Showing papers by "University of Wisconsin-Madison published in 2021"
University of Southern California1, French Institute for Research in Computer Science and Automation2, University of Oulu3, Princeton University4, University of Warwick5, Georgia Institute of Technology6, Rutgers University7, University of Virginia8, University of Washington9, Carnegie Mellon University10, École Polytechnique Fédérale de Lausanne11, University of Pittsburgh12, University of Wisconsin-Madison13, University of California, San Diego14, University of Illinois at Urbana–Champaign15, Nanyang Technological University16, Australian National University17, Stanford University18, IT University of Copenhagen19, Massachusetts Institute of Technology20, University of California, Berkeley21, Cornell University22, Emory University23, Hong Kong University of Science and Technology24
TL;DR: In this article, the authors describe the state-of-the-art in the field of federated learning from the perspective of distributed optimization, cryptography, security, differential privacy, fairness, compressed sensing, systems, information theory, and statistics.
Abstract: The term Federated Learning was coined as recently as 2016 to describe a machine learning setting where multiple entities collaborate in solving a machine learning problem, under the coordination of a central server or service provider. Each client’s raw data is stored locally and not exchanged or transferred; instead, focused updates intended for immediate aggregation are used to achieve the learning objective. Since then, the topic has gathered much interest across many different disciplines and the realization that solving many of these interdisciplinary problems likely requires not just machine learning but techniques from distributed optimization, cryptography, security, differential privacy, fairness, compressed sensing, systems, information theory, statistics, and more. This monograph has contributions from leading experts across the disciplines, who describe the latest state-of-the art from their perspective. These contributions have been carefully curated into a comprehensive treatment that enables the reader to understand the work that has been done and get pointers to where effort is required to solve many of the problems before Federated Learning can become a reality in practical systems. Researchers working in the area of distributed systems will find this monograph an enlightening read that may inspire them to work on the many challenging issues that are outlined. This monograph will get the reader up to speed quickly and easily on what is likely to become an increasingly important topic: Federated Learning.
2,144 citations
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
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, German Center for Neurodegenerative Diseases5, University of Bonn6, Harvard University7, University of Lausanne8, University of Padua9, National Research Council10, Heidelberg University11, Salk Institute for Biological Studies12, University of Minnesota13, Pasteur Institute14, Tel Aviv University15, Johns Hopkins University16, University of Portsmouth17, Katholieke Universiteit Leuven18, PSL Research University19, Trinity College, Dublin20, Baylor College of Medicine21, University College London22, University of Edinburgh23, Oregon Health & Science University24, National Institutes of Health25, Columbia University26, University of Rochester27, University of Copenhagen28, Ludwig Maximilian University of Munich29, University of Málaga30, Tufts University31, University of Freiburg32, Utrecht University33, Nihon University34, Max Delbrück Center for Molecular Medicine35, University of California, Los Angeles36, University of Yamanashi37, New York University38, University of British Columbia39, King Abdullah University of Science and Technology40, University of Wisconsin-Madison41, University of California, San Francisco42, McGill University43, University of Kentucky44, Kyushu University45, University of Bordeaux46, Polytechnic Institute of Cávado and Ave47, University of Minho48, University of Alabama at Birmingham49, University of Gothenburg50, University of Poitiers51, Cajal Institute52, King's College London53, University of Strasbourg54, Virginia Tech55, University of Düsseldorf56, Russian Academy of Sciences57, I.M. Sechenov First Moscow State Medical University58, University of Seville59, Georgia Institute of Technology60, University of Texas Health Science Center at Houston61, University of California, San Diego62, Universidade Federal do Rio Grande do Sul63, University of Ljubljana64, Ikerbasque65, University of Manchester66
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Abstract: Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.
