tbuckley/cabot-search huggingface dataset:
AB0193 Antibodies to Hnrnp B1 (RA33) in Patients with Systemic Sclerosis
Authors: A. Maslyanskiy, D. Roggenbuck, S. Lapin, A. Mazing, N. Lazareva, E. Ilivanova, E. Kolesova, V. Mazurov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterized by the occurrence of a wide range of autoantibodies (Aab) which can predict distinct clinical features of SSc. Aab to hnRNP A2 and its alternatively spliced variants B1 (anti-hnRNP B1) and B2 are generally referred to as anti-RA33 and have been extensively studied in rheumatoid arthritis (RA) [1]. However, the prevalence of anti-RA33 Aab in other autoimmune diseases, such as scleroderma, mixed connective tissue disease and systemic vasculitides, is far from determined [2–4]. <h3>Objectives</h3> To compare the frequency of anti-hnRNP B1 with other SSc-specific Aab and to determine an association thereof with the clinical phenotype in patients with SSc <h3>Methods</h3> We studied Aab prevalence in 64 patients with SSc, 29 with diffuse cutaneous SSc and 26 with limited cutaneous disease as well as 9 patients with overlap syndrome. Diagnosis of SSc in all patients was based on 1980 ACR (ARA) criteria and the disease phenotype was analyzed according to LeRoy9s classification criteria [7]. Serum samples from clinically healthy blood donors (n=174) were used as a control group. Skin involvement and disease severity was measured with Rodnan9s skin score and Valentini activity index. Vascular involvement was accessed by measurement of pulse wave velocity (PWV) and augmentation index (AI) with applanation tonometry (SphygmoCor system, AtCor Medical Pty Ltd., Sydney, Australia). Anti-hnRNP B1 IgG was assessed by an ELISA employing recombinant human hnRNP B1 expressed in E.coli (in.vent DIAGNOSTICA GmbH, Germany). SSc-specific Aab were measured with line immunoassay (Euroimmun AG, Germany) according to the manufacturer9s instructions. <h3>Results</h3> Anti-hnRNP B1 were found in 18.5% (12/64) of SSc patients and in 1.1% (2/174) of controls (p&lt;0.001). Median concentrations were also significantly higher in SSc patients (p&lt;0.001). There were no significant associations of anti-hnRNP B1 level with any other particular SSc-specific Aab, clinical form of the SSc, degree of skin involvement, and clinical activity. We found that anti-hnRNP B1 antibodies directly correlated with the presence (r=0.33 p=0.009) of arterial hypertension and vessel-wall stiffness parameters like PWV (r=0.39, p=0.004) and AI (r=0.35, p&lt;0.001). <h3>Conclusions</h3> Anti-hnRNP B1 (RA33) is an independent serological marker in SSc and is associated with vascular involvement. <h3>References</h3> Nell-Duxneuner Vet al. Ann Rheum Dis. 2010; 69(1):169-74. Tomoum HY et al. Pediatr Int. 2009;51(2):188-92. Siapka Set al. Autoimmunity. 2007;40(3):223-33. Cho SBetal.J Invest Dermatol. 2012;132:601-8. Hoffmann MH et al. J Immunol. 2007;179(11):7568-76. Steiner Get al. ClinExpRheumatol. 2002 Jul-Aug;20(4):517-24. LeRoy EC, et al. J Rheumatol 1988; 15:202-205. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2222
REMODELING OF SELF-EXPANDING TRANSCATHETER AORTIC VALVE IS RESPONSIBLE FOR REGRESSION OF PARAVALVULAR AORTIC REGURGITATION: AN OBSERVATION FROM COREVALVE PIVOTAL TRIAL
Authors: Jae K. Oh, Stephen Little, Sahar Abdelmoneim, Michael Reardon, Neal Kleiman, Grace Lin, David Bach, Linda Gillam, Biswajit Kar, Joseph Coselli, Partho Sengupta, Karanvir Grewal, James Chang, Yanping Chang, Mike Boulware, David Adams, Jeffrey Popma
Journal: Journal of the American College of Cardiology (2015)
Two problems with “self-deception”: No “self” and no “deception”
Authors: Robert Kurzban
Journal: Behavioral and Brain Sciences (2011)

