tbuckley/cabot-search huggingface dataset:
OP0037 Pulsed Cyclophosphamide in the Treatment of Rheumatoid Arthritis-Related Interstitial Lung Disease (RA-ILD)
Authors: C. Kelly, E. Palmer, J. Gordon, F. Woodhead, M. Nisar, S. Arthanari, A. Forbes-Price, D. Middleton, O. Dempsey, J. Dawson, N. Sathi, Y. Ahmad, G. Koduri
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There is little evidence base to guide clinicians in the management of patients with rheumatoid arthritis (RA) related interstitial lung disease (ILD). In the subgroup who have rapidly deteriorating respiratory function, pulsed cyclophosphamide has been advocated but no assessment of its efficacy has been published. The British Rheumatoid InterstitiaL Lung (BRILL) network has collected data on the treatment and outcomes of 260 patients with RA-ILD, which allow assessment of this therapeutic strategy. <h3>Objectives</h3> To assess the effect of pulsed IV cyclophosphamide on the outcome of patients with RA-ILD <h3>Methods</h3> We identified 260 patients across 16 UK centres who met the 2010 EULAR criteria for RA and had confirmation of ILD on high resolution computed tomography (HRCT) of the lungs. We analysed demography, all drug therapy, duration of disease, subtype and extent of ILD on HRCT, smoking history, serology and baseline pulmonary function. For each patient who had received pulsed intravenous cyclophosphamide, we identified two case controls with RA-ILD who had never received this drug and who were matched for age, gender, disease subtype and extent. We compared duration of both RA and of ILD between the two groups, as well as vital capacity (VC) and gas transfer (TLco). Mortality and mean survival times in each group were compared. <h3>Results</h3> We identified 21 patients who had received pulsed cyclophosphamide for progressive RA-ILD. Ten were male and the group median age was 71 (58-86) years. Most patients were smokers (13/21) and all were seropositive. Median duration of ILD and RA were 2 and 11 years respectively in both the cyclophosphamide treated group and in the case controls. In both groups, 14 patients had UIP (with 7 NSIP), and 14 patients had extensive disease (with 7 limited). Median baseline % predicted VC (range) was lower in the cyclophosphamide patients at 71% (40-117%) than in case controls 84% (55-134%) [p=0.015], as was TLco at 45% (25-109%) vs 57% (27-82%) [p=0.04]. Mortality was identical between the groups at 24%, with mean survival better in those treated with cyclophosphamide than in case controls (72 vs 43 months)[p=0.13]. <h3>Conclusions</h3> This data from the BRILL network shows that the use of pulsed cyclophosphamide for patients with progressive RA-ILD is associated with mortality and survival at least as good as in RA-ILD patients with lesser impairment of baseline pulmonary function. This retrospective analysis supports the early use of such therapy in patients with deteriorating RA-ILD. A prospective study similar to that conducted in scleroderma lung disease would now seem appropriate to confirm these results and define an optimal treatment regime. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2342
A6.3 The role of micro-RNA 155 in autoimmune arthritis
Authors: E Goncalves-Alves, V Saferding, A Puchner, R Benson, M Kurowska-Stolarska, J Brewer, C Schliehe, A Bergthaler, JS Smolen, K Redlich, S Blüml
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> MicroRNAs are a novel class of regulatory RNAs that have been demonstrated to control several important biological processes. They have been implicated in the pathogenesis of auto-immunity; however their true contribution in these diseases it is not truly clear. MicroRNA-155 (miR-155) has been demonstrated to be present in inflamed joints of patients suffering from rheumatoid arthritis (RA) as well as being essential for the development of collagen induced arthritis (CIA). Our goal is to understand which immune cells contribute for the resistance of miR-155 deficient mice to CIA. <h3>Methods</h3> MiR155 deficient mice were crossed into hTNFtg mice, arthritis development was evaluated. Activation and cytokine production of bone marrow derived dendritic cells (BMDC) was evaluated both <i>in vivo</i> and <i>in vitro</i>, by flow cytometry and qPCR. T cell stimulatory capacity was evaluated by mixed lymphocyte reaction with OTII T cells, containing an ovalbumin specific TCR. MiR-155 OTII deficient T cells were transferred into wild type mice or co-cultured with wild type (wt) BMDCs. Sorted naïve T cells were stimulated with anti-CD28 and anti-CD3. <h3>Results</h3> In hTNF innate immunity dependent arthritis model we saw no difference in disease development between miR-155<sup>-/-</sup> and wt mice. Expression of MHCII and co-stimulatory molecules after LPS stimulation was similar in miR-155 deficient and wt BMDCs. LPS treatment of wt and miR-155<sup>-/-</sup> mice revealed similar pro-inflammatory cytokine production (TNF, IL-6 and IL-23). Furthermore, T cell stimulatory capacity of wt and miR-155<sup>-/-</sup>was identical both <i>in vitro</i> and <i>in vivo</i>. Contrasting with the limited role in innate immune cells, miR-155 deficient T cells show a severely impaired proliferative capacity <i>in vivo</i> and <i>in vitro</i>. However, proliferation of naïve T cells was similar upon stimulation with anti-CD3 and anti-CD28 <h3>Conclusion</h3> Although role of miR-155 in innate immunity seem to be limited, it appears that the resistance to induction of CIA come from a defect in adaptive immunity. This is seen by the reduced proliferative capacity of miR-155 deficient cells when stimulated by wt BMDCs, both <i>in vivo</i> and <i>in vitro</i>. Therefore miR-155 might represent an interesting therapy target for autoimmune diseases such as rheumatoid arthritis.
TRANSFEMORAL TRICUSPID VALVE-IN-VALVE AND VALVE-IN-RING IMPLANTATION USING THE EDWARDS SAPIEN XT VALVE: ONE-YEAR FOLLOW-UP
Authors: Claire Bouleti, Dominique Himbert, Eric Brochet, Phalla Ou, Bernard Iung, Marina Urena, Walid Ghodbane, Amir-Ali Fassa, Patrick Nataf, Alec Vahanian
Journal: Journal of the American College of Cardiology (2016)
805 WEEK 4 AND 12 EFFICACY OF TELAPREVIR (TVR) IN COMBINATION WITH PEGINTERFERON alfa 2a/RIBAVIRIN (P/R) IN TREATMENT EXPERIENCED PATIENTS WITH GT-1 UNDER REAL LIFE CONDITIONS
Authors: S. Christensen, S. Mauss, C. Eisenbach, M.-C. Jung, M. Roessle, F. Emke, S. Pape, A.v. Lucadou, M. Frank Doss, M. Schuchmann, R. Ullrich, P. Erren, U. Alshuth, D. Hueppe, P. Buggisch
Journal: Journal of Hepatology (2013)
An American Thoracic Society Official Research Statement: Future Directions in Lung Fibrosis Research
Authors: Eric S. White, Zea Borok, Kevin K. Brown, Oliver Eickelberg, Andreas Guenther, R. Gisli Jenkins, Martin Kolb, Fernando J. Martinez, Jesse Roman, Patricia Sime
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsModeling Lung FibrosisEngaging Stakeholders to ...InfrastructureEstablishing Synergistic ...Development of a Global L...SummaryReferencesCITING ARTICLES
P5-02-05: Real-Time Subcellular Imaging of Breast Cancer Cell Attachment in Blood Vessels Using GFP-Labeled Paxillin in Live Mice.
Authors: A Suetsugu, M Digman, E Gratton, H Moriwaki, S Saji, M Bouvet, RM Hoffman
Journal: Cancer Research (2011)

