Showing papers by "University of Basel published in 2020"
TL;DR: The general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised, and autopsies are essential to elucidate COVID‐19‐associated organ alterations.
Abstract: Aims Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. Methods and results This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. Conclusions This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.
953 citations
University of California, San Diego1, University of Arizona2, Ghent University3, Université libre de Bruxelles4, University of Erlangen-Nuremberg5, California Institute of Technology6, University of Sheffield7, Spanish National Research Council8, University of Basel9, University of British Columbia10, University of California, San Francisco11, Anschutz Medical Campus12, Karolinska University Hospital13, Pompeu Fabra University14, University of South Australia15, Memorial Sloan Kettering Cancer Center16, National Taiwan University17, Hebrew University of Jerusalem18, University of Texas MD Anderson Cancer Center19, Princeton University20, Northeastern University21, Washington University in St. Louis22, University College London23, Duke University24, Royal Children's Hospital25, Claude Bernard University Lyon 126, PSL Research University27, Université Paris-Saclay28, University of Pennsylvania29, Kyoto University30, University of Toulouse31, Queensland University of Technology32, Massachusetts Institute of Technology33, University of Pittsburgh34, University of Kentucky35, Kumamoto University36
TL;DR: This Consensus Statement is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications to reduce misunderstanding and misinterpretation of research data generated in various experimental models.
Abstract: Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by 'the EMT International Association' (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
931 citations
Humanitas University1, University College Dublin2, Autonomous University of Madrid3, Cambridge University Hospitals NHS Foundation Trust4, Winterthur Museum, Garden and Library5, University of Basel6, Catholic University of the Sacred Heart7, Aarhus University Hospital8, University of Copenhagen9, Royal Liverpool University Hospital10, Aalborg University11, Mater Dei Hospital12, University of Bologna13, Barts Health NHS Trust14, Comenius University in Bratislava15, Sheba Medical Center16, University of Porto17, McMaster University18, Linköping University19, Seconda Università degli Studi di Napoli20, Katholieke Universiteit Leuven21, University of Padua22, Maastricht University Medical Centre23, Beaujon Hospital24, University of Zurich25, Imperial College London26
TL;DR: The present article addresses surgical management, including preoperative aspects and drug management before surgery, and provides technical advice for a variety of common clinical situations.
Abstract: This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.
563 citations
Rotem Botvinik-Nezer1, Rotem Botvinik-Nezer2, Felix Holzmeister3, Colin F. Camerer4 +217 more•Institutions (78)
TL;DR: The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
Abstract: Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.
551 citations
TL;DR: A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.
Abstract: Single-cell analyses have revealed extensive heterogeneity between and within human tumours1–4, but complex single-cell phenotypes and their spatial context are not at present reflected in the histological stratification that is the foundation of many clinical decisions. Here we use imaging mass cytometry5 to simultaneously quantify 35 biomarkers, resulting in 720 high-dimensional pathology images of tumour tissue from 352 patients with breast cancer, with long-term survival data available for 281 patients. Spatially resolved, single-cell analysis identified the phenotypes of tumour and stromal single cells, their organization and their heterogeneity, and enabled the cellular architecture of breast cancer tissue to be characterized on the basis of cellular composition and tissue organization. Our analysis reveals multicellular features of the tumour microenvironment and novel subgroups of breast cancer that are associated with distinct clinical outcomes. Thus, spatially resolved, single-cell analysis can characterize intratumour phenotypic heterogeneity in a disease-relevant manner, with the potential to inform patient-specific diagnosis. A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.
519 citations
TL;DR: Methods are presented that estimate symmetrical and antisymmetrical optical aberrations, as well as magnification anisotropy, in a cryo-EM data set, and considering these effects improves the resolution of the 3D reconstruction when these effects are present.
504 citations
TL;DR: The latest projections of climate and land use change are used to assess potential global soil erosion rates by water to address policy questions and provide insight into the potential mitigating effects attributable to conservation agriculture and the need for more effective policy instruments for soil protection.
