tbuckley/cabot-search huggingface dataset:
Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial
Authors: Amy Burd, Ross L. Levine, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Prapti Patel, Maria R. Baer, Wendy Stock, Michael Deininger, William Blum, Gary Schiller, Rebecca Olin, Mark Litzow, James Foran, Tara L. Lin, Brian Ball, Michael Boyiadzis, Elie Traer, Olatoyosi Odenike, Martha Arellano, Alison Walker, Vu. H. Duong, Tibor Kovacsovics, Robert Collins, Abigail B. Shoben, Nyla A. Heerema, Matthew C. Foster, Jo-Anne Vergilio, Tim Brennan, Christine Vietz, Eric Severson, Molly Miller, Leonard Rosenberg, Sonja Marcus, Ashley Yocum, Timothy Chen, Mona Stefanos, Brian Druker, John C. Byrd
Journal: Nature Medicine (2020)
Mitochondrial pyruvate carriers are required for myocardial stress adaptation
Authors: Yuan Zhang, Paul V. Taufalele, Jesse D. Cochran, Isabelle Robillard-Frayne, Jonas Maximilian Marx, Jamie Soto, Adam J. Rauckhorst, Fariba Tayyari, Alvin D. Pewa, Lawrence R. Gray, Lynn M. Teesch, Patrycja Puchalska, Trevor R. Funari, Rose McGlauflin, Kathy Zimmerman, William J. Kutschke, Thomas Cassier, Shannon Hitchcock, Kevin Lin, Kevin M. Kato, Jennifer L. Stueve, Lauren Haff, Robert M. Weiss, James E. Cox, Jared Rutter, Eric B. Taylor, Peter A. Crawford, E. Douglas Lewandowski, Christine Des Rosiers, E. Dale Abel
Journal: Nature Metabolism (2020)
Nailing the diagnosis: severe nail involvement in adult pulmonary Langerhans cell histiocytosis
Authors: Laure Delaval, Jean-David Bouaziz, Maxime Battistella, Gwenaël Lorillon, Abdellatif Tazi
Journal: Thorax (2020)

A 36-year-old male ex-smoker was referred for the management of pulmonary Langerhans cell histiocytosis (LCH) confirmed by surgical biopsy (figure 1A). He had been treated with desmopressin for 5 years for diabetes insipidus. One year before admission, dyspnoea on exertion had appeared. At the same time, the patient developed painful nail abnormalities on all 10 fingers with subungual hyperkeratosis, purpuric striae, paronychial erythema, longitudinal grooving, splinter haemorrhages, onycholysis, lunula deformation (figure 1B), with no underlying bone involvement on hand X-ray examination. Nail samples were negative for bacteria and fungi. Maculopapular and crusted lesions in the axillary fold, the scalp and the external auditory canal were also present. A nail biopsy showed hyperplastic epidermis, surmounted by thick parakeratosis. The upper dermis was infiltrated by pale histiocytes with eosinophilic cytoplasm and reniform nuclei that positively stained for CD1a antigen, …
TCT CONNECT-249 Real-World Dual Antiplatelet Therapy Following Polymer-free, Sirolimus-Eluting Stent Implantations to Treat Coronary Artery Disease
Authors: Markus Florian Krackhardt, Matthias Waliszewski, Michel Pansieri, Fernando Lozano, Tay Mok Heang, Martin Hudec, Martin Studencan, Josepa Mauri, Petr Toušek, Bruno Garcia, Taehoon Ahn, Viktor Kocka, Bronislav Janek, Laurent Sebagh, Denny Herberger, Gilles Levy, Vjekoslav Tomulic, Jérôme Rischner
Journal: Journal of the American College of Cardiology (2020)
THU0044 Methotrexate inhibits ex-vivo ifn-gamma production in whole blood of rheumatoid arthritis patients
Authors: AH Gerards, ER De Groot, AP Prins, BA Dijkmans, LA Aarden
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The mechanism by which methotrexate (MTX), a well known antifolate inhibits inflammation is still unknown. The inflammation in rheumatoid arthritis is mediated by pro-inflammatory cytokines such as TNFα and IFNγ. <h3>Objectives</h3> To assess whether cytokine production in blood of RA patients is inhibited after taking MTX. <h3>Methods</h3> Blood was obtained from 25 RA patients at T = 0 h and T = 2 h after taking MTX (10 mg or) for the first time. Heparinized Whole Blood Cultures (WBC; dilution 1/4) using anti-CD3 and anti-CD28 as stimulus were performed, with and without addition of folinic acid (40 g/ml) to the culture. Because MTX has been reported to induce IL-10 production all experiments were also carried out with and without excess neutralising mAb to IL-10. After incubation for 72 h supernatants were measured by ELISA. <h3>Results</h3> IFNγ production by WBC of 25 RA patients before (T = 0 h) and after (T = 2 h) MTX. <h3>Conclusion</h3> MTX inhibits <i>ex vivo</i> IFNγ production in RA patients by a folate dependent mechanism. MTX does not act via induction of IL-10. Similar results were found for TNFα and GM-CSF. IL-8 production is not affected by MTX.
