tbuckley/cabot-search huggingface dataset:
Abstract 16892: Impact of Catheter-Directed Thrombolysis on Hospital Readmission Rates in Patients With Acute Proximal and Caval Deep Vein Thrombosis
Authors: Irfan Shafi, Brooke Zlotshewer, Vladimir Lakhter, Huaqing Zhao, Riyaz Bashir
Journal: Circulation (2020)

Objective: To evaluate the readmission rate and identify the predictors of rehospitalization in patients with acute proximal and caval DVT. Background: Acute Deep Vein Thrombosis (DVT) is a significant cause of mortality and morbidity in the US that affects more than 600,000 patients each year. Catheter-directed thrombolysis (CDT) is a minimally invasive treatment option that improve acute symptoms as well as quality of life of patients with acute DVT. Methods: Patients with index hospitalization for acute proximal and caval DVT between 2016 and 2017 in the U.S. Nationwide Readmission Database were evaluated for the rates, predictors, and costs of unplanned readmission at 30 days. We used Cox proportional hazard model to determine predictors of 30 days readmissions. Results: This analysis included 58,306 patients (age&gt;=18 years) with index hospitalization for acute proximal and caval DVT; 8589 (14.7%) were readmitted within 30 days. The significant predictors for 30 day unplanned readmission were Malignancy (HR 1.60, 1.41-1.81), Charlson comorbidity index &gt; 3 (HR 1.43, 1.30-1.57), Insurance Medicare vs Private(HR 1.39, 1.25-1.57), Length of stay more than 2 days (HR 1.34, 1.24-1.45), and Acute Kidney Injury (HR 1.28, 1.17-1.40), COPD (HR 1.25, 1.13-1.38), Age (HR 0.77,0.70-0.85), Catheter directed thrombolysis ( HR 0.83, 0.76-0.90), and Acute Pulmonary Embolism(HR 0.83, 0.76-0.90)(Figure1). The cost of readmission was higher than index hospitalization ($ 56733 vs $ 47396). Conclusion: The 30 days readmission rate continue to be high in patients with acute DVT. Patient’s characteristics and comorbid conditions are predictors of readmission. Use of Catheter directed thrombolysis for treatment of acute DVT predicts reduced readmission risk.
Abstract 13017: Heart Transplantation Outcomes in Cardiac Sarcoidosis
Authors: Kamari C Jackson, Quentin R Youmans, Amy Zhou, Allen S Anderson, Alexandru B Chicos, Ashley Ezema, Edwin Mandieka, Ramael Ohiomoba, Duc Pham, Susan R Russell, Peter H Sporn, Clyde W Yancy, Ike S Okwuosa
Journal: Circulation (2019)

Introduction: Cardiac sarcoidosis (CS) is a progressive infiltrative cardiomyopathy that can lead to heart failure (HF), arrhythmia and death. The use of heart transplantation (HT) in CS patients w...
Studying PAR-Dependent Chromatin Remodeling to Tackle PARPi Resistance
Authors: Christina Andronikou, Sven Rottenberg
Journal: Trends in Molecular Medicine (2021)

Histone eviction and chromatin relaxation are important processes for efficient DNA repair. Poly(ADP) ribose (PAR) polymerase 1 (PARP1) is a key mediator of this process, and disruption of PARP1 activity has a direct impact on chromatin structure. PARP inhibitors (PARPis) have been established as a treatment for BRCA1- or BRCA2-deficient tumors. Unfortunately, PARPi resistance occurs in many patients and the underlying mechanisms are not fully understood. In particular, it remains unclear how chromatin remodelers and histone chaperones compensate for the loss of the PARylation signal. In this Opinion article, we summarize currently known mechanisms of PARPi resistance. We discuss how the study of PARP1-mediated chromatin remodeling may help in further understanding PARPi resistance and finding new therapeutic approaches to overcome it.
Epidemiology of human West Nile virus infections in the European Union and European Union enlargement countries, 2010 to 2018
Authors: Johanna J Young, Joana M Haussig, Stephan W Aberle, Danai Pervanidou, Flavia Riccardo, Nebojša Sekulić, Tamás Bakonyi, Céline M Gossner
Journal: Eurosurveillance (2021)

