tbuckley/cabot-search huggingface dataset:
Abstract 14589: The Zip Code Jeopardy: Living in Disadvantaged Areas is Associated With Significantly Increased Mortality After Percutaneous Coronary Intervention: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: Devraj Sukul, Milan Seth, Stephanie Spehar, Michael Thompson, Daniel Bonifacio, Daniel Lee, Maged Rizk, Abdul Osman, Hitinder S Gurm
Journal: Circulation (2020)

Introduction: Research suggests that neighborhood-level factors are associated with long-term health; however, there is a dearth of research evaluating this association among patients (pts) undergoing percutaneous coronary intervention (PCI), a population that is usually optimally treated with respect to long-term risk management. Hypothesis: We hypothesize that pts living in the most disadvantaged areas have a higher risk of post-discharge mortality after PCI compared with pts not living in the most disadvantaged areas. Methods: Using a clinical registry of pts with valid zip codes who underwent PCI between 1/2013 - 3/2018 at 47 Michigan hospitals linked to Medicare claims, we compared long-term outcomes between pts in the highest ADI decile (i.e. most disadvantaged) with the remainder. The Area Deprivation Index (ADI) is a zip-code-level composite measure of neighborhood disadvantage. Unadjusted mortality was depicted on a Kaplan-Meier plot. We used a Cox model to assess the association between the ADI and mortality after adjusting for pt factors. Results: Among 26,164 pts, 9.9% lived in the most disadvantaged zip codes and were more likely to be younger, of black race, have both Medicare and Medicaid insurance, and have more cardiovascular comorbidities. Unadjusted rates of mortality were higher among pts living in the most disadvantaged areas compared with the remainder (5-yr mortality: 64.5% vs 70.9%; Fig). After adjusting for pt factors, those living in the most disadvantaged areas had a significantly increased risk of long-term mortality (HR 1.16; 95% CI 1.08 - 1.25), a risk equivalent to an 8% reduction in one’s ejection fraction (HR for 8% EF reduction: 1.16; 95% CI 1.14 - 1.17). Conclusions: Medicare pts living in the most disadvantaged areas have a higher risk of post-PCI long-term mortality compared with the remainder. Policies targeting the deleterious health effects of neighborhood disadvantage and social risk are needed to improve survival after PCI.
Deformable Models for Surgical Simulation: A Survey
Authors: Jinao Zhang, Yongmin Zhong, Chengfan Gu
Journal: IEEE Reviews in Biomedical Engineering (2017)

This paper presents a survey of the state-of-the-art deformable models studied in the literature concerning soft tissue deformable modeling for interactive surgical simulation. It first introduces the challenges of surgical simulation, followed by discussions and analyses on the deformable models, which are classified into three categories: the heuristic modeling methodology, continuum-mechanical methodology, and other methodologies. It also examines linear and nonlinear deformable modeling, model internal forces, and numerical time integrations, together with modeling of soft tissue anisotropy, viscoelasticity, and compressibility. Finally, various issues in the existing deformable models are discussed to outline the remaining challenges of deformable models in surgical simulation.
Reproductive Outcomes After Breast Cancer in Women With vs Without Fertility Preservation
Authors: Anna Marklund, Frida E. Lundberg, Sandra Eloranta, Elham Hedayati, Karin Pettersson, Kenny A. Rodriguez-Wallberg
Journal: JAMA Oncology (2020)

