Showing papers by "University of Ljubljana published in 2021"
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, University of Bonn5, German Center for Neurodegenerative Diseases6, Harvard University7, University of Lausanne8, University of Padua9, National Research Council10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Copenhagen27, University of Rochester28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, University of Minho47, Polytechnic Institute of Cávado and Ave48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, Russian Academy of Sciences57, I.M. Sechenov First Moscow State Medical University58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, University of Manchester65, Ikerbasque66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
797 citations
TL;DR: The Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control.
Abstract: Summary Background Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1–14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15–21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3–14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov , NCT01558921 , and is now complete. Findings Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5–5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8–27·6) in the experimental group versus 30·4% (26·1–34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60–0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. Funding Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.
586 citations
Saarland University1, University of Parma2, Technical University of Denmark3, University of Giessen4, Pasteur Institute5, University of Lorraine6, Goethe University Frankfurt7, Max Planck Society8, University of Lisbon9, National Museum of Natural History10, Wageningen University and Research Centre11, University of Paris12, John Innes Centre13, University of Manchester14, University of Perugia15, University of Tübingen16, University of Strasbourg17, Jacobs University Bremen18, University Hospital Bonn19, University of Bristol20, Uppsala University21, University of Ljubljana22, Drugs for Neglected Diseases Initiative23, University of Dundee24, Novartis25
TL;DR: In this paper, the authors present a strategic blueprint to substantially improve our ability to discover and develop new antibiotics, and propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding.
Abstract: An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
255 citations
Max Planck Society1, Australian National University2, University of Sydney3, University of Ljubljana4, Uppsala University5, Stockholm University6, University of New South Wales7, Monash University8, Macquarie University9, Aarhus University10, Leibniz Institute for Astrophysics Potsdam11, University of Southern Queensland12, International Space Science Institute13, Lund University14, University of Western Australia15, Kapteyn Astronomical Institute16, University of Hertfordshire17, Swinburne University of Technology18, Johns Hopkins University19, Columbia University20, York University21
TL;DR: In this paper, the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab1242
Abstract: © 2021 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stab1242
235 citations
TL;DR: In this paper, a review of the current understanding of transport in one-dimensional lattice models, in particular in the paradigmatic example of the spin-1/2 XXZ and Fermi-Hubbard models, is reviewed, as well as state-of-theart theoretical methods, including both analytical and computational approaches.
Abstract: Over the last decade impressive progress has been made in the theoretical understanding of transport properties of clean, one-dimensional quantum lattice systems. Many physically relevant models in one dimension are Bethe-ansatz integrable, including the anisotropic spin-1/2 Heisenberg (also called the spin-1/2 XXZ chain) and the Fermi-Hubbard model. Nevertheless, practical computations of correlation functions and transport coefficients pose hard problems from both the conceptual and technical points of view. Only because of recent progress in the theory of integrable systems, on the one hand, and the development of numerical methods, on the other hand, has it become possible to compute their finite-temperature and nonequilibrium transport properties quantitatively. Owing to the discovery of a novel class of quasilocal conserved quantities, there is now a qualitative understanding of the origin of ballistic finite-temperature transport, and even diffusive or superdiffusive subleading corrections, in integrable lattice models. The current understanding of transport in one-dimensional lattice models, in particular, in the paradigmatic example of the spin-1/2 XXZ and Fermi-Hubbard models, is reviewed, as well as state-of-the-art theoretical methods, including both analytical and computational approaches. Among other novel techniques, matrix-product-state-based simulation methods, dynamical typicality, and, in particular, generalized hydrodynamics are covered. The close and fruitful connection between theoretical models and recent experiments is discussed, with examples given from the realms of both quantum magnets and ultracold quantum gases in optical lattices.
213 citations
TL;DR: The RIAD approach (RIAD) randomly removes partial image regions and reconstructs the image from partial inpaintings, thus addressing the drawbacks of auto-enocoding methods.
191 citations
TL;DR: The updated taxonomy of Negarnaviricota is presented, as now accepted by the ICTV, after the phylum was amended and emended in March 2020.
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
168 citations
TL;DR: In this article, the authors compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for adolescents and young adults with type 1 diabetes.
