tbuckley/cabot-search huggingface dataset:
Abstract 16088: Comparison of Aspirin and Clopidogrel Therapy With Clopidogrel Alone Use Following Coronary Stent Implantation in Patients With Acute Myocardial Infarction
Authors: Jin Sup Park, Kwang Soo Cha, Donghun Shin, Dae Sung Lee, Hye Won Lee, Jun-Hyok Oh, Jung Hyun Choi, Han Cheol Lee, Taek Jong Hong
Journal: Circulation (2014)

Introduction: Dual antiplatelet (DAP) therapy with aspirin and a thienopyridine following coronary stenting is superior to aspirin alone use in reducing cardiovascular events in both acute coronary syndrome and stable angina. However, there is a doubt whether DAP therapy is more effective and safer than clopidogrel alone use in secondary prevention. Hypothesis: We assessed the hypothesis that we compared retrospectively clopidogrel alone use with DAP therapy in acute myocardial infarction (MI) patients treated with coronary stent. Methods: From the Korean MI registry, we selected a total of 13,348 patients who underwent coronary stent implantation and were discharged on clopidogrel alone use (n = 85, 0.6%) and DAP therapy (n = 13,263, 99.4%). Propensity score matching was used and two cohorts of 1:5 nearest neighbor matched patients were obtained to eliminate biased estimates. The primary endpoint was the composite of major adverse cardiac events (MACE; all-cause death, MI, or revascularization) at one-year. Results: In the two matched cohorts of clopidogrel alone use (n = 85) and DAP therapy (n = 425), there was no difference in all-cause death (3.1 vs. 3.5%, p = 0.82), cardiovascular death (2.1 vs. 2.4%, p = 0.892), MI (1.6 vs. 1.2%, p = 0.75), revascularization (6.6 vs. 8.2%, p = 0.583), and the composite of cumulative MACE (11.3 vs. 12.9%, p = 0.665) at median follow-up period of 11.8 months. Compared to DAP therapy, clopidogrel alone use was not associated with increased risk of all-cause death (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.314-3.93, p = 0.871), MI (HR 0.38, 95% CI 0.17-11.2, p = 0.763), revascularization (HR 0.808, 95% CI 0.353-1.851, p = 0.615), and the composite of MACE (HR 1.129, 95% CI 0.585-2.178, p = 0.717) at one-year. Conclusions: This observational study showed that clopidogrel alone use following coronary stenting was not associated with increased mortality and worse clinical outcomes at one-year compared to DAP therapy in patients with acute MI. Further studies are needed to support this observational result.
A non-hierarchical organization of tumorigenic NG2 cells in glioblastoma promoted by EGFR
Authors: Talal F Al-Mayhani, Richard M Heywood, Vamsidhara Vemireddy, Justin D Lathia, Sara G M Piccirillo, Colin Watts
Journal: Neuro-Oncology (2018)

Expression of neuron-glial antigen 2 (NG2) identifies an aggressive malignant phenotype in glioblastoma (GBM). Mouse models have implicated NG2 in the genesis, evolution, and maintenance of glial cancers and have highlighted potential interactions between NG2 and epidermal growth factor receptor (EGFR). However, it is unknown whether the lineage relationship of NG2+ and NG2- cells follows a hierarchical or stochastic mode of growth. Furthermore, the interaction between NG2 and EGFR signaling in human GBM is also unclear.Single GBM NG2+ and NG2- cells were studied longitudinally to assess lineage relationships. Short hairpin RNA knockdown of NG2 was used to assess the mechanistic role of NG2 in human GBM cells. NG2+ and NG2- cells and NG2 knockdown (NG2-KD) and wild type (NG2-WT) cells were analyzed for differential effects on EGFR signaling.Expression of NG2 endows an aggressive phenotype both at single cell and population levels. Progeny derived from single GBM NG2- or GBM NG2+ cells consistently establish phenotypic equilibrium, indicating the absence of a cellular hierarchy. NG2 knockdown reduces proliferation, and mice grafted with NG2-KD survive longer than controls. Finally, NG2 promotes EGFR signaling and is associated with EGFR expression.These data support a dynamic evolution in which a bidirectional relationship exists between GBM NG2+ and GBM NG2- cells. Such findings have implications for understanding phenotypic heterogeneity, the emergence of resistant disease, and developing novel therapeutics.
Management of Relapse in Acute Promyelocytic Leukemia Treated with Upfront Arsenic Trioxide Based Regimens
Authors: Fouzia N., Vibhor Sharma, Anu Korula, Anup Joseph Devasia, Uday Prakash Kulkarni, Yasir Jeelani Samoon, Thenmozhi Mani, Jeyaseelan Lakshmanan, Alok Srivastava, Aby Abraham, Poonkuzhali Balasubramanian, Biju George, Vikram Mathews
Journal: Blood (2018)
Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta
Authors: Ling-juan Zhang, Stella Xiang Chen, Christian F. Guerrero-Juarez, Fengwu Li, Yun Tong, Yuqiong Liang, Marc Liggins, Xu Chen, Hao Chen, Min Li, Tissa Hata, Ye Zheng, Maksim V. Plikus, Richard L. Gallo
Journal: Immunity (2018)
Abstract 17250: Surgical Outcomes of Type A Aortic Dissection in the Octogenarians and Nonagenarians
Authors: Naonori Kawamoto, Kenji Minatoya, Hitoshi Matuda, Hiroaki Sasaki, Hiroshi Tanaka, Yutaka Iba, Tatsuya Oda, Masahiro Saito, Jyunpei Kobiki, Jyunjiro Kobayashi
Journal: Circulation (2013)

