Showing papers by "University of Montpellier published in 2021"
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Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
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
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Samsung Medical Center1, Peking University2, Cornell University3, Harvard University4, University of Montpellier5, Shanghai Jiao Tong University6, University of Ulsan7, Yonsei University8, Chang Gung University9, Prince of Songkla University10, Universidade Federal de Santa Maria11, Roswell Park Cancer Institute12, Kagawa University13, Merck & Co.14
TL;DR: In this paper, the authors compared pembrolizumab plus chemotherapy versus chemotherapy alone as a first-line treatment for advanced oesophageal cancer and Siewert type 1 gastro-oesophagesphageal junction cancer.
451 citations
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TL;DR: In this article, a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France was conducted to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences.
Abstract: Summary Background Treatment of locally advanced rectal cancer with chemoradiotherapy, surgery, and adjuvant chemotherapy controls local disease, but distant metastases remain common. We aimed to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences. Methods We did a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France. Eligible patients were adults aged 18–75 years and had newly diagnosed, biopsy-proven, rectal adenocarcinoma staged cT3 or cT4 M0, with a WHO performance status of 0–1. Patients were randomly assigned (1:1) to either the neoadjuvant chemotherapy group or standard-of-care group, using an independent web-based system by minimisation method stratified by centre, extramural extension of the tumour into perirectal fat according to MRI, tumour location, and stage. Investigators and participants were not masked to treatment allocation. The neoadjuvant chemotherapy group received neoadjuvant chemotherapy with FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 intravenously every 14 days for 6 cycles), chemoradiotherapy (50 Gy during 5 weeks and 800 mg/m2 concurrent oral capecitabine twice daily for 5 days per week), total mesorectal excision, and adjuvant chemotherapy (3 months of modified FOLFOX6 [intravenous oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2400 mg/m2 over 46 h every 14 days for six cycles] or capecitabine [1250 mg/m2 orally twice daily on days 1–14 every 21 days]). The standard-of-care group received chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (for 6 months). The primary endpoint was disease-free survival assessed in the intention-to-treat population at 3 years. Safety analyses were done on treated patients. This trial was registered with EudraCT (2011-004406-25) and ClinicalTrials.gov ( NCT01804790 ) and is now complete. Findings Between June 5, 2012, and June 26, 2017, 461 patients were randomly assigned to either the neoadjuvant chemotherapy group (n=231) or the standard-of-care group (n=230). At a median follow-up of 46·5 months (IQR 35·4–61·6), 3-year disease-free survival rates were 76% (95% CI 69–81) in the neoadjuvant chemotherapy group and 69% (62–74) in the standard-of-care group (stratified hazard ratio 0·69, 95% CI 0·49–0·97; p=0·034). During neoadjuvant chemotherapy, the most common grade 3–4 adverse events were neutropenia (38 [17%] of 225 patients) and diarrhoea (25 [11%] of 226). During chemoradiotherapy, the most common grade 3–4 adverse event was lymphopenia (59 [28%] of 212 in the neoadjuvant chemotherapy group vs 67 [30%] of 226 patients in the standard-of-care group). During adjuvant chemotherapy, the most common grade 3–4 adverse events were lymphopenia (18 [11%] of 161 in the neoadjuvant chemotherapy group vs 42 [27%] of 155 in the standard-of-care group), neutropenia (nine [6%] of 161 vs 28 [18%] of 155), and peripheral sensory neuropathy (19 [12%] of 162 vs 32 [21%] of 155). Serious adverse events occurred in 63 (27%) of 231 participants in the neoadjuvant chemotherapy group and 50 (22%) of 230 patients in the standard-of-care group (p=0·167), during the whole treatment period. During adjuvant therapy, serious adverse events occurred in 18 (11%) of 163 participants in the neoadjuvant chemotherapy group and 36 (23%) of 158 patients in the standard-of-care group (p=0·0049). Treatment-related deaths occurred in one ( Interpretation Intensification of chemotherapy using FOLFIRINOX before preoperative chemoradiotherapy significantly improved outcomes compared with preoperative chemoradiotherapy in patients with cT3 or cT4 M0 rectal cancer. The significantly improved disease-free survival in the neoadjuvant chemotherapy group and the decreased neurotoxicity indicates that the perioperative approach is more efficient and better tolerated than adjuvant chemotherapy. Therefore, the PRODIGE 23 results might change clinical practice. Funding Institut National du Cancer, Ligue Nationale Contre le Cancer, and R&D Unicancer.
