tbuckley/cabot-search huggingface dataset:
AB1031 Misdiagnosis of Rheumatoid Arthritis in A Colombian Specialized Center and Socio-Demographic Characterization
Authors: V. Giraldo, G. Saavedra-Martinez, A. Palomino, L. Villarreal, D. Gomez, J. Bello-Gualtero, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There is a lack of expertise in the rheumatoid arthritis (RA) diagnosis in primary level medical centers in Colombia, leading to misdiagnosis, which derives in wrong treatment for patients and pharmacoeconomic implications. <h3>Objectives</h3> The aim of this study was to describe demographic and clinical characteristics of a cohort of patients with misdiagnosis of RA in a specialized center in Colombia. <h3>Methods</h3> A descriptive, cross sectional study. Patients were referred from non-specialized centers to a RA specialized center in a 24 month period with presumptive diagnosis of this disease. A complete medical record was fulfilled by a rheumatologist; it was assessed rheumatoid factor and anti-citrullinated antibodies, and other laboratories depending on each case. Also were made x-rays of hands and foot, and in some cases of persistent doubt about the diagnosis was requested comparative MRI of hands. Frequencies and percentages were calculated for the demographic and clinical characteristics of the cohort of patients in which the diagnosis of RA was ruled-out. <h3>Results</h3> Of the 3665 patients evaluated, in 2214 patients (60.4%) diagnosis of RA was confirmed, the remaining 1451 patients (39.5%) had a wrong diagnosis of RA. Of these misdiagnosed patients, 1009 (69.5%) were women, and 442 (30.5%) men, with an average age of 59.7 (±12 years). Between differential diagnosis which were found in this cohort of misdiagnosed patients: osteoarthritis in 1116 patients (76.1%), systemic lupus erythematosus (SLE) in 85 patients (5.8%), Sjögren syndrome in 62 patients (4.3%), spondyloarthropathies in 22 patients (1.5%), gout in 32 patients (2.2%) and other diagnoses in the remaining population (8%). <h3>Conclusions</h3> Almost half patients with presumptive RA diagnosis in primary care centers in Colombia are misdiagnosed as shown in this large cohort. The most important cofounding diagnosis was osteoarthritis and many patients were receiving DMARDs for treatment. For this reason there is an urgent need of education strategies for primary care physicians and the implementation of centers of excellence in RA, in order to conduct a proper diagnose and avoid clinical and pharmacoeconomic consequences of misdiagnosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5327
Abstract 4132: Predictive classifiers for response to c-Met targeted therapies in lung and colon cancer
Authors: David Drubin, Natalie L. Catlett, Jennifer Park, Aaron A. Van Hooser, Brian P. Frushour, Renee Deehan Kenney
Journal: Cancer Research (2011)

Abstract A fundamental challenge in the development of cancer therapies is the co-development of companion biomarkers to select patients most likely to respond to treatment prior to the availability of clinical outcomes data. We developed a methodology that leverages large scale public ‘omics data to identify candidate predictive biomarker panels to identify patients with a greater likelihood of responding to targeted therapies. We applied this approach to generate mechanism-based predictive biomarkers using our causal Knowledgebase as a substrate, as well as standard gene expression-based biomarkers for c-Met targeted therapy use in lung and colon cancers, and validated the methodology using clinical data. Gene signatures for c-Met activation in lung and colon were applied to individual lung and colon cancer training set patients to stratify them by c-Met activation levels. Data from patients identified as having high and low levels of c-Met activation were used to develop mechanism-based and gene expression-based classifiers to predict response to c-Met targeted therapies in lung and colon cancer. Validation of these classifiers requires transcriptomic data with associated clinical outcomes from c-Met inhibitor trials. In the absence of such, we verified this general approach using data from Inflammatory Bowel Disease (IBD) patients treated with the TNF inhibitor Infliximab, for which published colon transcriptomic data and associated clinical outcomes data are available {GSE16879} We developed a gene signature to assess TNF pathway activation and stratify a training set of IBD patients, then generated gene expression and mechanism-based classifiers from patients with high and low TNF signaling. These classifiers were tested on an independent test set of IBD patients treated with Infliximab {GSE12251}; the mechanism and gene expression-based classifiers predicted responders with positive and negative predictive values of 85%/88% and 70%/100% respectively. This method can be applied to other targets, pathways and diseases and may facilitate companion diagnostic development by enabling the selection of appropriate patient populations prior to treatment and clinical trial participation. 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 4132. doi:10.1158/1538-7445.AM2011-4132
Abstract 1671: GSK3-beta as a therapeutic target in bladder cancer
Authors: Marie N. Becker, Christina A. von Roemeling, John A. Copland, Christopher R. Williams
Journal: Cancer Research (2011)

