tbuckley/cabot-search huggingface dataset:
Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants
Authors: Johan Rönnelid, Monika Hansson, Linda Mathsson-Alm, Martin Cornillet, Evan Reed, Per-Johan Jakobsson, Lars Alfredsson, Rikard Holmdahl, Karl Skriner, Guy Serre, Karin Lundberg, Lars Klareskog
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Introduction</h3> The second generation anticycliccitrullinated peptide (anti-CCP2) assay detects the majority but not all anticitrullinated protein/peptide antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay to detect multiple specific ACPA, we have investigated the fine specificity of individual ACPA responses and the biological impact of additional ACPA reactivity among anti-CCP2-negative patients. <h3>Methods</h3> We investigated 2825 patients with RA and 551 healthy controls with full data on anti-CCP2, HLA-DRB1* alleles and smoking history concerning reactivity against 16 citrullinated peptides and arginine control peptides with a multiplex array. <h3>Results</h3> The prevalence of the 16 ACPA specificities ranged from 9% to 58%. When reactivity to arginine peptides was subtracted, the mean diagnostic sensitivity increased by 3.2% with maintained 98% specificity. Of the anti-CCP2-negative patients, 16% were found to be ACPA positive. All ACPA specificities associated with SE, and all but one with smoking. Correction for arginine reactivity also conveyed a stronger association with SE for 13/16 peptides. Importantly, when all ACPA specificities were analysed together, SE and smoking associated with RA in synergy among ACPA positive, but not among ACPA-negative subjects also in the anti-CCP2-negative subset. <h3>Conclusions</h3> Multiplexing detects an enlarged group of ACPA-positive but anti-CCP2-negative patients with genetic and environmental attributes previously assigned to anti-CCP2-positive patients. The individual correction for arginine peptide reactivity confers both higher diagnostic sensitivity and stronger association to SE than gross ACPA measurement.
Abstract 14051: Changes in Medical Therapy and Lifestyle After Anatomical Versus Functional Testing for Coronary Artery Disease: The PROMISE Trial (PROspective Multicenter Imaging Study for Evaluation of Chest Pain)
Authors: Joseph A Ladapo, Udo Hoffmann, Kerry L Lee, Adrian Coles, Megan Huang, Daniel B Mark, Rowena L Dolor, Robert A Pelberg, Matthew Budoff, Gardar Sigurdsson, Harry W Severance, Pamela S Douglas
Journal: Circulation (2015)

Introduction: Diagnostic testing may represent a “teachable moment” for patients newly presenting with symptoms suggestive of CAD and requiring further evaluation, and may influence risk factor management, independent of test results. However, little is known about changes in medications and lifestyle after anatomical versus functional testing. Hypothesis: Patients assigned to coronary CTA will report greater use of preventive medications and lifestyle practices. Methods: We randomly assigned 10,003 symptomatic patients (53% women; mean age 61 yrs) to anatomical testing with CTA or functional testing (exercise ECG, nuclear stress, or stress echocardiography). We assessed use of preventive medications (aspirin, statin, beta blocker, and ACEi/ARB) and lifestyle practices (heart healthy diet, regular exercise, smoking, and obese/overweight status [BMI&gt;25]) at 60 days. Chi-square tests assessed between-group changes (initiation or discontinuation). Multivariable logistic regression models assessed the association between testing strategy and prevalence of medication use or lifestyle practices. Results: There were no differences in medications or lifestyle practices at baseline. At 60 days, the CTA strategy was associated with a higher proportion of patients newly initiating aspirin (11.6% vs 7.6%), statin (12.7% vs 6.2%), and beta blockers (8.2% vs 5.4%), compared to functional testing (p&lt;0.0001 for each). The CTA strategy was also associated with a higher incidence of weight loss among obese/overweight patients (2.8% vs 2.4%), but the difference was not significant (p=0.051). Overall prevalences of aspirin (aOR=1.55), statin (aOR=2.04), and beta blocker (aOR=1.32) use were higher after CTA (p&lt;0.001 for each). Eating a healthy diet (54.7% vs 50.8%) was increased after CTA (aOR=1.13 p=0.004), whereas obese/overweight status was reduced (aOR=0.79 p=0.047). Exercise and smoking cessation increased similarly in both arms. Benefits of CTA for statin use and weight loss persisted after adjusting for test results. Conclusions: Among patients with suspected CAD, anatomical testing is associated with greater favorable changes in preventive medical and lifestyle practices. This may represent a long term benefit of a CTA testing strategy.
Effects of Coal Fly Ash Particulate Matter on the Antimicrobial Activity of Airway Surface Liquid
Authors: Luis G. Vargas Buonfiglio, Imali A. Mudunkotuwa, Mahmoud H. Abou Alaiwa, Oriana G. Vanegas Calderón, Jennifer A. Borcherding, Alicia K. Gerke, Joseph Zabner, Vicki H. Grassian, Alejandro P. Comellas
Journal: Environmental Health Perspectives (2017)

