tbuckley/cabot-search huggingface dataset:
Abstract 16801: Papillary Muscle Tip Approximation in Repair of Ischemic Mitral Regurgitation in a Chronic Swine Model
Authors: Kanika Kalra, Samantha Zhan Moodie, Dongyang Xu, Muralidhar Padala
Journal: Circulation (2020)

Introduction: Mitral valve (MV) repair with undersized annuloplasty (UMA) for ischemic mitral regurgitation (IMR) is being abandoned in favor of valve replacement (MVR) following CTSN trial results. However, in patients with durable repair, survival and left ventricular function (LVF) were significantly better than MVR. Achieving a durable repair with UMA is challenging as it draws leaflets away from papillary muscle (PM) insertions, causing unphysiological tethering and unicuspid configuration that fails (FigA-B). Hypothesis: Drawing PM tips together with an approximating stitch (PMT-A) can relieve leaflet tethering and enable better repair (FigC). A chronic swine model of IMR was used to compare effects of isolated PMT-A, UMA and PMT-A+UMA on MV and LV at 3 months post surgery. Methods: Twenty-five farm swine underwent catheterization and occlusion of left circumflex artery, resulting in postero-lateral myocardial infarction (MI). Two months after MI, IMR severity of &gt;2+ was confirmed on echo, and animals underwent one of the 3 repairs: PMT-A (n=6), UMA (n=8), PMT-A+UMA (n=11). Echo was performed postoperatively and repeated with MRI at 3 months (FigD). MV kinematics, coaptation geometry, and LVF were assessed. Results: IMR was eliminated after all repairs and did not recur through the study. Annulus continued to grow after PMT-A, but not in UMA or PMT-A+UMA group (FigE1) without increasing severity of IMR. Compared to prerepair, tenting depth was significantly reduced only in PMT-A and PMT-A+UMA groups (FigE2). Both leaflet excursion angles (diastolic minus systolic angles) increased after PMT-A, but not in other groups (FigE3-4). LV size and LVF was similar between groups, confirming that PMT-A did not perturb diastolic filling. Conclusions: In this model of IMR, PMT-A improved leaflet mobility, compared to isolated UMA or PMT-A+UMA. PMT-A is a simple technique that can potentially improve durability of MV repair by restoring valvular kinematics.
Abstract 16958: Comparison of Clinical and Hemodynamic Outcomes Between Redo Surgical Aortic Valve Replacement versus Transcatheter Valve in Valve in Patient With Failed Aortic Bioprostheses
Authors: Sebastien Hecht, Jeremy Bernard, Lionel Tastet, nancy cote, Erwan Salaun, Leonardo Guimaraes, Eric Dumont, Siamak Mohammadi, Josep Rodés-Cabau, Philippe Pibarot
Journal: Circulation (2020)

Introduction: Transcatheter valve-in-valve implantation (ViV) has emerged as an alternative to redo surgery (REDO) for the treatment of failed surgical aortic bioprostheses. However, there are few studies comparing clinical and hemodynamic outcomes between REDO and ViV in both the short- and long- term follow-up. Objective: The aim of this study was to compare hemodynamic and clinical outcomes between REDO and ViV. Methods: A total of 184 patients who underwent REDO or ViV at our institution between 2003 and 2017 were included in this study. Clinical and transthoracic echocardiography (TTE) data were collected for each patient. TTE was performed prior and after the reintervention and were retrospectively analyzed in an echocardiography core laboratory. An inverse propensity treatment weighting (IPTW) was used to compare outcomes between groups. Results: 104 patients underwent REDO and 80 underwent ViV. Prevalence of suboptimal valve hemodynamics (mean gradient ≥ 20 mmHg and/or ≥ moderate aortic regurgitation) following reintervention was higher in ViV group (29.8% vs. 61.3%, p&lt;0.001), the rate of novel permanent pacemaker tended to be higher with REDO (10.6% vs. 3.8%, p=0.08). During a median follow-up of 5.0 (3.7-7.5) years, 60 patients died. There was a trend toward higher rate of 30-day mortality in the REDO vs. ViV group (8.6% vs. 2.5%, OR [95% CI]: 3.70[0.77-17.6], p=0.10) and a trend toward lower risk of long-term mortality in REDO (HR [95% CI]: 0.61[0.33-1.14], p=0.12). In multivariate cox proportional analysis adjusted for age, sex, EuroSCORE 2, ViV was significantly associated with increased risk of long-term mortality (HR [95% CI]: 2.28[1.25-4.15], p=0.03). Results were confirmed in IPTW analyses (30-day mortality in REDO vs. ViV: 3.39[3.25-3.53], p&lt;0.001; long-term mortality: 0.70[0.69-0.71], p&lt;0.001). Conclusions: ViV was associated with lower risk of 30-day but higher risk of long-term mortality compared to REDO.
Abstract 15533: Long-term Prognostic Utility of Low-density Lipoprotein (ldl) Triglyceride in Real-world Patients With Coronary Artery Disease and Diabetes or Prediabetes
Authors: Jinglu Jin, Yuanlin Guo, Huiwen Zhang, Yexuan Cao, Huihui Liu, Yan Zhang, Naqiong Wu, Chenggang Zhu, Ying Gao, Ruixia Xu, Chuanjue Cui, Geng Liu, Jing Sun, Qian Dong, Jianjun Li
Journal: Circulation (2020)