Abstract Bladder cancer is the 5th most commonly diagnosed cancer in the United States. Because superficial bladder cancer (SBC) recurs in about 60% of cases, standard treatment involves tumor resection followed by intravesical therapies to prevent recurrence, as well as lifelong periodic cystoscopy. There is an urgent need for better intravesical therapies to prevent both the recurrence and progression of SBC. Recent evidence has demonstrated that glycogen synthase kinase – 3 beta (GSK3β) plays an important role in pancreatic, ovarian and colon cancers; however, to date the possible role of this important kinase has not been examined in bladder cancer. We propose that GSK3β plays a cancer promoting role in bladder cancer and that inhibition of GSK3β will reduce bladder cancer growth. The GSK3β inhibitor, AR-A014418, has been demonstrated to reduce tumor growth in the previously cited cancers. AR-A014418 reduced cell proliferation of three bladder cancer cell lines (HT1376, T24 and UM-UC-3) with EC50 values of 17.5μM for HT1376, 8μM for T24, and 10μM for UM-UC-3 cells. The effect of AR-A014418 on downstream targets in these cell lines was evaluated by Western blots which indicated an increase in apoptosis in these cells in response to drug treatment as demonstrated by the presence by both PARP and caspase 3 cleavage. The NFkB downstream target XIAP also exhibited reduced protein levels after drug treatment. The HT1376 cell line was transduced with luciferase containing lentivirus particles to generate a luciferase expressing cell line, HT1376-LUC to use for both ectopic and orthotopic models of bladder cancer growth. The efficacy of AR-A014418 in reducing bladder cancer tumor growth was tested in an ectopic mouse model. HT1376-LUC cells mixed with matrigel were transplanted into the right flank of 50 female nude mice. After one week, mice containing tumors with an average volume of 52 mm3 were randomized into four treatment groups of 10 mice each. Mice were treated twice weekly via IP injection with placebo, 1, 5 or 7mg/kg AR-A014418. Tumor sizes were measured and imaged for luciferase activity once weekly. Tumor growth was inhibited by both 5mg/kg and 7mg/kg doses by 19 days of treatment (p &amp;lt; 0.05, Student's T test). Together, the in vitro and in vivo data suggest that GSK3β is a novel target for bladder cancer treatment. Future studies using an orthotopic model of bladder cancer are planned. 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 1671. doi:10.1158/1538-7445.AM2011-1671
Hiatus Hernia: A Potential Cause of False-Positive Iodine-131 Scan in Thyroid Carcinoma
Authors: YVONNE HO, RODNEY HICKS
Journal: Clinical Nuclear Medicine (1998)

A hiatus hernia mimicking iodine-131 avid pulmonary metastases was seen in a patient with follicular carcinoma of the thyroid. Uncertainty about results such as these can be diminished easily by chest radiography correlation.
Screening for Cardiovascular Disease in a Community
Authors: Walter O. Blanchard, William J. Zukel, Ernest M. Morris, Mary Alice Smith, Daniel A. Sullivan
Journal: New England Journal of Medicine (1954)

