tbuckley/cabot-search huggingface dataset:
SAT0230 The Minimum Clinically Important Improvement and Patient Acceptable Symptom State in Basdai and Basfi in Patients with Ankylosing Spondylitis
Authors: M. J. Kviatkovsky, S. Ramiro, R. Landewé, F. Tubach, M. Dougados, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) are clinically relevant measures that report the patient condition. These can be established using cutoffs in BASDAI and BASFI to assess disease activity and functional disability respectively, in patients with Ankylosing Spondylitis (AS). <h3>Objectives</h3> To estimate the MCII and PASS cutoff values for BASDAI and BASFI for patients with AS. <h3>Methods</h3> A multinational (Australia, France, Italy, Lebanon, Morocco, Spain and The Netherlands) cohort study was conducted where patients with AS received NSAIDs for 4-weeks. PASS and MCII were determined using external anchor questions for patient global assessment for BASDAI and functional impairment for BASFI. For PASS patients were asked to consider the ways AS has affected them during the last 48 hours and if this would be an acceptable state for the rest of their life. Patients who answered “acceptable” met criteria for PASS analysis. For MCII, patients were asked first to compare how they felt in the past 48 hours to how they felt at the start of the study. Secondly, if they felt improved, to consider how important the improvement was. Patients who reported improvement that was either moderate or slightly important met criteria for MCII analysis. Analyses were conducted using patients who met criteria based on the external anchor question and for comparison, also in patients who met the general rheumatic disease criteria published in the REFLECT study. These criteria recommend a value &lt;4 for PASS and relative improvement ≥20% for MCII.(1) The 75th percentile approach was used to establish cutoff values of MCII and PASS in BASDAI/ BASFI. <h3>Results</h3> Of 283 patients with AS, 214 were males (76%), 181 were HLA-B27 positive (64%) with a mean age of 42.9 years (13.5) and mean disease duration of 12.9 (9.7) years. PASS values were 4.1 for BASDAI and 3.8 for BASFI (Table). Both values were slightly lower in patients selected using REFLECT study cutoffs. The MCII in BASDAI was 0.7 for absolute and 16.7% for relative change and slightly higher using REFLECT study cutoffs. The MCII in BASFI was set 0.4 for absolute 8.7% for relative change with similar values found using REFLECT study cutoffs. <h3>Conclusions</h3> These disease specific PASS and MCII cut off values allow researchers and clinicians to use validated outcome measure instruments to dichotomize patients into those who achieve therapeutic success and those who do not. <h3>References</h3> Tubach et al, AC&amp;R 2012. <h3>Disclosure of Interest</h3> None Declared
Abstract 3885: A bi-functional fluorescent assay for the assessment of cytotoxicity and proliferation
Authors: Andrew L. Niles, Min Zhou, Laurent Bernad, Mark McDougall, Dan Lazar
Journal: Cancer Research (2012)

Abstract Cell-based models continue to be critical tools for cancer research. Therefore, the assessment of cytotoxic or cytostatic effects remains an obligate experimental activity. Although numerous enzyme activity chemistries exist for measuring cytotoxicity, biomarker degradation may cause underestimation of actual cytotoxicity and limit the utility of these activity measures when ascertained with long-term drug exposures (72hrs or more). We have developed a cell-impermeant probe which labels the DNA from cells with compromised membranes. The quantum efficiency (i.e. brightness) of this dye increases dramatically upon DNA binding, producing a fluorescent signal which can be measured using standard “green” fluorometry wavelengths (excitation 485nm/emission 530nm). Additionally, the dye is non-toxic and stable, allowing for introduction of the probe directly into the culture medium or compound dilutions prior to cell dosing. This “no step” addition feature allows for the measurement of cytotoxicity in real time or at a convenient endpoint. Furthermore, the dye is fully compatible with luminescent measures, allowing for same-well, multi-parametric assessment of the cytotoxic phenotype. Lastly, proliferative or anti-proliferative effects (relative to control) can be revealed by the introduction of a lytic detergent which enables the normally impermeant dye to bind to all DNA in the assay well. Herein, we detail our efforts to characterize and multiplex this dye when applied to suspension and adherent cell lines treated with agents which cause either primary or secondary necrosis in a 72hr time course. 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 3885. doi:1538-7445.AM2012-3885