Introduction: Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. Hypothesis: LDL-TG had impact on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. Methods: A total of 4381 patients with CAD were consecutively enrolled and categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. Plasma LDL-TG level was measured by an automated homogeneous assay. All subjects were followed up for the occurrence of MACEs. Results: During a median 5.1 (interquartile range 3.9 to 5.9) year follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride[hazard ratios (95% confidence intervals): 1.843(1.149-2.955), 1.828(1.165-2.867), 2.212(1.396-3.507), all p&lt;0.05]. Moreover, adding LDL-TG in the original model increased the C-statistic from 0.687 to 0.704 (ΔC-statistic=0.016, p=0.028) and from 0.734 to 0.749 (ΔC-statistic =0.014, p=0.002) in Pre-DM and DM respectively. Conclusions: In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.
Abstract 14757: Impact of Including Smoking Duration Data in Atherosclerotic Cardiovascular Disease Risk Estimation
Authors: Meredith S Duncan, Robert Greevy, Hilary A Tindle, Vasan S Ramachandran, Loren Lipworth, Melinda C Aldrich, Suman Kundu, Sean Coady, Donald M Lloyd-jones, Matthew S Freiberg
Journal: Circulation (2020)

Recent results from 5 decades of Framingham Heart Study (FHS) data suggest former heavy smokers (≥20 pack-years) have higher ASCVD risk than never smokers up to 16 years after quitting. However, the ASCVD Risk Estimator Plus, which is based on the 2013 Pooled Cohort Equations (PCE) does not account for pack-years smoked and considers former smokers to have ASCVD risk equal to never smokers after 5 years quit. Using data from 18,400 person-exams (exams 1-8) on 3,908 white FHS Offspring cohort participants, and follow-up through 12/31/2016, we built 5 sex-specific ASCVD risk prediction models to assess the added value of smoking history data. Models used pooled repeated Cox proportional hazards regression with 10-year follow-up blocks and age, SBP, antihypertensive medications, diabetes, total and HDL cholesterol, lipid-lowering medications, smoking status, pack-years smoked, and years since quitting smoking as predictors. We refit the 2013 PCE in the FHS person-exam sample (model 1) for fair model comparison. Subsequent models refit model 1 with continuous predictors on their natural scale (i.e., not logarithmically transformed) with polynomials to account for nonlinearity (model 2), and cumulatively adjusted for: former smoking (model 3), pack-years smoked (model 4), and years since quitting (model 5). We compared models by change in c-index, continuous net reclassification improvement (NRI(&gt;0)), and relative integrated discrimination improvement (rIDI).We included 1,895 men (358 events) and 2,013 women (197 events) with a mean age of 55 years and similar risk factor profiles. Over pooled examinations, ever smoking prevalence was high in men (77%) and women (78%), as was median pack-years smoked (M:39; W:32). Utilizing former smoking status, pack-years, and years quit (model 5) had significant but modest NRI(&gt;0) and rIDI values compared to the 2013 PCE on the natural scale in both sexes {Men: NRI(&gt;0)=0.23, rIDI=0.19; Women: NRI(&gt;0)=0.34, rIDI=0.11); the change in c-index (0.01) was significant only in men}. Pack-years smoked and years since quitting improved ASCVD risk prediction significantly but modestly in our sample. If validated in other race/ethnicity groups, these variables should be considered for improving ASCVD risk prediction tools.
Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer
Authors: Ying Liu, Zan Song, Yajie Liu, Xubin Ma, Wang Wang, Yu Ke, Yichao Xu, Dequan Yu, Hongmin Liu
Journal: Acta Pharmaceutica Sinica B (2021)

