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Showing papers by "Katholieke Universiteit Leuven published in 2021"


Journal ArticleDOI
09 Apr 2021-Science
TL;DR: Using a variety of statistical and dynamic modeling approaches, the authors estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants, and a fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases.
Abstract: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.

1,935 citations


Journal ArticleDOI
TL;DR: The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa guidelines summarise the most recent findings and advice for their use in clinical practice and include a strong recommendation to consider moderate hypofractionation in intermediate-risk patients.

1,369 citations


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
Nuno R. Faria, Thomas A. Mellan1, Charles Whittaker1, Ingra Morales Claro2, Darlan da Silva Candido3, Darlan da Silva Candido2, Swapnil Mishra1, Myuki A E Crispim, Flavia C. S. Sales2, Iwona Hawryluk1, John T. McCrone4, Ruben J.G. Hulswit3, Lucas A M Franco2, Mariana S. Ramundo2, Jaqueline Goes de Jesus2, Pamela S Andrade2, Thais M. Coletti2, Giulia M. Ferreira5, Camila A. M. Silva2, Erika R. Manuli2, Rafael Henrique Moraes Pereira, Pedro S. Peixoto2, Moritz U. G. Kraemer3, Nelson Gaburo, Cecilia da C. Camilo, Henrique Hoeltgebaum1, William Marciel de Souza2, Esmenia C. Rocha2, Leandro Marques de Souza2, Mariana C. Pinho2, Leonardo José Tadeu de Araújo6, Frederico S V Malta, Aline B. de Lima, Joice do P. Silva, Danielle A G Zauli, Alessandro C. S. Ferreira, Ricardo P Schnekenberg3, Daniel J Laydon1, Patrick G T Walker1, Hannah M. Schlüter1, Ana L. P. dos Santos, Maria S. Vidal, Valentina S. Del Caro, Rosinaldo M. F. Filho, Helem M. dos Santos, Renato Santana Aguiar7, José Luiz Proença-Módena8, Bruce Walker Nelson9, James A. Hay10, Melodie Monod1, Xenia Miscouridou1, Helen Coupland1, Raphael Sonabend1, Michaela A. C. Vollmer1, Axel Gandy1, Carlos A. Prete2, Vitor H. Nascimento2, Marc A. Suchard11, Thomas A. Bowden3, Sergei L Kosakovsky Pond12, Chieh-Hsi Wu13, Oliver Ratmann1, Neil M. Ferguson1, Christopher Dye3, Nicholas J. Loman14, Philippe Lemey15, Andrew Rambaut4, Nelson Abrahim Fraiji, Maria Perpétuo Socorro Sampaio Carvalho, Oliver G. Pybus3, Oliver G. Pybus16, Seth Flaxman1, Samir Bhatt1, Samir Bhatt17, Ester Cerdeira Sabino2 
21 May 2021-Science
TL;DR: In this article, the authors used a two-category dynamical model that integrates genomic and mortality data to estimate that P.1 may be 1.7-to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.
Abstract: Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

985 citations


Journal ArticleDOI
TL;DR: This work focuses on task incremental classification, where tasks arrive sequentially and are delineated by clear boundaries and study the influence of model capacity, weight decay and dropout regularization, and the order in which the tasks are presented, and qualitatively compare methods in terms of required memory, computation time and storage.
Abstract: Artificial neural networks thrive in solving the classification problem for a particular rigid task, acquiring knowledge through generalized learning behaviour from a distinct training phase. The resulting network resembles a static entity of knowledge, with endeavours to extend this knowledge without targeting the original task resulting in a catastrophic forgetting. Continual learning shifts this paradigm towards networks that can continually accumulate knowledge over different tasks without the need to retrain from scratch. We focus on task incremental classification, where tasks arrive sequentially and are delineated by clear boundaries. Our main contributions concern 1) a taxonomy and extensive overview of the state-of-the-art, 2) a novel framework to continually determine the stability-plasticity trade-off of the continual learner, 3) a comprehensive experimental comparison of 11 state-of-the-art continual learning methods and 4 baselines. We empirically scrutinize method strengths and weaknesses on three benchmarks, considering Tiny Imagenet and large-scale unbalanced iNaturalist and a sequence of recognition datasets. We study the influence of model capacity, weight decay and dropout regularization, and the order in which the tasks are presented, and qualitatively compare methods in terms of required memory, computation time and storage.