381 citations
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University of Manchester1, City University of New York2, Istanbul Technical University3, New York University4, Heidelberg University5, Niels Bohr Institute6, University of Edinburgh7, University of Bologna8, Academy of Athens9, Sapienza University of Rome10, University of Naples Federico II11, Stanford University12, Institut d'Astrophysique de Paris13, University of Portsmouth14, Cardiff University15, Universidade Federal do Espírito Santo16, University of Michigan17, Asia Pacific Center for Theoretical Physics18, University of New Mexico19, University of Barcelona20, University of St. Thomas (Minnesota)21, Princeton University22, National Autonomous University of Mexico23, California Institute of Technology24, INAF25, University of Chicago26, Michigan Technological University27, Lawrence Berkeley National Laboratory28, University of Cambridge29, Imperial College London30, Ruhr University Bochum31, University of Waterloo32, University of Oxford33, Johns Hopkins University34, University of Pennsylvania35, University of California, Davis36, Birla Institute of Technology and Science37, RWTH Aachen University38, Université libre de Bruxelles39, University of Padua40, Indian Institute of Technology Kharagpur41, Spanish National Research Council42, University of North Carolina at Chapel Hill43, University of Arizona44, University of Oslo45, Jamia Millia Islamia46, University of Southern Denmark47, National Institute for Space Research48, Fermilab49, Presidency University, Kolkata50, Université Paris-Saclay51, University of Montpellier52, University of Szczecin53, Korea Astronomy and Space Science Institute54, University of California, Los Angeles55, University of Paris56, Leiden University57, Swarthmore College58, University of Sheffield59, University of Amsterdam60, United College, Winnipeg61, Liaoning Normal University62
TL;DR: In this article, the authors focus on the 4.4σ tension between the Planck estimate of the Hubble constant H0 and the SH0ES collaboration measurements and discuss how the next decade's experiments will be crucial.
322 citations
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TL;DR: In this paper, the authors evaluated the specific benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery compared with receiving cytoreduction surgery alone.
Abstract: Summary Background The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone Methods We did a randomised, open-label, phase 3 trial at 17 cancer centres in France Eligible patients were aged 18–70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks) Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both The primary endpoint was overall survival, which was analysed in the intention-to-treat population Safety was assessed in all patients who received surgery This trial is registed with ClinicalTrialsgov , NCT00769405 , and is now completed Findings Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group After median follow-up of 63·8 months (IQR 53·0–77·1), median overall survival was 41·7 months (95% CI 36·2–53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1–49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63–1·58]; stratified log-rank p=0·99) At 30 days, two (2%) treatment-related deaths had occurred in each group Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035) Interpretation Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases Funding Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer
321 citations
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TL;DR: Tezepelumab as discussed by the authors is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma.
Abstract: Background Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell–derived cytokine implicated in the pathogenesis of asthma. The efficacy a...
