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The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes : an IMI DIRECT study

Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fa

Electron population dynamics in resonant non-linear x-ray absorption in nickel at a free-electron laser

Free-electron lasers provide bright, ultrashort, and monochromatic x-ray pulses, enabling novel spectroscopic measurements not only with femtosecond temporal resolution: The high fluence of their x-ray pulses can also easily enter the regime of the non-linear x-ray-matter interaction. Entering this regime necessitates a rigorous analysis and reliable prediction of the relevant non-linear processes

COMMISSIONING PLAN OF THE IFMIF-DONES ACCELERATOR

IFMIF-DONES (International Fusion Materials Irradiation Facility- DEMO-Oriented Neutron Early Source) - a powerful neutron irradiation facility for studies and certification of materials to be used in fusion reactors - is planned as part of the European roadmap to fusion electricity. Its main goal will be to characterize and to qualify materials under irradiation in a neutron field similar to the

Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice

Objectives: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. Patients and methods: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care w

Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer’s disease continuum

The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms usi

Sequence variants influencing the regulation of serum IgG subclass levels

Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci

Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic trai

Subspecialty training in Europe : A report by the European Network of Young Gynaecological Oncologists

Background: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (Eur

Dealing with contaminants in Coulomb excitation of radioactive beams

Data analysis of the Coulomb excitation experiment of the exotic 206Hg nucleus, recently performed at CERN's HIE-ISOLDE facility, needs to account for the contribution to target excitation due to the strongly-present beam contaminant 130Xe. In this paper, the contamination subtraction procedure is presented.

Kaonic atoms measurement at DA Φ NE : SIDDHARTA and SIDDHARTA-2

Light kaonic atoms studies provide the unique opportunity to perform experiments equivalent to scattering at threshold, being their atomic binding energies in the keV range. High precision atomic X-rays spectroscopy ensures that the energy shift and broadening of the lowest-lying states of the kaonic atoms, induced by the strong interaction between the kaon and nucleus, can be detected. Kaonic hyd

A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

Background: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, an

Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout

Objective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression mo

Structure of the Lysinibacillus sphaericus Tpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX.

The Lysinibacillus sphaericus proteins Tpp49Aa1 and Cry48Aa1 can together act as a toxin toward the mosquito Culex quinquefasciatus and have potential use in biocontrol. Given that proteins with sequence homology to the individual proteins can have activity alone against other insect species, the structure of Tpp49Aa1 was solved in order to understand this protein more fully and inform the desig

Myeloid Kdm6b deficiency results in advanced atherosclerosis

BACKGROUND AND AIMS: Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptiona

Lymphatic Disorder Management in Pediatric Patients With Congenital Heart Disease in European Pediatric Cardiology Centers : Current Status, Disparities, and Future Considerations

BACKGROUND: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pedia

Comparison between the EKFC-equation and machine learning models to predict Glomerular Filtration Rate

In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible so

Data-driven modeling of hydraulic head time series: results and lessons learned from the 2022 groundwater modeling challenge

This paper presents the results of the 2022 Groundwater Time Series Modelling Challenge, where 15 teams from different institutes applied various data-driven models to simulate hydraulic-head time series at four monitoring wells. Three of the wells were located in Europe and one was located in the USA in different hydrogeological settings in temperate, continental, or subarctic climates. Participa