Sustained exposure to ambient particulate matter (PM) is a global cause of mortality. Coal fly ash (CFA) is a byproduct of coal combustion and is a source of anthropogenic PM with worldwide health relevance. The airway epithelia are lined with fluid called airway surface liquid (ASL), which contains antimicrobial proteins and peptides (AMPs). Cationic AMPs bind negatively charged bacteria to exert their antimicrobial activity. PM arriving in the airways could potentially interact with AMPs in the ASL to affect their antimicrobial activity.We hypothesized that PM can interact with ASL AMPs to impair their antimicrobial activity.We exposed pig and human airway explants, pig and human ASL, and the human cationic AMPs β-defensin-3, LL-37, and lysozyme to CFA or control. Thereafter, we assessed the antimicrobial activity of exposed airway samples using both bioluminescence and standard colony-forming unit assays. We investigated PM-AMP electrostatic interaction by attenuated total reflection Fourier-transform infrared spectroscopy and measuring the zeta potential. We also studied the adsorption of AMPs on PM.We found increased bacterial survival in CFA-exposed airway explants, ASL, and AMPs. In addition, we report that PM with a negative surface charge can adsorb cationic AMPs and form negative particle-protein complexes.We propose that when CFA arrives at the airway, it rapidly adsorbs AMPs and creates negative complexes, thereby decreasing the functional amount of AMPs capable of killing pathogens. These results provide a novel translational insight into an early mechanism for how ambient PM increases the susceptibility of the airways to bacterial infection. https://doi.org/10.1289/EHP876.
TCT-105 Clinical Valve Thrombosis after Transcatheter Aortic Valve-in-Valve Implantation for Degenerated Bioprosthetic Valves: Incidence, Characteristics and Outcomes
Authors: Mohamed Abdel-Wahab, Azeem Latib, Patrick Goleski, Abdelhakim Allali, Eric Horlick, Luca Testa, Malek Kass, Creighton Don, Matheus Simonato dos Santos, John Webb, Danny Dvir
Journal: Journal of the American College of Cardiology (2017)
TCT-261 One-year outcomes of the hybrid CTO revascularization strategy: a sub-analysis of the multicenter RECHARGE Registr
Authors: Joren Maeremans, Alexandre Avran, Simon Walsh, Paul Knaapen, Benjamin Faurie, Pierfrancesco Agostoni, Erwan Bressollette, Dave Smith, Margaret McEntegart, William Smith, Alun Harcombe, John Irving, James Spratt, Joseph Dens
Journal: Journal of the American College of Cardiology (2017)
Cuticular Drusen
Authors: Chandrakumar Balaratnasingam, Svetlana Cherepanoff, Rosa Dolz-Marco, Murray Killingsworth, Fred K. Chen, Randev Mendis, Sarah Mrejen, Lay Khoon Too, Orly Gal-Or, Christine A. Curcio, K. Bailey Freund, Lawrence A. Yannuzzi
Journal: Ophthalmology (2017)
TCT-249 Clinical Outcomes of Biodegradable Polymer Sirolimus Eluting Stent in Diabetes Mellitus Patients.
Authors: Cosmo Godino, Carlo Andrea Pivato, Alessandro Beneduce, Alberto Cappelletti, Giuseppe Ferrante, Franco Fabbiocchi, Stefania Falcone, Alfonso Ielasi, Adele Pierri, Mauro Chiarito, Valeria Magni, Giulia Perfetti, Andrea Scotti, Matteo Montorfano, Stefano De Martini, Rosario Parisi, David Rutigliano, Nicola Locuratolo, Alberto Margonato, Alberto Benassi, Angelo Anzuini, Bernhard Reimers, Maurizio Tespilli, Carlo Briguori, Antonio Bartorelli, Antonio Colombo
Journal: Journal of the American College of Cardiology (2017)
TCT-541 Multi-center experience of MitraClip therapy in patients with Ischaemic and Non-ischaemic Functional Mitral Regurgitation: 2-year outcomes
Authors: Andrea Scotti, Maurizio Taramasso, Marianna Adamo, Marco Russo, Mauro Chiarito, Francesco Melillo, Alessandro Beneduce, Luca Baldetti, Carlo Andrea Pivato, Anna Salerno, Alberto Cappelletti, Valeria Magni, Stefano Stella, Gabriele Fragasso, Matteo Montorfano, Eustachio Agricola, Federica Ettori, Alberto Margonato, Francesco Maisano, Antonio Colombo, Cosmo Godino
Journal: Journal of the American College of Cardiology (2017)
TCT-378 Prognosis of Patients with Significant Coronary Artery Spasm without Fixed Stenosis and Treated with/without Calcium Channel Blockers
Authors: Woo Hyeun Kim, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Ahmed Mashaly, Won Young Jang, Eun Jin Park, Ja Yeon Choi, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2017)
Uptake of 68Ga–Prostate-Specific Membrane Antigen PET in Adrenal Gland
Authors: Pia Strele-Trieb, Andreas Dunzinger, Michael Sonnberger, Johannes Wolfsgruber, Robert Pichler
Journal: Clinical Nuclear Medicine (2017)

