tbuckley/cabot-search huggingface dataset:
Abstract 15636: Percutaneous Intervention (PCI) Improves Outcomes in Out of Hospital Cardiac Arrest (OHCA) Patients Receiving Coronary Angiography
Authors: Michael G Scutella, Francis Pike, James Fitzgibbon, Lindsey Kowalski, Clifton Callaway, Jon Rittenberger, Josh Reynolds, Cameron Dezfulian
Journal: Circulation (2015)

Introduction: Acute coronary occlusion is common after OHCA. PCI may reduce subsequent cardiac death and improve cerebral perfusion thus improving outcomes. Recent studies suggest these benefits may be attenuated in patients with more severe brain injury. Hypothesis: PCI will more strongly associate with improved outcome than just coronary angiography (CA) after OHCA with loss of association in those with greatest brain injury. Methods: In subjects with OHCA with unclear arrest etiology, we examined the association between CA (with or without PCI) and PCI with 1) hospital survival; 2) discharge cerebral performance category (CPC); 3) discharge modified Rankin scale (mRS); 4) discharge destination. All outcomes were dichotomized and associations adjusted for propensity to perform 1) CA and 2) PCI based on associated pre-CA factors. This analysis was repeated after stratifying the cohort based on early brain injury as measured by Pittsburgh Cardiac Arrest Category (PCAC) dichotomized as PCAC 4 (severe injury) and PCAC 1-3 (mild to moderate). Results: Early (&lt;24 h) CA was performed in 284/600 (47%) OHCA and PCI in 151/284 CA (53%). In unadjusted analysis, performance of both CA and PCI was strongly associated with improved outcomes (all p &lt; 0.0001). Adjustment based on propensity to perform CA reduced the average treatment effect (ATE) to a non-significant 7-8% trend whereas adjustment based on propensity to perform PCI demonstrated a highly significant ATE of ~14-15% (p &lt; 0.01) whereas those with less severe brain injury had trends to benefit with CA, which became significant (most p&lt;0.01) with PCI. Conclusion: Early selection for CA of OHCA survivors likely to require PCI without severe brain injury is associated with substantial outcome benefits. The observed treatment effect is significantly reduced in patients with early signs of significant brain injury.
A prospective, multicenter phase II trial of low-dose erlotinib monotherapy for patients with previously treated non-small cell lung cancer (NSCLC) with activating mutation of epidermal growth factor receptor (EGFR): Thoracic Oncology Research Group (TORG) 0911.
Authors: Yoshiro Nakahara, Yukio Hosomi, Kazuhiko Yamada, Hiroaki Okamoto, Terufumi Kato, Yuko Komase, Masanori Nishikawa, Satoshi Morita, Hideo Kunitoh, Koshiro Watanabe
Journal: Journal of Clinical Oncology (2014)

8080 Background: Erlotinib and gefitinib have been shown to have similar activity for EGFR mutation-positive (EGFRm+) NSCLC. Since the steady-state plasma trough concentration of erlotinib is approximately 3.5 times higher than that of gefitinib when administered at the respective approved dose, treatment with low-dose erlotinib may be as effective as full-dose therapy, with less toxicity and cost. Methods: Eligible patients had advanced EGFRm+ NSCLC with 1 to 3 prior chemotherapy treatments. Erlotinib with the initial daily dosage of 50 mg was administered. Dose was escalated to 150 mg in case of not achieving CR or PR by RECIST criteria at the evaluation after the first 4 weeks of treatment. Erlotinib was continued until disease progression or unacceptable toxicities. The primary endpoint was independent committee-determined objective response rate (ORR) to the low-dose erlotinib, with target ORR of 70% and threshold of 50%. The sample size was calculated to be 40, and the primary endpoint was met if 26 or more patients responded. Results: Thirty-four patients were enrolled between Apr. 2010 and Nov. 2012. Males/females 20/14; median age 67 (range 38-81); PS 0/1 16/18; Ad/Sq 33/1. One patient was excluded from evaluation due to absence of active tumor. The study was closed early according to the protocol definition when 15 of 33 evaluable patients failed to achieve CR/PR, making it impossible to meet the primary endpoint. ORR was 54.5% (95% C.I.: 36.4% to 71.9%), with disease control rate of 84.8%. Median progression free survival and overall survival were 9.5 months and 28.5 months, respectively. Grade 3 toxicities were 2 cases with transient neutropenia, and 1 with reversible AST/ALT elevation. No grade 4 toxicity or treatment-related death was observed. Conclusions: This trial is the first prospective study evaluating low-dose erlotinib. Although it appeared to have a certain efficacy, the primary endpoint was not met. Because of its low toxicity, it may be worth further evaluation in elderly and/or frail patients. Trial registry UMIN #000003313.
Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells
Authors: Fella Tamzalit, Mitchell S. Wang, Weiyang Jin, Maria Tello-Lafoz, Vitaly Boyko, John M. Heddleston, Charles T. Black, Lance C. Kam, Morgan Huse
Journal: Science Immunology (2019)