Abstract Background: Paxillin is involved in the assembly of focal adhesions. We wish to visualize paxillin behavior in breast cancer cells in vivo, as well as in vitro. Materials and Methods: Dual-photon confocal microscopy was used to image paxillin behavior by linking it to GFP. MDA-MB-231 human breast cancer cells expressing paxillin-GFP were imaged in vitro and in vivo adhering and trafficking in blood vessels in mice. 106 paxillin-GFP expressing breast cancer cells were injected in the epigastric cranialis vein. Results: In vitro, round breast cancer cells had greater paxillin movement than stretched cancer cells as seen by fluorescence imaging. Paxillin-GFP breast cancer cells in the epigastric cranialis vein were initially rounded and had GFP-expressing protrusions. At later timepoints, many paxillin-GFP-expressing breast cancer cells stretched. The breast cancer cells then extravasated and subsequently grew around the outer surface of the blood vessel after one week. Two weeks after injection, paxillin-GFP expressing breast cancer cells were imaged migrating along the vessel wall. Most of the paxillin-GFP expressing breast cancer cells were stretched and were not mobile. With anti-VEGF treatment, paxillin was observed in round structures within the cells rather than stretched structures and paxillin movement within the cell was arrested. Discussion: These results demonstrate that breast cancer cells brightly expressing paxillin-GFP and two-photon confocal microscopy can allow the visualization of the behavior of paxillin within breast cancer cells during adhesion and migration along the walls of blood vessels, as well as during anti-angiogenesis therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-02-05.
Abstract 3232: Oligonucleotide-selective sequencing (OS-Seq): a rapid and efficient targeting technology for ultra-deep detection of cancer mutations and rearrangements.
Authors: Erik S. Hopmans, Georges Natsoulis, Jason Buenrostro, Sue Grimes, John Bell, Hanlee P. Ji
Journal: Cancer Research (2013)

