tbuckley/cabot-search huggingface dataset:
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Authors: Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. Van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Krüger, David S. Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, Anthony R. Sotis, Gauthaman Sukumar, Camille Alba, Nathaniel Lott, Elisa McGrath Martinez, Meila Tuck, Jatinder Singh, Dagmar Bacikova, Xijun Zhang, Daniel N. Hupalo, Adelani Adeleye, Matthew D. Wilkerson, Harvey B. Pollard, Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram G. Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Edwin S. Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodríguez-Rodríguez, Jon Infante, Carmen Lage, Isabel González-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James B. Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering-Brown, Kelley Faber, Walter A. Kukull, Estrella Morenas-Rodriguez, Alberto Lleó, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Mike A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric J. Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis W. Dickson, Adriano Chiò, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, Sonja W. Scholz
Journal: Nature Genetics (2021)
Lymphocyte doubling time in chronic lymphocytic leukemia modern era: a real-life study in 848 unselected patients
Authors: Tycho Baumann, Riccardo Moia, Gianluca Gaidano, Julio Delgado, Adalgisa Condoluci, Neus Villamor, Anil Babu Payedimarri, Dolors Costa, Andrea Patriarca, Carlos Jiménez-Vicente, Davide Rossi, Emili Montserrat
Journal: Leukemia (2021)
Spirulina Supplementation and Obesity Related Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Sofía Lorena Bohórquez-Medina, Andrea Lisbet Bohórquez-Medina, Vicente Aleixandre Benites Zapata, Felipe Ignacio Cconchoy, Carlos J. Toro Huamanchumo, Guido Bendezu Quispe, Adrian V. Hernandez
Journal: Metabolism (2021)
Updating Race-Based Risk Assessment Algorithms in Clinical Practice: Time for a Systems Approach
Authors: Junaid Nabi, Atif Adam, Sophia Kostelanetz, Sana Syed
Journal: The American Journal of Bioethics (2021)

This article is referred to by:Looking Forward: A Response to Commentaries on "Race, Power and COVID-19: A Call for Advocacy within Bioethics"
Effect modification of the association between domestic mold report and wheeze by age and seroatopic predisposition among children living in lower-income New York City neighborhoods
Authors: Adnan Divjan, Karen Dannemiller, Luis Acosta, Lori Hoepner, Andrew Rundle, Julie Herbstman, Frederica Perera, Rachel Miller, Matthew Perzanowski
Journal: Journal of Allergy and Clinical Immunology (2021)
Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium
Authors: Yana Pikman, Sarah K. Tasian, Maria Luisa Sulis, Kristen Stevenson, Traci M. Blonquist, Beth Apsel Winger, Todd M. Cooper, Melinda Pauly, Kelly W. Maloney, Michael J. Burke, Patrick A. Brown, Nathan Gossai, Jennifer L. McNeer, Neerav N. Shukla, Peter D. Cole, Justine M. Kahn, Jing Chen, Matthew J. Barth, Jeffrey A. Magee, Lisa Gennarini, Asmani A. Adhav, Catherine M. Clinton, Nicole Ocasio-Martinez, Giacomo Gotti, Yuting Li, Shan Lin, Alma Imamovic, Cristina E. Tognon, Tasleema Patel, Haley L. Faust, Cristina F. Contreras, Anjali Cremer, Wilian A. Cortopassi, Diego Garrido Ruiz, Matthew P. Jacobson, Neekesh V. Dharia, Angela Su, Amanda L. Robichaud, Amy Saur Conway, Katherine Tarlock, Elliot Stieglitz, Andrew E. Place, Alexandre Puissant, Stephen P. Hunger, Annette S. Kim, Neal I. Lindeman, Lia Gore, Katherine A. Janeway, Lewis B. Silverman, Jeffrey W. Tyner, Marian H. Harris, Mignon L. Loh, Kimberly Stegmaier
Journal: Cancer Discovery (2021)

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. SIGNIFICANCE: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations.See related commentary by Bornhauser and Bourquin, p. 1322.This article is highlighted in the In This Issue feature, p. 1307.
Reply: About the recommendation of the GINA strategy report on asthma step 1
Authors: Helen K. Reddel
Journal: European Respiratory Journal (2021)

<b>The recommendation by GINA against SABA-only treatment of asthma for adults and adolescents is supported by evidence of harm from even modest SABA over-use, and strong evidence for as-needed ICS–formoterol as a safe and effective way to reduce asthma risk</b>https://bit.ly/3oy0tK2
RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia
Authors: Filip Matthijssens, Nitesh D. Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C. Cheung, Rishi S. Kotecha, Martijn D.P. Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F. Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska
Journal: Journal of Clinical Investigation (2021)