TCT CONNECT-214 Impact of the COVID-19 Pandemic on Acute Coronary Syndrome and Stroke Volumes in Non-Western Countries
Authors: Marouane Boukhris, Lorenzo Azzalini, Vitaly Baystrukov, Hatem Aloui, Evgeny Kretov, Marcelo Harada, Gustavo Neves de Araújo, Marco Wainstein, Ali Hillani, Samer Mansour, Amine Nasri, Maude Sestier, Sami Souissi, Faouzi Addad
Journal: Journal of the American College of Cardiology (2020)
David Oliver: How not to do covid-19 comms—copy our government
Authors: David Oliver
Journal: BMJ (2020)

I've been thinking for months that many failings in our pandemic response are really public communication failings.Compared with consistent communications and strategy in other countries, the UK government has fallen far short.Messaging should be clear, consistent, and easily understood.The evidence base and rationale for decisions should be shared openly and readily understandable.We should also know who's involved in advising, deciding, and consulting; who has final accountability for decisions, nationally and locally; and where the balance lies.For example, where did the recent decision on the 10 pm curfew arise?
Covid-19: Increased risk among ethnic minorities is largely due to poverty and social disparities, review finds
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Covid-19: Increased risk among ethnic minorities is largely due to poverty and social disparities, review finds Gareth IacobucciMost of the increased risk of infection and death from covid-19 among people from ethnic minorities is explained by factors such as occupation, where people live, their household composition, and pre-existing health conditions, a government review has concluded.
HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection
Authors: Yu Guo, Longjun Li, Tao Xu, Xiaomin Guo, Chaoming Wang, Yihui Li, Yanan Yang, Dong Yang, Bin Sun, Xudong Zhao, Genze Shao, Xiaopeng Qi
Journal: Journal of Clinical Investigation (2020)

The mechanism by which inflammasome activation is modulated remains unclear. In this study, we identified an AIM2-interacting protein, the E3 ubiquitin ligase HUWE1, which was also found to interact with NLRP3 and NLRC4 through the HIN domain of AIM2 and the NACHT domains of NLRP3 and NLRC4. The BH3 domain of HUWE1 was important for its interaction with NLRP3, AIM2, and NLRC4. Caspase-1 maturation, IL-1β release, and pyroptosis were reduced in Huwe1-deficient bone marrow-derived macrophages (BMDMs) compared with WT BMDMs in response to stimuli to induce NLRP3, NLRC4, and AIM2 inflammasome activation. Furthermore, the activation of NLRP3, NLRC4, and AIM2 inflammasomes in both mouse and human cells was remarkably reduced by treatment with the HUWE1 inhibitor BI8622. HUWE1 mediated the K27-linked polyubiquitination of AIM2, NLRP3, and NLRC4, which led to inflammasome assembly, ASC speck formation, and sustained caspase-1 activation. Huwe1-deficient mice had an increased bacterial burden and decreased caspase-1 activation and IL-1β production upon Salmonella, Francisella, or Acinetobacter baumannii infection. Our study provides insights into the mechanisms of inflammasome activation as well as a potential therapeutic target against bacterial infection.
Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation
Authors: Shiyang Liu, Nathan Harmston, Trudy Lee Glaser, Yunka Wong, Zheng Zhong, Babita Madan, David M. Virshup, Enrico Petretto
Journal: Genome Medicine (2020)

Abstract Background Wnt signaling is an evolutionarily conserved developmental pathway that is frequently hyperactivated in cancer. While multiple protein-coding genes regulated by Wnt signaling are known, the functional lncRNAs regulated by Wnt signaling have not been systematically characterized. Methods We comprehensively mapped Wnt-regulated lncRNAs from an orthotopic Wnt-addicted pancreatic cancer model and examined the response of lncRNAs to Wnt inhibition between in vivo and in vitro cancer models. We further annotated and characterized these Wnt-regulated lncRNAs using existing genomic classifications (using data from FANTOM5) in the context of Wnt signaling and inferred their role in cancer pathogenesis (using GWAS and expression data from the TCGA). To functionally validate Wnt-regulated lncRNAs, we performed CRISPRi screens to assess their role in cancer cell proliferation both in vivo and in vitro. Results We identified 3633 lncRNAs, of which 1503 were regulated by Wnt signaling in an orthotopic Wnt-addicted pancreatic cancer model. These lncRNAs were much more sensitive to changes in Wnt signaling in xenografts than in cultured cells. Our analysis suggested that Wnt signaling inhibition could influence the co-expression relationship of Wnt-regulated lncRNAs and their eQTL-linked protein-coding genes. Wnt-regulated lncRNAs were also implicated in specific gene networks involved in distinct biological processes that contribute to the pathogenesis of cancers. Consistent with previous genome-wide lncRNA CRISPRi screens, around 1% (13/1503) of the Wnt-regulated lncRNAs were found to modify cancer cell growth in vitro. This included CCAT1 and LINC00263 , previously reported to regulate cancer growth. Using an in vivo CRISPRi screen, we doubled the discovery rate, identifying twice as many Wnt-regulated lncRNAs (25/1503) that had a functional effect on cancer cell growth. Conclusions Our study demonstrates the value of studying lncRNA functions in vivo, provides a valuable resource of lncRNAs regulated by Wnt signaling, and establishes a framework for systematic discovery of functional lncRNAs.
The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia
Authors: Xiang Zhang, Xuewu Zhang, Xia Li, Yunfei Lv, Yanan Zhu, Jinghan Wang, Jie Jin, Wenjuan Yu
Journal: Journal of Hematology & Oncology (2020)

IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-allele CEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.
TCT CONNECT-445 Sex-Stratified Analysis of the Safety of Percutaneous Left Atrial Appendage Occlusion: An Insight From the National Readmission Database
Authors: Mohammed Osman, Brijesh Patel, Muhamad Munir, Akram Kawsara, Babikir Kheiri, Ramesh Daggubati, Erin Michos, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2020)
Risk factors for carbapenem-resistant Gram-negative bacterial infections: a systematic review
Authors: Zaira R. Palacios-Baena, Maddalena Giannella, Davide Manissero, Jesus Rodríguez-Baño, Pierluigi Viale, Sara Lopes, Katy Wilson, Rachael McCool, Christopher Longshaw
Journal: Clinical Microbiology and Infection (2020)

BackgroundRapid and widespread increases in carbapenem resistance (CR) necessitate identification of risk factors to guide appropriate interventions.ObjectivesWe aimed to identify risk factors for CR Gram-negative infection through a systematic literature review.Data sourcesWe searched MEDLINE (via OvidSP and PubMed) and Embase (via OvidSP) databases and the Cochrane Central Register of Controlled Trials.Study eligibility criteriaProspective or retrospective cohort and case–control studies reporting quantitative data on risk factors associated with infections due to CR Gram-negative pathogens in hospitalized patients were eligible.ParticipantsStudies included hospitalized patients with CR infection caused by Gram-negative bacterial pathogens (Enterobacterales and non-fermenters).MethodsSearches were conducted in January 2018/December 2019 to identify studies published since 2007. Risk factor data were extracted and grouped by factor. The primary metric was proportion of studies reporting a significant association with CR infection for each factor.ResultsIn total, 92 studies were identified. Risk factors most frequently reported as significantly associated with CR infection (>10 studies) were previous antibiotic use (91.1%; 72/79 studies); previous carbapenem use (82.6%; 57/69); previous colonization (72.7%; 8/11); mechanical ventilation (66.7%; 36/54); previous intensive care unit stay (64.4%; 38/59); dialysis (61.1%; 11/18); catheter (58.0%; 40/69); length of stay in hospital (54.5%; 30/55); comorbidities (52.7%; 39/74); APACHE II (51.7%; 15/29); and intubation (51.4%; 18/35). Risk factors were mostly consistent across different species and sites of infection.ConclusionsSeveral variables, particularly previous antibiotic use, are strong risk factors for CR infection. Interventions to mitigate against CR infection should target these factors.