166 citations
University of Paris1, French Institute of Health and Medical Research2, Rockefeller University3, National Institutes of Health4, University of Gothenburg5, University of Turin6, Medical Research Council7, University of Bergen8, Haukeland University Hospital9, Karolinska Institutet10, Necker-Enfants Malades Hospital11, University of Ljubljana12, Ljubljana University Medical Centre13, University of Tartu14, Alexandra Hospital15, University of California, San Francisco16
TL;DR: In this paper, the authors report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020.
Abstract: Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-e, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
165 citations
TL;DR: In this article, the authors acknowledge support from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, the Japan Society for the Promotion of Science (JSPS), and the Tau-Lepton Physics Research Center of Nagoya University.
Abstract: We acknowledge support from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, the Japan Society for the Promotion of Science (JSPS), and the Tau-Lepton Physics Research Center of Nagoya University; the Australian Research Council including Grants No. DP180102629, No. DP170102389, No. DP170102204, No. DP150103061, No. FT130100303; Austrian Science Fund (FWF); the National Natural Science Foundation of China under Contracts No. 11435013, No. 11475187, No. 11521505, No. 11575017, No. 11675166, No. 11705209; Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS), Grant No. QYZDJ-SSWSLH011; the CAS Center for Excellence in Particle Physics (CCEPP); the Shanghai Pujiang Program under Grant No. 18PJ1401000; the Ministry of Education, Youth and Sports of the Czech Republic under Contract No. LTT17020; the Carl Zeiss Foundation, the Deutsche Forschungsgemeinschaft, the Excellence Cluster Universe, and the VolkswagenStiftung; the Department of Science and Technology of India; the Istituto Nazionale di Fisica Nucleare of Italy; National Research Foundation (NRF) of Korea Grants No. 2016R1D1A1B01010135, No. 2016R1D1A1B02012900, No. 2018R1A2B3003643, No. 2018R1A6A1A06024970, No. 2018R1D1A1B07047294, No. 2019K1A3A7A09033840, No. 2019R1I1A3A01058933; Radiation Science Research Institute, Foreign Large-size Research Facility Application Supporting project, the Global Science Experimental Data Hub Center of the Korea Institute of Science and Technology Information, and KREONET/GLORIAD the Polish Ministry of Science and Higher Education and the National Science Center; the Ministry of Science and Higher Education of the Russian Federation, Agreement No. 14.W03.31.0026; University of Tabuk research Grants No. S-1440-0321, No. S-0256-1438, and No. S-0280-1439 (Saudi Arabia); the Slovenian Research Agency; Ikerbasque, Basque Foundation for Science, Spain; the Swiss National Science Foundation; the Ministry of Education and the Ministry of Science and Technology of Taiwan; and the U.S. Department of Energy and the National Science Foundation.
147 citations
Kangwon National University1, University of Pavia2, University of Basel3, Karlsruhe Institute of Technology4, Federal University of Mato Grosso do Sul5, Wageningen University and Research Centre6, University of Ljubljana7, National Research Council8, University of Valencia9, University of New England (Australia)10, National Taipei University of Technology11, International Crops Research Institute for the Semi-Arid Tropics12, University Corporation for Atmospheric Research13, Czech University of Life Sciences Prague14, Augsburg College15, University of Turin16, University of Bari17, Leibniz Association18, Tottori University19, University of Orléans20, University of Adelaide21, Free University of Bozen-Bolzano22, Yazd University23, Spanish National Research Council24, Beijing Normal University25, University of Twente26, University of Leicester27, Julius Kühn-Institut28, Ludwig Maximilian University of Munich29, Agricultural Research Service30, Council for Scientific and Industrial Research31, University of Nebraska–Lincoln32, University of Rouen33, Romanian Academy34, Universidade do Estado de Minas Gerais35, Université catholique de Louvain36, University of Pisa37, University of Tehran38, University of Milan39, University of Alaska Fairbanks40, Wuhan Institute of Technology41, University of Maryland, College Park42, Aristotle University of Thessaloniki43, University of Aveiro44, Northwest A&F University45
TL;DR: This database intends to support the upcoming country-based United Nations global soil-erosion assessment in addition to helping to inform soil erosion research priorities by building a foundation for future targeted, in-depth analyses.
TL;DR: Based on an overview of the current information about the spectral sensitivities of insect photoreceptors, covering 221 species in 13 insect orders, the evolution of color vision is discussed and present knowledge gaps and promising future research directions in the field are highlighted.
