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Showing papers by "University of British Columbia published in 2019"


Journal ArticleDOI
Evan Bolyen1, Jai Ram Rideout1, Matthew R. Dillon1, Nicholas A. Bokulich1, Christian C. Abnet2, Gabriel A. Al-Ghalith3, Harriet Alexander4, Harriet Alexander5, Eric J. Alm6, Manimozhiyan Arumugam7, Francesco Asnicar8, Yang Bai9, Jordan E. Bisanz10, Kyle Bittinger11, Asker Daniel Brejnrod7, Colin J. Brislawn12, C. Titus Brown4, Benjamin J. Callahan13, Andrés Mauricio Caraballo-Rodríguez14, John Chase1, Emily K. Cope1, Ricardo Silva14, Christian Diener15, Pieter C. Dorrestein14, Gavin M. Douglas16, Daniel M. Durall17, Claire Duvallet6, Christian F. Edwardson, Madeleine Ernst18, Madeleine Ernst14, Mehrbod Estaki17, Jennifer Fouquier19, Julia M. Gauglitz14, Sean M. Gibbons20, Sean M. Gibbons15, Deanna L. Gibson17, Antonio Gonzalez14, Kestrel Gorlick1, Jiarong Guo21, Benjamin Hillmann3, Susan Holmes22, Hannes Holste14, Curtis Huttenhower23, Curtis Huttenhower24, Gavin A. Huttley25, Stefan Janssen26, Alan K. Jarmusch14, Lingjing Jiang14, Benjamin D. Kaehler25, Benjamin D. Kaehler27, Kyo Bin Kang28, Kyo Bin Kang14, Christopher R. Keefe1, Paul Keim1, Scott T. Kelley29, Dan Knights3, Irina Koester14, Tomasz Kosciolek14, Jorden Kreps1, Morgan G. I. Langille16, Joslynn S. Lee30, Ruth E. Ley31, Ruth E. Ley32, Yong-Xin Liu, Erikka Loftfield2, Catherine A. Lozupone19, Massoud Maher14, Clarisse Marotz14, Bryan D Martin20, Daniel McDonald14, Lauren J. McIver24, Lauren J. McIver23, Alexey V. Melnik14, Jessica L. Metcalf33, Sydney C. Morgan17, Jamie Morton14, Ahmad Turan Naimey1, Jose A. Navas-Molina34, Jose A. Navas-Molina14, Louis-Félix Nothias14, Stephanie B. Orchanian, Talima Pearson1, Samuel L. Peoples20, Samuel L. Peoples35, Daniel Petras14, Mary L. Preuss36, Elmar Pruesse19, Lasse Buur Rasmussen7, Adam R. Rivers37, Michael S. Robeson38, Patrick Rosenthal36, Nicola Segata8, Michael Shaffer19, Arron Shiffer1, Rashmi Sinha2, Se Jin Song14, John R. Spear39, Austin D. Swafford, Luke R. Thompson40, Luke R. Thompson41, Pedro J. Torres29, Pauline Trinh20, Anupriya Tripathi14, Peter J. Turnbaugh10, Sabah Ul-Hasan42, Justin J. J. van der Hooft43, Fernando Vargas, Yoshiki Vázquez-Baeza14, Emily Vogtmann2, Max von Hippel44, William A. Walters32, Yunhu Wan2, Mingxun Wang14, Jonathan Warren45, Kyle C. Weber46, Kyle C. Weber37, Charles H. D. Williamson1, Amy D. Willis20, Zhenjiang Zech Xu14, Jesse R. Zaneveld20, Yilong Zhang47, Qiyun Zhu14, Rob Knight14, J. Gregory Caporaso1 
TL;DR: QIIME 2 development was primarily funded by NSF Awards 1565100 to J.G.C. and R.K.P. and partial support was also provided by the following: grants NIH U54CA143925 and U54MD012388.
Abstract: QIIME 2 development was primarily funded by NSF Awards 1565100 to J.G.C. and 1565057 to R.K. Partial support was also provided by the following: grants NIH U54CA143925 (J.G.C. and T.P.) and U54MD012388 (J.G.C. and T.P.); grants from the Alfred P. Sloan Foundation (J.G.C. and R.K.); ERCSTG project MetaPG (N.S.); the Strategic Priority Research Program of the Chinese Academy of Sciences QYZDB-SSW-SMC021 (Y.B.); the Australian National Health and Medical Research Council APP1085372 (G.A.H., J.G.C., Von Bing Yap and R.K.); the Natural Sciences and Engineering Research Council (NSERC) to D.L.G.; and the State of Arizona Technology and Research Initiative Fund (TRIF), administered by the Arizona Board of Regents, through Northern Arizona University. All NCI coauthors were supported by the Intramural Research Program of the National Cancer Institute. S.M.G. and C. Diener were supported by the Washington Research Foundation Distinguished Investigator Award.

