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Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the d

Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonym

BACKGROUND: ACURATE neo2 is a transcatheter aortic valve implantation system consisting of a self-expanding bioprosthetic valve with supra-annular leaflet position and featuring innovations to facilitate placement accuracy and reduce paravalvular regurgitation. METHODS AND RESULTS: The goal of the Early neo2 (Early neo2 Registry of the ACURATE neo2 TAVI Prosthesis) was to gather real-life data on

Acute myeloid leukemia (AML) is initiated and propagated by leukemia stem cells (LSCs), a self-renewing population of leukemia cells responsible for therapy resistance. Hence, there is an urgent need to identify new therapeutic opportunities targeting LSCs. Here, we performed an in vivo CRISPR knockout screen to identify potential therapeutic targets by interrogating cell surface dependencies of L

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

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

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

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

Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive

The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated

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.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systema

Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value 1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were i

Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcrip

BACKGROUND: The diagnostic role of signal-averaged ECG (SAECG) in arrhythmogenic right ventricular cardiomyopathy (ARVC) has lately been questioned. We assessed the value of SAECG-derived late ventricular potentials (LP) in ARVC diagnosis and its association with disease manifestations.METHODS AND RESULTS: Patients with definite ARVC diagnosis or genotype-positive family members who underwent SAEC

Disruptions in gut microbiome are implicated in cardiometabolic disorders and other health outcomes. Antibiotics are known gut microbiome disruptors, but their long-term consequences remain underexplored. Here we combined individual-level data from the Swedish Prescribed Drug Register with fecal metagenomes of 14,979 adults to examine the association between oral antibiotic use over 8 years and gu

Health applications have increasingly been used to improve physical, mental and social well-being. Chronic pain (CP) is defined as pain that lasts for a period of three months and causes sporadic or constant discomfort. In Portugal, the treatments for this type of pain are almost exclusively pharmacological and with known limited effects. Endowing patients with self-management skills, will help th

Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advan

Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlate