tbuckley/cabot-search huggingface dataset:
Abstract 9818: Self-Care Self-Efficacy and Perception of Income Adequacy Influence Self-Care Among African Immigrants with Chronic Disease
Authors: Onome H Osokpo, Lisa M Lewis, Uchechukwu Ikeaba, Jesse Chittams, Frances K Barg, Barbara J Riegel
Journal: Circulation (2021)

Introduction: Self-care is vital in chronic illness management. Little is known about the self-care behaviors of African immigrants living in the US. Objectives: I) Describe the self-care behaviors of adult African immigrants in the US living with hypertension, diabetes, or other chronic illness. II) Identify significant determinants of self-care. Methods: Using a cross-sectional design and purposive sampling, 88 African immigrants to the US were enrolled if they self-identified as sub-Saharan African immigrants, were ≥35 years of age, had a symptomatic chronic illness, and could speak and understand English. Self-care was measured with the Self Care of Chronic Illness Inventory and the Self-Care Self-Efficacy scale. Scores are standardized 0-100 with scores &gt;70 considered adequate. Acculturation was measured using a modified standardized acculturation instrument and predefined acculturation proxies (e.g., duration of residency and age at immigration). General linear modeling with backward elimination was used to identify potential determinants of self-care. Results: The 88 participants were between 35 and 78 years, most were married (67%) and reported either diabetes (18%) or hypertension (50%) as their major illness. Self-care scores were adequate (mean 78.6, 77.9, 75.6 for self-care maintenance, monitoring and management). Specific self-care behaviors low in this population were eating a special diet and monitoring for medication side-effects and fatigue. In response to symptoms, few modified their diet or called a healthcare provider. Most (56.8%) were acculturated and acculturation was not associated with self-care. Self-care self-efficacy was high (81.3) and a strong determinant of self-care maintenance (p&lt;0.0001), monitoring (p&lt;0.0001) and management (p&lt;0.0001). Perceived inadequacy of income was a significant determinant of poor self-care management (p= 0.03). Conclusions: In this sample of African immigrants with primarily diabetes and hypertension, self-care was adequate. Self-care self-efficacy and perceived income adequacy were determinants of self-care. These factors can be used to inform culturally concordant interventions to promote self-care.
BIOM-38. THE PROGNOSTIC ROLE OF THE IMMUNOHISTOCHEMICAL MARKERS H3K27me3, SSTR1-5 AND BAP1 IN MENINGIOMA
Authors: Felix Behling, Christina Fodi, Mirjam Renovanz, Frank Paulsen, Marco Skardelly, Jürgen Honegger, Marcos Tatagiba, Jens Schittenhelm, Ghazaleh Tabatabai
Journal: Neuro-Oncology (2021)

Abstract Meningiomas are the most common primary tumors of the nervous system. These slow growing tumors arise from the meninges. Most patients can be cured by surgical excision. Yet, approximately 20% of patients suffer tumor recurrence. Prognostic markers are warranted to facilitate the identification of patients with an increased risk of tumor recurrence. Immunohistochemical markers are very interesting candidates in this regard and could be integrated into the routine clinical workflow as an inexpensive tool for prognostication and risk stratification. We analyzed the prognostic impact of the immunohistochemical expression of H3K27me3, somatostatin receptors 1-5 and BAP1 in the Tübingen meningioma cohort including &amp;gt; 1200 meningiomas. We identified an independent negative prognostic impact of the loss of H3K27me3. An increased expression score for SSTR2A was associated with a shorter progression-free survival. Higher expression of SSTR5 indicated a more favorable prognosis. The loss of BAP1 expression in meningioma cells was a negative prognostic factor with a shorter progression-free survival. Taken together, we present potential candidate prognostic markers that could be further investigated in prospective cohorts to determine their clinical utility.
