tbuckley/cabot-search huggingface dataset:
Abstract 10161: Predicting Life-Threatening Ventricular Arrhythmias in Patients with Non-Ischemic Dilated Cardiomyopathy Using Electrocardiogram-Based Deep Neural Networks
Authors: Arjan Sammani, Rutger R Leur, Mathias Meine, Peter Loh, Rutger J Hassink, Daniel L Oberski, Michiel T Henkens, Stephane Heymans, Pieter Doevendans, Anneline S te Riele, Rene van Es, Folkert W Asselbergs
Journal: Circulation (2021)

Introduction: Patients with non-ischemic DCM are at risk of life-threatening ventricular arrhythmias. Improved patient selection for ICD implantation is warranted. Deep neural networks (DNN) can discover complex ECG features without the need for hand-crafted feature extraction. This study aimed to distinguish patients at risk of arrhythmias and detect and visualize ECG characteristics that attribute to the DNN classification. Methods: We trained a DNN model on baseline raw ECG samples of adult patients with DCM for the composite outcome of sustained ventricular arrhythmia, (aborted) sudden cardiac death and appropriate ICD therapy in the University Medical Centre Utrecht. Gradient-Weighted Class Activation Mapping was used for visual interpretation of the network. DNN performance was validated both internally and in an external cohort from the Maastricht University Medical University Center. Results: 26.628 ECGs were used for pre-training the network. In total, 317 patients with DCM were included in the primary cohort with a median age of 52 years (IQR 42 - 61), median LVEF of 25% (IQR 20-33), NYHA II and III (32% and 25%). 233 patients were ICD recipients. Subsequently 84 patients reached the outcome (median follow-up duration of 3.96 years (IQR 1.94 - 7.00)). The DNN focused on subtle but predictive differences in the terminal QRS-segment, the T-wave, and the P-wave (figure). The AUC of the DNN was 0.70 in cross-validation. External validation was similar, with an AUC of 0.66. Conclusion: In this study we trained and validated a deep neural network for prediction of life-threatening arrhythmic events. Even though the discriminatory changes on ECG segments were very subtle, the trained DNN was able to predict life-threatening events, focusing on the terminal QRS-segment, the T-wave, and the P-wave. Future studies are warranted to elucidate the identified ECG abnormalities and understand their electrophysiological substrates for LTA prediction in DCM.
Abstract 12274: Intensive Cardiac Rehabilitation: Impact on Mortality
Authors: Andrew F Lai, Mustafa Husaini, Susan B RACETTE, Elena Deych, Lauren Park, Serene Rashdi, Kristin McKenzie, Erin Mckenzie, Natalie A Stranczek, Nikhil Das, Nidhi Talpade, Karen Joynt Maddox, Lisa de las Fuentes, Michael W Rich, Linda R Peterson
Journal: Circulation (2021)

Introduction: Intensive cardiac rehabilitation (ICR) combines exercise sessions as in traditional cardiac rehabilitation (CR) with additional educational sessions focused on a heart-healthy diet and a healthy mindset. The effects of ICR, particularly outpatient Pritikin ICR, on mortality and cardiovascular outcomes have not been evaluated. Thus, the aim of our study is 1) to prospectively evaluate survival in a large cohort of patients enrolled in an outpatient Pritikin ICR program; and 2) to compare survival within a 5% Medicare sample between beneficiaries who participated in ICR versus those who did not participate in cardiac rehabilitation. Hypothesis: We hypothesize that 1) outpatient Pritikin ICR is associated with excellent survival (i.e. over 90% at 1 year) and 2) Medicare beneficiaries participating in ICR have better survival than those not participating in any cardiac rehabilitation. Methods: 1) This is a prospective longitudinal study of participants engaging in ICR at the first-ever outpatient Pritikin ICR center. For the single-center data, mortality was obtained via review of electronic medical records and direct patient follow-up for 1 year. 2) Within a 5% national Medicare sample, mortality was evaluated in all subjects utilizing a Cox proportional hazard model adjusted for age, gender, Medicaid status, number of comorbidities, and qualifying event type. The Kaplan-Meier curve is based on a subgroup matched for these same variables. Results: 1) There were 433 patients who participated in Pritikin ICR at our institution. The survival rate was 98% at 1 year. 2) In the Medicare sample, enrollees in ICR had a lower mortality than those not attending cardiac rehabilitation (HR = 0.49, 95% CI 0.28, 0.86) after adjustments; median follow-up time was 27.0 months. Conclusions: Outpatient Pritikin ICR is associated with an outstanding survival rate at 1 year. ICR in general is associated with better survival rates, even after multivariable adjustment.
Abstract 10829: Biradial Access Results in Lower Contrast Use and Fewer Complications Than Transfemoral Access in Alcohol Septal Ablation
Authors: Noah Blaker, Katrina Bidwell, Eric Taylor, Peyton Tharp, Daniel Cook, Chris Nielsen, VALERIAN Fernandes
Journal: Circulation (2021)