299 citations
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State University of New York Upstate Medical University1, Heidelberg University2, University of Melbourne3, Capital Medical University4, Harvard University5, Monash University, Clayton campus6, Icahn School of Medicine at Mount Sinai7, Montreal Children's Hospital8, Universidade Federal do Rio Grande do Sul9, Peking University10, University of Southampton11, University of Toronto12, University of Washington13, King Khalid University14, King's College London15, Aga Khan University16, Karolinska Institutet17, Radboud University Nijmegen18, Vrije Universiteit Brussel19, University of Nottingham20, Aarhus University21, University of Cologne22, Trinity College, Dublin23, University of Würzburg24, University of Bergen25, University Medical Center Groningen26, University of Wyoming27, University of California, Berkeley28, University of California, San Francisco29, Nottinghamshire Healthcare NHS Foundation Trust30, Duke University31, University of Amsterdam32, Örebro University33, Chongqing Medical University34, Tel Aviv University35, Washington University in St. Louis36, Federal University of Rio de Janeiro37, University College Cork38, University of British Columbia39, University of Pittsburgh40, Oregon Health & Science University41, University of Montpellier42, University of Ibadan43, University of São Paulo44, Hebrew University of Jerusalem45, University of Sydney46, Jawaharlal Institute of Postgraduate Medical Education and Research47, University of Canterbury48, Autonomous University of Barcelona49, Stellenbosch University50, University of California, Davis51, National Medical College52, Hofstra University53, University of Texas Health Science Center at Houston54, University of Southern Denmark55, University of California, Irvine56, Cardiff University57, Okinawa Institute of Science and Technology58, HU University of Applied Sciences Utrecht59, Katholieke Universiteit Leuven60, University of the Free State61, University of Turin62, Johns Hopkins University63, University of Zurich64
TL;DR: In this article, the authors presented 208 empirically supported statements about ADHD using meta-analysis, which allow for firm statements about the nature, course, outcome causes and treatments for disorders that are useful for reducing misconceptions and stigma.
295 citations
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University of California, Santa Barbara1, Utah State University2, IFREMER3, University of British Columbia4, Virginia Tech5, Leibniz Institute of Marine Sciences6, University of Freiburg7, University of Montpellier8, The Nature Conservancy9, Marine Conservation Institute10, University of Queensland11, Dalhousie University12, Oregon State University13
TL;DR: In this paper, a conservation planning framework is developed to prioritize highly protected marine protected areas in places that would result in multiple benefits today and in the future, by protecting biodiversity, boosting the yield of fisheries and securing marine carbon stocks that are at risk from human activities.
Abstract: The ocean contains unique biodiversity, provides valuable food resources and is a major sink for anthropogenic carbon. Marine protected areas (MPAs) are an effective tool for restoring ocean biodiversity and ecosystem services1,2, but at present only 2.7% of the ocean is highly protected3. This low level of ocean protection is due largely to conflicts with fisheries and other extractive uses. To address this issue, here we developed a conservation planning framework to prioritize highly protected MPAs in places that would result in multiple benefits today and in the future. We find that a substantial increase in ocean protection could have triple benefits, by protecting biodiversity, boosting the yield of fisheries and securing marine carbon stocks that are at risk from human activities. Our results show that most coastal nations contain priority areas that can contribute substantially to achieving these three objectives of biodiversity protection, food provision and carbon storage. A globally coordinated effort could be nearly twice as efficient as uncoordinated, national-level conservation planning. Our flexible prioritization framework could help to inform both national marine spatial plans4 and global targets for marine conservation, food security and climate action. Using a globally coordinated strategic conservation framework to plan an increase in ocean protection through marine protected areas can yield benefits for biodiversity, food provisioning and carbon storage.
265 citations
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TL;DR: Characterization by multiple techniques shows that all Fe–N4 sites formed via this approach are gas-phase and electrochemically accessible and have an active site density of 1.92 × 1020 sites per gram with 100% site utilization.
Abstract: Replacing scarce and expensive platinum (Pt) with metal–nitrogen–carbon (M–N–C) catalysts for the oxygen reduction reaction in proton exchange membrane fuel cells has largely been impeded by the low oxygen reduction reaction activity of M–N–C due to low active site density and site utilization. Herein, we overcome these limits by implementing chemical vapour deposition to synthesize Fe–N–C by flowing iron chloride vapour over a Zn–N–C substrate at 750 °C, leading to high-temperature trans-metalation of Zn–N4 sites into Fe–N4 sites. Characterization by multiple techniques shows that all Fe–N4 sites formed via this approach are gas-phase and electrochemically accessible. As a result, the Fe–N–C catalyst has an active site density of 1.92 × 1020 sites per gram with 100% site utilization. This catalyst delivers an unprecedented oxygen reduction reaction activity of 33 mA cm−2 at 0.90 V (iR-corrected; i, current; R, resistance) in a H2–O2 proton exchange membrane fuel cell at 1.0 bar and 80 °C. Replacing platinum with metal–nitrogen–carbon catalysts for the oxygen reduction reaction in proton exchange membrane fuel cells has been impeded by low activity. These limitations have now been overcome by the trans-metalation of Zn–N4 sites into Fe–N4 sites.
