Showing papers by "Wayne State University published in 2021"
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
TL;DR: In this paper, Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer and remains fatal despite recent advances in medical technology.
Abstract: Background Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-res...
696 citations
Sarah Cannon Research Institute1, Mount Sinai Hospital2, University of Chicago3, University of Pittsburgh4, University of Pennsylvania5, Princess Margaret Cancer Centre6, Medical College of Wisconsin7, City of Hope National Medical Center8, Memorial Sloan Kettering Cancer Center9, Wayne State University10, Harvard University11, Beth Israel Deaconess Medical Center12, Janssen Pharmaceutica13, Mayo Clinic14, University of California, San Francisco15
TL;DR: The CARITUDE-1 trial as discussed by the authors evaluated the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies.
494 citations
University of Washington1, University of Texas Southwestern Medical Center2, Harvard University3, Wayne State University4, Cornell University5, Laboratory of Molecular Biology6, Memorial Sloan Kettering Cancer Center7, Kettering University8, Fred Hutchinson Cancer Research Center9, Columbia University10, University of Würzburg11, St. Jude Children's Research Hospital12
TL;DR: The structures of many eukaryotic protein complexes are unknown, and there are likely many protein-protein interactions not yet identified as mentioned in this paper, but these structures play critical roles in biology.
Abstract: Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We take ...
215 citations
TL;DR: This Review surveys the basic principles, recent advances and promising future directions for wave-based-metamaterial analogue computing systems, and describes some of the most exciting applications suggested for these Computing metamaterials, including image processing, edge detection, equation solving and machine learning.
Abstract: Despite their widespread use for performing advanced computational tasks, digital signal processors suffer from several restrictions, including low speed, high power consumption and complexity, caused by costly analogue-to-digital converters. For this reason, there has recently been a surge of interest in performing wave-based analogue computations that avoid analogue-to-digital conversion and allow massively parallel operation. In particular, novel schemes for wave-based analogue computing have been proposed based on artificially engineered photonic structures, that is, metamaterials. Such kinds of computing systems, referred to as computational metamaterials, can be as fast as the speed of light and as small as its wavelength, yet, impart complex mathematical operations on an incoming wave packet or even provide solutions to integro-differential equations. These much-sought features promise to enable a new generation of ultra-fast, compact and efficient processing and computing hardware based on light-wave propagation. In this Review, we discuss recent advances in the field of computational metamaterials, surveying the state-of-the-art metastructures proposed to perform analogue computation. We further describe some of the most exciting applications suggested for these computing systems, including image processing, edge detection, equation solving and machine learning. Finally, we provide an outlook for the possible directions and the key problems for future research. Metamaterials provide a platform to leverage optical signals for performing specific-purpose computational tasks with ultra-fast speeds. This Review surveys the basic principles, recent advances and promising future directions for wave-based-metamaterial analogue computing systems.
175 citations
TL;DR: In this paper, the authors comprehensively review different effective techniques and controlling strategies used in the homogeneous charge compression ignition (HCCI) engine, and also summarize in the tables.
152 citations
TL;DR: In this article, the authors acknowledge support from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, the Japan Society for the Promotion of Science (JSPS), and the Tau-Lepton Physics Research Center of Nagoya University.