Abstract: Color vision is widespread among insects but varies among species, depending on the spectral sensitivities and interplay of the participating photoreceptors. The spectral sensitivity of a photoreceptor is principally determined by the absorption spectrum of the expressed visual pigment, but it can be modified by various optical and electrophysiological factors. For example, screening and filtering pigments, rhabdom waveguide properties, retinal structure, and neural processing all influence the perceived color signal. We review the diversity in compound eye structure, visual pigments, photoreceptor physiology, and visual ecology of insects. Based on an overview of the current information about the spectral sensitivities of insect photoreceptors, covering 221 species in 13 insect orders, we discuss the evolution of color vision and highlight present knowledge gaps and promising future research directions in the field. Expected final online publication date for the Annual Review of Entomology, Volume 66 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Linköping University1, Utrecht University2, Queen's University Belfast3, Carlos III Health Institute4, Maastricht University Medical Centre5, King's College London6, Vilnius University7, University of Valencia8, Imperial College Healthcare9, University of Cambridge10, University of Pennsylvania11, Rabin Medical Center12, Hannover Medical School13, The Volgograd State Medical University14, Karolinska University Hospital15, University of Ljubljana16, University of Porto17, University of Hasselt18, Sant'Anna School of Advanced Studies19, University of Belgrade20, Serbian Academy of Sciences and Arts21
TL;DR: Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.
Abstract: Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.
TL;DR: In this paper, a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3 is presented, which contains at least 92% of stars of stellar type M9 within 100pc of the sun.
Abstract: Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use.Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue.Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun.Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.
TL;DR: In this article, the ATLAS particle-flow reconstruction method is used to reconstruct the topo-clusters of the proton-proton collision data with a center-of-mass energy of 13$ TeV collected by the LHC.
Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.
University of Porto1, University of Brescia2, Saarland University3, Hannover Medical School4, Rabin Medical Center5, Cairo University6, National and Kapodistrian University of Athens7, Vilnius University8, University of Cyprus9, University of Ferrara10, Queen's University Belfast11, Wrocław Medical University12, Utrecht University13, Linköping University14, University of Ljubljana15, The Volgograd State Medical University16, Karolinska University Hospital17, University of Zagreb18, University of Hasselt19, University of Lisbon20, Charité21, University of Belgrade22, Serbian Academy of Sciences and Arts23, University of Warwick24
TL;DR: In this article, the authors identified nine patient profiles that may be relevant for treatment implementation in heart failure patients with a reduced ejection fraction, taking into account heart rate ( 70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate ( 30 mL/min/1.73 m2 ), or hyperkalaemia.
Abstract: Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naive to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate ( 70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate ( 30 mL/min/1.73 m2 ) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next.
Wouter van Rheenen1, Rick A.A. van der Spek1, Mark K Bakker1, Joke J.F.A. van Vugt1 +209 more•Institutions (82)
TL;DR: All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Across environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.
University of Virginia Health System1, Erasmus University Rotterdam2, Vanderbilt University Medical Center3, Ottawa Hospital Research Institute4, Health Science University5, University of Michigan6, Cardiff University7, University of Edinburgh8, University of Turin9, La Trobe University10, University of Helsinki11, Saarland University12, University of Louisville13, National Institutes of Health14, University of Ljubljana15, University of Turku16, University of Antwerp17, QIMR Berghofer Medical Research Institute18, Mahidol University19, Delft University of Technology20, Radboud University Nijmegen21, Swansea University22, Johns Hopkins University23, Southern Medical University24, Oslo University Hospital25, University of Oslo26
TL;DR: In this paper, the authors present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications and provide recommendations for improved rigor, reproducibility and interoperability in uEV research.
Abstract: Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.
TL;DR: It is shown that a LBD approach can be feasible not only for discovering drug candidates for COVID-19, but also for generating mechanistic explanations and can be generalized to other diseases as well as to other clinical questions.
IMDEA1, International University of Sarajevo2, University of Novi Sad3, Nicolaus Copernicus University in Toruń4, Saints Cyril and Methodius University of Skopje5, University of Tartu6, Université Paris-Saclay7, Silesian University of Technology8, Sarajevo School of Science and Technology9, University of Innsbruck10, South-West University "Neofit Rilski"11, University of Turku12, University of Porto13, University of Crete14, University of Bergen15, University of Ljubljana16, University College Cork17, University of Málaga18, Carlos III Health Institute19
TL;DR: In this paper, a review of the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities, is presented.