The practice of fertility preservation (FP) in women with breast cancer (BC) is spreading, but long-term reproductive outcomes after FP are largely unknown.To investigate the long-term reproductive outcomes in women who did or did not undergo FP at the time of BC diagnosis.A Swedish nationwide cohort study was conducted to investigate the long-term reproductive outcomes of women with BC receiving FP at 1 of the regional FP programs from 1994 to 2017 (n = 425). Population comparators with BC but without history of FP (n = 850) were sampled from regional BC registers, matched on age, calendar period of diagnosis, and county. Data on live births, assisted reproductive technology (ART) use, and mortality were retrieved from population-based registers. Data analysis was performed from January to September 2020.History of having received FP compared with no history of FP (unexposed).The primary outcome was hazard ratios (HRs) of live births and ART treatments following BC in women with vs without FP and the cumulative incidence of these events in the presence of the competing risk of death.Women who had undergone FP (n = 425) had lower parity (302 [71.1%] were nulliparous compared with 171 [20.1%] in the unexposed group), were younger (mean [SD] age, 32.1 [4.0] vs 33.3 [3.6] years), more often had estrogen receptor-positive tumors (289 [68.0%] vs 515 [60.6%]), and were more often scheduled for chemotherapy (399 [93.9%] vs 745 [87.7%]). Of 425 women exposed to FP, 97 (22.8%) had at least 1 post-BC live birth (mean follow-up, 4.6 years), compared with 74 of 850 women (8.7%) unexposed to FP (mean follow-up, 4.8 years). Overall, live birth rates after BC were significantly higher among women with FP (adjusted hazard ratio [aHR], 2.3; 95% CI, 1.6-3.3). The 5-year and 10-year cumulative incidence of post-BC live births was 19.4% and 40.7% among FP-exposed women vs 8.6% and 15.8% among comparators, respectively. Rates of ART use were also higher in the FP group (aHR, 4.8; 95% CI, 2.2-10.7). The all-cause mortality rate was lower in women exposed to FP (aHR, 0.4; 95% CI, 0.3-0.7), with 5-year cumulative incidence of death of 5.3% (95% CI, 3.1%-9.0%) vs 11.1% (95% CI, 8.7%-14.1%) for women with vs without FP.In this cohort study of Swedish women after a BC diagnosis, successful pregnancy after BC was possible both in women with and without FP at the time of diagnosis, but a significantly higher likelihood of post-BC live births and ART treatments was observed in women who underwent FP, without any negative association with all-cause survival. This information is valuable for health care clinicians responsible for oncologic treatment and reproductive counseling of women diagnosed with breast cancer at reproductive age.
Abstract 123: Intra-arrest Delivery of Intra-muscular Magnesium Sulfate in a Rat Model of Cardiac Arrest
Authors: Rui Zhang, Jinhui Liao, Sarita Raghunayakula, Xiaodan Ren, Kathleen Maheras, Erin Gruley, Yuguo Chen, Robert W Neumar, Thomas H Sanderson
Journal: Circulation (2020)

Introduction: Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective therapy that has the potential to reduce neuronal calcium overload via NMDA receptor modulation and prevent mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO4 during CPR has the potential to target these mechanisms within their presumed therapeutic window. Hypothesis: IM MgSO4 administrated during CPR will achieve therapeutic serum magnesium levels, which is ≥ 2 times of baseline, within 15 minutes after ROSC and improve neurologic outcomes. Methods: Male Long Evans rats were subjected to 8-minute asphyxial cardiac arrest. For the dose-finding study (n = 4/group), rats were block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO4 IM at the onset of CPR. Serial blood samples were collected at baseline, 15 min, 30 minutes, 1 hour and 2 hours after return of spontaneous circulation (ROSC) and analyzed for serum magnesium concentration. For the long-term outcome study (n = 9/group), rats subjected to cardiac arrest were blindly block randomized to the same treatment groups with the addition of a sham-operated group. Post-cardiac arrest care included maintenance of normothermia (36.7 °C - 37.3 °C) for 72 hours. Serial blood samples were collected at baseline, 15 min and 1 hour after ROSC and neurologic function score (NFS) was performed daily for 10 days. Good neurologic function was predefined as NFS ≥ 450. Results: IM MgSO4 during CPR had no effect on ROSC rate (p &gt; 0.05). The serum magnesium concentrations at 15 min after ROSC of 107 mg/kg group, 215 mg/kg group and 430 mg/kg group were 3.9 ± 0.9, 6.2 ± 1.8, and 7.6 ± 1.8 mg/dl, which were 2.0 fold, 3.1 fold and 4.2 fold of baseline respectively. IM MgSO4 had no statistically significant effect on 10-day survival or 10-day survival with good neurologic function. Conclusion: Single dose IM MgSO4 during CPR achieves up to 4-fold baseline magnesium levels within 15 min after ROSC in a rat model of asphyxia cardiac arrest. This treatment strategy did not improve survival or recovery of neurologic function. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.
Microbubbles Containing Lysolipid Enhance Ultrasound‐Mediated Blood–Brain Barrier Breakdown In Vivo
Authors: Oliver Vince, Sarah Peeters, Vanessa A. Johanssen, Michael Gray, Sean Smart, Nicola R. Sibson, Eleanor Stride
Journal: Advanced Healthcare Materials (2020)