797 citations
Northwestern University1, University of California, San Francisco2, University of Michigan3, City of Hope National Medical Center4, Vanderbilt University5, Seattle Cancer Care Alliance6, Fox Chase Cancer Center7, University of Wisconsin-Madison8, University of Texas Southwestern Medical Center9, University of Utah10, University of Nebraska Medical Center11, University of Alabama at Birmingham12, University of California, Los Angeles13, University of South Florida14, Mayo Clinic15, Washington University in St. Louis16, Yale Cancer Center17, Stanford University18, Case Western Reserve University19, University of Colorado Boulder20, Brigham and Women's Hospital21, Ohio State University22, Roswell Park Cancer Institute23, University of Texas MD Anderson Cancer Center24, Harvard University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of Tennessee29, Johns Hopkins University30, Duke University31, National Comprehensive Cancer Network32
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section as discussed by the authors.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
589 citations
University of Edinburgh1, Autonomous University of Madrid2, Pierre-and-Marie-Curie University3, University of Portsmouth4, University of Cape Town5, University of Wisconsin-Madison6, Moscow State University7, New Mexico State University8, New York University9, University of Utah10, University of Toronto11, Université Paris-Saclay12, University of Waterloo13, Sejong University14, Stanford University15, Max Planck Society16, University College London17, Texas Christian University18, National Autonomous University of Mexico19, University of Barcelona20, Universidad de Guanajuato21, Consejo Nacional de Ciencia y Tecnología22, Liverpool John Moores University23, Lawrence Berkeley National Laboratory24, Ohio State University25, École Polytechnique Fédérale de Lausanne26, University of Wyoming27, Haverford College28, University of Oxford29, University of Pittsburgh30, Perimeter Institute for Theoretical Physics31, California Institute of Technology32, Ohio University33, Swinburne University of Technology34, Fermilab35, University of Washington36, Korea Astronomy and Space Science Institute37, Brookhaven National Laboratory38, University of St Andrews39, Durham University40
TL;DR: In this article, the authors present the cosmological implications from final measurements of clustering using galaxies, quasars, and Lyα forests from the completed SDSS lineage of experiments in large-scale structure.
Abstract: We present the cosmological implications from final measurements of clustering using galaxies, quasars, and Lyα forests from the completed Sloan Digital Sky Survey (SDSS) lineage of experiments in large-scale structure. These experiments, composed of data from SDSS, SDSS-II, BOSS, and eBOSS, offer independent measurements of baryon acoustic oscillation (BAO) measurements of angular-diameter distances and Hubble distances relative to the sound horizon, rd, from eight different samples and six measurements of the growth rate parameter, fσ8, from redshift-space distortions (RSD). This composite sample is the most constraining of its kind and allows us to perform a comprehensive assessment of the cosmological model after two decades of dedicated spectroscopic observation. We show that the BAO data alone are able to rule out dark-energy-free models at more than eight standard deviations in an extension to the flat, ΛCDM model that allows for curvature. When combined with Planck Cosmic Microwave Background (CMB) measurements of temperature and polarization, under the same model, the BAO data provide nearly an order of magnitude improvement on curvature constraints relative to primary CMB constraints alone. Independent of distance measurements, the SDSS RSD data complement weak lensing measurements from the Dark Energy Survey (DES) in demonstrating a preference for a flat ΛCDM cosmological model when combined with Planck measurements. The combined BAO and RSD measurements indicate σ8=0.85±0.03, implying a growth rate that is consistent with predictions from Planck temperature and polarization data and with General Relativity. When combining the results of SDSS BAO and RSD, Planck, Pantheon Type Ia supernovae (SNe Ia), and DES weak lensing and clustering measurements, all multiple-parameter extensions remain consistent with a ΛCDM model. Regardless of cosmological model, the precision on each of the three parameters, ωΛ, H0, and σ8, remains at roughly 1%, showing changes of less than 0.6% in the central values between models. In a model that allows for free curvature and a time-evolving equation of state for dark energy, the combined samples produce a constraint ωk=-0.0022±0.0022. The dark energy constraints lead to w0=-0.909±0.081 and wa=-0.49-0.30+0.35, corresponding to an equation of state of wp=-1.018±0.032 at a pivot redshift zp=0.29 and a Dark Energy Task Force Figure of Merit of 94. The inverse distance ladder measurement under this model yields H0=68.18±0.79 km s-1 Mpc-1, remaining in tension with several direct determination methods; the BAO data allow Hubble constant estimates that are robust against the assumption of the cosmological model. In addition, the BAO data allow estimates of H0 that are independent of the CMB data, with similar central values and precision under a ΛCDM model. Our most constraining combination of data gives the upper limit on the sum of neutrino masses at mν<0.115 eV (95% confidence). Finally, we consider the improvements in cosmology constraints over the last decade by comparing our results to a sample representative of the period 2000-2010. We compute the relative gain across the five dimensions spanned by w, ωk, mν, H0, and σ8 and find that the SDSS BAO and RSD data reduce the total posterior volume by a factor of 40 relative to the previous generation. Adding again the Planck, DES, and Pantheon SN Ia samples leads to an overall contraction in the five-dimensional posterior volume of 3 orders of magnitude.