BackgroundWest Nile virus (WNV) circulates in an enzootic cycle involving mosquitoes and birds; humans are accidental hosts.AimWe analysed human WNV infections reported between 2010 and 2018 to the European Centre for Disease Prevention and Control to better understand WNV epidemiology.MethodsWe describe probable and confirmed autochthonous human cases of WNV infection reported by European Union (EU) and EU enlargement countries. Cases with unknown clinical manifestation or with unknown place of infection at NUTS 3 or GAUL 1 level were excluded from analysis.ResultsFrom southern, eastern and western Europe, 3,849 WNV human infections and 379 deaths were reported. Most cases occurred between June and October. Two large outbreaks occurred, in 2010 (n = 391) and in 2018 (n = 1,993). The outbreak in 2018 was larger than in all previous years and the first cases were reported unusually early. The number of newly affected areas (n = 45) was higher in 2018 than in previous years suggesting wider spread of WNV.ConclusionReal-time surveillance of WNV infections is key to ensuring that clinicians and public health authorities receive early warning about the occurrence of cases and potential unusual seasonal patterns. Human cases may appear shortly after first detection of animal cases. Therefore, public health authorities should develop preparedness plans before the occurrence of human or animal WNV infections.
Two-dimensional chemotherapy simulations demonstrate fundamental transport and tumor response limitations involving nanoparticles
Authors: V. Cristini
Journal: Journal of Clinical Oncology (2005)

2118 Zheng et al. (Bull. Math. Biol. 2004) developed a multiscale, two-dimensional simulator with the capability of showing tumoral lesion progression through the stages of diffusion-limited dormancy, neo-vascularization (angiogenesis) and consequent rapid growth and tissue invasion. In this paper (Sinek et al., Biomed. Microdev. 2004) we extend their simulator to describe delivery of chemotherapeutic drugs to a highly perfused tumoral lesion and the tumor’s response to the therapy. 2-D simulations based on a self-consistent parameter estimation demonstrate fundamental convective and diffusive transport limitations in delivering anticancer drug into tumors, whether this delivery is viafree drug administration (e.g., intravenous drip), or via100 nm nanoparticles injected into the bloodstream, extravasating and releasing the drug that then diffuses into the tumoral tissue, or viasmaller 1–10 nm nanoparticles that are capable of diffusing directly and targeting the individual tumor cell. Even in a best-case scenario involving: constant drug release from the nanoparticles; a homogenous tumor of one cell type, which is drug-sensitive and does not develop resistance; targeted nanoparticle delivery, with resulting low host tissue toxicity; and for model parameters calibrated to ensure sufficient drug or nanoparticle blood concentration to rapidly kill all cells in vitro; our analysis shows that fundamental transport limitations are severe in vivo and that drug levels inside the tumor are far less than in vitro, leaving large parts of the tumor with inadequate drug concentration. A comparison of cell death rates predicted by our simulations reveals that the in vivorate of tumor shrinkage is several orders of magnitude less than in vitrofor equal chemotherapeutic carrier concentrations in the blood serum and in vitro, and after some shrinkage the tumor may achieve a new mass equilibrium far above detectable levels. We also demonstrate that adjuvant anti-angiogenic therapy “normalizing” the vasculature may ameliorate transport limitations, although leading to unwanted tumor fragmentation. No significant financial relationships to disclose.
Transcriptome-wide association analysis identifies DACH1 as a kidney disease risk gene that contributes to fibrosis
Authors: Tomohito Doke, Shizheng Huang, Chengxiang Qiu, Hongbo Liu, Yuting Guan, Hailong Hu, Ziyuan Ma, Junnan Wu, Zhen Miao, Xin Sheng, Jianfu Zhou, Aili Cao, Jianhua Li, Lewis Kaufman, Adriana Hung, Christopher D. Brown, Richard Pestell, Katalin Susztak
Journal: Journal of Clinical Investigation (2021)