Abstract: Soil erosion is a major global soil degradation threat to land, freshwater, and oceans. Wind and water are the major drivers, with water erosion over land being the focus of this work; excluding gullying and river bank erosion. Improving knowledge of the probable future rates of soil erosion, accelerated by human activity, is important both for policy makers engaged in land use decision-making and for earth-system modelers seeking to reduce uncertainty on global predictions. Here we predict future rates of erosion by modeling change in potential global soil erosion by water using three alternative (2.6, 4.5, and 8.5) Shared Socioeconomic Pathway and Representative Concentration Pathway (SSP-RCP) scenarios. Global predictions rely on a high spatial resolution Revised Universal Soil Loss Equation (RUSLE)-based semiempirical modeling approach (GloSEM). The baseline model (2015) predicts global potential soil erosion rates of [Formula: see text] Pg yr-1, with current conservation agriculture (CA) practices estimated to reduce this by ∼5%. Our future scenarios suggest that socioeconomic developments impacting land use will either decrease (SSP1-RCP2.6-10%) or increase (SSP2-RCP4.5 +2%, SSP5-RCP8.5 +10%) water erosion by 2070. Climate projections, for all global dynamics scenarios, indicate a trend, moving toward a more vigorous hydrological cycle, which could increase global water erosion (+30 to +66%). Accepting some degrees of uncertainty, our findings provide insights into how possible future socioeconomic development will affect soil erosion by water using a globally consistent approach. This preliminary evidence seeks to inform efforts such as those of the United Nations to assess global soil erosion and inform decision makers developing national strategies for soil conservation.
492 citations
TL;DR: The single model composite score QMEAN is extended by introducing a consensus-based distance constraint (DisCo) score, which combines the accuracy of consensus methods with the broad applicability of single model approaches and demonstrates that CASP models are not the ideal data source to train predictive methods for model quality estimation.
Abstract: Motivation Methods that estimate the quality of a 3D protein structure model in absence of an experimental reference structure are crucial to determine a model's utility and potential applications. Single model methods assess individual models whereas consensus methods require an ensemble of models as input. In this work, we extend the single model composite score QMEAN that employs statistical potentials of mean force and agreement terms by introducing a consensus-based distance constraint (DisCo) score. Results DisCo exploits distance distributions from experimentally determined protein structures that are homologous to the model being assessed. Feed-forward neural networks are trained to adaptively weigh contributions by the multi-template DisCo score and classical single model QMEAN parameters. The result is the composite score QMEANDisCo, which combines the accuracy of consensus methods with the broad applicability of single model approaches. We also demonstrate that, despite being the de-facto standard for structure prediction benchmarking, CASP models are not the ideal data source to train predictive methods for model quality estimation. For performance assessment, QMEANDisCo is continuously benchmarked within the CAMEO project and participated in CASP13. For both, it ranks among the top performers and excels with low response times. Availability and implementation QMEANDisCo is available as web-server at https://swissmodel.expasy.org/qmean. The source code can be downloaded from https://git.scicore.unibas.ch/schwede/QMEAN. Supplementary information Supplementary data are available at Bioinformatics online.
433 citations
TL;DR: Why the testing strategy in Switzerland should be strengthened urgently, as a core component of a combination approach to control COVID-19 is explained.
Abstract: Switzerland is among the countries with the highest number of coronavirus disease-2019 (COVID-19) cases per capita in the world. There are likely many people with undetected SARS-CoV-2 infection because testing efforts are currently not detecting all infected people, including some with clinical disease compatible with COVID-19. Testing on its own will not stop the spread of SARS-CoV-2. Testing is part of a strategy. The World Health Organization recommends a combination of measures: rapid diagnosis and immediate isolation of cases, rigorous tracking and precautionary self-isolation of close contacts. In this article, we explain why the testing strategy in Switzerland should be strengthened urgently, as a core component of a combination approach to control COVID-19.
419 citations
University of Würzburg1, Technische Universität München2, University of Basel3, Swiss Federal Institute for Forest, Snow and Landscape Research4, University of Bayreuth5, University of Zurich6, ETH Zurich7, University of Freiburg8, Max Planck Society9, University of Göttingen10, Karlsruhe Institute of Technology11
TL;DR: In 2018, Central Europe experienced one of the most severe and long-lasting summer drought and heat wave ever recorded, which had a greater impact on forest ecosystems of Austria, Germany and Switzerland than the 2003 drought as discussed by the authors.
399 citations
Université de Sherbrooke1, Mayo Clinic2, University of Oslo3, University of Düsseldorf4, Kent State University5, Monash University, Clayton campus6, Cornell University7, University of Arizona8, Rhode Island Hospital9, University of Basel10, University of Dundee11, Heidelberg University12, French Institute of Health and Medical Research13, University of Coimbra14, MRC Mitochondrial Biology Unit15, Columbia University Medical Center16, University of Bordeaux17, University of Grenoble18, Johns Hopkins University School of Medicine19, University of Kansas20
TL;DR: The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes.