Objectives: The purpose of this study was to evaluate the early and mid-term outcomes of surgery for type A aortic dissection in the octogenarians and nonagenarians. Methods: Since 1995, 50 patient...
Fibrillin-2 is a key mediator of smooth muscle extracellular matrix homeostasis during mouse tracheal tubulogenesis
Authors: Wenguang Yin, Hyun-Taek Kim, ShengPeng Wang, Felix Gunawan, Rui Li, Carmen Buettner, Beate Grohmann, Gerhard Sengle, Debora Sinner, Stefan Offermanns, Didier Y.R. Stainier
Journal: European Respiratory Journal (2018)

Epithelial tubes, comprised of polarised epithelial cells around a lumen, are crucial for organ function. However, the molecular mechanisms underlying tube formation remain largely unknown. Here, we report on the function of fibrillin (FBN)2, an extracellular matrix (ECM) glycoprotein, as a critical regulator of tracheal tube formation.We performed a large-scale forward genetic screen in mouse to identify regulators of respiratory organ development and disease. We identified Fbn2 mutants which exhibit shorter and narrowed tracheas as well as defects in tracheal smooth muscle cell alignment and polarity.We found that FBN2 is essential for elastic fibre formation and Fibronectin accumulation around tracheal smooth muscle cells. These processes appear to be regulated at least in part through inhibition of p38-mediated upregulation of matrix metalloproteinases (MMPs), as pharmacological decrease of p38 phosphorylation or MMP activity partially attenuated the Fbn2 mutant tracheal phenotypes. Analysis of human tracheal tissues indicates that a decrease in ECM proteins, including FBN2 and Fibronectin, is associated with tracheomalacia.Our findings provide novel insights into the role of ECM homeostasis in mesenchymal cell polarisation during tracheal tubulogenesis.
Association of a Simulated Institutional Gender Equity Initiative With Gender-Based Disparities in Medical School Faculty Salaries and Promotions
Authors: Avani D. Rao, Sarah E. Nicholas, Bartlomiej Kachniarz, Chen Hu, Kristin J. Redmond, Curtiland Deville, Jean L. Wright, Brandi R. Page, Stephanie Terezakis, Akila N. Viswanathan, Theodore L. DeWeese, Barbara A. Fivush, Sara R. Alcorn
Journal: JAMA Network Open (2018)

Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings.To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI).Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885).Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives.Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from -2.6% (1.2%) (95% CI, -5.6% to -0.3%) to -1.9% (1.1%) (95% CI, -4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts.Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.
Comment on Wang et al. Incretin-Based Therapies and Diabetic Retinopathy: Real-World Evidence in Older U.S. Adults. Diabetes Care 2018;41:1998–2009
Authors: Sylvie Feldman-Billard
Journal: Diabetes Care (2018)

I read with great interest the article by Wang et al. (1) demonstrating that incretin-based therapies used for 1 year do not increase the risk of diabetic retinopathy (DR) compared with other glucose-lowering drugs in a population aged 65 years and older. Beyond these reassuring data, I would like to highlight one striking point. This study offers a quantitative overview of the risk of early worsening of diabetic retinopathy (EWDR) following intensification of treatment (IT) across comparative hypoglycemic groups in real life.