DDRE-03. THERAPEUTIC TARGETING OF THE ERK AND CDK PATHWAYS IN PRECLINICAL MODELS OF BRAIN METASTASES
Authors: Mohini Singh, Naema Nayyar, Ashish Dahal, Priscilla Brastianos
Journal: Neuro-Oncology (2021)

Abstract Brain metastases (BM) are the most common neoplasm to affect the adult central nervous system. BM develop in 40-50% of advanced lung adenocarcinoma (LUAD), but the lack of durable response to chemotherapy, immunotherapy, or targeted therapy results in death within a year of BM diagnosis. Several advances have been made in identifying genetic drivers of primary cancers. The cell cycle, RAS and ERK pathways have all been implicated in as critical oncogenic regulators, with aberrations linked to driving the progression and metastasis of LUAD. Abemaciclib is a targeted CDK4/6 inhibitor, and LY3214996 is selective ERK1/2 inhibitor, and have shown efficacy in preclinical tumor models as well as in clinical trials. Furthermore, both therapeutics can interfere with the cell cycle, abemaciclib through targeting CDK4/6 and LY3214996 through cyclinD1. Here we present data assessing abemaciclib and LY3214996, as single and combined agents, in cell lines across different KRAS and CDKN2A mutational backgrounds. Seven days post-intracranial inoculation of NSCLC and NSCLC-BM line, mice received either abemaciclib, LY3214996, or a combination P.O. daily for 21 days, and were monitored pre- and post-treatment for tumor growth with bioluminescent imaging. In vitro we demonstrated a dose-dependent reduction in cell growth with each treatment, as well as cell arrest in G1 phase. In vivo, whereas cell lines with a combined KRAS mutation and CDKN2A mutation/deletion had no significant reduction in BM growth, cell lines with a CDKN2A del or BRAF mutation had significant BM reduction, with single agents and combined treatment. Further research is necessary to elucidate under what genetic contexts abemaciclib, LY3214996 or the combination are most effective. Nonetheless, this work highlights that abemaciclib and LY3214996 should be further explored for CDKN2A or BRAF mutant BM.
Abstract 10715: The Quality of Coronary Artery Bypass Grafting on YouTube
Authors: Bradley Nus, Kylie Wu, Trey Sledge, Grant Torres, Sai Kamma, Sanjana Janumpally, Syed Gilani
Journal: Circulation (2021)

Objective: YouTube, the second most accessed site on the internet, has become a widespread source of healthcare information for patients. Videos for Coronary Artery Bypass Grafts (CABG) have accrued tens of millions of views on the platform, yet their educational quality is unknown. This study investigates the level of bias and misinformation in videos regarding CABG procedures on YouTube. Methods: YouTube was searched for various terms such as “Coronary Bypass Graft Procedure.” After applying exclusion criteria, 73 videos were assessed. Two independent reviewers rated the material with the Global Quality Scale (GQS; 5 = high quality, 3 = low quality) to judge educational value. A ratio of view count to days since upload was applied to assess video popularity. Source, modality, and date of upload were recorded for each video as well. Results: An average GQS score of 2.95 was found, indicating poor educational quality amongst the 73 YouTube videos for CABG procedures. Videos uploaded by physicians (56 or 76.7%) had a significantly higher average GQS score than those not uploaded by physicians (p&lt;0.001). In grouping cohorts by modality, physician-led presentations (24 or 32.9%) produced the highest average GQS score of 3.35; conversely, patient-friendly delivery methods (18 or 24.7%) yielded the lowest average GQS score of 2.36 (p&lt;0.001) (Fig 2.). Neither view ratio nor days since upload significantly correlated with educational quality of the video. Conclusion: Although Coronary Artery Bypass Graft videos are readily available on YouTube, they often contain considerable biases and misleading information. With online sources for healthcare education now commonplace, physicians must be aware of the vast quantities of low-quality videos patients often encounter when weighing different treatment options. Further analysis of CABG videos on YouTube may allow physicians to ameliorate this gap by producing videos that are not only high quality, but highly viewed on the platform.
