tbuckley/cabot-search huggingface dataset:
545MiR-139 expression is detrimental during pressure overload-induced heart failure
Authors: B Schroen, T Peters, W Verhesen, W Derks, L Zentlini, S Zacchigna, M Giacca, J Van Der Velden, L De Windt, S Heymans
Journal: Cardiovascular Research (2014)

Cardiac hypertrophy and consequent contractile dysfunction continue to burden Western society. Cardiomyocyte cyclic AMP (cAMP) and calcium are driving forces behind cardiomyocyte contraction. Distortion of their balance may induce HF, but specific therapies aiming at restoring physiological cAMP/calcium signaling are lacking. We recently identified microRNA-139 (miR-139) to be downregulated in failing human hearts. MiR-139 resides in the phosphodiesterase gene PDE2A and is predicted to target several phosphodiesterase messengers. In view of the central role of phosphodiesterases in controlling cardiac cAMP and calcium signaling, we hypothesized that miR-139 may affect HF progression by fine-tuning cAMP and calcium balances. Adeno-associated virus serotype 9 (AAV9), either empty control or expressing pre-miR-139, was administered to male C57Bl/6J mice. After allowing transgene expression for 3 weeks, mice were subjected to sham treatment or 4 weeks of pressure overload by subcutaneous Angiotensin II infusion (AngII, 2,5 mg/(kg·d). MiR-139 overexpression mildly aggravated HF development upon AngII with echocardiographically measured fractional shortening decreasing by 24±7% in AAV9-control AngII and by 46±5% in AAV9-pre-miR-139 AngII (n>11/group; p=0.14). In AAV9-control mice, AngII infusion led to concentric hypertrophy with an increased relative wall thickness (RWT) of 35±6%, whereas mice overexpressing miR-139 showed a rather eccentric form of hypertrophy with an increased RWT of 14±7% (p<0.05). The fraction of unphosphorylated cardiac troponin I (cTnI), a substrate of the cAMP dependent protein kinase A (PKA), tended to increase upon AngII infusion only in mice overexpressing miR-139 (n=4/group; p=0.11), indicating a reduced relaxation rate due to increased calcium sensitivity, a feature commonly observed in HF. Complimentary to these data, in vivo knockdown of mir-139 by cholesterol-tagged antagomiRs (20mg/kg) on three consecutive days before start of AngII infusion dampened the development of pressure overload-induced cardiac hypertrophy (increase in HW/TL: ctrl: 48±10%, n=4; antagomiR: 25±7%, n=7; p=0.16). In conclusion, cardiac downregulation of miR-139 upon pressure overload is a protective response to preserve cardiac function. AAV9-mediated overexpression of miR-139 promotes cardiac dilation and predisposes to HF. Upcoming experiments will aim at defining the molecular mechanism by which miR-139/phosphodiesterase signaling affects cardiac pathophysiology.
Abstract 3332: Inhibition of cancer stem-like properties in malignant glioma by delivery of microRNA145 with cationic polyurethanes-PEI
Authors: Shih-Hwa Chiou
Journal: Cancer Research (2012)

Abstract Malignant glioma, including Glioblastoma (GBM), is the most common primary brain tumor bearing dismal prognosis. CD133 has been considered a putative marker of cancer stem cells (CSCs) in malignant cancers, including GBM. MicroRNAs (miRNAs), highly conserved small RNA molecules, may target oncogenes and become a therapeutic strategy against cancer. However, the involvement of miRNAs in GBM-associated CSCs remained mostly unclear. Using miRNA/mRNA microarray analysis, we identified that miR145 (a tumor-suppressive miRNA) expression is inversely correlated with the levels of Oct4 and Sox2 in GBM-CD133+ cells and specimens of malignant glioma. Consistently, we demonstrated that miR145 negatively regulates tumor growth of GBM by directly targeting Oct4 and Sox2 in GBM-CD133+ cells. We therefore evaluated the treatment effect of polyurethane-short branch polyethylenimine-mediated miR145 (PU-PEI-miR145) on GBM-CSCs. PU-PEI-miR145 delivery in GBM-CD133+ significantly inhibited their tumorigenic and CSC-like abilities, and facilitated their differentiation into CD133α non-CSCs. Furthermore, PU-PEI-miR145 delivery in GBM-CD133+ effectively suppressed their expressions of drug-resistance and anti-apoptotic genes, and dramatically increased the sensitivity to radiation and chemotherapeutic drugs, including temozolomide. Finally, in vivo alone delivery of PU-PEI-miR145 significantly suppressed tumorigenesis, and synergistically improved survivals in orthotopic GBM-CD133+-transplanted immunocompromised mice, combined with radiotherapy and temozolomide. Therefore, PU-PEI-miR145 is potential therapeutic approach for malignant brain tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3332. doi:1538-7445.AM2012-3332
Robotic telecytology and EUS-FNA
Authors: D Robbins, E Rorat, G Sheridan, H Bodenheimer, B Wenig
Journal: Endoscopy (2006)

