tbuckley/cabot-search huggingface dataset:
Abstract 15554: Continuous Improvement in Cardiac Function After Transcatheter Aortic Valve Replacement Points to Preserved Cardiac Plasticity in Elderly Patients With Severe Aortic Stenosis
Authors: Kimi Sato, Arnav Kumar, Brandon M Jones, Samir R Kapadia, Brian P Griffin, L. Leonardo Rodriguez, Zoran P Popovic
Journal: Circulation (2016)

Background: While left ventricular (LV) unloading by transcatheter aortic valve replacement (TAVR) in elderly patients with severe aortic stenosis (AS) immediately improves LV hemodynamics, residua...
Abstract 16551: The Scavenger Receptor Class B Type I (SR-BI) Chaperones the Syndecan-1 Heparan Sulfate Proteoglycan to the Surface of Hepatocytes: Novel Role in the Clearance of Atherogenic Postprandial Remnant Lipoproteins
Authors: Keyang Chen, Kevin Jon Williams
Journal: Circulation (2013)

BACKGROUND: Syndecan-1 is a highly conserved receptor for postprandial remnant lipoproteins, directly mediating their endocytosis via a novel raft-dependent pathway (JCI 1997;100:1611; JBC 2013;288...
Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance
Authors: Zhentao Liu, Zuhua Chen, Jingyuan Wang, Mengqi Zhang, Zhongwu Li, Shubin Wang, Bin Dong, Cheng Zhang, Jing Gao, Lin Shen
Journal: Journal of Hematology & Oncology (2018)

No approved targeted agents are available for esophageal squamous cell carcinoma (ESCC). Informative genomic analysis and mouse patient-derived xenografts (PDX) also called mouse avatar can greatly expedite drug discovery. Six ESCC cell lines and 7 out of 25 PDX models derived from 188 biopsies with clear molecular features were employed to evaluate the sensitivity of several EGFR blockers in vitro and in vivo, as well as the underlying antitumor mechanisms of the most promising EGFR-TKI afatinib. Mechanisms involved in acquired resistance of afatinib were explored based on established resistant cell lines and PDX models followed by an attempt to reverse resistance. Compared with other EGFR blockers, the second-generation EGFR-TKI afatinib exerted superior antitumor effects in ESCC, and EGFR copy number gain (CNG) or overexpression was proposed to be predictive biomarkers. Afatinib played its antitumor effects by inhibiting EGFR downstream pathways, as well as inducing apoptosis and cell cycle arrest at G1. It was increased phosphorylation of Src family kinases (SFKs), rather than MET upregulation, that conferred to acquired resistance of afatinib. Dual blockade of EGFR and SFKs could overcome afatinib resistance and warrants validation in clinical practice. Both ESCC cell lines and PDXs with EGFR CNG or overexpression are potential candidates for afatinib, and concomitant EGFR/SFKs inhibition could reverse afatinib-acquired resistance caused by SFKs activation in ESCC.
Intrathecal Viral Vector Delivery of Trastuzumab Prevents or Inhibits Tumor Growth of Human HER2-Positive Xenografts in Mice
Authors: William T. Rothwell, Peter Bell, Laura K. Richman, Maria P. Limberis, Anna P. Tretiakova, Mingyao Li, James M. Wilson
Journal: Cancer Research (2018)

