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Early fate decisions in hematopoietic stem and progenitor cells. Through the lens of genomic and functional assays.

Hematopoietic stem cells (HSCs) are rare cells on top of the differentiation hierarchy of hematopoiesis. HSCs are unique in their combined capacity to differentiate into all mature blood lineages and self-renew to maintain the HSC pool. Based on classical models of hematopoiesis in mouse, the self-renewal potential of HSCs is gradually and step-wise lost during the transition from long term (LT)-H

Technical performance of a proximity extension assay inflammation biomarker panel with synovial fluid

The plasma proteome can provide a deeper understanding of the pathophysiology of different diseases and is a key source for detection of new biomarkers. Proximity extension assay (PEA), developed by Olink Proteomics (Uppsala, Sweden), detects proteins by using pairs of antibodies that are linked to oligonucleotides; upon target binding, the probes anneal when in proximity and the oligonucleotides

Translational opportunities of single-cell biology in atherosclerosis

The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease developmen

Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications

The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse cardiovascular outcomes. Atherosclerosis, a major underlying cause of cardiovascular disease, is conceptualized as lipid-driven inflammation in which macrophages play a nonredundant role. However, evidence emerging so far from single-cell atlases suggests a dichotomy between lipid-associa

The EAT-Lancet diet, genetic susceptibility and risk of atrial fibrillation in a population-based cohort

BACKGROUND: The EAT-Lancet Commission proposed a global reference diet with both human health benefits and environmental sustainability in 2019. However, evidence regarding the association of such a diet with the risk of atrial fibrillation (AF) is lacking. In addition, whether the genetic risk of AF can modify the effect of diet on AF remains unclear. This study aimed to assess the association of

Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes : Pooled Analysis of Population-Based Studies

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortiu

Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi

First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.

Background Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Methods In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of che

Farmland practices are driving bird population decline across Europe

Declines in European bird populations are reported for decades but the direct effect of major anthropogenic pressures on such declines remains unquantified. Causal relationships between pressures and bird population responses are difficult to identify as pressures interact at different spatial scales and responses vary among species. Here, we uncover direct relationships between population time-se

Ecological barriers mediate spatiotemporal shifts of bird communities at a continental scale

Species’ range shifts and local extinctions caused by climate change lead to community composition changes. At large spatial scales, ecological barriers, such as biome boundaries, coastlines, and elevation, can influence a community's ability to shift in response to climate change. Yet, ecological barriers are rarely considered in climate change studies, potentially hindering predictions of biodiv

Local colonisations and extinctions of European birds are poorly explained by changes in climate suitability

Climate change has been associated with both latitudinal and elevational shifts in species’ ranges. The extent, however, to which climate change has driven recent range shifts alongside other putative drivers remains uncertain. Here, we use the changing distributions of 378 European breeding bird species over 30 years to explore the putative drivers of recent range dynamics, considering the effect

Age and Referral Route Impact the Access to Diagnosis for Women with Advanced Ovarian Cancer

Purpose: The majority of women with ovarian cancer are diagnosed in late stages. Most women do have symptoms prior to diagnosis, sometimes several months before the diagnosis. The aim of this study was to evaluate the timeline from the first presentation of symptoms to a physician until there is a reasonable suspicion of cancer, among women diagnosed with advanced stage ovarian cancer. We wanted t

Radiomics-Derived Brain Age Predicts Functional Outcome after Acute Ischemic Stroke

Background and ObjectivesWhile chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age."We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors a

Unleashing Ascl1 : Exploring Cross-Lineage Potential in Reprogramming and Regenerative Frontiers

In the era of stem cell research and regenerative medicine, understanding the regulatory networks that drive cellular reprogramming is fundamental. The study entitled ‘‘Cross-lineage potential of Ascl1 uncovered by comparing diverse reprogramming regulatomes’’ published in Stem Cell Reports sheds light on the remarkable versatility of Ascl1, a transcription factor known for its pivotal role in neu

Immune challenge reduces daily activity period in free-living birds for three weeks

Non-lethal infections are common in free-living animals and the associated sickness behaviours can impact crucial life-history trade-offs. However, little is known about the duration and extent of such sickness behaviours in free-living animals, and consequently how they affect life-history decisions. Here, free-living Eurasian blackbirds, Turdus merula, were immune-challenged with lipopolysacchar

Case Study Report: Kalmar County

The content of this report is a Deliverable of the FP7 project RUFUS (Rural Future Networks) concerning the Swedish case studies that have been conducted within the project. Two regions in the south of Sweden – the counties of Kronoberg and Kalmar – have been studied in order to find out how social and economic development strategies are enacted in these rural regions. This report concerns Kalmar

Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium

BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.METHODS: We analyzed 64,901 individuals of European ancestry without