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4. Association Between Oral Bacteria and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Author

Sixin Liu, Stuart G. Dashper, and Rui Zhao

Subjects
Psychiatry and Mental health, Clinical Psychology, General Neuroscience, General Medicine, Geriatrics and Gerontology
Abstract

Background: Pre-clinical evidence implicates oral bacteria in the pathogenesis of Alzheimer’s disease (AD), while clinical studies show diverse results. Objective: To comprehensively assess the association between oral bacteria and AD with clinical evidence. Methods: Studies investigating the association between oral bacteria and AD were identified through a systematic search of six databases PubMed, Embase, Cochrane Central Library, Scopus, ScienceDirect, and Web of Science. Methodological quality ratings of the included studies were performed. A best evidence synthesis was employed to integrate the results. When applicable, a meta-analysis was conducted using a random-effect model. Results: Of the 16 studies included, ten investigated periodontal pathobionts and six were microbiome-wide association studies. Samples from the brain, serum, and oral cavity were tested. We found over a ten-fold and six-fold increased risk of AD when there were oral bacteria (OR = 10.68 95% CI: 4.48–25.43; p

Published
2023

6. An analysis of published trials found that current use of pragmatic trial labels is uninformative

Author

Monica Taljaard, Stuart G. Nicholls, Alison H. Howie, Hayden P. Nix, Kelly Carroll, Paxton M. Moon, Natalie M. Nightingale, Bruno Giraudeau, Spencer P. Hey, Sandra M. Eldridge, Charles Weijer, and Merrick Zwarenstein

Subjects
Epidemiology
Abstract

Randomized trials labelled as "pragmatic" are attractive to funders, patients, and clinicians as the label implies that the results are directly applicable to clinical care. We examined how authors justify use of the label (e.g., by referring to one or more PRECIS [PRagmatic Explanatory Continuum Indicator Summary]-2 domains).We reviewed primary trial reports published 2014-2019, registered in ClinicalTrials.gov and using the pragmatic label anywhere in the report.Among 415 trials, the label was justified by reference to at least one design element in 282 (68.0%); of these, 240 (85.1%) referenced trial characteristics that can be mapped to one or more of the PRECIS-2 domains, most commonly eligibility (91, 32.3%), setting (90, 31.9%), flexibility delivery (89, 31.6%), and organization (75, 26.6%); 42 (14.9%) referenced characteristics that are not PRECIS-2 domains, most commonly type of intervention/comparator (48, 17%), recruitment without consent (22, 7.8%), routinely collected data (22, 7.8%), and cluster randomization (20, 7.1%). Most reports referenced only one or two design elements. Overall, 9/415 (2.2%) provided PRECIS wheels.Current use of pragmatic labels is uninformative. Authors should clarify the decision the trial is intended to support and include a PRECIS-2 table to make the design transparent.

Published
2022

9. The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity

Author

Aziz Bousfiha, Abderrahmane Moundir, Stuart G. Tangye, Capucine Picard, Leïla Jeddane, Waleed Al-Herz, Charlotte C. Rundles, Jose Luis Franco, Steven M. Holland, Christoph Klein, Tomohiro Morio, Eric Oksenhendler, Anne Puel, Jennifer Puck, Mikko R. J. Seppänen, Raz Somech, Helen C. Su, Kathleen E. Sullivan, Troy R. Torgerson, and Isabelle Meyts

Subjects
Phenotype, Genotype, Neoplasms, Immunology, Immunologic Deficiency Syndromes, Hypersensitivity, Humans, Immunology and Allergy
Abstract

The International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) reports here the 2022 updated phenotypic classification, which accompanies and complements the most-recent genotypic classification. This phenotypic classification is aimed for clinicians at the bedside and focuses on clinical features and laboratory phenotypes of specific IEI. In this classification, 485 IEI underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity and auto-inflammation are described, including 55 novel monogenic defects and 1 autoimmune phenocopy. Therefore, all 485 diseases of the genetic classification are presented in this paper in the form of colored tables with essential clinical or immunological phenotype entries.