264 citations
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TL;DR: The results of this study suggest that personalised dosimetry is to improve outcomes in future trials of selective internal radiation therapy with yttrium-90-loaded glass microspheres and should be used in practice.
228 citations
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Stephen P.H. Alexander1, Arthur Christopoulos2, Anthony P. Davenport3, Eamonn Kelly4 +151 more•Institutions (85)
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.
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TL;DR: A conceptual framework of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) assays is proposed in this paper, which point out current challenges of CTC and ctDNA research.
Abstract: Over the past 10 years, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) have received enormous attention as new biomarkers and subjects of translational research. Although both biomarkers are already used in numerous clinical trials, their clinical utility is still under investigation with promising first results. Clinical applications include early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Here, we propose a conceptual framework of CTC and ctDNA assays and point out current challenges of CTC and ctDNA research, which might structure this dynamic field of translational cancer research. SIGNIFICANCE: The analysis of blood for CTCs or cell-free nucleic acids called "liquid biopsy" has opened new avenues for cancer diagnostics, including early detection of tumors, improved risk assessment and staging, as well as early detection of relapse and monitoring of tumor evolution in the context of cancer therapies.
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TL;DR: An empirically grounded conceptualization is developed that sets these two phenomena apart, finding that there are two distinctive differences: digital transformation activities leverage digital technology in (re)defining an organization’s value proposition, while IT-enabled organizational transformation activities Leverage digitalTechnology in supporting the value proposition.
Abstract: Although digital transformation offers a number of opportunities for today’s organizations, information systems scholars and practitioners struggle to grasp what digital transformation really is, particularly in terms of how it differs from the well-established concept of information technology (IT)-enabled organizational transformation. By integrating literature from organization science and information systems research with two longitudinal case studies—one on digital transformation, the other on IT-enabled organizational transformation—we develop an empirically grounded conceptualization that sets these two phenomena apart. We find that there are two distinctive differences: (1) digital transformation activities leverage digital technology in (re)defining an organization’s value proposition, while IT-enabled organizational transformation activities leverage digital technology in supporting the value proposition, and (2) digital transformation involves the emergence of a new organizational identity, whereas IT-enabled organizational transformation involves the enhancement of an existing organizational identity. We synthesize these arguments in a process model to distinguish the different types of transformations and propose directions for future research.
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University of Montpellier1, Centre national de la recherche scientifique2, Agricultural Research Service3, University of Dundee4, James Hutton Institute5, University of Natural Resources and Life Sciences, Vienna6, University of Manchester7, Wageningen University and Research Centre8, University of Reading9, Czech University of Life Sciences Prague10, Morton Arboretum11, University of Hamburg12, University of Göttingen13, Macquarie University14, Forschungszentrum Jülich15, Spanish National Research Council16, University of Georgia17, Polish Academy of Sciences18, Adam Mickiewicz University in Poznań19, ETH Zurich20, University of Minnesota21, Oak Ridge National Laboratory22, University of Auvergne23, Laurentian University24, University of Freiburg25, Leiden University26, Chinese Academy of Sciences27, Florida International University28, Leipzig University29
TL;DR: It is found that below-ground traits with widest importance in plant and ecosystem functioning are not those most commonly measured, and advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with strongest influence on the functions, and to link genotypes to plant andcosystem functioning.
