tbuckley/cabot-search huggingface dataset:
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals
Authors: Lasse Folkersen, Stefan Gustafsson, Qin Wang, Daniel Hvidberg Hansen, Åsa K. Hedman, Andrew Schork, Karen Page, Daria V. Zhernakova, Yang Wu, James Peters, Niclas Eriksson, Sarah E. Bergen, Thibaud S. Boutin, Andrew D. Bretherick, Stefan Enroth, Anette Kalnapenkis, Jesper R. Gådin, Bianca E. Suur, Yan Chen, Ljubica Matic, Jeremy D. Gale, Julie Lee, Weidong Zhang, Amira Quazi, Mika Ala-Korpela, Seung Hoan Choi, Annique Claringbould, John Danesh, George Davey Smith, Federico de Masi, Sölve Elmståhl, Gunnar Engström, Eric Fauman, Celine Fernandez, Lude Franke, Paul W. Franks, Vilmantas Giedraitis, Chris Haley, Anders Hamsten, Andres Ingason, Åsa Johansson, Peter K. Joshi, Lars Lind, Cecilia M. Lindgren, Steven Lubitz, Tom Palmer, Erin Macdonald-Dunlop, Martin Magnusson, Olle Melander, Karl Michaelsson, Andrew P. Morris, Reedik Mägi, Michael W. Nagle, Peter M. Nilsson, Jan Nilsson, Marju Orho-Melander, Ozren Polasek, Bram Prins, Erik Pålsson, Ting Qi, Marketa Sjögren, Johan Sundström, Praveen Surendran, Urmo Võsa, Thomas Werge, Rasmus Wernersson, Harm-Jan Westra, Jian Yang, Alexandra Zhernakova, Johan Ärnlöv, Jingyuan Fu, J. Gustav Smith, Tõnu Esko, Caroline Hayward, Ulf Gyllensten, Mikael Landen, Agneta Siegbahn, James F. Wilson, Lars Wallentin, Adam S. Butterworth, Michael V. Holmes, Erik Ingelsson, Anders Mälarstig
Journal: Nature Metabolism (2020)
What are protective antibody responses to pandemic SARS-CoV-2?
Authors: Jeffrey P. Henderson
Journal: Journal of Clinical Investigation (2020)

Human antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hold intense interest, with research efforts directed at optimizing antibody-based interventions and monitoring immune status. By relating individual variations in antibody response to coronavirus disease 2019 (COVID-19) severity, beneficial antiviral immune responses may be identified in detail. In this issue of the JCI, Secchi and collaborators describe antibody response profiles in 509 patients with COVID-19 from Italy during the 2020 pandemic. The research team found that multiple antibody types to multiple SARS-CoV-2 antigens developed over four weeks. Notably, IgG against the spike receptor binding domain (RBD) was predictive of survival and IgA against the viral spike protein (S protein) associated with rapid virologic clearance. These results may help guide selection of convalescent plasma, hyperimmune products, monoclonal antibodies, and vaccine strategies for COVID-19.
THU0185 Reliability of ra mri scoring
Authors: MN Lassere, F McQueen, M Ostergaard, P Conaghan, R Shnier, C Peterfy, M Klarlund, N Stewart, P O’Connor, P Bird, J Edmonds, P Emery, H Genant
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> At OMERACT5 recommendations were developed for acquisitions/scoring of MRI synovitis/bone destruction of hand/wrist in RA: OM5 RA MRI Score (Om5 RAMRIS).<sup>1</sup> These were based on results of a multicentre inter-reader agreement studies of two earlier MRI scoring methods, developed at EULAR 1999 and ACR 1999.<sup>2</sup> <h3>Objectives</h3> Determine whether reader calibration, standardisation of imaging protocols and more precise definitions of lesions improved inter-reader agreement of MRI scoring. <h3>Methods</h3> MRIs (1.5T, cor and axial T1&amp; T2, FS, iv Gd) of wrist (8)&amp; 2‑5 MCPJ(10) scored by experienced readers in 5 centres. Synovitis determined by Gd enhancement in synovial compartment by 2 methods: global score (0‑3)(wrist 3 sites, MCPJ 4 sites) and direct measure (mm) of maximal thickness of enhancing tissue (wrist 4 sites, MCPJ 2 sites). Bone erosion (wrist 15 sites, MCPJ 8 sites) was a bone defect with sharp margins, with a cortical break. Bone defect and bone oedema also defined. All measured 0‑10 by volume of defect as proportion of assessed bone volume by 10% increments judged on all images. <h3>Results</h3> Reliability for most sites for all lesions was good. Poor intraclass correlation coefficients for bone defect (but excellent agreement) were due to predominance of zero scores. Table 1 shows results of summated scores). Om5 RAMRIS performed better than our previous scoring methods. <h3>Conclusion</h3> We found Om5 RAMRIS has acceptable inter-reader reliability. Whether it can be further improved and degree to which it’s sensitive to change will need to be determined by its performance in longitudinal/intervention studies. <h3>References</h3> Conaghan, <i>et al</i>. J Rheum, in press Ostergaard, <i>et al</i>. J Rheum, in press
AI-driven quantification, staging and outcome prediction of COVID-19 pneumonia
Authors: Guillaume Chassagnon, Maria Vakalopoulou, Enzo Battistella, Stergios Christodoulidis, Trieu-Nghi Hoang-Thi, Severine Dangeard, Eric Deutsch, Fabrice Andre, Enora Guillo, Nara Halm, Stefany El Hajj, Florian Bompard, Sophie Neveu, Chahinez Hani, Ines Saab, Aliénor Campredon, Hasmik Koulakian, Souhail Bennani, Gael Freche, Maxime Barat, Aurelien Lombard, Laure Fournier, Hippolyte Monnier, Téodor Grand, Jules Gregory, Yann Nguyen, Antoine Khalil, Elyas Mahdjoub, Pierre-Yves Brillet, Stéphane Tran Ba, Valérie Bousson, Ahmed Mekki, Robert-Yves Carlier, Marie-Pierre Revel, Nikos Paragios
Journal: Medical Image Analysis (2020)
Appraisal needs to re-start now so doctors can reflect on coronavirus experiences
Authors: Susi Caesar, Graham Layer, Regi Alexander, Vicky Banks, Stephen Barasi, Susan Bews, Basant Chaudhury, Philippa Cockman, Maurice Conlon, Sunil Dasan, Tony Feltbower, David Fox, Steph Hughes, Bov Jani, Di Jelley, Nick Lewis-Barned, Sol Mead, Kashif Qureshi, Paul Twomey, Hugo van Woerden, John Woodhouse, Frances Yuille
Journal: BMJ (2020)