Published
2022

10. STAT5B restrains human B-cell differentiation to maintain humoral immune homeostasis

Author

Simon J. Pelham, Maria Soledad Caldirola, Danielle T. Avery, Joseph Mackie, Geetha Rao, Florian Gothe, Timothy J. Peters, Antoine Guerin, David Neumann, Doris Vokurkova, Vivian Hwa, Wenming Zhang, Shu-Chen Lyu, Iris Chang, Monali Manohar, Kari C. Nadeau, Maria Isabel Gaillard, Liliana Bezrodnik, Violeta Iotova, Norberto Walter Zwirner, Mavel Gutierrez, Waleed Al-Herz, Christopher C. Goodnow, Alexander Vargas-Hernández, Lisa R. Forbes Satter, Sophie Hambleton, Elissa K. Deenick, Cindy S. Ma, and Stuart G. Tangye

Subjects
Immunoglobulin Isotypes, Immunology, STAT5 Transcription Factor, Cytokines, Homeostasis, Humans, RNA, Immunology and Allergy, Cell Differentiation
Abstract

Lymphocyte differentiation is regulated by coordinated actions of cytokines and signaling pathways. IL-21 activates STAT1, STAT3, and STAT5 and is fundamental for the differentiation of human B cells into memory cells and antibody-secreting cells. While STAT1 is largely nonessential and STAT3 is critical for this process, the role of STAT5 is unknown.This study sought to delineate unique roles of STAT5 in activation and differentiation of human naive and memory B cells.STAT activation was assessed by phospho-flow cytometry cell sorting. Differential gene expression was determined by RNA-sequencing and quantitative PCR. The requirement for STAT5B in B-cell and CD4IL-21 activated STAT5 and strongly induced SOCS3 in human naive, but not memory, B cells. Deletion of STAT5B in B-cell lines diminished IL-21-mediated SOCS3 induction. PBMCs from STAT5B-null individuals contained expanded populations of immunoglobulin class-switched B cells, CD21These findings reveal novel roles for STAT5B in regulating IL-21-induced human B-cell differentiation. This is achieved by inducing SOCS3 to attenuate IL-21 signaling, and BCL6 to repress class switching and plasma cell generation. Thus, STAT5B is critical for restraining IL-21-mediated B-cell differentiation. These findings provide insights into mechanisms underpinning B-cell responses during primary and subsequent antigen encounter and explain autoimmunity and dysfunctional humoral immunity in STAT5B deficiency.

Published
2022

11. Coastal aeolian sediment transport in an active bed surface layer: Tracer study and conceptual model

Author

Charlotte F. K. Uphues, Christa O. van IJzendoorn, Caroline Hallin, Stuart G. Pearson, Bram C. van Prooijen, Graziela Miot da Silva, and Sierd de Vries

Subjects
field measurements, Geography, Planning and Development, armoring, sediment sorting, supply limited, Earth and Planetary Sciences (miscellaneous), beach, aeolian ripples, particle tracing, Earth-Surface Processes
Abstract

Coastal aeolian sediment transport is influenced by supply-limiting factors caused by sediment sorting by grain size. Sorting processes can lead to coarsening of the bed surface and influence the formation of aeolian ripples. However, the influence sorting processes and bedforms might have on the magnitude of the transport is not fully understood. This study explores sorting processes and their influence on the magnitude and mode of aeolian transport by using sediment tracers. Sand was painted in different colors according to particle size and placed on a supratidal beach in Noordwijk, the Netherlands. Several experiments were conducted with varying wind speeds. Surface sampling and cameras tracked the sand color movement on the bed surface, and wind velocity was measured. The tracer experiments showed that ripples developed in moderate wind conditions. Once the ripples had formed, the supply of finer tracer grains in the downwind direction decreased over time, while the supply of coarser grains remained constant. A linear relationship between ripple migration speed and wind speed was found. For higher wind speeds, no ripples or differences in transport of grain size fractions were observed. Instead, alternating phases of erosion and deposition of the bed surface were observed, which could not be related to local variations in wind velocity. Based on these results and literature, a conceptual model was developed for an active bed surface layer with two transport regimes corresponding to moderate (I) and high (II) wind speeds. The conceptual model is intended to guide the selection of aeolian sediment transport models as a function of wind speed, bed characteristics, and upwind sediment supply. For Regime I, transport could be modeled using a linear relationship between sediment transport and wind speed and for Regime II using a third power relationship in combination with a process-based model accounting for supply limitations.

