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Genetic regulation of RNA splicing in human pancreatic islets

BackgroundNon-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.ResultsWe examine splicing QTLs (sQTLs) in pancreatic islets fro

Artifact reduction in simultaneous tomosynthesis and mechanical imaging of the breast

Mechanical imaging (MI) uses a pressure sensor array to estimate the stiffness of lesions. Recent clinical studies have suggested that MI combined with digital mammography may reduce false positive findings and negative biopsies by over 30%. Digital breast tomosynthesis (DBT) has been adopted progressively in cancer screening. The tomographic nature of DBT improves lesion visibility by reducing ti

Landscape configurational heterogeneity by small-scale agriculture, not crop diversity, maintains pollinators and plant reproduction in western Europe

Agricultural intensification is one of the main causes for the current biodiversity crisis. While reversing habitat loss on agricultural land is challenging, increasing the farmland configurational heterogeneity (higher field border density) and farmland compositional heterogeneity (higher crop diversity) has been proposed to counteract some habitat loss. Here, we tested whether increased farmland

Associations Between Ambient Particle Radioactivity and Blood Pressure: The NAS (Normative Aging Study)

BACKGROUND: The cardiovascular effects of low-level environmental radiation exposures are poorly understood. Although particulate matter (PM) has been linked to cardiovascular morbidity and mortality, and elevated blood pressure (BP), the properties promoting its toxicity remain uncertain. Addressing a knowledge gap, we evaluated whether BP increased with higher exposures to radioactive components

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study

Background: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. Methods: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most

Molecular analyses of triple-negative breast cancer in the young and elderly

BACKGROUND: Breast cancer in young adults has been implicated with a worse outcome. Analyses of genomic traits associated with age have been heterogenous, likely because of an incomplete accounting for underlying molecular subtypes. We aimed to resolve whether triple-negative breast cancer (TNBC) in younger versus older patients represent similar or different molecular diseases in the context of g

Somatic mutation of immunoglobulin V genes in vitro

The molecular mechanism behind affinity maturation is the introduction of point mutations in immunoglobulin (Ig) V genes, followed by the selective proliferation of B cells expressing mutants with increased affinity for antigen. An in vitro culture system was developed in which somatic hypermutation of Ig V genes was sustained in primed B cells. Cognate T cell help and cross-linking of the surface

The GALAH survey and symbiotic stars - I. Discovery and follow-up of 33 candidate accreting-only systems

We have identified a first group of 33 new candidates for symbiotic stars (SySt) of the accreting-only variety among the 600 255 stars so far observed by the GALactic Archaeology with HERMES (GALAH) high-resolution spectroscopic survey of the Southern hemisphere, more than doubling the number of those previously known. GALAH aims to high latitudes and this offers the possibility to sound the Galax

Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease : 10-year follow-up of the multicentre randomised controlled SYNTAX trial

BACKGROUND: The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cau

‘Someone must do it’ : multiple views on family’s role in end-of-life care – an international qualitative study

Background: Family is a crucial social institution in end-of-life care. Family caregivers are encouraged to take on more responsibility at different times during the illness, providing personal and medical care. Unpaid work can be overburdening, with women often spending more time in care work than men. Objectives: This study explored multiple views on the family’s role in end-of-life care from a

The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation : Monthly Notices of the Royal Astronomical Society

WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable ‘mini’ integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph cove

Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling

Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six—IL-1

EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo : Current challenges and future solutions

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prur

Challenges and opportunities for early career medical professionals in cardiovascular magnetic resonance (CMR) imaging : a white paper from the Society for Cardiovascular Magnetic Resonance

The early career professionals in the field of Cardiovascular Magnetic Resonance (CMR) face unique challenges and hurdles while establishing their careers in the field. The Society for Cardiovascular Magnetic Resonance (SCMR) has expanded the role of the early career section within the society to foster the careers of future CMR leaders. This paper aims to describe the obstacles and available oppo

Impact of Neoadjuvant Therapy for Pancreatic Cancer : Transatlantic Trend and Postoperative Outcomes Analysis

BACKGROUND: The introduction of modern chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). A recent North American study demonstrated increased use of NAT and improved operative outcomes in patients with PDAC. The aims of this study were to compare the use of NAT and short-term outcomes in patients with PDAC unde

The selection function of the RAVE survey

We characterize the selection function of RAdial Velocity Experiment (RAVE) using 2 Micron All Sky Survey (2MASS) as our underlying population, which we assume represents all stars that could have potentially been observed.We evaluate the completeness fraction as a function of position, magnitude and colour in two ways: first, on a field-by-field basis, and second, in equal-size areas on the sky.

Lung Inflammatory Environments Differentially Alter Mesenchymal Stromal Cell Behavior

Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally-induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed

The deepest X-ray view of high-redshift galaxies : Constraints on low-rate black hole accretion

We exploit the 7 Ms Chandra observations in the Chandra Deep Field-South (CDF-S), the deepest X-ray survey to date, coupled with CANDELS/GOODS-S data, to measure the total X-ray emission arising from 2076 galaxies at 3.5 ≤ z < 6.5. This aim is achieved by stacking the Chandra data at the positions of optically selected galaxies, reaching effective exposure times of ≥109s.We detect significant (>3.

CD163+ macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins wer