Abstract Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood–brain barrier (BBB) permeability to therapeutics. To reduce off‐target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso‐MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso‐MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso‐MBs or control MBs and gadolinium‐DTPA (Gd‐DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak‐negative pressures 160–480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd‐DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation ( n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso‐MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid‐shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain.
Partitioned Gene-Tree Analyses and Gene-Based Topology Testing Help Resolve Incongruence in a Phylogenomic Study of Host-Specialist Bees (Apidae: Eucerinae)
Authors: Felipe V Freitas, Michael G Branstetter, Terry Griswold, Eduardo A B Almeida
Journal: Molecular Biology and Evolution (2020)

Incongruence among phylogenetic results has become a common occurrence in analyses of genome-scale data sets. Incongruence originates from uncertainty in underlying evolutionary processes (e.g., incomplete lineage sorting) and from difficulties in determining the best analytical approaches for each situation. To overcome these difficulties, more studies are needed that identify incongruences and demonstrate practical ways to confidently resolve them. Here, we present results of a phylogenomic study based on the analysis 197 taxa and 2,526 ultraconserved element (UCE) loci. We investigate evolutionary relationships of Eucerinae, a diverse subfamily of apid bees (relatives of honey bees and bumble bees) with >1,200 species. We sampled representatives of all tribes within the group and >80% of genera, including two mysterious South American genera, Chilimalopsis and Teratognatha. Initial analysis of the UCE data revealed two conflicting hypotheses for relationships among tribes. To resolve the incongruence, we tested concatenation and species tree approaches and used a variety of additional strategies including locus filtering, partitioned gene-trees searches, and gene-based topological tests. We show that within-locus partitioning improves gene tree and subsequent species-tree estimation, and that this approach, confidently resolves the incongruence observed in our data set. After exploring our proposed analytical strategy on eucerine bees, we validated its efficacy to resolve hard phylogenetic problems by implementing it on a published UCE data set of Adephaga (Insecta: Coleoptera). Our results provide a robust phylogenetic hypothesis for Eucerinae and demonstrate a practical strategy for resolving incongruence in other phylogenomic data sets.
Abstract 15865: Analysis of Left Ventricular Assist Device Hemodynamics During Right Heart Catheterization Ramp Studies
Authors: Alexander G Hajduczok, Katharine Julian, Carly Maucione, John P Boehmer
Journal: Circulation (2020)

Background: Although hemodynamic-driven Left Ventricular Assist Device (LVAD) speed changes have been shown to improve patient outcomes, there is no standardized algorithm for how to best adjust LVAD speed for optimization of cardiac output (CO) and decompression of left sided filling pressures as measured by pulmonary capillary wedge (PCW). Methods: We performed a retrospective study of LVAD patients at Penn State Hershey Medical Center from 2015 to present, to identify those that ramp studies during right heart catheterizations. 470 patients were identified, of which 60 had ramp studies. Only studies with at least 4 of 5 standard ramp speeds were included. Any study that did not exhibit at least a 20% decrease in PCW, suggesting improper LVAD function or recovered heart function, was also excluded. 32 studies were included in final analysis: 11 HVAD, 12 HMIII, and 9 HMII. CO measured by thermodilution was reported. Standard ramp speeds, in rpm, were as follows: HVAD (2100, 2400, 2700, 3000, 3300), HMIII (4500, 5000, 5500, 6000, 6500), and HMII (8000, 9000, 10,000, 11,000, 12,000). Results: Combined data showed an average CO improvement of 22.3% and average PCW decrease of 89.7%. HMII and HMIII had similar improvements in CO, 44.4% and 43.8%, respectively; much greater than HVAD (17.2%). HMIII had the largest magnitude of decompression 141.5% versus 106.4% for HMII and 56.1% for HVAD. Suction events occurred at an overall rate of 9.4%, and were greatest in HVADs. Conclusion: We report the ramp study hemodynamics for three separate LVADs. Overall, our results suggest the HMIII is most responsive to changes in speed in terms of improvement of CO and decreased PCW. Addition of samples to this analysis may allow for algorithm development to provide clinical guidance regarding LVAD speed settings.
Mechanisms of melanocyte death in vitiligo
Authors: Jianru Chen, Shuli Li, Chunying Li
Journal: Medicinal Research Reviews (2020)