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan Rabdosia rubescens with anti-tumor activity, unclear anti-tumor mechanisms and limited water solubility hamper its clinical application. Here, we showed a2, a new JDA derivative, inhibited the growth of gastric cancer cells. Subsequently, we discovered for the first time that a2 induced ferroptosis. Importantly, compound a2 decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity of a2. Furthermore, we demonstrated that a2 caused ferrous iron accumulation through the autophagy pathway, prevention of which rescued a2 induced ferrous iron elevation and cell growth inhibition. Moreover, a2 exhibited more potent anti-cancer activity than 5-fluorouracil in gastric cancer cell line-derived xenograft mice models. Patient-derived tumor xenograft models from different patients displayed varied sensitivity to a2, and GPX4 downregulation indicated the sensitivity of tumors to a2. Finally, a2 exhibited well pharmacokinetic characteristics. Overall, our data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2, and a2 will hopefully serve as a promising compound for gastric cancer treatment.
Uncovering a novel role of PLCβ4 in selectively mediating TCR signaling in CD8+ but not CD4+ T cells
Authors: Miwa Sasai, Ji Su Ma, Masaaki Okamoto, Kohei Nishino, Hikaru Nagaoka, Eizo Takashima, Ariel Pradipta, Youngae Lee, Hidetaka Kosako, Pann-Ghill Suh, Masahiro Yamamoto
Journal: The Journal of Experimental Medicine (2021)

Because of their common signaling molecules, the main T cell receptor (TCR) signaling cascades in CD4+ and CD8+ T cells are considered qualitatively identical. Herein, we show that TCR signaling in CD8+ T cells is qualitatively different from that in CD4+ T cells, since CD8α ignites another cardinal signaling cascade involving phospholipase C β4 (PLCβ4). TCR-mediated responses were severely impaired in PLCβ4-deficient CD8+ T cells, whereas those in CD4+ T cells were intact. PLCβ4-deficient CD8+ T cells showed perturbed activation of peripheral TCR signaling pathways downstream of IP3 generation. Binding of PLCβ4 to the cytoplasmic tail of CD8α was important for CD8+ T cell activation. Furthermore, GNAQ interacted with PLCβ4, mediated double phosphorylation on threonine 886 and serine 890 positions of PLCβ4, and activated CD8+ T cells in a PLCβ4-dependent fashion. PLCβ4-deficient mice exhibited defective antiparasitic host defense and antitumor immune responses. Altogether, PLCβ4 differentiates TCR signaling in CD4+ and CD8+ T cells and selectively promotes CD8+ T cell–dependent adaptive immunity.
Abstract 16884: Evaluating the Effectiveness of Atrial Fibrillation Ablation Guided by Spatiotemporal Electrogram Dispersion
Authors: Brian Liu, Arismendy Nunez-Garcia, Cao Tran, Michael Wu
Journal: Circulation (2020)

Introduction: Catheter ablation of atrial fibrillation (AF) guided by spatiotemporal dispersion (SD) of electrograms has been proposed as an ablation strategy to treat patients with persistent AF. However, external validation of this technique is lacking. Here we report a single center experience using ablation by SD. Hypothesis: Targeting regions with SD is associated with a high rate of termination and favorable freedom from AF among patients with persistent AF. Methods: Patients with persistent AF who underwent SD from November 2018 to January 2020 were included in this study. All patients underwent pulmonary vein isolation (PVI) in addition to targeting areas of SD. Lesions on areas of electrogram dispersion were anchored to the PVI or to mitral or posterior wall lines where appropriate. EKG, Holter, event monitors or device interrogations were obtained at 3 and 6 months to assess for arrhythmia recurrence. Results: 44 patients met the inclusion criteria and were included in the study. The patients had a mean age of 69±8 years and were 68 % male. The prevalence of comorbidities was as follows: hypertension (89%), diabetes (21%), OSA (37%) and CAD (26%). Average CHADSVASC score was 2.9±1.4, LVEF was 53±11% and left atrium (LA) diameter was 5.2±1 cm. The recurrence rate of AF at 6 months was 14% whereas the recurrence of atrial tachycardia was 20%. Acute AF termination was observed in 73% of the patients. Termination to sinus occurred in 38% of the patients and the remaining terminated to atrial tachycardia which was subsequently ablated to sinus. The mean procedure duration was 240±90 minutes. Univariate analysis showed recurrence was associated with LA diameter (r=.52; p&lt;.001). No recurrences were observed among patients with a LA diameter &lt; 5 cm. Termination rates were higher among patients with LA diameter &lt; 5 cm when compared to LA diameter ≥ 5 cm. However, it did not reach statistical significance (80% vs. 60%; p=.21). Conclusions: The target of electrograms with SD during AF ablation added to PVI was associated with a high termination rate and a good freedom from AF recurrence at 6 months. The ideal candidate for this procedure may be those with LA diameter &lt; 5 cm among persistent AF. The long-term efficacy of this technique merits further studies in larger populations.
94MO Quality of life (QoL) with fulvestrant (FUL)/palbociclib (PAL) versus FUL/placebo (PBO) in postmenopausal women with hormone receptor (HR)+/HER2- endocrine sensitive advanced breast cancer (ABC): Results from GEICAM/2014-12 (FLIPPER) study
Authors: A. Tibau, M.T. Martinez, M. Ramos, L. De la Cruz-Merino, A. Santaballa, M. O' Connor, N. Martinez-Jañez, F. Moreno, I. Fernandez-Perez, J.A. Virizuela, J. Alarcón, J. de la Haba-Rodríguez, P. Sánchez-Rovira, C.R. Albacar, C. Bueno, C. Kelly, M. Casas, S. Bezares, L. Rosell, J. Albanell
Journal: Annals of Oncology (2021)
Expression of secreted frizzled related protein-4 (sFRP-4) and associated Wnt signalling in breast cancer.
Authors: Arun Dharmarajan, Sally McLaren, Elizabeth White, Nik Zeps
Journal: Cancer Research (2006)