<h3>Abstract</h3> <h3>Background</h3> Respiratory diseases such as chronic obstructive pulmonary disease (COPD) have been associated with increased risk of severe SARS-CoV-2 infection, but the mechanisms and putative immune pathways are unclear. Besides, increased levels of several immune mediators in patients with severe coronavirus disease 19 (COVID-19) have been reported. <h3>Objective</h3> To perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma and COPD and to evaluate their relationship with biomarkers of severe COVID-19. <h3>Methods</h3> 92 protein biomarkers were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic. <h3>Results</h3> Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 and CCL3 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). Functional annotation revealed their enrichment in chemokine signaling pathways related with response to viral infections. Some of these proteins were found up-regulated upon SARS-Cov-2 infection of Calu-3 cells. Also, HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE have been found increased in patients with severe COVID-19. HGF, the most significant protein in this study as well as its correlated proteins could be associated with the increased risk of severe COVID-19 in COPD patients. <h3>Conclusions</h3> Asthma and COPD patients have altered plasma levels of proteins that have been found associated with increased risk of severe COVID-19. The reasons for sharing these profiles with this infection are unknown, but our study suggest that adult patients with asthma and COPD have a systemic dysregulation in chemokine networks that could make them more susceptible to severe COVID-19.
Long-term effects of PM2·5 on neurological disorders in the American Medicare population: a longitudinal cohort study
Authors: Liuhua Shi, Xiao Wu, Mahdieh Danesh Yazdi, Danielle Braun, Yara Abu Awad, Yaguang Wei, Pengfei Liu, Qian Di, Yun Wang, Joel Schwartz, Francesca Dominici, Marianthi-Anna Kioumourtzoglou, Antonella Zanobetti
Journal: The Lancet Planetary Health (2020)