Abstract: The effects of plants on the biosphere, atmosphere and geosphere are key determinants of terrestrial ecosystem functioning. However, despite substantial progress made regarding plant belowground components, we are still only beginning to explore the complex relationships between root traits and functions. Drawing on the literature in plant physiology, ecophysiology, ecology, agronomy and soil science, we reviewed 24 aspects of plant and ecosystem functioning and their relationships with a number of root system traits, including aspects of architecture, physiology, morphology, anatomy, chemistry, biomechanics and biotic interactions. Based on this assessment, we critically evaluated the current strengths and gaps in our knowledge, and identify future research challenges in the field of root ecology. Most importantly, we found that belowground traits with the broadest importance in plant and ecosystem functioning are not those most commonly measured. Also, the estimation of trait relative importance for functioning requires us to consider a more comprehensive range of functionally relevant traits from a diverse range of species, across environments and over time series. We also advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with the strongest links on functions, and to link genotypes to plant and ecosystem functioning.
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TL;DR: Glycans modify lipids and proteins to mediate inter-and intramolecular interactions across all domains of life as mentioned in this paper, and RNA is used as a third scaffold for glycosylation.
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University of Manchester1, City University of New York2, Istanbul Technical University3, New York University4, Heidelberg University5, Niels Bohr Institute6, University of Edinburgh7, University of Bologna8, Academy of Athens9, Sapienza University of Rome10, University of Naples Federico II11, Stanford University12, Institut d'Astrophysique de Paris13, University of Portsmouth14, Cardiff University15, Universidade Federal do Espírito Santo16, University of Michigan17, Asia Pacific Center for Theoretical Physics18, University of New Mexico19, University of Barcelona20, Centre national de la recherche scientifique21, Princeton University22, National Autonomous University of Mexico23, Jet Propulsion Laboratory24, INAF25, University of Chicago26, Michigan Technological University27, University of Cambridge28, Imperial College London29, Ruhr University Bochum30, University of Waterloo31, Johns Hopkins University32, University of Pennsylvania33, University of California, Davis34, Birla Institute of Technology and Science35, RWTH Aachen University36, Université libre de Bruxelles37, University of Padua38, Indian Institute of Technology Kharagpur39, Spanish National Research Council40, University of North Carolina at Chapel Hill41, University of Arizona42, University of Oslo43, Jamia Millia Islamia44, National Institute for Space Research45, Fermilab46, Presidency University, Kolkata47, Université Paris-Saclay48, University of Montpellier49, University of Szczecin50, Korea Astronomy and Space Science Institute51, University of California, Los Angeles52, Leiden University53, University of Southern Denmark54, Swarthmore College55, University of Sheffield56, University of Amsterdam57, United College, Winnipeg58, Liaoning Normal University59
TL;DR: In this article, the authors focus on the tension between Planck data and weak lensing measurements and redshift surveys, and discuss the importance of trying to fit multiple cosmological datasets with complete physical models, rather than fitting individual datasets with a few handpicked theoretical parameters.
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TL;DR: In this paper, the authors analyzed how the board characteristics could be associated with globally corporate social responsibility CSR and specific areas of CSR, and found that diversity in boards and diversity of boards globally are positively associated with corporate social performance.
Abstract: This study analyzes how the board’s characteristics could be associated with globally corporate social responsibility CSR and specific areas of CSR. It is drawn on all listed firms, in 2016, on the SBF120 between 2003 and 2016. Our results provide strong evidence that diversity in boards and diversity of boards globally are positively associated with corporate social performance. However, they influence differently specific dimensions of CSR performance. First, we show that large boards are positively associated with all areas of CSR performance, while specific and overall CSR scores are negatively associated with CEO-chair structures. Second, board gender diversity is positively associated with human rights and corporate governance dimensions. Third, age diversity is positively associated with corporate governance, human resources, human rights, and environmental activities. Also, our results provide evidence that outside directors care about CSR performance. Specifically, the presence of foreign directors is positively associated with environmental performance and community involvement, whereas CSR-Governance dimension is positively associated with the presence of independent directors. Regarding the director’s educational level, post-graduated directors are positively and significantly associated with overall CSR score and all CSR sub-scores, except the corporate governance one. When directors have multiple directorships, they are more concerned about human resources, environmental performance, and business ethics. Finally, our findings are robust only in non-family firms. In fact, family boards are less diverse than non-family ones; specifically, they have a lower number of independent, foreign, and high-educated directors.