Breast cancer brain metastases are a deadly sequela of primary breast tumors that overexpress human epidermal growth factor receptor 2 (HER2); median survival for patients with these tumors is 10 to 13 months from the time of diagnosis. Current treatments for HER2-positive breast cancer brain metastases are invasive, toxic, and largely ineffective. Here, we have developed an adeno-associated virus serotype 9 (AAV9) vector to express the anti-HER2 monoclonal antibody trastuzumab (Herceptin) in vivo A single prophylactic intrathecal administration of AAV9.trastuzumab vector in a novel orthotopic Rag1-/- murine xenograft model of HER2-positive breast cancer brain metastases significantly increased median survival, attenuated brain tumor growth, and preserved both the HER2 antigen specificity and the natural killer cell-associated mechanism of action of trastuzumab. When administered as a tumor treatment, AAV9.trastuzumab increased median survival. Dose-escalation studies revealed that higher doses of AAV9.trastuzumab resulted in smaller tumor volumes. Our results indicate that intrathecal AAV9.trastuzumab may provide significant antitumor activity in patients with HER2-positive breast cancer brain metastases.Significance: Intrathecal delivery of trastuzumab via adeno-associated virus has the potential to become a novel, integral part of adjuvant therapy for patients with HER2-positive breast cancer brain metastases. Cancer Res; 78(21); 6171-82. ©2018 AACR.
Liquid biopsy for liver diseases
Authors: Jelena Mann, Helen L Reeves, Ariel E Feldstein
Journal: Gut (2018)

With the growing number of novel therapeutic approaches for liver diseases, significant research efforts have been devoted to the development of liquid biopsy tools for precision medicine. This can be defined as non-invasive reliable biomarkers that can supplement and eventually replace the invasive liver biopsy for diagnosis, disease stratification and monitoring of response to therapeutic interventions. Similarly, detection of liver cancer at an earlier stage of the disease, potentially susceptible to curative resection, can be critical to improve patient survival. Circulating extracellular vesicles, nucleic acids (DNA and RNA) and tumour cells have emerged as attractive liquid biopsy candidates because they fulfil many of the key characteristics of an ideal biomarker. In this review, we summarise the currently available information regarding these promising and potential transformative tools, as well as the issues still needed to be addressed for adopting various liquid biopsy approaches into clinical practice. These studies may pave the way to the development of a new generation of reliable, mechanism-based disease biomarkers.
Evolutionary model of folk economics: That which is seen, and that which is not seen?
Authors: Dan Stastny, Petr Houdek
Journal: Behavioral and Brain Sciences (2018)

Although Boyer &amp; Petersen (B&amp;P) make the case for evolutionary roots of folk economics stronger, their evolutionary model ultimately does not deliver folk-economic explanations that are both novel and correct. We argue that (a) most current explanations are evolutionary already; (b) B&amp;P's model is as ad hoc as other theories, and proves too much; and (c) it overrates evolution at the cost of discounting other crucial factors.
Circulating melanoma cells and recurrence in stage III melanoma patients.
Authors: Anthony Lucci, Carolyn S. Hall, Mandar Karhade, Barbara A. Laubacher, Jessica Bowman Bauldry, Richard Eldon Royal, Joshua Upshaw, Christina Lynn Roland, Merrick I. Ross
Journal: Journal of Clinical Oncology (2015)