Genome-wide association studies (GWAS) for kidney function identified hundreds of risk regions; however, the causal variants, target genes, cell types, and disease mechanisms remain poorly understood. Here, we performed transcriptome-wide association studies (TWAS), summary Mendelian randomization, and MetaXcan to identify genes whose expression mediates the genotype effect on the phenotype. Our analyses identified Dachshund homolog 1 (DACH1), a cell-fate determination factor. GWAS risk variant was associated with lower DACH1 expression in human kidney tubules. Human and mouse kidney single-cell open chromatin data (snATAC-Seq) prioritized estimated glomerular filtration rate (eGFR) GWAS variants located on an intronic regulatory region in distal convoluted tubule cells. CRISPR-Cas9–mediated gene editing confirmed the role of risk variants in regulating DACH1 expression. Mice with tubule-specific Dach1 deletion developed more severe renal fibrosis both in folic acid and diabetic kidney injury models. Mice with tubule-specific Dach1 overexpression were protected from folic acid nephropathy. Single-cell RNA sequencing, chromatin immunoprecipitation, and functional analysis indicated that DACH1 controls the expression of cell cycle and myeloid chemotactic factors, contributing to macrophage infiltration and fibrosis development. In summary, integration of GWAS, TWAS, single-cell epigenome, expression analyses, gene editing, and functional validation in different mouse kidney disease models identified DACH1 as a kidney disease risk gene.
Abstract 17422: Transcatheter Mitral Valve Thrombosis: A Case Report and Literature Review
Authors: Mohammad Alarfaj, Joseph Krepp, Tushina Jain
Journal: Circulation (2020)

Background: Trans-catheter mitral valve replacement (TMVR) is an exciting alternative therapy for complex patients with mitral valve disease. The experience with TMVR is new and there is a lot yet to discover about their durability, long-term outcomes, and complications including, mitral transcatheter heart valve (THV) thrombosis. Many factors have been speculated to be associated with the increased risk of THV thrombosis. Here, we report a case of mitral THV thrombosis then discuss published data on the subject. Case presentation: A 72-year-old woman who underwent TMVR for severe mitral regurgitation with mitral annular calcification. She was discharged on aspirin and clopidogrel for thromboprophylaxis. She presented after 30 days with symptomatic heart failure. Her transesophageal echocardiogram showed increased mean trans-mitral gradient with severe subvalvular thickening with immobile neo-anterior leaflet. She was subsequently started on a heparin drip with bridge to warfarin with international normalized ratio goal of 2.5 to 3.5. Discussion: Since most patients undergoing TMVR are within a high-risk population, caution should be implemented to minimize complications, valve dysfunction, and failure. We reviewed 42 TMVR papers with total of 1484 patients including 60 with mitral THV thrombosis. We discussed the most common strategies used for mitral THV thromboprophylaxis and treatment. Conclusion: Given current evidence, post-TMVR anticoagulation should be considered for at least 3 months, especially in those without significant bleeding risk. Longer anti-coagulation therapy should be considered for patients with multiple risk factors for thrombus formation. Additionally, systematic active screening with close clinical follow up help promptly identify those with subclinical THV thrombosis or need longer anti-coagulation therapy.
Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands
Authors: Daniel N. Weinberg, Phillip Rosenbaum, Xiao Chen, Douglas Barrows, Cynthia Horth, Matthew R. Marunde, Irina K. Popova, Zachary B. Gillespie, Michael-Christopher Keogh, Chao Lu, Jacek Majewski, C. David Allis
Journal: Nature Genetics (2021)
Abstract 15181: The National Pediatric Cardiology Boot Camp Training Program - Five Years’ Evidence of Consistent Educational Benefit
Authors: Loren D Sacks, Kara S Motonaga, Catherine D Krawczeski, David M Axelrod, Lillian Su, Robert Bishop, Alisa Arunamata, David M Kwiatkowski, Inger Olson, Shiraz A Maskatia, Alaina K Kipps, Leo Lopez, Rajesh U SHENOY, Paul D Grossfeld, Michael Weidenbach, Angela M Kelle, Sonali S Patel, Robert H Pass, Lupe Romero-Villanueva, Holly Lewin, Scott R Ceresnak
Journal: Circulation (2020)

