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Showing papers by "University of Utah published in 2021"


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

1,129 citations


Journal ArticleDOI
TL;DR: 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


Journal ArticleDOI
TL;DR: The benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood as discussed by the authors.
Abstract: Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight US locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (628%) received both recommended mRNA doses and 477 (121%) received only one dose of mRNA vaccine† Among unvaccinated participants, 138 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days§ In contrast, among fully immunized (≥14 days after second dose) persons, 004 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 019 infections per 1,000 person-days were reported Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions COVID-19 vaccination is recommended for all eligible persons

576 citations


Journal ArticleDOI
Shadab Alam1, Marie Aubert, Santiago Avila2, Christophe Balland3, Julian E. Bautista4, Matthew A. Bershady5, Matthew A. Bershady6, Dmitry Bizyaev7, Dmitry Bizyaev8, Michael R. Blanton9, Adam S. Bolton10, Jo Bovy11, Jonathan Brinkmann7, Joel R. Brownstein10, Etienne Burtin12, Solène Chabanier12, Michael J. Chapman13, Peter Doohyun Choi14, Chia-Hsun Chuang15, Johan Comparat16, M. C. Cousinou, Andrei Cuceu17, Kyle S. Dawson10, Sylvain de la Torre, Arnaud de Mattia12, Victoria de Sainte Agathe3, Hélion du Mas des Bourboux10, Stephanie Escoffier, Thomas Etourneau12, James Farr17, Andreu Font-Ribera17, Peter M. Frinchaboy18, S. Fromenteau19, Héctor Gil-Marín20, Jean Marc Le Goff12, Alma X. Gonzalez-Morales21, Alma X. Gonzalez-Morales22, Violeta Gonzalez-Perez23, Violeta Gonzalez-Perez4, Kathleen Grabowski7, Julien Guy24, Adam J. Hawken, Jiamin Hou16, Hui Kong25, James C. Parker7, Mark A. Klaene7, Jean-Paul Kneib26, Sicheng Lin9, Daniel Long7, Brad W. Lyke27, Axel de la Macorra19, Paul Martini25, Karen L. Masters28, Faizan G. Mohammad13, Jeongin Moon14, Eva Maria Mueller29, Andrea Muñoz-Gutiérrez19, Adam D. Myers27, Seshadri Nadathur4, Richard Neveux12, Jeffrey A. Newman30, P. Noterdaeme3, Audrey Oravetz7, Daniel Oravetz7, Nathalie Palanque-Delabrouille12, Kaike Pan7, Romain Paviot, Will J. Percival13, Will J. Percival31, Ignasi Pérez-Ràfols3, Patrick Petitjean3, Matthew M. Pieri, Abhishek Prakash32, Anand Raichoor26, Corentin Ravoux12, Mehdi Rezaie33, J. Rich12, Ashley J. Ross25, Graziano Rossi14, Rossana Ruggeri4, Rossana Ruggeri34, V. Ruhlmann-Kleider12, Ariel G. Sánchez16, F. Javier Sánchez35, José R. Sánchez-Gallego36, Conor Sayres36, Donald P. Schneider, Hee-Jong Seo33, Arman Shafieloo37, Anže Slosar38, Alex Smith12, Julianna Stermer3, Amélie Tamone26, Jeremy L. Tinker9, Rita Tojeiro39, Mariana Vargas-Magaña19, Andrei Variu26, Yuting Wang, Benjamin A. Weaver, Anne-Marie Weijmans39, C. Yeche12, Pauline Zarrouk40, Pauline Zarrouk12, Cheng Zhao26, Gong-Bo Zhao, Zheng Zheng10 
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


Journal ArticleDOI
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


Journal ArticleDOI
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


Journal ArticleDOI
07 Jan 2021-PLOS ONE
TL;DR: It was showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously.
Abstract: Background University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general population. Therefore, when the nature of their educational experience radically changes—such as sheltering in place during the COVID-19 pandemic—the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts. Methods Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students. Results Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously. Conclusion Inadequate efforts to recognize and address college students’ mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.