Abstract Somatic mutations, chromosomal rearrangements and other genomic aberrations in cancer genomes are critical events in the development of cancer and increasingly used in identifying oncogenic events that may be indicators for targeted therapies. For rapid and high accuracy analysis of targeted candidate genes and regions from cancer genomes, we developed OS-Seq that can be used to simultaneously discover cancer point mutations, copy number variants and rearrangements. For this new sequencing technology, we re-engineer the immobilized oligonucleotide primer lawn on a solid phase support (e.g. Illumina flow cell) with capture “primer-probes” such that it functions for both genomic target capture and sequencing (Myllykangas et al. 2011, Nature Biotech). As a result, in a matter of days we can rapidly sequence target regions in cancer genomes. We designed an in-silico exome capture probe set, enabling rapid design of disease-specific targeted capture primer probe sets. Subsequently, we designed assays to cover 313 and 1,400 cancer genes. Using the 313-gene assay targeting 5,000 exons, we can routinely sequence cancer genomes with on-target coverage greater than 500X, including for the entire length of exons as large as 1 Mb regions. Using a smaller gene set we have established coverage depths over 8,000 that enables the investigation of tumor evolution via mutations with low allelic fractions. In addition, we have designed OS-Seq assays for characterizing loci that are involved in rearrangements. We design capture probes positioned on opposing strands upstream and downstream of suspected rearrangement breakpoints and by localized assembly were able to confirm certain rearrangements, including a long deletion and inversions. For our current studies, we are using OS-Seq to identify cancer mutations in colorectal adenocarcinoma and determine the extent of genetic heterogeneity prevalent in these tumors. OS-Seq provides high-depth, high quality cancer genome sequence data, opening the door to potential diagnostic analysis of cancer genetic heterogeneity as seen in tumor evolution and cancer rearrangements. Citation Format: Erik S. Hopmans, Georges Natsoulis, Jason Buenrostro, Sue Grimes, John Bell, Hanlee P. Ji. Oligonucleotide-selective sequencing (OS-Seq): a rapid and efficient targeting technology for ultra-deep detection of cancer mutations and rearrangements. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3232. doi:10.1158/1538-7445.AM2013-3232
PET Response Criteria for Solid Tumors Predict Survival at Three Months After Intra-Arterial Resin-Based 90Yttrium Radioembolization Therapy for Unresectable Intrahepatic Cholangiocarcinoma
Authors: Juan C. Camacho, Nima Kokabi, Minzhi Xing, David M. Schuster, Hyun S. Kim
Journal: Clinical Nuclear Medicine (2014)

PET Response Criteria for Solid Tumors (PERCIST) were assessed and correlated with survival analysis after resin-based 90Yttrium (90Y) radioembolization therapy for intrahepatic cholangiocarcinoma (ICC).Target and overall PERCIST and Response Criteria for Solid Tumors (RECIST) treatment responses were assessed in consecutive patients treated with Y radioembolization for ICC refractory to standard chemotherapy. Significant measurable tumor was defined as 1 cm or greater in diameter and SUVpeak of 2.5 or greater in targeted and nontargeted lesions. The PERCIST defines complete response as resolution of 18F-FDG uptake within measurable lesions, and partial response as 30% reduction in 18F-FDG peak standardized uptake value in measurable lesions. Objective response included partial response and complete response. Survival analysis by Kaplan-Meier and log-rank proportional models was performed using SPSS software version 20.0 (IBM, Armonk, NY), and significance was set at P < 0.05.Median overall survival (OS) of 9 consecutive patients (56% women; mean age, 58 years) from 90Y therapy was 21.7 months. At 3 months, PERCIST objective response rate of target lesions was 77.7%, and target objective response on PERCIST correlated significantly to prolonged OS (P = 0.022). Overall objective PERCIST response at 3 months had significant correlation with OS (P = 0.011). Probability of death was significantly higher in overall nonresponders by PERCIST (hazard ratio, 12.3). No objective response was seen with RECIST.In patients with unresectable ICC refractory to standard chemotherapy, PERCIST at 3 months for assessment of imaging response after 90Y radioembolization therapy predict OS.
Reduced F-18 Fluorodeoxyglucose Uptake Within Marrow After External Beam Radiation
Authors: M A Meyer, C A Nathan
Journal: Clinical Nuclear Medicine (2000)