9016 Background: There is a need for more sensitive and specific prognostic markers for advanced stage melanoma patients to help improve the risk-benefit ratio of systemic adjuvant therapies. While it has been demonstrated that circulating melanoma cells (CMCs) can be detected in melanoma patients, there is limited data regarding the prognostic significance of CMCs. The aim of this prospective study was to determine if CMCs predicted relapse in stage III melanoma patients. Methods: Serial CMC assessments (7.5mL blood) were performed in 101 patients with stage III cutaneous melanoma patients using the CellSearch system (Janssen). CD146+ cells were immunomagnetically enriched; CD146+, HMW-MAA+/, CD45-/, and CD34- nucleated cells were considered CMCs. Relapse-free survival was compared between patients with ≥1 CMC detected at baseline (first presentation to our clinic) or at second blood draw (6 months after baseline), versus those with no CMCs at baseline and at the second blood draw. Log-rank test and Cox regression analysis were applied to establish the association of CMCs with relapse-free survival. Results: CMCs were identified in 44 of 101 (44%) patients at either baseline or at second blood draw. Median follow up was 10 months. We observed no significant association between CMC presence and primary tumor factors including Breslow thickness, number of mitotic figures, or ulceration. Relapse was observed in 10 of 44 (23%) patients with ≥ 1 CMC, versus 4 of 57 (7%) of patients with no CMCs at baseline and at second blood draw (log-rank P = 0.04, HR 3.25, 95% CI 1.01 to 10.37; P = 0.04). Conclusions: CMCs at baseline or at a six month follow up blood draw predicted relapse in stage III melanoma patients. This data supports larger studies to confirm that presence of CMCs could be used to identify patients at risk for relapse, with an ultimate goal of early systemic intervention.
IL7R is associated with CNS infiltration and relapse in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Ameera Alsadeq, Lennart Lenk, Anila Vadakumchery, Antony Cousins, Christian Vokuhl, Ahmad Khadour, Fotini Vogiatzi, Felix Seyfried, Lueder-Hinrich Meyer, Gunnar Cario, Elias Hobeika, Klaus-Michael Debatin, Christina Halsey, Martin Schrappe, Denis M. Schewe, Hassan Jumaa
Journal: Blood (2018)
Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials
Authors: Samantha Meltzer-Brody, Helen Colquhoun, Robert Riesenberg, C Neill Epperson, Kristina M Deligiannidis, David R Rubinow, Haihong Li, Abdul J Sankoh, Christine Clemson, Amy Schacterle, Jeffrey Jonas, Stephen Kanes
Journal: The Lancet (2018)
Abstract 16033: A Paradoxical Relationship of Plasma Adiponectin to Cardiovascular Risk in Patients With Diabetes and Recent Acute Coronary Syndrome - the Alecardio Trial
Authors: Ilse C Schrieks, Anna Nozza, Barbara E Stähli, John B Buse, Klas Malmberg, Bruce Neal, Stephan J Nicholls, Lars Rydén, Anders Svensson, Hans Wedel, Arlette Weichert, A. Michael Lincoff, Jean-Claude Tardif, Diederick E Grobbee, Gregory G Schwartz
Journal: Circulation (2016)

Introduction: Adiponectin (Adn), a hormone secreted by adipocytes, modulates insulin action and sensitivity, and has putative anti-atherogenic effects. Observational cohort studies show an inverse ...
Stratifin expression in epithelial ovarian cancer: the role of methylation in vitro and in vivo
Authors: Jennifer Sarno, William Welch, Samuel Mok, Elizabeth Garner
Journal: Cancer Research (2007)

1057   Introduction:  To examine stratifin (SFN) gene and protein expression in malignant and non-malignant ovarian epithelial cells in relation to the methylation status of the SFN coding region.  Procedures:  Normal human ovarian surface epithelial cells (HOSE) were obtained from scrapings of 8 normal ovaries of women undergoing surgery for unrelated gynecologic conditions. Cells were grown in culture and harvested at passage 2 to obtain genomic DNA, RNA, and protein. Established ovarian epithelial carcinoma cell lines were treated similarly. Genomic DNA was bisulfite-treated, followed by methylation-specific PCR (MSPCR) and bisulfite sequencing, to study the methylation status of the SFN coding region. SFN mRNA expression was analyzed by real-time PCR. Western blotting was performed to analyze SFN protein expression. Immunohistochemistry was used to identify the spatial and semi-quantitative expression of SFN in vivo.  Results:  All eight normal HOSE demonstrated positive methylation, two of these also showing a weaker unmethylated PCR product. Among the cell lines, 6/6 serous were unmethylated, one of these demonstrating partial methylation. Two out of two mucinous cell lines were unmethylated and 1/1 endometrioid was methylated. One clear cell line was methylated, while the other 2 were unmethylated. Bisulfite sequencing confirmed MSPCR results. Samples with positive methylation showed reduced SFN mRNA and protein expression. Those with no methylation showed greater SFN mRNA and protein expression. Immunohistochemistry revealed an expression pattern in endometrioid and clear cell cancers that appeared to be specific to certain aggregations of cancer cells. Serous tissue, on the other hand, demonstrated negative to weakly positively SFN expression throughout the specimen.  Conclusions:  Previous studies have suggested an important role of the SFN gene, a negative cell cycle regulator, in ovarian cancer pathogenesis. The current study reveals that regulation of the SFN gene is likely controlled at least in part by the methylation status of the coding region. The in vitro data from ovarian cancer cell lines show a consistent correlation between SFN methylation status and gene and protein expression. Based on the variation of SFN expression in ovarian cancer tissues, it is clear that the expression of SFN is not as clear-cut in vivo as it seems in vitro. It is possible that this tissue variation in SFN expression may be due to different clonal origins of groups of cells. Other as of yet unidentified processes may also explain these interesting variations. Further studies are needed to understand the regulation of SFN methylation between cells or groups of cells within epithelial ovarian cancer tissues.
Ending Use of Oral Poliovirus Vaccine — A Difficult Move in the Polio Endgame
Authors: Mark A. Pallansch
Journal: New England Journal of Medicine (2018)