Abstract: We acknowledge support from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, the Japan Society for the Promotion of Science (JSPS), and the Tau-Lepton Physics Research Center of Nagoya University; the Australian Research Council including Grants No. DP180102629, No. DP170102389, No. DP170102204, No. DP150103061, No. FT130100303; Austrian Science Fund (FWF); the National Natural Science Foundation of China under Contracts No. 11435013, No. 11475187, No. 11521505, No. 11575017, No. 11675166, No. 11705209; Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS), Grant No. QYZDJ-SSWSLH011; the CAS Center for Excellence in Particle Physics (CCEPP); the Shanghai Pujiang Program under Grant No. 18PJ1401000; the Ministry of Education, Youth and Sports of the Czech Republic under Contract No. LTT17020; the Carl Zeiss Foundation, the Deutsche Forschungsgemeinschaft, the Excellence Cluster Universe, and the VolkswagenStiftung; the Department of Science and Technology of India; the Istituto Nazionale di Fisica Nucleare of Italy; National Research Foundation (NRF) of Korea Grants No. 2016R1D1A1B01010135, No. 2016R1D1A1B02012900, No. 2018R1A2B3003643, No. 2018R1A6A1A06024970, No. 2018R1D1A1B07047294, No. 2019K1A3A7A09033840, No. 2019R1I1A3A01058933; Radiation Science Research Institute, Foreign Large-size Research Facility Application Supporting project, the Global Science Experimental Data Hub Center of the Korea Institute of Science and Technology Information, and KREONET/GLORIAD the Polish Ministry of Science and Higher Education and the National Science Center; the Ministry of Science and Higher Education of the Russian Federation, Agreement No. 14.W03.31.0026; University of Tabuk research Grants No. S-1440-0321, No. S-0256-1438, and No. S-0280-1439 (Saudi Arabia); the Slovenian Research Agency; Ikerbasque, Basque Foundation for Science, Spain; the Swiss National Science Foundation; the Ministry of Education and the Ministry of Science and Technology of Taiwan; and the U.S. Department of Energy and the National Science Foundation.
147 citations
TL;DR: Comparisons between indoor localization systems in terms of accuracy, cost, advantages, and disadvantages are summarized and different detection techniques are presented.
Abstract: This paper introduces a review article on indoor localization techniques and technologies. The paper starts with current localization systems and summarizes comparisons between these systems in terms of accuracy, cost, advantages, and disadvantages. Also, the paper presents different detection techniques and compare them in terms of accuracy and cost. Finally, localization methods and algorithms, including angle of arrival (AOA), time of arrival (TOA), and recived signal strength (RSS) are introduced. The study contains concepts, requirements, and specifications for each category of methods presents pros and cons for investigated methods, and conducts comparisons between them.
144 citations
University of Las Palmas de Gran Canaria1, Sanford Health2, Wayne State University3, Hebron University4, Sunnybrook Health Sciences Centre5, Shaare Zedek Medical Center6, University of Sydney7, University of California, Los Angeles8, Kansai Medical University9, Merck & Co.10, University of Chicago11
TL;DR: Pembrolizumab plus pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) as discussed by the authors.
142 citations
Lawrence Berkeley National Laboratory1, National University of Singapore2, Stanford University3, University of Wisconsin-Madison4, National Ecological Observatory Network5, Oak Ridge National Laboratory6, McMaster University7, University of Nebraska–Lincoln8, University of California, Berkeley9, Agricultural Research Service10, University of British Columbia11, University of Colorado Boulder12, Ohio State University13, University of Florida14, University of Guelph15, University of Kansas16, Michigan State University17, Pacific Northwest National Laboratory18, United States Department of Agriculture19, University of New Mexico20, National Research Council21, Marine Biological Laboratory22, University of Alberta23, Virginia Commonwealth University24, University of Minnesota25, Université de Montréal26, Dalhousie University27, Carleton University28, Shinshu University29, Japan Agency for Marine-Earth Science and Technology30, Northern Arizona University31, Oregon State University32, Yale University33, Washington State University34, Harvard University35, Texas A&M University36, Indiana University37, Florida International University38, San Diego State University39, California State University, East Bay40, Wayne State University41, University of Sydney42, Wilfrid Laurier University43, University of Alabama44, Environment Canada45, United States Geological Survey46, Argonne National Laboratory47, Osaka Prefecture University48, University of Delaware49, University of Missouri50, University of Sheffield51
TL;DR: In this article, the authors evaluate the representativeness of flux footprints and evaluate potential biases as a consequence of the footprint-to-target-area mismatch, which can be used as a guide to identify site-periods suitable for specific applications.
