tbuckley/cabot-search huggingface dataset:
Drug Candidates for Covid-19 Treatment in Brazil
Authors: Luciano Silva
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Background: COVID-19 has emerged worldwide in less than 6 months, leaving millions of deaths behind. While scientist search for new drugs, an old arsenal has been proposed as a form of treatment. Objective: This article was designed as a literature review, scrutinizing antiparasitic chloroquine, ivermectin, nitazoxanide; and also glucocorticoids, as candidates to be applied in patients with COVID-19 in some Brazilian hospitals. Methodology: clinical evidence of COVID-infected patients and literature consultation have been accomplished for the construction of this article. On line searches and gray literature have also been consulted, whose database include PUBMED Central, BVS/BIREME, Web of Science, Science Direct, Higher Level Personnel Improvement Coordinator (CAPES), Periodic Door (Portal de Periódicos da CAPES, The Cochrane Library and PROSPERO). Results: chloroquine, ivermectin and nitazoxanide do present antiviral characteristics to support their usage in phase 1 of COVID-19 symptoms. Glucocorticoids, especially methylprednisolone and dexamethasone, seem to be efficient in patients with pulmonary symptoms, such as those present in phase 2B and 3 of the disease. Conclusion: After analyzing the literature, antiparasitic agents constitute a promising approach for patients with COVID-19. However, their usage seems to be efficient in the very beginning of the symptoms. Methylprednisolone and dexamethasone are best indicated for hospitalized patients with pulmonary commitment.
Abstract 11329: Prospective Analysis of Vascular Resistance in Patients with Persistent Tachycardia and or Dyspnea on Exertion in the Post Acute Sequela of Covid-19 Syndrome
Authors: david landers, Sameer Jamal, Zoltan Turi, Marian Vandyck-Acquah, Steven Hollenberg, Taya GLotzer, Brent Klinkhammer, Jana Tancredi, Joseph E Parrillo
Journal: Circulation (2021)

Introduction: The cause of tachycardia and dyspnea on exertion (DOE) in the Post Acute Sequelae CoV-2 syndrome (PASC) has yet to be identified. While endothelial invasion of the virus is well documented, how that might explain PASC is unknown. Hypothesis: Covid induced changes in vascular signaling to autonomic regulatory centers can induce sinus tachycardia and DOE. Methods: In a prospective, observational study, we enrolled 18 PASC patients who reported DOE or inappropriate tachycardia. All patients had normal left ventricular function, CXR, Hgb and thyroid studies. None had preexisting autonomic dysfunction. Vascular resistance was assessed by echocardiographic measurement of aortic-vascular impedance (Zva)=(systolic BP + mean Ao valve gradient)/stroke volume index. Ambulatory heart rate monitoring and head-up tilt table testing (HUTT) were performed. Results: Consecutively enrolled patients (18) were studied (17 females, ages 27 to 64). None had a significant aortic valve gradient. Zva was elevated in 17 of 18 patients. Ambulatory monitoring revealed episodes of symptomatic sinus tachycardia. Higher average daily heart rates correlated significantly with higher Zva levels (fig1). The 14 patients with DOE trended to higher average Zva levels than the 4 patients without dyspnea (4.13 +- 0.85 vs 3.5 +- 0.24, P=0.14). Of the 17 patients who had HUTT, 16 demonstrated patterns of orthostatic intolerance consistent with excess sympathetic tone including both postural orthostatic tachycardia and neurogenic cardiac syncope. Conclusions: PASC associated sinus tachycardia and HUTT abnormalities result from excess sympathetic tone. Covid-19 vascular injury as evidenced by abnormal Zva values may result in abnormal vascular signaling to autonomic regulatory centers. Resultant increases in sympathetic output may produce inappropriate sinus tachycardia, vasomotor dysregulation and DOE via peripheral vasoconstriction.