Introduction: The transition from residency to subspecialty fellowship in pediatric cardiology is challenging, with the daunting requirement to rapidly acquire a broad scope of knowledge and skill. In 2015, a pediatric cardiology boot camp was designed as an educational tool to help prepare trainees for this transition. Hypothesis: A national pediatric cardiology boot camp consistently improves knowledge and decreases anxiety for prospective fellows. Methods: In late spring each year (2015-2019), a 2.5-day intensive program was provided for trainees prior to beginning fellowship in July. Hands-on, simulation-based experiences were provided on topics including anatomy, auscultation, echocardiography, catheterization, cardiovascular intensive care, electrophysiology, heart failure, pulmonary hypertension, and cardiac surgery. Knowledge based exams and surveys were completed by each participant pre- and post-training. Pre- and post-training exam results were compared via paired t-tests and survey results were compared via Wilcoxon rank sum. Results: Over 5 years 144 participants (72 female, 50%) completed the course, representing 40 fellowship programs in the United States and Canada. In aggregate, significant improvement was seen in participants’ knowledge assessment (pre 45 ± 11% vs. post 71 ± 9%; p&lt;0.0001). Post-intervention tests showed significant increases in knowledge every year, with a similar mean rate of improvement from year to year (25±10%; p=0.15). Participants in 2015 did score higher on both pre and post testing (pre 55±10%, post 85±7%; p&lt;0.0001), but the improvement rate remained consistent. Pre- and post-program surveys showed significant improvement in 38 of 38 domains assessing comfort and anxiety (p&lt;0.001 for each domain). All participants strongly agreed (97%) or agreed (3%) that the boot camp was a valuable learning experience and 98% strongly agreed (66%) or agreed (32%) that boot camp alleviated anxieties about starting fellowship. Conclusions: The Pediatric Cardiology Boot Camp provides a significant and reproducible educational benefit to participants nationwide. This intensive program simultaneously improves learners’ knowledge and alleviates anxiety as they transition to subspecialty training.
Donor and Recipient HLA Class I Molecule Are Required for Maximum NK Cells Cytotoxicity Reconstitution Post Haploidentical Hematopoietic Stem Cells Transplantation
Authors: Xiangyu Zhao, Xingxing Yu, Mingrui Huo, Xiaosu Zhao, Xueyi Luo, Yingjun Chang, Xiaohui Zhang, Lanping Xu, Kaiyan Liu, Xiao-Jun Huang
Journal: Blood (2017)
Between competence and warmth: the remaining place of the physician in the era of artificial intelligence
Authors: David Drummond
Journal: npj Digital Medicine (2021)

Competence and warmth are two essential dimensions of patient care. During the twentieth century, the industrial revolution in data collection, with the increasing use of machines and the division of labor that led to the development of many subspecialities, increased the overall competence of physicians at the expense of the warmth dimension. The spread of patient-centered care principles aimed to rebalance the two dimensions. In the twenty-first century, the industrial revolution in data processing with the emergence of algorithmic decision-making systems based on artificial intelligence is likely to disrupt further this balance. Competence will no longer be the prerogative of physicians, but a dimension to be shared between physicians and autonomous algorithmic decision-making systems, by contrast to warmth which should remain a human attribute. In this comment, we discuss the extent to which competence and warmth can remain the core dimensions of physician care in the era of artificial intelligence.
Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes
Authors: Gerasimos Filippatos, George L. Bakris, Bertram Pitt, Rajiv Agarwal, Peter Rossing, Luis M. Ruilope, Javed Butler, Carolyn S.P. Lam, Peter Kolkhof, Luke Roberts, Christoph Tasto, Amer Joseph, Stefan D. Anker
Journal: Journal of the American College of Cardiology (2021)

Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin–angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53–0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993)
DcR3 regulation and its effect on radiation treatment
Authors: Ying Su, Sunghee Kim, Shanmin Yang, Zhenyu Xiao, Peter Keng, Ivan Ding, Paul Okunieff, Lurong Zhang
Journal: Cancer Research (2005)