5281  We examined the interplay between Wnt and Secreted Frizzled Related Protein-4 (sFRP4) in estradiol induced cell growth in breast cancer cells (MCF-7), and also determined the in vivo distribution of sFRP-4 in human breast cancer. MCF-7 Cells were treated with estradiol, sFRP-4 conditioned media and a combination of the two. Real-time RT-PCR and Western blot analysis were used to determine the expression of the sFRP-4 and its associated Wnt signalling molecules following treatment. Immunohistochemistry was performed to examine sFRP-4 expression patterns in human breast cancers. Estradiol treatment up-regulated the expression of the Wnt signalling genes Wnt-10b, beta-catenin and fz-4 (p
Abstract 15760: Survival Following Durable Ventricular Assist Device Implantation is Associated With Provider Teamwork: A Social Network Analysis
Authors: Russell J Funk, Michael D Fetters, Francis D Pagani, Hechuan Hou, Min Zhang, Guangyu Yang, Keith D Aaronson, John M Hollingsworth, P. P Chandanabhumma, Lourdes Cabrera, Donald S Likosky
Journal: Circulation (2020)

Introduction: Health systems with more robust provider teamwork have lower mortality rates for coronary artery bypass grafting. Patients undergoing durable ventricular assist device (VAD) therapy have complex comorbidities and develop adverse events requiring multidisciplinary provider teamwork. Hypothesis: Provider teamwork is associated with 180-day mortality following durable VAD implantation. Methods: Data (linked Medicare claims+INTERMACS) were analyzed from primary durable VADs implanted across 119 hospitals over a five-year period. Claims were used to identify provider interactions (cardiac surgeons, cardiologists, anesthesiologists, intensivists, nurse practitioners, physician assistants) for previously shared VAD patients during the 1-year period ending 6-months before each patient’s VAD implant admission. Provider teamwork was assessed at the hospital level using a clustering coefficient (range: 0-1; higher values = greater teamwork), an established and validated measure capturing the prevalence of tightly connected groups in a network. Provider teamwork level was associated with a patient’s 180-day mortality rate using multivariable regression adjusting for baseline characteristics reported to INTERMACS. Results: The study cohort included 2,807 VAD patients (mean age 63 years, 53% for destination therapy, 19% female, 74% white) with 10.8% identified as INTERMACS Profile 1. There were 468 deaths (16.7%) within 180 days of implantation. Provider teamwork (clustering coefficient) was inversely associated with 180-day mortality (beta=-0.79; 95%CI: -1.26, -0.11). A 1SD increase in provider teamwork was associated with a 13.4% decrease in the predicted probability of 180-day mortality, Figure. Conclusions: Social networks characterized by greater provider teamwork are important determinants of mortality following VAD implantation and may serve as targets for optimizing outcomes and greater adoption for this therapy.
Sample Sequence Analysis Uncovers Recurrent Horizontal Transfers of Transposable Elements among Grasses
Authors: Minkyu Park, Pascal-Antoine Christin, Jeffrey L Bennetzen
Journal: Molecular Biology and Evolution (2021)

