tbuckley/cabot-search huggingface dataset:
S73 4-Metre gait speed as a functional outcome measure in patients with Chronic Obstructive Pulmonary Disease (COPD)
Authors: A. V. Donaldson, B. E. Garfield, M. S. Patel, A. L. Clark, M. I. Polkey, W. D. Man
Journal: Thorax (2010)

<h3>Introduction</h3> Well-established functional outcome measures in COPD include the 6-min walk test (6MW) and incremental shuttle walk test (ISW). However, these tests require space, repetition, and can be time-consuming. In the elderly population, gait speed alone has been shown to be a significant predictor of disability and mortality. We hypothesised that the 4-m gait speed in COPD patients would correlate well with the 6MW and ISW, and with validated COPD mortality composite scores such as BODE and ADO. <h3>Methods</h3> 26 well-characterised COPD patients were studied. Each underwent 6MW test as per ATS guidelines, ISW test and completed a 4-m walk in random order. For the 4-m walk, participants were instructed to walk at their usual speed along a marked, flat unobstructed course. Timing was stopped when the first foot completely crossed the 4-m mark. The faster of two timed walks was used for scoring purposes, and a gait speed was calculated in m/s. Data were analysed using Spearman9s rank correlation to assess association between 4-m gait speed and 6MW, ISW, BODE score and ADO index. <h3>Results</h3> Baseline characteristics are presented as mean (SD) or median (25th, 75th percentile): 11M: 15 F; age=69 (8); FEV1% predicted=43 (20); 6MW=330 (83); ISW=291 (122.5); MRC dyspnoea 3 (2, 4); St George9s Respiratory Questionnaire (SGRQ)=49.6 (21.0); BMI=25.9 (4.9); BODE=4.5 (1.75, 6.0), ADO=5 (4, 6). Mean (SD) 4-m gait speed was 0.96 (0.20) m/s. There was a significant correlation between 4-m gait speed and 6MW (r=0.62, p=&lt;0.001), ISW (r=0.80, p=&lt;0.0001)—see Abstract S73 Figure 1, BODE score (r=−0.56, p=0.003) and ADO index (r=−0.43, p=0.03). <h3>Conclusions</h3> 4-m gait speed correlates well with existing functional outcome measures and validated mortality composite scores used in COPD. It is an easy and quick to perform field test, and does not require specialist training or equipment. Further longitudinal and intervention studies are required to validate the 4-m gait speed as an assessment tool.
FRI0236 Ultrasonographic Assessment of Joint Inflammation in Rheumatoid Arthritis: Predictive Value in Response to Tumor Necrosis Factor-α Inhibitor Treatment: Table 1.
Authors: N. Inanc, G. Ozen, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tumor necrosis factor-α inhibitors (TNFi) are highly effective in patients with RA, while not effective in all, with predictors of response being necessary. Although genetic, inflammatory and serologic biomarkers are under major investigation for this purpose, little is known about the predictive value of ultrasonographic parameters in RA. <h3>Objectives</h3> To investigate the ability of ultrasonographic parameters to predict which patients with RA will benefit from the treatment with TNFi in terms of EULAR response. <h3>Methods</h3> Biologic-naive RA patients starting treatment with TNFi were examined longitudinally by ultrasonography (US) (Gray-Scale [GS] and Power Doppler [PD]) of 28 joints according to standard scans of EULAR guideline and clinically (Tender/swollen joint count, DAS28, HAQ scores) at baseline and 3rd, 6th and 12th months. US examinations were performed by an experienced sonographer (NI) using MyLab 70 US machine (Esaote, Italy). US synovitis GS and PD signals were semiquantitatively graded from 0 to 3. Total PD and GS synovitis scores of all sites are recorded as sum scores of PD and GS, respectively. The clinical response was evaluated according to the EULAR response criteria at 3rd month. Potential ultrasonographic predictors of response were identified using multivariate binary logistic regression models. <h3>Results</h3> The study cohort consisted of 43 RA patients (F/M=34/9, mean disease duration 8.0±6.7 years, mean DAS28 score 5.4±1.1) who were either RF or Anti-CCP positive. Baseline characteristics of TNFi responders (28/43) and non-responders (15/43) are shown in Table 1. Pain VAS (<i>P</i>=0.005), sum scores of baseline PD (<i>P</i>=0.049), GS (<i>P</i>=0.045) and PD+GS (<i>P</i>=0.045) differed significantly between responders and non-responders. Baseline PD sum score was the only US parameter in the multivariate analysis predicting which patients achieve good/moderate EULAR response with TNFi at 3rd month (OR=0.9; CI:95% 0.79-0.94, <i>P</i>=0.04). Responders at 3rd month were also more likely to achieve LDA or remission at 1 year (<i>P</i>=0.019 and <i>P</i>=0.008, respectively). The mean PD and GS sum scores decreased significantly from baseline to 3rd month (<i>P</i>&lt;0.001 for both) whereas decrease between 3rd and 6th months was nonsignificant (<i>P</i> =0.68 and <i>P</i>=0.77, respectively). <h3>Conclusions</h3> Our data underline that baseline PD scores, despite similar clinical features, can predict which patients will respond to TNFi therapy. Responders at 3rd month mostly preserve initial response and more likely to achieve LDA at 1 year. Ultrasonographic response to TNFi treatment can be achieved substantially in the first 3 months. Beyond 3rd month changes in US scores are mostly nonsignificant. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1918