TO discover persons with a high probability of cardiovascular disease and refer them to their physicians for diagnosis and treatment, a case-finding program was started in Newton, Massachusetts, in July, 1949. This report summarizes the experience and results of screening in 15 groups totaling approximately 8000 persons from July, 1949, to March, 1952.Case finding was one portion of a general community heart project established jointly by the Newton Health Department, the Massachusetts Department of Public Health and the United States Public Health Service to determine what a community can do about its heart-disease problems. The complete program, as reviewed . . .
Government changes are jeopardising public health
Authors: Delan Devakumar, Kate L Mandeville, Jennifer Hall, Shailen Sutaria, Ingrid Wolfe
Journal: BMJ (2016)

On some health markers, the United Kingdom compares well with similar countries-for example, access to health services. 1However, it fares poorly on many health risk factors, such as alcohol consumption and poor diet, and in some population outcomes such as child health.For example, the UK is 32nd out of the 34 countries in the Organisation for Economic Cooperation and Development for childhood obesity. 1 2 "Prevention is better than cure" is a central argument in the NHS Five Year Forward View strategy, yet the Health and Social Care Act 2012 and recent austerity budgets have reduced the power of public health as well as the specialist workforce, jeopardising the health of the public. 3
Metastatic Mediastinal Carcinoid Presenting as Superior Mediastinal Syndrome and Treated With Peptide Receptor Radionuclide Therapy
Authors: Gaurav Malhotra, Ramesh V. Asopa
Journal: Clinical Nuclear Medicine (2013)

A 43-year-old man with known superior mediastinal syndrome due to (99m)Tc HYNIC DOTA SPECT/CT and (18)F-FDG PET tracer avid inoperable metastatic carcinoid received peptide receptor based radionuclide therapy (PRRT) with (177)Lu-DOTATATE. Repeat evaluation at 3 months post-therapy demonstrated stable disease with alleviation of patient's symptoms and remarkable improvement in the quality of life. PRRT with (177)Lu-DOTATATE may be an option for inoperable mediastinal carcinoids with superior mediastinal syndrome.
OXIMETRY PARADOXUS: SUPERIORITY OVER PULSUS PARADOXUS IN THE CLINICAL DIAGNOSIS OF CARDIAC TAMPONADE
Authors: Michael J. Shih, Briana T. Costello, Gabriel Improvola, Juan M. Munoz-Pena, Bosko Margeta, Charlotte Bai, Rami Doukky
Journal: Journal of the American College of Cardiology (2015)
Abstract IA-6: Single nucleotide polymorphisms in the p53 pathway
Authors: Arnold J. Levine
Journal: Cancer Research (2009)

Abstract The p53 protein and the signal transduction pathway controlled by that protein responds to a wide variety of stress signals which can disrupt the fidelity of DNA replication and cell division. To prevent these errors or mutations the p53 pathway responds by initiating a process of cell cycle arrest, senescence or apoptosis which either permits repair of these errors or kills the clone of cells that contain these mutations. Central to this pathway are a series of proteins that respond to the stress signals and regulate the levels and activity of the p53 pathway. We have identified a number of single nucleotide polymorphisms (SNP) in those genes that regulate p53 activity and functions and these SNPs can play a role in the incidence of cancers in a population, the age of onset of cancers and the response to therapy. Some of the haplotypes containing these SNPs appear to be under positive evolutionary selection pressures in some human populations. The reason for this appears to be the role of p53 in the implantation of embryos into the uterus and the impact of some of these SNPs upon the fecundity of mice and humans. This process is mediated by the p53 regulated gene, Leukemia Inhibitory Factor or LIF, a cytokine that is essential for the implantation of embryos. SNPs in the p53 gene, the MDM-4 gene and the LIF gene regulate the efficiency of implantation of embryos in humans. It could well be that the p53 protein is also involved in the surveillance of developmental abnormalities. Citation Information: Cancer Res 2009;69(23 Suppl):IA-6.
DIRECT TRANSCATHETER AORTIC VALVE REPLACEMENT VERSUS IMPLANTATION WITH BALLOON PREDILATATION: INSIGHTS FROM THE BRAZILIAN TAVR REGISTRY
Authors: Fernando Bernardi, Henrique Ribeiro, Luiz Carvalho, Rogerio Sarmento-Leite, José Mangione, Eduardo Sousa, Pedro Lemos, Eberhard Grube, Josep Rodes-Cabau, Fabio Brito
Journal: Journal of the American College of Cardiology (2016)
Abstract 617: High-throughput screens identify PARP inhibition as being synthetically lethal with ERCC1 deficiency in non-small cell lung cancer cell lines.
Authors: Sophie C. Postel-Vinay, Ilirjana Bajrami, Luc Friboulet, Marieke Aarts, Yari Fontebasso, Fabrice Andre, Ken Olaussen, Jean-Charles Soria, Chris Lord, Alan Ashworth
Journal: Cancer Research (2013)