Abstract: The number of microbiome-related studies has notably increased the availability of data on human microbiome composition and function. These studies provide the essential material to deeply explore host-microbiome associations and their relation to the development and progression of various complex diseases. Improved data-analytical tools are needed to exploit all information from these biological datasets, taking into account the peculiarities of microbiome data, i.e., compositional, heterogeneous and sparse nature of these datasets. The possibility of predicting host-phenotypes based on taxonomy-informed feature selection to establish an association between microbiome and predict disease states is beneficial for personalized medicine. In this regard, machine learning (ML) provides new insights into the development of models that can be used to predict outputs, such as classification and prediction in microbiology, infer host phenotypes to predict diseases and use microbial communities to stratify patients by their characterization of state-specific microbial signatures. Here we review the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on the application of ML in microbiome studies related to association and clinical use for diagnostics, prognostics, and therapeutics. Although the data presented here is more related to the bacterial community, many algorithms could be applied in general, regardless of the feature type. This literature and software review covering this broad topic is aligned with the scoping review methodology. The manual identification of data sources has been complemented with: (1) automated publication search through digital libraries of the three major publishers using natural language processing (NLP) Toolkit, and (2) an automated identification of relevant software repositories on GitHub and ranking of the related research papers relying on learning to rank approach.
TL;DR: In this article, the potentiality of electrochemical impedance spectroscopy (EIS) for understanding the battery charge storage mechanisms is still to be fully exploited, focusing on improved experimental design of experiments and advanced data analysis using physics-based models.
Abstract: Lithium-based batteries are a class of electrochemical energy storage devices where the potentiality of electrochemical impedance spectroscopy (EIS) for understanding the battery charge storage mechanisms is still to be fully exploited. Generally considered as an ancillary technique, the application of EIS should be promoted focusing on improved experimental design of experiments and advanced data analysis using physics-based models. Electrochemical impedance spectroscopy is a key technique for understanding Li-based battery processes. Here, the authors discuss the current state of the art, advantages and challenges of this technique, also giving an outlook for future developments.
TL;DR: Suggestions for a “normal,” safe, and desirable range of concentrations that presumably are beneficial for health are proposed.
Abstract: There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels (including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations <1000 nmol/L have been related to increased chronic disease risk, no dietary reference intakes (DRIs) exist. Although high total plasma/serum carotenoid concentrations of up to 7500 nmol/L are achievable after supplementation, a plateauing effect for higher doses and prolonged intake is apparent. In this review and position paper, the current knowledge on carotenoids in serum/plasma and tissues and their relationship to dietary intake and health status is summarized with the aim of proposing suggestions for a "normal," safe, and desirable range of concentrations that presumably are beneficial for health. Existing recommendations are likewise evaluated and practical dietary suggestions are included.
TL;DR: In this article, the authors review the mechanisms of cell death after electroporation reported in literature, cell injuries that may lead to cell death, and membrane repair mechanisms involved, and identify the targets of electric field in cells need to be identified to optimize existing and develop of new electrophoration-based techniques used in medicine, biotechnology, and food technology.
TL;DR: Cholesterol and lipoproteins are potential markers for monitoring the viral infection status where mechanistic inconsistencies warrant immediate further research.
Max Planck Society1, Doncaster R.F.C.2, University of Nice Sophia Antipolis3, University of Padua4, Areva5, Institut national de la recherche agronomique6, Polytechnic University of Catalonia7, French Institute for Research in Computer Science and Automation8, Delft University of Technology9, Beihang University10, Seoul National University11, Eindhoven University of Technology12, University of Ljubljana13, Technische Universität München14, Georgia State University15, Commissariat à l'énergie atomique et aux énergies alternatives16, École Polytechnique Fédérale de Lausanne17, University of Alberta18
TL;DR: JOREK as mentioned in this paper is a massively parallel fully implicit non-linear extended magneto-hydrodynamic (MHD) code for realistic tokamak X-point plasmas.