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TL;DR: In this article, a nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids is presented.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and sensitive protein detection and quantification in simple and robust formats for widespread point-of-care applications. Here, we report on nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids. The sensors combine a solution-processable conjugated polymer in the transistor channel and high-density and orientation-controlled bioconjugation of nanobody–SpyCatcher fusion proteins on disposable gate electrodes. The devices provide results after 10 min of exposure to 5 μl of unprocessed samples, maintain high specificity and single-molecule sensitivity in human saliva and serum, and can be reprogrammed to detect any protein antigen if a corresponding specific nanobody is available. We used the sensors to detect green fluorescent protein, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) spike proteins, and for the COVID-19 screening of unprocessed clinical nasopharyngeal swab and saliva samples with a wide range of viral loads. Organic electrochemical transistors functionalized with antigen-specific nanobodies can rapidly detect attomolar-to-nanomolar levels of the antigens in complex bodily fluids.
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Centre national de la recherche scientifique1, Oak Ridge National Laboratory2, Agricultural Research Service3, University of Natural Resources and Life Sciences, Vienna4, Polish Academy of Sciences5, Macquarie University6, Forschungszentrum Jülich7, Pennsylvania State University8, Adam Mickiewicz University in Poznań9, James Hutton Institute10, University of Dundee11, VU University Amsterdam12, ETH Zurich13, University of Minnesota14, University of Hamburg15, Wageningen University and Research Centre16, University of Auvergne17, Laurentian University18, University of Freiburg19, Leiden University20, University of Montpellier21, Chinese Academy of Sciences22, Florida International University23, Leipzig University24, University of Georgia25, University of Leeds26, Institute of Ecosystem Studies27, Universidade Federal de Goiás28, University of Western Australia29, Clemson University30, Morton Arboretum31
TL;DR: A major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers’ views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning.
Abstract: In the context of a recent massive increase in research on plant root functions and their impact on the environment, root ecologists currently face many important challenges to keep on generating cutting-edge, meaningful and integrated knowledge. Consideration of the below-ground components in plant and ecosystem studies has been consistently called for in recent decades, but methodology is disparate and sometimes inappropriate. This handbook, based on the collective effort of a large team of experts, will improve trait comparisons across studies and integration of information across databases by providing standardised methods and controlled vocabularies. It is meant to be used not only as starting point by students and scientists who desire working on below-ground ecosystems, but also by experts for consolidating and broadening their views on multiple aspects of root ecology. Beyond the classical compilation of measurement protocols, we have synthesised recommendations from the literature to provide key background knowledge useful for: (1) defining below-ground plant entities and giving keys for their meaningful dissection, classification and naming beyond the classical fine-root vs coarse-root approach; (2) considering the specificity of root research to produce sound laboratory and field data; (3) describing typical, but overlooked steps for studying roots (e.g. root handling, cleaning and storage); and (4) gathering metadata necessary for the interpretation of results and their reuse. Most importantly, all root traits have been introduced with some degree of ecological context that will be a foundation for understanding their ecological meaning, their typical use and uncertainties, and some methodological and conceptual perspectives for future research. Considering all of this, we urge readers not to solely extract protocol recommendations for trait measurements from this work, but to take a moment to read and reflect on the extensive information contained in this broader guide to root ecology, including sections I-VII and the many introductions to each section and root trait description. Finally, it is critical to understand that a major aim of this guide is to help break down barriers between the many subdisciplines of root ecology and ecophysiology, broaden researchers' views on the multiple aspects of root study and create favourable conditions for the inception of comprehensive experiments on the role of roots in plant and ecosystem functioning.
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TL;DR: In this article, the authors analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort and showed that viral dynamics after hospital admission was an independent predictor of mortality.