575 citations
TL;DR: In this article, the authors discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CART cell therapy in both B cell leukemia or lymphoma.
Abstract: Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
509 citations
Mayo Clinic1, Johns Hopkins University2, Seattle Cancer Care Alliance3, University of Colorado Boulder4, University of Utah5, Fox Chase Cancer Center6, Northwestern University7, Case Western Reserve University8, University of Texas MD Anderson Cancer Center9, Brigham and Women's Hospital10, Duke University11, University of South Florida12, University of Texas Southwestern Medical Center13, Yale Cancer Center14, University of California, San Francisco15, Roswell Park Cancer Institute16, Harvard University17, University of Wisconsin-Madison18, University of Michigan19, Stanford University20, Vanderbilt University21, City of Hope National Medical Center22, Washington University in St. Louis23, University of Tennessee Health Science Center24, Ohio State University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of California, Los Angeles29, National Comprehensive Cancer Network30
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC as mentioned in this paper.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
495 citations
TL;DR: In this paper, the authors present a formalization of the notion of grounded theory for coding procedures emanating from grounded theory, which were limited by technologies of the 1960s: colored pens, scissors, and index cards.
Abstract: Qualitative coding procedures emanating from grounded theory were limited by technologies of the 1960s: colored pens, scissors, and index cards. Today, electronic documents can be flexibly stored, ...
467 citations
Fox Chase Cancer Center1, Vanderbilt University2, University of Tennessee Health Science Center3, University of Utah4, Washington University in St. Louis5, University of Pennsylvania6, University of Alabama at Birmingham7, Johns Hopkins University8, Roswell Park Cancer Institute9, University of California, Los Angeles10, Northwestern University11, University of Colorado Boulder12, Stanford University13, University of South Florida14, University of Texas MD Anderson Cancer Center15, University of California, San Francisco16, Duke University17, University of Michigan18, Seattle Cancer Care Alliance19, Memorial Sloan Kettering Cancer Center20, Case Western Reserve University21, University of Nebraska Medical Center22, Ohio State University23, Harvard University24, University of California, San Diego25, City of Hope National Medical Center26, Mayo Clinic27, University of Wisconsin-Madison28, Brigham and Women's Hospital29, National Comprehensive Cancer Network30
TL;DR: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies as mentioned in this paper.
Abstract: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
455 citations
University of California, San Francisco1, University of South Florida2, University of Michigan3, University of Tennessee Health Science Center4, Northwestern University5, Vanderbilt University6, Seattle Cancer Care Alliance7, City of Hope National Medical Center8, Duke University9, University of Colorado Boulder10, Ohio State University11, University of California, Los Angeles12, Fox Chase Cancer Center13, Harvard University14, Roswell Park Cancer Institute15, Case Western Reserve University16, Washington University in St. Louis17, University of Nebraska Medical Center18, Yale Cancer Center19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Johns Hopkins University23, University of Texas Southwestern Medical Center24, University of Alabama at Birmingham25, Memorial Sloan Kettering Cancer Center26, University of Utah27, Stanford University28, University of Pennsylvania29, University of Texas MD Anderson Cancer Center30, Brigham and Women's Hospital31, National Comprehensive Cancer Network32
Abstract: Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.
