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Showing papers by "Université de Sherbrooke published in 2021"


Journal ArticleDOI
TL;DR: The MetaboAnalyst 5.0 as mentioned in this paper is the latest version of the web-based platform for comprehensive metabolomics data analysis and interpretation, aiming to narrow the gap from raw data to functional insights for global metabolomics based on HRMS.
Abstract: Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resolution mass spectrometry (HRMS). Three modules have been developed to help achieve this goal, including: (i) a LC-MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization and resumable analysis to significantly lower the barriers to LC-MS1 spectra processing; (ii) a Functional Analysis module which expands the previous MS Peaks to Pathways module to allow users to intuitively select any peak groups of interest and evaluate their enrichment of potential functions as defined by metabolic pathways and metabolite sets; (iii) a Functional Meta-Analysis module to combine multiple global metabolomics datasets obtained under complementary conditions or from similar studies to arrive at comprehensive functional insights. There are many other new functions including weighted joint-pathway analysis, data-driven network analysis, batch effect correction, merging technical replicates, improved compound name matching, etc. The web interface, graphics and underlying codebase have also been refactored to improve performance and user experience. At the end of an analysis session, users can now easily switch to other compatible modules for a more streamlined data analysis. MetaboAnalyst 5.0 is freely available at https://www.metaboanalyst.ca.

1,530 citations


Journal ArticleDOI
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

1,129 citations


Journal ArticleDOI
TL;DR: In this article, a survey of 2,678 healthcare workers involved in general population immunisation in France, French-speaking Belgium and Quebec, Canada was conducted to assess acceptance of future COVID-19 vaccines and its determinants.
Abstract: In October and November 2020, we conducted a survey of 2,678 healthcare workers (HCWs) involved in general population immunisation in France, French-speaking Belgium and Quebec, Canada to assess acceptance of future COVID-19 vaccines (i.e. willingness to receive or recommend these) and its determinants. Of the HCWs, 48.6% (n = 1,302) showed high acceptance, 23.0% (n = 616) moderate acceptance and 28.4% (n = 760) hesitancy/reluctance. Hesitancy was mostly driven by vaccine safety concerns. These must be addressed before/during upcoming vaccination campaigns.

275 citations


Journal ArticleDOI
TL;DR: The Concise Guide to PHARMACOLOGY 2021/22 as mentioned in this paper provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands.
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

223 citations


Journal ArticleDOI
14 Oct 2021-BMJ
TL;DR: In this paper, the authors evaluated the effects of therapeutic heparin compared with prophylactic hepharmin among moderately ill patients with covid-19 admitted to hospital wards.
Abstract: Objective To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. Design Randomised controlled, adaptive, open label clinical trial. Setting 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. Participants 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). Interventions Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. Main outcome measures The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. Results The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). Conclusions In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. Trial registration ClinicalTrials.gov NCT04362085.

210 citations


Journal ArticleDOI
01 Jan 2021
TL;DR: This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index and posits that the physiology underlying frailty is a critically dysregulated complex dynamical system.
Abstract: Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index. We focus on integrating the converging evidence on the conceptualization of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction, severely compromising homeostasis. Our exegesis posits that the physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems. We then consider how this framework can drive future research to further understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations. Linda Fried and colleagues argue that physical frailty reflects the dysregulation of a complex dynamical system underpinning health and resilience, and discuss the implications for new prevention and treatment approaches.

159 citations


Journal ArticleDOI
TL;DR: In this paper, the authors provide comprehensive recommendations and practical tips for the pharmacologic management of patients with heart failure with reduced ejection fraction (HFrEF) including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators.