Immunogenicity of Extended mRNA SARS-CoV-2 Vaccine Dosing Intervals
Authors: Brian Grunau, David M. Goldfarb, Michael Asamoah-Boaheng, Liam Golding, Tracy L. Kirkham, Paul A. Demers, Pascal M. Lavoie
Journal: JAMA (2021)

Brian J. Boyarsky, MD; William A. Werbel, MD; Robin K. Avery, MD; Aaron A. R. Tobian, MD, PhD; Allan B. Massie, PhD; Dorry L. Segev, MD, PhD; Jacqueline M. Garonzik-Wang, MD, PhD
Evaluating Outcomes Using Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil As Gvhd Prophylaxis Compared with Methotrexate/Tacrolimus in Matched-Related and Matched-Unrelated Hematopoietic Stem Cell Transplant in Relation to the Haploidentical Setting in Acute Lymphoblastic Leukemia: A Single Center Experience
Authors: Sami Dwabe, Hugo Martinez, Jack Rodman, Eric Tam, Abdullah Ladha, Karrune Woan, Preet M. Chaudhary, George Yaghmour
Journal: Blood (2021)
Abstract P374: Functional Impairment Of Cardiac Endothelial Cells In Diabetic Failing Heart Via Dysregulated Exosomal Mirnas
Authors: Prabhat Ranjan, Sumanta K Goswami, Prasanna Krishnamurthy, Gangjian Qin, Suresh Verma
Journal: Circulation Research (2021)

Introduction: Cardiac endothelial cells (ECs) and fibroblasts (FBs) together maintain cardiac homeostasis. Their functional impairment aggravates complications in the heart. In diabetes, acute inflammation leads to cardiac FBs activation, which predisposes the diabetic myocardium to severe fibrosis. Further, inflammation-related vascular dysfunction is a major end-organ complication in diabetics. However, it is not known, whether myofibroblast regulates ECs function in a diseased diabetic heart. Therefore, we hypothesized that “myofibroblast in diabetic heart secretes exosomes packed with antiangiogenic/profibrotic factors, which impede EC function and exaggerate pathological remodelling in pressure-overloaded (PO) myocardium. Methods: Exosomes were isolated from diabetic mice plasma and FB condition media by ultracentrifugation and characterized by nanosight &amp; electron microscopy. We cultured mouse primary heart ECs in growth media and treated with exosomes derived from FBs (treated with 25mM glucose or 500nM Angiotensin II (AngII) or both) for 48 hr. Mannitol (25mM) served as control. Results: Ang II and glucose significantly activate FBs as shown by qPCR (fibronectin, collagenase1α1) and western blot (pSmad2, p-p38). Exosomes derived from diabetic Ang II treated FBs significantly impaired ECs function as shown by Matrigel tube formation and Boyden chamber migration assays. Interestingly, ECs markers (eNOS, VEGF, CD31) genes and proteins expression were significantly inhibited in ECs treated with exosomes-derived from glucose and Ang II treated FBs. We, further, checked the effect of diabetic mice plasma exosomes on ECs function and found significantly impaired as shown by tube formation and migration data. Finally, microRNA (miR) array and qPCR analysis revealed that miR-216a-5p, miR-26a-5p and miR7a-5p were highly upregulated in exosomes derived from FBs co-treated with glucose and AngII. Conclusions: Taken together, this study demonstrates that glucose and AngII co-treated FBs-derived exosomes are enriched in pro-fibrotic factors and can lead to EC dysfunction and promotes cardiac fibrosis in PO myocardium. In future studies, we will modulate the target miRs in diabetic FBs to see whether it rescue reparative function of ECs and inhibits fibrosis in failing heart.
