tbuckley/cabot-search huggingface dataset:
Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsis
Authors: Jia-feng Wang, Yun-peng Wang, Jian Xie, Zhen-zhen Zhao, Sahil Gupta, Yu Guo, Song-hui Jia, Jean Parodo, John C. Marshall, Xiao-ming Deng
Journal: Blood (2021)
Abstract MP50: Neighborhood Social And Economic Environment And Heart Failure Risk Among Adults With &amp; Without Diabetes: The Reasons For Geographic And Racial Differences In Stroke (regards) Study
Authors: Gargya Malla, Andrea Cherrington, Monika M Safford, Parag Goyal, Doyle M Cummings, Tara McAlexander, Shanika De Silva, Suzanne E Judd, Bertha Hidalgo, Emily B Levitan, April P Carson
Journal: Circulation (2021)

Background: Heart failure (HF) mortality rates have been increasing since 2011. Individual-level education and occupation have been inversely associated with HF mortality among those with diabetes mellitus (DM) but not among those without DM. However, less is known about the association between neighborhood social and economic environment (NSEE) and HF risk and whether this association varies by DM status. Methods: This study included 21,244 Black and White adults age &gt;=45 years at baseline (2003-07) from the REGARDS Study. NSEE quartiles were created using z-scores based on 6 census tract variables from year 2000 (% &lt;high school education, % unemployed, % household with &lt;$30,000, % living in poverty, % on public assistance, % without car). Incident HF events (fatal or non-fatal) were adjudicated based on hospitalization with HF signs and symptoms, supportive imaging or biomarkers. Diabetes was defined as fasting glucose &gt;=126 mg/dL or random glucose &gt;=200 mg/dL or use of diabetes medications. Cox proportional hazards regression was used to obtain hazard ratios (95% CI) with HF follow-up through 2016. Results: Mean age was 65 years, 54% were women, 61% were White and 18% had prevalent DM at baseline. During a median 10.1 years, 829 incident HF events occurred. Among adults with DM, neighborhood disadvantage was associated with an increased HF risk , but this association was not statistically significant (Table). Among adults without DM, the risk of HF was higher for participants living in any neighborhood that was not the most advantaged, and the magnitude of association was smiliar across NSEE quartiles. Conclusion: Adults living in disadvantaged neighborhoods had a higher risk of HF, particularly among those without DM. Addressing neighborhood social and economic conditions may be important for HF prevention.
Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci
Authors: Stephanie Sungalee, Yuanlong Liu, Ruxandra A. Lambuta, Natalya Katanayeva, Maria Donaldson Collier, Daniele Tavernari, Sandrine Roulland, Giovanni Ciriello, Elisa Oricchio
Journal: Nature Genetics (2021)
Abstract 15347: Impact of Covid-19 Pandemia on Provision of Surgical Treatment for Patients With Cardiovascular Disease
Authors: Mauro Iafrancesco, Piero Farina, Piergiorgio Bruno, Natalia Pavone, Andrea Mazza, Federico Cammertoni, Marialisa Nesta, Giovanni Alfonso Chiariello, Maria Grandinetti, Gianluca Comerci, Annalisa Pasquini, Laura Manfredonia, Claudio Spalletta, Massimo Massetti
Journal: Circulation (2020)