Ending Use of Oral Poliovirus Vaccine The global health community has taken the first step toward eliminating use of oral poliovirus vaccine: switching from trivalent to bivalent vaccine. The polio endgame requires monitoring the effects on circulating viruses, followed by other challenging steps.
Abstract 326: Total Liquid Ventilation Offers Ultrafast and Whole-Body Cooling in Large Animals
Authors: Renaud Tissier, Fanny Lidouren, Alice Hutin, Mourad Chenoune, Aurélien Seeman, Matthias Kohlhauer, Luc Lotteau, Jean-Damien Ricard, Pierre Carli, Benoit Vivien, Bijan Ghaleh, Alain Berdeaux
Journal: Circulation (2014)

Introduction: Total liquid ventilation with perfluorocarbons (TLV) has been shown to cool down the entire body very rapidly (<10-15 min) in rabbits after cardiac arrest. Hypothesis: We hypothesized that TLV could also induce rapid and whole-body cooling in larger animals under normal conditions (beating hearts) or during cardiopulmonary resuscitation (CPR). Methods: In a first set of experiments, anesthetized pigs of 20-30 kg were randomly maintained under conventional gas ventilation or submitted to TLV using a specific prototype for large animals. TLV was instituted using perfluoro-N-octane at 15°C (5 cycles/min; tidal volume = 15 ml/kg; end-expiratory volume = 15 ml/kg). In a second set of experiments, pigs were submitted untreated ventricular fibrillation during 15 min. Cardiopulmonary resuscitation (CPR) was initiated using an automated device (Thumper ®). One group was maintained under conventional CPR with the continuous compression ventilation mode (Control group). Another group was switched to TL...
Increased Skeletal Muscle FDG Uptake Due to Sexual Activity on PET/CT in a Middle Age Woman
Authors: Wei Wang, Ying Kan, Jie Liu, Leilei Yuan, Jigang Yang
Journal: Clinical Nuclear Medicine (2018)

Abstract A 48-year-old woman with gradually growing left lung nodule underwent FDG PET/CT scan, which demonstrated mild 18 F-FDG uptake in the nodule of the left lobe, suggestive of malignancy. Unexpectedly, increased FDG uptake in bilateral gluteus medius, gluteus minimus, and piriformis was shown. She described having sexual activity in missionary position the night prior. The case emphasizes the importance of avoiding sexual activity before the FDG PET/CT study.
MicroRNA-532-5p Regulates Pericyte Function by Targeting the Transcription Regulator BACH1 and Angiopoietin-1
Authors: Sadie C. Slater, Eva Jover, Andrea Martello, Tijana Mitić, Iker Rodriguez-Arabaolaza, Rosa Vono, Valeria V. Alvino, Simon C. Satchell, Gaia Spinetti, Andrea Caporali, Paolo Madeddu
Journal: Molecular Therapy (2018)