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 was required for survival of immature and KMT2A-R T-ALL cells in vitro and in vivo. We report direct transcriptional regulation of CXCR4 signaling by RUNX2, thereby promoting chemotaxis, adhesion, and homing to medullary and extramedullary sites. RUNX2 enabled these energy-demanding processes by increasing metabolic activity in T-ALL cells through positive regulation of both glycolysis and oxidative phosphorylation. Concurrently, RUNX2 upregulation increased mitochondrial dynamics and biogenesis in T-ALL cells. Finally, as a proof of concept, we demonstrate that immature and KMT2A-R T-ALL cells were vulnerable to pharmacological targeting of the interaction between RUNX2 and its cofactor CBFβ. In conclusion, we show that RUNX2 acts as a dependency factor in high-risk subtypes of human T-ALL through concomitant regulation of tumor metabolism and leukemic cell migration.
Abstract 13614: Mechanical Thrombectomy by Solotariedevice for Persistent Thrombus in Acute Coronary Syndrome
Authors: Daoyuan Si, Xingyu Fan, Yaliang Tong, Hongliang Yang, Yuquan He
Journal: Circulation (2019)

Introduction: High thrombus burden still poses technical challenge during primary percutaneous coronary intervention (PCI), and avialble options are limited when repeated aspiration therapy fails. ...
Epigenome-Wide Association Study Identifies Differentially Methylated Sites and Pathways Associated with Antidiabetic Drugs in Subjects with Metabolic Syndrome
Authors: Ignacio M. Gimenez-Alba, José V. Sorlí, Rebeca Fernandez-Carrión, Eva C. Pascual, I. González-Monge, Francesc Francés, Andrea Álvarez-Sala, Carolina Ortega-Azorín, Patricia Guillem-Saiz, Dolores Corella, Oscar Coltell
Journal: Metabolism (2021)
Bioproduced Proteins On Demand (Bio-POD) in hydrogels using Pichia pastoris
Authors: Shuo-Fu Yuan, Sierra M. Brooks, Annalee W. Nguyen, Wen-Ling Lin, Trevor G. Johnston, Jennifer A. Maynard, Alshakim Nelson, Hal S. Alper
Journal: Bioactive Materials (2021)

Traditional production of industrial and therapeutic proteins by eukaryotic cells typically requires large-scale fermentation capacity. As a result, these systems are not easily portable or reusable for on-demand protein production applications. In this study, we employ Bioproduced Proteins On Demand (Bio-POD), a F127-bisurethane methacrylate hydrogel-based technique that immobilizes engineered
Sexual Orientation Disparities in Risk Factors for Adverse COVID-19–Related Outcomes, by Race/Ethnicity — Behavioral Risk Factor Surveillance System, United States, 2017–2019
Authors: Kevin C. Heslin, Jeffrey E. Hall
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Sexual minority persons experience health disparities associated with sexual stigma and discrimination and have a high prevalence of several health conditions that have been associated with severe coronavirus disease 2019 (COVID-19) (1,2).Current COVID-19 surveillance systems do not capture information about sexual orientation.To begin bridging the gap in knowledge about COVID-19 risk among sexual minority adults, CDC examined disparities between sexual minority and heterosexual adults in the prevalence of underlying conditions with strong or mixed evidence of associations with severe COVID-19-related illness (3), by using data from the 2017-2019 Behavioral Risk Factor Surveillance System (BRFSS).*When age, sex, and survey year are adjusted, sexual minority persons have higher prevalences than do heterosexual persons of self-reported cancer, kidney disease, chronic obstructive pulmonary disease (COPD), heart disease (including myocardial infarction, angina, or coronary heart disease), obesity, smoking, diabetes, asthma, hypertension, and stroke.Sexual minority adults who are members of racial/ethnic minority groups disproportionately affected by the pandemic also have higher prevalences of several of these health conditions than do racial/ethnic minority adults who are heterosexual.Collecting data on sexual orientation in COVID-19 surveillance and other studies would improve knowledge about disparities in infection and adverse outcomes by sexual orientation, thereby informing more equitable responses to the pandemic.
Virtual Care, Telemedicine Visits, and Real Connection in the Era of COVID-19
Authors: Donna M. Zulman, Abraham Verghese
Journal: JAMA (2021)