Cytotoxic T lymphocytes (CTLs) kill by forming immunological synapses with target cells and secreting toxic proteases and the pore-forming protein perforin into the intercellular space. Immunological synapses are highly dynamic structures that boost perforin activity by applying mechanical force against the target cell. Here, we used high-resolution imaging and microfabrication to investigate how CTLs exert synaptic forces and coordinate their mechanical output with perforin secretion. Using micropatterned stimulatory substrates that enable synapse growth in three dimensions, we found that perforin release occurs at the base of actin-rich protrusions that extend from central and intermediate locations within the synapse. These protrusions, which depended on the cytoskeletal regulator WASP and the Arp2/3 actin nucleation complex, were required for synaptic force exertion and efficient killing. They also mediated physical deformation of the target cell surface during CTL-target cell interactions. Our results reveal the mechanical basis of cellular cytotoxicity and highlight the functional importance of dynamic, three-dimensional architecture in immune cell-cell interfaces.
Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation
Authors: Andrea Schlegel, Xavier Muller, Marit Kalisvaart, Beat Muellhaupt, M. Thamara P.R. Perera, John R. Isaac, Pierre-Alain Clavien, Paolo Muiesan, Philipp Dutkowski
Journal: Journal of Hepatology (2018)
Abstract 12205: Prognosis After Endovascular Treatment in Claudicant Patients With Iliofemoral Artery Disease
Authors: Takashi Miura, Yoshimitsu Soga, Yusuke Miyashita, Osamu Iida, Souichirou Ebisawa, Takeshi Tomita, Jun Koyama, Uichi Ikeda
Journal: Circulation (2013)

Background: The natural history of patients with intermittent claudication (IC) has been reported. However, little is known about prognosis of claudicant patients after endvascular therapy (EVT). Methods: This study was performed as a large-scale multicenter, retrospective registry. A total of 2,930 consecutive patients (mean age, 71.5±8.9 years, 78.7% male) with IC treated by EVT for a de novo ilio-femoral lesion were enrolled. The primary outcome measure was overall survival, and the secondary outcome measure were freedom from major adverse cardiovascular events (MACE; all-cause death, myocardial infarction and stroke), and major adverse cardiovascular and limb events (MACLE; any repeat revascularization for limb and leg amputation in addition to MACE). Results: The overall survival rate was 97.2%, 90.8%, and 83.4% at 1, 3 and 5 years. The cause of death was cardiovascular in 42.8%. Freedom from MACE (MACLE) was 96.7% (84.5%), 88.6% (68.1%), and 77.3% (58.7%) at 1, 3and 5 years. Elderly age, Dialysis, L...
P3.11-16 Comparative Analysis of Health-Care Resources and Economic Costs of Lung Cancer Patients Treated Medically or Surgically in Catalunya
Authors: A. Guirao, L. Molins, R. Guzman, M. Cleries, E. Vela, D. Magen, D. Sanchez, M. Boada, J.A. Espinas, J.M. Borras, J.M. Argimon, A. Agusti
Journal: Journal of Thoracic Oncology (2018)
Cholesterol Homeostatic Regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome Activation and Cholesterol Biosynthetic Signaling in Macrophages
Authors: Chuansheng Guo, Zhexu Chi, Danlu Jiang, Ting Xu, Weiwei Yu, Zhen Wang, Sheng Chen, Li Zhang, Qianyun Liu, Xingchen Guo, Xue Zhang, Wenxin Li, Linrong Lu, Yingliang Wu, Bao-Liang Song, Di Wang
Journal: Immunity (2018)
A hybrid of mPEG-b-PCL and G1-PEA dendrimer for enhancing delivery of antibiotics
Authors: Calvin A. Omolo, Rahul S. Kalhapure, Nikhil Agrawal, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender
Journal: Journal of Controlled Release (2018)
Abstract 15123: QSOX1 Function During the Adaptation of the Heart to Angiotensin2 Induced Hypertension
Authors: Anaïs Caillard, Mourad jérome, Sadoune Malha, Zhenlin Li, Alexandre Mebazaa, Nicolas Vodovar, Jane-Lise Samuel
Journal: Circulation (2016)