8,821 citations


Journal ArticleDOI
TL;DR: In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
Abstract: Background Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium...

3,233 citations


Journal ArticleDOI
TL;DR: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery.
Abstract: Background Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) an...

2,917 citations


Journal ArticleDOI
Daniel Conroy-Beam1, David M. Buss2, Kelly Asao2, Agnieszka Sorokowska3, Agnieszka Sorokowska4, Piotr Sorokowski3, Toivo Aavik5, Grace Akello6, Mohammad Madallh Alhabahba7, Charlotte Alm8, Naumana Amjad9, Afifa Anjum9, Chiemezie S. Atama10, Derya Atamtürk Duyar11, Richard Ayebare, Carlota Batres12, Mons Bendixen13, Aicha Bensafia14, Boris Bizumic15, Mahmoud Boussena14, Marina Butovskaya16, Marina Butovskaya17, Seda Can18, Katarzyna Cantarero19, Antonin Carrier20, Hakan Cetinkaya21, Ilona Croy4, Rosa María Cueto22, Marcin Czub3, Daria Dronova16, Seda Dural18, İzzet Duyar11, Berna Ertuğrul23, Agustín Espinosa22, Ignacio Estevan24, Carla Sofia Esteves25, Luxi Fang26, Tomasz Frackowiak3, Jorge Contreras Garduño27, Karina Ugalde González, Farida Guemaz, Petra Gyuris28, Mária Halamová29, Iskra Herak20, Marina Horvat30, Ivana Hromatko31, Chin Ming Hui26, Jas Laile Suzana Binti Jaafar32, Feng Jiang33, Konstantinos Kafetsios34, Tina Kavčič35, Leif Edward Ottesen Kennair13, Nicolas Kervyn20, Truong Thi Khanh Ha19, Imran Ahmed Khilji36, Nils C. Köbis37, Hoang Moc Lan19, András Láng28, Georgina R. Lennard15, Ernesto León22, Torun Lindholm8, Trinh Thi Linh19, Giulia Lopez38, Nguyen Van Luot19, Alvaro Mailhos24, Zoi Manesi39, Rocio Martinez40, Sarah L. McKerchar15, Norbert Meskó28, Girishwar Misra41, Conal Monaghan15, Emanuel C. Mora42, Alba Moya-Garófano40, Bojan Musil30, Jean Carlos Natividade43, Agnieszka Niemczyk3, George Nizharadze, Elisabeth Oberzaucher44, Anna Oleszkiewicz4, Anna Oleszkiewicz3, Mohd Sofian Omar-Fauzee45, Ike E. Onyishi10, Barış Özener11, Ariela Francesca Pagani38, Vilmante Pakalniskiene46, Miriam Parise38, Farid Pazhoohi47, Annette Pisanski42, Katarzyna Pisanski3, Katarzyna Pisanski48, Edna Lúcia Tinoco Ponciano, Camelia Popa49, Pavol Prokop50, Pavol Prokop51, Muhammad Rizwan, Mario Sainz52, Svjetlana Salkičević31, Ruta Sargautyte46, Ivan Sarmány-Schuller53, Susanne Schmehl44, Shivantika Sharad41, Razi Sultan Siddiqui54, Franco Simonetti55, Stanislava Stoyanova56, Meri Tadinac31, Marco Antonio Correa Varella57, Christin-Melanie Vauclair25, Luis Diego Vega, Dwi Ajeng Widarini, Gyesook Yoo58, Marta Zaťková29, Maja Zupančič59 
University of California, Santa Barbara1, University of Texas at Austin2, University of Wrocław3, Dresden University of Technology4, University of Tartu5, Gulu University6, Middle East University7, Stockholm University8, University of the Punjab9, University of Nigeria, Nsukka10, Istanbul University11, Franklin & Marshall College12, Norwegian University of Science and Technology13, University of Algiers14, Australian National University15, Russian Academy of Sciences16, Russian State University for the Humanities17, İzmir University of Economics18, University of Social Sciences and Humanities19, Université catholique de Louvain20, Ankara University21, Pontifical Catholic University of Peru22, Cumhuriyet University23, University of the Republic24, ISCTE – University Institute of Lisbon25, The Chinese University of Hong Kong26, National Autonomous University of Mexico27, University of Pécs28, University of Constantine the Philosopher29, University of Maribor30, University of Zagreb31, University of Malaya32, Central University of Finance and Economics33, University of Crete34, University of Primorska35, Institute of Molecular and Cell Biology36, University of Amsterdam37, Catholic University of the Sacred Heart38, VU University Amsterdam39, University of Granada40, University of Delhi41, University of Havana42, Pontifical Catholic University of Rio de Janeiro43, University of Vienna44, Universiti Utara Malaysia45, Vilnius University46, University of British Columbia47, University of Sussex48, Romanian Academy49, Slovak Academy of Sciences50, Comenius University in Bratislava51, University of Monterrey52, SAS Institute53, DHA Suffa University54, Pontifical Catholic University of Chile55, South-West University "Neofit Rilski"56, University of São Paulo57, Kyung Hee University58, University of Ljubljana59
TL;DR: This work combines this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets and finds that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.
Abstract: Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.