Abstract Limited genome resources are a bottleneck in the study of horizontal transfer (HT) of DNA in plants. To solve this issue, we tested the usefulness of low-depth sequencing data generated from 19 previously uncharacterized panicoid grasses for HT investigation. We initially searched for horizontally transferred LTR-retrotransposons by comparing the 19 sample sequences to 115 angiosperm genome sequences. Frequent HTs of LTR-retrotransposons were identified solely between panicoids and rice (Oryza sativa). We consequently focused on additional Oryza species and conducted a nontargeted investigation of HT involving the panicoid genus Echinochloa, which showed the most HTs in the first set of analyses. The comparison of nine Echinochloa samples and ten Oryza species identified recurrent HTs of diverse transposable element (TE) types at different points in Oryza history, but no confirmed cases of HT for sequences other than TEs. One case of HT was observed from one Echinochloa species into one Oryza species with overlapping geographic distributions. Variation among species and data sets highlights difficulties in identifying all HT, but our investigations showed that sample sequence analyses can reveal the importance of HT for the diversification of the TE repertoire of plants.
Peroral cholangioscopy via an endoscopic ultrasound-guided hepaticojejunostomy route for distal bile duct cancer with Roux-en-Y reconstruction
Authors: Haruka Okano, Shinsuke Koshita, Yoshihide Kanno, Takahisa Ogawa, Hiroaki Kusunose, Toshitaka Sakai, Kei Ito
Journal: Endoscopy (2021)

A 70-year-old man who had undergone total gastrectomy with Roux-en-Y reconstruction was referred to our hospital with liver dysfunction. Imaging studies revealed a distal biliary stricture with dilated intrahepatic bile ducts ([Fig. 1]), indicating possible distal cholangiocarcinoma. In order to perform peroral cholangioscopy to determine malignancy and extent of superficial spread, we planned to construct an endoscopic ultrasound-guided hepaticojejunostomy (EUS-HJS) route.
Favorable Impact of Allogeneic Stem Cell Transplantation in Patients with Therapy-Related Myelodysplasia Regardless of TP53 Mutational Status
Authors: Ryotaro Nakamura, Ibrahim Aldoss, Anh Pham, Sierra Min Li, Ketevan Gendzekhadze, Michelle Afkhami, Milhan Telatar, Hao Hong, Abbas Padeganeh, Victoria Bedell, Thai Cao, Samer Khaled, Monzr M. Al Malki, Amandeep Salhotra, Haris Ali, Ahmed Aribi, Joycelynne M. Palmer, Patricia Aoun, Ricardo Spielberger, Anthony S. Stein, David S. Snyder, Margaret R. O'Donnell, Joyce Murata-Collins, David Senitzer, Dennis D. Weisenburger, Stephen J. Forman, Vinod Pullarkat, Guido Marcucci, Raju Pillai
Journal: Blood (2017)
Abstract 12944: Geographical Variations in Cardiovascular Health in China: A Nationwide Population-based Survey of 74,771 Adults
Authors: Mei Zhang, Yu Shi, Oumin Shi, Zhenping Zhao, Xiao Zhang, Chun Li, Zhengjing Huang, Limin Wang, Yichong Li, Xinhua Li
Journal: Circulation (2020)

Background: Cardiovascular disease is the leading cause of death in China. Objectives: We aimed to evaluate the levels of cardiovascular health among Chinese adults and to understand the geographic patterns based on a nationally and provincially representative survey. Methods: In 2015, a total of 74,771 respondents aged ≥ 20 years with no history of cardiovascular disease were randomly sampled from 298 counties/districts of 31 provinces in mainland China and were interviewed. Seven metrics, including smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting glucose, were determined. Ideal cardiovascular health was defined as the simultaneous presence of all metrics at the ideal level. A score ranging from 0 to 14 was calculated as the sum of all seven metrics for each province. Scores for four health behaviors and four health factors were also calculated. Results: The age-adjusted prevalence of ideal cardiovascular health was only 1.13% among Chinese adults above 20 years old in 2015 (0.50% among men and 1.77% among women; 1.63% among urban residents and 0.68% among rural residents). The age-adjusted prevalence varied greatly across provinces, ranging from 0.05% in Qinghai to 2.97% in Heilongjiang. Ideal diet (7.4%) was the least common among seven cardiovascular health metrics and ideal blood pressure (32.2%) was the second least one. We also saw significant heterogeneity among provinces in age-adjusted cardiovascular health score, health behavior score, and health factors score. In all provinces, women had higher scores than men for cardiovascular health, health behaviors and health factors. Differences in cardiovascular health and health behavior scores between urban and rural areas were associated with levels of socio-economic development. Conclusions: Strategies for addressing poor cardiovascular health require geographic targeting and localized consideration.