Introduction: Preliminary results from our group suggested a protective role of cardiac QSOX1 induction during acute cardiac stress. QSOX1, a sulfhydryl oxidase, is detected in the media of large a...
Publisher Correction: Ancient hybridization and strong adaptation to viruses across African vervet monkey populations
Authors: Hannes Svardal, Anna J Jasinska, Cristian Apetrei, Giovanni Coppola, Yu Huang, Christopher A Schmitt, Beatrice Jacquelin, Vasily Ramensky, Michaela Müller-Trutwin, Martin Antonio, George Weinstock, J Paul Grobler, Ken Dewar, Richard K Wilson, Trudy R Turner, Wesley C Warren, Nelson B Freimer, Magnus Nordborg
Journal: Nature Genetics (2018)
Abstract 15702: Role of the Drp-1 Receptors Mid49 and Mid51 in Regulating Fission and Cell Proliferation in Pulmonary Arterial Hypertension
Authors: Asish Dasgupta, Kuang-Hueih Chen, Stephen L Archer
Journal: Circulation (2015)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction that is partially due to hyperproliferation of apoptosis-resistant pulmonary arterial smooth muscle cells (PASMCs). This “neoplastic phenotype” of PAH PASMCs is due, in part, to excessive mitochondrial fission caused by activation of dynamin related protein-1 (Drp-1). A pool of Drp-1 exists in the cytosol. Upon activation it is recruited to the mitochondrial outer membrane by Drp-1 receptor proteins, such as MiD49 and MiD51. The biological functions of these newly discovered Drp-1 receptors in diseases, including PAH, is poorly understood. We hypothesize that in PAH increased expression of MiD49 and MiD51 contribute to increased mitochondrial fission and excessive cell proliferation. Methods: Immunoblots quantified MiD49 and MiD51 expression in human control (n=3) and PAH PASMCs (n=6). The effects of silencing expression of MiD49 and MiD51, using small interfering RNA (siRNA), on cell proliferation, cell cycle progression, and rates of apoptosis were assessed using flow cytometry, and a cell death ELISA assay, respectively. Mitochondrial network structure was assessed using confocal imaging of cells stained with tetramethylrhodamine (TMRM). Results: MiD49 and MiD51 expression was increased in human PAH PASMCs vs control PASMCs (P&lt;0.05). There was marked inter-individual variation in expression profile with some patients expressing excess MiD49 and others excess MiD51. PAH PASMCs had fragmented mitochondrial networks and both siMiD49 and siMiD51 increased mitochondrial fusion. Either siMiD49 or siMiD51 completely blocked the proliferation of PAH PASMCs by arresting the cells in the G1/G0 phase. In contrast, only siMiD51 induced apoptosis in PAH PASMCs. Conclusion: MiD49 and MiD51 are critically involved in mitochondrial fission and cell proliferation in human PAH PASMCs. Inhibition of MiD49 or MiD51 enhances mitochondrial fusion and reduces cell proliferation, while silencing MiD51 also induces apoptosis. These newly discovered Drp-1 binding partners are promising therapeutic targets in PAH.
バーチャルヒストロジーIVUS(VH-IVUS)を用いたACS患者のためのアディポネクチンと冠状動脈プラーク構成物との間の関連の調査
Authors: Ishimori Hiroshi, Muramatsu Toshiya, Tsukahara Reiko, Kabuki Takayuki, Takamura Kazuhisa
Journal: Circulation (2007)
P3.09-19 Matched Thai Lung Cancer Patients Tissue and cfDNA Molecular Profile by NGS
Authors: N. Trachu, S. Detarkom, P. Incharoen, K. Kamprerasart, N. Iemwimangsa, L. Arsa, W. Chantratita, D. Muntham, E. Sirachainan, T. Reungwetwattana
Journal: Journal of Thoracic Oncology (2018)
Cholesteryl Ester Transfer Protein Influences High-Density Lipoprotein Levels and Survival in Sepsis
Authors: Mark Trinder, Kelly R. Genga, HyeJin Julia Kong, Lisanne L. Blauw, Cody Lo, Xuan Li, Mihai Cirstea, Yanan Wang, Patrick C. N. Rensen, James A. Russell, Keith R. Walley, John H. Boyd, Liam R. Brunham
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

