Showing papers by "University of Iowa published in 2020"
Leiden University1, Loyola University Chicago2, University of North Carolina at Chapel Hill3, Utrecht University4, Erasmus University Rotterdam5, Moscow State University6, Texas A&M University–Texarkana7, University of Iowa8, University of Hong Kong9, Spanish National Research Council10, University of Giessen11
TL;DR: The independent zoonotic transmission of SARS-CoV and SARS -CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance.
Abstract: The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
5,527 citations
Donostia International Physics Center1, Rovira i Virgili University2, Victoria University of Wellington3, MacDiarmid Institute for Advanced Materials and Nanotechnology4, University of Cambridge5, University of California, Santa Barbara6, Queen's University Belfast7, Technical University of Denmark8, University of Victoria9, Chung-Ang University10, University of Jena11, Leibniz Institute of Photonic Technology12, Rutgers University13, University of Strathclyde14, University of Liverpool15, University of Iowa16, University of Minnesota17, Heidelberg University18, National Institute of Advanced Industrial Science and Technology19, Chalmers University of Technology20, Humboldt University of Berlin21, University of Michigan22, Jiangnan University23, Stanford University24, Xiamen University25, Ludwig Maximilian University of Munich26, Hokkaido University27, Seoul National University28, University of Illinois at Urbana–Champaign29, Kwansei Gakuin University30, University of Vigo31, Free University of Berlin32, Northwestern University33, University of Duisburg-Essen34, National Research Council35, Indian Institute of Science Education and Research, Thiruvananthapuram36, Duke University37, Northeastern University (China)38, Temple University39, Wuhan University40, Japan Advanced Institute of Science and Technology41, Jilin University42, Ikerbasque43
TL;DR: Prominent authors from all over the world joined efforts to summarize the current state-of-the-art in understanding and using SERS, as well as to propose what can be expected in the near future, in terms of research, applications, and technological development.
Abstract: The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article.
1,768 citations
Johns Hopkins University School of Medicine1, Tufts University2, University of New South Wales3, Aarhus University4, Aarhus University Hospital5, Heidelberg University6, University of Melbourne7, Duke University8, McGill University9, University of Iowa10, Southern University of Science and Technology11, University of Toronto12, University of Washington13, Dalhousie University14, Aichi Medical University15, Queen's University16
TL;DR: This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period.
Abstract: The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.
1,432 citations
Leiden University Medical Center1, Moscow State University2, Loyola University Chicago3, University of North Carolina at Chapel Hill4, Utrecht University5, Charité6, Texas A&M University–Texarkana7, University of Iowa8, University of Hong Kong9, Spanish National Research Council10, University of Giessen11
TL;DR: The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses assessed the novelty of the human pathogen tentatively named 2019-nCoV and formally recognizes this virus as a sister to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Abstract: The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
1,057 citations
Romina Ahumada1, Carlos Allende Prieto2, Carlos Allende Prieto3, Andres Almeida4 +342 more•Institutions (94)
TL;DR: The most recent data release from the Sloan Digital Sky Surveys (SDSS-IV) is DR16 as mentioned in this paper, which is the fourth and penultimate from the fourth phase of the survey.
Abstract: This paper documents the sixteenth data release (DR16) from the Sloan Digital Sky Surveys; the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the southern hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey (TDSS) and new data from the SPectroscopic IDentification of ERosita Survey (SPIDERS) programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).
803 citations
TL;DR: For the third time in as many decades, a zoonotic coronavirus has crossed species to infect human populations and this virus, provisionally called 2019-nCoV, was first identified in Wuhan, China, in 2016.
Abstract: For the third time in as many decades, a zoonotic coronavirus has crossed species to infect human populations. This virus, provisionally called 2019-nCoV, was first identified in Wuhan, China, in p...
774 citations
TL;DR: The role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN) are discussed, which is broadly utilized by medical oncologists and hematologists in their daily practice.
Abstract: Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.
724 citations
TL;DR: Inspired by earlier works, the application of deep learning models to detect COVID-19 patients from their chest radiography images and shows that the generated heatmaps contain most of the infected areas annotated by the authors' board certified radiologist.