Accumulating evidence links fine particulate matter (PM2·5) to premature mortality, cardiovascular disease, and respiratory disease. However, less is known about the influence of PM2·5 on neurological disorders. We aimed to investigate the effect of long-term PM2·5 exposure on development of Parkinson's disease or Alzheimer's disease and related dementias.We did a longitudinal cohort study in which we constructed a population-based nationwide open cohort including all fee-for-service Medicare beneficiaries (aged ≥65 years) in the contiguous United States (2000-16) with no exclusions. We assigned PM2·5 postal code (ie, ZIP code) concentrations based on mean annual predictions from a high-resolution model. To accommodate our very large dataset, we applied Cox-equivalent Poisson models with parallel computing to estimate hazard ratios (HRs) for first hospital admission for Parkinson's disease or Alzheimer's disease and related dementias, adjusting for potential confounders in the health models.Between Jan 1, 2000, and Dec 31, 2016, of 63 038 019 individuals who were aged 65 years or older during the study period, we identified 1·0 million cases of Parkinson's disease and 3·4 million cases of Alzheimer's disease and related dementias based on primary and secondary diagnosis billing codes. For each 5 μg/m3 increase in annual PM2·5 concentrations, the HR was 1·13 (95% CI 1·12-1·14) for first hospital admission for Parkinson's disease and 1·13 (1·12-1·14) for first hospital admission for Alzheimer's disease and related dementias. For both outcomes, there was strong evidence of linearity at PM2·5 concentrations less than 16 μg/m3 (95th percentile of the PM2·5 distribution), followed by a plateaued association with increasingly larger confidence bands.We provide evidence that exposure to annual mean PM2·5 in the USA is significantly associated with an increased hazard of first hospital admission with Parkinson's disease and Alzheimer's disease and related dementias. For the ageing American population, improving air quality to reduce PM2·5 concentrations to less than current national standards could yield substantial health benefits by reducing the burden of neurological disorders.The Health Effects Institute, The National Institute of Environmental Health Sciences, The National Institute on Aging, and the HERCULES Center.
Closure of Iatrogenic Atrial Septal Defect After Transcatheter Mitral Valve Repair
Authors: Philipp Lurz, Matthias Unterhuber, Karl-Philipp Rommel, Karl-Patrik Kresoja, Tobias Kister, Christian Besler, Karl Fengler, Marcus Sandri, Ingo Daehnert, Holger Thiele, Maximilian von Roeder, Stephan Blazek
Journal: Circulation (2020)
Symptomatic Efficacy of Pharmacological Treatments for Knee Osteoarthritis: A Systematic Review and a Network Meta-Analysis with a 6-Month Time Horizon
Authors: C. Beaudart, L. Lengelé, V. Leclercq, A. Geerinck, D. Sanchez-Rodriguez, O. Bruyère, J. Y. Reginster
Journal: Drugs (2020)

Several pharmacological treatments aiming at a better symptomatic control of osteoarthritis (OA) are used in daily practice but their efficacy is often disputed. The purpose of this network meta-analysis (NMA) is to assess the efficacy on pain and function of the drugs that are most widely prescribed against knee OA. Medline, Scopus, and Cochrane database of systematic reviews were searched for randomized controlled trials published up to August 2019 and assessing the efficacy of knee OA treatments using a 6-month time horizon. Pain and function changes from baseline were the primary outcomes. A Bayesian network meta-analysis was run and standardized mean differences (SMDs) with 95% credibility intervals (95% CrIs) were calculated. 9697 references were identified and 80 RCTs were concordant with our inclusion criteria (79 studies involving 15,609 individuals reported pain outcomes and 55 studies involving 13,655 individuals reported function outcomes). A significant decrease in pain was observed for the intra-articular (IA) combination of hyaluronic acid (HA) and triamcinolone (SMD − 0.49, 95% CrI − 0.78; − 0.19), vitamin D (SMD − 0.31, 95% CrI − 0.56; − 0.06), IA HA (SMD − 0.29, 95% CrI − 0.40; − 0.17), prescription-grade crystalline glucosamine sulfate (pCGS) (SMD − 0.29, 95% CrI − 0.58; − 0.004), and prescription-grade chondroitin sulfate (pCS) (SMD − 0.26, 95% CrI − 0.44; − 0.08). Significant improvements in physical function were found with pCGS (SMD − 0.44, 95% CrI − 0.66; − 0.21), vitamin D (SMD − 0.30, 95% CrIs − 0.49; − 0.11) and IA HA (SMD − 0.21, 95% CrIs − 0.31; − 0.11). Six months of treatment with IA HA, pCGS, pCS, vitamin D and the combination of IA HA and triamcinolone improve pain and/or physical function in patients suffering from knee OA.
A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study)
Authors: Erica Brivio, Franco Locatelli, Marta Lopez-Yurda, Andrea Malone, Cristina Díaz-de-Heredia, Bella Bielorai, Claudia Rossig, Vincent H. J. van der Velden, Anneke C. J. Ammerlaan, Adriana Thano, Inge M. van der Sluis, Monique L. den Boer, Ying Chen, Barbara Sleight, Benoit Brethon, Karsten Nysom, Lucie Sramkova, Ingrid Øra, Luciana Vinti, Christiane Chen-Santel, Christian Michel Zwaan
Journal: Blood (2020)
Treatment effect of aspirin for primary prevention does not differ according to baseline ASCVD risk
Authors: Sean P. Haley, Alexander Chessman
Journal: Annals of Internal Medicine (2020)