Published
2022

13. Virus taxonomy and the role of the International Committee on Taxonomy of Viruses (ICTV)

Author

Siddell, Stuart G., Smith, Donald B., Adriaenssens, Evelien, Alfenas-Zerbini, Poliane, Dutilh, Bas E., Garcia, Maria Laura, Junglen, Sandra, Krupovic, Mart, Kuhn, Jens H., Lambert, Amy J., Lefkowitz, Elliot J., Łobocka, Małgorzata, Mushegian, Arcady R., Oksanen, Hanna M., Robertson, David L., Rubino, Luisa, Sabanadzovic, Sead, Simmonds, Peter, Suzuki, Nobuhiro, Van Doorslaer, Koenraad, Vandamme, Anne-Mieke, Varsani, Arvind, Zerbini, F. Murilo, University of Bristol [Bristol], University of Oxford, Quadram Institute, Biotechnology and Biological Sciences Research Council (BBSRC), Universidade Federal de Viçosa = Federal University of Viçosa (UFV), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Utrecht University [Utrecht], Instituto de Biotecnología y Biología Molecular [La Plata] (IBBM), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), Free University of Berlin (FU), Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention (CDC), University of Alabama at Birmingham [ Birmingham] (UAB), Institute of Biochemistry and Biophysics [Warsaw] (IBB), National Science Foundation [Arlington] (NSF), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, MRC - University of Glasgow Centre for Virus Research, CNR Istituto per la Protezione Sostenibile delle Piante [Torino, Italia] (IPSP), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Mississippi State University [Mississippi], Okayama University, University of Arizona, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Arizona State University [Tempe] (ASU), D.B.S. is supported by a grant from the Microbiology Society. B.E.D. is supported by the European Research Council (ERC) Consolidator grant 865694: DiversiPHI, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany ́s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Alexander von Humboldt Foundation in the context of an Alexander von Humboldt-Professorship founded by German Federal Ministry of Education and Research, and the European Union’s Horizon 2020 research and innovation programme, under the Marie Skłodowska-Curie Actions Innovative Training Networks grant agreement no. 955 974 (VIROINF). E.J.L. – this publication was supported by the National Institutes of Health (NIH) National Institute of Allergy And Infectious Diseases (NIAID), under Award Number U24AI162625. This work was also supported in part through the Laulima Government Solutions, LLC, prime contract with the NIH NIAID, under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC, under Contract No. HHSN272201800013C. A.R.M. is a Program Director at the U.S. National Science Foundation (NSF), the statements and opinions expressed herein are made in a personal capacity and do not constitute endorsement by NSF or the government of the United States. H.M.O. was supported by the University of Helsinki and Academy of Finland funding for FINStruct, part of Biocenter Finland and Instruct-ERIC. D.L.R. is funded by the MRC (MC_UU_12014/12). S.S. acknowledges support from the Mississippi Agricultural and Forestry Experiment Station (MAFES), USDA-ARS project 58-6066-9-033 and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project, under Accession Number 1021 494., European Project: 865694,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),DiversiPHI(2020), Instituto de Higiene e Medicina Tropical (IHMT), Global Health and Tropical Medicine (GHTM), and TB, HIV and opportunistic diseases and pathogens (THOP)

Subjects
ICTV, Infectious Diseases, Science & Technology, SDG 3 - Good Health and Well-being, Biotechnology & Applied Microbiology, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, virus nomenclature, virus taxonomy, virus classification, QR355 Virology, Life Sciences & Biomedicine, International Committee on Taxonomy of Viruses
Abstract

The taxonomy of viruses is developed and overseen by the International Committee on Taxonomy of Viruses (ICTV), which scrutinizes, approves and ratifies taxonomic proposals, and maintains a list of virus taxa with approved names (https://ictv.global). The ICTV has approximately 180 members who vote by simple majority. Taxon-specific Study Groups established by the ICTV have a combined membership of over 600 scientists from the wider virology community; they provide comprehensive expertise across the range of known viruses and are major contributors to the creation and evaluation of taxonomic proposals. Proposals can be submitted by anyone and will be considered by the ICTV irrespective of Study Group support. Thus, virus taxonomy is developed from within the virology community and realized by a democratic decision-making process. The ICTV upholds the distinction between a virus or replicating genetic element as a physical entity and the taxon category to which it is assigned. This is reflected by the nomenclature of the virus species taxon, which is now mandated by the ICTV to be in a binomial format (genus + species epithet) and is typographically distinct from the names of viruses. Classification of viruses below the rank of species (such as, genotypes or strains) is not within the remit of the ICTV. This article, authored by the ICTV Executive Committee, explains the principles of virus taxonomy and the organization, function, processes and resources of the ICTV, with the aim of encouraging greater understanding and interaction among the wider virology community.