Purpose: The authors examined the delayed effects of external beam radiation on the metabolism of intravertebral marrow cavities. Materials and Methods: Two neurologically normal persons who had completed a full course of external beam radiotherapy for squamous cell carcinoma of the head and neck had positron emission tomography (PET) scans with F-18 fluorodeoxyglucose (FDG) to identify residual neoplasm. Results: Abnormally low uptake of F-18 FDG was noted within the central marrow cavities of the cervical vertebral bodies in both cases. Conclusions: Diminished metabolic activity within irradiated marrow can be revealed by F-18 FDG PET imaging techniques. Further correlative MRI PET studies are needed to determine if this postradiation phenomenon is related to fatty infiltration of the marrow cavity.
Trends of hepatitis B notification rates in Turkey, 1990 to 2012
Authors: P Ay, M A Torunoglu, S Com, Z Çipil, S Mollahaliloğlu, Y Erkoç, U Dilmen
Journal: Eurosurveillance (2013)

Turkey is a country with intermediate endemicity for hepatitis B, and approximately 4% of the population are HBsAg-positive. A number of measures have been implemented to prevent hepatitis B infection. In 1998, hepatitis B antigen was included in the national immunisation programme, and infants have since been vaccinated with three doses. Catch-up strategies, vaccination for high risk groups and screening measures were also adopted. The aim of this study was to evaluate the impact of the prevention and control strategies on hepatitis B notification rates in Turkey in the period from 1990 to 2012, using data from the national surveillance system. Secular trends revealed that rates showed an initial increasing trend, followed by a steady decline from 2005. The most dramatic decline occurred among children younger than 15 years, highlighting the benefits of vaccination and catch-up strategies. However, vaccination cannot fully explain the decrease in this age group. Socioeconomic development, through interrupting the horizontal transmission may also have contributed. After 2005, a steady decline was achieved also among those 15 years and older. The rates in adults were higher, which indicates that stronger prevention measures are needed to target this group, particularly men.
Endoscopic submucosal resection of esophageal subepithelial lesions using band ligation
Authors: D. Lee, G. Kim, D. Park, J. Jeong, J. Moon, B. Lee, I. Hosuk, G. Song
Journal: Endoscopy (2011)

Subepithelial lesions (SELs) are occasionally found in the esophagus during upper endoscopy. Sometimes endoscopic resection is needed for accurate diagnosis or in the rare cases of malignant transformation of SELs. In this case series, we evaluated the usefulness of endoscopic submucosal resection with a ligation device (ESMR-L) in esophageal SELs. Twenty-three patients with 25 esophageal SELs that were no larger than 13 mm and were localized within the muscularis mucosae or submucosa were enrolled. ESMR-L was successfully performed in all 25 SELs. The en bloc resection rate was 100% (25/25), and histologically complete resection was achieved in 24 lesions (24/25, 96%). After resection of the lesion by snare, minor immediate bleeding occurred in four cases, but there was no delayed bleeding or perforation.
P249 Physicians' opinion: ceilings of therapy in chronic obstructive pulmonary disease (PILOT study)
Authors: J. L. Gallagher, B. Morton, I. Clegg, J. Walker, L. Davies
Journal: Thorax (2010)