866 citations


Journal ArticleDOI
Carole Escartin1, Elena Galea2, Andras Lakatos3, James P. O'Callaghan4, Gabor C. Petzold5, Gabor C. Petzold6, Alberto Serrano-Pozo7, Christian Steinhäuser5, Andrea Volterra8, Giorgio Carmignoto9, Giorgio Carmignoto10, Amit Agarwal11, Nicola J. Allen12, Alfonso Araque13, Luis Barbeito14, Ari Barzilai15, Dwight E. Bergles16, Gilles Bonvento1, Arthur M. Butt17, Wei Ting Chen18, Martine Cohen-Salmon19, Colm Cunningham20, Benjamin Deneen21, Bart De Strooper22, Bart De Strooper18, Blanca Diaz-Castro23, Cinthia Farina, Marc R. Freeman24, Vittorio Gallo25, James E. Goldman26, Steven A. Goldman27, Steven A. Goldman28, Magdalena Götz29, Antonia Gutierrez30, Philip G. Haydon31, Dieter Henrik Heiland32, Elly M. Hol33, Matthew Holt18, Masamitsu Iino34, Ksenia V. Kastanenka7, Helmut Kettenmann35, Baljit S. Khakh36, Schuichi Koizumi37, C. Justin Lee, Shane A. Liddelow38, Brian A. MacVicar39, Pierre J. Magistretti40, Pierre J. Magistretti8, Albee Messing41, Anusha Mishra24, Anna V. Molofsky42, Keith K. Murai43, Christopher M. Norris44, Seiji Okada45, Stéphane H. R. Oliet46, João Filipe Oliveira47, João Filipe Oliveira48, Aude Panatier46, Vladimir Parpura49, Marcela Pekna50, Milos Pekny50, Luc Pellerin51, Gertrudis Perea52, Beatriz G. Pérez-Nievas53, Frank W. Pfrieger54, Kira E. Poskanzer42, Francisco J. Quintana7, Richard M. Ransohoff, Miriam Riquelme-Perez1, Stefanie Robel55, Christine R. Rose56, Jeffrey D. Rothstein16, Nathalie Rouach19, David H. Rowitch3, Alexey Semyanov57, Alexey Semyanov58, Swetlana Sirko29, Harald Sontheimer55, Raymond A. Swanson42, Javier Vitorica59, Ina B. Wanner36, Levi B. Wood60, Jia Qian Wu61, Binhai Zheng62, Eduardo R. Zimmer63, Robert Zorec64, Michael V. Sofroniew36, Alexei Verkhratsky65, Alexei Verkhratsky66 
Université Paris-Saclay1, Autonomous University of Barcelona2, University of Cambridge3, National Institute for Occupational Safety and Health4, University of Bonn5, German Center for Neurodegenerative Diseases6, 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 Copenhagen27, University of Rochester28, 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, University of Manchester65, Ikerbasque66
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


Journal ArticleDOI
TL;DR: In this article, a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expecable clinical outcomes with the use of idecabtagene vicleucel (ide-cel), also called bb2121.
Abstract: Background Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expec...

776 citations


Journal ArticleDOI
TL;DR: It is found that more than 40% of persons worldwide have FGIDs, which affect quality of life and healthcare use, and similar trends and relative distributions were found in people who completed internet vs personal interviews.

763 citations



Journal ArticleDOI
TL;DR: In this paper, no adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageaal...
Abstract: Background No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal...

596 citations


Journal ArticleDOI
TL;DR: The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice and guide the clinician in the discussion with the patient on the treatment decisions to be taken.

Journal ArticleDOI
TL;DR: Improved standardization of available invasive and noninvasive diagnostic tools and a consensus on their specific use are needed to allow specific diagnosis and stratification of patient cohorts for the implementation of aetiology-based therapies.
Abstract: Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Journal ArticleDOI
27 Jul 2021-ACS Nano
TL;DR: A comprehensive review of metal-halide perovskite nanocrystals can be found in this article, where researchers having expertise in different fields (chemistry, physics, and device engineering) have joined together to provide a state-of-the-art overview and future prospects of metalhalide nanocrystal research.
Abstract: Metal-halide perovskites have rapidly emerged as one of the most promising materials of the 21st century, with many exciting properties and great potential for a broad range of applications, from photovoltaics to optoelectronics and photocatalysis. The ease with which metal-halide perovskites can be synthesized in the form of brightly luminescent colloidal nanocrystals, as well as their tunable and intriguing optical and electronic properties, has attracted researchers from different disciplines of science and technology. In the last few years, there has been a significant progress in the shape-controlled synthesis of perovskite nanocrystals and understanding of their properties and applications. In this comprehensive review, researchers having expertise in different fields (chemistry, physics, and device engineering) of metal-halide perovskite nanocrystals have joined together to provide a state of the art overview and future prospects of metal-halide perovskite nanocrystal research.