Published
2023

18. Multicenter Evaluation of Multiparametric MRI Clear Cell Likelihood Scores in Solid Indeterminate Small Renal Masses

Author

Nicola Schieda, Matthew S. Davenport, Stuart G. Silverman, Barun Bagga, Daniel Barkmeier, Zane Blank, Nicole E. Curci, Ankur M. Doshi, Ryan T. Downey, Elizabeth Edney, Elon Granader, Isha Gujrathi, Rebecca M. Hibbert, Nicole Hindman, Cynthia Walsh, Tim Ramsay, Atul B. Shinagare, and Ivan Pedrosa

Subjects
Male, Cross-Sectional Studies, Humans, Radiology, Nuclear Medicine and imaging, Middle Aged, Multiparametric Magnetic Resonance Imaging, Magnetic Resonance Imaging, Carcinoma, Renal Cell, Article, Kidney Neoplasms, Retrospective Studies
Abstract

BACKGROUND: Solid small renal masses (SRMs, ≤4 cm) represent benign and malignant tumors. Among SRMs, clear cell renal cell carcinoma (ccRCC) is frequently aggressive. Compared to invasive percutaneous biopsies, a proposed clear cell likelihood score (ccLS) aims to diagnose ccRCC non-invasively using multiparametric MRI (mpMRI), but lacks external validation. PURPOSE: To evaluate the performance of and interobserver agreement for ccLS to diagnose ccRCC among solid SRMs. MATERIALS AND METHODS: This retrospective, multicenter, cross-sectional study included patients with consecutive solid (≥25% approximate volume enhancement) SRMs undergoing mpMRI between December 2012 and December 2019 at five academic medical centers with histological confirmation of diagnosis. Masses with macroscopic fat were excluded. After a 1.5-hour training session, two abdominal radiologists per center independently rendered a ccLS for 50 masses. The diagnostic performance for ccRCC was calculated using random-effects logistic regression modeling. The distribution of ccRCC by ccLS was tabulated. Interobserver agreement for ccLS was evaluated with Fleiss Kappa. RESULTS: 241 patients (mean±SD age, 60 ± 13 years, 174 men) with 250 solid SRMs were evaluated. The mean ±SD size was 25±8 mm (range 10–39 mm). 48% (119/250) of SRMs were ccRCC. The sensitivity, specificity, and positive predictive value for the diagnosis of ccRCC (95% CI) when ccLS≥4 were 75% (68%, 81%), 78% (72%, 84%), and 76% (69%, 81%), respectively. The negative predictive value of ccLS≤2 was 88% (81%, 93%). The percentages of ccRCC according to the ccLS were 6% (range, 0%–18%), 38% (range, 0%–100%), 32% (range, 18%–53%), 72% (range, 20%–100%), and 81% (range, 50%–100%) for ccLS 1–5, respectively. The mean interobserver agreement was moderate (Kappa=0.58 [95% CI: 0.42, 0.75]). CONCLUSION: The clear cell likelihood score applied to multiparametric MRI had moderate interobserver agreement and differentiated clear cell renal cell carcinoma from other solid renal masses with a negative predictive value of 88%. SUMMARY: Clear cell likelihood scores provide a framework for standardized multiparametric MRI assessment of solid small renal masses with moderate diagnostic accuracy for clear cell renal cell carcinoma.

Published
2022

19. Platform for isolation and characterization of SARS-CoV-2 variants enables rapid characterization of Omicron in Australia

Author

Anupriya Aggarwal, Alberto Ospina Stella, Gregory Walker, Anouschka Akerman, Camille Esneau, Vanessa Milogiannakis, Deborah L. Burnett, Samantha McAllery, Mariana Ruiz Silva, Yonghui Lu, Charles S. P. Foster, Fabienne Brilot, Aleha Pillay, Sabastiaan Van Hal, Vennila Mathivanan, Christina Fichter, Andrea Kindinger, Alexandra Carey Hoppe, Mee Ling Munier, Supavadee Amatayakul-Chantler, Nathan Roth, Germano Coppola, Geoff P. Symonds, Peter Schofield, Jennifer Jackson, Helen Lenthall, Jake Y. Henry, Ohan Mazigi, Hans-Martin Jäck, Miles P. Davenport, David R. Darley, Gail V. Matthews, David S. Khoury, Deborah Cromer, Christopher C. Goodnow, Daniel Christ, Roselle Robosa, Damien J. Starck, Nathan W. Bartlett, William D. Rawlinson, Anthony D. Kelleher, and Stuart G. Turville

