tbuckley/cabot-search huggingface dataset:
Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses
Authors: Jeng-Chang Chen, Cheng-Chi Chan, Chia-Jen Wu, Liang-Shiou Ou, Hsiu-Yueh Yu, Hsueh-Ling Chang, Li-Yun Tseng, Ming-Ling Kuo
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system.Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses.In utero injection of adjuvant-free ovalbumin (OVA) was conducted in Gestational Day 14 FVB/N mouse fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and then they were examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology. Fluorescent conjugates of OVA were used for further studies of mechanisms.This presumed tolerogenic action turned out to be a sensitization process with the development of anaphylaxis or heightened recall, T-helper cell type 2-skewed responses to postnatal encounter with OVA. Further postnatal aerosolized OVA stress triggered allergic lungs with functional and structural alterations of airways. The unintended consequence resulted from macrophage-like fetal phagocytes that took up OVA and differentiated toward dendritic cells. These fetal dendritic cell progenitors attenuated proteolysis of endocytosed OVA for delayed presentation in postnatal life. This specialty of fetal phagocytes effectively retains the memory of antigens internalized early before full development of the immune system, leading to an event of in utero sensitization.Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases.
GW27-e0225 The Effects of Atorvastatin on Myocardial Ultrastructure and RhoA Activity in Rats With Coronary Artery Spasm
Authors: Su Linbo, Kaijun Wang, Lijun Wang, Fengqiang Dang, Yifan Zhang, Lianna Xie
Journal: Journal of the American College of Cardiology (2016)
TCT-446 Outcomes Among Patients Enrolled Versus Not Enrolled In Interventional Cardiovascular Clinical Trials: Insights From A Single-center Analysis
Authors: Omar A. Meelu, Samantha Sartori, Kleanthis Theodoropoulos, Swathi Roy, Roja Thapi, Usman Baber, Pedro R. Moreno, Prakash Krishnan, George Dangas, Annapoorna Kini, Samin K. Sharma, Roxana Mehran
Journal: Journal of the American College of Cardiology (2015)
Targeted Gene Correction of Glanzmann Thrombasthenia Induced Pluripotent Stem Cells Restores Surface Expression and Fibrinogen Binding of Integrin αIIbβ3,
Authors: Spencer Sullivan, Jason A. Mills, Li Zhai, Prasuna Paluru, Guohua Zhao, Lin Lu, Michele Lambert, Deborah L. French, Mortimer Poncz, Paul Gadue
Journal: Blood (2011)
TCT-404 Risk of Stroke of Percutaneous Coronary Intervention in Patients with Stable Coronary Artery Disease: a Systematic Review and Meta-analysis of Contemporary Randomized Clinical Trials
Authors: Nevio Taglieri, Maria Letizia Bacchi Reggiani, Gabriele Ghetti, Francesco Saia, Pamela Gallo, Carolina Moretti, Gianni Dall'Ara, Tullio Palmerini, Cinzia Marrozzini, Antonio Marzocchi, Claudio Rapezzi
Journal: Journal of the American College of Cardiology (2015)
GW27-e1181 Delta cardiac troponin levels for 60-day risk of adverse events in patients with non-st elevation acute coronary syndrome
Authors: Jiang Peng, Ye Zi, Huang Ying-xiong, Xiong Yan, Cai Rui-bing, Xiao Xiao-yong, Huang Zhen-hua, Zhan Hong
Journal: Journal of the American College of Cardiology (2016)
TCT-495 Drug-Eluting Stent and Drug-Coated Balloon for Coronary In-Stent Restenosis: A Pair-Wise Meta-Analysis of Randomized Trials Implemented with Trial Sequential Analysis
Authors: Daniele Giacoppo, Giuseppe Gargiulo, Patrizia Aruta, Piera Capranzano, Corrado Tamburino, Davide Capodanno