1,827 citations


Journal ArticleDOI
TL;DR: Progression‐free survival was significantly longer with avelumab plus axitinib than with sunit inib among patients who received these agents as first‐line treatment for advanced renal‐cell carcinoma.
Abstract: Background In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously...

1,597 citations


Journal ArticleDOI
TL;DR: A new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes, able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants.
Abstract: The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.

1,526 citations


Journal ArticleDOI
TL;DR: This is the first study to report global prevalence of obstructive sleep apnoea; with almost 1 billion people affected, and with prevalence exceeding 50% in some countries, effective diagnostic and treatment strategies are needed to minimise the negative health impacts and to maximise cost-effectiveness.

1,487 citations


Journal ArticleDOI
TL;DR: In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs, and 156 PFMs were updated, and the genomic tracks, inference tool, and TF-binding profile similarity clusters were updated.
Abstract: JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, we created a Q&A forum to ease the communication between the user community and JASPAR curators. Finally, we updated the genomic tracks, inference tool, and TF-binding profile similarity clusters. All the data is available through the JASPAR website, its associated RESTful API, and through the JASPAR2020 R/Bioconductor package.

1,219 citations


Journal ArticleDOI
TL;DR: Enough evidence was available to conclude that specific doses of aerobic, combined aerobic plus resistance training, and/or resistance training could improve common cancer-related health outcomes, including anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life.
Abstract: PurposeThe number of cancer survivors worldwide is growing, with over 15.5 million cancer survivors in the United States alone—a figure expected to double in the coming decades. Cancer survivors face unique health challenges as a result of their cancer diagnosis and the impact of treatments

1,174 citations


Journal ArticleDOI
TL;DR: Blood eosinophils are recommended as a biomarker to support clinical decisions regarding the use of inhaled corticosteroids in chronic obstructive pulmonary disease patients, based on recent evidence from clinical trials.
Abstract: Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up. Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.

1,122 citations


Journal ArticleDOI
Peter A. R. Ade1, James E. Aguirre2, Z. Ahmed3, Simone Aiola4  +276 moreInstitutions (53)
TL;DR: The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s as mentioned in this paper.
Abstract: The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping ≈ 10% of the sky to a white noise level of 2 μK-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of σ(r)=0.003. The large aperture telescope will map ≈ 40% of the sky at arcminute angular resolution to an expected white noise level of 6 μK-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.

Journal ArticleDOI
TL;DR: The growing application of gene expression profiling demands powerful yet user-friendly bioinformatics tools to support systems-level data understanding and NetworkAnalyst was first released in 2014 to address the key need for interpreting gene expression data within the context of protein-protein interaction networks.
Abstract: The growing application of gene expression profiling demands powerful yet user-friendly bioinformatics tools to support systems-level data understanding. NetworkAnalyst was first released in 2014 to address the key need for interpreting gene expression data within the context of protein-protein interaction (PPI) networks. It was soon updated for gene expression meta-analysis with improved workflow and performance. Over the years, NetworkAnalyst has been continuously updated based on community feedback and technology progresses. Users can now perform gene expression profiling for 17 different species. In addition to generic PPI networks, users can now create cell-type or tissue specific PPI networks, gene regulatory networks, gene co-expression networks as well as networks for toxicogenomics and pharmacogenomics studies. The resulting networks can be customized and explored in 2D, 3D as well as Virtual Reality (VR) space. For meta-analysis, users can now visually compare multiple gene lists through interactive heatmaps, enrichment networks, Venn diagrams or chord diagrams. In addition, users have the option to create their own data analysis projects, which can be saved and resumed at a later time. These new features are released together as NetworkAnalyst 3.0, freely available at https://www.networkanalyst.ca.