402 citations
TL;DR: A web-based tool (covid-omics.app) is presented enabling interactive exploration of the compendium and its utility through a machine learning approach for prediction of COVID-19 severity is illustrated.
Abstract: We performed RNA-seq and high-resolution mass spectrometry on 128 blood samples from COVID-19-positive and COVID-19-negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many of which were involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity.
University of Las Palmas de Gran Canaria1, Kingston General Hospital2, University of Sydney3, Meir Medical Center4, Ben-Gurion University of the Negev5, University of Wollongong6, The Royal Marsden NHS Foundation Trust7, Okayama University8, University of Wisconsin-Madison9, University of California, Davis10, Merck & Co.11, Johns Hopkins University12
TL;DR: The first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC) was reported in this article.
Abstract: PURPOSEWe report the first 5-year follow-up of any first-line phase III immunotherapy trial for non–small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an op...
Northwestern University1, Memorial Sloan Kettering Cancer Center2, University of Wisconsin-Madison3, University of South Florida4, Johns Hopkins University5, University of Nebraska Medical Center6, Mayo Clinic7, Vanderbilt University8, University of California, San Diego9, Case Western Reserve University10, Stanford University11, Ohio State University12, University of Tennessee Health Science Center13, Harvard University14, Washington University in St. Louis15, Roswell Park Cancer Institute16, University of Alabama at Birmingham17, University of California, San Francisco18, University of Utah19, University of Pennsylvania20, Duke University21, Seattle Cancer Care Alliance22, University of California, Los Angeles23, Fox Chase Cancer Center24, University of Michigan25, University of Colorado Boulder26, City of Hope National Medical Center27, Yale University28, University of Texas MD Anderson Cancer Center29, University of Texas Southwestern Medical Center30, National Comprehensive Cancer Network31
TL;DR: The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts as discussed by the authors.
Abstract: The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
TL;DR: In this article, the authors provide an answer to the question "How Were the Elements from Iron to Uranium Made?" (Abridged) by combining new results and important breakthroughs in the related nuclear, atomic and astronomical fields of science.
Abstract: The production of about half of the heavy elements found in nature is assigned to a specific astrophysical nucleosynthesis process: the rapid neutron capture process (r-process). Although this idea has been postulated more than six decades ago, the full understanding faces two types of uncertainties/open questions: (a) The nucleosynthesis path in the nuclear chart runs close to the neutron-drip line, where presently only limited experimental information is available, and one has to rely strongly on theoretical predictions for nuclear properties. (b) While for many years the occurrence of the r-process has been associated with supernovae, more recent studies have cast substantial doubts on this environment. Alternative scenarios include the mergers of neutron stars, neutron-star black hole mergers, but possibly also rare classes of supernovae as well as hypernovae/collapsars with polar jet ejecta and also accretion disk outflows related to the collapse of fast rotating massive stars with high magnetic fields. Stellar r-process abundance observations, have provided insights into, and constraints on the frequency of and conditions in the responsible stellar production sites. One of them, neutron star mergers, was just identified and related to the Gravitational Wave event GW170817. High resolution observations, increasingly more precise due to improved experimental atomic data, have been particularly important in defining the heavy element abundance patterns of the old halo stars, and thus determining the extent, and nature, of the earliest nucleosynthesis in our Galaxy. Combining new results and important breakthroughs in the related nuclear, atomic and astronomical fields of science, this review attempts to provide an answer to the question "How Were the Elements from Iron to Uranium Made?" (Abridged)
Mayo Clinic1, Harvard University2, Roswell Park Cancer Institute3, University of California, Irvine4, University of Wisconsin–Milwaukee5, Rutgers University6, City of Hope National Medical Center7, Boston University8, University of Wisconsin-Madison9, American Cancer Society10, University of Southern California11, University of Oxford12, Stanford University13, Fred Hutchinson Cancer Research Center14, University of Washington15, National Institutes of Health16, Vanderbilt University17, Cornell University18, University of Utah19, University of Pennsylvania20
TL;DR: In this paper, population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and risk assessment.