Journal: Journal of the American College of Cardiology (2015)
Genomic Analysis of Endothelial Progenitor Cells In Multiple Myeloma Reveals Aberrant Gene Pathways Common to Tumor Cells
Authors: Marc J Braunstein, Sadeaqua Scott, Eric LP Smith, Danielle F Joseph, Jason Gonsky, Ruben Carrasco, Kumar Sukhdeo, Alexei Protopopov, Kenneth C Anderson, Olcay Batuman
Journal: Blood (2010)
Incidence, Risk Factors and Prognosis of Transformation in Follicular Lymphoma: a Multicentre Retrospective Analysis of 1763 Patients from the Geltamo Spanish Lymphoma Cooperative Group
Authors: Sara Alonso*, Miguel Alcoceba*, Laura Magnano, Marcio Andrade, María García-Álvarez, Santiago Mercadal, Guillermo Rodríguez, Olga Garcia, Juan-Manuel Sancho, Antonio Salar, Francesc Pasarolls, Maria Jose Terol, Carlos Grande, Sonia González de Villambrosia, Raul Cordoba, Silvana Novelli, Lourdes López, Carlos Montalbán, Erik de Cabo, Maria Stefania Infante, Emilia Pardal, Javier Lopez-Jimenez, Beatriz Antelo, Reyes Arranz, Marcos González, Alejandro Martín, Armando López-Guillermo‡, Maria Dolores Caballero‡
Journal: Blood (2015)
GW27-e0523 The effect of Ginsenoside Rb1 on the expression of SOD and MDA in HUVECs injured by homocysteine
Authors: Liu Dinghui, Shujie Yu, Bin Zhou, Lin Wu, Min Wang, Yong Liu, Baoshun Hao, Zhenda Zheng, Xiaoxian Qian
Journal: Journal of the American College of Cardiology (2016)
DJ-1/PARK7 Impairs Bacterial Clearance in Sepsis
Authors: Hajera Amatullah, Yuexin Shan, Brittany L. Beauchamp, Patricia L. Gali, Sahil Gupta, Tatiana Maron-Gutierrez, Edwin R. Speck, Alison E. Fox-Robichaud, Jennifer L. Y. Tsang, Shirley H. J. Mei, Tak W. Mak, Patricia R. M. Rocco, John W. Semple, Haibo Zhang, Pingzhao Hu, John C. Marshall, Duncan J. Stewart, Mary-Ellen Harper, Patricia C. Liaw, W. Conrad Liles, Claudia C. dos Santos
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Effective and rapid bacterial clearance is a fundamental determinant of outcomes in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger.Because cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role of DJ-1 in bacterial sepsis.We used cell and murine models with gain- and loss-of-function experiments, plasma, and cells from patients with sepsis.Stimulation of bone marrow-derived macrophages (BMMs) with endotoxin resulted in increased DJ-1 mRNA and protein expression. Cellular and mitochondrial ROS was increased in DJ-1-deficient (-/-) BMMs compared with wild-type. In a clinically relevant model of polymicrobial sepsis (cecal ligation and puncture), DJ-1-/- mice had improved survival and bacterial clearance. DJ-1-/- macrophages exhibited enhanced phagocytosis and bactericidal activity in vitro, and adoptive transfer of DJ-1-/- bone marrow-derived mononuclear cells rescued wild-type mice from cecal ligation and puncture-induced mortality. In stimulated BMMs, DJ-1 inhibited ROS production by binding to p47phox, a critical component of the NADPH oxidase complex, disrupting the complex and facilitating Nox2 (gp91phox) ubiquitination and degradation. Knocking down DJ-1 (siRNA) in THP-1 (human monocytic cell line) and polymorphonuclear cells from patients with sepsis enhanced bacterial killing and respiratory burst. DJ-1 protein levels were elevated in plasma from patients with sepsis. Higher levels of circulating DJ-1 were associated with increased organ failure and death.These novel findings reveal DJ-1 impairs optimal ROS production for bacterial killing with important implications for host survival in sepsis.