Journal ArticleDOI
TL;DR: In this paper, the authors proposed that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels.
Abstract: Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

Journal ArticleDOI
TL;DR: In this article, the early effect of the COVID-19 pandemic on suicide rates around the world was assessed using real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature.

Journal ArticleDOI
16 Apr 2021-Science
TL;DR: A suite of electrophysiological tools comprising a miniaturized high-density probe, recoverable chronic implant fixtures, and algorithms for automatic post hoc motion correction are demonstrated, enabling an order-of-magnitude increase in the number of sites that can be recorded in small animals, such as mice, and the ability to record from them stably over long time scales.
Abstract: Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

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.

Journal ArticleDOI
09 Aug 2021
TL;DR: The Task Force on sports cardiology and exercise in patients with cardiovascular disease of the European Society of Cardiology (ESC) concludes that sports medicine and exercise should be combined for the prevention of heart attack and stroke.
Abstract: The Task Force on sports cardiology and exercise in patients with cardiovascular disease of the European Society of Cardiology (ESC)

Journal ArticleDOI
TL;DR: Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular ...
Abstract: Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and 'modern' cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.


Journal ArticleDOI
TL;DR: In this paper, the authors present a set of guidelines for analysing critical data from lignin-first approaches, including feedstock analysis and process parameters, with the ambition of uniting the lignIN-first research community around a common set of reportable metrics, including fractionation efficiency, product yields, solvent mass balances, catalyst efficiency, and requirements for additional reagents such as reducing, oxidising, or capping agents.
Abstract: The valorisation of the plant biopolymer lignin is now recognised as essential to enabling the economic viability of the lignocellulosic biorefining industry. In this context, the “lignin-first” biorefining approach, in which lignin valorisation is considered in the design phase, has demonstrated the fullest utilisation of lignocellulose. We define lignin-first methods as active stabilisation approaches that solubilise lignin from native lignocellulosic biomass while avoiding condensation reactions that lead to more recalcitrant lignin polymers. This active stabilisation can be accomplished by solvolysis and catalytic conversion of reactive intermediates to stable products or by protection-group chemistry of lignin oligomers or reactive monomers. Across the growing body of literature in this field, there are disparate approaches to report and analyse the results from lignin-first approaches, thus making quantitative comparisons between studies challenging. To that end, we present herein a set of guidelines for analysing critical data from lignin-first approaches, including feedstock analysis and process parameters, with the ambition of uniting the lignin-first research community around a common set of reportable metrics. These guidelines comprise standards and best practices or minimum requirements for feedstock analysis, stressing reporting of the fractionation efficiency, product yields, solvent mass balances, catalyst efficiency, and the requirements for additional reagents such as reducing, oxidising, or capping agents. Our goal is to establish best practices for the research community at large primarily to enable direct comparisons between studies from different laboratories. The use of these guidelines will be helpful for the newcomers to this field and pivotal for further progress in this exciting research area.

Journal ArticleDOI
TL;DR: This survey provides a well-rounded view on state-of-the-art deep learning approaches for MTL in computer vision, explicitly emphasizing on dense prediction tasks.
Abstract: With the advent of deep learning, many dense prediction tasks, i.e. tasks that produce pixel-level predictions, have seen significant performance improvements. The typical approach is to learn these tasks in isolation, that is, a separate neural network is trained for each individual task. Yet, recent multi-task learning (MTL) techniques have shown promising results w.r.t. performance, computations and/or memory footprint, by jointly tackling multiple tasks through a learned shared representation. In this survey, we provide a well-rounded view on state-of-the-art deep learning approaches for MTL in computer vision, explicitly emphasizing on dense prediction tasks. Our contributions concern the following. First, we consider MTL from a network architecture point-of-view. We include an extensive overview and discuss the advantages/disadvantages of recent popular MTL models. Second, we examine various optimization methods to tackle the joint learning of multiple tasks. We summarize the qualitative elements of these works and explore their commonalities and differences. Finally, we provide an extensive experimental evaluation across a variety of dense prediction benchmarks to examine the pros and cons of the different methods, including both architectural and optimization based strategies.