Abstract Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation. Genome‐wide associated studies have identified single‐nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background. Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, a minority of melanocyte demise, and melanocyte‐specific antigens exposure. Of note, the self‐responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo. The aberrantly heightened innate immunity, type‐1‐skewed T helper, and incompetent regulatory T cells tip the balance toward autoreaction and CD8 + cytotoxic T lymphocytes finally execute the killing of melanocytes, possibly alarmed by resident memory T cells. In addition to the well‐established apoptosis and necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, and necroptosis that are probably employed in melanocyte destruction. This review focuses on the various mechanisms of melanocytic death in vitiligo pathogenesis to demonstrate a panorama of that. We hope to provide new insights into vitiligo pathogenesis and treatment strategies by the review.
Analogies and differences between cirrhotic cardiomyopathy and hepatopulmonary syndrome
Authors: Enrico Maria Zardi, Chiara Giorgi, Aldo Dobrina, Elena Vecile, Domenico Maria Zardi
Journal: Medicinal Research Reviews (2020)

Abstract Cirrhotic cardiomyopathy and hepatopulmonary syndrome are two quite frequent clinical entities that may complicate the course of liver cirrhosis. The common pathophysiological origin and the same clinical presentation make them difficult to compare. Cirrhotic cardiomyopathy and hepatopulmonary syndrome may start with dyspnea and breathlessness but the former is characterized by a chronic cardiac dysfunction and the latter by a defect of oxygenation due to pulmonary shunts formation. The focus is to differentiate them as soon as possible since the treatment is different until the patient undergoes liver transplant that is the real unique cure for them.
Abstract 13101: Assessment of Left Ventricular Myocardial Fibrosis Using Two-dimensional and Three-dimensional Speckle Tracking Echocardiography in Patients With End-stage Heart Failure
Authors: Mingxing XIE, TiAN Fangyan, Li Yuman
Journal: Circulation (2020)

Background: Previous studies showed that 2-dimensional speckle-tracking echocardiography (2D-STE) correlates with the extent of left ventricular(LV)myocardial fibrosis (MF). However, the utility of 3D-STE in predicting LV MF remains unknown. We aimed to identify which LV strain assessed by 2D- and 3D-STE is the most reliable parameter to predict LV MF in patients with end-stage HF. Methods: 105 patients with end-stage HF undergoing heart transplantation were enrolled in our study. LV global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) were measured by 2D- and 3D-STE. LV ejection fraction (EF) was determined by 3D-STE.The degree of MF was quantified by using Masson trichrome stain in LV myocardial samples. The study population was divided into 3 groups according to the degree of MF on histology (mild, moderate, and severe MF). Results: Patients with severe MF had lower 2D-STE, 3D-STE, and LVEF compared with those with mild and moderate MF. LV MF strongly correlated with 3D-LVGLS (r =0.73; P &lt; 0.001), modestly with 3D-LVGRS (r =0.53; P&lt; 0.001), weakly with 2D-LVGLS (r =0.49, P&lt;0.001), 3D-LVGCS(r = 0.37, P &lt;0.01), and LVEF (r =-0.46, P&lt;0.001), but did not correlated with 2D-LVGCS and 2D-LVGRS. 3D-LVGLS correlated best with the degree of MF (r = 0.73 vs 0.37~0.53; P&lt;0.05) compared with other 2D- and 3D-STE, and LVEF. 3D-LVGLS had the highest accuracy for detecting severe MF (area under the curve 0.90 VS 0.62~0.80; P&lt; 0.05) compared with the 2D- and 3D-STE, and LVEF. Stepwise multivariate analysis showed that 3D-LVGLS (β=0.79, p &lt; 0.001) was the only independent predictor of the degree of MF. Conclusion: 3D-LVGLS may be an ideal surrogate marker for LV MF in patients with end-stage HF.
Abstract 14410: A Machine Learning Approach to Predicting Risk of Anthracycline Cardiotoxicity in Pediatric Cancer Survivors
Authors: Marie Chaix, Neha Parmar, Myriam Lafreniere-Roula, Oyediran Akinrinade, Roderick Yao, Anastasia Miron, Emily Lam, Guoliang Meng, Anne Christie, Ashok Kumar Manickaraj, Stacey Marjerrison, Rejane Dillenburg, Mylène Bassal, Jane Lougheed, Shayna Zelcer, Herschel Rosenberg, David Hodgson, leonard sender, Peter Liu, Paul F Kantor, Cedric Manlhiot, James Ellis, Luc Mertens, Paul C. Nathan, Seema Mital
Journal: Circulation (2020)