444 citations


Journal ArticleDOI
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


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1692 moreInstitutions (195)
TL;DR: In this article, the authors reported the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries.
Abstract: We report the observation of gravitational waves from two compact binary coalescences in LIGO’s and Virgo’s third observing run with properties consistent with neutron star–black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO–Virgo detectors. The source of GW200105 has component masses 8.9−1.5+1.2 and 1.9−0.2+0.3M⊙ , whereas the source of GW200115 has component masses 5.7−2.1+1.8 and 1.5−0.3+0.7M⊙ (all measurements quoted at the 90% credible level). The probability that the secondary’s mass is below the maximal mass of a neutron star is 89%–96% and 87%–98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are 280−110+110 and 300−100+150Mpc , respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of 45−33+75Gpc−3yr−1 when assuming that GW200105 and GW200115 are representative of the NSBH population or 130−69+112Gpc−3yr−1 under the assumption of a broader distribution of component masses.

374 citations


Journal ArticleDOI
TL;DR: The Q-Chem quantum chemistry program package as discussed by the authors provides a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, and methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques.
Abstract: This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.

360 citations


Journal ArticleDOI
TL;DR: Among patients with heart failure and a reduced ejection, patients who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo.
Abstract: Background The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect ...

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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.

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TL;DR: In this paper, the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) was evaluated.
Abstract: Background Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) in preventing infection with ...

Journal ArticleDOI
TL;DR: The review discusses the new classes of RiPPs that have been discovered, the advances in the understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates.

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TL;DR: In this paper, a case-control analysis was conducted among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021.
Abstract: Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.

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TL;DR: COVID and associated educational/governmental mitigation strategies had a modest but persistent impact on mood and wellness behaviors of first-year university students and Colleges should prepare to address the continued mental health impacts of the pandemic.
Abstract: Objective To test the impact of the coronavirus disease 2019 (COVID) pandemic on the emotions, behavior, and wellness behaviors of first-year college students. Method A total of 675 first-year university students completed a full assessment of behavioral and emotional functioning at the beginning of the spring semester 2020. Of these, 576 completed the same assessment at the end of the spring semester, 600 completed at least 1 item from a COVID-related survey after the onset of COVID pandemic, and 485 completed nightly surveys of mood and wellness behaviors on a regular basis before and after the onset of the COVID crisis. Results Externalizing problems (mean = −0.19, 95% CI = −0.06 to 0.33, p = .004) and attention problems (mean = −0.60, 95% CI = −0.40 to 0.80, p Conclusion COVID and associated educational/governmental mitigation strategies had a modest but persistent impact on mood and wellness behaviors of first-year university students. Colleges should prepare to address the continued mental health impacts of the pandemic.