Abstract: The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes. Accumulating evidence indicates that impaired glucose metabolism in the brain is involved in the cause and progression of neurodegenerative disorders of ageing such as Alzheimer disease. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by rescuing, protecting or normalizing brain energetics.
TL;DR: The evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact are discussed.
TL;DR: It is shown that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions, and the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of the estimated effects of federal travel restrictions.
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.
University of California, San Francisco1, University of Pennsylvania2, Cleveland Clinic3, Vita-Salute San Raffaele University4, Stony Brook University5, Washington University in St. Louis6, University Hospital of Basel7, Hebron University8, University of Warmia and Mazury in Olsztyn9, University of Münster10, Novartis11, University of Basel12
TL;DR: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide, and this data indicates that this drug should be considered as a second-line treatment for relapsing multiple sclerosis.
Abstract: Background Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activ...
TL;DR: The ECNP Resilience members advocate for an increased focus on mental health during the coronavirus pandemic and highlight the urgent need of augmenting the authors' focus on resilience and on strategies to enhance it.
TL;DR: In a future world, with an assumed absolute shortage of mineral P fertilizer, agricultural soils worldwide will be depleted by between 4–19 kg ha−1 yr−1, with average losses of P due to erosion by water contributing over 50% of total P losses.
Abstract: Soil phosphorus (P) loss from agricultural systems will limit food and feed production in the future. Here, we combine spatially distributed global soil erosion estimates (only considering sheet and rill erosion by water) with spatially distributed global P content for cropland soils to assess global soil P loss. The world’s soils are currently being depleted in P in spite of high chemical fertilizer input. Africa (not being able to afford the high costs of chemical fertilizer) as well as South America (due to non-efficient organic P management) and Eastern Europe (for a combination of the two previous reasons) have the highest P depletion rates. In a future world, with an assumed absolute shortage of mineral P fertilizer, agricultural soils worldwide will be depleted by between 4–19 kg ha−1 yr−1, with average losses of P due to erosion by water contributing over 50% of total P losses. Phosphorus is an essential nutrient critical for agriculture, but because it is non-renewable its future availability is threatened. Here the authors show that across the globe most nations have net losses of phosphorus, with soil erosion as the major route of loss in Europe, Africa and South America.
TL;DR: This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas and implicate unexpected cell types in diseases such as macular degeneration.
University of Basel1, European University Cyprus2, Kore University of Enna3, University of Nicosia4, Cyprus University of Technology5, The Cyprus Institute of Neurology and Genetics6, The Chinese University of Hong Kong7, Universidad de La Sabana8, University College Cork9, University College Dublin10, Babeș-Bolyai University11, International Sleep Products Association12, University of Lisbon13, University of Grenoble14, University of Cádiz15, European University of Madrid16, University of Zaragoza17, University of Jyväskylä18, Ljubljana University Medical Centre19, Université du Québec à Trois-Rivières20, Duke University21, University of Cyprus22
TL;DR: In this paper, the authors conducted a study to determine mental health outcomes during pandemic induced lockdowns and examined known predictors of mental health outcome, including country, sociodemographic factors, lockdown characteristics, social factors, and psychological factors.
Abstract: BACKGROUND: The COVID-19 pandemic triggered vast governmental lockdowns. The impact of these lockdowns on mental health is inadequately understood. On the one hand such drastic changes in daily routines could be detrimental to mental health. On the other hand, it might not be experienced negatively, especially because the entire population was affected. METHODS: The aim of this study was to determine mental health outcomes during pandemic induced lockdowns and to examine known predictors of mental health outcomes. We therefore surveyed n = 9,565 people from 78 countries and 18 languages. Outcomes assessed were stress, depression, affect, and wellbeing. Predictors included country, sociodemographic factors, lockdown characteristics, social factors, and psychological factors. RESULTS: Results indicated that on average about 10% of the sample was languishing from low levels of mental health and about 50% had only moderate mental health. Importantly, three consistent predictors of mental health emerged: social support, education level, and psychologically flexible (vs. rigid) responding. Poorer outcomes were most strongly predicted by a worsening of finances and not having access to basic supplies. CONCLUSIONS: These results suggest that on whole, respondents were moderately mentally healthy at the time of a population-wide lockdown. The highest level of mental health difficulties were found in approximately 10% of the population. Findings suggest that public health initiatives should target people without social support and those whose finances worsen as a result of the lockdown. Interventions that promote psychological flexibility may mitigate the impact of the pandemic.