700 citations
Bernhard Nocht Institute for Tropical Medicine1, Public Health England2, World Health Organization3, Icahn School of Medicine at Mount Sinai4, University of North Carolina at Chapel Hill5, European Medicines Agency6, Peking Union Medical College7, Katholieke Universiteit Leuven8, National Institutes of Health9, University of Alabama at Birmingham10, University of Pittsburgh11, University of Saskatchewan12, University of Maryland, Baltimore13, Erasmus University Medical Center14, Center for Biologics Evaluation and Research15, Université Paris-Saclay16, Wageningen University and Research Centre17, Columbia University18, University of California, San Diego19, University of Texas Medical Branch20, Autonomous University of Barcelona21, Friedrich Loeffler Institute22, Li Ka Shing Faculty of Medicine, University of Hong Kong23, University of Iowa24, Kansas State University25, Tulane University26, Geelong Football Club27, University of York28, Beth Israel Deaconess Medical Center29
TL;DR: The findings of a World Health Organization expert working group that is developing animal models to test vaccines and therapeutic agents for the treatment of COVID-19, and their relevance for preclinical testing, are reviewed.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.
630 citations
TL;DR: Evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15 suggests that requiring face maskUse in public might help in mitigating COVID-19 spread.
Abstract: State policies mandating public or community use of face masks or covers in mitigating the spread of coronavirus disease 2019 (COVID-19) are hotly contested. This study provides evidence from a natural experiment on the effects of state government mandates for face mask use in public issued by fifteen states plus Washington, D.C., between April 8 and May 15, 2020. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage points in 1-5, 6-10, 11-15, 16-20, and 21 or more days after state face mask orders were signed, respectively. Estimates suggest that as a result of the implementation of these mandates, more than 200,000 COVID-19 cases were averted by May 22, 2020. The findings suggest that requiring face mask use in public could help in mitigating the spread of COVID-19.
579 citations
Rotem Botvinik-Nezer1, Rotem Botvinik-Nezer2, Felix Holzmeister3, Colin F. Camerer4 +217 more•Institutions (78)
TL;DR: The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
Abstract: Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.
Children's Hospital of Philadelphia1, Great Ormond Street Hospital2, McMaster University3, Boston Children's Hospital4, St Mary's Hospital5, University of Queensland6, University of Cape Town7, University of Liverpool8, Durham University9, French Institute of Health and Medical Research10, South University11, University of Cambridge12, University Hospital Southampton NHS Foundation Trust13, Nationwide Children's Hospital14, Erasmus University Medical Center15, All India Institute of Medical Sciences16, Radboud University Nijmegen17, Royal Children's Hospital18, Children's Hospital Los Angeles19, New York University20, Stony Brook University21, Apollo Hospitals22, Johns Hopkins University23, University of the West of England24, University of Iowa25, St. Jude Children's Research Hospital26, Cincinnati Children's Hospital Medical Center27, Seattle Children's28, University of British Columbia29, Centre national de la recherche scientifique30
TL;DR: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations.
Abstract: OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
TL;DR: The evidence on the optimal strategies to prevent, diagnose, and treat venous thromboembolism in patients with COVID-19 is sparse, but rapidly evolving.
TL;DR: Transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues and passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss.
TL;DR: Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry, and high-levels of neutralizing antibodies were induced in both severe and mild patients which were higher in the severe group.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus 2019 (COVID-19) pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity, and neutralization antibody response in patients with COVID-19. Two groups of patients with RT-PCR-confirmed COVID-19 were enrolled in this study: 12 severely ill patients in intensive care units who needed mechanical ventilation and 11 mildly ill patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severely ill patients had viral shedding in a variety of tissues for 20-40 days after onset of disease (8/12, 66.7%), while the majority of mildly ill patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA 10 days after onset (9/11, 81.8%). Mildly ill patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both the severe and mild groups at 9 days after onset, and remained at a high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS. High levels of neutralizing antibodies were induced after about 10 days after onset in both severely and mildly ill patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from patients with COVID-19 inhibited SARS-CoV-2 entry. Sera from convalescent patients with SARS or Middle East respiratory syndrome (MERS) did not. Anti-SARS-CoV-2 S and N IgG levels exhibited a moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in humans after SARS-CoV-2 infection.
Book•
30 Jun 2020TL;DR: The third edition of the Bioassays with Arthropods, Third Edition as discussed by the authors, offers the best of both worlds by translating the terse, precise language of the statistician into language used by the laboratory scientist.
Abstract: Imagine a statistics book for bioassays written by a statistician. Next, imagine a statistics book for bioassays written for a layman. Bioassays with Arthropods, Third Edition offers the best of both worlds by translating the terse, precise language of the statistician into language used by the laboratory scientist. The book explains the statistical basis and analysis for each kind of quantal response bioassay in just the right amount of detail. The first two editions were a great reference for designing, conducting, and interpreting bioassays: this completely revised and updated third edition will also train the laboratory scientist to be an expert in estimation of dose response curves.