137 citations


Journal ArticleDOI
TL;DR: The authors investigated how exposure to and trust in information sources, and anxiety and depression, are associated with conspiracy and misinformation beliefs in eight countries/regions (Belgium, Canada, England, Philippines, Hong Kong, New Zealand, United States, Switzerland) during the COVID-19 pandemic.
Abstract: While COVID-19 spreads aggressively and rapidly across the globe, many societies have also witnessed the spread of other viral phenomena like misinformation, conspiracy theories, and general mass suspicions about what is really going on. This study investigates how exposure to and trust in information sources, and anxiety and depression, are associated with conspiracy and misinformation beliefs in eight countries/regions (Belgium, Canada, England, Philippines, Hong Kong, New Zealand, United States, Switzerland) during the COVID-19 pandemic. Data were collected in an online survey fielded from May 29, 2020 to June 12, 2020, resulting in a multinational representative sample of 8,806 adult respondents. Results indicate that greater exposure to traditional media (television, radio, newspapers) is associated with lower conspiracy and misinformation beliefs, while exposure to politicians and digital media and personal contacts are associated with greater conspiracy and misinformation beliefs. Exposure to health experts is associated with lower conspiracy beliefs only. Higher feelings of depression are also associated with greater conspiracy and misinformation beliefs. We also found relevant group- and country differences. We discuss the implications of these results.

118 citations


Journal ArticleDOI
TL;DR: In this paper, a generalized Landauer-like theory is derived to describe heat exchange mediated by thermal photons in arbitrary reciprocal and non-reciprocal multi-terminal systems.
Abstract: Many-body physics aims to understand emergent properties of systems made of many interacting objects. This article reviews recent progress on the topic of radiative heat transfer in many-body systems consisting of thermal emitters interacting in the near-field regime. Near-field radiative heat transfer is a rapidly emerging field of research in which the cooperative behavior of emitters gives rise to peculiar effects which can be exploited to control heat flow at the nanoscale. Using an extension of the standard Polder and van Hove stochastic formalism to deal with thermally generated fields in $N$-body systems, along with their mutual interactions through multiple scattering, a generalized Landauer-like theory is derived to describe heat exchange mediated by thermal photons in arbitrary reciprocal and non-reciprocal multi-terminal systems. In this review, we use this formalism to address both transport and dynamics in these systems from a unified perspective. Our discussion covers: (i) the description of non-additivity of heat flux and its related effects, including fundamental limits as well as the role of nanostructuring and material choice, (ii) the study of equilibrium states and multistable states, (iii) the relaxation dynamics (thermalization) toward local and global equilibria, (iv) the analysis of heat transport regimes in ordered and disordered systems comprised of a large number of objects, density and range of interactions, and (v) the description of thermomagnetic effects in magneto-optical systems and heat transport mechanisms in non-Hermitian many-body systems. We conclude this review by listing outstanding challenges and promising future research directions.

112 citations


Journal ArticleDOI
TL;DR: Although telehealth has been implemented quickly as a response to a health care crisis, and is not a one-size-fits-all intervention, it offers great opportunities to increase the accessibility, cost-effectiveness and family-centredness of services, to best support families of children with disabilities.
Abstract: Telehealth is being rapidly adopted by physical and occupational therapists in pediatrics as a strategy to maintain services during the COVID-19 crisis. This perspective presents a mix of theoretic...

109 citations


Journal ArticleDOI
19 Jan 2021
TL;DR: For a snapshot of the most recent developments in the field, and to identify outstanding challenges and emerging opportunities, the Quantum Materials Roadmap collection as mentioned in this paper is a collection of experts in each discipline sharing their viewpoint and articulate their vision for quantum materials.
Abstract: In recent years, the notion of "Quantum Materials" has emerged as a powerful unifying concept across diverse fields of science and engineering, from condensed-matter and cold-atom physics to materials science and quantum computing. Beyond traditional quantum materials such as unconventional superconductors, heavy fermions, and multiferroics, the field has significantly expanded to encompass topological quantum matter, two-dimensional materials and their van der Waals heterostructures, Moire materials, Floquet time crystals, as well as materials and devices for quantum computation with Majorana fermions. In this Roadmap collection we aim to capture a snapshot of the most recent developments in the field, and to identify outstanding challenges and emerging opportunities. The format of the Roadmap, whereby experts in each discipline share their viewpoint and articulate their vision for quantum materials, reflects the dynamic and multifaceted nature of this research area, and is meant to encourage exchanges and discussions across traditional disciplinary boundaries. It is our hope that this collective vision will contribute to sparking new fascinating questions and activities at the intersection of materials science, condensed matter physics, device engineering, and quantum information, and to shaping a clearer landscape of quantum materials science as a new frontier of interdisciplinary scientific inquiry.

