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Burden of cardiovascular disease across 29 countries and GPs’ decision to treat hypertension in oldest-old

Objectives: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences. Design: This is a survey study using case-vignettes of oldest-old patients with different como

The Gaia-ESO survey : Matching chemodynamical simulations to observations of the Milky Way

The typical methodology for comparing simulated galaxies with observational surveys is usually to apply a spatial selection to the simulation to mimic the region of interest covered by a comparable observational survey sample. In this work, we compare this approach with a more sophisticated post-processing in which the observational uncertainties and selection effects (photometric, surface gravity

Hematologically important mutations : The autosomal forms of chronic granulomatous disease (third update)

Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe, recurrent bacterial and fungal infections. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is subsequently metabolized to hydrogen peroxide and other reactive oxy

Study of exotic decay of Cs isotope close to the proton drip line

The neutron-deficient 115Cs was produced at ISOLDE, CERN by spallation reaction using 1.4 GeV proton on LaC2 target. The exotic decay modes were studied by using a charged particle array (DSSD and pad detectors) and a γ-detector array (four Clovers) at the ISOLDE decay station (IDS). In this report, results on observed β-delayed particle emission from 115Cs, a nucleus close to proton drip line, is

The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis

The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protei

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. Objectives: We expl

Sex differences in the effectiveness of first-line tumour necrosis factor inhibitors in axial spondyloarthritis : Results from the EuroSpA Research Collaboration Network

Objective Evidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi. Methods Data from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were po

Feebly-interacting particles : FIPs 2022 Workshop Report

Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to famil

Attosecond photoelectron spectroscopy using high-harmonic generation and seeded free-electron lasers

In this work, we use attosecond time-resolved techniques to investigate photoionization dynamics on its natural timescale, employing both high harmonic generation and seeded free-electron lasers to generate extreme ultraviolet attosecond pulse trains for our studies. With the former approach, we examine the role of nuclear motion in molecular photoionization dynamics, while with the latter we intr

Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study

Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. Results: In total, 279 g

The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020 : an international register-based observational study among countries in Africa, Europe, North America, and Oceania

Background and purpose — Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods — This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty

Habitability for a connected, unequal and changing world

As global climate change intensifies, the question of what makes a place habitable or uninhabitable is critical, particularly in the context of a potential future climate outside the realm of lived experience, and the possible concurrent redistribution of populations partly associated with such climatic shifts. The concept of habitability holds the potential for advancing the understanding of the

Review article : Drought as a continuum – memory effects in interlinked hydrological, ecological, and social systems

Droughts are often long-lasting phenomena, without a distinct start or end and with impacts cascading across sectors and systems, creating long-term legacies. Nevertheless, our current perceptions and management of droughts and their impacts are often event-based, which can limit the effective assessment of drought risks and reduction of drought impacts. Here, we advocate for changing this perspec

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate

Recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated s

Considerations for widespread implementation of blood-based biomarkers of Alzheimer's disease

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited un

Tangential Versus Segmental Portomesenteric Venous Resection During Pancreatoduodenectomy for Pancreatic Cancer : An International Multicenter Cohort Study on Surgical and Oncological Outcome

Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement. Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer inc

RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells

Conventional dendritic cells (cDCs) are potent antigen-presenting cells (APCs) that integrate signals from their environment allowing them to direct situation-adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross-species transcriptomics to show that RORγt+ DCs are a co

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem. Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance. Methods: Leveraging protein profiles from