Introduction: Transradial cardiac catheterization has equivalent efficacy, reduced vascular complications, and is more comfortable and convenient for patients than transfemoral catheterization. The biradial approach for alcohol septal ablation (ASA) has not been well studied. Since 2013, the biradial approach has become the standard approach for alcohol septal ablation at MUSC. This project tested the hypothesis that the biradial approach is equally efficacious and results in fewer complications than the transfemoral approach in ASA. Methods: In this study 274 consecutive patients were retrospectively analyzed from the MUSC alcohol septal ablation database (137= biradial approach, 137=femoral approach) and the changes in left ventricular outflow tract gradient (LVOTG), amount of contrast, fluoroscopy time, and complications were recorded. Groups were not significantly different in pre-ASA LVOTG (p=0.88 and 0.06 for resting and provoked LVOTG respectively). Results: The procedures were equally efficacious at reducing LVOTG with a mean reduction of resting LVOTG of 91.24% (SEM=1.21) in biradial access and 92.37% (SEM=1.14) in femoral access (p=0.5), and a mean reduction of provoked LVOTG of 80.31% (SEM=1.90) in biradial access and 82.17% (SEM=1.74) in femoral access (p=.47). The biradial approach was associated with significantly less contrast use than the femoral approach (mean of 98.1 ccs, SEM of 3.60, and 110.89 ccs, SEM of 4.84, respectively; p=.035). There were statistically significant differences in fluoroscopy time and incidence of complications between the procedures (fluoroscopy time mean of 17.42 min. (SEM=0.93) biradial and 13 min. (SEM=0.72) femoral; (p= 0.00028). Incidence of cardiac complications of .13 biradial and .23 femoral; (p= 0.04)). Conclusions: In this largest study to date, the transradial approach is equally efficacious and is associated with significantly lower contrast use, and fewer complications, albeit with increased fluoroscopy time, than the transfemoral approach in ASA.
Abstract 12678: Marketplace Plan Designs for Cardiometabolic Therapies in Rural and Urban Counties in the US
Authors: Zachary Hermes, David A Bunn, Duaa AbdelHameid, Zainab Jaji, Sara Machado, Muthiah Vaduganathan
Journal: Circulation (2021)

Introduction: In the US, important variation exists in cardiovascular risk factor burden and rates of death across rural and urban counties. Affordability and non-financial mechanisms can present as barriers to treatment, yet little is known about if there may be systematic variation in plan design by rural and urban settings. We assessed whether rural or urban county type is associated with insurance plan design for sacubitril/valsartan, dapagliflozin, and empagliflozin. Methods: We evaluated the median premium silver-level plan from 26 selected states with federally-facilitated marketplaces based on the Bureau of Economic Analysis Regions. We then examined features such as coverage, tier, copay or coinsurance, expected out-of-pocket costs for 30 day supply, and coverage contingent non-financial elements including prior authorization, step therapy, and quantity limits. Logistic regression models, stratified by medication and state, assessed if rural/urban county type was a predictor of cost-sharing mechanism, coverage contingent elements, or out-of-pocket costs. Results: The mean population of urban and rural counties was 1.2M (±1.3M) and 19,364 (± 40,006), respectively. Urban counties had a higher proportion of Black/Hispanic individuals (31% vs. 16%) and higher median household incomes ($65,835 ± $17,452 vs. $47,212 ± $10,549); all P &lt; 0.01. Over 90% of plans covered each of the three medications, irrespective of rural/urban county type. Across each of the three medications and states, plans in urban counties had higher odds of including prior authorization (OR: 10.59; 95% CI: 2.55-43.96; P = 0.001) and use of coinsurance (OR: 9.06; 95% CI: 2.55-32.20; P = 0.001) compared with plans in rural counties. For each drug, predicted out-of-pocket costs differed as much as $250 between rural and urban counties for a given state. Conclusion: Most plans cover these newer cardiometabolic therapies across sampled US counties, but there was substantial variation in plan architecture across counties with greater utilization of prior authorization and coinsurance as a cost-sharing mechanism in urban counties. Given a greater population density, these mechanisms may guard against moral hazard and overutilization in urban settings.
Venetoclax Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia
Authors: Jasson Villarreal Hernandez, Maria Condom, Helena Pomares, Susana Vives, Rosa Coll, Marta Cervera, Clara Maluquer, Gladys Ibarra Fernandez, Albert Torrents, Mercedes Galiano, Anna Sureda, Montserrat Arnan Sangerman
Journal: Blood (2021)
Abstract 11577: Clinical Presentation and Medium-Term Outcomes in Anomalous Aortic Origin of a Coronary Artery with High Take-Off
Authors: Jack Y Chang, Dana Reaves-O'neal, Carlos Bonilla-Ramirez, Tam Doan, Shagun Sachdeva, prakash masand, Athar M Qureshi, Jeffrey S HEINLE, Christopher Caldarone, Carlos M Mery, Silvana Molossi
Journal: Circulation (2021)