Journal ArticleDOI
15 Mar 2021
TL;DR: This work implements new randomized protocols that find very high quality contraction paths for arbitrary and large tensor networks, and introduces a hyper-optimization approach, where both the method applied and its algorithmic parameters are tuned during the path finding.
Abstract: Tensor networks represent the state-of-the-art in computational methods across many disciplines, including the classical simulation of quantum many-body systems and quantum circuits. Several applications of current interest give rise to tensor networks with irregular geometries. Finding the best possible contraction path for such networks is a central problem, with an exponential effect on computation time and memory footprint. In this work, we implement new randomized protocols that find very high quality contraction paths for arbitrary and large tensor networks. We test our methods on a variety of benchmarks, including the random quantum circuit instances recently implemented on Google quantum chips. We find that the paths obtained can be very close to optimal, and often many orders or magnitude better than the most established approaches. As different underlying geometries suit different methods, we also introduce a hyper-optimization approach, where both the method applied and its algorithmic parameters are tuned during the path finding. The increase in quality of contraction schemes found has significant practical implications for the simulation of quantum many-body systems and particularly for the benchmarking of new quantum chips. Concretely, we estimate a speed-up of over 10,000$\times$ compared to the original expectation for the classical simulation of the Sycamore `supremacy' circuits.

Journal ArticleDOI
05 Mar 2021
TL;DR: In this paper, a promising building block for a fault-tolerant quantum processor is demonstrated: Exponential protection against relaxation and first-order protection against dephasing is achieved in a superconducting qubit.
Abstract: A promising building block for a fault-tolerant quantum processor is demonstrated: Exponential protection against relaxation and first-order protection against dephasing is achieved in a superconducting qubit.

Journal ArticleDOI
TL;DR: Diffusion MRI‐based tractography is the most commonly‐used technique when inferring the structural brain connectome, i.e., the comprehensive map of the connections in the brain.
Abstract: Diffusion MRI-based tractography is the most commonly-used technique when inferring the structural brain connectome, i.e., the comprehensive map of the connections in the brain. The utility of graph theory-a powerful mathematical approach for modeling complex network systems-for analyzing tractography-based connectomes brings important opportunities to interrogate connectome data, providing novel insights into the connectivity patterns and topological characteristics of brain structural networks. When applying this framework, however, there are challenges, particularly regarding methodological and biological plausibility. This article describes the challenges surrounding quantitative tractography and potential solutions. In addition, challenges related to the calculation of global network metrics based on graph theory are discussed.Evidence Level: 5Technical Efficacy: Stage 1.

Journal ArticleDOI
TL;DR: In this article, the authors used ultrasound velocity to probe the superconducting state of strontium ruthenate and found that the order parameter is of a two-component nature.
Abstract: The quasi-two-dimensional metal Sr2RuO4 is one of the best characterized unconventional superconductors, yet the nature of its superconducting order parameter is still under debate1–3. This information is crucial to determine the pairing mechanism of Cooper pairs. Here we use ultrasound velocity to probe the superconducting state of Sr2RuO4. This thermodynamic probe is sensitive to the symmetry of the material, and therefore, it can help in identifying the symmetry of the superconducting order parameter4,5. Indeed, we observe a sharp jump in the shear elastic constant c66 as the temperature is increased across the superconducting transition. This directly implies that the superconducting order parameter is of a two-component nature. On the basis of symmetry arguments and given the other known properties of Sr2RuO4 (refs. 6–8), we discuss which states are compatible with this requirement and propose that the two-component order parameter {dxz; dyz} is the most likely candidate. Ultrasound experiments show that the superconducting order parameter in strontium ruthenate must have two components.

Journal ArticleDOI
15 Jul 2021-BMJ
TL;DR: In this article, the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD) was evaluated using Cox proportional hazard multivariable models, with hazard ratios with 95% confidence intervals.
Abstract: Objective To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). Design Prospective cohort study. Setting 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). Participants 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. Main outcome measures The main outcome was development of IBD, including Crohn’s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. Results Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn’s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with Conclusions Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. Study registration ClinicalTrials.gov NCT03225586.