High-density lipoprotein (HDL) cholesterol (HDL-C) levels decline during sepsis, and lower levels are associated with worse survival. However, the genetic mechanisms underlying changes in HDL-C during sepsis, and whether the relationship with survival is causative, are largely unknown.We hypothesized that variation in genes involved in HDL metabolism would contribute to changes in HDL-C levels and clinical outcomes during sepsis.We performed targeted resequencing of HDL-related genes in 200 patients admitted to an emergency department with sepsis (Early Infection cohort). We examined the association of genetic variants with HDL-C levels, 28-day survival, 90-day survival, organ dysfunction, and need for vasopressor or ventilatory support. Candidate variants were further assessed in the VASST (Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock Trial) cohort (n = 632) and St. Paul's Hospital Intensive Care Unit 2 (SPHICU2) cohort (n = 203).We identified a rare missense variant in CETP (cholesteryl ester transfer protein gene; rs1800777-A) that was associated with significant reductions in HDL-C levels during sepsis. Carriers of the A allele (n = 10) had decreased survival, more organ failure, and greater need for organ support compared with noncarriers. We replicated this finding in the VASST and SPHICU2 cohorts, in which carriers of rs1800777-A (n = 35 and n = 12, respectively) had significantly reduced 28-day survival. Mendelian randomization was consistent with genetically reduced HDL levels being a causal factor for decreased sepsis survival.Our results identify CETP as a critical regulator of HDL levels and clinical outcomes during sepsis. These data point toward a critical role for HDL in sepsis.
Abstract 12691: The Combination of Depression and Diabetes is Associated With Short-Term Risk of Death and Myocardial Infarction Among Patients Undergoing Angiography for Acute Coronary Syndrome
Authors: Heidi T May, Stacey Knight, Jeffrey L Anderson, Benjamin D Horne, Viet T Le, Tami L Bair, Joseph B Muhlestein
Journal: Circulation (2014)

Background: Depression and diabetes have been shown to be associated with adverse cardiovascular (CV) events. However, whether there is an increased risk when both conditions are present is unknown. Methods: Patients of the Intermountain Heart Collaborative Study were studied if they underwent angiography for acute coronary syndrome (ACS) and had no prior history of CV disease (no CAD [coronary artery disease], MI [myocardial infarction], stroke, or heart failure). Patients were stratified based on their diabetes and depression status: none, diabetes only, depression only, and diabetes and depression. Multivariable Cox hazard regression was utilized to evaluate the association of diabetes/depression groups to death and MI at 30 days, 6 months, and 1 year. Results: A total of 4,321 (62.7% male; 61.3±12.9 years) patients were studied. The distribution of patients within each diabetes/depression category was: no depression or diabetes: 74.9% (3,236), diabetes only: 18.5% (800), depression only: 4.4% (192), diabetes and depression: 2.2% (93). A total of 46.2% presented with an MI and 61.4% were diagnosed with CAD. Those with both a diabetes and depression diagnosis were at greater risk of short-term death and, in particular, MI (Table). Conclusion: Among those without a history of CV disease undergoing angiography for ACS, the presence of both diabetes and depression indicated a higher risk of short-term death and, in particular, incident MI, than either one alone or neither diagnosis. Such patients may need greater care and evaluation following angiography for ACS in an effort to reduce short-term morbidity and mortality.
Phase II study of cemiplimab, a human monoclonal anti-PD-1, in patients with advanced basal cell carcinoma (BCC) who experienced progression of disease on, or were intolerant of prior hedgehog pathway inhibitor (HHI) therapy
Authors: K.D. Lewis, M.G. Fury, E. Stankevich, M. Mathias, K.K. Mohan, S. Li, K. Nunnink, C. Perry, A. Narwal
Journal: Annals of Oncology (2018)
Abstract 16: Economic Cost of Type 2 Diabetes Attributable to Physical Inactivity in the United States in 2012
Authors: Priyank P Shah, Fayez Shamoon, Mahesh Bikkina, Harold Kohl
Journal: Circulation (2016)