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) confers risk of sudden death in the young. Paucity of data exists in AAOCA with high take-off (ht-AAOCA) from the aorta. Hypothesis: Patients with ht-AAOCA may be at risk of inducible myocardial ischemia and surgery might be indicated in a small subset with good medium-term outcomes. Methods: Patients with ht-AAOCA, defined as origin at the sinotubular junction and above by CTA, &lt;25 years old were prospectively enrolled. Myocardial functional studies were obtained under provocative stress: exercise stress test, stress nuclear perfusion imaging, dobutamine stress cardiac MRI, or cardiac catherization (in select patients). These studies were repeated 3 months post-operatively (post-op) in surgical patients. Results: A total of 71 patients (45 male, 63%) with ht-AAOCA were enrolled, median age 15 [IQR 12; 19] years. ht-AAOCA of the right (ht-AAORCA) was seen in 66/71 patients (93%): 15 (23%) had exertional symptoms, 13 (20%) had nonexertional symptoms, 14 (21%) had both, 24 (37%) were asymptomatic. Ht-AAOCA of the left (ht-AAOLCA) was seen in 5/71 patients (7%), only 1 (20%) had exertional symptoms. In ht-AAORCA patients, 50/66 (76%) had abnormal ostia and 6/66 (9%) juxtacommissural origin, as compared to 3/5 (60%) and 2/5 (40%), respectively, in ht-AAOLCA patients. Average intramural course in ht-AAORCA was 4.46 mm and 2.36 mm in ht-AAOLCA. Abnormal functional testing corresponding to the affected territory was seen in 11/71 (15%) ht-AAOCA patients. Surgery was recommended for 18/71 (25%) patients due to concerning symptoms, coronary anatomy, or abnormal functional testing. Of these, 13/18 (72%) underwent coronary artery unroofing (in 12) or reimplantation (in 1), 3 declined surgery, 2 pending decision. All surgical patients have returned to unrestricted exercise after reassuring post-op studies, but 1/18 (6%) awaits completion. At median follow up of 1.8 years (range 0.1-8.9), all patients are alive and well, 93% are exercising with no restrictions. Conclusion: Although ht-AAOCA appears benign in most patients, 15% shows inducible myocardial ischemia. Surgery may be indicated in a subset of patients, with overall excellent medium-term outcomes and freedom from exercise restrictions.
Abstract 13770: Systemic Intervention to Increase the Frequency of Genetic Counseling and Testing in Eligible Dilated Cardiomyopathy Patients
Authors: Akanksha Mohananey, Andrew Rosenbaum, Teresa M Kruisselbrink, Carri A Prochnow, Grace Lin, Margaret M Redfield, Naveen L Pereira
Journal: Circulation (2021)