Journal ArticleDOI
TL;DR: The proposed SMA-AGDE is a promising optimization tool for global and combinatorial optimization problems and engineering design problems and over different function landscapes.
Abstract: The Slime Mould Algorithm (SMA) is a recent metaheuristic inspired by the oscillation of slime mould. Similar to other original metaheuristic algorithms (MAs), SMA may suffer from drawbacks, such as being trapped in minimum local regions and improper balance between exploitation and exploration phases. To overcome these weaknesses, this paper proposes a hybrid algorithm: SMA combined to Adaptive Guided Differential Evolution Algorithm (AGDE) (SMA-AGDE). The AGDE mutation method is employed to enhance the swarm agents’ local search, increase the population’s diversity, and help avoid premature convergence. The SMA-AGDE’s performance is evaluated on the CEC’17 test suite, three engineering design problems – tension/compression spring, pressure vessel, and rolling element bearing – and two combinatorial optimization problems – bin packing and quadratic assignment. The SMA-AGDE is compared with three categories of optimization methods: (1) The well-studied MAs, i.e., Biogeography-Based Optimizer (BBO), Gravitational Search Algorithm (GSA), and Teaching Learning-Based Optimization (TLBO), (2) Recently developed MAs, i.e., Harris Hawks Optimization (HHO), Manta Ray Foraging optimization (MRFO), and the original SMA, and (3) High-performance MAs, i.e., Evolution Strategy with Covariance Matrix Adaptation (CMA-ES), and AGDE. The overall simulation results reveal that the SMA-AGDE ranked first among the compared algorithms, and so, over different function landscapes. Thus, the proposed SMA-AGDE is a promising optimization tool for global and combinatorial optimization problems and engineering design problems.

Journal ArticleDOI
TL;DR: In this paper, orthogonal-acting inhibitors of protein arginine methyltransferase 5 (PRMT5) have been shown to cause widespread disruption of splicing across the transcriptome.
Abstract: Glioblastoma (GBM) is a deadly cancer in which cancer stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising target in GBM Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition of PRMT5 suppresses the growth of a cohort of 46 patient-derived GBM stem cell cultures, with the proneural subtype showing greater sensitivity We show that PRMT5 inhibition causes widespread disruption of splicing across the transcriptome, particularly affecting cell cycle gene products We identify a GBM splicing signature that correlates with the degree of response to PRMT5 inhibition Importantly, we demonstrate that LLY-283 is brain-penetrant and significantly prolongs the survival of mice with orthotopic patient-derived xenografts Collectively, our findings provide a rationale for the clinical development of brain penetrant PRMT5 inhibitors as treatment for GBM

Journal ArticleDOI
TL;DR: In this paper, the authors select plasma from a cohort of convalescent patients with COVID-19 and selectively deplete immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma.

Journal ArticleDOI
TL;DR: In this article, the authors point out the increasing scientific evidence for increased resilience and ecosystem service provision of functionally and species diverse planted forests compared to monospecific ones and propose five concrete steps to foster the adoption of diverse planted forest.
Abstract: As of 2020, the world has an estimated 290 million ha of planted forests and this number is continuously increasing. Of these, 131 million ha are monospecific planted forests under intensive management. Although monospecific planted forests are important in providing timber, they harbor less biodiversity and are potentially more susceptible to disturbances than natural or diverse planted forests. Here, we point out the increasing scientific evidence for increased resilience and ecosystem service provision of functionally and species diverse planted forests (hereafter referred to as diverse planted forests) compared to monospecific ones. Furthermore, we propose five concrete steps to foster the adoption of diverse planted forests: (1) improve awareness of benefits and practical options of diverse planted forests among land-owners, managers, and investors; (2) incentivize tree species diversity in public funding of afforestation and programs to diversify current maladapted planted forests of low diversity; (3) develop new wood-based products that can be derived from many different tree species not yet in use; (4) invest in research to assess landscape benefits of diverse planted forests for functional connectivity and resilience to global-change threats; and (5) improve the evidence base on diverse planted forests, in particular in currently under-represented regions, where new options could be tested.