Abstract: Background Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and...
TL;DR: A randomized, double-blind, randomized, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) was conducted to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma as discussed by the authors.
Abstract: Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.
TL;DR: Strategies for infectious diseases clinicians to apply risk communication principles and frameworks to improve patient care and public message development in response to COVID-19 are proposed.
Abstract: A number of important principles in effective risk communication established in the late 20th century can provide important scientific insight into patient response to the risks posed by COVID-19 [1-3]. Early risk communication scholars studied public perceptions of risk in response to environmental disasters, or infectious disease outbreaks. They found acceptability of risk, and any limitations and acceptability of response by experts was shaped by two key components: hazard and outrage. The number of people who are exposed, infected and fall ill can be considered the hazard. How the public and patients perceive the risk and respond to messages regarding risk mitigation relates to outrage. Social and cultural factors, immediacy, uncertainty, familiarity, personal control, scientific uncertainty and trust in institutions and media all shape acceptability of response. These outrage factors influence the ever-changing public understanding of COVID-19 risk, as well as the public's acceptance of personal and societal mitigation strategies. Risk perceptions and acceptability of mitigation strategies are also largely shaped in the context of culture and society. In concert, hazard and outrage along with cultural and economic context shape adherence to, and overall acceptance of, personal mitigation strategies including wearing facemasks, and social distancing among the general public. The spread of misinformation on social media in the context of crisis communication provides both challenges and opportunities for experts and officials to effectively communicate and influence these outrage factors. Social media offers an opportunity for experts to quickly convey true information about hazards, but offers others the opportunity to counter this with the spread of misinformation and exacerbate outrage. We propose strategies for infectious diseases clinicians to apply risk communication principles and frameworks to improve patient care and public message development in response to COVID-19.
Johns Hopkins University1, Vanderbilt University2, Mayo Clinic3, University of Wisconsin-Madison4, University of Colorado Boulder5, Duke University6, University of California, San Francisco7, City of Hope National Medical Center8, Harvard University9, University of Texas at Austin10, Fred Hutchinson Cancer Research Center11, Memorial Sloan Kettering Cancer Center12, University of South Florida13, Fox Chase Cancer Center14, Stanford University15, University of California, Los Angeles16, Brigham and Women's Hospital17, Case Western Reserve University18, University of Pennsylvania19, Northwestern University20, University of California, San Diego21, University of Michigan22, University of Texas Southwestern Medical Center23, Ohio State University24, Yale University25, University of Nebraska Medical Center26, University of Utah27, Roswell Park Cancer Institute28, National Comprehensive Cancer Network29
TL;DR: In this paper, the authors examined the occurrence of co-infections and superinfection and their outcomes among patients with SARS-CoV-2 infection and found that the presence of either coinfection or super-infection was associated with poor outcomes, including increased mortality.
Abstract: INTRODUCTION: The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. PATIENTS AND METHODS: We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763. RESULTS: Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively). CONCLUSIONS: Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.
Georgetown University1, Mayo Clinic2, The Chinese University of Hong Kong3, university of lille4, Hospital Universitario La Paz5, University of Manchester6, Japanese Foundation for Cancer Research7, University of Wisconsin-Madison8, Seoul National University Bundang Hospital9, Genentech10, Vanderbilt University Medical Center11
TL;DR: In this article, the authors demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to car crash prevention was beneficial.
Abstract: PURPOSE:IMpower133 (ClinicalTrials.gov identifier: NCT02763579), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to car...