Journal ArticleDOI
13 Dec 2019-Science
TL;DR: The first integrated global-scale intergovernmental assessment of the status, trends, and future of the links between people and nature provides an unprecedented picture of the extent of the authors' mutual dependence, the breadth and depth of the ongoing and impending crisis, and the interconnectedness among sectors and regions.
Abstract: The human impact on life on Earth has increased sharply since the 1970s, driven by the demands of a growing population with rising average per capita income. Nature is currently supplying more materials than ever before, but this has come at the high cost of unprecedented global declines in the extent and integrity of ecosystems, distinctness of local ecological communities, abundance and number of wild species, and the number of local domesticated varieties. Such changes reduce vital benefits that people receive from nature and threaten the quality of life of future generations. Both the benefits of an expanding economy and the costs of reducing nature's benefits are unequally distributed. The fabric of life on which we all depend-nature and its contributions to people-is unravelling rapidly. Despite the severity of the threats and lack of enough progress in tackling them to date, opportunities exist to change future trajectories through transformative action. Such action must begin immediately, however, and address the root economic, social, and technological causes of nature's deterioration.

Journal ArticleDOI
TL;DR: Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression.
Abstract: Background Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer. Methods In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events. Results A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P Conclusions Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).

Journal ArticleDOI
TL;DR: It is confirmed that eukaryotes form at least two domains, the loss of monophyly in the Excavata, robust support for the Haptista and Cryptista, and suggested primer sets for DNA sequences from environmental samples that are effective for each clade are provided.
Abstract: This revision of the classification of eukaryotes follows that of Adl et al., 2012 [J. Euk. Microbiol. 59(5)] and retains an emphasis on protists. Changes since have improved the resolution of many ...


Journal ArticleDOI
TL;DR: It is shown how ecosystem service assessments can be expanded to include mental health, and a heuristic, conceptual model for doing so is provided.
Abstract: A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.

Journal ArticleDOI
TL;DR: The authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types to illustrate how common clinical problems are being addressed.
Abstract: Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.

Journal ArticleDOI
TL;DR: A panorama of the latest advancements in the rational design and development of semiconductor polymeric graphitic carbon nitride (g-C3N4) photocatalysts for visible-light-induced hydrogen evolution reaction (HER) is presented in this paper.
Abstract: Semiconductor polymeric graphitic carbon nitride (g-C3N4) photocatalysts have attracted dramatically growing attention in the field of the visible-light-induced hydrogen evolution reaction (HER) because of their facile synthesis, easy functionalization, attractive electronic band structure, high physicochemical stability and photocatalytic activity. This review article presents a panorama of the latest advancements in the rational design and development of g-C3N4 and g-C3N4-based composite photocatalysts for HER application. Concretely, the review starts with the development history, synthetic strategy, electronic structure and physicochemical characteristics of g-C3N4 materials, followed by the rational design and engineering of various nanostructured g-C3N4 (e.g. thinner, highly crystalline, doped, and porous g-C3N4) photocatalysts for HER application. Then a series of highly efficient g-C3N4 (e.g., metal/g-C3N4, semiconductor/g-C3N4, metal organic framework/g-C3N4, carbon/g-C3N4, conducting polymer/g-C3N4, sensitizer/g-C3N4) composite photocatalysts are exemplified. Lastly, this review provides a comprehensive summary and outlook on the major challenges, opportunities, and inspiring perspectives for future research in this hot area on the basis of pioneering works. It is believed that the emerging g-C3N4-based photocatalysts will act as the “holy grail” for highly efficient photocatalytic HER under visible-light irradiation.