Journal ArticleDOI
TL;DR: A gene coding for apolipoprotein E protein (apoE) is one risk factor for Alzheimer's disease (AD) as mentioned in this paper. But apoE is a major lipid transporter that plays a pivotal role in the development, maintenance, and repair of the CNS, and regulates multiple important signaling pathways.
Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular amyloid β (Aβ) and intraneuronal tau protein aggregations. One risk factor for developing AD is the APOE gene coding for the apolipoprotein E protein (apoE). Humans have three versions of APOE gene: e2, e3, and e4 allele. Carrying the e4 allele is an AD risk factor while carrying the e2 allele is protective. ApoE is a component of lipoprotein particles in the plasma at the periphery, as well as in the cerebrospinal fluid (CSF) and in the interstitial fluid (ISF) of brain parenchyma in the central nervous system (CNS). ApoE is a major lipid transporter that plays a pivotal role in the development, maintenance, and repair of the CNS, and that regulates multiple important signaling pathways. This review will focus on the critical role of apoE in AD pathogenesis and some of the currently apoE-based therapeutics developed in the treatment of AD.

Journal ArticleDOI
TL;DR: The Global Root Trait Database (GRooT) as mentioned in this paper provides a set of core root traits relevant to the description of plant form and function based on an assessment by experts, maximized species coverage through data standardization within and among traits, and implemented data quality checks.
Abstract: Motivation: Trait data are fundamental to the quantitative description of plant form and function. Although root traits capture key dimensions related to plant responses to changing environmental conditions and effects on ecosystem processes, they have rarely been included in large-scale comparative studies and global models. For instance, root traits remain absent from nearly all studies that define the global spectrum of plant form and function. Thus, to overcome conceptual and methodological roadblocks preventing a widespread integration of root trait data into large-scale analyses we created the Global Root Trait (GRooT) Database. GRooT provides ready-to-use data by combining the expertise of root ecologists with data mobilization and curation. Specifically, we (a) determined a set of core root traits relevant to the description of plant form and function based on an assessment by experts, (b) maximized species coverage through data standardization within and among traits, and (c) implemented data quality checks. Main types of variables contained: GRooT contains 114,222 trait records on 38 continuous root traits. Spatial location and grain: Global coverage with data from arid, continental, polar, temperate and tropical biomes. Data on root traits were derived from experimental studies and field studies. Time period and grain: Data were recorded between 1911 and 2019. Major taxa and level of measurement: GRooT includes root trait data for which taxonomic information is available. Trait records vary in their taxonomic resolution, with subspecies or varieties being the highest and genera the lowest taxonomic resolution available. It contains information for 184 subspecies or varieties, 6,214 species, 1,967 genera and 254 families. Owing to variation in data sources, trait records in the database include both individual observations and mean values. Software format: GRooT includes two csv files. A GitHub repository contains the csv files and a script in R to query the database.