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Richard R. Orlandi1, Todd T. Kingdom2, Timothy L. Smith3, Benjamin S. Bleier4, Adam S. DeConde5, Amber U Luong6, David M. Poetker7, Zachary M. Soler8, Kevin C. Welch9, Sarah K. Wise10, Nithin D. Adappa11, Jeremiah A. Alt1, Wilma Terezinha Anselmo-Lima12, Claus Bachert13, Claus Bachert14, Claus Bachert15, Fuad M. Baroody16, Pete S. Batra17, Manuel Bernal-Sprekelsen18, Daniel M. Beswick19, Neil Bhattacharyya4, Rakesh K. Chandra20, Eugene H. Chang21, Alexander G. Chiu22, Naweed I. Chowdhury20, Martin J. Citardi6, Noam A. Cohen11, David B. Conley9, John M. DelGaudio10, Martin Desrosiers23, Richard G. Douglas24, Jean Anderson Eloy25, Wytske Fokkens26, Stacey T. Gray4, David A. Gudis27, Daniel L. Hamilos4, Joseph K. Han28, Richard J. Harvey29, Peter Hellings30, Eric H. Holbrook4, Claire Hopkins31, Peter H. Hwang32, Amin R. Javer33, Rong San Jiang, David N. Kennedy11, Robert C. Kern9, Tanya M. Laidlaw4, Devyani Lal34, Andrew P. Lane35, Heung Man Lee36, Jivianne T. Lee19, Joshua M. Levy10, Sandra Y. Lin35, Valerie J. Lund, Kevin C. McMains37, Ralph Metson4, Joaquim Mullol18, Robert M. Naclerio35, Gretchen M. Oakley1, Nobuyoshi Otori38, James N. Palmer11, Sanjay R. Parikh39, Desiderio Passali40, Zara M. Patel32, Anju T. Peters9, Carl Philpott41, Alkis J. Psaltis42, Vijay R. Ramakrishnan2, Murugappan Ramanathan35, Hwan Jung Roh43, Luke Rudmik44, Raymond Sacks29, Rodney J. Schlosser8, Ahmad R. Sedaghat45, Brent A. Senior46, Raj Sindwani47, Kristine A. Smith48, Kornkiat Snidvongs49, Michael G. Stewart50, Jeffrey D. Suh19, Bruce K. Tan9, Justin H. Turner20, Cornelis M. van Drunen26, Richard Louis Voegels12, De Yun Wang51, Bradford A. Woodworth52, Peter-John Wormald42, Erin D. Wright53, Carol H. Yan5, Luo Zhang54, Bing Zhou54 
University of Utah1, University of Colorado Denver2, Oregon Health & Science University3, Harvard University4, University of California, San Diego5, University of Texas Health Science Center at Houston6, Medical College of Wisconsin7, Medical University of South Carolina8, Northwestern University9, Emory University10, University of Pennsylvania11, University of São Paulo12, Sun Yat-sen University13, Karolinska Institutet14, Ghent University15, University of Chicago16, Rush University Medical Center17, University of Barcelona18, University of California, Los Angeles19, Vanderbilt University20, University of Arizona21, University of Kansas22, Université de Montréal23, University of Auckland24, Rutgers University25, University of Amsterdam26, Columbia University27, Eastern Virginia Medical School28, University of New South Wales29, Katholieke Universiteit Leuven30, Guy's Hospital31, Stanford University32, University of British Columbia33, Mayo Clinic34, Johns Hopkins University35, Korea University36, Uniformed Services University of the Health Sciences37, Jikei University School of Medicine38, University of Washington39, University of Siena40, University of East Anglia41, University of Adelaide42, Pusan National University43, University of Calgary44, University of Cincinnati45, University of North Carolina at Chapel Hill46, Cleveland Clinic47, University of Winnipeg48, Chulalongkorn University49, Cornell University50, National University of Singapore51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in the understanding and treatment of rhinologic disease.
Abstract: I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

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TL;DR: In this paper, a detailed review of the physical processes during 3D printing and the fundamental science of densification after sintering and post-heat treatment steps are provided to understand the microstructural evolution and properties of binder jetted parts.

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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...

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TL;DR: Twenty editors‐in‐chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues.
Abstract: Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors-in-chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.


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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

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TL;DR: In this article, a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection was conducted to determine the prevalence and associated mortality of well defined neurologic diagnoses among COVID-19 patients.
Abstract: OBJECTIVE: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS: We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS: Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS: Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

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TL;DR: In this article, a nine-week wastewater epidemiology study of ten wastewater facilities, serving 39% of the state of Utah or 1.26 million individuals was conducted in April and May of 2020.


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TL;DR: In this paper, the authors evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of KCCQ-CS, a measure of heart failure-related health status, at 12 weeks after treatment initiation.
Abstract: Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF. In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking.

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TL;DR: In this paper, the effectiveness of partial or full vaccination with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥ 65 years.
Abstract: Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination† with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

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12 Mar 2021-Science
TL;DR: In this article, the authors used chiral-induced spin selectivity (CISS) to produce spin-polarized carriers and demonstrated a spin-LED that operates at room temperature without magnetic fields or ferromagnetic contacts.
Abstract: In traditional optoelectronic approaches, control over spin, charge, and light requires the use of both electrical and magnetic fields. In a spin-polarized light-emitting diode (spin-LED), charges are injected, and circularly polarized light is emitted from spin-polarized carrier pairs. Typically, the injection of carriers occurs with the application of an electric field, whereas spin polarization can be achieved using an applied magnetic field or polarized ferromagnetic contacts. We used chiral-induced spin selectivity (CISS) to produce spin-polarized carriers and demonstrate a spin-LED that operates at room temperature without magnetic fields or ferromagnetic contacts. The CISS layer consists of oriented, self-assembled small chiral molecules within a layered organic-inorganic metal-halide hybrid semiconductor framework. The spin-LED achieves ±2.6% circularly polarized electroluminescence at room temperature.

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16 Jul 2021-Science
TL;DR: In this paper, an analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak.
Abstract: On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders >20 m in diameter, and scoured the valley walls up to 220 m above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.