Abstract: The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort The model predicted a median peak viral load that coincided with symptom onset Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P 20) Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 131, P < 10-3) Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 20 and 29 d in patients of age <65 y and ≥65 y, respectively Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors Our results show that viral dynamics is associated with mortality in hospitalized patients Strategies aiming to reduce viral load could have an effect on mortality rate in this population
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TL;DR: In insights into how personality predicts concerns and behaviours related to the COVID-19 pandemic, age moderated several trait-response associations, suggesting that some of the responses were associated more strongly in older adults, a group at risk for complications of CO VID-19.
Abstract: This study examined the associations between personality traits and psychological and behavioural responses to the coronavirus disease 2019 (COVID-19) pandemic. Personality was assessed in January/February 2020 when the public was not aware of the spread of coronavirus in the USA. Participants were reassessed in late March 2020 with four sets of questions about the pandemic: concerns, precautions, preparatory behaviours, and duration estimates. The sample consisted of N = 2066 participants (mean age = 51.42; range = 18-98; 48.5% women). Regression models were used to analyse the data with age, gender, education, race, and ethnicity as covariates. Consistent with the preregistered hypotheses, higher neuroticism was related to more concerns and longer duration estimates related to COVID-19, higher extraversion was related to shorter duration estimates, and higher conscientiousness was associated with more precautions. In contrast to the preregistered hypotheses, higher neuroticism was associated with fewer precautions and unrelated to preparatory behaviours. Age moderated several trait-response associations, suggesting that some of the responses were associated more strongly in older adults, a group at risk for complications of COVID-19. For example, older adults high in conscientiousness prepared more. The present findings provide insights into how personality predicts concerns and behaviours related to the COVID-19 pandemic. © 2020 European Association of Personality Psychology.
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TL;DR: In this paper, the authors focus on the potential dark side of social media use among Generation Z (Gen Z) in the UK during the COVID-19 pandemic lockdown between March and May 2020, and reveal that information overload through social media had a negative impact on Gen Z social media users' psychological well-being.
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University of London1, Stockholm University2, National Institutes of Health3, French Institute of Health and Medical Research4, University of Washington5, Utrecht University6, Aristotle University of Thessaloniki7, Masaryk University8, Finnish Environment Institute9, Harvard University10, University of Exeter11, University of Montpellier12, Imperial College London13
TL;DR: COVID-19 will have a long-lasting impact on the environmental health field and will open new research perspectives and policy needs and the mechanisms of these interactions deserve additional scrutiny.
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TL;DR: In this paper, the authors characterized in depth host cell responses against SARS-CoV-2 in primary human airway epithelia (HAE) and immortalized cell lines.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 19 (COVID-19), which ranges from mild respiratory symptoms to acute respiratory distress syndrome, and death in the most severe cases. Immune dysregulation with altered innate cytokine responses is thought to contribute to disease severity. Here, we characterized in depth host cell responses against SARS-CoV-2 in primary human airway epithelia (HAE) and immortalized cell lines. Our results demonstrate that primary HAE and model cells elicit a robust induction of type I and III interferons (IFNs). Importantly, we show for the first time that melanoma differentiation associated gene (MDA)-5 is the main sensor of SARS-CoV-2 in lung cells. IFN exposure strongly inhibited viral replication and de novo production of infectious virions. However, despite high levels of IFNs produced in response to SARS-CoV-2 infection, the IFN response was unable to control viral replication in lung cells, contrary to what was previously reported in intestinal epithelial cells. Altogether, these results highlight the complex and ambiguous interplay between viral replication and the timing of IFN responses.IMPORTANCE Mammalian cells express sensors able to detect specific features of pathogens and induce the interferon response, which is one of the first line of defenses against viruses and help controlling viral replication. The mechanisms and impact of SARS-CoV-2 sensing in lung epithelial cells remained to be deciphered. In this study, we report that despite a high production of type I and III interferons specifically induced by MDA-5-mediated sensing of SARS-CoV-2, primary and immortalized lung epithelial cells are unable to control viral replication. However, exogenous interferons potently inhibited replication, if provided early upon viral exposure. A better understanding of the ambiguous interplay between the interferon response and SARS-CoV-2 replication is essential to guide future therapeutical interventions.