A 76-year-old man with prostate cancer pT2c N0 M0 R1 GS9 (4+5) operated 2009 and radiated postoperatively underwent restaging by Ga-PSMA-PET in January 2017 because of PSA rise at 0.44 ng/ml under medication with GnRH analogues. An intense focal uptake of the diffusely enlarged left adrenal gland was observed as the only pathological finding. Further evaluation by MRI imaging revealed a plump left adrenal gland with a relatively enlarged diameter of 2 cm and excluded tumor and nodular hyperplasia as well. Without any change of the therapeutic regime the patient presented in July 2017 with a PSA level of 0.05 ng/ml and no sign of cancer progress.
Valor da vacina da gripe durante um surto de gripe Influenza A num lar de 3ª idade, Pirenéus Atlânticos, França, Novembro-Dezembro de 1995
Authors: A Infuso, S Baron, H Fauveau, M Melon, H Fleury, J C Desenclos
Journal: Eurosurveillance (1996)

Na regiao de Puglia no sudeste da Italia (populacao: 4 milhoes de habitantes), o numero de notificacoes de hepatite a virus A (HAV) aumenta em ciclos de 2 anos. Em 1992 registou-se um grande surto, mas nao foi feita qualquer investigacao epidemiologica. A maior parte dos casos sao notificados no inicio do ano (figura 1). Em finais de 1995, Puglia aderiu ao projecto nacional para a informatizacao do sistema de vigilância das doencas infecciosas (Sistema de Informacao das Doencas Infecciosas, SIDI).
miR-519d Promotes Melanoma Progression by Downregulating EphA4
Authors: Kuo-Tai Hua, Jin-Bong Hong, Yi-Shuan Sheen, Hsin-Yi Huang, Yi-Ling Huang, Jau-Shiuh Chen, Yi-Hua Liao
Journal: Cancer Research (2017)

Abstract Increasing evidence suggests that there is a unique cell subpopulation in melanoma that can form nonadherent melanospheres in serum-free stem cell medium, mimicking aggressive malignancy. Using melanospheres as a model to investigate progression mechanisms, we found that miR-519d overexpression was sufficient to promote cell proliferation, migration, invasion, and adhesion in vitro and lung metastatic capability in vivo. The cell adhesion receptor EphA4 was determined to be a direct target of miR-519d. Forced expression of EphA4 reversed the effects of miR-519d overexpression, whereas silencing of EphA4 phenocopied the effect of miR-519d. Malignant progression phenotypes were also affected at the level of epithelial-to-mesenchymal transition and the ERK1/2 signaling pathway inversely affected by miR-519d or EphA4 expression. In clinical specimens of metastatic melanoma, we observed significant upregulation of miR-519d and downregulation of EphA4, in the latter case correlated inversely with overall survival. Taken together, our results suggest a significant functional role for miR-519d in determining EphA4 expression and melanoma progression. Significance: These results suggest a significant role for miR-519d in determining expression of a pivotal cell adhesion molecule that may impact risks of malignant progression in many cancers. Cancer Res; 78(1); 216–29. ©2017 AACR.
Triple therapy reduced mortality more than oseltamivir alone in patients admitted for severe influenza infection
Authors: Nikolaos Andreatos, Eleftherios Mylonakis
Journal: Annals of Internal Medicine (2017)