Journal ArticleDOI
Kurt G. Schilling1, François Rheault2, Laurent Petit3, Colin B. Hansen1, Vishwesh Nath1, Fang-Cheng Yeh4, Gabriel Girard, Muhamed Barakovic5, Jonathan Rafael-Patino6, Thomas Yu6, Elda Fischi-Gomez6, Marco Pizzolato7, Mario Ocampo-Pineda8, Simona Schiavi8, Erick J. Canales-Rodríguez6, Alessandro Daducci8, Cristina Granziera5, Giorgio M. Innocenti9, Jean-Philippe Thiran6, Laura Mancini, Stephen J. Wastling, Sirio Cocozza, Maria Petracca10, Giuseppe Pontillo, Matteo Mancini11, Sjoerd B. Vos12, Vejay N. Vakharia12, John S. Duncan13, Helena Melero14, Lidia Manzanedo14, Emilio Sanz-Morales14, Ángel Peña-Melián15, Fernando Calamante16, Arnaud Attyé16, Ryan P. Cabeen17, Laura Korobova17, Arthur W. Toga17, Anupa Ambili Vijayakumari18, Drew Parker18, Ragini Verma18, Ahmed Radwan19, Stefan Sunaert19, Louise Emsell19, Alberto De Luca, Alexander Leemans, Claude J. Bajada20, Hamied A. Haroon21, Hojjatollah Azadbakht, Maxime Chamberland22, Sila Genc22, Chantal M. W. Tax22, Ping Hong Yeh23, Rujirutana Srikanchana23, Colin D. McKnight24, Joseph Yuan-Mou Yang25, Jian Chen, Claire E. Kelly, Chun-Hung Yeh26, Jerome Cochereau, Jerome Joseph Maller27, Thomas Welton, Fabien Almairac, Kiran K. Seunarine, Chris A. Clark, Fan Zhang28, Nikos Makris28, Alexandra J. Golby28, Yogesh Rathi28, Lauren J. O'Donnell28, Yihao Xia17, Dogu Baran Aydogan29, Yonggang Shi17, Francisco Guerreiro Fernandes, Mathijs Raemaekers, Shaun Warrington30, Stijn Michielse31, Alonso Ramirez-Manzanares32, Luis Concha33, Ramón Aranda34, Mariano Rivera Meraz32, Garikoitz Lerma-Usabiaga35, Lucas Roitman35, Lucius S. Fekonja36, Navona Calarco37, Michael Joseph37, Hajer Nakua37, Aristotle N. Voineskos37, Philippe Karan2, Gabrielle Grenier2, Jon Haitz Legarreta2, Nagesh Adluru38, Veena A. Nair38, Vivek Prabhakaran38, Andrew L. Alexander38, Koji Kamagata39, Yuya Saito39, Wataru Uchida39, Christina Andica39, Masahiro Abe39, Roza G. Bayrak1, Claudia A. M. Wheeler-Kingshott40, Egidio D'Angelo41, Fulvia Palesi41, Giovanni Savini, Nicolò Rolandi41, Pamela Guevara42, Josselin Houenou43, Narciso López-López42, Jean-François Mangin43, Cyril Poupon43, C. Roman42, Andrea Vázquez42, Chiara Maffei44, Mavilde Arantes45, José Paulo Andrade45, Susana M. Silva45, Vince D. Calhoun46, Eduardo Caverzasi47, Simone Sacco47, Michael Lauricella47, Franco Pestilli48, Daniel Bullock48, Yang Zhan49, Edith Brignoni-Pérez35, Catherine Lebel50, Jess E. Reynolds50, Igor Nestrasil51, René Labounek51, Christophe Lenglet51, Amy Paulson51, Štefánia Aulická52, Sarah R. Heilbronner51, Katja Heuer53, Bramsh Qamar Chandio54, Javier Guaje54, Wei Tang54, Eleftherios Garyfallidis54, Rajikha Raja55, Adam W. Anderson24, Bennett A. Landman1, Maxime Descoteaux2 
Vanderbilt University1, Université de Sherbrooke2, University of Bordeaux3, University of Pittsburgh4, University of Basel5, École Polytechnique Fédérale de Lausanne6, Technical University of Denmark7, University of Verona8, Karolinska Institutet9, University of Naples Federico II10, Brighton and Sussex Medical School11, University College London12, Epilepsy Society13, King Juan Carlos University14, Complutense University of Madrid15, University of Sydney16, University of Southern California17, University of Pennsylvania18, Katholieke Universiteit Leuven19, University of Malta20, Manchester Academic Health Science Centre21, Cardiff University22, Walter Reed National Military Medical Center23, Vanderbilt University Medical Center24, Royal Children's Hospital25, Chang Gung University26, GE Healthcare27, Brigham and Women's Hospital28, Aalto University29, University of Nottingham30, Maastricht University31, Centro de Investigación en Matemáticas32, National Autonomous University of Mexico33, Ensenada Center for Scientific Research and Higher Education34, Stanford University35, Charité36, Centre for Addiction and Mental Health37, University of Wisconsin-Madison38, Juntendo University39, UCL Institute of Neurology40, University of Pavia41, University of Concepción42, Université Paris-Saclay43, Harvard University44, University of Porto45, Georgia Institute of Technology46, University of California, San Francisco47, University of Texas at Austin48, Chinese Academy of Sciences49, University of Calgary50, University of Minnesota51, Masaryk University52, University of Paris53, Indiana University54, University of Arkansas for Medical Sciences55
TL;DR: Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects.

Journal ArticleDOI
TL;DR: Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI) and may reduce the risk of long-term memory loss.
Abstract: Introduction Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI). Methods Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44). Results Free and cued recall (Trial 1; P = .047), verbal fluency (categories; P = .024), Boston Naming Test (total correct answers; P = .033), and the Trail-Making Test (total errors; P = .017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre-intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged. Conclusions This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease.