<h3>Introduction</h3> Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a common reason for hospital admission. Treatment depends upon the severity of presentation and background physiological status. The COPD NICE guidelines (2010) state that when patients are started on NIV, there should be a clear plan covering what to do in the event of deterioration and ceilings of therapy should be agreed.1 We sought to explore decision making among clinicians with responsibility for interventional treatments in difficult scenarios. <h3>Method</h3> We questioned intensive care and respiratory clinicians in two deaneries. We described six hypothetical patients with COPD who presented to an A&amp;E department in hypercapnic respiratory failure. The histories given were of end stage COPD, ischaemic heart disease, complicated diabetes mellitus, advanced age, potentially curable bronchial carcinoma and non-concordance with treatment. <h3>Results</h3> One hundred and thirteen questionnaires were collected; 58 intensive care medicine (ICM) clinicians (28 consultant and 30 specialist trainees) and 55 respiratory medicine physicians (13 consultant and 42 specialist trainees). The majority of respondents would intervene in the presented scenarios, either with invasive or non-invasive ventilation as illustrated in graph 1. No statistical difference in decision making was demonstrated between ICM and respiratory clinicians. Statistical kappa analysis (Intercooled Stata 9.0) demonstrated ‘fair’ agreement among ICM trainees, respiratory trainees and consultants when choosing non-invasive (0.32, 0.41, 0.33) and invasive ventilation (0.29, 0.39, 0.36) with ‘slight’ agreement among ICM consultants (non-invasive 0.12 and invasive ventilation 0.22). Some respiratory physicians felt that they required additional information, such as results of spirometry, to make informed decisions. However, in an acute setting, such information is often unavailable so was not included in the vignettes. The opportunistic nature of data collection meant that a response rate could not be calculated. <h3>Conclusion</h3> This pilot study did not demonstrate a difference in decision making between respiratory and intensive care specialities. With development of the vignettes this methodology could form the basis for a national survey on ceilings of therapy in COPD to inform the individual clinician when making difficult decisions.
P830 THE −11391G/A POLYMORPHISM IN THE PROMOTER REGION OF THE ADIPOQ GENE PROTECTS FROM SEVERE STEATOSIS IN NONALCOHOLIC FATTY LIVER DISEASE
Authors: M.J. Brochado, F.A. Domenici, A.L. Martinelli, A.C. Teixeira, L.N. Ramalho, H.D. Vannucchi
Journal: Journal of Hepatology (2014)
Ameloblastoma of the Jaw
Authors: Robert Goldwyn, John Constable, Joseph E. Murray
Journal: New England Journal of Medicine (1963)

A MELOBLASTOMA, or adamantinoma, of the jaw is uncommon, and its treatment controversial.1 2 3 4 5 6 The terms "ameloblastoma" (Old French, amel, enamel, plus Greek, blastos, germ) and "adamantinoma" (Greek, adamos, hard substance) are both misnomers for this tumor because ameloblasts that elaborate enamel need not be present, and since enamel is not produced, the tumor is not hard. What is by custom called an ameloblastoma or adamantinoma is a characteristic epithelial tumor that may arise from one of many dental sources: the epithelial lining of a dentigerous cyst; the remnants of the dental lamina or of the enamel organ; . . .
Abstract B19: Cigarette smoke promotes human airway epithelial migration through temporal coordination of p120-catenin-dependent and -independent pathways
Authors: Lili Zhang, Marianne Gallup, Lorna Zlock, Walter E. Finkbeiner, Nancy A. McNamara
Journal: Cancer Research (2011)

Abstract Background: Cigarette smoking has been linked to almost all major types of cancer. Emerging evidence suggests that smoking initiates transformed cell growth and migration by disrupting cell-cell interactions in the polarized mucosal epithelium. Together with other adherens junction proteins, p120-catenin (p120ctn) maintains cell-cell adhesion through its direct interaction with E-cadherin. Mislocalization and/or loss of p120ctn have been reported in all lung cancer subtypes and are related to poor prognosis. Our purpose was to investigate the initiating (intact p120ctn) and late (loss of 120ctn) events of smoke-promoted lung carcinogenesis using primary human bronchial epithelial (HBE) cells. Methods: Wide-type and p120ctn-knockdown HBE cells exposed to cigarette smoke-conditioned medium were used to mimic the early and late progressive stages of lung cancer. Signaling cascades and cell migration under the two conditions were investigated. Results: Src and Jnk activation by smoke were delayed in p120ctn-knockdown cells and inhibition of migration through the chemical blockade of EGFR, Src, and/or Jnk was dependent on p120ctn. In contrast, chemical inhibition of signaling via Akt (cell survival) or Erk (cell proliferation) was sufficient to block smoke-induced migration independent of p120ctn. Also independent of p120ctn was smoke's effect on the RhoGTPase, Rac1. Rac1 knockdown abolished dephosphorylation of actin binding protein, cofilin, in the presence and absence of p120ctn, indicating its essential role in smoke-induced cell migration. Conclusions: These studies provide unprecedented insight regarding the multiple and interdependent molecular strategies employed by smoke to escape tightly regulated cellular processes such as cell migration, proliferation, and survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B19.