Abstract 14081: Predictors of Left Atrial Ejection Fraction in Patients With Nonischemic Cardiomyopathy
Authors: Donna Salam, Tom K Wang, Nicholas Chan, Mustafa Turkmani, Wai Hong W Tang, Brian P Griffin, Scott D Flamm, Deborah H Kwon
Journal: Circulation (2021)

Background: The impact of cardiomyopathy on left atrial function is currently unclear. The aim of this study was to assess the predictors of left atrial function in patients with non-ischemic dilated cardiomyopathy (NICM) utilizing cardiovascular magnetic resonance (CMR) assessment. Methods: We evaluated 251 NICM patients who underwent CMR in our study, between 12/2008 - 1/2014. LA volumes were measured by the modified biplane method from 2- and 4-chamber long axis views at end-systole and end-diastole. Left atrial ejection fraction (LAEF) was calculated. Multivariable linear regression was performed to determine significant covariate associations with LA EF. Results: We studied 251consecutive patients (61 % male), mean age of 52.5 ± 15.5 years . The results of the multivariable linear regression are provided in Figure 1. Younger age, female sex, and less myocardial fibrosis were significantly associated with higher LAEF (p=0.008, p= 0.004, and p= 0.031, respectively). Additionally, increasing left ventricular end diastolic volume index (LVEDVi) and left ventricular ejection fraction (LVEF) was significantly associated with increasing LAEF (both with a significance of p&lt;0.0001). Increased LA volume index (LAVi) was significantly associated with decreased LAEF (p&lt;0.0001). Of note, there was a trend towards less mitral regurgitation fraction being significantly associated with higher LA EF, but did not demonstrate a significant effect on the LAEF (p=0.083). Similarly, right ventricular size and function were not significantly associated with LA EF. Conclusions: In patients with NICM, age, sex, LVEDVi, LVEF, myocardial fibrosis, and LAVi were independently associated with LAEF. Keywords: Nonischemic cardiomyopathy, left atrial ejection fraction, left atrial function, cardiovascular magnetic resonance
Efficacy and Safety of Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients with Cancer and Central Venous Catheter: A Systematic Review and Meta-Analysis
Authors: Allen Li, Willem Brandt, Cameron Brown, Tzu-Fei Wang, Rick Ikesaka, Aurelien Delluc, Philip S. Wells, Marc Carrier
Journal: Blood (2021)
Use of Mixture Dosing and Nonlinear Mixed Effect Modeling of Eight Environmental Contaminants in Rabbits to Improve Extrapolation Value of Toxicokinetic Data
Authors: Véronique Gayrard, Jessika Moreau, Nicole Picard-Hagen, Virginie Helies, Philippe Marchand, Jean-Philippe Antignac, Pierre-Louis Toutain, Roger Leandri
Journal: Environmental Health Perspectives (2021)

Background: Although in vivo studies of internal exposure to hazardous substances have been carried out for many years, there is room for progress to improve their informative value while adhering to the four R's: replacement, reduction, refinement, and responsibility rule. Objectives: The objective of the study was to illustrate how toxicokinetic (TK) study design and data analysis can be implemented under the 4R rule to plan a chronic dosage regimen for investigating TK/toxicodynamic (TD) relationships. Methods: The intravenous (IV) and oral serum concentrations of eight hazardous environmental contaminants including 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (pp′DDE), ß-Hexachlorocyclohexane (β-HCH), hexachlorobenzene (HCB), 2,2′4,4′-tetrabromodiphenyl ether (BDE-47), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di(2ethylhexyl)phthalate (DEHP), and bisphenol S (BPS) were obtained after mixture dosing in rabbits using a sparse sampling design. Data were comprehensively analyzed using nonlinear mixed effect (NLME) modeling. Results: The short persistence of BPS and of the DEHP metabolite (mono-2-ethylhexyl phthalate), reflected by their mean residence times (MRT) of a few hours, was due to their efficient clearance (CL, 3.2 and 0.47L/kg/h). The longer MRT of the other compounds (1–48 d) resulted either from their extremely low clearance (lower than 0.01L/kg/h for PFOA and PFOS) or from their very large volume of distribution (VSS) ranging from 33 to 45L/kg. Estimates of CL, VSS, and bioavailability were used to compute the oral loading and daily maintenance doses required to attain a nominal steady-state serum concentration of 1 ng/mL. Simulations with the NLME model were applied to predict the serum concentration profile and to contrast the differential rates of accumulation in the central vs. peripheral compartments. Conclusion: NLME modeling of the IV and oral TK of hazardous environmental contaminants, in rabbits while fulfilling the 4R rule, was able to provide the physiological basis for interspecies extrapolation of exposure rates in a TK/TD approach to risk assessment. https://doi.org/10.1289/EHP8957