137 citations
TL;DR: A scoring system for COVID-19-coagulopathy (CIC Scoring) and stratification of patients for the purpose of anticoagulation therapy based on risk categories is proposed and therapeutic guidelines are proposed.
TL;DR: In this paper, the performance of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC is presented, based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$.
Abstract: The performance is presented of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC. The reported results are based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$. Results obtained from lead-lead collision data collected at $\sqrt{s_\mathrm{NN}}=$ 5.02 TeV are also presented. Innovative techniques are used to reconstruct the electron and photon signals in the detector and to optimize the energy resolution. Events with electrons and photons in the final state are used to measure the energy resolution and energy scale uncertainty in the recorded events. The measured energy resolution for electrons produced in Z boson decays in proton-proton collision data ranges from 2 to 5%, depending on electron pseudorapidity and energy loss through bremsstrahlung in the detector material. The energy scale in the same range of energies is measured with an uncertainty smaller than 0.1 (0.3)% in the barrel (endcap) region in proton-proton collisions and better than 1 (3)% in the barrel (endcap) region in heavy ion collisions. The timing resolution for electrons from Z boson decays with the full 2016-2018 proton-proton collision data set is measured to be 200 ps.
TL;DR: In this paper, the authors evaluated the worldwide evolution of antimicrobial resistance during the COVID-19 pandemic, because pathogens do not respect borders, and this issue takes on even greater importance in developing countries, where data on resistance patterns are scarce, conditions for infectious pathogen transmission are optimal, and treatment resources are suboptimal.
University of Cologne1, Cornell University2, NewYork–Presbyterian Hospital3, Federal University of Rio de Janeiro4, Collaborative Drug Discovery5, University of California, San Diego6, Innsbruck Medical University7, University of Nizwa8, University of Genoa9, Federal University of São Paulo10, Masaryk University11, Goethe University Frankfurt12, Amrita Institute of Medical Sciences and Research Centre13, Medical University of Graz14, University of Manchester15, Wayne State University16, University of Melbourne17, Peter MacCallum Cancer Centre18, Heidelberg University19, Hamad Medical Corporation20, University of Exeter21, University of Hong Kong22, University of Minnesota23, University of Hamburg24, University of Belgrade25, University of Angers26, University of Colombo27, University of Delhi28, Radboud University Nijmegen29, National and Kapodistrian University of Athens30, Palacký University, Olomouc31, Federal University of Paraná32, University of Texas Health Science Center at San Antonio33, Sheba Medical Center34, Trinity College, Dublin35, University of Toronto36, University of Indonesia37, Universitas Kristen Indonesia38
TL;DR: The One World One Guideline initiative as mentioned in this paper has been used to incorporate regional differences in the epidemiology and management of rare mold infections, including Fusarium, Lomentospora, Scedosporium, dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces and Purpureocillium species.
Abstract: With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
City of Hope National Medical Center1, Fred Hutchinson Cancer Research Center2, University of Pennsylvania3, Duke University4, University of California, Los Angeles5, Columbia University6, University of Washington7, Yale University8, University of Michigan9, Wayne State University10, Alliance for Clinical Trials in Oncology11, University of California, Davis12
TL;DR: Sunitinib was compared with cabozantinib, crizotinib, and savolitinib for treatment of patients with metastatic renal cell carcinoma (PRCC).
Charité1, University of Southampton2, University College Cork3, University of Copenhagen4, Copenhagen University Hospital5, National University of Singapore6, Boston Children's Hospital7, University of Rennes8, Wayne State University9, Odense University Hospital10, Technische Universität München11, Hospital Clínico San Carlos12, Newcastle University13, University Medical Center Groningen14, University Hospital Southampton NHS Foundation Trust15, St Mary's Hospital16
TL;DR: The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline as discussed by the authors, which was developed using the AGREE II framework and the GRADE approach.
Abstract: Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognise and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritise clinical trials with the potential to improve the management of patients at risk of anaphylaxis.