Northwestern University1, Stanford University2, Johns Hopkins University3, Duke University4, University of Pennsylvania5, Fred Hutchinson Cancer Research Center6, Harvard University7, Mayo Clinic8, University of Texas Southwestern Medical Center9, City of Hope National Medical Center10, Memorial Sloan Kettering Cancer Center11, Fox Chase Cancer Center12, Washington University in St. Louis13, Roswell Park Cancer Institute14, University of Wisconsin-Madison15, University of California, San Diego16, Case Western Reserve University17, Vanderbilt University18, University of South Florida19, University of California, Los Angeles20, University of Tennessee Health Science Center21, University of California, San Francisco22, Ohio State University23, University of Michigan24, University of Nebraska Medical Center25, University of Utah26, National Comprehensive Cancer Network27
TL;DR: The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease Recommendations for disease monitoring and treatment of recurrent disease are also included as mentioned in this paper.
Abstract: The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease Recommendations for disease monitoring and treatment of recurrent disease are also included The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities This article summarizes the panel's discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer
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.
University of Chicago1, University of Delaware2, ETH Zurich3, Ames Research Center4, Oregon State University5, University of Southern California6, Stanford University7, University of Helsinki8, Cleveland Clinic Lerner College of Medicine9, Cleveland Clinic Lerner Research Institute10, Swedish Defence Research Agency11, Smithsonian Tropical Research Institute12, University of New South Wales13, Montana State University14, University of Wisconsin-Madison15, Carleton College16, University of Copenhagen17, IFREMER18, Marine Biological Laboratory19, Université Paris-Saclay20, University of Washington21
TL;DR: The workflows designed to enable researchers to interpret data can constrain the biological questions that can be asked as discussed by the authors, but the workflows can also be difficult to adapt to real-world applications.
Abstract: Big data abound in microbiology, but the workflows designed to enable researchers to interpret data can constrain the biological questions that can be asked. Five years after anvi’o was first published, this community-led multi-omics platform is maturing into an open software ecosystem that reduces constraints in ‘omics data analyses.
TL;DR: In this paper, the Sofia SARS Antigen Fluorescent Immunoassay (FIA) was compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin.
Abstract: Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).
25 Mar 2021
TL;DR: In this paper, the porous matrix of natural wood is deconstructed to form a homogeneous cellulose-lignin slurry that features nanoscale entanglement and hydrogen bonding between the regenerated lignin and cellulose micro/nanofibrils.
Abstract: Renewable and biodegradable materials derived from biomass are attractive candidates to replace non-biodegradable petrochemical plastics. However, the mechanical performance and wet stability of biomass are generally insufficient for practical applications. Herein, we report a facile in situ lignin regeneration strategy to synthesize a high-performance bioplastic from lignocellulosic resources (for example, wood). In this process, the porous matrix of natural wood is deconstructed to form a homogeneous cellulose–lignin slurry that features nanoscale entanglement and hydrogen bonding between the regenerated lignin and cellulose micro/nanofibrils. The resulting lignocellulosic bioplastic shows high mechanical strength, excellent water stability, ultraviolet-light resistance and improved thermal stability. Furthermore, the lignocellulosic bioplastic has a lower environmental impact as it can be easily recycled or safely biodegraded in the natural environment. This in situ lignin regeneration strategy involving only green and recyclable chemicals provides a promising route to producing strong, biodegradable and sustainable lignocellulosic bioplastic as a promising alternative to petrochemical plastics. There is growing interest in the development of biodegradable plastics from renewable resources. Here the authors report an in situ process involving only green chemicals to deconstruct natural wood, forming lignocellulosic bioplastics that are mechanically strong, stable against water and sustainable.
Ohio State University1, Indiana University2, University of Maryland, Baltimore3, University of Michigan4, University of Iowa5, Indiana University – Purdue University Indianapolis6, Michigan State University7, University of Nebraska–Lincoln8, University of Wisconsin-Madison9, Purdue University10, University of Minnesota11, Northwestern University12, University of Maryland, College Park13, Pennsylvania State University14, Rutgers University15, University of Nebraska Medical Center16
TL;DR: The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches for safe return to play as mentioned in this paper.