Introduction: COVID-19 pandemia determined a reduction of healthcare offer to the general population. Hypothesis: COVID-19 pandemia increased the number of emergency operations and in particular of life-saving procedures because of the diagnostic delay due to missed follow-up or unwillingness to present to Emergency Departments for the fear of contracting the coronavirus. Methods: Retrospective analysis of surgical activity in a large Cardiac Surgery Department from 01 March to 31 May 2020 (study period) compared to the same months of 2019 (control period). Results: During the study period there were 191 operations (14% elective and 86% urgent/emergency) versus 225 (44% elective and 56% urgent/emergency) in the control period. Moreover, during the study period four patients presented acutely due to delay of diagnosis: one with ventricular septal defect and free wall rupture due to an evolving acute myocardial infarction (MI) with late presentation; another, who suffered an acute inferior MI several months earlier and did not attend regular follow-up, was operated for a ruptured pseudoaneurysm who was not previously diagnosed; another was operated for aortic and mitral valve endocarditis complicated by cardiogenic shock due to delay caused by a misdiagnosed COVID-19 pneumonia; last patient, previously operated for an acute type A aortic dissection (ATAAD), refused to attend the Emergency Department after the acute onset of back pain and was later diagnosed with severe dilatation (1.4 cm over 6 months) of the thoracic aorta and underwent endovascular stent-grafting. The first patient (who suffered a cardiac arrest after induction of anesthesia) survived with neurological deficit, the second died in the operating room, the third and fourth survived without complications. There were no similar cases in the control period. Finally, two patients were operated for an ATAAD (one COVID-19 positive died of hemorrhagic shock) in the study period versus nine in the control period. Conclusions: COVID-19 pandemia resulted in a significant reduction of cardiac surgical activity, mainly related to decrease of elective surgery and an increased number of surgical procedures for life-threatening conditions caused by delayed presentation of acute patients.
Correction: Endoscopic direct visualization of gallbladder polypoid lesion using peroral digital single-operator cholangioscopy
Authors: Hideki Kamada, Hideki Kobara, Hiroki Yamana, Keiichi Okano, Yasuyuki Suzuki, Naoki Fujita, Tsutomu Masaki
Journal: Endoscopy (2021)

Correction to: Endoscopic direct visualization of gallbladder polypoid lesion using peroral digital single-operator cholangioscopyEndoscopy 2021; 53(07): E263-E264DOI: 10.1055/a-1252-2704
Abstract 17492: Chronic Treatment With a Mavacamten-Like Myosin-Modulator (MYK-581) Prevents Left-Atrial Remodeling, Decreases Cardiac Troponin Leakage, and Blunts Mortality in a Mini-Pig Model of Inherited Hypertrophic Cardiomyopathy
Authors: Kaylyn M Bell, David M Ryba, Trisha Smit, Frank Rohret, Daniel Chin, Emily Hollenbeck, Sheerin Shahidi-Latham, Marcus Henze, Carlos L del Rio
Journal: Circulation (2020)

Introduction: Hypertrophic cardiomyopathy (HCM) is a progressive disease characterized by cardiac remodeling, impaired relaxation, left-atrial enlargement, and exertional intolerance. Direct myosin-inhibition with mavacamten can normalize contractility and improve exercise capacity in patients with obstructive HCM (oHCM). However, mavacamten also limits residual cross-bridges during diastole, and therefore, may offer cardiac benefits beyond obstruction relief. This in vivo study evaluated the chronic effects of MYK-581, a mavacamten surrogate, in a genetic large-animal model of HCM. Methods: Young cloned Yucatan mini-pigs with a heterozygous MYH7 R403Q mutation were randomly assigned to one of two arms: untreated-controls (CTRL, n = 29) or daily MYK-581 (n = 22; PO); wild-type pigs (WT) untreated served as disease-controls. After 14 weeks of treatment, pigs underwent in vivo cMR imaging, including T1 mapping and extracellular volume (ECV) assessments. In a subset of pigs, biomechanical studies were performed in skinned left-ventricular (LV) and left-atrial (LV) fibers. *, #: P&lt;0.05 vs. CTRL or WT. Results: In HCM pigs, MYK-581 treatment decreased mortality (9.0* vs. 37.9% in CTRL). MYK-581 blunted cTnT leakage, reducing both absolute values (21.2 ± 3.2* vs. 34.0 ± 4.3 ng/L in CTRL) and the incidence of cTnT &gt; 20 ng/L (36* vs. 81% in CTRL). Treated pigs had smaller LA volumes (16 ± 1* vs. 29 ± 4mL in CTRL) with lower LV T1-times and ECV (27 ± 1* vs. 32 ± 2% in CTRL). LA fibers from untreated HCM pigs showed biomechanical remodeling characteristic of chronic overload: increased maximal force (21.8 ± 1.5# vs. 14.7 ± 1.4 mN/mm2 in WT) and slowed cross-bridge formation rates (Ktr: 4.9 ± 0.4 # vs. 6.6 ± 0.6 s-1 in WT) consistent with a switch towards slow-myosin isoforms. MYK-581 prevented this remodeling (e.g., Ktr: 8.1 ± 1.3 s-1*), preserving normal LA (fast) myosin content. Conclusions: Chronic direct myosin attenuation with a mavacamten surrogate prevented left-atrial remodeling, a known prognostic indicator in HCM. Chronic treatment also reduced cardiac troponin leakage characteristic HCM, and, more importantly, decreased mortality. Taken together, these pre-clinical observations show potential salutary effects beyond obstruction relief in HCM.
Targeting syk kinase for the treatment of B-cell lymphoma
Authors: J. P. Sharman, J. Irish, G. Coffey, D. Czerwinski, Y. Hitoshi, R. Levy
Journal: Journal of Clinical Oncology (2007)

