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Levosimendan: Molecular mechanisms and clinical implications Consensus of experts on the mechanisms of action of levosimendan

The molecular background of the Ca2+-sensitizing effect of levosimendan relates to its specific interaction with the Ca2+-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of

In vitro Transcription/Translation System: A Versatile Tool in the Search for Missing Proteins

Approximately 18% of all human genes purported to encode proteins have not been directly evidenced at the protein level, according to the validation criteria established by neXtProt, and are considered as “missing” proteins. One of the goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to identify as many of these “missing” proteins as possible in human samples using mass spectromet

Development of patient-centred standards of care for osteoarthritis in Europe: the eumusc.net-project.

The eumusc.net project is an initiative founded by the European Community and the European League Against Rheumatism. One aim of the project was to facilitate equal standards for musculoskeletal health across Europe. The aim of this work-package was to develop patient-centred and consensus based standards of care (SOC) for osteoarthritis (OA), which should be available in a professional and a pati

Surface Area and Porosity

The BET surface area was found to be 10.5 (±0.5), 10.1 (±0.5) and 11.0 (±0.5) m2 g−1 for sample EL10, EL10V1 and EL10V8, respectively. No microporosity was observed for any of the samples. In all cases, a bimodal distribution of porosity was observed, indicating intraparticle macroporosity with radii about 0.1–0.2 and interparticle porosity radii around 10 μm. The TiO2 support is composed of parti

Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study.

OBJECTIVE: To obtain large scale and generalisable data on the long term predictive value of cytology and human papillomavirus (HPV) testing for development of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). DESIGN: Multinational cohort study with joint database analysis. SETTING: Seven primary HPV screening studies in six European countries. PARTICIPANTS: 24,295 women attending cerv

Challenges in elevated CO2 experiments on forests

Current forest Free Air CO2 Enrichment (FACE) experiments are reaching completion. Therefore, it is time to define the scientific goals and priorities of future experimental facilities. In this opinion article, we discuss the following three overarching issues (i) What are the most urgent scientific questions and how can they be addressed? (ii) What forest ecosystems should be investigated? (iii)

Development of screening guidelines and clinical criteria for predementia Alzheimer's disease

Background: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the mu

Ecosystem service supply and vulnerability to global change in Europe

Global change will alter the supply of ecosystem services that are vital for human well-being. To investigate ecosystem service supply during the 21st century, we used a range of ecosystem models and scenarios of climate and land-use change to conduct a Europe-wide assessment. Large changes in climate and land use typically resulted in large changes in ecosystem service supply. Some of these trend

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

BACKGROUND: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.METHODS: Patients with TRK fusion-positive primary C

Hofbauer cells and coronavirus disease 2019 (COVID-19) in pregnancy : Molecular pathology analysis of villous macrophages, endothelial cells, and placental findings from 22 placentas infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with and without fetal transmission

CONTEXT: - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillosaaitis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. Methods: Using EULAR standardis

The GALAH survey and Gaia DR2 : (non-)existence of five sparse high-latitude open clusters

Sparse open clusters can be found at high galactic latitudes where loosely populated clusters are more easily detected against the lower stellar background. Because most star formation takes place in the thin disc, the observed population of clusters far from the Galactic plane is hard to explain. We combined spectral parameters from the GALAH survey with the Gaia DR2 catalogue to study the dynami

Momentum-resolved resonant inelastic soft X-ray scattering (qRIXS) endstation at the ALS

A momentum resolved resonant inelastic X-ray scattering (qRIXS) experimental station with continuously rotatable spectrometers and parallel detection is designed to operate at different beamlines at synchrotron and free electron laser (FEL) facilities. This endstation, currently located at the Advanced Light Source (ALS), has five emission ports on the experimental chamber for mounting the high-th

Genetically identical twin-pair difference models support the amyloid cascade hypothesis

The amyloid cascade hypothesis has strongly impacted the Alzheimer's disease research agenda and clinical trial designs over the past decades, but precisely how amyloid-β pathology initiates the aggregation of neocortical tau remains unclear. We cannot exclude the possibility of a shared upstream process driving both amyloid-β and tau in an independent manner instead of there being a causal relati

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

Objectives: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each

Genome-wide association study on 13,167 individuals identifies regulators of hematopoietic stem and progenitor cell levels in human blood

Understanding how hematopoietic stem and progenitor cells (HSPCs) are regulated is of central importance for the development of new therapies for blood disorders and stem cell transplantation. To date, HSPC regulation has been extensively studied in vitro and in animal models, but less is known about the mechanisms in vivo in humans. Here, in a genome-wide association study on 13,167 individuals,

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy : a systematic review and meta-analysis

Background: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. Methods: Areas under receiving operator characteristic curve (A

Duration of Venoarterial Extracorporeal Membrane Oxygenation and Mortality in Postcardiotomy Cardiogenic Shock

Objective: The optimal duration of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients affected by postcardiotomy cardiogenic shock (PCS) remains controversial. The present study was conducted to investigate the effect of VA-ECMO duration on hospital outcomes. Design: Retrospective analysis of an international registry. Setting: Multicenter study including 19 tertiary university

The Gaia-ESO Survey : Preparing the ground for 4MOST and WEAVE galactic surveys: Chemical evolution of lithium with machine learning

Context. With its origin coming from several sources (Big Bang, stars, cosmic rays) and given its strong depletion during its stellar lifetime, the lithium element is of great interest as its chemical evolution in the Milky Way is not well understood at present. To help constrain stellar and galactic chemical evolution models, numerous and precise lithium abundances are necessary for a large range