Aim: To explore the feasibility of integrating robotic telecytology with endoscopic ultrasound fine-needle aspiration (EUS-FNA). Background: The diagnostic accuracy of EUS-FNA is critically dependent on the use of 'in-room' cytologic assessment of FNA specimen adequacy. A major problem facing EUS centers is the cost and limited availability of cytopathologists. One solution might be dynamic robotic telepathology (DT), a sophisticated technique in which light microscopy is transmitted in real-time to an off-site pathologist. Methods: EUS-FNA was performed on an 18×15mm pancreatic cystic lesion. The cystic fluid was treated with 95% ethyl alcohol and Toluidine Blue by a cytotechnician. The portable DT system (MedMicro, Trestle Corporation, Irvine, CA, USA) included an Olympus BX50 microscope with 2–40x objectives mounted on a motorized nosepiece. The microscope was fitted with an x, y, z-axis motorized stage (Prior Scientific, Rockland, MA, USA) and an Olympus PMTV camera linked to an internal digitizer and network. A 600×395 pixel image was sent to an off-site pathologist with full control of the microscope. The DT virtual slide was compared to conventional static cytopathology (CT). Results: The time estimated to review the entire slide by DT was 15 minutes and 4 minutes by CT. Adequacy was insufficient by DT or CT, but image quality by DT was sufficient to make the determination. Challenges include movement artifact from wet mounted slides, inability to focus rapidly through cell layers, and slow scanning in pauci-cellular aspirates. Conclusion: This case demonstrates the feasibility of DT in conjunction with EUS-FNA. With minor refinements, DT EUS-FNA might provide a critical physician-physician link expanding the reach and improving the accuracy of EUS-FNA.
Abstract LB-1: An investigator-initiated, phase II randomized, double-blind, placebo-controlled trial of GDC-0449 for prevention of BCCs in basal cell nevus syndrome (BCNS) patients.gg
Authors: Jean Y. Tang, Julian M. Mackay-Wiggan, Michelle Aszterbaum, Joselyn Lindgren, Kris Chang, Carol Coppola, Angela Campbell, Anita Chanana, Jackleen Marji, Chris Callahan, Robert Yauch, David R. Bickers, Ervin H. Epstein
Journal: Cancer Research (2011)

Abstract Purpose: GDC-0449 (Genentech) is a new hedgehog pathway inhibitor that has been shown in a Phase I trial to reduce locally advanced/metastatic BCCs. We tested the efficacy of GDC-0449 for BCC prevention in a randomized, double-blind, placebo-controlled trial in patients with Basal Cell Nevus Syndrome (BCNS). Methods: We enrolled 41 BCNS patients from 3 clinical centers from September 2009 to January 2011. Subjects were randomized 2:1 to receive once daily oral GDC-0449 (150 mg) or placebo. The primary endpoint was to assess the number of new surgically eligible BCCs per month after 3 months; secondary endpoints included assessment of the change in size of existing BCCs and safety/tolerability. Results: 36 subjects (24 GDC-0449, 12 placebo) have been enrolled for greater than 1 month. Upon review of results at the interim analysis, the DSMB ended the placebo arm of the trial due to statistically significant differences between the 2 groups. Subjects treated with GDC-0449 developed 0.07 new BCCs per month vs. 1.74 BCCs per month for those receiving placebo (p&amp;lt;0.0001). The change from baseline in the aggregate size of existing BCCs was −24 cm vs. −3 cm for GDC-0449 and placebo, respectively (p=0.006). Some subjects achieved near complete remission with no BCC developing resistance. Common grade 1–2 adverse events (GDC-0449 vs. placebo) included taste loss (83% vs. 8%), muscle cramps (67% vs. 8%), and weight loss (50% vs. 8%). Two GDC-0449 subjects experienced grade 3–4 adverse events (muscle cramp, suicide attempt). Overall 20% of GDC-0449 subjects discontinued drug participation due to adverse events. BCC samples from 23 subjects treated with GDC-0449 or placebo were available for molecular analysis. The anti-BCC efficacy of GDC-0449 was associated with on-target reduction of the Hedgehog pathway as Gli1 mRNA levels were decreased by 200-fold (p&amp;lt;0.001) after 1month in BCCs. Gli1 mRNA levels were not changed in BCCs from placebo subjects. GDC-0449 also decreased tumor proliferation (Ki67) but had no effect on apoptosis (CC3). Biopsies of lesions taken after 3 months of GDC-0449 showed histologic clearance in 7 out of 11 samples. Conclusion: GDC-0449 has anti-BCC efficacy in BCNS patients and may be a potential new drug for BCC prevention and treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-1. doi:10.1158/1538-7445.AM2011-LB-1
EUS-guided Transesophageal Treatment of Gastric Fundal Varices with Combined Intravariceal Coiling And Cyanoacrylate Glue Injection using a front-view forward-array echoendoscope
Authors: F Weilert, JN Shah, FP Marson, KF Binmoeller
Journal: Endoscopy (2011)