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TL;DR: In this article, a qualitative study examined how teachers fostered student engagement in blended learning (BL), i.e., blended, blended online, and blended synchronous courses that combine synchronous and asynchronous activities.
Abstract: This qualitative study examined how teachers fostered student engagement in blended learning (BL), i.e., blended, blended online, and blended synchronous courses that combine synchronous and asynchronous activities. Twenty semi-structured interviews with teachers in various disciplines, at the undergraduate or graduate level in four universities, were conducted and analyzed using an inductive approach. Therefore, the study proposed a broad and comprehensive picture of teachers’ strategies to enhance student engagement in BL, that were classified in three meta-categories concerning (i) the course structure and pace; (ii) the selection of teaching and learning activities; and (iii) the teacher’s role and course relationships. Strategies were also linked with student engagement dimensions (behavioral, emotional, cognitive), whenever possible. The findings particularly emphasized the importance of a well-structured and -paced course, fully exploiting and integrating synchronous and asynchronous modes of BL. Clearly communicating how the course would unfold and corresponding expectations as well as establishing trusting relationships at the beginning of the semester also appeared as key to foster student engagement in BL. The use of various digital tools was also highlighted to promote student behavioral and emotional engagement at the undergraduate level, whereas cognitive and emotional engagement of graduate students was mainly targeted through experience-sharing and learning co-construction between students.

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TL;DR: In this paper, poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries.
Abstract: Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries...

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TL;DR: In this article, a new metaheuristic optimization algorithm, called social network search (SNS), is employed for solving mixed continuous/discrete engineering optimization problems, which mimics the social network user's efforts to gain more popularity by modeling the decision moods in expressing their opinions.
Abstract: In this paper, a new metaheuristic optimization algorithm, called social network search (SNS), is employed for solving mixed continuous/discrete engineering optimization problems. The SNS algorithm mimics the social network user’s efforts to gain more popularity by modeling the decision moods in expressing their opinions. Four decision moods, including imitation, conversation, disputation, and innovation, are real-world behaviors of users in social networks. These moods are used as optimization operators that model how users are affected and motivated to share their new views. The SNS algorithm was verified with 14 benchmark engineering optimization problems and one real application in the field of remote sensing. The performance of the proposed method is compared with various algorithms to show its effectiveness over other well-known optimizers in terms of computational cost and accuracy. In most cases, the optimal solutions achieved by the SNS are better than the best solution obtained by the existing methods.

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TL;DR: In this article, the authors examined the influence of caring for COVID-19 patients on nurse's perception of chronic fatigue, quality of care, satisfaction at work and intention to leave their organisation and the profession.
Abstract: Aim This study aims to examine, through the lens of the Job Demands-Resources model, the influence of caring for COVID-19 patients on nurse's perception of chronic fatigue, quality of care, satisfaction at work and intention to leave their organisation and the profession. Background Studies have examined how fear of COVID-19 contributes to the mental, physical and work adjustment among nurses. To date, few studies have been conducted examining how caring for patients with COVID-19 contributes to work outcomes among nurses. Methods This is a cross-sectional survey involving 1705 frontline nurses and licensed practical nurses in Quebec, Canada. From these, 782 reported caring for COVID-19 patients. Results High chronic fatigue, poor quality of care, lower work satisfaction and higher intention to leave their organisation were found for nurses caring for COVID-19 patients. Poorly prepared and overwhelmed nurses showed higher turnover intention than those well prepared and in control. Conclusions There is an urgent need to provide support to nurses during the pandemic, with a long-term strategy to increase their retention. Implications for nursing management Nurse administrators play an important role in supporting their nurses during a pandemic in the form of education, training and policy development to positively impact quality of care and retention.

Journal ArticleDOI
21 Sep 2021-JAMA
TL;DR: In this paper, the authors evaluated the effect of L rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU).
Abstract: Importance Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. Objective To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). Design, setting, and participants Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). Interventions Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. Main outcomes and measures The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. Results Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P Conclusions and relevance Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients. Trial registration ClinicalTrials.gov Identifier: NCT02462590.

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TL;DR: The inflammaging concept was introduced in 2000 by Prof. Franceschi as discussed by the authors, which was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress.
Abstract: The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.