MicroRNAs regulate endothelial function and angiogenesis, but their implication in pericyte biology remains undetermined. A PCR array, covering a panel of 379 human microRNAs, showed microRNA-532-5p to be one of the most differentially modulated by hypoxia, which was confirmed by qPCR in both skeletal muscle and adventitial pericytes. Furthermore, microRNA-532-5p was upregulated in murine muscular pericytes early after experimentally induced ischemia, decreasing below baseline after reperfusion. Transfection of human pericytes with anti-microRNA, microRNA-mimic, or controls indicates microRNA-532-5p modulates pro-angiogenic activity via transcriptional regulation of angiopoietin-1. Tie-2 blockade abrogated the ability of microRNA-532-5p-overexpressing pericytes to promote endothelial network formation in vitro. However, angiopoietin-1 is not a direct target of microRNA-532-5p. In silico analysis of microRNA-532-5p inhibitory targets associated with angiopoietin-1 transcription indicated three potential candidates, BACH1, HIF1AN, and EGLN1. Binding of microRNA-532-5p to the BACH1 3' UTR was confirmed by luciferase assay. MicroRNA-532-5p silencing increased BACH1, while a microRNA-532-5p mimic decreased expression. Silencing of BACH1 modulated angiopoietin-1 gene and protein expression. ChIP confirmed BACH1 transcriptional regulation of angiopoietin-1 promoter. Finally, microRNA-532-5p overexpression increased pericyte coverage in an in vivo Matrigel assay, suggesting its role in vascular maturation. This study provides a new mechanistic understanding of the transcriptional program orchestrating angiopoietin-1/Tie-2 signaling in human pericytes.
Association of Rapid Molecular Testing With Duration of Respiratory Isolation for Patients With Possible Tuberculosis in a US Hospital
Authors: Lelia H. Chaisson, David Duong, Adithya Cattamanchi, Marguerite Roemer, Margaret A. Handley, Dean Schillinger, Matthew Sur, Phong Pham, Mary Ann Lin, L. Elizabeth Goldman, Judy Quan, Saida Perez, Michael Healy, Julie Higashi, Lisa Winston, Barbara Haller, Anne F. Luetkemeyer, J. Lucian Davis
Journal: JAMA Internal Medicine (2018)

New guidelines recommend that molecular testing replace sputum-smear microscopy to guide discontinuation of respiratory isolation in patients undergoing evaluation for active tuberculosis (TB) in health care settings.To evaluate the implementation and impact of a molecular testing strategy to guide discontinuation of isolation.Prospective cohort study with a pragmatic, before-and-after-implementation design of 621 consecutive patients hospitalized at Zuckerberg San Francisco General Hospital and Trauma Center who were undergoing sputum examination for evaluation for active pulmonary TB from January 2014 to January 2016.Implementation of a sputum molecular testing algorithm using GeneXpert MTB/RIF (Xpert; Cepheid) to guide discontinuation of isolation.We measured the proportion of patients with molecular testing ordered and completed; the accuracy of the molecular testing algorithm in reference to mycobacterial culture; the duration of each component of the testing and isolation processes; length of stay; mean days in isolation and in hospital; and mean cost. We extracted data from hospital records and compared measures before and after implementation.Clinicians ordered sputum testing for TB for 621 patients at ZSFG during the 2-year study period. Of 301 patients in the preimplementation period with at least 1 sputum microscopy and culture ordered, clinicians completed the rapid TB testing evaluation process for 233 (77%).Among 320 patients evaluated in the postimplementation period, clinicians ordered molecular testing for 234 (73%) patients and received results for 295 of 302 (98%) tests ordered. Median age was 54 years (interquartile range, 44-63 years), and 161 (26%) were women. The molecular testing algorithm accurately diagnosed all 7 patients with culture-confirmed TB and excluded TB in all 251 patients with Mycobacterium tuberculosis (MTB) culture-negative results. Compared with the preimplementation period, there were significant decreases in median times to final rapid test result (39.1 vs 22.4 hours, P < .001), discontinuation of isolation (2.9 vs 2.5 days, P = .001), and hospital discharge (6.0 vs 4.9 days, P = .003), on average saving $13 347 per isolated TB-negative patient.A sputum molecular testing algorithm to guide discontinuation of respiratory isolation for patients undergoing evaluation for active TB was safe, feasible, widely and sustainably adopted, and provided substantial clinical and economic benefits. Molecular testing may facilitate more efficient, patient-centered evaluation for possible TB in US hospitals.
Abstract 17992: Observed versus Predicted Myocardial Infarction Among Individuals With Human Immunodeficiency Virus by American College of Cardiology/American Heart Association Pooled Cohort Equation Risk Strata: Center for AIDS Research Network of Integrated Clinical Systems
Authors: Matthew J Feinstein, Daniel R Drozd, Hongyan Ning, Joseph A Delaney, Robin Nance, William C Matthews, Chad J Achenbach, Heidi Crane, Donald M Lloyd-Jones
Journal: Circulation (2015)