Abstract: Importance Myocarditis is a leading cause of sudden death in competitive athletes Myocardial inflammation is known to occur with SARS-CoV-2 Different screening approaches for detection of myocarditis have been reported The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches Objective To determine the prevalence of myocarditis in athletes with COVID-19 and compare screening strategies for safe return to play Design, Setting, and Participants Big Ten COVID-19 Cardiac Registry principal investigators were surveyed for aggregate observational data from March 1, 2020, through December 15, 2020, on athletes with COVID-19 For athletes with myocarditis, presence of cardiac symptoms and details of cardiac testing were recorded Myocarditis was categorized as clinical or subclinical based on the presence of cardiac symptoms and CMR findings Subclinical myocarditis classified as probable or possible myocarditis based on other testing abnormalities Myocarditis prevalence across universities was determined The utility of different screening strategies was evaluated Exposures SARS-CoV-2 by polymerase chain reaction testing Main Outcome and Measure Myocarditis via cardiovascular diagnostic testing Results Representing 13 universities, cardiovascular testing was performed in 1597 athletes (964 men [604%]) Thirty-seven (including 27 men) were diagnosed with COVID-19 myocarditis (overall 23%; range per program, 0%-76%); 9 had clinical myocarditis and 28 had subclinical myocarditis If cardiac testing was based on cardiac symptoms alone, only 5 athletes would have been detected (detected prevalence, 031%) Cardiac magnetic resonance imaging for all athletes yielded a 74-fold increase in detection of myocarditis (clinical and subclinical) Follow-up CMR imaging performed in 27 (730%) demonstrated resolution of T2 elevation in all (100%) and late gadolinium enhancement in 11 (407%) Conclusions and Relevance In this cohort study of 1597 US competitive athletes with CMR screening after COVID-19 infection, 37 athletes (23%) were diagnosed with clinical and subclinical myocarditis Variability was observed in prevalence across universities, and testing protocols were closely tied to the detection of myocarditis Variable ascertainment and unknown implications of CMR findings underscore the need for standardized timing and interpretation of cardiac testing These unique CMR imaging data provide a more complete understanding of the prevalence of clinical and subclinical myocarditis in college athletes after COVID-19 infection The role of CMR in routine screening for athletes safe return to play should be explored further
TL;DR: The "Coping with COVID-19" survey assessed US healthcare worker stress as mentioned in this paper and found that stress is highest among nursing assistants, medical assistants, social workers, inpatient workers, women and persons of color.
TL;DR: In this paper, Cardiac involvement among hospitalized patients with severe coronavirus disease 2019 (COVID-19) is common and associated with adverse outcomes, and a study aimed to determine the prevale...
Abstract: Background: Cardiac involvement among hospitalized patients with severe coronavirus disease 2019 (COVID-19) is common and associated with adverse outcomes. This study aimed to determine the prevale...
TL;DR: In this article, the authors presented a study of patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) who have limited options that offer objective r...
Abstract: PURPOSEPatients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective r...
Ohio State University1, University of Nebraska Medical Center2, Northwestern University3, University of California, San Francisco4, Harvard University5, Brigham and Women's Hospital6, Vanderbilt University7, University of Tennessee Health Science Center8, University of California, San Diego9, University of Michigan10, Mayo Clinic11, University of Texas MD Anderson Cancer Center12, Johns Hopkins University13, University of California, Los Angeles14, University of Alabama at Birmingham15, City of Hope National Medical Center16, Case Western Reserve University17, Yale Cancer Center18, Roswell Park Cancer Institute19, University of Colorado Boulder20, Seattle Cancer Care Alliance21, Memorial Sloan Kettering Cancer Center22, University of Texas Southwestern Medical Center23, Stanford University24, University of Utah25, University of Pennsylvania26, University of South Florida27, Washington University in St. Louis28, University of Wisconsin-Madison29, Fox Chase Cancer Center30, Duke University31, National Comprehensive Cancer Network32
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia as mentioned in this paper.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.