Source Citation Nudy M, Cooper J, Ghahramani M, et al. Aspirin for primary atherosclerotic cardiovascular disease prevention as baseline risk increases: a meta-regression analysis. Am J Med. 2020;133:1056-64. 32445718
An epitope-based approach of HLA-matched platelets for transfusion: a noninferiority crossover randomized trial
Authors: Judith C. Marsh, Simon J. Stanworth, Laura A. Pankhurst, Delordson Kallon, Adeline Z. Gilbertson, Collette Pigden, Alison J. Deary, Ana S. Mora, Joanne Brown, Emma S. Laing, Louise L. Choo, Renate Hodge, Charlotte A. Llewelyn, Kay Harding, Deborah Sage, Aleksandar Mijovic, Ghulam J. Mufti, Cristina V. Navarrete, Colin J. Brown
Journal: Blood (2020)
Multiplex enCas12a screens detect functional buffering among paralogs otherwise masked in monogenic Cas9 knockout screens
Authors: Merve Dede, Megan McLaughlin, Eiru Kim, Traver Hart
Journal: Genome biology (2020)

Pooled library CRISPR/Cas9 knockout screening across hundreds of cell lines has identified genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the number of essential genes detected from these monogenic knockout screens is low compared to the number of constitutively expressed genes in a cell.
48P EAPC-36: A potent microtubule-targeting agent active against a broad spectrum of solid tumours
Authors: S. Boichuk, A. Galembikova, P. Dunaev, I. Nurgatina, A. Aukhadieva, S. Zykova, F. Bikinieva, N. Igidov
Journal: Annals of Oncology (2020)
27P Development of DNA methylation markers panels for neoadjuvant chemotherapy response prediction in triple-negative breast cancer
Authors: V.O. Sigin, A.I. Kalinkin, E. Ignatova, G. Chesnokova, I.Y. Vinogradov, I.I. Vinogradov, M.I. Vinogradov, V.V. Strelnikov, D.V. Zaletaev, A.S. Tanas
Journal: Annals of Oncology (2020)
Inapparent Congenital Cytomegalovirus Infection
Authors: John G. Starr, Robert D. Bart, Eu Gold
Journal: New England Journal of Medicine (1970)

Twenty-six infants born during 12 months at a general hospital had congenital cytomegalovirus infection. Clustering of cases was not apparent either by date of birth or by geographic location, suggesting that the observed attack rate of congenital infection (1.2 per cent) was not the result of a community epidemic. Clinically apparent cytomegalic inclusion disease was present in only one infected infant. The birth weight of nine infected infants was less than 2500 gm, but the occurrence of neonatal problems such as jaundice and hepatosplenomegaly was similar to that found among uninfected control infants. Mothers of infected babies were younger and more likely to be primiparas than mothers of uninfected controls. During a mean follow-up of eight months, unfavorable clinical outcome was observed in three infected infants with low birth weights and in no controls.
The SIOP-Renal Tumour Study Group consensus statement on flank target volume delineation for highly conformal radiotherapy
Authors: Geert O Janssens, Patrick Melchior, Joeri Mul, Daniel Saunders, Stephanie Bolle, Alison L Cameron, Line Claude, Kristin Gurtner, Kees P van de Ven, Martine van Grotel, Semi Harrabi, Yasmin Lassen-Ramshad, Naomi Lavan, Henriette Magelssen, Xavier Muracciole, Tom Boterberg, Henry Mandeville, Jan Godzinski, Norbert Graf, Marry M van den Heuvel-Eibrink, Christian Rübe
Journal: The Lancet Child & Adolescent Health (2020)
Increasing Incidence of Microscopic Colitis in a Population-Based Cohort Study in Switzerland
Authors: Hugo Maye, Ekaterina Safroneeva, Sébastien Godat, Christine Sempoux, Pu Yan, Hanifa Bouzourène, Walter Seelentag, Edouard Stauffer, Lorenzo Taminelli, Frank Seibold, Alain M. Schoepfer
Journal: Clinical Gastroenterology and Hepatology (2020)
Effect of Doxorubicin on Myocardial Bicarbonate Production From Pyruvate Dehydrogenase in Women With Breast Cancer
Authors: Jae Mo Park, Galen D. Reed, Jeff Liticker, William C. Putnam, Alvin Chandra, Katarina Yaros, Aneela Afzal, James MacNamara, Jaffar Raza, Ronald G. Hall, Jeannie Baxter, Kelley Derner, Salvador Pena, Raja Reddy Kallem, Indhu Subramaniyan, Vindhya Edpuganti, Crystal E. Harrison, Alagar Muthukumar, Cheryl Lewis, Sangeetha Reddy, Nisha Unni, Dawn Klemow, Samira Syed, Hsiao Li, Suzanne Cole, Thomas Froehlich, Colby Ayers, James de Lemos, Craig R. Malloy, Barbara Haley, Vlad G. Zaha
Journal: Circulation Research (2020)
An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics
Authors: Phuc H. Hoang, Alex J. Cornish, Amy L. Sherborne, Daniel Chubb, Scott Kimber, Graham Jackson, Gareth J. Morgan, Gordon Cook, Ben Kinnersley, Martin Kaiser, Richard S. Houlston
Journal: Blood Cancer Journal (2020)