Background: Although genetic testing (GT) in dilated cardiomyopathy (DCM) enables molecular diagnosis, family screening and provides prognostic information, it is underutilized. Our hypothesis was that systemic intervention (INT) in the heart failure (HF) clinic could increase the frequency of GT for DCM. Methods: Eligible DCM patients in a 17-month period before and after the INT were compared for frequency of genetic counseling and GT uptake. The INT comprised of the following: 1. Pre-emptive cardiovascular genomics e-consult (with a specialist in genetic DCM) for all new HF patients that could be canceled by the treating physician if the patient was considered ineligible or was uninterested. If eligible and patient was willing, 2. They were shown a video in person on genetic testing for DCM prepared by a genetics counselor 3. A trained HF clinic nurse provided answers to questions and completed the test requisition 4. Educational material was provided to the patient 5. Results were reviewed electronically and communicated to the patient via letter or phone call by the physician completing the e-consult. Clinical genetics consultation was available throughout the study period. Standard commercially available cardiomyopathy gene panels were used for GT. Results: There were 162 eligible DCM patients before and 194 after the INT. DCM patients were more likely to undergo genetic counseling post-INT versus (vs) pre-INT (33.5% vs 14.8%, OR 2.9, 95% CI 1.7-4.8, P &lt;.0001). Similarly, DCM patients were more likely to undergo GT post-INT vs pre-INT (27.3% vs 13%, OR 2.5, 95% CI 1.4-4.3, P =.001). Consequently, the total number of patients who were diagnosed to have likely pathogenic or pathogenic DCM-related genetic variants increased from 2 pre-INT to 6 post-INT. These variants were detected in the following genes: FLNC (n=2), TTN (n=2), DES , LMNA , PLN and TNNT2 . Conclusion: An intervention that was pre-emptive, easily accessible and available to the healthcare provider was successful in raising the rates of genetic counseling and testing in DCM patients seen in the HF clinic. Whether such low-cost interventions will enhance cascade screening and provide an opportunity for precision medicine remains to be determined.
Abstract 10491: CSL112 Suppresses Inflammation in Human Monocyte-Derived Macrophages
Authors: Svetlana A Didichenko, Jacqueline Adam, Alexey V Navdaev, Mae Wong, Monther Alhamdoosh, Moritz Saxenhofer, Elena Velkoska, Samuel D Wright, Bronwyn A Kingwell
Journal: Circulation (2021)

Introduction: Inflammatory monocytes and tissue-resident macrophages play a key role in the pathogenesis of atherosclerosis. Pro-inflammatory macrophages promote formation of unstable plaques whereas anti-inflammatory macrophages contribute to plaque stabilization. HDL (high-density lipoprotein) stimulates atherosclerosis regression in animal models and alters the inflammatory properties of monocyte-derived cells present in plaques. CSL112, human apoA-I formulated with phosphatidylcholine, is currently in a phase 3 clinical trial (AEGIS-II [ApoA-I Event Reducing in Ischemic Syndromes II]) to prevent major adverse cardiovascular events (MACE) in the 90-day high-risk period following myocardial infarction. Objective: To investigate the effects of CSL112 on human monocyte-macrophage differentiation and pro-inflammatory macrophage activation. Methods: Human blood monocytes from healthy donors were differentiated into macrophages in the absence or presence of CSL112, and then treated with/without the toll-like receptor 2/1 agonist P3CSK4. Gene expression analysis was performed using RNA sequencing technology; secreted cytokines were measured by ELISA. Results: CSL112 did not affect macrophage maturation or cause macrophage polarization towards the M1 or M2 phenotype in the absence of an inflammatory stimulus. After P3CSK4 stimulation, CSL112 exerted broad anti-inflammatory effects by significantly modulating the expression of multiple genes implicated in atherosclerosis. Specifically, CSL112 reduced gene and protein expression of CCL2, CCL4, TNFα and IL-6, decreased the expression of membrane bound receptor expressed on myeloid cells 1 (TREM-1) and inhibited the release of soluble TREM-1. Additionally, CSL112 suppressed P3CSK4-induced IL-18 secretion, while upregulated the expression of IL-18 binding protein, a natural antagonist of IL-18. Conclusion: Our findings demonstrate anti-inflammatory effects of CSL112 that may stabilize vulnerable atherosclerotic plaques and potentially contribute to reduction in MACE in the subacute period following myocardial infarction.
Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over &gt;32 years
Authors: Natalie McCormick, Chio Yokose, Na Lu, Amit D Joshi, Gary C Curhan, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To evaluate the joint (combined) association of excess adiposity and genetic predisposition with the risk of incident female gout, and compare to their male counterparts; and determine the proportion attributable to body mass index (BMI) only, genetic risk score (GRS) only, and to their interaction. Methods We prospectively investigated potential gene-BMI interactions in 18 244 women from the Nurses’ Health Study and compared with 10 888 men from the Health Professionals Follow-Up Study. GRS for hyperuricaemia was derived from 114 common urate-associated single nucleotide polymorphisms. Results Multivariable relative risk (RR) for female gout was 1.49 (95% CI 1.42 to 1.56) per 5 kg/m 2 increment of BMI and 1.43 (1.35 to 1.52) per SD increment in the GRS. For their joint association of BMI and GRS, RR was 2.18 (2.03 to 2.36), more than the sum of each individual factor, indicating significant interaction on an additive scale (p for interaction &lt;0.001). The attributable proportions of joint effect for female gout were 42% (37% to 46%) to adiposity, 37% (32% to 42%) to genetic predisposition and 22% (16% to 28%) to their interaction. Additive interaction among men was smaller although still significant (p interaction 0.002, p for heterogeneity 0.04 between women and men), and attributable proportion of joint effect was 14% (6% to 22%). Conclusions While excess adiposity and genetic predisposition both are strongly associated with a higher risk of gout, the excess risk of both combined was higher than the sum of each, particularly among women.
Bioadhesive injectable hydrogel with phenolic carbon quantum dot supported Pd single atom nanozymes as a localized immunomodulation niche for cancer catalytic immunotherapy
Authors: Huan He, Ziying Fei, Tailin Guo, Yue Hou, Da Li, Kefeng Wang, Fuzeng Ren, Kelong Fan, Daijun Zhou, Chaoming Xie, Chao Wang, Xiong Lu
Journal: Biomaterials (2021)
Recruitment of NK Cells during Autologous Apheresis Allows Efficient NK Cell Collection for Immunotherapy
Authors: Katarzyna Aleksandra Aleksandra Jalowiec, Christoph Bocksrucker, Thomas Pabst, Krzysztof Krasuski, Noel Frey, Ioannis Chanias, Kristina Vrotniakaite-Bajerciene, Urban Novak, Ulrike Bacher, Michael Daskalakis, Behrouz Teleghani Mansouri, Sacha Sergio Zeerleder
Journal: Blood (2021)
Feature selection revisited in the single-cell era
Authors: Pengyi Yang, Hao Huang, Chunlei Liu
Journal: Genome biology (2021)