First, physicians must be aware that EWDR is not just a consequence of insulin IT, as initially described in young patients with type …
Best supportive care in advanced lung cancer—more than a label?
Authors: Jo Bowden, Stephen Fenning, Brooke Marron, Catriona Macpherson, Steinunn Boyce, Varrie Wardrope, Karen Campbell, Lucy Johnston
Journal: BMJ (2018)

We should be accountable for delivering the right care in the right place for people nearing the end of life, say Jo Bowden and colleagues
Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy
Authors: Jun Lu, Hua Zhong, Tianqing Chu, Xueyan Zhang, Rong Li, Jiayuan Sun, Runbo Zhong, Yuqin Yang, Mohammad Shah Alam, Yuqing Lou, Jianlin Xu, Yanwei Zhang, Jun Wu, Xiaowei Li, Xiaodong Zhao, Kai Li, Liming Lu, Baohui Han
Journal: European Respiratory Journal (2018)

Anlotinib has been demonstrated in clinical trials to be effective in prolonging the progression-free survival (PFS) and overall survival (OS) of refractory advanced nonsmall cell lung cancer (NSCLC) patients. However, the underlying molecular mechanisms and predictive biomarkers of anlotinib are still unclear.A retrospective analysis of anlotinib administered to 294 NSCLC patients was performed to screen for underlying biomarkers of anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the antitumour molecular mechanisms of anlotinib. Changes in serum CCL2 levels were analysed to examine the correlation of the anlotinib response between responders and nonresponders.Anlotinib therapy was beneficial for prolonging OS in NSCLC patients harbouring positive driver gene mutations, especially patients harbouring the epithelial growth factor receptor (EGFR)T790M mutation. Moreover, anlotinib inhibited angiogenesis in an NCI-H1975-derived xenograft model via inhibiting CCL2. Finally, anlotinib-induced serum CCL2 level decreases were associated with the benefits of PFS and OS in refractory advanced NSCLC patients.Our study reports a novel anti-angiogenesis mechanism of anlotinib via inhibiting CCL2 in an NCI-H1975-derived xenograft model and suggests that changes in serum CCL2 levels may be used to monitor and predict clinical outcomes in anlotinib-administered refractory advanced NSCLC patients using third-line therapy or beyond.
Abstract 16097: The Effects of MEDI6012 on Lipoproteins in Familial LCAT Deficiency Patients and a New NMR Method for Quantifying Lipoprotein-X
Authors: Lita A Freeman, Maureen L Sampson, Robert D Shamburek, Boris L Vaisman, John Le Lay, Irina Shalaurova, James D Otvos, Sotirios K Karathanasis, Alan T Remaley
Journal: Circulation (2017)

Introduction: Lecithin:cholesterol acyltransferase (LCAT), a key enzyme for HDL maturation, catalyzes esterification of cholesterol to cholesteryl ester in plasma. Functional LCAT is absent in patients with Familial LCAT Deficiency (FLD), an autosomal recessive disorder characterized by very low HDL-cholesterol, anemia, nephropathy, and circulating lipoprotein-X (LP-X). LP-X is an abnormal multilamellar particle, enriched in phospholipids and unesterified cholesterol, and is nephrotoxic in mice. Objectives: To characterize the effects of MEDI6012 (rhLCAT) on LP-X in plasma from FLD patients and to compare LP-X measured by agarose gel electrophoresis with a novel assay utilizing nuclear magnetic resonance (NMR) spectroscopy. Methods: We incubated MEDI6012 with fresh plasma from FLD patients and investigated changes in lipoproteins either by Sebia gel electrophoresis or by a novel proton NMR assay on the Vantera analyzer, which detects and quantifies LP-X by exploiting the unique spectral shape and position...
Avadomide (CC-122), a Novel Cereblon Modulating Agent, Plus Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma
Authors: Loretta J. Nastoupil, Fontanet Bijou, Vincent Ribrag, Julio C. Chavez, Thomas E. Witzig, David J. Andorsky, Leonard M. Klein, Daniel Greenwald, Armando Santoro, Paolo Corradini, Ian W. Flinn, Randeep Sangha, Vaishalee P. Kenkre, Shailaja Uttamsingh, Patrick R. Hagner, Anita K. Gandhi, Tianlei Chen, Kristen Hege, Michael Pourdehnad, John Kuruvilla
Journal: Blood (2018)
Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study
Authors: Feng Sun, Yang Li, Yu Chen, Wenlong Guan, Xiangao Jiang, Xiaomeng Wang, Pengfei Ren, Junlian Li, Jichan Shi, Guiqing He, Meiying Wu, Peijun Tang, Fei Wang, Yunfeng Sheng, Fuli Huang, Zumo Zhou, Heqing Huang, Liang Hong, Qihui Liu, Ying Zhang, Wenhong Zhang
Journal: European Respiratory Journal (2018)