3600 Background: B-Cells require constitutive signaling from the B-Cell Receptor (BCR). Elimination of the BCR induces cell death. Since the BCR lacks enzymatic activity and relies upon the non-receptor tyrosine kinase Syk to initiate a signal transduction cascade, we hypothesized that R406; a small molecule Syk kinase inhibitor might eliminate the constitutive BCR signal and therefore have selective cytotoxicity for B-cells. Methods: Signal transduction changes were evaluated in cell lines and primary normal B-Cells via western blotting and phosphoflow cytometry. Effects on B-Cell, T-Cell, and Myeloid lineage cell lines were evaluated by 3H-thymidine proliferation assays, BRDU cell cycle analysis, and Annexin-V staining. Primary tumor samples were evaluated for B-Cell selective toxicity by evaluation of active caspase activity. Results: In cell culture R406 significantly alters the basal phosphorylation status of multiple proteins. Proliferation of B-Cell lines is reduced with an IC50 range of 625nM to 2.5uM without effect on T-Cell or Myeloid lineage cell lines. Cell cycle analysis reveals a reduction in B-Cell S-Phase with increase in G1/G0. Apoptosis is also increased in the B-cell lines without significant increase in the non-B cell lines. Primary normal B-Cells show reduced phosphorylation of BTK, Erk, and p38 in response to BCR cross linking. Primary tumor samples reveal activity against B-Cell neoplasms. In samples containing both malignant B-Cells and normal T-Cells, the induction of active caspase-3 is restricted to the malignant B-Cell population. Conclusions: 1) R406 alters signal transduction in B-Cells. 2) R406 demonstrates selective anti-B-Cell activity among cell lines. 3) Primary tumor samples reveal cytotoxic activity against malignant B-Cells without toxicity to T-Cells within the same specimen. 4) This compound has been safely tested in humans for non-malignant diseases with an appropriate pharmacokinetic profile; therefore these results support the initiation of an upcoming multicenter phase I/II clinical trial in patients with lymphoma. No significant financial relationships to disclose.
Abstract 16045: Buprenorphine and Methadone Treatment is Associated With Less Heart Failure Hospitalizations in Patients With Opioid Use Disorder
Authors: Maciej Tysarowski, Maryam Kazmi, Rakhee Barai, Ranye Efobi, Daniel Matassa, Emily Gordon
Journal: Circulation (2020)