Evaluation of a Prediction Model for the Development of Atrial Fibrillation in a Repository of Electronic Medical Records
Authors: Matthew J. Kolek, Amy J. Graves, Meng Xu, Aihua Bian, Pedro Luis Teixeira, M. Benjamin Shoemaker, Babar Parvez, Hua Xu, Susan R. Heckbert, Patrick T. Ellinor, Emelia J. Benjamin, Alvaro Alonso, Joshua C. Denny, Karel G. M. Moons, Ayumi K. Shintani, Frank E. Harrell, Dan M. Roden, Dawood Darbar
Journal: JAMA Cardiology (2016)

Atrial fibrillation (AF) contributes to substantial morbidity, mortality, and health care expenditures. Accurate prediction of incident AF would enhance AF management and potentially improve patient outcomes.To validate the AF risk prediction model originally developed by the Cohorts for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation (CHARGE-AF) investigators using a large repository of electronic medical records (EMRs).In this prediction model study, deidentified EMRs of 33 494 individuals 40 years or older who were white or African American and had no history of AF were reviewed and analyzed. The participants were followed up in the internal medicine outpatient clinics at Vanderbilt University Medical Center for incident AF from December 31, 2005, until December 31, 2010. Adjusting for differences in baseline hazard, the CHARGE-AF Cox proportional hazards model regression coefficients were applied to the EMR cohort. A simple version of the model with no echocardiographic variables was also evaluated. Data were analyzed from October 31, 2013, to January 31, 2014.Incident AF. Predictors in the model included age, race, height, weight, systolic and diastolic blood pressure, treatment for hypertension, smoking status, type 2 diabetes, heart failure, history of myocardial infarction, left ventricular hypertrophy, and PR interval.Among the 33 494 participants, the median age was 57 (interquartile range, 49-67) years; 57% of patients were women, 43% were men, 85.7% were white, and 14.3% were African American. During the mean (SD) follow-up of 4.8 (0.9) years, 2455 individuals (7.3%) developed AF. Both models had poor calibration in the EMR cohort, with underprediction of AF among low-risk individuals and overprediction of AF among high-risk individuals (10th and 90th percentiles for predicted probability of incident AF, 0.005 and 0.179, respectively). The full CHARGE-AF model had a C index of 0.708 (95% CI, 0.699-0.718) in our cohort. The simple model had similar discrimination (C index, 0.709; 95% CI, 0.699-0.718; P = .70 for difference between models).Despite reasonable discrimination, the CHARGE-AF models showed poor calibration in this EMR cohort. This study highlights the difficulties of applying a risk model derived from prospective cohort studies to an EMR cohort and suggests that these AF risk prediction models be used with caution in the EMR setting. Future risk models may need to be developed and validated within EMR cohorts.
Engineered Basement Membranes for Regenerating the Corneal Endothelium
Authors: Rachelle N. Palchesko, James L. Funderburgh, Adam W. Feinberg
Journal: Advanced Healthcare Materials (2016)

Basement membranes are protein-rich extracellular matrices (ECM) that are essential for epithelial and endothelial tissue structure and function. Aging and disease cause changes in the physical properties and ECM composition of basement membranes, which has spurred research to develop methods to repair and/or regenerate these tissues. An area of critical clinical need is the cornea, where failure of the endothelium leads to stromal edema and vision loss. Here, an engineered basement membrane (EBM) is developed that consists of a dense layer of collagen IV and/or laminin ≈5-10 nm thick, created using surface-initiated assembly, conformally attached to a collagen I film. These EBMs are used to engineer a corneal endothelium (CE) that mimics the structure of Descemet's membrane with a thin stromal layer, toward use as a graft for lamellar keratoplasty. Results show that bovine and human CE cells form confluent monolayers on the EBM, express ZO-1 at the cell-cell borders, and achieve a density of ≈1600 cells mm-2 for 28 and 14 d, respectively. These results demonstrate that the technique is capable of fabricating EBMs with structural and compositional properties that mimic native basement membranes and that EBM may be a suitable carrier for engineering transplant quality CE grafts.
Phase I study of capecitabine and erlotinib with radiotherapy in locally advanced nonoperable pancreatic cancer.
Authors: Y. Jiang, E. Kimchi, N. J. Gusani, H. B. Mackley, K. Staveley-O'Carroll
Journal: Journal of Clinical Oncology (2010)

e14680 Background: Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of radiation therapy, we evaluated the safety and feasibility of the combination of capecitabine (C) and erlotinib (E) with radiotherapy in this group of patients. Methods: A classic “3+3” dose escalation design was adopted in the study. A total of 4 dose levels were planned: dose level I: C 600 mg/m2 bid, E 100 mg daily; level II: C 700 mg/m2 bid, E 100 mg daily; level III: C 825 mg/m2 bid, E 100 mg daily; level IV: C 925 mg/m2 bid, E 100 mg. C and E were administered daily from Monday through Friday, concurrent with radiotherapy for 50.4 Gy. Results: At present time, a total of 8 patients were enrolled. 3 patients were treated at dose level I. No dose limiting toxicity was observed. One of the patients at dose level II experienced grade 3 nausea and required dose reduction in both medications and treatment interruption for 1 week. The dose level II cohort was expanded to 6 patients. So far, 5 patients have been enrolled at the dose level II. The most frequent side effects were nausea, vomiting, diarrhea and skin rashes. Except for one grade 3 nausea, other side effects were grade 1 or 2 and were manageable. Of 7 patients with available data, the median progression-free survival is 214 days and overall survival has not been reached yet. The study is ongoing and recruiting. Conclusions: The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is feasible at the dose level of C 700 mg/m2 bid and E 100 mg daily. The MTD has not reached. The efficacy and safety of higher dose levels continue to be evaluated. The study is supported by Genentech/OSI pharmaceuticals. No significant financial relationships to disclose.