Lori Uscher-Pines, PhD, MSc; Jessica Sousa, MSW, MPH; Maggie Jones, MPH; Christopher Whaley, PhD; Christopher Perrone, MPP; Colleen McCullough, MPA; Allison J. Ober, PhD
Methods for Identifying and Reconciling Allergy Information in the Electronic Health Record
Authors: Carlos Ortega, Ying-Chih Lo, Suzanne Blackley, Sachin Vallamkonda, Frank Chang, Oliver James, Sharmitha Yerneni, Diane Seger, Liqin Wang, Kimberly Blumenthal, Foster Goss, Paige Wickner, Li Zhou
Journal: Journal of Allergy and Clinical Immunology (2021)
Costs and Outcomes of 1-year post-discharge care trajectories of patients admitted with infection due to antibiotic-resistant bacteria
Authors: Mehdi Touat, Christian Brun-Buisson, Marion Opatowski, Jérôme Salomon, Didier Guillemot, Philippe Tuppin, Grégoire de Lagasnerie, Laurence Watier
Journal: Journal of Infection (2021)

BackgroundThe impact of antibiotic resistance (AMR) on initial hospital management has been extensively studied but its consequences after hospital discharge remain largely unknown. We aimed to analyze hospital care trajectories, cumulative length of hospital stays (c-LOS) and associated costs of care over a 1-year period after hospitalization with incident AMR infection.MethodAll incident bacterial infection-related hospitalizations occurring from January 1, 2015, to December 31, 2015 and recorded in the French national health data information system were extracted. Bacterial resistance ICD-10 codes determined six infection status. Inpatient and outpatient care consumption and associated costs were studied. The impact of resistance on c-LOS was estimated using a Poisson regression. A sequence analysis through optimal matching method was conducted to identify hospital trajectories along with an extrapolation.FindingOf the 73,244 patients selected, 15.9% had AMR infection, thus providing 58,286 incident AMR infections after extrapolation. c-LOS was significantly longer for infections with resistant bacteria, reaching 20.4 days and 2.9 additional days IC95%[2.6; 3.2] for skin and soft tissue infections. An estimated 29,793 (51.1%) patients had hospital readmission within the following year, for a total cost of €675 million. Five post-discharge trajectories were identified: Post-hospitalization mainly at home (68.4% of patients); Transition to home from rehabilitation care (12.3%); Early death (<3 months) (9.7%); Late death (7.4%), and Long-term hospitalization (2.2%).InterpretationAMR has an impact on patients' c-LOS stay beyond the initial hospitalization. Half of patients hospitalized due to AMR are readmitted to hospital within the ensuing year, along five different trajectories.FundingFrench Ministry of health.
Monoclonal Antibody for Patients with Covid-19
Journal: New England Journal of Medicine (2021)

Fil: Jaworski, Juan Pablo. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Virologia E Innovaciones Tecnologicas. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Virologia E Innovaciones Tecnologicas.; Argentina
Clinical characteristics of fatal anaphylaxis: A Spanish nationwide 17- year series
Authors: Jimena Laiseca Garcia, Lucia Gonzalez-Bravo, Sabela Codesido, Marianela Managua Brandoni Petrone, Marta Goyanes Malumbres, Patricia Alejandra Andraden Garban, Miguel A. Tejedor
Journal: Journal of Allergy and Clinical Immunology (2021)
Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study
Authors: Brian T Bateman, Sonia Hernandez-Diaz, Loreen Straub, Yanmin Zhu, Kathryn J Gray, Rishi J Desai, Helen Mogun, Nileesa Gautam, Krista F Huybrechts
Journal: BMJ (2021)