Subjects
Microbiology (medical), SARS-CoV-2, Immunology, Australia, Genetics, COVID-19, Humans, Cell Biology, Pandemics, Applied Microbiology and Biotechnology, Microbiology
Abstract

Genetically distinct variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged since the start of the COVID-19 pandemic. Over this period, we developed a rapid platform (R-20) for viral isolation and characterization using primary remnant diagnostic swabs. This, combined with quarantine testing and genomics surveillance, enabled the rapid isolation and characterization of all major SARS-CoV-2 variants circulating in Australia in 2021. Our platform facilitated viral variant isolation, rapid resolution of variant fitness using nasopharyngeal swabs and ranking of evasion of neutralizing antibodies. In late 2021, variant of concern Omicron (B1.1.529) emerged. Using our platform, we detected and characterized SARS-CoV-2 VOC Omicron. We show that Omicron effectively evades neutralization antibodies and has a different entry route that is TMPRSS2-independent. Our low-cost platform is available to all and can detect all variants of SARS-CoV-2 studied so far, with the main limitation being that our platform still requires appropriate biocontainment.

Published
2022

20. Rational engineering of lung alveolar epithelium

Author

Katherine L. Leiby, Yifan Yuan, Ronald Ng, Micha Sam Brickman Raredon, Taylor S. Adams, Pavlina Baevova, Allison M. Greaney, Karen K. Hirschi, Stuart G. Campbell, Naftali Kaminski, Erica L. Herzog, and Laura E. Niklason

Subjects
Biomedical Engineering, Medicine (miscellaneous), Cell Biology, Developmental Biology
Abstract

Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds in order to guide AEC2 behavior for epithelial regeneration. First, endothelial cells coordinate with fibroblasts, in the presence of soluble growth and maturation factors, to promote alveolar scaffold population with surfactant-secreting AEC2s. Subsequent withdrawal of Wnt and FGF agonism synergizes with tidal-magnitude mechanical strain to induce the differentiation of AEC2s to squamous type 1 AECs (AEC1s) in cultured alveoli, in situ. These results outline a rational strategy to engineer an epithelium of AEC2s and AEC1s contained within epithelial-mesenchymal-endothelial alveolar-like units, and highlight the critical interplay amongst cellular, biochemical, and mechanical niche cues within the reconstituting alveolus.

Published
2023

22. Enhanced functional detection of synaptic calcium-permeable AMPA receptors using intracellular NASPM

Author

Ian Coombs, Cécile Bats, Craig A Sexton, Dorota Studniarczyk, Stuart G Cull-Candy, and Mark Farrant

Subjects
General Immunology and Microbiology, General Neuroscience, General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) contribute to many forms of synaptic plasticity and pathology. They can be distinguished from GluA2-containing calcium-impermeable AMPARs by the inward rectification of their currents, which reflects voltage-dependent channel block by intracellular spermine. However, the efficacy of this weakly permeant blocker is differentially altered by the presence of AMPAR auxiliary subunits – including transmembrane AMPAR regulatory proteins, cornichons, and GSG1L – which are widely expressed in neurons and glia. This complicates the interpretation of rectification as a measure of CP-AMPAR expression. Here, we show that the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution results in a complete block of GluA1-mediated outward currents irrespective of the type of associated auxiliary subunit. In neurons from GluA2-knockout mice expressing only CP-AMPARs, intracellular NASPM, unlike spermine, completely blocks outward synaptic currents. Thus, our results identify a functional measure of CP-AMPARs, that is unaffected by their auxiliary subunit content.

Published
2023

23. MAF file for CNVs from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

MAF file for copy number variations identified in the cohort

Published
2023

24. Supplementary Table S4 from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

Treatment history for patients enrolled on the PancSeq protocol.

Published
2023

25. Supplementary Table S3 from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

PancSeq protocol gene list for CLIA-certified somatic and germline analysis from whole exome sequencing data.

Published
2023

26. Supplementary Figures from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

Supplementary Figure S1: Overview of workflow and data generation. Supplementary Figure S2: Analysis of neoplastic cellularity. Supplementary Figure S3: Recurrent copy number alterations. Supplementary Figure S4: Mutational signature analysis. Supplementary Figure S5: Analysis of PDAC gene expression signatures. Supplementary Figure S6: Clinically relevant alterations in the cohort.