Source Citation Hung IFN, To KKW, Chan JFW, et al. Efficacy of clarithromycin–naproxen–oseltamivir combination in the treatment of patients hospitalized for influenza A(H3N2) infection: an open-label randomized, controlled, phase IIb/III trial. Chest. 2017;151:1069-80. 27884765
Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation
Authors: Valentina Cambiano, Alec Miners, David Dunn, Sheena McCormack, Koh Jun Ong, O Noel Gill, Anthony Nardone, Monica Desai, Nigel Field, Graham Hart, Valerie Delpech, Gus Cairns, Alison Rodger, Andrew N Phillips
Journal: The Lancet Infectious Diseases (2017)
TCT-309 Underlying Plaque, not Platelet Inhibition Is Associated with Optical Coherence Tomography Detected Intra-Procedural Thrombus
Authors: Masaru Ishida, Gary Mintz, Mitsuaki Matsumura, Dong Yin, Allen Jeremias, Ziad Ali, Jane Cao, Jeronimo Rodriguez, Fernando Sosa, Jeffrey W. Moses, Elizabeth Haag, Richard Shlofmitz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2017)
Frailty in Older Adults Undergoing Aortic Valve Replacement
Authors: Jonathan Afilalo, Sandra Lauck, Dae H. Kim, Thierry Lefèvre, Nicolo Piazza, Kevin Lachapelle, Giuseppe Martucci, Andre Lamy, Marino Labinaz, Mark D. Peterson, Rakesh C. Arora, Nicolas Noiseux, Andrew Rassi, Igor F. Palacios, Philippe Généreux, Brian R. Lindman, Anita W. Asgar, Caroline A. Kim, Amanda Trnkus, José A. Morais, Yves Langlois, Lawrence G. Rudski, Jean-Francois Morin, Jeffrey J. Popma, John G. Webb, Louis P. Perrault
Journal: Journal of the American College of Cardiology (2017)
Longer-Term Impact of High and Low Temperature on Mortality: An International Study to Clarify Length of Mortality Displacement
Authors: Ben Armstrong, Michelle L. Bell, Micheline de Sousa Zanotti Stagliorio Coelho, Yue-Liang Leon Guo, Yuming Guo, Patrick Goodman, Masahiro Hashizume, Yasushi Honda, Ho Kim, Eric Lavigne, Paola Michelozzi, Paulo Hilario Nascimento Saldiva, Joel Schwartz, Matteo Scortichini, Francesco Sera, Aurelio Tobias, Shilu Tong, Chang-fu Wu, Antonella Zanobetti, Ariana Zeka, Antonio Gasparrini
Journal: Environmental Health Perspectives (2017)

BACKGROUND: In many places, daily mortality has been shown to increase after days with particularly high or low temperatures, but such daily timeseries studies cannot identify whether such increases reflect substantial life shortening or short-term displacement of deaths (harvesting).OBJECTIVES: To clarify this issue, we estimated the association between annual mortality and annual summaries of heat and cold in 278 locations from 12 countries.METHODS: Indices of annual heat and cold were used as predictors in regressions of annual mortality in each location, allowing for trends over time and clustering of annual count anomalies by country and pooling estimates using meta-regression.We used two indices of annual heat and cold based on preliminary standard daily analyses: a) mean annual degrees above/below minimum mortality temperature (MMT), and b) estimated fractions of deaths attributed to heat and cold.The first index was simpler and matched previous related research; the second was added because it allowed the interpretation that coefficients equal to 0 and 1 are consistent with none (0) or all (1) of the deaths attributable in daily analyses being displaced by at least 1 y.RESULTS: On average, regression coefficients of annual mortality on heat and cold mean degrees were 1.7% [95% confidence interval (CI): 0.3, 3.1] and 1.1% (95% CI: 0.6, 1.6) per degree, respectively, and daily attributable fractions were 0.8 (95% CI: 0.2, 1.3) and 1.1 (95% CI: 0.9, 1.4).The proximity of the latter coefficients to 1.0 provides evidence that most deaths found attributable to heat and cold in daily analyses were brought forward by at least 1 y.Estimates were broadly robust to alternative model assumptions.CONCLUSIONS: These results provide strong evidence that most deaths associated in daily analyses with heat and cold are displaced by at least 1 y.
Analysis of Bcl-2 family protein expression after treatment of leukemia cell lines with homoharringtonine
Authors: David Segal, Shawnya Michaels, Adam Craig, William Plunkett, Dennis Brown
Journal: Cancer Research (2008)