Abstract 11646: <i>ATVB Outstanding Research Award</i> : WDFY3 is Required for the Efficient Degradation of Engulfed Apoptotic Cells by Macrophages During Efferocytosis
Authors: Xun Wu, Ziyi Wang, Jianting Shi, Fang Li, Young Joo Yang, Rebecca M. Moore, Margot K. Chirikjian, Ira A. Tabas, Ai Yamamoto, Hanrui Zhang
Journal: Circulation (2021)

Introduction: Defective clearance of apoptotic cells (ACs) by macrophages (efferocytosis) contributes to unresolved inflammation. Our recent genome-wide CRISPR screen has discovered WDFY3 as a novel regulator required for the efficient uptake of ACs during efferocytosis. WDFY3 is well known as a scaffold protein facilitating the autophagic degradation of aggregated proteins in neurons. Yet, if and how WDFY3 may also be required for the efficient degradation of engulfed ACs by macrophages have not been characterized. Hypothesis: WDFY3 is responsible for the efficient degradation of ACs by interacting with other autophagic proteins to facilitate phagosome-lysosome fusion, a process known as LC3-associated phagocytosis (LAP). Methods: Bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs), and mice with myeloid-specific Wdfy3 knockout (LysMCre +/- Wdfy3 fl/fl ) or transgenic overexpression of human WDFY3 ( hWDFY3 Tg ) were used for in vitro and in vivo assays. Results: Wdfy3 knockout BMDMs and PMs showed impaired lysosomal acidification and degradation of engulfed ACs. Mechanistically, Wdfy3 knockout impedes efficient LC3 lipidation upon AC engulfment, the last step required for phagosome-lysosome fusion and subsequent lysosomal degradation. Pull-down assay supports that WDFY3 interacts with GABARAP, but not LC3B, to mediate LC3 lipidation, supporting the direct involvement of WDFY3 protein in the process. At the transcriptomic level, RNA-seq and pathway analyses further revealed that gene sets of ROS/RNS production by phagocytes, fatty acid oxidation, and autophagosome were enriched in differentially expressed genes downregulated in Wdfy3 knockout BMDM, supporting the secondary effects of WDFY3-deficiency on the mRNA expression of genes and pathways essential for cargo degradation. Intriguingly, BMDMs and PMs from hWDFY3 Tg mice showed enhanced AC uptake and degradation both in vitro and in vivo , suggesting that WDFY3 has a wide dynamic range in its regulatory capacity. Conclusion: We discovered a novel role of WDFY3 in the degradation of ACs during macrophage efferocytosis. Enhancing WDFY3 may represent a therapeutic approach to promote the resolution of inflammation in diseases due to defective efferocytosis.
Erythropoiesis Stimulating Agents (ESAS) in Supportive Care of Low-Risk Myelodysplastic Syndromes: Recamds Registry FINAL Results
Authors: Claudio Cerchione, Fiorella Alfinito, Orsola Vitagliano, Ilaria Soriente, Paolo Danise, Giuseppe Cerciello, Fabrizio Pane, Giovanni Martinelli
Journal: Blood (2021)
Abstract 10430: Characteristics and Outcomes Surrounding Out-of-Hospital Cardiac Arrests Due to Drug Overdose in the United States
Authors: Aditya C Shekhar, Selcuk Adabag
Journal: Circulation (2021)

Introduction: Sudden deaths due to drug overdose have increased significantly in the US in the last decade. However, little is known about the characteristics and outcomes of out-of-hospital arrests in these patients. Two important factors that predict survival include the rates of pre-EMS CPR and return of spontaneous circulation (ROSC) achievement. Methods: We assessed the circumstances and outcomes of out-of-hospital arrests due to drug overdose, from January 2017 to December 2019 using a nationwide database of EMS calls in the United States (NEMSIS). The comparison group included patients documented to have had an out-of-hospital cardiac arrest due to presumed cardiac causes. Special attention was paid to whether or not pre-EMS CPR was performed, the first monitored arrest rhythm, and whether ROSC was achieved. Results: There were a total of 10,094 out-of-hospital cardiac arrests that were determined by EMS to have been caused by a drug overdose and 189,031 that were presumed to be due to cardiac causes (Table 1). Rates of pre-EMS CPR were similar for both overdose-related arrests (55.0%) and presumed cardiac-related arrests (54.5%) (p=0.35). First monitored rhythms that were shockable were significantly more common in presumed cardiac-related arrests (17.7 %) than overdose-related arrests (5.2%) (p&lt;0.001). Despite this, ROSC achievement was more common in overdose-related arrests (30.3%) than presumed cardiac-related arrests (26.0%) (p&lt;0.001). Conclusions: Out-of-hospital cardiac arrests due to drug overdose are less likely to involve shockable first monitored arrest rhythms but are more likely to result in ROSC achievement than those due to presumed cardiac causes. Further studies should more closely examine factors surrounding cardiac arrests due to drug overdose.