Background: Endoscopic treatment of gastric varices (GV) is challenging due to their location, large size, and severity of bleeding. Endoscopic injection of cyanoacrylate (CYA) glue is a widely accepted treatment for gastric varices. Risks of endoscopic CYA injection are extravariceal and pulmonary and/or systemic embolization of CYA. EUS-guided injection of CYA ensures accurate intravariceal injection. Deployment of a coil before CYA injection may decrease the amount of glue needed to achieve obliteration and act as a scaffold to retain CYA at the injection site to prevent embolization.
NT-25 * EARLY JAPANESE EXPERIENCE WITH NovoTTF-100A SYSTEM FOR RECURRENT GBM
Authors: Y. Muragaki, M. Nitta, T. Okumura, Y. Tabei, T. Maruyama, S. Kaneko, I. Suzuki
Journal: Neuro-Oncology (2014)

BACKGROUND: NovoTTF-100A System is an FDA-approved treatment for recurrent glioblastoma (GBM) and is defined as a device of high unmet medical need in Japan. Subsequently, the device has been made available on a restricted case basis for compassionate use in Japan. Here we report initial experience with 10 patients treated at Tokyo Women's Medical University, Kashiwaba Neurosurgical Hospital and Japanese Red Cross Medical Center. METHODS: Using retrospective chart review, we analyzed patient demographics, tumor size, location, and treatment compliance with NovoTTF-100A System from the device log files. Duration of therapy was estimated using the Kaplan-Meier estimate. Adverse event frequency and severity was also evaluated. RESULTS: Ten (10) patients with supra-tentorial recurrent GBM were treated between July 8, 2013 and June 3, 2014 at 3 Japanese hospitals. 80% were male and 20% female. The median age was 41 years (range 32-66). The average baseline tumor burden was 13.3 cm2. 40% of patients had bi-hemispheric tumors and 30% left hemispheric tumors. The K-M median duration of therapy was 7.8 months. Average daily device compliance was 17.4 hours. This is consistent with prior global studies which have demonstrated average daily device compliance of 70-80%. The device was well-tolerated with no reported serious adverse events. The only device-related adverse events were mild skin irritation. CONCLUSIONS: NovoTTF-100A System was safe and well-tolerated in an initial cohort of Japanese patients with GBM. Device usage and compliance was consistent with that observed in non-Japanese patients.
FRI0229 Survival on treatment of the second line biologic therapy: switch or swap strategy?
Authors: E. G. Favalli, M. Biggioggero, A. E. Penatti, A. Marchesoni, P. L. Meroni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The strategy for the choice of the second biologic agent after the failure of the first TNF inhibitor is still an unclear aspect in the treatment of rheumatoid arthritis (RA). <h3>Objectives</h3> To evaluatein a real-life settingthe survival on treatment of the second biologic agent in anti-TNF non-responders, comparing patients treated with a second anti-TNF (switch strategy) with patients treated with a different mechanism of action (abatacept, rituximab, or tocilizumab; swap strategy). <h3>Methods</h3> We extracted data from a local registry that includes all RA patients treated with biologic therapies between October 1999 and December 2012 in our Rheumatology Unit. We limited our analysis to the period after the first biologic agent other than anti-TNF became available (January 2007-December 2012), in order to minimise differences in exposure among biologics. Patients who stopped a first course TNF inhibitor and started a second line biotherapy since January 2007 were included in the analysis. The rate of drug discontinuation in both subgroups were retrospectively estimated by Kaplan-Meier analysis and compared by log-rank (Mantel-Cox) test. <h3>Results</h3> Between 1999 and 2012, 641 patients were treated with etanercept (n=192), infliximab (n=221), adalimumab (n=192), golimumab (n=14), or certolizumab pegol (n=22) as first line biotherapy. Since