Abstract Most patients with multiple myeloma (MM) die from progressive disease after relapse. To advance our understanding of MM evolution mechanisms, we performed whole-genome sequencing of 80 IGH -translocated tumour-normal newly diagnosed pairs and 24 matched relapsed tumours from the Myeloma XI trial. We identify multiple events as potentially important for survival and therapy-resistance at relapse including driver point mutations (e.g., TET2 ), translocations ( MAP3K14 ), lengthened telomeres, and increased genomic instability (e.g., 17p deletions). Despite heterogeneous mutational processes contributing to relapsed mutations across MM subtypes, increased AID/APOBEC activity is particularly associated with shorter progression time to relapse, and contributes to higher mutational burden at relapse. In addition, we identify three enhanced major clonal evolution patterns of MM relapse, independent of treatment strategies and molecular karyotypes, questioning the viability of “evolutionary herding” approach in treating drug-resistant MM. Our data show that MM relapse is associated with acquisition of new mutations and clonal selection, and suggest APOBEC enzymes among potential targets for therapy-resistant MM.
Post-Transplantation Cyclophosphamide Induces Alloreactive T-Cell Functional Impairment and Depends on Foxp3+ Regulatory T Cells Not Selective Elimination or Intrathymic Clonal Deletion of Alloreactive T Cells
Authors: Lucas P. Wachsmuth, Michael T. Patterson, Michael A. Eckhaus, Ronald E. Gress, Christopher G. Kanakry
Journal: Blood (2017)
Abstract 14809: Augmenting the Efficiency of ECG Interpretation With Artificial Intelligence
Authors: Sameer Mehta, Edgardo Escobar, Francisco Fernandez, Sebastian Niklitschek, Carlos Villagran, Felipe Vera, Roberto Rocuant, Jorge Avila, German Cardenas, Alejandra Frauenfelder, Daniel Vieira, Gladys Pinto, Lorena Pisana, Jorge Mazzini, Rodrigo Safie, Anibal Munguia, Estefania Cecilio, Isabella Vallenilla, Carlos Peña, Jose S Aguilar, Genesis Del Nogal, Daniela Bou Daher, Pedro Cruz, Jorge Cardenas, Benjamin Wood, Akhil Vaid
Journal: Circulation (2019)

Introduction: Artificial Intelligence (AI) is incrementally performing medical tasks and improving decision-making. In this quest, ECG interpretation seems a logical foray. We have been performing ...
Outcomes of persons with coronavirus disease 2019 in hospitals with and without standard treatment with (hydroxy)chloroquine
Authors: Edgar JG. Peters, Didier Collard, Sander Van Assen, Martijn Beudel, Marije K. Bomers, Jacqueline Buijs, Lianne R. De Haan, Wouter De Ruijter, Renée A. Douma, Paul WG. Elbers, Abraham Goorhuis, Niels C. Gritters van den Oever, Lieve GHH. Knarren, Hazra S. Moeniralam, Remy LM. Mostard, Marian JR. Quanjel, Auke C. Reidinga, Roos Renckens, Joop PW. Van Den Bergh, Imro N. Vlasveld, Jonne J. Sikkens
Journal: Clinical Microbiology and Infection (2020)

To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19.