Journal ArticleDOI
TL;DR: The Chicago Classification v4.4.0 as discussed by the authors is the most recent version of the Chicago Classification, which uses high-resolution manometry (HRM) for motility disorders.
Abstract: Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.


Journal ArticleDOI
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, Karolinska Institutet13, Ghent University14, Sun Yat-sen 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.

Journal ArticleDOI
Stephen V. Faraone1, Tobias Banaschewski2, David Coghill3, Yi Zheng4, Joseph Biederman5, Mark A. Bellgrove6, Jeffrey H. Newcorn7, Martin Gignac8, Nouf M. Al Saud, Iris Manor, Luis Augusto Rohde9, Li Yang10, Samuele Cortese11, Doron Almagor12, Mark A. Stein13, Turki H. Albatti, Haya F. Aljoudi, Mohammed Alqahtani14, Philip Asherson15, Lukoye Atwoli16, Sven Bölte17, Jan K. Buitelaar18, Cleo L. Crunelle19, David Daley20, Søren Dalsgaard21, Manfred Döpfner22, Stacey Espinet, Michael Fitzgerald23, Barbara Franke18, Manfred Gerlach24, Jan Haavik25, Catharina A. Hartman26, Cynthia M. Hartung27, Stephen P. Hinshaw28, Stephen P. Hinshaw29, Pieter J. Hoekstra26, Chris Hollis30, Scott H. Kollins31, J. J. Sandra Kooij32, Jonna Kuntsi15, Henrik Larsson17, Henrik Larsson33, Tingyu Li34, Jing Liu10, Eugene Merzon35, Gregory Mattingly36, Paulo Mattos37, Suzanne McCarthy38, Amori Yee Mikami39, Brooke S. G. Molina40, Joel T. Nigg41, D. Purper-Ouakil42, Olayinka Omigbodun43, Guilherme V. Polanczyk44, Yehuda Pollak45, Alison Poulton46, Ravi Philip Rajkumar47, Andrew Reding, Andreas Reif, Katya Rubia15, Julia J. Rucklidge48, Marcel Romanos, J. Antoni Ramos-Quiroga49, Arnt F. A. Schellekens18, Anouk Scheres18, Renata Schoeman50, Julie B. Schweitzer51, Henal Shah52, Mary V. Solanto53, Edmund J.S. Sonuga-Barke21, Edmund J.S. Sonuga-Barke15, Cesar Soutullo54, Hans-Christoph Steinhausen55, James M. Swanson56, Anita Thapar57, Gail Tripp58, Geurt van de Glind59, Wim van den Brink32, Saskia Van der Oord60, André Venter61, Benedetto Vitiello62, Benedetto Vitiello63, Susanne Walitza64, Yufeng Wang10 
State University of New York Upstate Medical University1, Heidelberg University2, University of Melbourne3, Capital Medical University4, Harvard University5, Monash University, Clayton campus6, Icahn School of Medicine at Mount Sinai7, Montreal Children's Hospital8, Universidade Federal do Rio Grande do Sul9, Peking University10, University of Southampton11, University of Toronto12, University of Washington13, King Khalid University14, King's College London15, Aga Khan University16, Karolinska Institutet17, Radboud University Nijmegen18, Vrije Universiteit Brussel19, University of Nottingham20, Aarhus University21, University of Cologne22, Trinity College, Dublin23, University of Würzburg24, University of Bergen25, University Medical Center Groningen26, University of Wyoming27, University of California, Berkeley28, University of California, San Francisco29, Nottinghamshire Healthcare NHS Foundation Trust30, Duke University31, University of Amsterdam32, Örebro University33, Chongqing Medical University34, Tel Aviv University35, Washington University in St. Louis36, Federal University of Rio de Janeiro37, University College Cork38, University of British Columbia39, University of Pittsburgh40, Oregon Health & Science University41, University of Montpellier42, University of Ibadan43, University of São Paulo44, Hebrew University of Jerusalem45, University of Sydney46, Jawaharlal Institute of Postgraduate Medical Education and Research47, University of Canterbury48, Autonomous University of Barcelona49, Stellenbosch University50, University of California, Davis51, National Medical College52, Hofstra University53, University of Texas Health Science Center at Houston54, University of Southern Denmark55, University of California, Irvine56, Cardiff University57, Okinawa Institute of Science and Technology58, HU University of Applied Sciences Utrecht59, Katholieke Universiteit Leuven60, University of the Free State61, Johns Hopkins University62, University of Turin63, University of Zurich64
TL;DR: In this article, the authors presented 208 empirically supported statements about ADHD using meta-analysis, which allow for firm statements about the nature, course, outcome causes and treatments for disorders that are useful for reducing misconceptions and stigma.