Published
2023

27. Supplementary Experimental Methods from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

Supplementary Experimental Methods

Published
2023

28. MAF file for mutations from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

MAF file for mutations identified in the cohort

Published
2023

29. Supplementary Table S2 from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine

Author

Brian M. Wolpin, Scott L. Carter, Ryan B. Corcoran, William C. Hahn, Jen Jen Yeh, Nikhil Wagle, David A. Tuveson, Paul B. Shyn, Jeffrey W. Miller, Robert J. Mayer, Matthew H. Kulke, Bruce E. Johnson, Jason L. Hornick, Gad Getz, Levi A. Garraway, Charles S. Fuchs, Matthew B. Yurgelun, Dean J. Welsch, Deborah Knoerzer, Richard B. Lanman, Rebecca J. Nagy, Stuart G. Silverman, Ewa Sicinska, Geoffrey I. Shapiro, Marvin Ryou, Douglas A. Rubinson, Michael H. Rosenthal, Kimberly Perez, Anuj K. Patel, Kimmie Ng, Janet E. Murphy, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kunal Jajoo, Leona A. Doyle, James M. Cleary, Thomas Clancy, Kelly P. Burke, Joseph P. St. Pierre, Heather A. Shahzade, Emily E. Van Seventer, Brandon Nadres, Annacarolina Da Silva, Ana Babic, Nelly Oliver, Karla Helvie, Kristin Anderka, Lori Marini, Devin McCabe, Emma Reilly, Marisa W. Welch, Dorisanne Ragon, Lauren K. Brais, Jaegil Kim, Srivatsan Raghavan, Mehlika Hazar-Rethinam, Arezou A. Ghazani, Richard A. Moffitt, Nicholas D. Camarda, Jonathan A. Nowak, and Andrew J. Aguirre

Abstract

Characteristics of biopsies obtained on PancSeq protocol.

Published
2023

38. Improving social justice in observational studies: protocol for the development of a global and Indigenous STROBE-equity reporting guideline

Author

Sarah Funnell, Janet Jull, Lawrence Mbuagbaw, Vivian Welch, Omar Dewidar, Xiaoqin Wang, Miranda Lesperance, Elizabeth Ghogomu, Anita Rizvi, Elie A. Akl, Marc T. Avey, Alba Antequera, Zulfiqar A. Bhutta, Catherine Chamberlain, Peter Craig, Luis Gabriel Cuervo, Alassane Dicko, Holly Ellingwood, Cindy Feng, Damian Francis, Regina Greer-Smith, Billie-Jo Hardy, Matire Harwood, Janet Hatcher-Roberts, Tanya Horsley, Clara Juando-Prats, Mwenya Kasonde, Michelle Kennedy, Tamara Kredo, Alison Krentel, Elizabeth Kristjansson, Laurenz Langer, Julian Little, Elizabeth Loder, Olivia Magwood, Michael Johnson Mahande, G. J. Melendez-Torres, Ainsley Moore, Loveline Lum Niba, Stuart G. Nicholls, Miriam Nguilefem Nkangu, Daeria O. Lawson, Ekwaro Obuku, Patrick Okwen, Tomas Pantoja, Jennifer Petkovic, Mark Petticrew, Kevin Pottie, Tamara Rader, Jacqueline Ramke, Alison Riddle, Larissa Shamseer, Melissa Sharp, Bev Shea, Peter Tanuseputro, Peter Tugwell, Janice Tufte, Erik Von Elm, Hugh Sharma Waddington, Harry Wang, Laura Weeks, George Wells, Howard White, Charles Shey Wiysonge, Luke Wolfenden, and Taryn Young

Subjects
Health Policy, Public Health, Environmental and Occupational Health
Abstract