TAMI-37. STEAROYL-COA DESATURASE 1 IS ESSENTIAL FOR THE GROWTH OF IDH MUTANT GLIOMA
Authors: Tomohiro Yamasaki, Lumin Zhang, Tyrone Dowdy, Adrian Lita, Mark Gilbert, Mioara Larion
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Increased de novo lipogenesis is a hallmark of cancer metabolism. In this study, we interrogated the role of de novo lipogenesis in IDH1 mutated glioma’s growth and identified the key enzyme, Stearoyl-CoA desaturase 1 (SCD1) that provides this growth advantage. MATERIALS ANDMETHODS We prepared genetically engineered glioma cell lines (U251 wild-type: U251WT and U251 IDHR132H mutant: U251RH) and normal human astrocytes (empty vector induced-NHA: NHAEV and IDHR132H mutant: NHARH). Lipid metabolic analysis was conducted by using LC-MS and Raman imaging microscopy. SCD1 expression was investigated by The Cancer Genome Atlas (TCGA) data analysis and Western-blotting method. Knock-out of SCD1 was conducted by using CRISPR/Cas9 and shRNA. RESULTS Previously, we showed that IDH1 mut glioma cells have increased monounsaturated fatty acids (MUFAs). TCGA data revealed IDH mut glioma shows significantly higher SCD1 mRNA expression than wild-type glioma. Our model systems of IDH1 mut (U251RH, NHARH) showed increased expression of this enzyme compared with their wild-type counterpart. Moreover, addition of D-2HG to U251WT increased SCD1 expression. Herein, we showed that inhibition of SCD1 with CAY10566 decreased relative cell number and sphere forming capacity in a dose-dependent manner. Furthermore, addition of MUFAs were able to rescue the SCD1 inhibitor induced-cell death and sphere forming capacity. Knock out of SCD1 revealed decreased cell proliferation and sphere forming ability. Decreasing lipid content from the media did not alter the growth of these cells, suggesting that glioma cells rely on de novo lipid synthesis rather than scavenging them from the microenvironment. CONCLUSION Overexpression of IDH mutant gene altered lipid composition in U251 cells to enrich MUFA levels and we confirmed that D-2HG caused SCD1 upregulation in U251WT. We demonstrated the glioma cell growth requires SCD1 expression and the results of the present study may provide novel insights into the role of SCD1 in IDH mut gliomas growth.
Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses
Authors: Alexandra Tauzin, Shang Yu Gong, Guillaume Beaudoin-Bussières, Dani Vézina, Romain Gasser, Lauriane Nault, Lorie Marchitto, Mehdi Benlarbi, Debashree Chatterjee, Manon Nayrac, Annemarie Laumaea, Jérémie Prévost, Marianne Boutin, Gérémy Sannier, Alexandre Nicolas, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Guillaume Goyette, Yuxia Bo, Josée Perreault, Laurie Gokool, Chantal Morrisseau, Pascale Arlotto, Renée Bazin, Mathieu Dubé, Gaston De Serres, Nicholas Brousseau, Jonathan Richard, Roberta Rovito, Marceline Côté, Cécile Tremblay, Giulia C. Marchetti, Ralf Duerr, Valérie Martel-Laferrière, Daniel E. Kaufmann, Andrés Finzi
Journal: Cell Host & Microbe (2021)
Abstract 10713: Long-Term Impact of Alcohol Septal Ablation on Left Ventricular Remodeling and Diastolic Function: Retrospective Echocardiographic Assessment
Authors: Daniel Cook, Katrina Bidwell, Noah Blaker, Eric Taylor, Peyton Tharp, Davis Leaphart, Chris Nielsen, VALERIAN Fernandes
Journal: Circulation (2021)