TL;DR: This paper introduces the attention mechanism directly to the generative adversarial network (GAN) architecture and proposes a novel spatial attention GAN model (SPA-GAN) for image-to-image translation tasks.
Abstract: Image-to-image translation is to learn a mapping between images from a source domain and images from a target domain. In this paper, we introduce the attention mechanism directly to the generative adversarial network (GAN) architecture and propose a novel spatial attention GAN model (SPA-GAN) for image-to-image translation tasks. SPA-GAN computes the attention in its discriminator and use it to help the generator focus more on the most discriminative regions between the source and target domains, leading to more realistic output images. We also find it helpful to introduce an additional feature map loss in SPA-GAN training to preserve domain specific features during translation. Compared with existing attention-guided GAN models, SPA-GAN is a lightweight model that does not need additional attention networks or supervision. Qualitative and quantitative comparison against state-of-the-art methods on benchmark datasets demonstrates the superior performance of SPA-GAN.
TL;DR: The principles of the GaMD algorithms and recent applications in biomolecular simulations and drug design are presented and are advantageous for simulating complex biological processes.
Abstract: Gaussian accelerated molecular dynamics (GaMD) is a robust computational method for simultaneous unconstrained enhanced sampling and free energy calculations of biomolecules. It works by adding a harmonic boost potential to smooth biomolecular potential energy surface and reduce energy barriers. GaMD greatly accelerates biomolecular simulations by orders of magnitude. Without the need to set predefined reaction coordinates or collective variables, GaMD provides unconstrained enhanced sampling and is advantageous for simulating complex biological processes. The GaMD boost potential exhibits a Gaussian distribution, thereby allowing for energetic reweighting via cumulant expansion to the second order (i.e., “Gaussian approximation”). This leads to accurate reconstruction of free energy landscapes of biomolecules. Hybrid schemes with other enhanced sampling methods, such as the replica‐exchange GaMD (rex‐GaMD) and replica‐exchange umbrella sampling GaMD (GaREUS), have also been introduced, further improving sampling and free energy calculations. Recently, new “selective GaMD” algorithms including the Ligand GaMD (LiGaMD) and Peptide GaMD (Pep‐GaMD) enabled microsecond simulations to capture repetitive dissociation and binding of small‐molecule ligands and highly flexible peptides. The simulations then allowed highly efficient quantitative characterization of the ligand/peptide binding thermodynamics and kinetics. Taken together, GaMD and its innovative variants are applicable to simulate a wide variety of biomolecular dynamics, including protein folding, conformational changes and allostery, ligand binding, peptide binding, protein–protein/nucleic acid/carbohydrate interactions, and carbohydrate/nucleic acid interactions. In this review, we present principles of the GaMD algorithms and recent applications in biomolecular simulations and drug design.
Imperial College London1, Madras Medical College2, Bangabandhu Sheikh Mujib Medical University3, University of Kelaniya4, University of Colombo5, Government Medical College, Thiruvananthapuram6, Bangalore Medical College and Research Institute7, Great Ormond Street Hospital8, National Institute for Health Research9, Maulana Azad Medical College10, Wayne State University11
TL;DR: In this paper, a randomized controlled trial was conducted to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia.
03 May 2021
TL;DR: In this paper, the authors examined the association between race/ethnicity and rejection of COVID-19 vaccine trial participation and vaccine uptake and investigated whether racial/ethnic group-based medical mistrust is a potential mediator of this association.