<i>Pklr</i> Is a Genetic Modifier of Sickle Cell Disease
Authors: Xunde Wang, Mickias Tegegn, Fayaz Seifuddin, Stephan Menzel, Hamel Patel, Yi-Ping Fu, Neal Jeffries, Mehdi Pirooznia, Kate Gardner, Swee Lay Thein
Journal: Blood (2021)
Bob.1 Blocks a SYK Protein Degradation Pathway in Mice That Develop Chronic Graft Versus Host Disease Manifestations
Authors: Wei Jia, Jonathan C Poe, Hsuan Su, Rachel A. DiCioccio, Sonali Bracken, Jonathan Visentin, Lauren S. Riley, Serach C. Patterson, Benny J. Chen, Nelson J. Chao, Stefanie Sarantopoulos
Journal: Blood (2021)
Role of SMURF1 amplification in pancreatic oncogenesis
Authors: Kevin Kwei, Murali Bashyam, Anirban Maitra, Matt van de Rijn, Kelli Montgomery, Jonathan Pollack
Journal: Cancer Research (2007)

4435  Pancreatic cancer accounts for more than 30,000 deaths per year, making it the fourth leading cause of cancer death in the United States. A better understanding of the genetic and molecular basis of pancreatic cancer is needed in order to develop novel and effective diagnostic and therapeutic targets against this disease. Previously, we used array-based Comparative Genomic Hybridization (aCGH) to identify novel regions of DNA amplification in a panel of pancreatic cancer cell lines. The current study is focused on SMURF1, a candidate oncogene found within a highly-localized amplicon at chromosomal region 7q21. SMURF1 is an E3 ubiqutin ligase which has been characterized to inhibit TGF-beta signaling and to promote cell motility, but its role in pancreatic carcinogenesis remains unexplored. We now show that pancreatic cancer cell lines with SMURF1 amplification exhibit elevated SMURF1 mRNA and protein levels. By fluorescence in situ hybridization (FISH) and immunohistochemistry on paraffin sections, we also find that SMURF1 is amplified and/or overexpressed in a subset of primary pancreatic adenocarcimomas. Finally, overexpression of SMURF1 in NIH-3T3 fibroblasts leads to cell transformation (increased focus formation). Our findings support a novel role of SMURF1 amplification in the pathogenesis of pancreatic cancer.
Phase II Study of Venetoclax in Combination with Obinutuzumab and Bendamustine in Patients with High Tumor Burden Follicular Lymphoma As Front Line Therapy (PrECOG 0403)
Authors: Craig A. Portell, Opeyemi Jegede, Nina D. Wagner-Johnston, Grzegorz S. Nowakowski, Christopher D. Fletcher, Jonathon B. Cohen, Kevin A. David, Nadia Khan, Lori J Rosenstein, Brad S. Kahl
Journal: Blood (2021)
High-Dimensional Analysis Identifies Mechanisms of Gilteritinib Resistance in <i>FLT3</i>-Mutated AML
Authors: Daelynn R Buelow, Bhavana Bhatnagar, Jae Yoon Jeon, Megan Zavorka Thomas, Eric Eisenmann, Jack Stromatt, Shelley Orwick, Navjot Pabla, James S. Blachly, Sharyn Baker, Bradley W Blaser
Journal: Blood (2021)
Interim Results of a Multicenter Pilot Study Evaluating Brentuximab Vedotin with Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP) for the Treatment of Aggressive Adult T-Cell Leukemia/Lymphoma
Authors: Christopher Dittus, Matthew J Weinstock, Jeffrey A Barnes, Jose Sandoval-Sus, Xianming Tan, Xinyi Zhang, Areej El-Jawahri, Shayna Sarosiek, John Mark Sloan
Journal: Blood (2021)
Effectiveness of Implantable Cardioverter-Defibrillators to Reduce Mortality in Patients With Long QT Syndrome
Authors: Meng Wang, Derick R. Peterson, Spencer Rosero, Scott McNitt, David Q. Rich, Christopher L. Seplaki, Bronislava Polonsky, Ilan Goldenberg, Wojciech Zareba
Journal: Journal of the American College of Cardiology (2021)

The effectiveness of implantable cardioverter-defibrillators (ICDs) on reducing mortality has not been well studied in patients with long QT syndrome (LQTS).