Abstract Recent advances in single-cell biotechnologies have resulted in high-dimensional datasets with increased complexity, making feature selection an essential technique for single-cell data analysis. Here, we revisit feature selection techniques and summarise recent developments. We review their application to a range of single-cell data types generated from traditional cytometry and imaging technologies and the latest array of single-cell omics technologies. We highlight some of the challenges and future directions and finally consider their scalability and make general recommendations on each type of feature selection method. We hope this review stimulates future research and application of feature selection in the single-cell era.
INNV-18. EFFECT OF DURATION OF TUMOR TREATING FIELDS THERAPY ON CELLULARITY DISTRIBUTIONS BEYOND T1W MRI CONTRAST ENHANCING MARGIN AT AUTOPSY IN GLIOMA PATIENTS: PRELIMINARY RESULTS
Authors: Samuel Bobholz, Allison Lowman, Michael Brehler, John Sherman, Savannah Duenweg, Fitzgerald Kyereme, Jennifer Connelly, Elizabeth Cochran, Wade Mueller, Anjishnu Banerjee, Peter LaViolette
Journal: Neuro-Oncology (2021)

Abstract Tumor treating fields (TTFields) are thought to disrupt the cell division process in glioma. This study uses autopsy tissue samples from patients recruited for brain donation to determine whether TTFields treatment duration and usage affects cellularity distributions beyond the gadolinium contrast enhancing region on T1-weighted (T1w) magnetic resonance imaging (MRI). At autopsy, 43 tissue samples from 18 patients who had undergone TTFields treatment (inclusion criteria: &amp;gt;50% compliance and 25-day duration) were collected from brain slices sectioned in-line with slices from the patients’ final MRI prior to death. Nuclei were segmented on the digitized hematoxylin and eosin (HE) stained tissue samples, which were then used to compute cell count across the slides. Tissue was then aligned to the patient’s final MRI scan prior to death using a custom in-house software, where manually defined control points were used to compute a nonlinear transform to warp the tissue to match the MRI. Histogram features including mean, median, 90th percentile, variance, and skewness, were computed from the cellularity distributions within regions outside the traditional tumor margin defined by T1w contrast enhancement for each subject. General linear models were fit to assess the effects of TTFields usage (percent of day) and duration (in days) on each histogram feature, controlling for age, overall survival, and time between TTFields treatment and death, as well as time between MRI acquisition and death. Longer TTFields treatment duration and overall survival was associated with significantly decreased skewness in the non-enhancing cellularity distributions (p&amp;lt; 0.05) while associations with other metrics remained statistically insignificant. These preliminary results in a small patient cohort suggest that TTFields duration may reduce the presence of high cellularity tails in the non-contrast enhancing distributions. Additional research in larger patient populations is warranted to better understand these findings given the number of confounding factors.
Mismatch-Repair Deficiency in Follicular Lymphoma Tumors Is Common and Associated with a Favorable Overall Survival
Authors: Jithma P. Abeykoon, Dominick E Nowakowski, Jonas Paludo, Michelle K. Manske, Rebecca L. King, Adam J Wood, Surendra Dasari, Gordon Ruan, Matthew J. Maurer, Xiaosheng Wu, Grzegorz S. Nowakowski, Thomas E. Witzig
Journal: Blood (2021)