Abstract: Importance: The impact of COVID-19 in the US has been far-reaching and devastating, especially in Black populations. Vaccination is a critical part of controlling community spread, but vaccine acceptance has varied, with some research reporting that Black individuals in the US are less willing to be vaccinated than other racial/ethnic groups. Medical mistrust informed by experiences of racism may be associated with this lower willingness. Objective: To examine the association between race/ethnicity and rejection of COVID-19 vaccine trial participation and vaccine uptake and to investigate whether racial/ethnic group-based medical mistrust is a potential mediator of this association. Design, Setting, and Participants: This cross-sectional survey study was conducted from June to December 2020 using a convenience sample of 1835 adults aged 18 years or older residing in Michigan. Participants were recruited through community-based organizations and hospital-academic networks. Main Outcomes and Measures: Separate items assessed whether respondents, if asked, would agree to participate in a research study to test a COVID-19 vaccine or to receive a COVID-19 vaccine. Participants also completed the suspicion subscale of the Group-Based Medical Mistrust Scale. Results: Of the 1835 participants, 1455 (79%) were women, 361 (20%) men, and 19 (1%) other gender. The mean (SD) age was 49.4 (17.9) years, and 394 participants (21%) identified as Black individuals. Overall, 1376 participants (75%) reported low willingness to participate in vaccine trials, and 945 (52%) reported low willingness to be vaccinated. Black participants reported the highest medical mistrust scores (mean [SD], 2.35 [0.96]) compared with other racial/ethnic groups (mean [SD] for the total sample, 1.83 [0.91]). Analysis of path models revealed significantly greater vaccine trial and vaccine uptake rejection among Black participants (vaccine trial: B [SE], 0.51 [0.08]; vaccine uptake: B [SE], 0.51 [0.08]; both P < .001) compared with the overall mean rejection. The association was partially mediated by medical mistrust among Black participants (vaccine trial: B [SE], 0.04 [0.01]; P = .003; vaccine uptake: B [SE], 0.07 [0.02]; P < .001) and White participants (vaccine trial: B [SE], -0.06 [0.02]; P = .001; vaccine uptake: B [SE], -0.10 [0.02]; P < .001). Conclusions and Relevance: In this survey study of US adults, racial/ethnic group-based medical mistrust partially mediated the association between individuals identifying as Black and low rates of acceptance of COVID-19 vaccine trial participation and actual vaccination. The findings suggest that partnerships between health care and other sectors to build trust and promote vaccination may benefit from socially and culturally responsive strategies that acknowledge and address racial/ethnic health care disparities and historical and contemporary experiences of racism.
TL;DR: In this paper, the first evidence of a non-monotonic variation in the kurtosis times variance of the net-proton number (proxy for net-baryon number) distribution as a function of collision energy was reported.
Abstract: Nonmonotonic variation with collision energy (sqrt[s_{NN}]) of the moments of the net-baryon number distribution in heavy-ion collisions, related to the correlation length and the susceptibilities of the system, is suggested as a signature for the quantum chromodynamics critical point. We report the first evidence of a nonmonotonic variation in the kurtosis times variance of the net-proton number (proxy for net-baryon number) distribution as a function of sqrt[s_{NN}] with 3.1 σ significance for head-on (central) gold-on-gold (Au+Au) collisions measured solenoidal tracker at Relativistic Heavy Ion Collider. Data in noncentral Au+Au collisions and models of heavy-ion collisions without a critical point show a monotonic variation as a function of sqrt[s_{NN}].
TL;DR: Embedding two gate-tunable Al/InAs Josephson junctions in a loop geometry confirms that the signatures of a topological transition are compatible with the emergence of Majorana bound states.
Abstract: Topological superconductivity holds promise for fault-tolerant quantum computing. While planar Josephson junctions are attractive candidates to realize this exotic state, direct phase measurements as the fingerprint of the topological transition are missing. By embedding two gate-tunable $\mathrm{Al}/\mathrm{InAs}$ Josephson junctions in a loop geometry, we measure a $\ensuremath{\pi}$ jump in the junction phase with an increasing in-plane magnetic field ${\mathbit{B}}_{\ensuremath{\parallel}}$. This jump is accompanied by a minimum of the critical current, indicating a closing and reopening of the superconducting gap, strongly anisotropic in ${\mathbit{B}}_{\ensuremath{\parallel}}$. Our theory confirms that these signatures of a topological transition are compatible with the emergence of Majorana bound states.