01 Oct 2020
TL;DR: In this paper, the emergence and characterization of Majorana bound states in realistic devices based on hybrid semiconducting nanowires and their connection to more conventional Andreev bound states are discussed.
Abstract: Inhomogeneous superconductors can host electronic excitations, known as Andreev bound states (ABSs), below the superconducting energy gap. With the advent of topological superconductivity, a new kind of zero-energy ABS with exotic qualities, known as a Majorana bound state (MBS), has been discovered. A special property of MBS wavefunctions is their non-locality, which, together with non-Abelian braiding, is the key to their promise in topological quantum computation. We focus on hybrid superconductor–semiconductor nanowires as a flexible and promising experimental platform to realize one-dimensional topological superconductivity and MBSs. We review the main properties of ABSs and MBSs, state-of-the-art techniques for their detection and theoretical progress beyond minimal models, including different types of robust zero modes that may emerge without a band-topological transition. Topological Majorana bound states have potential for encoding, manipulating and protecting quantum information in condensed-matter systems. This Review discusses emergence and characterization of Majorana bound states in realistic devices based on hybrid semiconducting nanowires and their connection to more conventional Andreev bound states.
TL;DR: It is found that CD36 was selectively upregulated in intrautumoral T reg cells as a central metabolic modulator and elicited additive antitumor responses with anti-programmed cell death protein 1 therapy.
Abstract: Depleting regulatory T cells (Treg cells) to counteract immunosuppressive features of the tumor microenvironment (TME) is an attractive strategy for cancer treatment; however, autoimmunity due to systemic impairment of their suppressive function limits its therapeutic potential. Elucidating approaches that specifically disrupt intratumoral Treg cells is direly needed for cancer immunotherapy. We found that CD36 was selectively upregulated in intrautumoral Treg cells as a central metabolic modulator. CD36 fine-tuned mitochondrial fitness via peroxisome proliferator-activated receptor-β signaling, programming Treg cells to adapt to a lactic acid-enriched TME. Genetic ablation of Cd36 in Treg cells suppressed tumor growth accompanied by a decrease in intratumoral Treg cells and enhancement of antitumor activity in tumor-infiltrating lymphocytes without disrupting immune homeostasis. Furthermore, CD36 targeting elicited additive antitumor responses with anti-programmed cell death protein 1 therapy. Our findings uncover the unexplored metabolic adaptation that orchestrates the survival and functions of intratumoral Treg cells, and the therapeutic potential of targeting this pathway for reprogramming the TME.
University of Barcelona1, University of Liverpool2, Vita-Salute San Raffaele University3, University of Tübingen4, Charles University in Prague5, Medical University of Vienna6, Freeman Hospital7, Autonomous University of Barcelona8, Netherlands Cancer Institute9, Royal Free London NHS Foundation Trust10, Heidelberg University11, University of Patras12, Leeds Teaching Hospitals NHS Trust13, University of Ioannina14, University of Modena and Reggio Emilia15, Zhejiang University16, Radboud University Nijmegen17, Umeå University18, University of Paris19, Istanbul Medipol University20, University of Basel21, Erasmus University Rotterdam22, Praxis23, Innsbruck Medical University24, University of St. Gallen25, Ghent University Hospital26, St. George's University27, University College London Hospitals NHS Foundation Trust28, European Association of Urology29, University of Sheffield30, Katholieke Universiteit Leuven31, Dresden University of Technology32, University of Copenhagen33, University of Aberdeen34
TL;DR: It is hoped that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.
Fred Hutchinson Cancer Research Center1, University of Washington2, Seattle Children's3, University of Basel4, Swiss Institute of Bioinformatics5, University of California, San Francisco6, Public Health – Seattle & King County7, Washington State Department of Health8, National Center for Immunization and Respiratory Diseases9, Centers for Disease Control and Prevention10, Howard Hughes Medical Institute11
TL;DR: It is found that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.
Abstract: After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.