January 2007, 183 of these patients discontinued the TNF blocker because of inefficacy (56%) or safety (44%) issues and switched to a second anti-TNF (n=107) or swapped to abatacept (n=21), rituximab (n=40), or tocilizumab (n=15). The drug survival was significantly greaterin swap thanin switch subgroup(p=0.0009; figure). This difference was confirmed after the stratification of both subgroups according to cause of first anti-TNF discontinuation (inefficacy, p=0.03; safety, p=0.01). No significant differences emerged comparing the retention rate of abatacept, rituximab, and tocilizumab (p=0.2). <h3>Image/graph</h3> <h3>Conclusions</h3> In a set of clinical practice, the choice of a second biologic agent with different mechanism of action seems to be a better strategy to treat anti-TNF non-responders, irrespective of the cause of TNF blocker discontinuation. <b>References:</b> Caporali R, et al. Autoimmun Rev 2010; 9(6):465-9. <b>Disclosure of Interest</b>: None Declared
SP0041 Vintage B27 (The Role of HLA-B27 in Ankylosing Spondylitis Pathogenesis)
Authors: P. Bowness
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The Human Leukocyte Antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides including Ankylosing Spondylitis and Reactive Arthritis (ReA). The link between HLA-B27 and Ankylosing Spondylitis was first discovered independently by groups in Britain and the USA in 1973 [1–3]. We still do not know for sure why B27 causes AS, but we do know that the natural function of HLA-B27 is to bind and present intracellular antigenic peptides for cell surface presentation to Cytotoxic T lymphocytes (CTL). HLA-B27 may cause AS by presenting "arthritogenic" peptides to pathogenic T cells. Alternatively HLA-B27 may cause AS because it has an abnormal cell biology. Thus B27 can form homodimers (B27<sub>2</sub>) both intracellularly and on the cell surface [4]. Cell surface B27<sub>2</sub> may have a pathogenic role in AS by binding Natural Killer family receptors, including KIRs (killer Ig-like receptors) and/or LILRs (leukocyte Ig-like receptors). KIRs are expressed on both Natural Killer Cells and T cells, whilst LILRs are found on monocytes, B lymphocytes and dendritic cells. We have shown that, in SpA, an increased number of peripheral blood NK and CD4 T cells express the KIR3DL2 receptor compared to healthy controls and RA patients. These cells are enriched for IL17 production. Recent GWAS studies have implicated the Th17 pathway (and confirmed the role of HLA-B27). The mysterious and ever changing role of B27 from 1973 to 2014 will be discussed in this presentation. <h3>References</h3> Caffrey M &amp; James DCO Human Lymphocyte Antigen Association in Ankylosing Spondylitis Nature 242, 121 (09 March 1973). Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med. 1973 Apr 5;288(14):704-6. Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973 Apr 28;1(7809):904-7. Allen, RL, O9 Callaghan C, McMichael AJ and Bowness P. Cutting edge: HLA B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure J. Immunol. 1999. 162, 5045-5048. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6104
LONG-TERM (7-YEAR) CLINICAL OUTCOMES OF BIFURCATION LESIONS AFTER BIODEGRADABLE POLYMER-BASED BIOMATRIX BIOLIMUS-ELUTING STENT IMPLANTATION ACCORDING TO STENTING STRATEGY
Authors: Masanobu Ohya, Kazushige Kadota, Yusuke Hyodo, Suguru Otsuru, Daiji Hasegawa, Takeshi Tada, Seiji Habara, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2016)
THE IMPACT OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ON ASYMMETRIC DIMETHYLARGININE IN ORTHOTOPIC HEART TRANSPLANTATION RECIPIENTS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Authors: Rushi Parikh, Kiran Khush, Sean Sana, Tiffany Daun, Helen Luikart, Vedant Pargaonkar, Seema Sinha, Garrett Cohen, Hannah Valantine, Alan Yeung, Jon Kobashigawa, William Fearon
Journal: Journal of the American College of Cardiology (2016)
Move to reform GPs' committee fails
Authors: L. Beecham
Journal: BMJ (1995)