1231  Aim: DcR3 is a newly discovered decoy receptor (secretary soluble receptor) in the TNFR superfamily. It binds to three important apoptotic ligands: FasL, TL1A and LIGHT, it competes with their intact death receptors, and therefore blocks the death signaling. We investigated DcR3 regulation and its effect on radiation response. Methods: SW480 cancer cells were irradiated and the level of DcR3 was measured by ELISA. DcR3 regulation was evaluated using a panel of inhibitors for various signaling pathways. The extent of apoptosis in irradiated cancer cells was measured by Annexin V and Calcein AM staining. Results: Upon radiation, SW480 cells upregulated DcR3 expression in a dose- and time-dependent manner. The up-regulation of DcR3 can be inhibited by the MEK inhibitor (PD98059), but not the P38/MAPK inhibitor (SB203580). The radiation-induced apoptosis of SW480 cells was enhanced by addition of PD98059 and was blocked by SB203580, as evidenced by a higher percentage of living cells stained with Annexin V and Calcein AM compared to the controls. Conclusion: The induction of DcR3 protects cancer cells from radiation-induced apoptosis. The up-regulation of DcR3 is associated with the MEK signaling pathway, but not the P38/MAPK pathway. It seems that the level of DcR3 is a critical factor determining the fate of irradiated cells. Potential radiation sensitization should occur if the DcR3 effect is down-regulated. This can be accomplished by siRNA, MEK inhibitor, or by blocking its function using of neutralization antibody.
30P Expression signature of Let-7a, miR-34a and miR-486-5p in young triple-negative breast cancer patients overexpressing PDL1: A step towards precision immuno-oncology
Authors: C.J. Kiriacos, M.R. Khedr, M.M. Tadros, H.M. Hafez, R.A. Youness
Journal: Annals of Oncology (2021)
Abstract 14817: Assessing the Burden of Cardiovascular Risk Factors and Disease Across PVDOMICS Cohorts
Authors: Jane A Leopold, Brett Larive, Erika Rosenzweig, Robert Frantz, Paul Hassoun, Anna R Hemnes, Franz Rischard, Miriam Jacob, Evelyn M Horn
Journal: Circulation (2020)

Longitudinal trends demonstrate an increase in the prevalence of cardiovascular (CV) risk factors in the general population; however, the burden of CV risk factors or established disease in patients across WSPH groups remains unknown. Accordingly, we examined the prevalence of CV risk factors and established disease in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) cohort. PVDOMICS enrolled 1,097 subjects with pulmonary hypertension (PH) (mPA ≥ 25 mmHg) and at-risk disease comparators (mPa &lt; 25 mmHg) from six US centers. Compared to participants with PH attributable to left heart disease (LHD-PH; WSPH Group 2, n=145) who are expected to have a high burden of CV risk factors and disease, patients with WSPH Groups 1,3,4,and 5 (non-LHD-PH)(n=618) were younger (56.2 ± 14.5 vs 67.7 ± 11.7 yrs, p&lt;0.02) with no difference in %female or race. Non-LHD-PH had a lower prevalence of the CV disease risk factors hypertension (38.6% vs. 66.7%, p&lt;0.02), diabetes mellitus (21.4 vs. 41.0%, p&lt;0.02), and metabolic syndrome (30.8 vs. 48.4%, p&lt;0.02) compared to LHD-PH, while smoking, hypercholesterolemia, and family history of CV disease were similar between groups. The prevalence of established CV disease, including myocardial infarction, CABG or stent, stroke, arrhythmia, or peripheral arterial disease was significantly lower in non-LHD-PH than in LHD-PH. At right heart catheterization, although mPA pressures were similar between the groups, PVR (5.5[3.3, 8.7] vs. 3.7[7.2, 5.7] WU, p&lt;0.02), and cardiac output were higher (5.4 ± 1.9 vs. 4.9 ± 1.6 L/min, p&lt;0.02) in non-LHD-PH compared to LHD-PH. This corresponded to a higher left ventricular ejection fraction by echo (62.2 ± 8.2 vs. 54.0 ± 14.0 %, p&lt;0.02) and greater 6-minute walk distance (361.8 ± 134.7 vs. 294.7 ± 118.7 m, p&lt;0.02). Non-LHD-PH also had better cardiovascular health compared to LHD-PH with higher modified American Heart Association Life’s Simple 7 scores (6.7 ± 1.6 vs. 5.8 ± 1.5, P&lt;0.02). Taken together, these data demonstrate that CV disease risk factors and CV disease are frequent comorbidities that occur in patients with non-LHD-PH, although CV health is not as impaired as in patients with LHD-PH. How this affects PH-related outcomes remains to be determined.