Objective: Type 2 diabetes has grown to epidemic proportions in the U.S. and physical activity levels in the population continues to remain low, although it is a major primary preventive strategy for diabetes. The objectives of this study were to estimate the direct medical costs of type 2 diabetes attributable to not meeting physical activity Guidelines and to physical inactivity in the U.S. in 2012. Methods: This was a cross sectional study that used physical activity prevalence data from the 2012 Behavioral Risk Factor Surveillance System (BRFSS). Estimates of relative risk of type 2 diabetes for subjects not engaging in any leisure time physical activity and those not meeting physical activity guidelines were obtained for multiple studies published in the literature. Using the prevalence of not meeting physical activity guidelines, physical inactivity and the respective relative risks, the population attributable risk percentage (PAR%) for type 2 diabetes was estimated by Levin’s formula. These data were combined with the prevalence and cost data of type 2 diabetes (in 2012) to estimate the cost of type 2 diabetes attributable to not meeting physical activity Guidelines, and to physical inactivity in 2012. Sensitivity analyses were done for i) varying the prevalence of not meeting physical activity guidelines from 30-70%, and ii) varying the average annual cost of type 2 diabetes from $4394 (for person less than 45 years of age) to $11825 (for person greater than 65 years of age). Results: The prevalence of U.S. population meeting physical activity guidelines and engaging in no leisure time activity was 50% and 30% respectively in 2012. The average annual cost attributable to type 2 diabetes in the US, was $7888 per person. The cost of type 2 diabetes in the U.S. in 2012, attributable to not meeting physical activity guidelines was estimated to be $18.6 billion, and that attributable to physical inactivity was estimated to be $5.9 billion. Based on sensitivity analyses, these estimates ranged from $10.36 billion to $27.9 billion for not meeting physical activity guidelines and $3.3 billion to $8.87 billion for physical inactivity in the year 2012. Conclusions: This study shows that billions of dollars could be saved annually just in terms of type 2 diabetes cost in the U.S., if the entire adult population was active enough to meet physical activity guidelines. Physical activity promotion, particularly at the environmental and policy level should be a priority in the population.
Abstract B35: Reactivation of p53 signaling in hepatoblastoma with a stapled peptide dual inhibitor of MDM2 and MDM4
Authors: Sarah E. Woodfield, Roma H. Patel, Aryana M. Ibarra, Zhenghu Chen, Sanjeev A. Vasudevan
Journal: Cancer Research (2018)

Abstract Introduction: Hepatoblastoma is the most common pediatric liver malignancy. Despite aggressive therapeutic regimens, long-term survival of patients with high-risk, metastatic disease is less than 50%. Most cases of hepatoblastoma do not carry mutations in the TP53 tumor suppressor gene; therefore, we hypothesized that targeting the two major regulators of p53, MDM2 and MDM4, with the stapled peptide dual inhibitor, ATSP-7041, to reactivate p53 signaling would be an effective therapeutic strategy for hepatoblastoma. Methods: Levels of MDM2 and MDM4 gene expression were examined in HB cell lines and in a cohort of 18 primary HB patient samples from stage III (n=12) and IV (n=6) patients in comparison to expression in four adjacent uninvolved liver samples with qPCR experiments. The effects of the dual MDM2/MDM4 inhibitor ATSP-7041 (Aileron Therapeutics) on the same cell lines were analyzed with MTT assays for cytotoxicity and qPCR experiments to look at changes in mRNA expression of p53 targets Bax, Puma, CDKN1A, and MDM2. Results: In 16 of 18 samples, MDM4 expression was higher than average in the uninvolved liver samples; in five samples expression was at least 5-fold higher and in four samples expression was at least 10-fold higher. Of note, all four samples with at least 10-fold higher expression were from stage IV patients. In comparison, MDM2 expression was only elevated in one of the 18 patient samples. All three hepatoblastoma cell lines showed expression of both MDM2 and MDM4. Treatment with ATSP-7041 showed cytotoxic (5.7-8.6 μM) effects in all cell lines tested. All cell lines also showed upregulation of p53 targets Bax (1.4- to 2.4-fold), Puma (2.4- to 3.2-fold), CDKN1A (2.4- to 7.2-fold), and MDM2 (6.1- to 8.3-fold) with treatment. Conclusions: Dual inhibition of MDM2 and MDM4 shows efficacy in preclinical models of hepatoblastoma by upregulating p53 tumor-suppressor signaling in TP53 wild-type cells and is a promising therapeutic strategy for high-risk patients with wild-type TP53. Citation Format: Sarah E. Woodfield, Roma H. Patel, Aryana M. Ibarra, Zhenghu Chen, Sanjeev A. Vasudevan. Reactivation of p53 signaling in hepatoblastoma with a stapled peptide dual inhibitor of MDM2 and MDM4 [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B35.
GW29-e1692 Exosomes Derived from Mesenchymal Stromal Cells Attenuate Myocardial Ischemia-Reperfusion through Modifying Macrophage Polarization
Authors: Jinxuan Zhao, Jun Xie, Xuan Sun, Xueling Li, Fu Chen, Biao Xu
Journal: Journal of the American College of Cardiology (2018)