Introduction: Patients with opioid use disorder (OUD) who receive medication for opioid use disorder (MOUD), either buprenorphine or methadone, have decreased all-cause and overdose mortality. Although in patients with congestive heart failure, OUD is associated with a greater number of heart failure hospitalizations (HFH), no studies were conducted on the outcomes of MOUD in this population. Hypothesis: We hypothesized that in patients with OUD and congestive heart failure, MOUD is associated with a decreased number of HFH. Methods: We retrospectively reviewed records of patients treated at the Rutgers NJMS Ambulatory Care Center, diagnosed with both heart failure and opioid use disorder between 2016 and 2018. We conducted multivariate linear regression to identify predictors of HFH. Results: Among 91 included patients, 60% were male, mean age was 58 ± 7 years old. The majority (75%) of patients were of African American ethnicity. Mean left ventricular ejection fraction (LVEF) was 41 ± 18%; 32% patients had preserved, 22% had mid-range and 46% had reduced LVEF. Over the 2-year period, 57% of patients were treated with buprenorphine, and 76% with methadone - a total of 87% of all patients were on MOUD. Less than half (37%) of the patients had medical insurance. Median number of HFH was 2.0 (IQR 0.0 - 8.5). In multivariate analysis ( table ), number of HFH correlated positively with the presence of insurance (β = 4.02 [95% CI 1.06 to 6.98], p = 0.008) and number of missed appointments (β = 0.33 [95% CI 0.11 to 0.55], p = 0.003), and negatively with MOUD (β = –5.41 [95% CI -9.52 to -1.31], p = 0.01). HFH were not associated with LVEF (p = 0.746), diastolic dysfunction (p = 0.855) or age and gender. Conclusions: In patients with OUD and congestive heart failure, MOUD is independently associated with less HFH and is one of its strongest predictors. Expanding access to methadone and buprenorphine appears to be critical in improving the quality of care of this vulnerable and underserved population.
Adherence at 2 years with distribution of essential medicines at no charge: The CLEAN Meds randomized clinical trial
Authors: Nav Persaud, Michael Bedard, Andrew Boozary, Richard H. Glazier, Tara Gomes, Stephen W. Hwang, Peter Juni, Michael R. Law, Muhammad Mamdani, Braden Manns, Danielle Martin, Steven G. Morgan, Paul Oh, Andrew D. Pinto, Baiju R. Shah, Frank Sullivan, Norman Umali, Kevin E. Thorpe, Karen Tu, Andreas Laupacis
Journal: PLoS Medicine (2021)

Background Adherence to medicines is low for a variety of reasons, including the cost borne by patients. Some jurisdictions publicly fund medicines for the general population, but many jurisdictions do not, and such policies are contentious. To our knowledge, no trials studying free access to a wide range of medicines have been conducted. Methods and findings We randomly assigned 786 primary care patients who reported not taking medicines due to cost between June 1, 2016 and April 28, 2017 to either free distribution of essential medicines ( n = 395) or to usual medicine access ( n = 391). The trial was conducted in Ontario, Canada, where hospital care and physician services are publicly funded for the general population but medicines are not. The trial population was mostly female (56%), younger than 65 years (83%), white (66%), and had a low income from wages as the primary source (56%). The primary outcome was medicine adherence after 2 years. Secondary outcomes included control of diabetes, blood pressure, and low-density lipoprotein (LDL) cholesterol in patients taking relevant treatments and healthcare costs over 2 years. Adherence to all appropriate prescribed medicines was 38.7% in the free distribution group and 28.6% in the usual access group after 2 years (absolute difference 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). There were no statistically significant differences in control of diabetes (hemoglobin A1c 0.27; 95% CI −0.25 to 0.79, p = 0.302), systolic blood pressure (−3.9; 95% CI −9.9 to 2.2, p = 0.210), or LDL cholesterol (0.26; 95% CI −0.08 to 0.60, p = 0.130) based on available data. Total healthcare costs over 2 years were lower with free distribution (difference in median CAN$1,117; 95% CI CAN$445 to CAN$1,778, p = 0.006). In the free distribution group, 51 participants experienced a serious adverse event, while 68 participants in the usual access group experienced a serious adverse event ( p = 0.091). Participants were not blinded, and some outcomes depended on participant reports. Conclusions In this study, we observed that free distribution of essential medicines to patients with cost-related nonadherence substantially increased adherence, did not affect surrogate health outcomes, and reduced total healthcare costs over 2 years. Trial registration ClinicalTrials.gov NCT02744963 .
Abstract 16821: An ECG Derived Risk Score Predicts In-Hospital Death in Patients With COVID-19
Authors: Stephen McCullough, Parag Goyal, Udhay Krishnan, Adam Vohra, Jennifer Huang, Lisa Zhang, Justin Choi, Monika M Safford, Peter M Okin
Journal: Circulation (2020)