TL;DR: It was found that, on one hand, the restrictions reduced the mismatch between external (social) and internal (biological) sleep–wake timing, as indexed by significant reductions in social jetlag and social sleep restriction, with a concomitant increase in sleep duration.
Hospital General Universitario Gregorio Marañón1, King's College London2, Heidelberg University3, University of Lübeck4, University of Basel5, Dresden University of Technology6, Maastricht University7, University of Amsterdam8, University of Freiburg9, Paris Descartes University10, Ludwig Maximilian University of Munich11, South London and Maudsley NHS Foundation Trust12, University of Lausanne13
TL;DR: This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified and needs-based and psychological interventions should still be offered.
Abstract: Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohend = 0.57) or educational functioning (Cohend = 0.21), social functioning (Cohend = 1.25), and quality of life (Cohend = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohend = 0.35) and negative symptoms (Cohend = 0.39) as well as low functioning (Cohend = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.
Goethe University Frankfurt1, University of Debrecen2, University of Bologna3, Katholieke Universiteit Leuven4, University of Padua5, University of Turin6, Autonomous University of Barcelona7, Royal Free Hospital8, Université libre de Bruxelles9, University of Alcalá10, Hospital General Universitario Gregorio Marañón11, University of Pavol Jozef Šafárik12, Ludwig Maximilian University of Munich13, Medical University of Vienna14, University of Cambridge15, Wittenberg University16, Leipzig University17, RWTH Aachen University18, Leiden University Medical Center19, Medical University of Graz20, Innsbruck Medical University21, University of Lugano22, Aarhus University Hospital23, Université Paris-Saclay24, Marmara University25, Nottingham University Hospitals NHS Trust26, University of Paris27, Ghent University Hospital28, Hannover Medical School29, University Hospital Bonn30, University of Münster31, University of Basel32, University of Birmingham33, Derriford Hospital34, University of Copenhagen35
TL;DR: Acute decompensation without ACLF is a heterogeneous condition with three different clinical courses and two major pathophysiological mechanisms: systemic inflammation and portal hypertension.
Pacific Northwest National Laboratory1, Columbia University2, Brookhaven National Laboratory3, University of Minnesota4, Princeton University5, Northwestern University6, University of Oregon7, Georgia Institute of Technology8, University of Pittsburgh9, Dow Chemical Company10, University of Utah11, University of Toronto12, Massachusetts Institute of Technology13, University of Illinois at Urbana–Champaign14, Merck & Co.15, University of Pennsylvania16, University of Basel17, University of California, Irvine18
TL;DR: It is asserted that nature’s blueprint provides essential principles for vastly expanding the use of EAMs in sustainable catalysis, pointing to an overarching need for improved theories and computational methods that accurately treat their multiconfigurational electronic structure.
Abstract: BACKGROUND Catalysis has had a transformative impact on society, playing a crucial role in the production of modern materials, medicines, fuels, and chemicals. Precious metals have been the cornerstone of many industrial catalytic processes for decades, providing high activity, stability, and tolerance to poisons. In stark contrast, redox catalysis essential to life is carried out by metalloenzymes that feature exclusively Earth-abundant metals (EAMs). The terrestrial abundance of some EAMs is 104 times that of precious metals, and thus their increased use would lead to reduced cost and environmental footprint. In addition to these practical considerations, EAMs display distinct reactivity profiles that originate from their characteristic electronic structure, thermochemistry, and kinetics. The behavior of EAMs provides compelling scientific opportunities for catalyst design. We assert that nature’s blueprint provides essential principles for vastly expanding the use of EAMs in sustainable catalysis. ADVANCES Exquisite tuning of the local environment around EAM active sites is key to enabling their use in catalysis. Such control is achieved in enzymatic catalysis by directed evolution of the amino acid environment, resulting in engineered enzymes with extraordinary catalytic performance. Similarly in molecular catalysis, modifying the steric and electronic properties of ligands can lead to some EAM catalysts with performance superior to that obtained from precious metal catalysts. In addition, for heterogeneous catalysts, the local environment and electronic structure of active sites can be modified by bonding to other metals or main-group elements, facilitating reaction pathways distinct from those involving precious metals. Innovations in the design of EAM catalysts demonstrate their potential to catalyze many of the reactions that traditionally relied on precious metals, although further improvements are needed in activity, selectivity, lifetime, or energy efficiency. The characteristics of EAMs point to an overarching need for improved theories and computational methods that accurately treat their multiconfigurational electronic structure. OUTLOOK The remarkable ability of enzymes to catalyze a variety of reactions under mild conditions, using only EAMs, highlights compelling opportunities for the discovery of new catalysis. Although enzymes are versatile platforms for harnessing the properties of EAMs, they are insufficiently robust under the harsh pH, temperature, pressure, and solvent conditions required for some industrial catalytic processes. Thus, systematic strategies are needed for directed evolution to extend the reactivity and persistence of engineered enzymes. For molecular catalysts, the tunability of the ligands provides opportunities for systematically varying the activities of EAMs. Key challenges include enhancing metal-ligand cooperativity, controlling transport to EAM active sites, and mastering the interactions of EAM centers with both metal-based and organic-based redox-active ligands. In heterogeneous catalysis, tuning the lattice environment of EAMs offers new opportunities for catalyst discovery, but for practical applications EAM catalysts should exhibit long-term stability and high active-site density. Thus, advances are needed in the synthesis of materials with tunable phase and nanostructure, as well as insights into how EAM catalysts undergo electronic and structural changes under sustained catalytic turnover. Strategies for controlling EAM reactivity patterns, coupled with advances in synthetic methods and spectroscopic and computational techniques, are critical for the systematic use of EAMs in sustainable catalysis.