Abstract 713: GLRX3, a secretory biomarker of pancreatic cancer based on pancreatic cancer stem cell characteristics
Authors: Sun A Kim, Soo Bin Park, Si Young Song
Journal: Cancer Research (2012)

Abstract A. BACKGROUND/AIMS Pancreatic cancer is one of the most lethal diseases, which is difficult to diagnose and resistant to conventional treatment such as chemotherapy and radiotherapy. Cancer stem cells are involved in carcinogenesis, cancer progression and recurrence. We tried to find secretory biomarkers associated with pancreatic cancer stem cells using proteomic analysis. B. METHODS Pancreatic cancer stem like cells were enriched using sphere culture method. Proteomic analysis was done with secreted protein in culture medium of sphere and adherent cells. Identified proteins were confirmed with Western blot and immunohistochemical staining. ELISA was done to detect blood levels of validated proteins in pancreatic cancer patients. shRNA for GLRX3 was used to study the function of GLRX3 in pancreatic cancer. C. RESULTS Proteomic analysis showed that total of 55 protein spots from sphere cells were increased compared to adherent cells. Among them, 41 spots were identified using MALDI-TOF. Proteins known to be associated with cancer stem cells such as HSP90AB1, ALDH, and vimentin were expressed in sphere cells. The overexpression of 5 proteins including GLRX3 was confirmed by western blot in sphere cells and patient serum. Immunohistochemical staining in TMA of human pancreatic cancer tissue revealed that GLRX3 was detected in 15 (57.7%) out of 25 pancreatic cancer tissues regardless of cancer stages. To examine GLRX3 involvement in pancreatic carcinogenesis, we used shRNA to generate GLRX3-knockdown cells. Compared to the mock, knockdown of GLRX3 in human pancreatic cancer cell lines decreased in vitro proliferation, clonogenecity, and sphere formation. GLRX3 knockdown reverses epithelial-mesenchymal transition in pancreatic cancer cells. ELISA showed patients with unresectable pancreatic cancer and high blood GLRX3 levels had poor survival compared to those with low blood GLRX3 levels (155 days vs 463 days, p-value &amp;lt;0.000). D. CONCLUSION This study shows that secretory protein GLRX3 may be a useful prognostic marker in pancreatic cancer. More researches are needed to find their roles in cancer stem cells and clinical implication. 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 713. doi:1538-7445.AM2012-713
Case 18-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David B. Smith, Carolyn K. Pettit
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 70-year-old man with treated lymphoma was admitted to the hospital because of fever and weakness.The patient was well until 16 years earlier, when a periumbilical mass developed. Medical evaluation at another hospital, including a laparotomy, showed a diffuse, well-differentiated lymphocytic lymphoma and a paraproteinemia. A modified program of cyclophosphamide, vincristine, and prednisone (CVP) was administered during the following two years. The patient was then well until three years before admission, when cervical and axillary lymphadenopathy was found. A computed tomographic (CT) scan of the abdomen revealed two low-attenuation abnormalities in the right hepatic lobe, believed . . .
Effects of Acetylsalicylic Acid Ingestion on Maternal and Neonatal Hemostasis
Authors: Marie J. Stuart, Steven J. Gross, Haim Elrad, Janet E. Graeber
Journal: New England Journal of Medicine (1982)

In a case–control study, we evaluated the effects of maternal ingestion of acetylsalicylic acid (aspirin) within 10 days of delivery on maternal and neonatal hemostasis. Only one of 34 control maternal-neonatal pairs (3 per cent) had hemostatic abnormalities. In 10 pairs, when maternal aspirin ingestion occurred within five days of delivery, 6 of the 10 mothers and 9 of the 10 infants had bleeding tendencies. Seven maternal-neonatal pairs in which aspirin was ingested 6 to 10 days before delivery were free of clinical bleeding. Among seven other mothers who ingested aspirin in the immediate post-partum period four of the seven (57 per cent) also had impaired hemostasis. Neonatal hemostatic abnormalities included numerous petechiae over the presenting part, hematuria, a cephalhematoma, subconjunctival hemorrhage, and bleeding from a circumcision. Maternal bleeding was confined to excessive intrapartum or post-partum blood loss. We conclude that aspirin should be avoided during pregnancy. If ingestion has occurred within five days of delivery, the neonate should be evaluated for the presence of bleeding. (N Engl J Med. 1982; 307:909–12.)