Motions aimed at reforming the way that general practitioners are represented on the BMA's General Medical Services Committee were defeated last week at an extraordinary general meeting of the association. The meeting endorsed without opposition, however, the motion from the BMA's council that “Council understands that there is concern regarding the constitution of the GMSC and believes that the current review of that constitution should be brought to an early conclusion.”

Dr David Roberts, a general practitioner in Northamptonshire, had requisitioned the meeting by obtaining the signatures of 100 voting members. The quorum of 100 was reached, however, only because the meeting was held on the same day as a meeting of the GMSC and after Dr Roberts realised that he had not signed the attendance book. Although …
SP0100 A Comorbid SjÖGren Patient: Which Organ Has Priority?
Authors: M. Fleck
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Primary Sjögren9s syndrome (pSS) is a systemic autoimmune disorder that predominantly affects exocrine glands leading to eye and mouth dryness, fatigue and pain. However, up to 40% of the affected patients will develop extraglandular involvement during the disease course attributed to lymphocytic infiltration of affected organs including the lungs, kidneys and liver. In addition, immune complex mediated manifestations might occur as purpura, peripheral neuropathy or glomerulonephritis. It is not uncommon for this disease entity to present itself as a diagnostic dilemma and to pose therapeutic challenges especially in cases of multiple organ involvement. To underline the complexity of this condition, we will present two difficult cases outlining the disease course right from the initial presentation and ending with the most recent clinical status. This will be followed by a detailed discussion pertaining to the diagnostic and therapeutic challenges as well as the respective complications that may arise. The first case involves a 78 year old female patient, who developed severe pulmonary involvement in the form of nonspecific interstitial pneumonia (NSIP) and pulmonary hypertension. The second case presentation will focus on a 71 year old female patient developing severe neurological manifestations with progressive polyneuropathy leading to tetraparesis of the extremities. Both cases should raise awareness to the wide array of clinical presentations, their ambiguity especially in the lack of histological evidence, the sequelae that follow and last but not least, the degree of associated morbidity not only related to the pathophysiology of this condition but also to that resulting from immunosuppressive therapy. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6192
A dynamic case definition is warranted for adequate notification in an extended epidemic setting: the Dutch Q fever outbreak 2007–2009 as exemplar
Authors: G Jaramillo-Gutierrez, M C Wegdam-Blans, R ter Schegget, J M Korbeeck, R van Aken, H A Bijlmer, J H Tjhie, M P Koopmans
Journal: Eurosurveillance (2013)

Binary file ES_Abstracts_Final_ECDC.txt matches
Comparative study of NOTES rectosigmoidectomy in a swine model: E-NOTES vs. P-NOTES
Authors: D. Sohn, S.-Y. Jeong, J. Park, J. Kim, J. Hwang, D.-W. Kim, S.-B. Kang, J. Oh
Journal: Endoscopy (2011)

Background and study aims: Several reports have demonstrated the safety of pure natural-orifice transluminal endoscopic surgery (P-NOTES) using transanal endoscopic microsurgery (TEM) and embryonic NOTES (E-NOTES; laparoscopic surgery through the umbilicus). This study was performed to compare the safety and applicability of NOTES rectosigmoidectomy between E-NOTES and P-NOTES in a swine model.
A COMPREHENSIVE COMPARISON OF THE PATHOPHYSIOLOGICAL AND PROGNOSTIC SIGNIFICANCE OF CORONARY FLOW RESERVE AND THE INDEX OF MICROVASCULAR RESISTANCE IN THE CULPRIT CORONARY ARTERY OF PATIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTION
Authors: David Carrick, Caroline Haig, Jamie Layland, Nadeem Ahmed, Margaret McEntegart, Mark Petrie, Hany Eteiba, Stuart Hood, Stuart Watkins, Martin Lindsay, Ahmad Mahrous, Sam Rauhalammi, Ify Mordi, Ian Ford, Naveed Sattar, Aleksandra Radjenovic, Keith Oldroyd, Colin Berry
Journal: Journal of the American College of Cardiology (2016)