TL;DR: In this paper, the FCHL19 representation for atomic environments in molecules or condensed-phase systems is introduced, where the representation is discretized and the individual features are rigorously optimized using Monte Carlo optimization.
Abstract: We introduce the FCHL19 representation for atomic environments in molecules or condensed-phase systems. Machine learning models based on FCHL19 are able to yield predictions of atomic forces and energies of query compounds with chemical accuracy on the scale of milliseconds. FCHL19 is a revision of our previous work [F. A. Faber et al., J. Chem. Phys. 148, 241717 (2018)] where the representation is discretized and the individual features are rigorously optimized using Monte Carlo optimization. Combined with a Gaussian kernel function that incorporates elemental screening, chemical accuracy is reached for energy learning on the QM7b and QM9 datasets after training for minutes and hours, respectively. The model also shows good performance for non-bonded interactions in the condensed phase for a set of water clusters with a mean absolute error (MAE) binding energy error of less than 0.1 kcal/mol/molecule after training on 3200 samples. For force learning on the MD17 dataset, our optimized model similarly displays state-of-the-art accuracy with a regressor based on Gaussian process regression. When the revised FCHL19 representation is combined with the operator quantum machine learning regressor, forces and energies can be predicted in only a few milliseconds per atom. The model presented herein is fast and lightweight enough for use in general chemistry problems as well as molecular dynamics simulations.
Juliette Alimena1, James Baker Beacham2, Martino Borsato3, Yangyang Cheng4 +213 more•Institutions (105)
TL;DR: In this paper, the authors present a survey of the current state of LLP searches at the Large Hadron Collider (LHC) and chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC.
Abstract: Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton–proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments—as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER—to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
TL;DR: It is concluded that research so far has not shown Plastisphere communities to starkly differ from microbial communities on other inert surfaces, which is particularly true for mature biofilm assemblages.
Abstract: Plastics become rapidly colonized by microbes when released into marine environments. This microbial community-the Plastisphere-has recently sparked a multitude of scientific inquiries and generated a breadth of knowledge, which we bring together in this review. Besides providing a better understanding of community composition and biofilm development in marine ecosystems, we critically discuss current research on plastic biodegradation and the identification of potentially pathogenic "hitchhikers" in the Plastisphere. The Plastisphere is at the interface between the plastic and its surrounding milieu, and thus drives every interaction that this synthetic material has with its environment, from ecotoxicity and new links in marine food webs to the fate of the plastics in the water column. We conclude that research so far has not shown Plastisphere communities to starkly differ from microbial communities on other inert surfaces, which is particularly true for mature biofilm assemblages. Furthermore, despite progress that has been made in this field, we recognize that it is time to take research on plastic-Plastisphere-environment interactions a step further by identifying present gaps in our knowledge and offering our perspective on key aspects to be addressed by future studies: (I) better physical characterization of marine biofilms, (II) inclusion of relevant controls, (III) study of different successional stages, (IV) use of environmentally relevant concentrations of biofouled microplastics, and (V) prioritization of gaining a mechanistic and functional understanding of Plastisphere communities.