TCT-635 Valve-In-Valve With The New Recapturable CoreValve Evolut R™ For Degenerated Small Aortic Bioprostheses
Authors: Franco Fabbiocchi, Paolo Olivares, Manuela Muratori, Luca Salvi, Francesco Alamanni, Antonio L. Bartorelli
Journal: Journal of the American College of Cardiology (2015)
Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer
Authors: Tomasz M. Beer, Eugene D. Kwon, Charles G. Drake, Karim Fizazi, Christopher Logothetis, Gwenaelle Gravis, Vinod Ganju, Jonathan Polikoff, Fred Saad, Piotr Humanski, Josep M. Piulats, Pablo Gonzalez Mella, Siobhan S. Ng, Dirk Jaeger, Francis X. Parnis, Fabio A. Franke, Javier Puente, Roman Carvajal, Lisa Sengeløv, M. Brent McHenry, Arvind Varma, Alfonsus J. van den Eertwegh, Winald Gerritsen
Journal: Journal of Clinical Oncology (2016)

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.
Perioperative chemotherapy vs. adjuvant chemotherapy for potentially resectable gastric cancer: A randomized and multicenter phase III study in locally advanced gastric cancer with D2 dissection.
Authors: Qun Zhao, Yong Li, Changhong Lian, Baozhong Li, Wenxin Li, Zhibin Huo, Zunyi Wang, Yimin Wang, Yuan Tian, Shuzhe Xie, Shoumiao Li
Journal: Journal of Clinical Oncology (2015)

TPS4133 Background: The MAGIC and ACTS-GC/CLASSIC trials demonstrated benefit in resectable gastric cancer from both perioperative and postoperative adjuvant chemotherapy, although such management remains controversial for locally advanced gastric cancer (LAGC) after D2 lymph node dissection. Methods: A Phase III 1:1:1 randomized, open label, multicenter, trial comparing adjuvant (Arm A) or perioperative SOX (Arm B), and perioperative XELOX (Arm C) was initiated in February 2012, in T3/4, node+ gastric cancer patients after R0 resection. SOX included S-1 40 mg/m2 bid day 1-14, Oxaliplatin 130 mg/m2 on day 1, XELOX included Capecitabine 1000 mg/m2 bid day1-14, plus Oxaliplatin 130 mg/m2 on day, each cycle was 3 weeks, each patient received 8 cycles. Arm B and C patients received 2 cycles prior to surgery, and 6 cycles post op. Patients were stratified by tumor stage, ECOG PS and institution. The study was powered to show superiority of perioperative over adjuvant SOX, and non-inferiority of SOX to XELOX. Eligibility included histologically proven gastric cancer (including gastroesophageal junction), age 18-75, D2 or more extensive surgery with no residual disease, ECOG score ≤ 2, and no distant metastasis. Primary endpoint was R0-resection rate, secondary endpoints included overall survival, disease–free survival, safety. Up until January 2015, 638 subjects from 7 centers have been enrolled. Hematological toxicities included neutropenia, anemia, and thrombocytopenia. Non-hematological toxicities included fatigue, abnormal hepatic/renal function, neurotoxicity, and skin pigmentation, most adverse events were tolerable. No treatment related death was observed. Updated safety data will be presented. This study was registered with Clinicaltrials.gov, NCT01516944. Clinical trial information: NCT01516944.
A network meta-analysis-based cost-effectiveness analysis of systematic therapies in advanced pancreatic cancer.