TCT CONNECT-343 Early Feasibility Study of Ventricular Restoration System in Heart Failure Patients With FMR: 6-Month Outcomes
Authors: Satya Shreenivas, Steven Martin, Hosakote Nagaraj, Guilherme Silva, Mark Reisman, Creigthon Don, Hemal Gada, Kendra Grubb, Dean Kereiakes, Paul Sorajja, Daniel Burkhoff
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-375 Gender Differences on the Rate of Success of Percutaneous Lower Limb Arteries Revascularization
Authors: Carlos Giuliani, Ezequiel Zaidel, Gerardo Nau, Sebastian Peralta, Juan Grieve, Guillermo Jubany, Luis Murillo, Carlos Sztejfman, Matias Sztejfman, Marcelo Bettinotti
Journal: Journal of the American College of Cardiology (2020)
Coronavirus Disease 2019 and the Athletic Heart
Authors: Jonathan H. Kim, Benjamin D. Levine, Dermot Phelan, Michael S. Emery, Mathew W. Martinez, Eugene H. Chung, Paul D. Thompson, Aaron L. Baggish
Journal: JAMA Cardiology (2020)

Cardiac injury with attendant negative prognostic implications is common among patients hospitalized with coronavirus disease 2019 (COVID-19) infection. Whether cardiac injury, including myocarditis, also occurs with asymptomatic or mild-severity COVID-19 infection is uncertain. There is an ongoing concern about COVID-19-associated cardiac pathology among athletes because myocarditis is an important cause of sudden cardiac death during exercise.Prior to relaxation of stay-at-home orders in the US, the American College of Cardiology's Sports and Exercise Cardiology Section endorsed empirical consensus recommendations advising a conservative return-to-play approach, including cardiac risk stratification, for athletes in competitive sports who have recovered from COVID-19. Emerging observational data coupled with widely publicized reports of athletes in competitive sports with reported COVID-19-associated cardiac pathology suggest that myocardial injury may occur in cases of COVID-19 that are asymptomatic and of mild severity. In the absence of definitive data, there is ongoing uncertainty about the optimal approach to cardiovascular risk stratification of athletes in competitive sports following COVID-19 infection.This report was designed to address the most common questions regarding COVID-19 and cardiac pathology in athletes in competitive sports, including the extension of return-to-play considerations to discrete populations of athletes not addressed in prior recommendations. Multicenter registry data documenting cardiovascular outcomes among athletes in competitive sports who have recovered from COVID-19 are currently being collected to determine the prevalence, severity, and clinical relevance of COVID-19-associated cardiac pathology and efficacy of targeted cardiovascular risk stratification. While we await these critical data, early experiences in the clinical oversight of athletes following COVID-19 infection provide an opportunity to address key areas of uncertainty relevant to cardiology and sports medicine practitioners.