Abstract: JOREK is a massively parallel fully implicit non-linear extended magneto-hydrodynamic (MHD) code for realistic tokamak X-point plasmas. It has become a widely used versatile simulation code for studying large-scale plasma instabilities and their control and is continuously developed in an international community with strong involvements in the European fusion research programme and ITER organization. This article gives a comprehensive overview of the physics models implemented, numerical methods applied for solving the equations and physics studies performed with the code. A dedicated section highlights some of the verification work done for the code. A hierarchy of different physics models is available including a free boundary and resistive wall extension and hybrid kinetic-fluid models. The code allows for flux-surface aligned iso-parametric finite element grids in single and double X-point plasmas which can be extended to the true physical walls and uses a robust fully implicit time stepping. Particular focus is laid on plasma edge and scrape-off layer (SOL) physics as well as disruption related phenomena. Among the key results obtained with JOREK regarding plasma edge and SOL, are deep insights into the dynamics of edge localized modes (ELMs), ELM cycles, and ELM control by resonant magnetic perturbations, pellet injection, as well as by vertical magnetic kicks. Also ELM free regimes, detachment physics, the generation and transport of impurities during an ELM, and electrostatic turbulence in the pedestal region are investigated. Regarding disruptions, the focus is on the dynamics of the thermal quench (TQ) and current quench triggered by massive gas injection and shattered pellet injection, runaway electron (RE) dynamics as well as the RE interaction with MHD modes, and vertical displacement events. Also the seeding and suppression of tearing modes (TMs), the dynamics of naturally occurring TQs triggered by locked modes, and radiative collapses are being studied.
TL;DR: Resilience may be a major protective factor required for an adaptive response of an individual in stressful situations such as pandemic and the associated lockdown.
Serbian Academy of Sciences and Arts1, University of Belgrade2, European Society of Cardiology3, Wrocław Medical University4, Queen Mary University of London5, University of Leeds6, Leeds Teaching Hospitals NHS Trust7, Karolinska University Hospital8, The Volgograd State Medical University9, University of Ljubljana10
TL;DR: The Heart Failure Association (HFA) developed the HFA Atlas to provide a contemporary description of heart failure epidemiology, resources, reimbursement of guideline-directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in 42 ESC member countries as mentioned in this paper.
Abstract: Aims The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) developed the HFA Atlas to provide a contemporary description of heart failure (HF) epidemiology, resources, reimbursement of guideline-directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in ESC member countries. Methods and results The HFA Atlas survey was conducted in 2018-2019 in 42 ESC countries. The quality and completeness of source data varied across countries. The median incidence of HF was 3.20 [interquartile range (IQR) 2.66-4.17] cases per 1000 person-years, ranging from ≤2 in Italy and Denmark to >6 in Germany. The median HF prevalence was 17.20 (IQR 14.30-21) cases per 1000 people, ranging from ≤12 in Greece and Spain to >30 in Lithuania and Germany. The median number of HF hospitalizations was 2671 (IQR 1771-4317) per million people annually, ranging from 6000 in Romania, Germany and Norway. The median length of hospital stay for an admission with HF was 8.50 (IQR 7.38-10) days. Diagnostic and management resources for HF varied, with high-income ESC member countries having substantially more resources compared with middle-income countries. The median number of hospitals with dedicated HF centres was 1.16 (IQR 0.51-2.97) per million people, ranging from 7 in Norway and Italy. Nearly all countries reported full or partial reimbursement of standard GDMT, except ivabradine and sacubitril/valsartan. Almost all countries reported having NHFS or working groups and nearly half had HF patient organizations. Conclusions The first report from the HFA Atlas has shown considerable heterogeneity in HF disease burden, the resources available for its management and data quality across ESC member countries. The findings emphasize the need for a systematic approach to the capture of HF statistics so that inequalities and improvements in care may be quantified and addressed.
TL;DR: It is confirmed the perceived benefits of AV are vital factors for AV adoption whereas the perceived safety of AV significantly reduces the influence of various concerns regarding AV.
TL;DR: Big data, algorithmic analytics and machine learning in criminal justice settings shows how these new tools are blurring contemporary regulatory boundaries, undercutting the safeguards built into regulatory regimes, and abolishing subjectivity and case-specific narratives.
Abstract: The article focuses on big data, algorithmic analytics and machine learning in criminal justice settings, where mathematics is offering a new language for understanding and responding to crime. It ...