Abstract While the idea that being wrong can be strategically advantageous in the context of social strategy is sound, the idea that there is a “self” to be deceived might not be. The modular view of the mind finesses this difficulty and is useful – perhaps necessary – for discussing the phenomena currently grouped under the term “self-deception.”
Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model
Authors: Rik J B Loymans, Persijn J Honkoop, Evelien H Termeer, Jiska B Snoeck-Stroband, Willem J J Assendelft, Tjard R J Schermer, Kian Fan Chung, Ana R Sousa, Peter J Sterk, Helen K Reddel, Jacob K Sont, Gerben ter Riet
Journal: Thorax (2016)

<h3>Background</h3> Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. <h3>Methods</h3> We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+Fe<sub>NO</sub>. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer–Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes). <h3>Results</h3> 80/611 (13.1%) participants experienced ≥1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and ≥1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer–Lemeshow p value 0.35). Adding spirometry and Fe<sub>NO</sub> subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.72 (95% CI 0.70 to 0.73; 71 to 0.74 and 0.71 to 0.73) for the three models, respectively; calibration was best for the spirometry model. <h3>Conclusions</h3> A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of Fe<sub>NO</sub> is modest. These models merit an implementation study in clinical practice to assess their utility. <h3>Trial registration number</h3> NTR 1756.
FRI0264 Treatment with rituximab in patients with systemic sclerosis
Authors: O. Desinova, M. Starovoytova, O. Koneva, O. Ovsyannikova, L. Ananieva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lung involvement in the form of interstitial lung disease (ILD) is one of the most serious manifestations of systemic sclerosis (SSc). ILD develops in up to 80% of patients with SSc overall and may be life threatening and require aggressive therapy. Patients with severe SSC-associated ILD have a survival rate of only 58% within 10 years from disease onset. Rituximab (RTX) is monoclonal antibody against human CD20 that targets B cells. We assessed the safety and a possible effect of treatment with RTX in patients with SSc. <h3>Objectives</h3> To assess the safety and efficacy of treatment with RTX in patients with SSc. <h3>Methods</h3> There were 16 SSc patients (pts) in the study. The female/male ratio was 14/2. The mean (SD) age of the pts was 48,2 (12,4) years. The duration of disease from the first non Raynaud’s phenomenon was 5,2 (4,7) years. A total of 12 (87,5%) pts had diffuse SSc, 4 (12,5%) had limited cutaneous SSc. All patients had SSc-assotiated ILD, more of them were treated previously with immunosuppressive agent (n=14). 16 pts with SSc received 1cycle of RTX and 9 pts went on RTX treatment and had a follow-up of 1,5 year. All pts were treated by prednizolon 10-15 mg per day. One patient had co-treatment with cyclophosphamide during 6 month after RTX. We evaluated the modified Rodnan skin score (mRSS), forced vital capacity (FVC), diffusing capacity of carbon monoxide (DLCO), the Valentini Disease Activity index, levels of B-cells in peripheral blood before, in 6 months, in one year and in 1,5 years after completed RTX. <h3>Results</h3> We found a linear improvement of lung function and skin thickening during 1,5 years of 1st course RTX treatment. After six months pts presented a median decrease of the skin score was significantly compared to baseline (mean ± SD: 8,2±5,6 vs 12,9±8,1, respectively, p&lt;0,02). The Valentini Disease Activity index compared to baseline also significantly decreased in 1 year (mean ± SD: 1,2±0,4 vs 2,9±1,7, respectively, p&lt;0,01). The median percentage of improvement of FVC in 1,5 years was 10%, however these results were not significant. The median percentage of DLCO in 1,5 years increased insignificantly only 3%. Complete depletion of peripheral blood B-cells was observed in all pts and persistence during year. During RTX treatment infections occurred in 2 pts, one of them had herpes zoster after 2 weeks, and another one had acute bronchitis after 2 month. These infections were successfully treated and did not have complications. Two pts had ST instability on ECG after 10 days after RTX infusion without consequences. <h3>Conclusions</h3> Our results indicate possible beneficial effect of RTX therapy on skin fibrosis and lung involvement in SSc pts. RTX therapy causes stabilization and improvement of SSc. This study reported also the safety of RTX in SSc pts. <h3>Disclosure of Interest</h3> None Declared
Systemic Embolism in Chronic Sinoatrial Disorder
Authors: Andrew J. Fairfax, Colin D. Lambert, Aubrey Leatham
Journal: New England Journal of Medicine (1976)

We attempted to estimate the prevalence of systemic embolism in patients with chronic sinoatrial disorder. In a group of 100 patients, evidence of embolism was found in 16, of whom 15 had the bradycardia-tachycardia syndrome. In 712 controls with chronic complete heart block, who were matched for age and sex, embolism had occurred in only 1.3 per cent (P<0.001). A second group of 41 patients with chronic ventricular bradycardia and atrial flutter or fibrillation had an embolic prevalence of 7.3 per cent, which was also greater than that in the controls (P<0.05). All patients with sinoatrial disorder in whom systemic embolism developed were over 54 years of age; multiple episodes occurred in six. The risk of embolization remains even if the bradycardia-tachycardia syndrome is replaced by stable atrial fibrillation. Impaired atrial function appears to be a key factor in predisposing to intracardiac thrombosis, and paroxysmal supraventricular tachycardia increases the risk of subsequent embolization. (N Engl J Med 295:190–192, 1976)
Abstract 216: HMGB1 regulates homing capacity of human mesenchymal stromal cells into colon cancer.
Authors: Go Hoshino, Hiroshi Yagi, Hirotoshi Hasegawa, Yoshiyuki Ishii, Takashi Endo, Koji Okabayashi, Akimasa Yasuda, Masaya Nakamura, Hideyuki Okano, Yumi Matsuzaki, Yuko Kitagawa
Journal: Cancer Research (2013)

Abstract Recently a growing corpus of studies has highlighted the important aspect of Mesenchymal Stem Cell (MSC) therapy: systemically administered MSCs home to sites of cancer. In this study, we focused on a homing mechanism of human MSCs into cancer. First, we examined if cultured medium from cancer cell lines could modulate migration of MSCs, the secretion level of HMGB1 from six different colon cancer cell lines affected the migration capacity of MSCs. In addition, recombinant HMGB1 could increase the migration capacity in dose dependent manner. Finally, we applied MSCs intracutaneously into mice bearing colon cancer using a cell line which secreted high level of HMGB1. The in vivo bioluminescence live-image showed that MSCs surrounded the tumors within 48hours after their injection, additionally the immunohistochemistry revealed the existence of MSCs in the tumors. These findings are critical in understanding the role of MSCs in solid cancer, further they might facilitate therapeutic application of MSCs in the treatment of cancer. Citation Format: Go Hoshino, Hiroshi Yagi, Hirotoshi Hasegawa, Yoshiyuki Ishii, Takashi Endo, Koji Okabayashi, Akimasa Yasuda, Masaya Nakamura, Hideyuki Okano, Yumi Matsuzaki, Yuko Kitagawa. HMGB1 regulates homing capacity of human mesenchymal stromal cells into colon cancer. [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 216. doi:10.1158/1538-7445.AM2013-216
Abstract 4548: Identify novel molecular structures targeting X-Linked Inhibitor of Apoptosis Protein by ligand-based virtual screening.
Authors: Jin Wang, Charles B. Duke, Wei Li
Journal: Cancer Research (2013)

Abstract Resistance to apoptosis is believed as one of the mechanism underlying a number of human malignancies notorious resistances to current chemotherapeutics. The X-linked inhibitor of apoptosis protein (XIAP) inhibits apoptosis by directly binding and deactivating caspase-9, caspase-3/7. Elevated XIAP expression in tumor tissue is closely associated with metastatic progression. Mimicking the XIAP-binding motif of second mitochondria-derived activator of caspase (SMAC) is the most widely used strategy to discover or design therapeutic agents targeting XIAP. Here we screened a large database of 362K compounds (the University of Cincinnati's Drug Discovery Center Library) in silico to find molecules with novel structures that can strongly interact with the third BIR domain of XIAP. We chose AVPI tetrapeptide from the SMAC as the lead structure and run the shape similarity search using program Canvas, version 1.4 (Schrodinger, LLC, New York, USA). Then top 10,000 structures of the similarity rank were docked into SMAC binding sites in two different SMAC-BIR3 domain complexes crystal structure (PDB ID: 1TW1 and 1G73) separately. The highest docking score of the screened structures is up to -9.0 in both of complexes while the SMAC AVPI tetrapeptide showed docking score at -9.4. Considering the docking scores in both complexes and the flexibility of chemical scaffolds, we manually selected 72 compounds with docking scores varied from -8.4 to -5.5 for in vitro anti-proliferation and caspase functional testing. Four compounds which haven't been reported with any anti-cancer activity, inhibited the cell growth by over 70% in two human melanoma cell lines (A375 and MDA-MB-435) and two human prostate cell lines (PC-3 and LNCap) at the concentration of 10uM after 48hr incubation. IC50 values of those compounds were at least 4 folds smaller than that of Embelin, a well-recognized XIAP inhibitor, in all four cell lines tested. The best of them, compound 402112, have IC50 values of 650nM to 2.5uM against the four tested cancer cell lines. Caspase functional assay showed that compound 402112 activates capase-9 activity at 4 μM, significantly better than Embelin did at a 10-fold higher concentration (40 μM) after 48hr treatment in PC-3 and A375 cells. Taken together, our study identified novel molecule structures which are amicable to further extensive modification for the development of high potent XIAP inhibitors. Citation Format: Jin Wang, Charles B. Duke, Wei Li. Identify novel molecular structures targeting X-Linked Inhibitor of Apoptosis Protein by ligand-based virtual screening. [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 4548. doi:10.1158/1538-7445.AM2013-4548
The Prognostic Value of Exercise Testing in Patients with Cystic Fibrosis
Authors: Patricia A. Nixon, David M. Orenstein, Sheryl F. Kelsey, Carl F. Doershuk
Journal: New England Journal of Medicine (1992)

Previous studies have shown female sex, impaired pulmonary function, older age, malnutrition, and colonization of the respiratory tract by Pseudomonas cepacia to be associated with a poor prognosis in patients with cystic fibrosis. We sought to determine the prognostic value of exercise testing in addition to the other prognostic factors.
PTH-064 Are Outcomes Following Endoscopy For Emergency Upper Gi Bleeding Worse At Night And Weekends?
Authors: A Rehman, P Mundre, B Rembacken
Journal: Gut (2014)

<h3>Introduction</h3> Patients admitted out of hours or at weekends may have an excess mortality due to the fact that they undergo emergency endoscopy by junior staff. We retrospectively looked at the predictors of mortality in patients undergoing emergency endoscopy for severe bleeding in Leeds. <h3>Methods</h3> The survival of patients with the most significant upper GI bleeding lesions who underwent emergency endoscopy in Leeds between end of April 2008 and middle of December 2011 were selected for retrospective analysis using data from our endoscopy reporting system and hospital records. <h3>Results</h3> A total of 1663 emergency endoscopies were carried out during this period. From this number, 390 examinations (23% of total) were selected for more careful scrutiny as the following significant bleeding lesions had been recorded; 136 duodenal ulcers, 84 gastric ulcers, 134 oesophageal varices, 25 gastric varices, 11 Dieulafoy’s and 9 other bleeding lesions. After 23% of procedures (91/390), the patient died within 30 days. As expected, patients who died had a significantly higher Rockall score (7.5 vs. 5.9 p &lt; 0.0001), a higher ASA level (3.5 vs. 2.8 p &lt; 0.001) and a lower systolic BP at the time of the examination (95 vs. 102 p = 0.025). Patients who died following endoscopy for bleeding ulcers were significantly older than those who survived (76.6 vs. 67.2 yrs, p = 0.006). There was no significant difference in mortality with the type of bleeding lesion, Hb (7.9 vs. 8.0) or heart rate (100 vs. 102 bpm) at the time of the endoscopy between those who survived and those who died. Furthermore, undergoing an emergency gastroscopy at night or during the weekend or bank holiday was not associated with an increased risk of death (P = 0.24 and p = 0.53 respectively). Whether the examination was carried out by an SpR or a Consultant made no difference to the survival of the patient. The only link between endoscopic intervention and patient outcome was the finding that patients with varices requiring balloon tamponade where significantly more likely to die (15/36 vs. 16/98 p = 0.01). <h3>Conclusion</h3> Our study had the statistical power to detect all the recognised risk factors for death following admission with an acute upper GI bleed including advancing age, increasing comorbidity and hypotension. We found no evidence that undergoing an emergency endoscopy at night or during the weekend or a bank holiday had any adverse effect on outcomes. Similarly, the level of seniority of the endoscopist did not affect outcomes. <h3>Disclosure of Interest</h3> None Declared.
Sedation and Analgesia for Procedures in Children
Authors: Baruch Krauss, Steven M. Green
Journal: New England Journal of Medicine (2000)

The management of acute pain and anxiety in children undergoing therapeutic and diagnostic procedures outside the operating room has developed substantially in the past 15 years. The widespread availability of noninvasive monitoring, short-acting opioids and sedatives, and specific opioid and benzodiazepine antagonists has enabled clinicians to administer sedation safely for procedures in diverse settings. The goal of procedural sedation is the safe and effective control of pain, anxiety, and motion so as to allow a necessary procedure to be performed and to provide an appropriate degree of memory loss or decreased awareness. This article reviews the current status of sedation . . .
Abstract 707: Acquisition of chemoresistance and epithelial to mesenchymal phenotype is linked with activation of the endothelin A receptor pathway in ovarian carcinoma cells
Authors: Roberta Cianfrocca, Laura Rosanò, Valeriana Di Castro, Francesca Spinella, Maria Rita Nicotra, Alessandro Lucidi, Gabriella Ferrandina, Pier Giorgio Natali, Anna Bagnato
Journal: Cancer Research (2011)

Abstract Understanding the molecular mechanisms underlying chemoresistance is of utmost importance for improving the treatment of epithelial ovarian cancer (EOC). Emerging evidence suggests molecular and phenotypic association between chemoresistance and epithelial-mesenchymal transition (EMT) in cancer cells. Endothelin-1 (ET-1) and the endothelin A receptor (ETAR) axis is implicated in the pathobiology of EOC by driving different tumor-promoting effects, including EMT. By employing two cisplatin- and taxol-resistant ovarian cancer cell lines, we demonstrated that in the resistant EOC cells ET-1 and ETAR are upregulated, at both mRNA and protein level, paralleled by enhanced MAPK and AKT phosphorylation and cell proliferation. To assess whether the chemoresistance in A2780 cells was associated with EMT molecular changes, we examined the expression of epithelial and mesenchymal markers. Enhanced Snail, Slug, Twist, N-cadherin and vimentin mRNA expression was observed in resistant cells, associated with a concomitant decrease in E-cadherin expression and promoter activity. Moreover, ET-1 induced a significant induction of Snail promoter activity in resistant cells, and the E-cadherin promoter sequences were detected bound to Snail in a time-dependent manner, as demonstrated by chromatin immunoprecipitation assays, suggesting that the ET-1-dependent and sustained binding of Snail in the E-cadherin promoter might account for EMT and chemoresistant phenotype of these cells. Moreover, the invasiveness and proteinase activity of chemoresistant cells was greater, compared with sensitive cells. Interestingly, ETAR blockade with the specific ETAR antagonist, zibotentan, or its silencing with siRNA, reverted EMT, restored drug sensitivity to cytotoxic-induced apoptosis, and inhibited the invasive potential of resistant cells. In vivo, zibotentan inhibited tumor growth of sensitive and resistant EOC xenografts, and sensitized to chemotherapy. Finally, analysis of EOC tissues, with different responses to chemotherapy, revealed that ETAR is overexpressed in resistant tumors and is associated with EMT marker expression. All these data indicate that blockade of ETAR-driven EMT can overcome chemoresistance in EOC, improving the outcome of EOC patients’ treatment. Supported by AIRC 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 707. doi:10.1158/1538-7445.AM2011-707
Improved Detection of Allele Loss in Renal Cell Carcinomas After Removal of Leukocytes by Immunologic Selection
Authors: M. Linehan, E. Miller, P. Anglard, M. Merino, B. Zbar
Journal: JNCI Journal of the National Cancer Institute (1989)

We used immunologic selection to remove contaminating leukocytes from primary renal cell carcinomas and to improve detection of chromosome 3p allele loss. Leukocytes were removed from disaggregated renal cell carcinomas by a double-antibody, magnetic bead separation technique. Before immunologic selection, the preparations contained 26% +/- 15% (SD) tumor cells (n = 7); after immunologic selection, the preparations contained 76% +/- 12% tumor cells. The recovery of tumor cells in the purified preparations was about 10%. Detection of allele deletion was facilitated by immunologic selection. This method may be useful in allele deletion analysis of other human solid tumors that are contaminated with host leukocytes and, with appropriate modification, may be applied to tumors that are contaminated with other cell types.
THE IMPACT OF EJECTION FRACTION ON FRACTIONAL FLOW RESERVE: INSIGHTS FROM THE FAME (FRACTIONAL FLOW RESERVE VERSUS ANGIOGRAPHY FOR MULTIVESSEL EVALUATION) TRIAL
Authors: Yuhei Kobayashi, Pim Tonino, Bernard De Bruyne, Hyoung-Mo Yang, Hong-Seok Lim, Nico Pijls, William Fearon
Journal: Journal of the American College of Cardiology (2015)