Abstract Objective To evaluate the risk of first trimester exposure to prescription opioids for major congenital malformations, previously reported to be associated with such exposure. Design Population based cohort study. Setting Nationwide sample of publicly and commercially insured pregnant women linked to their liveborn infants, nested in the Medicaid Analytic eXtract (MAX, 2000-14) and the MarketScan Research Database (MarketScan, 2003-15). Participants 1 602 580 publicly insured (MAX) and 1 177 676 commercially insured (MarketScan) pregnant women with eligibility from at least three months before pregnancy to one month after delivery; infants with eligibility for at least three months after birth. Interventions Use of prescription opioids was ascertained by requiring two or more dispensations of any opioid during the first trimester. Main outcomes measures Major malformations overall, cardiac malformations overall, ventricular septal defect, secundum atrial septal defect/patent foramen ovale, neural tube defect, clubfoot, and oral cleft, defined based on validated algorithms. Propensity score stratification was used to adjust for potential confounders and/or proxies for confounders. Estimates from each database were combined using meta-analysis. Results 70 447 (4.4%) of 1 602 580 publicly insured and 12 454 (1.1%) of 1 177 676 commercially insured pregnant women had two or more dispensations of an opioid during the first trimester. Absolute risk of malformations overall was 41.0 (95% confidence interval 39.5 to 42.5) per 1000 pregnancies exposed to opioids versus 32.0 (31.7 to 32.3) per 1000 unexposed pregnancies in the MAX cohort, and 42.6 (39.0 to 46.1) and 37.3 (37.0 to 37.7) per 1000, respectively, in the MarketScan cohort. Pooled unadjusted relative risk estimates were raised for all outcomes but shifted substantially toward the null after adjustment; for malformations overall (relative risk 1.06, 95% confidence interval 1.02 to 1.10), cardiovascular malformations (1.09, 1.00 to 1.18), ventricular septal defect (1.07, 0.95 to 1.21), atrial septal defect/patent foramen ovale (1.04, 0.88 to 1.24), neural tube defect (0.82, 0.53 to 1.27), and clubfoot (1.06, 0.88 to 1.28). The relative risk for oral clefts remained raised after adjustment (1.21, 0.98 to 1.50), with a higher risk of cleft palate (1.62, 1.23 to 2.14). Conclusions Prescription opioids used in early pregnancy are not associated with a substantial increase in risk for most of the malformation types considered, although a small increase in the risk of oral clefts associated with their use is possible.
Analysis of Patient Income in the 5 Years Following a Fracture Treated Surgically
Authors: Nathan N. O’Hara, Gerard P. Slobogean, Niek S. Klazinga, Dionne S. Kringos
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Orthopedic injury is assumed to bear negative socioeconomic consequences. However, the magnitude and duration of a fracture's impact on patient income and social insurance benefits remain poorly quantified. <h3>Objective</h3> To characterize the association between orthopedic injury and patient income using state tax records. <h3>Design, Setting, and Participants</h3> This cohort study included adult patients surgically treated for an orthopedic fracture at a US academic trauma center from January 2003 through December 2014. Hospital data were linked to individual-level state tax records using a difference-in-differences analysis performed from November 2019 through August 2020. The control group comprised of data resampled from fracture patients at least 6 years prior to injury. <h3>Exposures</h3> An operatively treated fracture of the appendicular skeleton. <h3>Main Outcomes and Measures</h3> The primary outcome was individual annual earnings up to 5 years postinjury. Secondary outcomes included annual household income and US Social Security benefits for 5 years postinjury and catastrophic wage loss within 2 years of injury. <h3>Results</h3> A total of 9997 fracture patients (mean [SD] age, 44.6 [18.9] years; 6725 [67.3%] men) to 34 570 prefracture control participants (mean [SD] age, 40.0 [20.5] years; 21 666 [62.7%] men). The median (interquartile range) of preinjury wage earnings was $16 847 ($0 to $52 221). The mean annual decline in individual earnings during the 5 years following injury was $9865 (95% CI, −$10 686 to −$8862). Annual household income declined by $5259 (95% CI, −$6337 to −$4181) over the same period. A fracture was associated with a $206 (95% CI, $147 to $265) mean annual increase in Social Security benefits in the 5 years after injury. An injury increased the risk of catastrophic wage loss by 11.6% (95% CI, 10.5% to 12.7%). Substantial relative income loss was observed in patients with preinjury earnings in the top 3 quartiles, but changes in income were negligible for patients with preinjury earnings in the bottom quartile (19%; 95% CI, −4% to 48%). <h3>Conclusions and Relevance</h3> In this cohort study of patients surgically treated for an orthopedic fracture at a US academic trauma center, fractures were associated with substantial individual and household income loss up to 5 years after injury, and 1 in 5 patients sustained catastrophic income loss in the 2 years after fracture. Gains in Social Security benefits offset less than 10% of annual income losses.
Incidence Of Fatal Anaphylaxis: A Systematic Review And Meta-analysis Of Observational Studies. Sources Of Information
Authors: Lucia Gonzalez-Bravo, Jimena Laiseca-Garcia, Sabela Codesido, Marianela Brandoni-Petrone, Patricia Andrade-Garban, Marta Goyanes-Malumbres, Miguel Tejedor
Journal: Journal of Allergy and Clinical Immunology (2021)