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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

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

Prevalence and incidence of non-gout crystal arthropathy in southern Sweden

Objective: To estimate the prevalence and incidence of non-gout crystal arthropathy in relation to socioeconomic factors in southern Sweden. Methods: All patients (age ≥ 18 years) with at least one visit to a physician with the diagnosis of interest in the Skåne region (population of 1.3 million) in 1998-2014 were identified. Non-gout crystal arthropathy (ICD-10 codes M11.0-M11.9) was subclassifie

Uptake of nanowires by human lung adenocarcinoma cells

Semiconductor nanowires are increasingly used in optoelectronic devices. However, their effects on human health have not been assessed fully. Here, we investigate the effects of gallium phosphide nanowires on human lung adenocarcinoma cells. Four different geometries of nanowires were suspended in the cell culture for 48 hours. We show that cells internalize the nanowires and that the nanowires ha

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide si

Interpretation of conventional survival analysis and competing risk analysis : An example of hypertension and prostate cancer

Most clinical studies use conventional methods for survival analysis and calculate the risk of the event of interest, however, it is important to understand that the study population is also at risk of competing events, for example death from other causes. Moreover, the risk of competing events may be dependent on the participants' characteristics. Whether competing risks are taken into account or

Monocyte-derived macrophages contribute to spontaneous long-term functional recovery after stroke in mice

Stroke is a leading cause of disability and currently lacks effective therapy enabling long-term functional recovery. Ischemic brain injury causes local inflammation, which involves both activated resident microglia and infiltrating immune cells, including monocytes. Monocyte-derived macrophages (MDMs) exhibit a high degree of functional plasticity. Here, we determined the role of MDMs in longterm

All-cause mortality in knee and hip osteoarthritis and rheumatoid arthritis

BACKGROUND:: While increased mortality in rheumatoid arthritis (RA) is well established there is conflicting evidence on the association between osteoarthritis (OA) and mortality. Our aim was to estimate all-cause mortality in Swedish patients with RA and OA compared with the general population. METHODS:: Cohort study of the population of Skåne region, Sweden (1.3 million), based on physicians’ di

Hohfeld relations and spielraum for action

The paper intends to show, (1) that W.N. Hohfeld’s theory of fundamental jural relations is relevant to economic theory, and (2) that Hohfeld’s system can be reconstructed by the concepts of ‘liberty space’ and ‘ability space’, understood as an agent’s Spielraum for action. The first half of the paper is devoted to an exposition of Hohfeld’s system and to the question of its relation to the econom

A comparison of the tetrapyrrole cofactors in nature and their tuning by axial ligands

This chapter illustrates how quantum chemical calculations can be used to elucidate structural and functional aspects of tetrapyrrole cofactors, focusing on porphyrins, cobalamins, coenzyme F430, and chlorophyll. A particular emphasis is put on the biochemical significance of axial ligands, which can tune the function of the tetrapyrroles. With the use of quantum chemical calculations, it is possi

Kallikrein markers performance in pretreatment blood to predict early prostate cancer recurrence and metastasis after radical prostatectomy among very high-risk men

Background: To assess whether a prespecified statistical model based on the four kallikrein markers measured in blood—total, free, and intact prostate-specific antigen (PSA), together with human kallikrein-related peptidase 2 (hK2)—or any individual marker measured in pretreatment serum were associated with biochemical recurrence-free (BCR) or metastasis-free survival after radical prostatectomy (

Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy

Background: Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective: We sought to delineate putative beneficial effects of the Pr

The β2-Adrenergic Receptor Is a Molecular Switch for Neuroendocrine Transdifferentiation of Prostate Cancer Cells

The incidence of treatment-related neuroendocrine prostate cancer (t-NEPC) is rising as more potent drugs targeting the androgen signaling axis are clinically implemented. Neuroendocrine transdifferentiation (NEtD), an putative initial step in t-NEPC development, is induced by androgen-deprivation therapy (ADT) or anti-androgens, and by activation of the β2-adrenergic receptor (ADRB2) in prostate