University of Otago1, University of Regensburg2, Trinity College, Dublin3, University of Salzburg4, University of Zurich5, University College London6, Seoul National University Bundang Hospital7, Linköping University8, Nottingham University Hospitals NHS Trust9, British Hospital10, Katholieke Universiteit Leuven11, University of Calgary12, Maastricht University13, Mario Negri Institute for Pharmacological Research14, University of Antwerp15, University of Nottingham16, Assiut University17, National and Kapodistrian University of Athens18, University of Valencia19, University of Minnesota20, National Taiwan University21, University of Granada22, Charité23, University of Texas at Dallas24, University of Münster25, Catholic University of Korea26, Washington University in St. Louis27, RWTH Aachen University28, Georgetown University29, University at Buffalo30, University of São Paulo31, University of Auckland32, Wayne State University33
TL;DR: In this article, the authors proposed that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and Tinnitus Disorder for the latter, which is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source.
Abstract: As for hypertension, chronic pain, epilepsy and other disorders with particular symptoms, a commonly accepted and unambiguous definition provides a common ground for researchers and clinicians to study and treat the problem. The WHO's ICD11 definition only mentions tinnitus as a nonspecific symptom of a hearing disorder, but not as a clinical entity in its own right, and the American Psychiatric Association's DSM-V doesn't mention tinnitus at all. Here we propose that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and "Tinnitus Disorder" for the latter. The proposed definition then becomes "Tinnitus is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source, which becomes Tinnitus Disorder "when associated with emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioural changes and functional disability.". In other words "Tinnitus" describes the auditory or sensory component, whereas "Tinnitus Disorder" reflects the auditory component and the associated suffering. Whereas acute tinnitus may be a symptom secondary to a trauma or disease, chronic tinnitus may be considered a primary disorder in its own right. If adopted, this will advance the recognition of tinnitus disorder as a primary health condition in its own right. The capacity to measure the incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address acute tinnitus as a symptom but chronic tinnitus as a disorder.
The George Institute for Global Health1, University College London2, University of Texas Southwestern Medical Center3, AstraZeneca4, University Medical Center Groningen5, Stanford University6, University of Utah7, Southern Medical University8, University of Glasgow9, Pontifícia Universidade Católica do Paraná10, University of Copenhagen11, Steno Diabetes Center12, Wayne State University13, Henry Ford Hospital14
TL;DR: The Dapagliflifliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial as discussed by the authors showed that 10mg of dapaglia-lozin 10mg or placebo reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy.
University of California, Berkeley1, University of Arizona2, University of California, Davis3, University of Notre Dame4, Colorado College5, University of Massachusetts Amherst6, St. John Fisher College7, Colorado State University8, University of California, San Diego9, Syracuse University10, Siena College11, University of New Hampshire12, University of Massachusetts Lowell13, Oregon State University14, Wayne State University15, Utah State University16, Tulane University17, University of Idaho18, University of Maine19, University of Rochester20
TL;DR: In this article, the authors present the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period.
Abstract: Wastewater surveillance for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging approach to help identify the risk of a coronavirus disease (COVID-19) outbreak. This tool can contribute to public health surveillance at both community (wastewater treatment system) and institutional (e.g., colleges, prisons, and nursing homes) scales. This paper explores the successes, challenges, and lessons learned from initial wastewater surveillance efforts at colleges and university systems to inform future research, development and implementation. We present the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period. We describe the broad range of approaches, findings, resources, and impacts from these initial efforts. These institutions range in size, social and political geographies, and include both public and private institutions. Our analysis suggests that wastewater monitoring at colleges requires consideration of local information needs, sewage infrastructure, resources for sampling and analysis, college and community dynamics, approaches to interpretation and communication of results, and follow-up actions. Most colleges reported that a learning process of experimentation, evaluation, and adaptation was key to progress. This process requires ongoing collaboration among diverse stakeholders including decision-makers, researchers, faculty, facilities staff, students, and community members.