Abstract Background: Non-small cell lung cancer (NSCLC) harbors frequent DNA-repair defects that represent therapeutic opportunities. Notably, Excision Repair Cross-Complementation group 1 (ERCC1) deficiency has been described in a subset of tumors and correlated with platinum sensitivity. The use of mechanism-based approaches, such as synthetic lethality, could allow targeting more selectively such DNA repair defects, with reduced systemic toxicity. Methods: To identify ERCC1-selective synthetic lethal interactions, we adopted an integrated functional and molecular profiling approach. An isogenic model of ERCC1-deficient NSCLC cells, consisting of one parental ERCC1-proficient cell line and 3 ERCC1-deficient clones, was functionally profiled by high throughput drug sensitivity screening using a library containing commonly used oncology agents as well as a large number of in-development targeted agents. This was integrated with data from molecular profiling, including high throughput siRNA screens. Results: The comparison of functional viability profiles for ERCC1-deficient models enabled the identification of synthetic lethal effects that could represent therapeutic opportunities for ERCC1-deficient tumors. Notably, ERCC1-deficient cells showed increased sensitivity to several PARP inhibitors, representing promising preliminary results that could be translated in the clinical setting. Mechanistic studies revealed a significant delay in double-strand break repair associated with a G2/M arrest following PARP inhibitor treatment in the ERCC1-deficient population only. Further in vitro work is providing deeper insight into the mechanisms underlying this PARP inhibitors sensitivity and in vivo work is underway. Conclusions: ERCC1-deficiency sensitizes human NSCLC cell lines to PARP inhibitors. In vitro and in vivo revalidations of these results and now underway to further dissect the molecular mechanisms responsible for these ERCC1-deficient selective effects, which could represent therapeutic opportunities. Citation Format: Sophie C. Postel-Vinay, Ilirjana Bajrami, Luc Friboulet, Marieke Aarts, Yari Fontebasso, Fabrice Andre, Ken Olaussen, Jean-Charles Soria, Chris Lord, Alan Ashworth. High-throughput screens identify PARP inhibition as being synthetically lethal with ERCC1 deficiency in non-small cell lung cancer cell lines. [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 617. doi:10.1158/1538-7445.AM2013-617
SAT0501 Clinical Predictors of Functional Disability in Patients with Gout: Analysis from A Multicentre Observational Study of the Italian Society for Rheumatology:
Authors: C.A. Scirè, G. Carrara, M. Manara, M. Cimmino, M. Govoni, F. Salaffi, L. Punzi, C. Montecucco, M. Matucci-Cerinic, G. Minisola
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Gout is the most prevalent arthritis and significantly impacts on function. Identifying disease-related prognostic factors may help to improve management and prevent disability. <h3>Objectives</h3> This study aims to evaluate the association of disease-related factors with functional disability over time and relative importance in patients with gout. <h3>Methods</h3> This is prospective analysis of a multicentre cohort study including patients with a clinical diagnosis of gout (KING Study, promoted by SIR, NCT01549210) recruited between June 2011 and January 2012. All patients underwent full clinical evaluation, recording variables belonging to five different domains: socio-demographics, life-styles and comorbidities, treatments, gout-related variables (diagnosis, duration, pattern of disease, tophi burden, joint examination and serum uric acid (sUA) levels). Functional disability was assessed by the health assessment questionnaire (HAQ) at baseline and 12 months. The primary outcome was defined as persistency of or worsening of functional disability at 12 months (according to the following HAQ classes: absent 0–0.5; mild 0.5–1; moderate 1–2; severe 2–3). Logistic models were used to explore the relationship between predictors and outcome. A prognostic model was built selecting variables (backward) within the domains, and combining them thereafter. Discrimination and calibration of the final model was tested by the area under the ROC curve (AUC) and the Hosmer-Lemeshow test. Bootstrap internal validation was performed. Results are presented as odds ratio (OR) and 95% confidence interval (CI). <h3>Results</h3> A total of 446 patients were included in the analyses. 90% were men and mean (SD) age was 63.9 (11.6) years. Gout-related factors associated with worse functional outcome after 12 months are reported in Table. A comprehensive prognostic model for 12-month disability was developed, finally including: baseline HAQ (OR [95% CI]: 7.52 [4.16-13.59]), sUA levels [cut off: 6 mg/dl] (2.13 [1.09-4.16]), index of comorbidity (1.12 [1.02-1.22]) and number of tender joints (1.55 [0.73-3.28] 2-4 vs 0-1; 3.32 [1.42-7.78] &gt;4 vs 0-1). The model showed a good performance (AUC of 0.877), calibration and internal validity. <h3>Conclusions</h3> Disease-specific variables independently impact on function over time, suggesting that a stricter control of the disease may improve the excess of disability observed in gout. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1775
Abstract 2088: <i>miR-133a</i> as a tumor suppressive microRNA by targeting multiple oncogenes in head and neck squamous cell carcinoma (HNSCC)
Authors: Toyoyuki Hanazawa, Naoko Kikkawa, Nijoro Nohata, Homare Suzuki, Takeshi Chiyomaru, Hideki Enokida, Masayuki Nakagawa, Yoshitaka Okamoto, Naohiko Seki
Journal: Cancer Research (2010)

