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Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. Here, we report that inhibition of the epigenetic regulator Lysine-specific histone demethylase 1A (LSD1) induces a rapid expansion of human cord blood derived CD34+ cells and promotes in vitro propagation of long-term repopulating HSCs by preventing differentiation. The phenot

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD usin

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved.MethodsIn a cro

Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better

Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors

Erythropoiesis is intimately coupled to cell division, and deletion of the cell cycle regulator retinoblastoma protein (pRb) causes anemia in mice. Erythroid-specific deletion of pRb has been found to result in inefficient erythropoiesis because of deregulated coordination of cell cycle exit and mitochondrial biogenesis. However, the pathophysiology remains to be fully described, and further chara

AIMS: We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort.METHODS AND RESULTS: Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making T

In the Western world, gender/sex is traditionally viewed as binary, with people falling into one of two categories: male or female. This view of gender/sex has started to change, triggering some resistance. This research investigates psychological mechanisms underlying that resistance. Study 1 (N = 489, UK) explored the role of individual gender identification in defense of, and attempts to reinfo

Osteoarthritis (OA) constitutes a major and increasing burden on patients, health care systems and the broader society. It is estimated that around a quarter of the adult population is affected by OA in the knee and hip and that the prevalence of OA will increase over the coming decades largely due to aging and adverse life-style factors. Prevention and effective care are critical to manage the ch

BACKGROUND: Gleason grading is the standard diagnostic method for prostate cancer and is essential for determining prognosis and treatment. The dearth of expert pathologists, the inter- and intraobserver variability, as well as the labour intensity of Gleason grading all necessitate the development of a user-friendly tool for robust standardisation.OBJECTIVE: To develop an artificial intelligence

The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A meta-analysis of 10 studies was performed to determine the impact of the PCSK9 R46L variant on CAVS, and the authors found that CAVS was less prevalent in carriers of this variant (odds ratio: 0.80 [95% confidence interval: 0.70 to 0.91]; p = 0.0011) compared with no

Global handel är ett försummat område i debatten om Antropocen, men spelar en implicit roll i många av dess definitioner. Handelns roll i att förskjuta miljöbelastning över Jorden skiljer sig väsentligt mellan det 'Columbianska utbytet' (1492-1800), den Industriella Revolutionen (~1800-1950), och den Stora Accelerationen (efter 1950). Vår systematiska översikt över forskningsläget visar emellertidGlobal trade is a neglected topic in debates on the Anthropocene, but plays an implicit role in several suggested definitions of it. Trade’s role in shifting environmental burdens around the globe differed substantially between the Columbian Exchange (1492−1800), the Industrial Revolution (~1800−1950) and the Great Acceleration (post-1950). However, this systematic state-of-the-art review shows th

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of inc

The semantics of programming languages comprise many concepts that are alternatives to each other, such as by-reference and by-value parameter passing. To help teach these concepts, Diwan et al. introduced the programming language Mystery, with fixed syntax but configurable semantics, and described how this language enables new approaches to teaching programming languages concepts. In this paper,

The 2019 Global Award for Entrepreneurship Research has been awarded to Professor Boyan Jovanovic at New York University in the USA. Boyan Jovanovic has developed pioneering research that advances our understanding of the competitive dynamics between incumbent firms and new entrants, entrepreneurial learning and selection processes, and the importance of entrepreneurship for the economy. Key persp

Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids. Methods: Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms

Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driv

Partially Premixed Combustion (PPC) has shown its potential by combining high combustion controllability with emission characteristics that are close to those of an HCCI engine. In order to get PPC the ignition delay needs to be long enough for the fuel and air to mix prior to combustion. This can be achieved by injecting the fuel sufficiently early while running with high EGR.In order to find out

Lung cancer accounts for 1.6 million deaths per year worldwide. The majority of patients are diagnosed at advanced stages of the disease and often present with metastasis. Thus, the 5-year survival rate of lung cancer remains around 15%. Early diagnosis of lung cancer allows for better control of the disease with 5-year survival rates up to around 70%. Chest radiography is the most common techniqu