Background Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity. The goal of this project is to develop a STROBE-Equity reporting guideline extension. Methods We assembled a diverse team across multiple domains, including gender, age, ethnicity, Indigenous background, disciplines, geographies, lived experience of health inequity and decision-making organizations. Using an inclusive, integrated knowledge translation approach, we will implement a five-phase plan which will include: (1) assessing the reporting of health equity in published observational studies, (2) seeking wide international feedback on items to improve reporting of health equity, (3) establishing consensus amongst knowledge users and researchers, (4) evaluating in partnership with Indigenous contributors the relevance to Indigenous peoples who have globally experienced the oppressive legacy of colonization, and (5) widely disseminating and seeking endorsement from relevant knowledge users. We will seek input from external collaborators using social media, mailing lists and other communication channels. Discussion Achieving global imperatives such as the Sustainable Development Goals (e.g., SDG 10 Reduced inequalities, SDG 3 Good health and wellbeing) requires advancing health equity in research. The implementation of the STROBE-Equity guidelines will enable a better awareness and understanding of health inequities through better reporting. We will broadly disseminate the reporting guideline with tools to enable adoption and use by journal editors, authors, and funding agencies, using diverse strategies tailored to specific audiences.

Published
2023

46. On the self-regulation of sport practice: Moving the narrative from theory and assessment toward practice

Author

Bradley W. Young, Stuart G. Wilson, Sharleen Hoar, Lisa Bain, Malgorzata Siekańska, and Joseph Baker

Subjects
General Psychology
Abstract

This paper reviews theoretical developments specific to applied research around the “psychology of practice” in skill acquisition settings, which we argue is under-considered in applied sport psychology. Centered upon the Self-Regulation of Sport Practice Survey (SRSP), we explain how self-regulated learning conceptually underpins this survey and review recent data supporting its empirical validation for gauging athletes’ psychological processes in relation to sport practice. This paper alternates between a review of applied research on self-regulated sport practice and new data analyses to: (a) show how scores on the SRSP combine to determine an expert practice advantage and (b) illustrate the large scope of self-organized or athlete-led time to which SRSP processes may apply. At this stage, the SRSP has been established as a reliable and valid tool in the empirical, theoretical domain. In order to move the narrative from theory and assessment toward applied practice, we present evidence to propose that it has relevance as a dialogue tool for fostering meaningful discussions between athletes and sport psychology consultants. We review initial case study insights on how the SRSP could be located in consultation in professional practice, propose initial considerations for its practical use and invite practitioners to examine its utility in applied settings.

Published
2023

48. Engaging patients in anesthesiology research: a rewarding frontier

Author

Michael Verret, Dean A. Fergusson, Stuart G. Nicholls, Megan Graham, Fiona Zivkovic, Maxime Lê, Allison Geist, Nhat Hung Lam, Ian D. Graham, Alexis F. Turgeon, Daniel I. McIsaac, and Manoj M. Lalu

Subjects
Anesthesiology and Pain Medicine, General Medicine
Published
2023

49. Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2

Author

Tina Nguyen, Anthony Lau, Julia Bier, Kristen C. Cooke, Helen Lenthall, Stephanie Ruiz-Diaz, Danielle T. Avery, Henry Brigden, David Zahra, William A Sewell, Luke Droney, Satoshi Okada, Takaki Asano, Hassan Abolhassani, Zahra Chavoshzadeh, Roshini S. Abraham, Nipunie Rajapakse, Eric W. Klee, Joseph A. Church, Andrew Williams, Melanie Wong, Christoph Burkhart, Gulbu Uzel, David R. Croucher, David E. James, Cindy S. Ma, Robert Brink, Stuart G. Tangye, and Elissa K. Deenick

Subjects
Immunology, Immunology and Allergy
Abstract

Heterozygous loss-of-function (LOF) mutations in PIK3R1 (encoding phosphatidylinositol 3-kinase [PI3K] regulatory subunits) cause activated PI3Kδ syndrome 2 (APDS2), which has a similar clinical profile to APDS1, caused by heterozygous gain-of-function (GOF) mutations in PIK3CD (encoding the PI3K p110δ catalytic subunit). While several studies have established how PIK3CD GOF leads to immune dysregulation, less is known about how PIK3R1 LOF mutations alter cellular function. By studying a novel CRISPR/Cas9 mouse model and patients’ immune cells, we determined how PIK3R1 LOF alters cellular function. We observed some overlap in cellular defects in APDS1 and APDS2, including decreased intrinsic B cell class switching and defective Tfh cell function. However, we also identified unique APDS2 phenotypes including defective expansion and affinity maturation of Pik3r1 LOF B cells following immunization, and decreased survival of Pik3r1 LOF pups. Further, we observed clear differences in the way Pik3r1 LOF and Pik3cd GOF altered signaling. Together these results demonstrate crucial differences between these two genetic etiologies.

Published
2023

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