ASSESSING LEVEL OF AGREEMENT FOR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK CATEGORIZATION BETWEEN CORONARY ARTERY CALCIUM SCORE AND THE AMERICAN COLLEGE OF CARDIOLOGY/AMERICAN HEART ASSOCIATION CARDIOVASCULAR PREVENTION GUIDELINES AND POTENTIAL IMPACT ON TREATMENT RECOMMENDATIONS
Authors: David B. Min, Hussain Ismaeel, Laila Al-Shaar, Sandra Halliburton, Paul Schoenhagen, Dermot Phelan
Journal: Journal of the American College of Cardiology (2015)
IS THERE ANY EVIDENCE TO PREFER ONE ARTERIAL GRAFT OVER THE OTHER? A META-ANALYSIS COMPARING RADIAL ARTERY VERSUS RIGHT INTERNAL THORACIC ARTERY FOR CORONARY ARTERY BYPASS GRAFTING
Authors: Mahesh Anantha Narayanan, Harish Devineni, Jeff Murray, Arun Kanmanthareddy, Janani Baskaran, Rakesh M. Suri
Journal: Journal of the American College of Cardiology (2016)
Abstract 4956: Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma
Authors: Junko Hamamoto, Satoshi Yoda, Katsuhiko Naoki, Sohei Nakayama, Ryosuke Satomi, Hideki Terai, Shinnosuke Ikemura, Takashi Sato, Yuichiro Hayashi, Kenzo Soejima
Journal: Cancer Research (2011)

Abstract Introduction: Recent advances in the treatment of non-small-cell lung cancer (NSCLC) with new agents require accurate histological subtyping at diagnosis in order to avoid the higher risk of an adverse response and obtain a maximum therapeutic response. However, interobserver variability, tumor heterogeneity and the degree of differentiation may influence the decision concerning a pathological diagnosis of NSCLC. We therefore in this study attempted to identify specific microRNAs as standardized biomarkers with high sensitivity and specificity for distinguishing between squamous cell carcinoma (SCC) and adenocarcinoma (AC). Methods: Quantitative real time polymerase chain reaction (qRT-PCR) based microRNA array was performed to identify microRNAs differentially expressed between SCC and AC using 86 resected NSCLC samples as well as adjacent normal tissues. The results were confirmed by independent qRT-PCR assays with the same test samples and an additional 88 validation samples and the usefulness of the identified microRNAs as biomarkers to distinguish between SCC and AC was evaluated. Results: Three microRNAs (hsa-miR-196b, hsa-miR-205 and hsa-miR-375) were identified. Discriminant analysis combining all 3 microRNAs appeared to distinguish SCC from AC accurately in the test samples and the validation samples, showing sensitivity and specificity of 76% and 80%, and 85% and 83%, respectively. Conclusions: Hsa-miR-196b, hsa-miR-205 and hsa-miR-375 were identified as biomarkers capable of distinguishing between lung SCC and lung AC. These newly identified microRNAs may prove to be highly valuable molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of each subtype of NSCLC. 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 4956. doi:10.1158/1538-7445.AM2011-4956
Abstract 2191: GABA but not baclofen prevents gemcitabine resistance induced by low dose nicotine in pancreatic cancer xenografts.