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Agostino Gemelli University Polyclinic1, Catholic University of the Sacred Heart2, University of Cologne3, University of Milan4, University of California, San Diego5, Medical University of Graz6, University of Cambridge7, University of Insubria8, University of Milano-Bicocca9, Ankara University10, Masaryk University11, Churchill Hospital12, Autonomous University of Barcelona13, University Medical Center Groningen14, Palacký University, Olomouc15, Hamad Medical Corporation16, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico17, King's College London18, University of Rijeka19, Hospital General Universitario Gregorio Marañón20, Gomel State Medical University21, University of Szeged22, Mansoura University23, Marmara University24, Katholieke Universiteit Leuven25, Karolinska University Hospital26, University of Rome Tor Vergata27, Vanderbilt University Medical Center28, Hospital Universitario La Paz29, University of Belgrade30, Sultan Qaboos University31, Spanish National Research Council32, Wrocław Medical University33, University of Hamburg34, University Hospital of Basel35, Innsbruck Medical University36, Paris-Sorbonne University37, University of Montpellier38, Federal University of Rio de Janeiro39, University of Zagreb40, University Hospital Centre Zagreb41
TL;DR: In this paper, the authors studied the risk factors for adverse outcomes in patients with hematological malignancies (HM) who developed COVID-19 and analyzed predictors of mortality.
Abstract: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.
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TL;DR: In this paper, a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3 is presented, which contains at least 92% of stars of stellar type M9 within 100pc of the sun.
Abstract: Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use.Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue.Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun.Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.
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Newcastle University1, University of Helsinki2, Université Paris-Saclay3, Gulf University for Science and Technology4, University of the French West Indies and Guiana5, Leibniz Institute of Marine Sciences6, University of Lisbon7, King's College London8, South African Institute for Aquatic Biodiversity9, University of Vienna10, University of Montpellier11, American Museum of Natural History12, Woods Hole Oceanographic Institution13, University of South Florida14, Institut Universitaire de France15
TL;DR: The authors in this paper determined patterns and trends in economic costs of aquatic IAS by examining: (i) the distribution of these costs across taxa, geographic regions and cost types; (ii) the temporal dynamics of global costs; and (iii) knowledge gaps, especially compared to terrestrial IAS.
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University of Southampton1, University Hospital Southampton NHS Foundation Trust2, University of Amsterdam3, University of Chicago4, University of Washington5, University of North Carolina at Chapel Hill6, Jagiellonian University Medical College7, Dresden University of Technology8, Steno Diabetes Center9, University of Copenhagen10, University of California, San Diego11, University of Montpellier12, University of Miami13, VU University Amsterdam14, State University of New York Upstate Medical University15, University of Southern California16
TL;DR: The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults.
Abstract: The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycemia, behavioral considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management, and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that health care professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors.
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TL;DR: A review of 3D genome organization analysis can be found in this article, where the most commonly used techniques and their contribution to our current knowledge of nuclear architecture are discussed and a perspective on up-and-coming methods that open possibilities for future major discoveries is provided.
Abstract: Understanding how chromatin is folded in the nucleus is fundamental to understanding its function. Although 3D genome organization has been historically difficult to study owing to a lack of relevant methodologies, major technological breakthroughs in genome-wide mapping of chromatin contacts and advances in imaging technologies in the twenty-first century considerably improved our understanding of chromosome conformation and nuclear architecture. In this Review, we discuss methods of 3D genome organization analysis, including sequencing-based techniques, such as Hi-C and its derivatives, Micro-C, DamID and others; microscopy-based techniques, such as super-resolution imaging coupled with fluorescence in situ hybridization (FISH), multiplex FISH, in situ genome sequencing and live microscopy methods; and computational and modelling approaches. We describe the most commonly used techniques and their contribution to our current knowledge of nuclear architecture and, finally, we provide a perspective on up-and-coming methods that open possibilities for future major discoveries.
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TL;DR: In this article, the authors develop and test a model that examines key drivers of visitors' COVID-19-induced social distancing behavior and its effect on their intent to use virtual reality-based (vs in-person) attraction site tours during and post-COVID19.