University of Washington1, Fred Hutchinson Cancer Research Center2, Yale Cancer Center3, University of Chicago4, University of Ulsan5, Asan Medical Center6, Netherlands Cancer Institute7, Université Paris-Saclay8, Columbia University Medical Center9, Vita-Salute San Raffaele University10, University of Tsukuba11, Durham University12, Samsung Medical Center13, University of Southern California14, Wayne State University15, Memorial Sloan Kettering Cancer Center16, Astellas Pharma17, Harvard University18
TL;DR: Enfortumab vedotin is an antibody-drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma as discussed by the authors.
Abstract: Summary Background Locally advanced or metastatic urothelial carcinoma is generally incurable and has scarce treatment options, especially for cisplatin-ineligible patients previously treated with PD-1 or PD-L1 therapy. Enfortumab vedotin is an antibody–drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma. We aimed to evaluate the efficacy and safety of enfortumab vedotin in the post-immunotherapy setting in cisplatin-ineligible patients. Methods EV-201 is a multicentre, single-arm, phase 2 study of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with PD-1 or PD-L1 inhibitors. Cohort 2 included adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status score of 2 or less who were considered ineligible for cisplatin at enrolment and who had not received platinum-containing chemotherapy in the locally advanced or metastatic setting. Enfortumab vedotin was given intravenously at a dose of 1·25 mg/kg on days 1, 8, and 15 of every 28-day cycle. The primary endpoint was confirmed objective response rate per Response Evaluation Criteria in Solid Tumours version 1.1 assessed by blinded independent central review. Efficacy and safety were analysed in all patients who received at least one dose of enfortumab vedotin. EV-201 is an ongoing study and the primary analysis is complete. This study is registered with Clinicaltrials.gov , NCT03219333 . Findings Between Oct 8, 2017, and Feb 11, 2020, 91 patients were enrolled at 40 sites globally, of whom 89 received treatment. Median follow-up was 13·4 months (IQR 11·3–18·9). At data cutoff (Sept 8, 2020), the confirmed objective response rate was 52% (46 of 89 patients; 95% CI 41–62), with 18 (20%) of 89 patients achieving a complete response and 28 (31%) achieving a partial response. 49 (55%) of 89 patients had grade 3 or worse treatment-related adverse events. The most common grade 3 or 4 treatment-related adverse events were neutropenia (eight [9%] patients), maculopapular rash (seven [8%] patients), and fatigue (six [7%] patients). Treatment-related serious adverse events occurred in 15 (17%) patients. Three (3%) patients died due to acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome (one [1%] each) within 30 days of first dose and these deaths were considered by the investigator to be related to treatment; a fourth death from pneumonitis occurred more than 30 days after the last dose and was also considered to be related to treatment. Interpretation Treatment with enfortumab vedotin was tolerable and confirmed responses were seen in 52% of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1 or PD-L1 inhibitors. These patients have few treatment options, and enfortumab vedotin could be a promising new therapy for a patient population with a high unmet need. Funding Astellas Pharma Global Development and Seagen.
Cedars-Sinai Medical Center1, University of Minnesota2, Michigan State University3, Wayne State University4, Baptist Hospital of Miami5, Sentara Norfolk General Hospital6, Christiana Care Health System7, Mercy Health8, Our Lady of the Lake Regional Medical Center9, Beth Israel Deaconess Medical Center10
TL;DR: A prospective, single-arm, multicenter study as discussed by the authors evaluated the safety and efficacy of the Indigo aspiration system in submassive acute pulmonary embolism (PE) in sub-massive PE patients.