Introduction: COVID-19 is a respiratory syndrome with high rates of mortality, and findings from the ECG on hospital presentation have been shown to increase the odds of death. We thus hypothesized that findings from the presenting ECG could discriminate the risk of death in high risk subgroups, and sought to create an ECG risk score for death in COVID-19. Methods: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics were manually abstracted from the electronic health record; ECG data were digitally extracted from the first ECG in each patient, and Bazett-corrected QT interval and ST segment deviation at the M-point (STm, in μV) were quantified in all 12 leads. Our primary outcome was death. Results: 710 patients who presented to a large teaching hospital with COVID-19 underwent an ECG. The mean age was 63 ± 16 years, 37% were women, 62% of patients were non-white, and 56% had hypertension; 78 (11%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (OR=3.56, 95% CI 1.80-7.02, p&lt;0.001), a right bundle branch block or intraventricular block (OR=2.73, 95% CI 1.41-5.32, p=0.003), maximal STm in V5 or V6 (STmV5V6) ≤ -50 μV (OR=3.01, 95% CI 1.41-6.41, p=0.004), STmV2 &lt;0 μV (OR=3.41, 95% CI 1.88-6.18, p&lt;0.001), and QTc ≥480 ms (OR=2.84, 95% CI 1.52-5.29, p=0.001) predicted death. When each variable was assigned a point value of 1, in additive fashion an ECG score=1 or ≥2 similarly predicted death (OR=4.49, 95% CI 2.17-9.25, p&lt;0.001 and OR=11.23, 95% CI 5.27-23.93, p&lt;0.001, respectively), and discriminated risk within high risk age groups (&lt;60, 70-80, &gt;80, Figure ). Conclusions: A simple ECG risk score (including APCs, RBBB/IVB, STmV5V6 ≤ -50 μV, STmV2 &lt;0 μV, and QTc ≥480 ms) on initial hospitalization predicted in hospital death in COVID-19, and further discriminated risk of death in high risk age groups.
Abstract 81: Amplitude Spectrum Area Predicts the Success of Defibrillation on Rats During Cardiopulmonary Resuscitation
Authors: Xiaobo Wu, Yinlun Weng, Shijie Sun, Max H Weil, Wanchun Tang
Journal: Circulation (2010)

Amplitude spectrum area (AMSA) has been used for predicting the success of defibrillation during CPR. However, the efficacy of AMSA on predicting the success of defibrillation on small animals rema...
Abstract 13400: Patients Less Than or Equal to 2.5kg Have Higher Morbidity and Mortality After Norwood-sano Palliation
Authors: Konstantin Averin, Lindsay Ryerson, Morteza Hajihosseini, Irina A Dinu, Darren H Freed, Gwen Bond, Ari Joffe, viljee jonker, Charlene M Robertson, Joseph Atallah
Journal: Circulation (2020)

