationale for a Swedish cohort consortium

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants’ data, better

Association between added sugar intake and mortality is nonlinear and dependent on sugar source in 2 Swedish population-based prospective cohorts

Background: Although sugar consumption has been associated with several risk factors for cardiometabolic diseases, evidence for harmful long-term effects is lacking. In addition, most studies have focused on sugar-sweetened beverages (SSBs), not sugar per se. Objective: The aim of this study was to examine the associations between added and free sugar intake, intake of different sugar sources, a

Developing defined substrates for stem cell culture and differentiation

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation proc

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes article

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Se

Cell-based therapy for Parkinson's disease : A journey through decades toward the light side of the Force

This review describes the history, development, and evolution of cell-based replacement therapy for Parkinson's disease (PD), from the first pioneering trials with fetal ventral midbrain progenitors to future trials using stem cells as well as reprogrammed cells. In the spirit of Tom Isaacs, the review takes parallels to the storyline of Star Wars, including the temptations from the dark side and

The Role of Maf Transcription Factors in Islet Inflammation and Βeta Cell Function

Endocrine disorders that lead to a state of chronic high blood glucose levels are collectively referred to as diabetes. This metabolic disease is mainly categorized into type 1 (T1D) and type 2 diabetes (T2D). These diabetic forms originate from distinct triggering environmental, genetic, and altered mechanisms. T2D is a consequence of metabolic load, peripheral insulin resistance, and failure of

Challenges in transdisciplinary research : Example from a study on people as part of energy and ventilation systems in residential buildings (PEIRE)

Energy efficiency measures in residential buildings typically include changes in ventilation and heating systems, and increased thermal insulation of the building envelope. The expected energy efficiency is not always reached, despite large knowledge and professional implementation of each separate measure. Thereis a lack in understanding of how technical systems interact, and how the ocupants are

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of melanoma families and whether performance improvements can be achieved.METHODS: 2,116 familial melanoma cases were ascertained by the inte

Functional connectivity changes in core resting state networks are associated with cognitive performance in systemic lupus erythematosus

To investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms by examining functional connectivity changes correlating with results of cognitive testing. Structural MRI and resting state-fMRI (rs-fMRI) were performed in 61 female SLE patients (mean age: 36.8 years, range 18.2–52.0 years) and 20 healthy controls (HC) (mean age 36.2 years, range 23.3–52.2 year

Cardiovascular risk factors and autonomic indices in relation to fatal and non-fatal coronary events

OBJECTIVE: Mortality caused by coronary artery disease has markedly decreased in recent years. However, a substantial proportion of patients suffering a coronary event (CE) die within the first day, most of them out of hospital. We aimed to investigate how established cardiovascular (CV) risk factors and CV autonomic indices associate with fatal versus non-fatal CEs in the population.METHODS: 33 0