Background: Human immunodeficiency virus (HIV)-infected individuals are at elevated risk for cardiovascular disease (CVD) due to an interplay between traditional CVD risk factors, chronic inflammation persisting despite HIV viral suppression, and side effects of antiretroviral therapy. Previous studies evaluating CVD risk prediction models in HIV populations have generally been small in size and assessed non-U.S. cohorts. The 2013 ACC/AHA ASCVD Risk Estimator has not been evaluated in a large, multi-center HIV cohort. Hypothesis: Our primary hypothesis was that the ACC/AHA ASCVD Risk Estimator would underestimate ASCVD risk across risk strata for HIV-infected patients. Methods: We evaluated this risk prediction tool in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) multi-center U.S.-based cohort of approximately 30,000 HIV-infected adults with rigorous central adjudication of myocardial infarction (MI) and differentiation between type I and II MI. We compared MI and ASCVD risks predicted by the ASCVD Risk Estimator to actual rates of MI observed in the CNICS cohort. Results: A total of 132 MIs were observed during follow-up, compared with 103 MIs that would have been expected based on the ASCVD risk estimator. Observed MI rates were higher than expected across most predicted risk levels, particularly among black participants and those with low (&lt;5%) predicted 10-year ASCVD risk. This under-prediction was relatively uniform across risk strata among white men; the observed MI rates were 68%, 68%, 67%, and 67% greater than expected, respectively, for white men with &lt;5%, 5% to &lt;7.5%, 7.5% to &lt;10%, and 10% or greater predicted 10-year ASCVD risk. Conclusions: These data suggest that the ACC/AHA Risk Estimator under-predicts MI risk among HIV-infected individuals. The under-prediction was relatively uniform across risk strata for white men. These data highlight the need for accurate HIV-specific CVD risk prediction tools.
Implausible discussions in saturated fat ‘research’; definitive solutions won’t come from another million editorials (or a million views of one)
Authors: David Nunan, Duane Mellor, Nicola Guess, Ian M Lahart
Journal: British Journal of Sports Medicine (2018)

The British Journal of Sports Medicine published an opinion editorial advocating a revision of public health guidance on saturated fat [1].Here we offer a rebuttal, incorporating evidence-based principles absent in the original editorial, focusing on the quality of the evidence presented and we discuss contradictory evidence in relation to saturated fat, low-density lipoprotein cholesterol (LDL-C), specific dietary interventions, and cardiovascular disease (CVD) alongside future directions. Effects of reducing saturated fat intake on cardiovascular diseaseThe authors cite a 2015 'landmark' meta-analysis of observational studies showing a lack of an association between saturated fat consumption and both all-cause mortality and cardiovascular outcomes [2].According to best practice evidence-based methods, these types of studies provide low-quality evidence [3].Indeed, the authors of the cited meta-analysis reported that the likelihood of the reported associations was 'very low'[2], meaning we can have very little confidence in the findings.