Abstract Head and neck squamous cell carcinomas (HNSCC) represent 6% of all cancers. Despite of considerable advances in surgery, radiotherapy and chemotherapy, the overall 5-year survival rate for patients is less than 40% in advanced stage. The understanding of the new molecular pathways of HNSCC carcinogenesis would be helpful in improving diagnosis and therapy of the disease. MicroRNA(miRNA) are endogenous short non-coding RNA molecules, which regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNA over-expression could result in down-regulation of tumor suppressor genes, whereas their under-expression could lead to oncogenes activation. Expression levels of 665 human mature miRNAs were screened using the stem-loop real-time quantitative PCR method. We identified several down-regulated miRNAs based on miRNA expression signatures in HNSCC. A comparison of miRNA signatures from HSCC and our previous reports (Ichimi et al., Int J Cancer 2009, 125:342-352; Kano et al., AACR 2009, #552; Kikkawa et al., AACR 2009, #587) identified miR-133a that is down-regulated in common, suggesting that miR-133a is candidate tumor suppressor. Gain-of-function analysis revealed that miR-133a transfectant inhibits cell proliferation and cell invasion in cancer cells. For target genes silenced by miR-133a in cancer cells, we performed genome-wide screening (oligo microarray analysis and public database searche). Among the genome-wide analysis, several candidate genes were identified, such as, fascin homolog 1 (FSCN1) and glutathione S-transferase P1 (GSTP1). We focused on FSCN1, an actin-bundling protein, which induces parallel actin bundles in cell protrusions and increases cell motility in several human cancers. The miR-133a which has conserved sequence in the 3′UTR of FSCN1, inhibited of FSCN1 expression. The signal from a luciferase reporter assay was significantly decreased at miR-133a site, suggesting miR-133a directly regulate FSCN1. An FSCN1 loss-of-function assay found significant cell growth and invasion inhibition in HNSCC cells implying an FSCN1 is associated with HSCC carcinogenesis. Tumor suppressive miRNAs and target oncogenes may provide new insights into the mechanisms in cancer. Our findings have therapeutic implications and may be exploited for future HSCC treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2088.