TCT CONNECT-406 Effect of a Prescriptive Optical Coherence Tomography-Guided Strategy on Treatment of In-Stent Restenosis: Insights from the LightLab Initiative
Authors: Kevin Croce, Mordechai Golomb, Jana Buccola, Richard Rapoza, Nick West, John Lopez, Jason Wollmuth, Brian Bergmark
Journal: Journal of the American College of Cardiology (2020)
Assessment of Rates of Suicide Risk Screening and Prevalence of Positive Screening Results Among US Veterans After Implementation of the Veterans Affairs Suicide Risk Identification Strategy
Authors: Nazanin Bahraini, Lisa A. Brenner, Catherine Barry, Trisha Hostetter, Janelle Keusch, Edward P. Post, Chad Kessler, Cliff Smith, Bridget B. Matarazzo
Journal: JAMA Network Open (2020)

<h3>Importance</h3> In 2018, the Veterans Health Administration (VHA) implemented the Veterans Affairs (VA) Suicide Risk Identification Strategy to improve the identification and management of suicide risk among veterans receiving VHA care. <h3>Objectives</h3> To examine the prevalence of positive suicide screening results among veterans in ambulatory care and emergency departments (EDs) or urgent care clinics (UCCs) and to compare acuity of suicide risk among patients screened in these settings. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the VA's Corporate Data Warehouse (CDW) to assess veterans with at least 1 ambulatory care visit (n = 4 101 685) or ED or UCC visit (n = 1 044 056) at 140 VHA medical centers from October 1, 2018, through September 30, 2019. <h3>Exposures</h3> Standardized suicide risk screening and evaluation tools. <h3>Main Outcomes and Measures</h3> One-year rate of suicide risk screening and evaluation, prevalence of positive primary and secondary suicide risk screening results, and levels of acute and chronic risk based on the VHA's Comprehensive Suicide Risk Evaluation. <h3>Results</h3> A total of 4 101 685 veterans in ambulatory care settings (mean [SD] age, 62.3 [16.4] years; 3 771 379 [91.9%] male; 2 996 974 [73.1%] White) and 1 044 056 veterans in ED or UCC settings (mean [SD] age, 59.2 [16.2] years; 932 319 [89.3%] male; 688 559 [66.0%] White) received the primary suicide screening. The prevalence of positive suicide screening results was 3.5% for primary screening and 0.4% for secondary screening in ambulatory care and 3.6% for primary screening and 2.1% in secondary screening for ED and UCC settings. Compared with veterans screened in ambulatory care, those screened in the ED or UCC were more likely to endorse suicidal ideation with intent (odds ratio [OR], 4.55; 95% CI, 4.37-4.74;<i>P</i> &lt; .001), specific plan (OR, 3.16; 95% CI, 3.04-3.29;<i>P</i> &lt; .001), and recent suicidal behavior (OR, 1.95; 95% CI, 1.87-2.03;<i>P</i> &lt; .001) during secondary screening. Among the patients who received a Comprehensive Suicide Risk Evaluation, those in ED or UCC settings were more likely than those in ambulatory care settings to be at high acute risk (34.1% vs 8.5%;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this cross-sectional study, population-based suicide risk screening and evaluation in VHA ambulatory care and ED or UCC settings may help identify risk among patients who may not be receiving mental health treatment. Higher acuity of risk among veterans in ED or UCC settings compared with those in ambulatory care settings highlights the importance of scaling up implementation of brief evidence-based interventions in the ED or UCC to reduce suicidal behavior.
TCT CONNECT-241 Rates of Periprocedural Complications in Patients With Percutaneous Coronary Intervention of Chronic Total Occlusions and Impact on Mortality
Authors: Niya Mileva, Dobrin Vassilev, Pavel Nikolov, Georgi Dimitrov, Kiril Karamfiloff, Carlos Collet
Journal: Journal of the American College of Cardiology (2020)
Clinical and Angiographic Features of Patients With Out-of-Hospital Cardiac Arrest and Acute Myocardial Infarction
Authors: Shumpei Kosugi, Kazuya Shinouchi, Yasunori Ueda, Haruhiko Abe, Taku Sogabe, Kenichiro Ishida, Tsuyoshi Mishima, Tatsuhisa Ozaki, Kohtaro Takayasu, Yoshinori Iida, Takuya Ohashi, Chieko Toriyama, Masayuki Nakamura, Yasuhiro Ueda, Shun Sasaki, Mikiko Matsumura, Takashi Iehara, Motoo Date, Mitsuo Ohnishi, Masaaki Uematsu, Yukihiro Koretsune
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-300 Rates and Impact of Stroke After Revascularization for Left Main Coronary Artery Disease: The EXCEL Trial
Authors: Mahesh Madhavan, Bjorn Redfors, Bahira Shahim, Mitchell Elkind, Ditian Li, Aaron Crowley, Nicholas Lembo, William Brown, Bela Merkely, Jose Luis Pomar, Manel Sabate, Roxana Mehran, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-15 Risk Stratification Guided by the Index of Microcirculatory Resistance and Left Ventricular End-Diastolic Pressure During Primary Percutaneous Coronary Intervention
Authors: Annette Maznyczka, Peter McCartney, Keith Oldroyd, John Greenwood, James Cotton, Robin Weir, Alex McConnachie, Colin Berry
Journal: Journal of the American College of Cardiology (2020)