Introduction: In patients with single ventricle heart disease, prematurity and low weight at the Norwood operation are risk factors for mortality. Reports assessing peri-operative and long-term outcomes of Norwood palliation in patients ≤ 2.5kg are limited. Methods: All patients who underwent Norwood-Sano procedure between 2005-2020 were identified. Patients ≤ 2.5kg at the time of the Norwood operation (cases) were matched 1:3 with patients ≥ 3.0 kg (comparisons) for year of surgery and cardiac diagnosis. Demographic and peri-operative characteristics, survival to hospital discharge and 2-year neurodevelopmental outcomes were compared. Results: Twenty-seven cases (mean±SD weight 2.2±0.3 kg, mean age 15.6±14.1 days at surgery) and 81 comparisons (mean weight 3.5±0.4 kg, mean age 10.9±7.9 days at surgery) were identified. There was no statistically significant difference in the presence of chromosomal abnormalities (7.4% vs. 12.3%, p=0.485), prenatal diagnosis made (88.9% vs. 75.3%, p=0.141), or duration of cardiopulmonary bypass (140.7±65.6 vs. 121.3±42.3 min, p=0.068) between cases and comparisons, respectively. Cases had a longer time to post-operative lactate &lt; 2 mmol/L (33.1±27.5 vs. 17.9±12.2 hours, p&lt;0.001), longer duration of ventilation (30.5±24.5 vs. 18.6±17.5 days, p=0.005), higher need for dialysis (48.1% vs. 19.8%, p=0.007) and greater need for extracorporeal membrane oxygenation support (29.6% vs. 12.3%, p=0.004). Cases also had significantly higher in-hospital (25.9% vs. 1.2%, p&lt;0.001) and 2-year (59.2% vs. 11.1%, p&lt;0.001) mortality. The 2-year Bayley Scales of Infant and Toddler Development, III, was completed on all living cases (n=11) and most comparisons (n=63; 1 refusal and 8 too young); delay, a score of &lt; 70, showed the following differences between cases vs. comparisons for cognitive (86.9 vs. 91, p=0.363), language (84.9 vs. 88.2, p=0.494) and motor (73.6 vs. 87.3, p=0.013). Conclusions: Patients ≤ 2.5kg at the time of Norwood-Sano have significantly higher post-operative morbidity and mortality up to 2-year follow-up, and worse 2-year neurodevelopmental motor outcomes. Additional studies are warranted to assess the outcome of alternative therapeutic options in this patient population.
The Covid-19 Infodemic — Applying the Epidemiologic Model to Counter Misinformation
Authors: David Scales, Jack Gorman, Kathleen H. Jamieson
Journal: New England Journal of Medicine (2021)

The Covid-19 Infodemic Millions of people have been exposed to deceptive material about Covid-19. An approach to counteracting deceptions and misconceptions could parallel epidemiologic models by f...
Bacitracin inhibits glioma cell migration and invasion in vitro.
Authors: Dorota P. Goplen, Jian Wang, Berit B. Tysnes, A.J. Terzis, Rolf Bjerkvig, Ole D. Laerum
Journal: Cancer Research (2005)

3773  By serial transplantation of human glioblastoma biopsies in nude rats two different tumor phenotypes are obtained; one that is highly invasive and one that is predominantly angiogenic. Using a global proteomics approach on the phenotypes, we identified a number of unique proteins that were differentially expressed in the invasive phenotype. The proteins were identified by peptide mass fingerprinting and verified by Western blots and on immunostained biopsy specimens. Protein disulfide isomerase (PDI) A6 precursor was identified as one of the overexpressed proteins in the invasive phenotype. PDI is a chaperone protein, that mediates integrin dependent cell adhesion. It is present both in the cytosol and at the cell surface. Immunofluorescent staining of glioma spheroids in vitroshowed that migrating cells expressed PDI. Since cell migration is a part of the tumor invasion process and PDI more strongly expressed in the invasive glioma phenotype, we tested the effect of the PDI inhibitor bacitracin on migration of glioma cells in different invasion assays. Both tumor spheroids derived from human glioblastoma xenografts in the nude rat brain, as well as cell line spheroids were used. The human glioma cell lines (U373, U251, D54, GaMg, U87) expressed PDI. Bacitracin at concentrations as low as of 5 mM inhibited tumor cell migration and invasion. The anti-invasive effect of bacitracin was reversible after withdrawal of the inhibitor, indicating a specific, non-toxic effect. In conclusion, using a global proteomics approach, PDI was identified to play an important role in glioma cell invasion and its action was effectively inhibited by bacitracin.