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18-24 months and has a poor cure rate of 50-60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB.We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome.Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3% versus 55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1% versus 62.1%, p=0.009).Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen.
Twelve Blessings for a Surgeon
Authors: J. A. O’Hare
Journal: JAMA (2018)

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Abstract 9812: The Symptom Status Questionnaire is a Reliable and Valid Symptom Instrument for Patients With Heart Failure
Authors: Seongkum Heo, Debra K Moser, Sandra B Dunbar, Susan J Pressler, Jinshil Kim, Terry A Lennie
Journal: Circulation (2013)

Background and Purpose: Patients with heart failure (HF) experience physical symptoms, poor health-related quality of life (HRQOL), and high rates of hospitalization. Physical symptoms are associated with HRQOL and are major antecedents of hospitalization. However, reliable and valid physical symptom instruments have not been established for use in patients with HF. This study, therefore, examined the psychometric properties of the Symptom Status Questionnaire-Heart Failure (SSQ-HF) in patients with HF. Method: Data on symptoms were collected from 249 Patients (age 61, 67% male, 45% in New York Heart Association functional class III/IV). Internal consistency reliability was assessed using Cronbach’s alpha. Item homogeneity was assessed using item-total and inter-item correlations. Construct validity was assessed using factor analysis and testing hypotheses on known relationships. The SSQ-HF is a 7-item questionnaire asking about the presence, frequency, severity, and distress of common HF symptoms during the past 4 weeks. Data on depressive symptoms (using the Beck Depression Inventory II), HRQOL (using the Minnesota Living with Heart Failure Questionnaire), and event-free survival were collected to test known relationships. Event-free survival was defined as the time from enrollment to the first event of all-cause hospitalization, emergency department visit, or death. Results: Cronbach’s alpha was .80, supporting internal consistency reliability. Item-total correlation coefficients and inter-item correlation coefficients were acceptable. One factor was extracted, and all the items demonstrated moderate to strong loadings (&gt; .40), indicating acceptable construct validity. As hypothesized, more severe symptoms were associated with more depressive symptoms, poorer HRQOL, and shorter event-free survival, providing further evidence for the construct validity of the SSQ-HF. Conclusions: The findings of this study support the reliability and validity of the SSQ-HF. Clinicians and researchers can use this instrument to assess physical symptoms in patients with HF.
Abstract 16675: Intraplaque Hemorrhage-induced Atherosclerotic Plaque Progression as the Bridge Between Intact and Ulcerated Plaques: An Imaging-based Natural History Study
Authors: Jie Sun, Jin Liu, Niranjan Balu, Daniel S Hippe, Dongxiang Xu, Gador Canton, Thomas S Hatsukami, Chun Yuan
Journal: Circulation (2015)

Introduction: Previous studies have associated intraplaque hemorrhage (IPH) with future ischemic events, of which the mechanisms are less understood. Hypothesis: Understanding morphological features and progression behaviors of plaques with and without IPH would allow us to define the role of IPH in the natural history of atherosclerosis. Methods: In an ongoing study, asymptomatic subjects with 16-79% stenosis on ultrasound underwent 3-dimensional carotid MRI. Those with carotid plaque(s) on MRI were recruited and a follow-up scan was performed 1-year later using the same protocol. Individual plaques (maximum thickness&gt;1.5 mm) within scan coverage were identified in bilateral carotids, of which morphological data were collected at baseline and plaque progression was determined by comparing both scans while blinded to the time sequence. Results: Twenty-nine subjects have completed the study. A total of 64 de novo plaques were identified, of which 15 (23.4%) demonstrated IPH. Plaques with IPH are more likely to have an ulcerated surface than those without IPH (60.0% vs. 8.2%, odds ratio: 16.9 [3.9, 72.3]). Furthermore, there was a stepwise progression in baseline morphological measures from IPH-/ulcer- plaques to IPH+/ulcer- plaques and to ulcer+ plaques (Table), suggesting that IPH+/ulcer- plaques may be at the intermediate stage between IPH-/ulcer- and ulcer+ plaques. During the 1-year period, IPH+/ulcer- plaques had significantly greater increases in mean wall thickness and percent luminal stenosis compared to IPH-/ulcer- plaques, indicating further progression towards ulcer+ plaques. In contrast, ulcer+ plaques, as the most stenotic group, showed little plaque burden change on average. Conclusions: Collectively, our data support the conjecture that IPH promotes plaque progression and appears to be an intermediate step toward surface ulceration. IPH could be a critical step in phenotype transition from asymptomatic to symptomatic plaques.