Identification of a Novel Epigenetic Mechanism of <i>MYC</i> Deregulation in Smoldering and Newly Diagnosed Multiple Myeloma Patients
Authors: Mahshid Rahmat, Kendell Clement, Romanos Sklavenitis-Pistofidis, Rohan Kodgule, Charles Fulco, Jean-Baptiste Alberge, Cody J. Boehner, Michael P. Agius, Elizabeth Morgan Kitzenberg, David Dorfman, Russell J. H. Ryan, Luca Pinello, Irene M. Ghobrial
Journal: Blood (2021)
ELN 2017 Classification Significantly Impacts on the Risk of Early Death in Acute Myeloid Leukemia Patients Receiving Intensive Induction Chemotherapy
Authors: Naama Keren Froim, Gabriel Heering, Gal Sharvit, Maya Zlotnick, Arnon Nagler, Avichai Shimoni, Abraham Avigdor, Jonathan Canaani
Journal: Blood (2021)
Abstract 9827: Impact of Standard Interventions for Dyslipidemia and Elevated Blood Pressure in Childhood Cancer Survivors
Authors: Karina Javalkar, Yisong Huang, Shannon Lyon, Hannah Palfrey, Jacob Hartz, Ming Hui Chen, Sarah D De Ferranti
Journal: Circulation (2021)

Introduction: Childhood cancer survivors (CCS) have an increased risk of premature cardiovascular disease (CVD). Whether they respond equally well to guideline-directed lifestyle and pharmacologic interventions for elevated BP, BMI, and dyslipidemia as those without history of childhood cancer is unknown. We hypothesized that CCS may have impaired response to these interventions when compared to controls. Methods: This retrospective case-control study included CCS and 3:1 age- and sex-matched controls treated in Boston Children’s Hospital Preventive Cardiology (2010-2019) using a quality improvement protocol based on NHLBI 2011 guidelines. Change in body mass index (BMI), blood pressure (BP), and lipids from baseline to follow-up were compared between groups using Mann-Whitney and regression analyses in SPSS. Results: We included 62 CCS and 186 controls. Both groups had a median age of 16 years and were 63% female. Among CCS, 46% received anthracycline and 71% received radiation. CCS and controls did not significantly differ in BP or BMI, total cholesterol, or LDL-C at baseline. CCS had higher fasting triglycerides (p&lt;0.001) and lower HDL-C (p&lt;0.001) than controls at baseline. Median follow-up time was 18 weeks. CCS had greater improvement in fasting triglycerides than controls (median -50 mg/dL vs. -0 mg/dL, p=0.003), even after adjusting for BMI (p=0.016). Change in BMI, LDL-C, and HDL-C did not significantly differ between groups. Approximately 35% of CCS had elevated BP at both baseline and follow-up, while elevated BP among controls decreased from 55% to 40% (p=0.036) (Figure 1). Conclusions: CCS demonstrated greater improvement in triglycerides compared to controls in response to standard interventions, but similar change in regard to other lipid parameters and BMI. In contrast, BP was less likely to improve in CCS compared to controls. Further study is needed to determine if more aggressive interventions are needed for CCS with elevated BP.