Introduction: Alcohol septal ablation (ASA) is a percutaneous procedure for patients with refractory hypertrophic obstructive cardiomyopathy (HOCM). Asymmetric septal hypertrophy (ASH) and systolic anterior motion of the mitral valve (SAM) results in a dynamic left ventricular outflow tract gradient (LVOTG). LVOTG leads to concentric left ventricular hypertrophy and diastolic dysfunction. Hypothesis: We tested the hypothesis that patients who underwent ASA for treatment of HOCM would experience left ventricular remodeling and long-term improvement in diastolic function. Methods: Using a patient database maintained internally we analyzed the echocardiograms of 96 patients (36:60 M:F)(Age=60.5±13.2 years) who underwent successful ASA and had a follow-up echocardiogram at least 270 days following the procedure. Parameters used to describe diastology included interventricular septal thickness (IVSd), LV mass index (LVd mass index), LV diastolic internal diameter (LVIDd), LV end diastolic volume index (LVEDVi), left atrial end systolic volume index (LAESVi), early and late velocities across the mitral valve (MV E and A, respectively), and the MV E/A ratio. A paired t-test was used to compare baseline and follow-up echocardiogram values within individual subjects. Results: The time between ASA and follow-up echocardiogram was 653.9±350.4 days (mean±SD). At follow-up, the resting and provoked gradients were significantly reduced. Baseline and follow-up echocardiogram values were compared, revealing a significant difference in IVSd, LVPWd, LVd mass index, LVEDVi, LAESVi, MV E velocity, MV A velocity and MV E/A ratio. (Figure 1) Conclusions: Alcohol septal ablation induces significant regression of left ventricular hypertrophy and improvement in diastolic function. These changes likely contribute to long-term symptomatic improvement in patients who undergo alcohol septal ablation for treatment of hypertrophic obstructive cardiomyopathy.
Abstract 13584: Outcomes and Associated Costs With Temporary Mechanical Circulatory Support Devices in Patients With Cardiogenic Shock
Authors: Aroosa Malik, TANIMA BASU, Supriya Shore
Journal: Circulation (2021)

Objective: Clinical outcomes and costs associated with different temporary mechanical circulatory support (tMCS) devices has not been previously described. We describe outcomes and costs among heart failure (HF) patients who received tMCS i.e. Impella, intra-aortic balloon pump (IABP) or extra-corporeal membrane oxygenator (ECMO). Methods: This was a retrospective study of a large administrative claims dataset between 01/01/10 and 12/31/19. We included patients with HF or cardiogenic shock who received tMCS i.e. Impella, IABP or ECMO in the absence of an acute myocardial infarction (AMI) or coronary revascularization. Outcomes studied included 30-day mortality, in-hospital stroke and bleeding. We used logistic regression techniques to evaluate association between tMCS device, outcomes and cost. Results: We included 2205 HF unique patients receiving tMCS in the study: 1503 (68%) with ischemic cardiomyopathy (ICM) and 702 (32%) with non-ischemic cardiomyopathy (NICM). Rate of 30-day mortality was higher with ECMO compared to IABP or Impella respectively (22% vs. 15% vs. 17%) with higher stroke (21% vs. 12% vs. 16%) and bleeding rates (42% vs. 25% vs. 33%). This association persisted with multivariable adjustment for all adverse events. ECMO has higher odds of all adverse events vs IABP. Impella has higher odds than IABP for bleeding only. Median standardized cost was highest with ECMO $210383.0 (IQR: $165,760-$239,373), followed by Impella $142,518 (IQR: $126,845-$179938) and IABP $132,059.7 (IQR: $113,794-$160,243.7). Overall, we noted a decrease in cost with ECMO and IABP device types during the study period per year (Figure1). Conclusion: In a cohort of HF patients without AMI or coronary revascularization, use of ECMO was associated with higher rates of 30-day mortality, in-hospital stroke and bleeding compared to IABP and Impella. Associated costs with tMCS use are rising with an increase in survival over time.