Journal ArticleDOI
Andrea Cossarizza1, Hyun-Dong Chang, Andreas Radbruch, Andreas Acs2  +459 moreInstitutions (160)
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Posted ContentDOI
Daniel Taliun1, Daniel N. Harris2, Michael D. Kessler2, Jedidiah Carlson3  +191 moreInstitutions (61)
06 Mar 2019-bioRxiv
TL;DR: The nearly complete catalog of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and non-coding sequence variants to phenotypic variation as well as resources and early insights from the sequence data.
Abstract: Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency

Journal ArticleDOI
Nasim Mavaddat1, Kyriaki Michailidou2, Kyriaki Michailidou1, Joe Dennis1  +307 moreInstitutions (105)
TL;DR: This PRS, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset is developed and empirically validated and is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Journal ArticleDOI
TL;DR: Simulation results reveal that the proposed system is effective and feasible in collecting, calculating, and storing trust values in vehicular networks.
Abstract: Vehicular networks enable vehicles to generate and broadcast messages in order to improve traffic safety and efficiency. However, due to the nontrusted environments, it is difficult for vehicles to evaluate the credibilities of received messages. In this paper, we propose a decentralized trust management system in vehicular networks based on blockchain techniques. In this system, vehicles can validate the received messages from neighboring vehicles using Bayesian Inference Model. Based on the validation result, the vehicle will generate a rating for each message source vehicle. With the ratings uploaded from vehicles, roadside units (RSUs) calculate the trust value offsets of involved vehicles and pack these data into a “block.” Then, each RSU will try to add their “blocks” to the trust blockchain which is maintained by all the RSUs. By employing the joint proof-of-work (PoW) and proof-of-stake consensus mechanism, the more total value of offsets (stake) is in the block, the easier RSU can find the nonce for the hash function (PoW). In this way, all RSUs collaboratively maintain an updated, reliable, and consistent trust blockchain. Simulation results reveal that the proposed system is effective and feasible in collecting, calculating, and storing trust values in vehicular networks.

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TL;DR: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists and has the potential to be used for other chronic neurologic conditions.
Abstract: Objective To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. Methods A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. Results The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1–310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1–451.6) for women and 159.7 (95% CI 158.7–160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. Conclusion The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

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TL;DR: The regulatory approval of Onpattro, a lipid nanoparticle-based short interfering RNA drug for the treatment of polyneuropathies induced by hereditary transthyretin amyloidosis, paves the way for clinical development of many nucleic acid-based therapies enabled by nanoparticle delivery.
Abstract: The regulatory approval of Onpattro, a lipid nanoparticle-based short interfering RNA drug for the treatment of polyneuropathies induced by hereditary transthyretin amyloidosis, paves the way for clinical development of many nucleic acid-based therapies enabled by nanoparticle delivery.

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Mark Chaisson1, Mark Chaisson2, Ashley D. Sanders, Xuefang Zhao3, Xuefang Zhao4, Ankit Malhotra, David Porubsky5, David Porubsky6, Tobias Rausch, Eugene J. Gardner7, Oscar L. Rodriguez8, Li Guo9, Ryan L. Collins4, Xian Fan10, Jia Wen11, Robert E. Handsaker4, Robert E. Handsaker12, Susan Fairley13, Zev N. Kronenberg2, Xiangmeng Kong14, Fereydoun Hormozdiari15, Dillon Lee16, Aaron M. Wenger17, Alex Hastie, Danny Antaki18, Thomas Anantharaman, Peter A. Audano2, Harrison Brand4, Stuart Cantsilieris2, Han Cao, Eliza Cerveira, Chong Chen10, Xintong Chen7, Chen-Shan Chin17, Zechen Chong10, Nelson T. Chuang7, Christine C. Lambert17, Deanna M. Church, Laura Clarke13, Andrew Farrell16, Joey Flores19, Timur R. Galeev14, David U. Gorkin18, David U. Gorkin20, Madhusudan Gujral18, Victor Guryev5, William Haynes Heaton, Jonas Korlach17, Sushant Kumar14, Jee Young Kwon21, Ernest T. Lam, Jong Eun Lee, Joyce V. Lee, Wan-Ping Lee, Sau Peng Lee, Shantao Li14, Patrick Marks, Karine A. Viaud-Martinez19, Sascha Meiers, Katherine M. Munson2, Fabio C. P. Navarro14, Bradley J. Nelson2, Conor Nodzak11, Amina Noor18, Sofia Kyriazopoulou-Panagiotopoulou, Andy Wing Chun Pang, Yunjiang Qiu20, Yunjiang Qiu18, Gabriel Rosanio18, Mallory Ryan, Adrian M. Stütz, Diana C.J. Spierings5, Alistair Ward16, Anne Marie E. Welch2, Ming Xiao22, Wei Xu, Chengsheng Zhang, Qihui Zhu, Xiangqun Zheng-Bradley13, Ernesto Lowy13, Sergei Yakneen, Steven A. McCarroll12, Steven A. McCarroll4, Goo Jun23, Li Ding24, Chong-Lek Koh25, Bing Ren20, Bing Ren18, Paul Flicek13, Ken Chen10, Mark Gerstein, Pui-Yan Kwok26, Peter M. Lansdorp5, Peter M. Lansdorp27, Peter M. Lansdorp28, Gabor T. Marth16, Jonathan Sebat18, Xinghua Shi11, Ali Bashir8, Kai Ye9, Scott E. Devine7, Michael E. Talkowski4, Michael E. Talkowski12, Ryan E. Mills3, Tobias Marschall6, Jan O. Korbel13, Evan E. Eichler2, Charles Lee21 
TL;DR: A suite of long-read, short- read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms are applied to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner.
Abstract: The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.