Authors: Jheelam Banerjee, Mohammed H. Al-Wadei, Hussein A. N. Al-Wadei, Hildegard M. Schuller
Journal: Cancer Research (2013)

Abstract Pancreatic ductal adenocarinoma (PDAC) is a leading cause of cancer deaths in developed countries. The nucleoside analog Gemcitabine, which induces apoptosis, is widely used for the therapy of pancreatic cancer. Smoking and alcoholism are risk factors for pancreatic cancer. Nicotine replacement therapy often accompanies chemotherapy while the GABA-B receptor (GABA-B-R) agonist Baclofen has recently been suggested as an effective agent for the treatment of alcohol dependence. Our laboratory has shown that the proliferation and migration of PDAC and pancreatic duct epithelial cells in vitro is regulated by the nicotinic receptor-mediated synthesis and release of stress neurotransmitters that bind to beta-adrenoreceptors (beta-ARs). We have additionally shown that nicotine in the drinking water at a high dose (432 μmole/L) comparable to nicotine exposure in heavy smokers significantly stimulated the growth of PDAC xenografts whereas identical exposure of mice to low dose nicotine (1 μmole/L) reduced gemcitabine-induced apoptosis, thus significantly increasing resistance to gemcitabine. In the current study, we have investigated the potential prevention of nicotine-induced gemcitabine resistance by γ-aminobutyric acid (GABA) and Baclofen in PDAC xenografts. We found that GABA significantly reduced nicotine-induce drug resistance. By contrast, Baclofen failed to reduce nicotine-induced resistance to gemcitabine while even slightly increasing xenograft growth in mice not exposed to nicotine. Investigation of xenograft tissues for the expression levels of the GABA-B-R, intracellular cAMP and signaling proteins associated with cell proliferation, apoptosis and metastasis by immunoassays and western blots revealed effective inhibition of cAMP-dependent signaling in xenografts of mice treated with GABA. By contrast, Baclofen did not inhibit cAMP-dependent signaling and decreased the protein expression of the GABA-R, suggesting downregulation of the receptor. Our findings identify GABA as a promising agent for the prevention of nicotine-induced resistance to gemcitabine in PDAC. On the other hand, our data suggest that treatment of alcohol dependence by Baclofen should be avoided in PDAC patients. Supported by grants RO1CA130888 and RO1CA042829 with the National Cancer Institute. Citation Format: Jheelam Banerjee, Mohammed H. Al-Wadei, Hussein A. N. Al-Wadei, Hildegard M. Schuller. GABA but not baclofen prevents gemcitabine resistance induced by low dose nicotine in pancreatic cancer xenografts. [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 2191. doi:10.1158/1538-7445.AM2013-2191
PROGNOSTIC IMPACT OF URINARY SODIUM CONCENTRATION IN PATIENTS WITH ACUTE HEART FAILURE
Authors: Satoshi Honda, Toshiyuki Nagai, Yasuo Sugano, Tatsuhiro Shibata, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
Journal: Journal of the American College of Cardiology (2015)
SAT0023 Clinical and Laboratory Predictors of Distinct Histological Classes of Lupus Nephritis-Can They Substitute the Renal Biopsy?
Authors: C.P. Mavragani, G.E. Fragoulis, A.G. Tzioufas, H.M. Moutsopoulos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The type of histological class of lupus nephritis dictates treatment approaches among lupus patients with renal involvement. Risk stratification may facilitate therapeutic decisions, when renal biopsy is contraindicated or poses high patient risk. <h3>Objectives</h3> To develop risk scores predicting distinct classes of lupus nephritis by using clinical variables and simple laboratory measures. <h3>Methods</h3> Demographic, clinical, serological and histopathological variables were recorded from 163 consecutive patients with biopsy-confirmed lupus nephritis. A risk score was developed to estimate the risk for developing distinct histological classes of lupus nephritis. Two-sided Fisher9s exact and Mann-Whitney or ANOVA tests were used to compare qualitative and quantitative characteristics, respectively, between patient groups. Both univariate and multivariate models were considered. Measures of discrimination [Receiver operating characteristic (ROC) statistic] were also calculated <h3>Results</h3> Variables independently associated (p&lt;0.10) with type II class included age ≤44 years (p=0.087), no malar rash (p=0.051), negative anti-dsDNA (p=0.008) and ≤5 urine leucocytes (p=0.027). The presence of musculoskeletal (MSK) manifestations (p=0.002), new-onset hypertension (p=0.056), positive anti-dsDNA (p&lt;0.0001), &gt;5 urine leucocytes/hpf (p=0.002), creatinine levels&gt;1.2mg/dl (p=0.028) and absence of nephrotic range proteinuria (NRP) (p=0.002) were independently associated with III/IV histological classes. Age&gt;44 years (p=0.011), malar rash (p=0.002), absence of MSK complaints (p=0.002) or leucopenia (p=0.027), NRP (p=0.001), and ≤9 erythrocytes/hpf in urinalysis (p=0.001) were associated with type V lupus nephritis. A risk score for the prediction of specific histological classes was calculated for each patient, with OR [95%CI] for the presence of ≥3 of the aforementioned risk factors of 4.86 [1.99-11.85] for type II, 9.30 [4.09-21.13] for types III/IV and 7.61[2.76-21] for type V, respectively. When ROC curves for the predictive models were fitted, area under the curve (AUC) were 0.711 (p=0.001) for type II nephritis, 0.819 (p&lt;0.0001) for type III/IV nephritis and 0.823 (p&lt;0.0001) for type V. <h3>Conclusions</h3> The identification of independent factors associated with specific types of lupus nephritis and a risk score for prediction can provide guidance in selecting specific therapeutic modalities, particularly in cases where renal biopsy is contraindicated or poses unacceptably high patient morbidity and eventually mortality. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4621
P1269 VITAMIN D STATUS, PNPLA3 GENOTYPE AND RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE SEVERITY IN A UK PAEDIATRIC POPULATION
Authors: P.S. Gibson, E. Fitzpatrick, A. Quaglia, A. Dhawan, K. Hart, S. Lanham-New, J.B. Moore
Journal: Journal of Hepatology (2014)
Abstract 1672: Mitochondrial and bacterial peptides act on the formyl peptide receptor (FPR) to promote migration and proliferation in high grade glioblastoma cells
Authors: Jennifer C. Boer, Urszula M. Domanska, Roeliene C. Kruizinga, Ingrid Boer, Carla J.C. de Haas, Elisabeth G. de Vries, Wilfred F.A. Den Dunnen, Jos A.G. van Strijp, Annemiek M. Walenkamp
Journal: Cancer Research (2011)

Abstract Background: Recently several aberrant molecular pathways and underlying genetic defects are elucidated in astrocytomas, among which the role of the formylpeptide receptor (FPR) malignant behavior. In a highly malignant human astrocytoma cell line FPR promotes cell motility, growth, and angiogenesis by interacting with host-derived agonists originating from necrotic cell material. Until now the only known ligands of FPR are N-formyl peptides, which are cleavage products of bacterial proteins like N-formyl-methionyl-leucyl-phenylalanine (fMLF). In humans the only conserved N-formyl peptides are the cleavage products of mitochondrial proteins. This study aims to identify these peptides as responsible ligands for FPR expressing high grade glioma cells. Methods: We used FITC-fMLF and flow cytometry to confirm binding to FPR-expressing high grade human gliobastoma cell line U87. In addition, U937 cells (human promonocytic cell line) transfected with the FPR (U937FPR) and empty expression vectors were generated. The hallmark of chemokine receptor activation is a rapid and transient increase in the free intracellular Ca2+ level upon ligand binding. Formylated mitochondrial peptides fMLKLIV/fMLALV and FPR's natural peptide ligand fMLF were used to induce Ca2+ mobilization, chemotaxis as determined by the Neuro Probe® system and proliferation in U87 cells, analyzed by MTT assay. Results: FITC-fMLF bound to FPR expressing U87 and U937FPR cells. Increasing concentrations of fMLF (10−8 M-10−5 M) caused a dose dependent calcium mobilization in FPR expressing U87 cells. Increasing concentrations of fMLF/fMLKLIV/fMLALV (10−8 M- 10−5M) were tested in U937FPR cells, again showing dose dependent calcium mobilization. In the chemotaxis assay, respectively 22, 20 and 24% of U937FPR cells migrated towards fMLF/fMLKLIV/fMLALV as compared to 4% towards 0.05% FCS. A 2.5 fold increase in migration of U87 cells towards 10−7 M fMLF was found as compared to 0.05% FCS. Respectively 20, 21 and 15% increase in U87 cell proliferation was found when cells were stimulated with 10−6 M fMLF/fMLKLIV/fMLALV. Conclusions: These results indicate that mitochondrial peptides present in necrotic tumor material serve as ligands for FPR, expressed on high grade human gliobastoma cell line U87. Activation of FPR via N-formyl peptides causes increased cell growth and motility and is a potential target for anti-cancer therapy. Supported by grant RUG 4622 of the Dutch Cancer Society 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 1672. doi:10.1158/1538-7445.AM2011-1672