2350  The natural product alkaloid Homoharringtonine (HHT) [omacetaxine mepesuccinate- USAN/INN designation] has produced encouraging results in clinical trials as a therapy for patients with CML resistant to tyrosine kinase inhibitor therapies. HHT has been shown to be an effective inhibitor of proteins synthesis (via inhibition of the elongation step of polypeptide synthesis) and to induce apoptosis and inhibit angiogenesis. In clinical studies of CML patients that are resistant to imatinib mesylate, HHT treatment has been shown to decrease BCR-ABL transcript levels which raises the possibility that HHT may be affecting alternate molecular pathways. Long term HHT treatment (>16 hr) of BCR-ABL and non-BCR-ABL positive leukemia cells activates apoptosis and modulates expression of bcl-2 family proteins and proapoptotic caspases. To further delineate the early (
Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery
Authors: Wanling Liang, Alan Y.L. Chan, Michael Y.T. Chow, Fiona F.K. Lo, Yingshan Qiu, Philip C.L. Kwok, Jenny K.W. Lam
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The therapeutic potential of small nucleic acids such as small interfering RNA (siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled formulation. In this study, spray freeze drying was employed to prepare dry powder of small nucleic acids. Mannitol and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. Formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope (SEM) images showed that the porosity of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry powder formulation containing 2% w/w DNA had a median diameter of 12.5 µm, and the aerosol performance study using next generation impactor (NGI) showed an emitted fraction (EF) and fine particle fraction (FPF) of 91% and 28% respectively. This formulation (5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently to produce siRNA powder. The gel retardation and liquid chromatography assays showed that the siRNA remained intact after spray freeze drying even in the absence of delivery vector. The siRNA powder formulation exhibited a high EF of 92.4% and a modest FPF of around 20%. Further exploration of this technology to optimise inhaled siRNA powder formulation is warranted.
Nearly Neutral Evolution across the Drosophila melanogaster Genome
Authors: David Castellano, Jennifer James, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2018)

Under the nearly neutral theory of molecular evolution, the proportion of effectively neutral mutations is expected to depend upon the effective population size (Ne). Here, we investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from North American and African lines. We show that the ratio of the number of nonsynonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the nonindependence is accounted for. The relationship is such that the proportion of effectively neutral nonsynonymous mutations increases by ∼45% as Ne is halved. However, we also show that this relationship is steeper than expected from an independent estimate of the distribution of fitness effects from the site frequency spectrum. We investigate a number of potential explanations for this and show, using simulation, that this is consistent with a model of genetic hitchhiking: Genetic hitchhiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites.
Comparison Between Different PET and CT-Based Imaging Interpretation Criteria at Interim Imaging in Patients With Diffuse Large B-Cell Lymphoma
Authors: Lucia Baratto, Guido A. Davidzon, Mateen Moghbel, Negin Hatami, Andrei Iagaru, Erik S. Mittra
Journal: Clinical Nuclear Medicine (2017)

To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0.We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria.The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively).The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.
Intravesical and Intradermal Bacillus Calmette-Guérin Application
Authors: L.M.H. Schreinemachers, A.P.M. van der Meijden, J. Wagenaar, P.A. Steerenberg, W.F.J. Feitz, D.G. Groothuis, R.H. Tiesjema, W.H. deJong, F.M.J. Debruyne, E.J. Ruitenberg
Journal: European Urology (1988)
TCT-476 Hemodynamic Effects of Valve Asymmetry in Sapien 3 Transcatheter Aortic Valves
Authors: Daniel Mangels, Mary Siki, Rohan Menon, Joseph Bavaria, Saif Anwaruddin, Jay Giri, Nimesh Desai, Wilson Y. Szeto, Prashanth Vallabhajosyula, Howard Herrmann
Journal: Journal of the American College of Cardiology (2017)