New in the Third Edition:
Introduces four new Windows and Apple-based computer programs (PoloJR, OptiDose, PoloMixture and PoloMulti) for the analyses of binary and multiple response analyses, respectively
Replaces out-of-date GLIM examples with R program samples
Includes a new chapter, Population Toxicology, and takes a systems approach to bioassays
Expands the coverage of invasive species and quarantine statistics
Building on the foundation set by the much-cited first two editions, the authors clearly delineate applications and ideas that are exceptionally challenging for those not already familiar with their use. They lead you through the methods with such ease and organization, that you suddenly find yourself readily able to apply concepts that you never thought you would understand.
To order the PoloSuite computer software described in Bioassays with Arthropods, Third Edition, use the order form found at www.leora-software.com or contact the LeOra Software Company at leorasoftware@gmail.com.
Boston University1, University of Virginia2, Icahn School of Medicine at Mount Sinai3, University of Pennsylvania4, Brighton and Sussex Medical School5, Harvard University6, Johns Hopkins University7, Cleveland Clinic8, Vanderbilt University9, Maastricht University10, University of Iowa11, Medical University of South Carolina12, Albany Medical College13, University of Colorado Denver14, University of California, San Francisco15, Aarhus University16, Ohio State University17, Kaiser Permanente18, Morehouse School of Medicine19, University of Cincinnati20
TL;DR: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis.
Abstract: Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or mo...
TL;DR: The β−coronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.
TL;DR: A murine model of broad and immediate utility is described to investigate COVID-19 pathogenesis, and to evaluate new therapies and vaccines.
TL;DR: In this paper, wide-ranging revisions to the Standardized World Income Inequality Database (SWIID) were presented to maximize the comparability of income inequality estimates for the broadest possible coverage of countries and years, and two k-fold cross-validations, by observation and by country, were used to evaluate the SWIID's success in predicting the Luxembourg Income Study.
Abstract: Objective This article documents wide‐ranging revisions to the Standardized World Income Inequality Database (SWIID), which seeks to maximize the comparability of income inequality estimates for the broadest possible coverage of countries and years. Methods Two k‐fold cross‐validations, by observation and by country, are used to evaluate the SWIID's success in predicting the Luxembourg Income Study (LIS), recognized in the field as setting the standard for comparability. Results The cross‐validations indicate that the new SWIID's estimates and their uncertainty are even more accurate than previous versions, extending its advantage in comparability over alternate income inequality data sets. Conclusion Given its superior coverage and comparability, the SWIID remains the optimum source of data for broadly cross‐national research on income inequality.
TL;DR: Melanoma cells in lymph experience less oxidative stress and less ferroptosis in lymph than in blood, owing to higher levels of oleic acid in lymph, and thus exposure to the lymphatic environment increases subsequent metastasis through blood.
Abstract: Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1-4; however, the reason for this is unclear Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4 Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood
Children's Hospital of Philadelphia1, Great Ormond Street Hospital2, McMaster University3, Boston Children's Hospital4, St Mary's Hospital5, University of Queensland6, University of Cape Town7, University of Liverpool8, Durham University9, South University10, French Institute of Health and Medical Research11, University of Cambridge12, University Hospital Southampton NHS Foundation Trust13, Nationwide Children's Hospital14, Erasmus University Medical Center15, All India Institute of Medical Sciences16, Radboud University Nijmegen17, University Health System18, Royal Children's Hospital19, Children's Hospital Los Angeles20, New York University21, Stony Brook University22, Apollo Hospitals23, Johns Hopkins University24, University of the West of England25, University of Iowa26, St. Jude Children's Research Hospital27, Cincinnati Children's Hospital Medical Center28, Seattle Children's29, University of British Columbia30, Centre national de la recherche scientifique31
TL;DR: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations.
Abstract: OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
TL;DR: In this article, a cellular-nanoporation method for the production of large quantities of exosomes containing therapeutic mRNAs and targeting peptides was reported, and the exosome-containing exosomal mRNA transcripts were shown to restore tumour-suppressor function, enhanced inhibition of tumour growth and increased survival.
Abstract: Exosomes are attractive as nucleic-acid carriers because of their favourable pharmacokinetic and immunological properties and their ability to penetrate physiological barriers that are impermeable to synthetic drug-delivery vehicles. However, inserting exogenous nucleic acids, especially large messenger RNAs, into cell-secreted exosomes leads to low yields. Here we report a cellular-nanoporation method for the production of large quantities of exosomes containing therapeutic mRNAs and targeting peptides. We transfected various source cells with plasmid DNAs and stimulated the cells with a focal and transient electrical stimulus that promotes the release of exosomes carrying transcribed mRNAs and targeting peptides. Compared with bulk electroporation and other exosome-production strategies, cellular nanoporation produced up to 50-fold more exosomes and a more than 103-fold increase in exosomal mRNA transcripts, even from cells with low basal levels of exosome secretion. In orthotopic phosphatase and tensin homologue (PTEN)-deficient glioma mouse models, mRNA-containing exosomes restored tumour-suppressor function, enhanced inhibition of tumour growth and increased survival. Cellular nanoporation may enable the use of exosomes as a universal nucleic-acid carrier for applications requiring transcriptional manipulation.