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TL;DR: The steps and extensive considerations involved in performing SP3 in bottom-up proteomics are described, using a simplified protein cleanup scenario for illustration.
Abstract: A critical step in proteomics analysis is the optimal extraction and processing of protein material to ensure the highest sensitivity in downstream detection. Achieving this requires a sample-handling technology that exhibits unbiased protein manipulation, flexibility in reagent use, and virtually lossless processing. Addressing these needs, the single-pot, solid-phase-enhanced sample-preparation (SP3) technology is a paramagnetic bead–based approach for rapid, robust, and efficient processing of protein samples for proteomic analysis. SP3 uses a hydrophilic interaction mechanism for exchange or removal of components that are commonly used to facilitate cell or tissue lysis, protein solubilization, and enzymatic digestion (e.g., detergents, chaotropes, salts, buffers, acids, and solvents) before downstream proteomic analysis. The SP3 protocol consists of nonselective protein binding and rinsing steps that are enabled through the use of ethanol-driven solvation capture on the surface of hydrophilic beads, and elution of purified material in aqueous conditions. In contrast to alternative approaches, SP3 combines compatibility with a substantial collection of solution additives with virtually lossless and unbiased recovery of proteins independent of input quantity, all in a simplified single-tube protocol. The SP3 protocol is simple and efficient, and can be easily completed by a standard user in ~30 min, including reagent preparation. As a result of these properties, SP3 has successfully been used to facilitate examination of a broad range of sample types spanning simple and complex protein mixtures in large and very small amounts, across numerous organisms. This work describes the steps and extensive considerations involved in performing SP3 in bottom-up proteomics, using a simplified protein cleanup scenario for illustration. This protocol describes a single-pot, solid-phase-enhanced sample-preparation (SP3) method for rapid, robust, and efficient processing of protein samples for proteomic analysis.

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TL;DR: Evidence is provided that the proportional effect of SGLT2 inhibitors might attenuate with declining kidney function and there was clear, separate evidence of benefit for all eG FR subgroups, including for participants with a baseline eGFR 30-45 mL/min per 1·73 m2.

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TL;DR: The programmatic developments and institutional context for the Landsat program and the unique ability of Landsat to meet the needs of national and international programs are described and the key trends in Landsat science are presented.

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TL;DR: The use of hydrogen as a fuel, when generated from water using semiconductor photocatalysts and driven by sunlight, is a sustainable alternative to fossil fuels as discussed by the authors, however, our understanding of the key properties underlying their photoinitiated redox processes has not kept pace, and this impedes further progress to generate cost-competitive technologies.
Abstract: The use of hydrogen as a fuel, when generated from water using semiconductor photocatalysts and driven by sunlight, is a sustainable alternative to fossil fuels. Polymeric photocatalysts are based on Earth-abundant elements and have the advantage over their inorganic counterparts in that their electronic properties are easily tuneable through molecular engineering. Polymeric photocatalysts have developed rapidly over the past decade, resulting in the discovery of many active materials. However, our understanding of the key properties underlying their photoinitiated redox processes has not kept pace, and this impedes further progress to generate cost-competitive technologies. Here, we discuss state-of-the-art polymeric photocatalysts and our microscopic understanding of their activities. We conclude with a discussion of five outstanding challenges in this field: non-standardized reporting of activities, limited photochemical stability, insufficient knowledge of reaction mechanisms, balancing charge carrier lifetimes with catalysis timescales and the use of unsustainable sacrificial reagents. Solar-driven photocatalytic water splitting provides a clean pathway for production of hydrogen fuel. This Review examines both amorphous and crystalline polymeric materials for water splitting, exploring polymer design strategies, theoretical understanding and challenges for the field.