Background: Despite known clinical and genetic risk factors, predicting anthracycline cardiotoxicity remains challenging. Objective: To develop a risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. Methods: We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 cases with LV ejection fraction (LVEF) ≤55% despite low-dose doxorubicin (DOX) (≤250 mg/m2), and 106 controls with LVEF &gt;55% despite DOX &gt;250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between cases and controls. The top-ranked genes were functionally evaluated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. Results: Thirty-one genes were differentially enriched for variants between cases and controls (p&lt;0.001). Only 42.6% cases harbored a variant in these genes compared to 89.6% controls [Odds ratio (95% CI), 0.086 (0.043-0.171), p=3.98x10 -15 ] suggesting that absence of these variants may predispose to cardiotoxicity. A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical model. In vitro inhibition of gene-associated pathways ( PI3KR2, ZNF827 ) provided protection from cardiotoxicity in CMs. Conclusions: Our study identified variants that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and also provided new targets in autophagy genes for development of cardio-protective drugs.
Abstract 15091: Significant Reductions in Both Adjudicated and Investigator-Reported Ischemic Events in REDUCE-IT
Authors: Deepak L Bhatt, Robert Giugliano, Philippe G Steg, Michael Miller, Eliot A Brinton, Terry A Jacobson, Steven Ketchum, Rebecca Juliano, Lisa Jiao, Ralph Doyle, Craig Granowitz, Jean-Claude Tardif, Christie M Ballantyne, Duane S Pinto, Matthew J Budoff, C M Gibson
Journal: Circulation (2020)

Introduction: REDUCE-IT was an event-driven trial that randomized 8,179 statin-treated patients with controlled LDL-C and moderately elevated triglycerides to icosapent ethyl (IPE) 4g daily or placebo, with a median of 4.9 years of follow-up. There was a significant reduction in the prespecified adjudicated rates of the primary endpoint (cardiovascular [CV] death, non-fatal myocardial infarction [MI], non-fatal stroke, coronary revascularization, and unstable angina requiring hospitalization) and of the key secondary endpoint (CV death, MI, stroke), as well as in all the primary endpoint components. We sought to determine the effect of IPE on investigator-reported events. Methods: The Clinical Endpoint Committee (CEC) blindly adjudicated investigator-reported events according to a prespecified charter. Medical records and reports were also reviewed to assess for clinical events not reported by investigators. An endpoint management team compiled and electronically provided event packets to the CEC via an adjudication database. The CEC Chair provided final adjudication if the two primary adjudicators could not reach consensus. Results: IPE significantly reduced the rate of the primary endpoint (hazard ratio 0.74, p=0.0000000002) and the key secondary endpoint (hazard ratio 0.75, p=0.000007) as reported by the site investigators, with consistent benefits in each component of the primary endpoint (Table). There was a high degree of concordance between investigator-reported and adjudicated endpoints. Conclusions: Icosapent ethyl significantly reduced multiple types of ischemic events, both by independent, blinded adjudication as well as by investigator-reported assessment. These results underscore the robustness of the benefits of icosapent ethyl seen in REDUCE-IT.