Authors: Kelvin K. Chan, Yoo-Joung Ko, Keya Shah, Kelly Lien, Henry Lam, Doug Coyle
Journal: Journal of Clinical Oncology (2015)

6611 Background: For advanced pancreatic cancer, there are new treatment options that are more effective than gemcitabine alone (G). In this analysis we utilized data from a recently published Bayesian network meta-analysis (NMA) to assess the cost effectiveness of G, G+5-fluorouracil (GF), G+capecitabine (GCap), G+cisplatin (GCisp), G+oxaliplatin, G+erlotinib, G+nab-paclitaxel (GnP) and FOLFIRINOX from a Canadian health care perspective. Methods: Analysis was conducted through a three-state Markov model which follows a cohort of patients with advanced pancreatic cancer until death. Analysis used data on the progression of disease with treatment from the G arms of RCTs combined with estimates from the NMA of the effect of the newer regimens on disease progression and adverse events. Estimates of heath care costs were obtained from local providers and utilities were derived from the literature. The Markov model estimated the effect of treatment regimens on costs and quality adjusted life years (QALYs) discounted at 5% per annum. Detailed sensitivity analyses were conducted. Results: If a decision maker was willing to pay between $15,259 and $182,723 for a QALY, GF would be the optimal treatment regimen. For a willingness to pay of greater than $182,723, FOLFIRINOX would be optimal. Based on a willingness to pay for a QALY of $50,000, the price of oxaliplatin would need to be reduced by 83.4% for FOLFIRINOX to be optimal, whilst the price of nab-paclitaxel would need to be reduced by 93.1% for GnP to be optimal. At this threshold, the probability that GF is optimal is 52.7%, compared to 26.8% for GCisp, 19.0% for GCap and 1.6% for G and 0% for all other treatment regimens. Conclusions: At the current time with current drug prices and from the Canadian health care perspective, GF is the optimal treatment regimen based on the criteria of cost effectiveness. The acquisition costs of oxaliplatin is expected to decrease significantly once generic, and may make FOLFIRINOX more cost effective in advanced pancreatic cancer. GnP does not appear to be cost-effective regardless of willingness to pay threshold with its current pricing.
Abstract 10860: Association Between Fractional Flow Reserve and Coronary Plaque Characteristics Assessed by Optical Coherence Tomography
Authors: Seung-Yul Lee, Myeong-Ki Hong
Journal: Circulation (2015)

Introduction: The assessment of fractional flow reserve (FFR) in coronary lesions determines the strategy of percutaneous coronary intervention. However, the association between FFR and characteristics of underlying coronary plaque has not been sufficiently investigated. Methods: A total of 110 coronary lesions in 106 patients were evaluated using both FFR and optical coherence tomography (OCT). Coronary plaque was classified into fibrous, fibrocalcific, or fibroatheroma according to OCT evaluation at the site of minimal lumen area. Plaque microstructures such as cap thickness, macrophage accumulation, intimal vasculature, or cholesterol crystal were also evaluated. Results: Compared to lesions with FFR &gt;0.8, those with FFR ≤0.8 showed a higher frequency of fibroatheroma, macrophage accumulation, and cholesterol crystal. However, multiple linear regression analysis revealed that any morphological characteristics of plaques assessed by OCT were not independently associated with FFR. Minimal lumen area (coefficient, 0.036; 95% confidence interval [CI], 0.022-0.049; p&lt;0.001) and area stenosis (coefficient, - 0.003; 95% CI, -0.005--0.001; p&lt;0.001) assessed by OCT significantly correlated with FFR. Thin-cap fibroatheroma was identified in 12 (10.9%) of all 110 lesions. There were no significant differences of minimal lumen area, area stenosis, or FFR between lesions with and without thin-cap fibroatheroma. Conclusions: Morphological characteristics of coronary plaque are not directly related to FFR. Conversely, the extent of functional or anatomical stenosis cannot identify the lesion with thin-cap fibroatheroma.
TCT-702 Association of Learning Curve with Procedural Results and Recurrence of Mitral Regurgitation After Percutaneous Mitral Valve Repair with MitraClip System
Authors: Shunsuke Kubo, Yukiko Mizutani, Emily Tat, Asma Hussaini, Mamoo Nakamura, Takahiro Shiota, Robert Siegel, Alfredo Trento, Saibal Kar
Journal: Journal of the American College of Cardiology (2015)