Impact of tumor mutational burden on checkpoint inhibitor drug eligibility and outcomes across racial groups
Authors: David Hsiehchen, Magdalena Espinoza, Cristina Valero, Chul Ahn, Luc G T Morris
Journal: Journal for ImmunoTherapy of Cancer (2021)

The FDA approval of immune checkpoint inhibitors for cancers with tumor mutation burden (TMB) of at least 10 mut/Mb is postulated to reduce healthcare disparities by broadly expanding treatment eligibility. In a cohort of 39,400 patients with available genomic and race data, black and Asian patients were less likely to have TMB-high cancers in multiple types of malignancies based on the currently approved cut-off. Decreasing TMB thresholds preferentially increased the eligibility of minority patients for immune checkpoint inhibitors while retaining predictive value of treatment benefit in a cohort of immune checkpoint inhibitor treated patients. This study highlights differing distributions of TMB-high cancers between racial groups and provides guidance in developing more rational eligibility criteria for immune checkpoint inhibitors.
Dermatology is finally talking about race
Authors: J. Guckian, J.R. Ingram, N. Rajan, E. Linos
Journal: British Journal of Dermatology (2021)

a n, N. a n d Lino s, E. 2 0 2 1. D e r m a t olo gy is fin ally t alki n g a b o u t r a c e .Britis h Jou r n al of D e r m a t olo gy 1 8 5 (5) , p p. 8 7 5-8 7 6. 1 0.
Investing in public health is our best route to sustainable healthcare
Authors: Fiona Godlee
Journal: BMJ (2021)

Has it all been worth it: the handwashing, the mask wearing, the standing 2 m apart? The available evidence suggests it has. A systematic review published this week finds that these measures have reduced transmission of SARS-CoV-2 and deaths from covid-19 (doi:10.1136/BMJ-2021-068302).1

The conclusions are encouraging, but the paucity of good evidence for public health interventions during the pandemic is not. Among 35 studies good enough to evaluate, only one was a randomised trial, and it was too small (doi:10.1136/bmj.n2729).2 The others were all observational studies, including natural experiments, and the effects are likely to result from “bundles” of protective behaviours rather …
Safety and Efficacy of Mitapivat (AG-348), an Oral Activator of Pyruvate Kinase R, in Subjects with Sickle Cell Disease: A Phase 2, Open-Label Study (ESTIMATE)
Authors: Myrthe J. van Dijk, Minke A.E. Rab, Anita W. Rijneveld, Erfan Nur, Marije Bartels, Judith J.M. Jans, Wouter W. van Solinge, Roger E.G. Schutgens, Richard van Wijk, Eduard J. Van Beers
Journal: Blood (2021)
Chronic Graft-Versus-Host Disease Immunoprofiling Reveals T Cell Clonal Dynamics That Correlate with Disease Activity: A Novel Molecular "Biomarker"?