Abstract: Objectives This study sought to prospectively evaluate the safety and efficacy of the Indigo aspiration system in submassive acute pulmonary embolism (PE). Background PE treatment with thrombolytics has bleeding risks. Aspiration thrombectomy can remove thrombus without thrombolytics, but data are lacking. Methods This study was a prospective, single-arm, multicenter study that enrolled patients with symptomatic acute PE ≤14 days, systolic blood pressure ≥90 mm Hg, and right ventricular-to-left ventricular (RV/LV) ratio >0.9. The primary efficacy endpoint was change in RV/LV ratio from baseline to 48 h post-procedure on core lab–adjudicated computed tomography angiography. The primary safety endpoint was a composite of 48-h major adverse events: device-related death, major bleeding, and device-related serious adverse events (clinical deterioration, pulmonary vascular, or cardiac injury). All sites received Institutional Review Board approval. Results A total of 119 patients (mean age 59.8 ± 15.0 years) were enrolled at 22 U.S. sites between November 2017 and March 2019. Median device insertion to removal time was 37.0 (interquartile range: 23.5 to 60.0) min. Two (1.7%) patients received intraprocedural thrombolytics. Mean RV/LV ratio reduction from baseline to 48 h post-procedure was 0.43 (95% confidence interval: 0.38 to 0.47; p Conclusions In this prospective, multicenter study the Indigo aspiration system was associated with a significant reduction in the RV/LV ratio and a low major adverse event rate in submassive PE patients. Intraprocedural thrombolytic drugs were avoided in 98.3% of patients. (Evaluating the Safety and Efficacy of the Indigo aspiration system in Acute Pulmonary Embolism [EXTRACT-PE]; NCT03218566 )
TL;DR: DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-Gene analysis.
Abstract: Essential genes refer to genes that are required by an organism to survive under specific conditions. Studies of the minimal-gene-set for bacteria have elucidated fundamental cellular processes that sustain life. The past five years have seen a significant progress in identifying human essential genes, primarily due to the successful use of CRISPR/Cas9 in various types of human cells. DEG 15, a new release of the Database of Essential Genes (www.essentialgene.org), has provided major advancements, compared to DEG 10. Specifically, the number of eukaryotic essential genes has increased by more than fourfold, and that of prokaryotic ones has more than doubled. Of note, the human essential-gene number has increased by more than tenfold. Moreover, we have developed built-in analysis modules by which users can perform various analyses, such as essential-gene distributions between bacterial leading and lagging strands, sub-cellular localization distribution, enrichment analysis of gene ontology and KEGG pathways, and generation of Venn diagrams to compare and contrast gene sets between experiments. Additionally, the database offers customizable BLAST tools for performing species- and experiment-specific BLAST searches. Therefore, DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-gene analysis.
TL;DR: The development of XPO1 inhibitors, from basic research to clinical approval, is described and the potential of emerging combination therapies and biomarkers of response is discussed.
Abstract: Exportin 1 (XPO1), also known as chromosome region maintenance protein 1, plays a crucial role in maintaining cellular homeostasis via the regulated export of a range of cargoes, including proteins and several classes of RNAs, from the nucleus to the cytoplasm. Dysregulation of this protein plays a pivotal role in the development of various solid and haematological malignancies. Furthermore, XPO1 is associated with resistance to several standard-of-care therapies, including chemotherapies and targeted therapies, making it an attractive target of novel cancer therapies. Over the years, a number of selective inhibitors of nuclear export have been developed. However, only selinexor has been clinically validated. The novel mechanism of action of XPO1 inhibitors implies a different toxicity profile to that of other agents and has proved challenging in certain settings. Nonetheless, data from clinical trials have led to the approval of the XPO1 inhibitor selinexor (plus dexamethasone) as a fifth-line therapy for patients with multiple myeloma and as a monotherapy for patients with relapsed and/or refractory diffuse large B cell lymphoma. In this Review, we summarize the progress and challenges in the development of nuclear export inhibitors and discuss the potential of emerging combination therapies and biomarkers of response.
Ohio State University1, University of California, Berkeley2, Duke University3, Wayne State University4, McGill University5, University of São Paulo6, Lawrence Livermore National Laboratory7, Massachusetts Institute of Technology8, University of Tennessee9, Texas A&M University10, Central China Normal University11, Lawrence Berkeley National Laboratory12, Brookhaven National Laboratory13
TL;DR: Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, Bayesian model averaging is propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.
Abstract: Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.