TL;DR: Low‐molecular‐weight heparin is the guideline‐endorsed treatment for cancer‐associated venous thromboembolism (VTE) and apixaban is approved for the treatment of acute VTE.
TL;DR: Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension.
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
Hospital for Special Surgery1, University of Texas Southwestern Medical Center2, Oklahoma Medical Research Foundation3, University of California, San Diego4, Duke University5, University of Michigan6, McMaster University7, University of Utah8, New York University9, Johns Hopkins University10, Baylor University11, Stanford University12, University of Toronto13, Drexel University14, Georgetown University Medical Center15, Brigham and Women's Hospital16, McGill University17, University of Mississippi18, University of California, San Francisco19, University of Iowa20, American College of Rheumatology21, ECRI Institute22, University of Pittsburgh23
TL;DR: To develop an evidence‐based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).
Abstract: Objective To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). Methods We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. Results This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. Conclusion This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.
TL;DR: Ordered Quantile (ORQ) normalization is introduced, a one-to-one transformation that is designed to consistently and effectively transform a vector of arbitrary distribution into a vector that follows a normal (Gaussian) distribution.
Abstract: Normalization transformations have recently experienced a resurgence in popularity in the era of machine learning, particularly in data preprocessing. However, the classical methods that can be ada...
University of Washington1, University of Florida2, University of Düsseldorf3, University of Iowa4, Oregon Health & Science University5, University of California, Irvine6, Alfred I. duPont Hospital for Children7, Thomas Jefferson University8, University of Texas Southwestern Medical Center9, St Thomas' Hospital10, Columbia University11, Maastricht University12, University of Regensburg13, Emory University14
TL;DR: These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.
Abstract: Disclaimer: The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.
National Radio Astronomy Observatory1, University of Manitoba2, Cornell University3, United States Naval Research Laboratory4, Space Telescope Science Institute5, University of Toronto6, Saint Anselm College7, California Institute of Technology8, University of California, Berkeley9, Max Planck Society10, Drexel University11, University of Alberta12, University of Minnesota13, University of Cape Town14, University of the Western Cape15, Universidad de Guanajuato16, Harvard University17, University of Bristol18, Academia Sinica Institute of Astronomy and Astrophysics19, Pennsylvania State University20, University of Iowa21, West Virginia University22, University of Colorado Boulder23, Newcastle University24, Leiden University25, Hebrew University of Jerusalem26, University of Washington27, University of Oxford28, Smithsonian Institution29, University of Illinois at Urbana–Champaign30, National Autonomous University of Mexico31, Spanish National Research Council32, European Southern Observatory33, University of Hamburg34, INAF35
TL;DR: The Very Large Array Sky Survey (VLASS) as discussed by the authors is a synoptic, all-sky radio sky survey with a unique combination of high angular resolution (≈2.5"), sensitivity (a 1σ goal of 70 μJy/beam in the coadded data), full linear Stokes polarimetry, time domain coverage, and wide bandwidth (2-4 GHz).
Abstract: The Very Large Array Sky Survey (VLASS) is a synoptic, all-sky radio sky survey with a unique combination of high angular resolution (≈2.5\"), sensitivity (a 1σ goal of 70 μJy/beam in the coadded data), full linear Stokes polarimetry, time domain coverage, and wide bandwidth (2-4 GHz). The first observations began in September 2017, and observing for the survey will finish in 2024. VLASS will use approximately 5500 hours of time on the Karl G. Jansky Very Large Array (VLA) to cover the whole sky visible to the VLA (Declination > −40∘), a total of 33,885 deg^2. The data will be taken in three epochs to allow the discovery of variable and transient radio sources. The survey is designed to engage radio astronomy experts, multi-wavelength astronomers, and citizen scientists alike. By utilizing an \"on the fly\" interferometry mode, the observing overheads are much reduced compared to a conventional pointed survey. In this paper, we present the science case and observational strategy for the survey, and also results from early survey observations.
University of Chicago1, American Heart Association2, University of Missouri–Kansas City3, University of Iowa4, University of Alberta5, Hofstra University6, University of Pennsylvania7, Queen's University8, University of Calgary9, University of Oklahoma10, American Academy of Pediatrics11, Stanford University12, University of Texas at Arlington13, Ohio State University14, Virginia Commonwealth University15, Boston Children's Hospital16, Liberty University17, Columbia University18, New York University19