Journal ArticleDOI
Alexander Kurilshikov1, Carolina Medina-Gomez2, Rodrigo Bacigalupe3, Djawad Radjabzadeh2, Jun Wang3, Jun Wang4, Ayse Demirkan1, Ayse Demirkan5, Caroline I. Le Roy6, Juan Antonio Raygoza Garay7, Casey T. Finnicum8, Xingrong Liu9, Daria V. Zhernakova1, Marc Jan Bonder1, Tue H. Hansen10, Fabian Frost11, Malte C. Rühlemann12, Williams Turpin7, Jee-Young Moon13, Han-Na Kim14, Kreete Lüll15, Elad Barkan16, Shiraz A. Shah17, Myriam Fornage18, Joanna Szopinska-Tokov, Zachary D. Wallen19, Dmitrii Borisevich10, Lars Agréus9, Anna Andreasson20, Corinna Bang12, Larbi Bedrani7, Jordana T. Bell6, Hans Bisgaard17, Michael Boehnke21, Dorret I. Boomsma22, Robert D. Burk13, Annique Claringbould1, Kenneth Croitoru7, Gareth E. Davies8, Gareth E. Davies22, Cornelia M. van Duijn23, Cornelia M. van Duijn2, Liesbeth Duijts2, Gwen Falony3, Jingyuan Fu1, Adriaan van der Graaf1, Torben Hansen10, Georg Homuth11, David A. Hughes24, Richard G. IJzerman25, Matthew A. Jackson23, Matthew A. Jackson6, Vincent W. V. Jaddoe2, Marie Joossens3, Torben Jørgensen10, Daniel Keszthelyi26, Rob Knight27, Markku Laakso28, Matthias Laudes, Lenore J. Launer29, Wolfgang Lieb12, Aldons J. Lusis30, Ad A.M. Masclee26, Henriette A. Moll2, Zlatan Mujagic26, Qi Qibin13, Daphna Rothschild16, Hocheol Shin14, Søren J. Sørensen10, Claire J. Steves6, Jonathan Thorsen17, Nicholas J. Timpson24, Raul Y. Tito3, Sara Vieira-Silva3, Uwe Völker11, Henry Völzke11, Urmo Võsa1, Kaitlin H Wade24, Susanna Walter31, Kyoko Watanabe22, Stefan Weiss11, Frank Ulrich Weiss11, Omer Weissbrod32, Harm-Jan Westra1, Gonneke Willemsen22, Haydeh Payami19, Daisy Jonkers26, Alejandro Arias Vasquez33, Eco J. C. de Geus22, Katie A. Meyer34, Jakob Stokholm17, Eran Segal16, Elin Org15, Cisca Wijmenga1, Hyung Lae Kim35, Robert C. Kaplan36, Tim D. Spector6, André G. Uitterlinden2, Fernando Rivadeneira2, Andre Franke12, Markus M. Lerch11, Lude Franke1, Serena Sanna1, Serena Sanna37, Mauro D'Amato, Oluf Pedersen10, Andrew D. Paterson7, Robert Kraaij2, Jeroen Raes3, Alexandra Zhernakova1 
TL;DR: In this article, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts) and found high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples.
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.

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TL;DR: In this paper, the authors focus on the fact that metastasizing cancer cells selectively and dynamically adapt their metabolism at every step during the metastatic cascade, enabling survival and growth in the new environment.
Abstract: Metastasis formation is the major cause of death in most patients with cancer. Despite extensive research, targeting metastatic seeding and colonization is still an unresolved challenge. Only recently, attention has been drawn to the fact that metastasizing cancer cells selectively and dynamically adapt their metabolism at every step during the metastatic cascade. Moreover, many metastases display different metabolic traits compared with the tumours from which they originate, enabling survival and growth in the new environment. Consequently, the stage-dependent metabolic traits may provide therapeutic windows for preventing or reducing metastasis, and targeting the new metabolic traits arising in established metastases may allow their eradication.

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TL;DR: In this paper, the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis.
Abstract: Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice