tbuckley/cabot-search huggingface dataset:
A5.3 Clinical application and limitations of quantiferon TB gold test for the diagnosis of latent tuberculosis in inflammatory rheumatic patients in Hungary
Authors: E Nagy, G Pálvölgyi, E Kiss, P Gergely, G Poór
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> TNF-α plays an important role in host defense against various infections and in the pathogenesis of chronic inflammatory diseases. Therapeutic blockade of TNF-α could be an effective treatment in such cases. However, anti-TNF-α therapy increases the risk of reactivation of serious infections, including tuberculosis (TB). Thus, screening for TB became mandatory, prior to the initiation of TNF-α inhibitor therapy. <h3>Aim of the study</h3> To assess the performance and characteristics of the Quantiferon TB Gold test (QFT) by screening for TB in three different populations in Hungary: patients with inflammatory rheumatic diseases (RD), health-care workers who serve homeless people (HW) and homeless clients (HL). <h3>Methods</h3> Between April 2011 and March 2014, samples of 1430 consecutive RD patients, who required or already underwent TNF-a blocking therapy, were screened for latent TB. Two untreated groups, (i) 120 HL and (ii) 46 HW, both considered to be at high risk for TB, were also tested. The QFT was performed according to the manufacturer instructions. The amount of released IFN-g was measured by ELISA in samples stimulated by TB Antigen, saline (NIL) and phytohemagglutinin A (PHA). <h3>Results</h3> In the RD group, the QFT was negative in 87%, positive in 11%, and indeterminate in 2%. Of the 265 patients, 36 (13.6%) showed inconsistent results on repeat testing. In the HW group, the QFT was negative in 63% and positive in 37%. In the HL group, the QFT was negative in 50.8%, positive in 46.7% and indeterminate in 2.5%. In the RD group, low mitogen response (caused mainly by low lymphocyte count and/or improper specimen handling) and positive results close to the cut-off value of 0.35 IU/mL account for 86% of inconsistent results, while true reversions or conversions only for 14%. <h3>Conclusions</h3> Based on our results, for better differentiation of non-specific variations, we suggest that a grey zone close to the cut-off value of 0.35 IU/mL (0.35–0.800 IU/mL) should be defined. As for the mitogen response, results higher than 0.5 IU/mL (cut-off), but lower than 2 IU/mL should be interpreted carefully. Repeat testing in such cases could prevent misinterpretations caused by technical errors.
Abstract 2962: A rapid alternative method for cell cycle analysis using the Cellometer Vision
Authors: Leo L. Chan, Xuemei Zhong, Jean Qiu, Peter Li, Bo Lin
Journal: Cancer Research (2011)

Abstract Traditional cell cycle analysis instrumentation involves the use of fluorescence microscopy, laser scanning cytometry, and flow cytometry. In this work, we demonstrate a rapid alternative device, the Cellometer Vision, which utilizes an imaging cytometry method for analyzing cell cycle measurement. This method employs both bright-field and fluorescence imaging of a disposable cell counting chamber to quickly provide concentration and percentages of cell subpopulations. Signal measurement and data analysis could be performed less than five min. Cell cycle assay was demonstrated by detection of changes in phase percentage within a cell population when Jurkat cells were induced with three different drugs, nocodazole, etoposide, and aphidicolin that arrest cell cycle at G2/M, S, and G0/G1 phase, respectively. Jurkat cells were fixed with 75% ethanol and stained with propidium iodide. Individual cells were identified by the software and the fluorescence intensity was measured from within the cell. The imaging cytometry method was able to detect and analyze fluorescence from the Jurkat cells, which generated cell cycle data plot for each drug at three different concentrations. The cell cycle analysis results were highly consistent with the results obtained from FACScalibur flow cytometer. This imaging cytometry method provides a rapid and cost-effective tool for cell concentration measurements, as well as cell cycle analysis, which may benefit smaller research laboratories, where flow cytometer is not readily available. 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 2962. doi:10.1158/1538-7445.AM2011-2962
SP0206 Generalising from Clinical Trials to Treatment Recommendations
Authors: R. Buchbinder
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The main aim of evidence-based treatment recommendations and guidelines are to translate findings from health research into clinical practice. When implemented successfully these should improve quality of care and lead to improved health outcomes. However many and varied obstacles stand in the way of achieving these endpoints. These range from a paucity of high quality trials to inform the recommendations; lack of a transparent and systematic approach to evidence synthesis and assessing the quality of that evidence (which sometimes leads to conflicting recommendations); and lack of a suitably targeted dissemination strategy. In addition while physicians may be aware of published recommendations, this does not necessarily translate into altered physician behaviour. This presentation will consider the generalisability of clinical trials to treatment recommendations. To be clinically useful, both clinical trials and treatment recommendations must be applicable to patients typically seen in routine care, i.e. they require external validity. They also need to address relevant clinical problems. Different methods for generating treatment recommendations will also be discussed - from the all-purpose method of generating treatment recommendations by an assembled panel of experts in the field, to the alternate approach taken by the 3e (Evidence, Expertise, Exchange) Initiative which involved a large number of rheumatologists from different countries generating practical recommendations on a range of topics relevant to clinical practice by integrating evidence synthesis with expert exchange. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6283
Coronary Arteriosclerosis and Myocardial Hypertrophy
Authors: E. P. Connolly, David Littmann
Journal: New England Journal of Medicine (1951)

CARDIAC hypertrophy commonly occurs with disturbances that increase the work of the heart. These include valvular defects, intracardiac or other vascular shunts and hypertension of either the pulmonary or the systematic circuits. In these situations the cause is apparent and the result follows naturally. The heart is subjected to unusual or excessive work, and it follows that the myocardium enlarges in a manner analogous to the development of increased muscle mass in weight lifters and wrestlers.Other conditions with myocardial hypertrophy exist, however, in which the cause is either less clear or totally obscure. Myocarditis may result in myocardial hypertrophy, . . .
PID1 IS A NOVEL SENSITIZER OF BRAIN TUMOR CELLS TO CHEMOTHERAPY
Authors: A. Erdreich-Epstein, J. Xu, X. Ren
Journal: Neuro-Oncology (2014)

BACKGROUND: PID1 is a phosphotyrosine binding domain-containing protein of unknown function in cancer. We recently provided the first report of PID1 in brain tumors (and in cancer). PID1 inhibits growth and proliferation and induces cell death, apoptosis and mitochondrial depolarization in glioblastoma, medulloblastoma and ATRT cell lines. PID1 siRNA had the opposite effect on mitochondrial depolarization. PID1 mRNA level was directly correlated with survival of patients with medulloblastoma or glioma: PID1 mRNA was lowest in tumor subgroups with the poorest prognosis and highest in the more favorable prognosis groups within each diagnosis. The mechanism by which PID1 affects these tumors is currently unknown, and is the focus of studies in our laboratory. METHODS: Experiments were conducted in tissue culture in primary and established cell lines using established methods to assess mRNA, proliferation and signal transduction. RESULTS: Since lower PID1 mRNA was associated with poorer outcome in medulloblastoma and gliomas and higher PID1 was associated with improved outcome, we hypothesized that PID1 level may affect responsiveness of these brain tumors to therapy: higher responsiveness in tumors with high PID1 and resistance when it is low. Indeed, while both cisplatin (10 µg/ml) or transient PID1 overexpression increased apoptosis of glioma and medulloblastoma cell lines (indicated by increased AnnexinV, caspase-3 cleavage and mitochondrial depolarization), combining cisplatin with PID1 caused a markedly higher effect than each alone. Moreover, knockdown of PID1 by siRNA inhibited the cisplatin-induced mitochondrial membrane depolarization and apoptosis (AnnexinV and caspase-3 cleavage), suggesting that PID1 may be required for cisplatin-induced apoptosis. This supports our hypothesis that PID1 may sensitize brain tumor cells to chemotherapy. Intriguingly, PID1 mRNA increased in response to cisplatin (5 µg/ml) as well as to etoposide (5 µg/ml) and vincristine (50ng/ml), in a time- and dose-dependent manner in the brain tumor cell lines. Further, etoposide and cisplatin also increased PID1 luciferase promoter activity. Interestingly, the increase in chemotherapy-induced PID1 promoter reporter activity as well as the chemotherapy-induced increase in PID1 mRNA were both blocked by inhibitors of NFκB, consistent with presence of an NBκB recognition site in the promoter of PID1, and indicating that regulation of PID1 may be an NFκB-dependent mechanism. CONCLUSIONS: Our data suggest that PID1 mediates glioma and medulloblastoma cell response to chemotherapy in an NFκB-dependent manner. Moreover, these data also suggest that PID1 sensitizes medulloblastoma and glioma to chemotherapy, providing the initial mechanistic step to understand the correlation between higher PID1 mRNA and survival in patients. SECONDARY CATEGORY: Pediatrics.
Abstract 3458: Wnt activation is implicated in glioblastoma radioresistance
Authors: Yonghyun Kim, Kang Ho Kim, Hyewon Lee, Heekyoung Yang, Donggeon Kim, Wonyoung Kang, Juyoun Jin, Kyeung Min Joo, Jeongwu Lee, Do-Hyun Nam
Journal: Cancer Research (2012)

Abstract Glioblastoma (GBM) patients have dismal median survival even with the most rigorous treatments currently available. Radiotherapy is the most effective non-surgical therapy for GBM patients; however, patients succumb due to tumor recurrence within a year. To develop a curative therapeutic approach, we need to better understand the underlying molecular mechanism of radiation resistance in GBM. Towards this goal, we developed an in vivo orthotopic GBM model system that mimics the radiation response of human GBM, using both established-GBM cell line and patient-derived freshly dissociated GBM specimen. In-vivo ionizing radiation (IR) treatment prolonged the survival of mice with intracranical tumor derived from U373MG, but failed to prevent tumor recurrence. U373MG and GBM578 cells isolated after in-vivo IR (U373-IR and 578-IR) were more clonogenic and enriched with stem cell-like characteristics, compared with mock-treated control tumor cells. Transcriptomic analyses and quantitative real-time reverse-transcription PCR analyses using these matched GBM cells before and after radiation treatment revealed that Wnt pathways were preferentially activated in post-IR GBM cells. U373-IR cells and 578-IR were enriched with cells positive for both active b-catenin (ABC) and Sox2 population, and this subpopulation was further increased after additional in-vitro radiation treatment, suggesting that radiation resistance of GBM is mediated due, in part, to the activation of stem cell-associated pathways including Wnt. Finally, pharmacological and siRNA inhibition of Wnt pathway significantly decreased the survival and clonogenicity of GBM cells and reduced their ABCþ/Sox2þ population. Together, these data suggest that Wnt activation is a molecular mechanism to confer GBM radioresistance and an important therapeutic target. 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 3458. doi:1538-7445.AM2012-3458
AB0877 Sleep quality in patients with ankylosing spondylitis
Authors: E. Aydin, K. Bayraktar, Y. Turan, I. Kurt Omurlu, E. Tastaban, O.F. Sendur
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The main clinical phenomena in ankylosing spondylitis (AS) are pain and body limitation which effect daily activities and quality of life. Because of the postural alterations, inflammatory night pain and stiffness, sleep disturbances are also likely in patients with ankylosing spondilitis. There is a number of studies that demonstrate poor sleep quality in these patients. <h3>Objectives</h3> This study aimed to determine differences in sleep quality between patients with AS and healthy controls and to assess relationship between disease activity and sleep quality in AS patients. <h3>Methods</h3> Forty patients with AS (29 men, 11 women; age, 44±9 yrs) who fulfilled the modified New York criteria and forty comparable controls (29 men, 11 women; age, 43±9 yrs) completed the Pittsburgh sleep quality index (PSQI) to assess sleep quality. BASDAI was collected for assessing disease activity. <h3>Results</h3> Significant differences in sleep disturbances (P=0.044), daytime dysfunction (p=0.027) and total PSQI score (P=0.017) but not for the sleep quality, sleep latency, sleep duration, habitual sleep efficiency and sleep medication use were found; between patients with AS and healthy controls. Significant positive correlations between BASDAI scores with sleep quality (P=0.008), sleep latency (P=0.006), sleep duration (P=0.015), habitual sleep efficiency (P=0.003), sleep disturbances (P=0.002), day time dysfunction (P&lt;0.001) and total PSQI score (P&lt;0.001) were found in patients with AS. In addition, BASDAI scores that suggest active disease (≥4) were significantly correlated with sleep quality (P=0.02), sleep latency (P=0.003), habitual sleep efficiency (P=0.014), sleep disturbances (P=0.019), day time dysfunction (P=0.027) and total PSQI score (p&lt;0.001). <h3>Conclusions</h3> In the current study, we found that sleep disturbances were significantly higher in patients with AS and disease activity was associated with sleep quality. <h3>References</h3> Günaydin R, Göksel Karatepe A, Cesmeli N, Kaya T. Fatigue in patients with ankylosing spondylitis: relationships with disease-specific variables, depression, and sleep disturbance. Clin Rheumatol. 2009; 28(9):1045-51. Hultgren S, Broman JE, Gudbjörnsson B, Hetta J, Lindqvist U. Sleep disturbances in outpatients with ankylosing spondylitisa questionnaire study with gender implications. Scand J Rheumatol. 2000;29(6):365-9. <h3>Disclosure of Interest</h3> None Declared
Abstract 870: Synergistic antitumor activity of AKT inhibitor MK2206 and FUS1-nanoparticles in LKB1 mutant NSCLC
Authors: Jieru Meng, Humberto Lara-Guerra, Lin Ji, Jack A. Roth
Journal: Cancer Research (2012)

Abstract FUS1, a novel tumor suppressor gene in the human chromosome 3p21.3 region, is deleted in many cancers. A phase I clinical trial assessing FUS1-mediated molecular therapy has reported antitumor activity in lung cancer patients. Previous studies showed that FUS1 regulates the activation of multiple oncogenic kinases. MK2206 is a highly selective non-ATP-competitive allosteric inhibitor of AKT currently being evaluated in early-phase clinical trials for treatment of patients with lung cancer. In this study, we evaluated the combined effects of the tumor suppressor gene FUS1 and MK2206 on tumor cell growth and apoptosis induction in NSCLC cells and explored the molecular mechanism of their mutual action. We found that exogenous expression of FUS1 sensitized the response of NSCLC cells to MK2206, resulting in a marked increase in growth suppression and apoptosis in LKB1-mutant NSCLC cells. However, FUS1 had no effect on the response of LKB1-wild-type NSCLC cells to MK2206. Systemic treatment with a combination of FUS1-nanoparticles and MK2206 in an LKB1 mutant H322 lung cancer subcutaneous xenograft mouse model enhanced the therapeutic efficacy of MK2206. The mice receiving the combination of MK2206 and FUS1-nanoparticles showed a significantly reduced mean tumor volume (364±164 mm3) compared with mice receiving empty vector/MK2206 (728±101 mm3), MK2206 alone (926±250 mm3), FUS1 alone (1171±294 mm3), or empty vector (2405±737 mm3) by day 21 (P&amp;lt;0.01 for all three comparisons). Our results show that FUS1 may play a role in modulating the sensitivity of lung cancer cells to AKT inhibition, and suggests that a combination of FUS1-nanoparticles and MK2206 may be an effective treatment strategy for LKB1 mutant human lung cancers. 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 870. doi:1538-7445.AM2012-870
Abstract 3883: Miniaturizing the GloSensor™ cAMP assay for MC4R screening using the Echo® acoustic liquid handler
Authors: Tracy J. Worzella, Tim Allison, Pete Stecha, Mei Cong, Chad Zimprich, Kevin Kershner, Richard L. Somberg
Journal: Cancer Research (2012)

Abstract As biological assays used for HTS and uHTS are miniaturized, it is critical to maintain assay sensitivity while minimizing reagent volumes and maximizing throughput. The GloSensor™ cAMP Assay provides an extremely sensitive and easy to use, real-time luminescent assay format for the interrogation of over expressed or endogenous GPCRs that signal via changes in the intracellular concentration of cAMP. Tipless, touchless transfers with the Echo® liquid handler eliminate the need for costly disposable tips and greatly simplify assay development efforts. Precise and accurate drop placement eliminates cross-contamination. In this work, we demonstrate optimization of the GloSensor cAMP Assay in low-volume format using a stably transfected HEK293 cell line model expressing the melanocortin 4 receptor (MC4R) and a cAMP-sensing variant of firefly luciferase. We show that the Echo liquid handler is able to titrate small molecule and peptide agonists and antagonists, as well as transfer the GloSensor cAMP Reagent, providing robust assay results that are achieved with significantly reduced volumes of cells and compound. 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 3883. doi:1538-7445.AM2012-3883
PMO-108 Diagnosis of pancreatic solid lesions with EUS and FNA: a report of accuracy
Authors: S R Kadri, K Law, M James, K Ragunath, G Aithal
Journal: Gut (2012)

<h3>Introduction</h3> Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an accurate method for cytological confirmation of pancreatic lesions, but it is unclear whether its diagnostic accuracy is affected by it9s size, location, or size of needles used for biopsy. Our aim was to investigate the accuracy of EUS-FNA for suspected pancreatic lesions in relation to these factors, especially to the size of lesions, size of the needle used for biopsy and number of passes. <h3>Methods</h3> In this tertiary referral centre, EUS-FNAs for 186 solid pancreatic lesions from 1 April 2010 to 31 March 2011 were evaluated retrospectively. Size of the lesion, site of the lesions were obtained as well as the information on size of the needle used to take biopsy and number of passes made and adequacy of the sample obtained. <h3>Results</h3> 87 males and 85 females had 186 EUS FNA for solid pancreatic lesions.71% (123/172) of then were aged between 51 and 80 years. 79 lesions were in the head of the pancreas alone. Information on adequacies for sampling was available for 149 procedures. Overall adequacy of EUS-FNA sampling was 76% (114/149). Adequacy for the sample for lesions &lt;10 mm was 77% (10/13) and for more than 10mm was 68% (104/153); those for lesions in the head was 70% (55/79) and for rest of the pancreas was 75% (59/79). Success rate for single, two, three and four passes made to obtain sample were 58%, 75%, 70% and 80% respectively. Accuracies for 19, 22 and 25-gauge needle sampling were 67%, 76% and 85% respectively. <h3>Conclusion</h3> EUS-FNA has high accuracy in the evaluation of suspected pancreatic lesions regardless of its size, location of the lesion. It was useful also in confirming small pancreatic lesions that were &lt;10 mm. 25-gauge needle produced best tissue yield out of all the types of the needles used for sampling. <h3>Competing interests</h3> None declared.
QUANTIFICATION OF SHUNT VOLUME THROUGH VENTRICULAR SEPTAL DEFECTS OF VARIED AREA, SHAPE AND NUMBER USING REAL-TIME 3D COLOR DOPPLER ECHOCARDIOGRAPHY: AN IN VITRO STUDY
Authors: David J. Sahn, Evan Tracy, Kim Dang, Joanne Tran, Meihua Zhu, Muhammad Ashraf
Journal: Journal of the American College of Cardiology (2016)