Authors: Anna Vardi, Elisavet Vlachonikola, Dimitra Gkouvelou, Evdoxia Koravou, Electra Sofou, Sofia Gkagkaridou, Maria Karipidou, Panagiota Zerva, Christos Demosthenous, Asimina Fylaktou, Ioannis Batsis, Apostolia Papalexandri, Anastasia Papadopoulou, Evangelia Yannaki, Ioanna Sakellari, Kostas Stamatopoulos, Achilles Anagnostopoulos, Anastasia Chatzidimitriou
Journal: Blood (2021)
The Impact of Trial Eligibility Criteria on Outcomes in a Nationwide Cohort of Newly Diagnosed DLBCL Patients Treated with R-CHOP
Authors: Freja Tang Severinsen, Laura Mors Haunstrup, Rasmus Kuhr Jensen, Matthew J. Maurer, Arushi Khurana, Paw Jensen, Judit M. Jørgensen, Thomas Stauffer Larsen, Michael Roost Clausen, Christian Bjørn Poulsen, Peter de Nully Brown, Tarec Christoffer El-Galaly, Lasse H. Jakobsen
Journal: Blood (2021)
New Opioid Use and Risk of Emergency Department Visits Related to Motor Vehicle Collisions in Ontario, Canada
Authors: Qi Guan, Daniel McCormack, David N. Juurlink, Susan E. Bronskill, Hannah Wunsch, Tara Gomes
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Opioids can impair motor skills and may affect the ability to drive; however, the association of opioid use with driving ability is not well established. <h3>Objective</h3> To examine the risk of motor vehicle collisions (MVCs) among drivers starting opioid therapy compared with that among drivers starting nonsteroidal anti-inflammatory drug (NSAID) therapy. <h3>Design, Setting, and Participants</h3> This population-based, retrospective cohort study included all residents of Ontario aged 17 years or older who started new prescription analgesic therapy between March 1, 2008, and March 17, 2019. <h3>Exposures</h3> Initiation of opioid therapy or NSAID therapy, ascertained through prescription dispensing records in administrative data. <h3>Main Outcomes and Measures</h3> The primary outcome was an emergency department visit for injuries sustained as a driver in an MVC during the 14 days after starting analgesic therapy. Inverse probability treatment weighting was used to balance baseline covariates, and weighted Cox proportional hazards regression models were used to assess the association between new analgesic therapy and hazard of an emergency department visit after an MVC. <h3>Results</h3> Of the 1 454 824 individuals included in the study, 765 464 (52.6%) were new opioid recipients and 689 360 (47.4%) were new NSAID recipients. Most participants were aged 65 years or older (75.2%), and 55.2% were women. Of 194 individuals who had emergency department visits for injuries from an MVC within 14 days of initiating therapy, 98 (50.5%) were opioid recipients (3.41 per 1000 person-years; 95% CI, 2.80-4.15 per 1000 person-years) and 96 (49.5%) were NSAID recipients (3.64 per 1000 person-years; 95% CI, 2.98-4.45 per 1000 person-years). There was no significant difference in the risk of an emergency department visit for MVC injuries between opioid and NSAID recipients (weighted hazard ratio, 0.94; 95% CI, 0.70-1.25). <h3>Conclusions and Relevance</h3> The findings of this study suggest that the hazard of an emergency department visit for injuries relating to an MVC as a driver is similar between individuals starting prescription opioids and those starting prescription NSAIDs. These results may be useful for patients, clinicians, and caregivers when considering new analgesic therapy.
Validation of Amphiregulin As a Monitoring Biomarker during Treatment of Life-Threatening Acute Gvhd: A Secondary Analysis of 2 Prospective Clinical Trials
Authors: Michael A. Pratta, Najla H El Jurdi, Armin Rashidi, Brian C. Betts, John P Galvin, Margaret L. MacMillan, Daniel J. Weisdorf, Angela Panoskaltsis-Mortari, Shernan G Holtan
Journal: Blood (2021)
Targeted Next Generation Sequencing Reveals a Third Breakpoint Cluster Region and New Partner Genes in the <i>KMT2A</i> Recombinome
Authors: Claus Meyer, Patrizia Larghero, Bruno Lopes, Aurélie Caye-Eude, Hélène Cavé, Marius Külp, Matthew James Smith, Rosemary Sutton, Nicola Venn, Karin Nebral, Susanne Kubetzko, Beat Schaefer, Grazia Fazio, Giovanni Cazzaniga, Mariana Emerenciano, Rolf Marschalek
Journal: Blood (2021)
Prediction of Malignant Cell Infiltration Patterns with Texture Features of Biopsy-Correlated Positron Emission Tomography of Osteolytic Lesions in Multiple Myeloma
Authors: Michael Laurence Langsen, Jerry Thwin Wong, Maximilian Merz, Brian Yu, Hemn Mohammadpour, Philip L. McCarthy, Jens Hillengass
Journal: Blood (2021)