PARE0003 A finnish wikibook called sle-terminologiaa (sle terminology)
Authors: K. H. Myllys
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We need more material on SLE in Finnish, but we do not have financial resources to publish material. Publishing is an expensive and slow process. Also, no one has produced any new material on SLE in Finnish for years apart from the published academic papers. <h3>Objectives</h3> The main objective is to create Finnish material on SLE. Wikimedia community is a good way to create an instructional guide, because it is a free space on the internet and also open content, which makes it public immediately. Anyone can edit the content or discuss it. This is a start, a pilot project, and in the future we may have many Finnish projects on SLE on Wikimedia community. <h3>Methods</h3> A Wikibook called SLE-terminologiaa (SLE Terminology) has been set up at&nbsp; http://fi.wikibooks.org/wiki/SLE-terminologiaa. It is an open content textbook that anyone can edit and comment on. The book is also being discussed on a closed Facebook group for Finnish SLE patients called Siipien havinaa at https://www.facebook.com/groups/176741655794865/ and on our discussion forum at http://www.sle-yhdistys.fi/forum/. SLE patients may share ideas and give criticism either on Facebook, discussion forum or the Wikibooks page itself. The idea is to activate patients to produce material on SLE in Finnish. The book is created by patients for patients. <h3>Results</h3> The Wikibook SLE-terminologiaa is being written gradually, entry by entry. A link to it will be added on Lupus Finland web site at http://www.sle-yhdistys.fi/. Also, we will carry out a survey in late April to find out if this Wikibook has made any difference to any of the Finnish lupus patients in coping with their illness. <h3>Conclusions</h3> We can have Finnish material on SLE with little resources on Wikimedia community. Once we have copyright to a text published by some bigger organisations outside Finland, we can translate the text and set it up as a book at Wikimedia community. Also, a book may come out as a result of a workshop at a seminar. Patients can produce written material on living with SLE or on important issues about coping with the illness without having to apply huge sums of money. <h3>Disclosure of Interest</h3> None Declared
OP0088 Changes in Baseline Severity of Inflammatory Polyarthritis Over Time
Authors: J. Diffin, M. Lunt, T. Marshall, J. Chipping, D. Symmons, S. Verstappen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous research has suggested that the severity of rheumatoid arthritis (RA) has decreased over time. <h3>Objectives</h3> To examine the pattern of disease severity in patients with inflammatory polyarthritis (IP) at time of registration into the Norfolk Arthritis Register (NOAR). <h3>Methods</h3> NOAR is a primary-care-based cohort of adults with recent onset IP (≥2 swollen joints lasting for &gt;4 weeks). Disease related information collected at baseline includes 51- swollen and tender joint counts, HAQ, and DAS28. Blood is collected and C - reactive protein (CRP), Rheumatoid Factor (RF), and Anti-Citrullinated Peptide Antibodies (ACPA) are measured. In this study, patients with a symptom duration of &lt;2 years at baseline were grouped into four cohorts depending on the NOAR recruitment phase: (1) 1990-1994; (2) 1995-1999; (3) 2000-2004; (4) 2005-2008. Three sub-samples were also evaluated: i) referred first to NOAR by their general practitioner; ii) DMARD naive at baseline; iii) met the ACR/EULAR 2010 RA criteria at baseline. Linear or median regression analyses were conducted to examine baseline HAQ or DAS28 scores over time. A quadratic term for calendar year of assessment by NOAR was included as a predictor and if significant, cohort was included to examine if the rate of change in scores over time differed between cohorts. Confounders included gender, RF and ACPA positivity, and age at symptom onset. <h3>Results</h3> In total 3045 patients were evaluated: Cohort 1=1022; Cohort 2=883; Cohort 3=631; Cohort 4=509 (Table). Calendar year of assessment was a significant predictor of lower DAS28 scores over time for the total sample (adjß= -0.0007, 95% CI -0.001, -0.0001), and each sub-sample, indicating improved disease activity over time. Within the total sample, and the DMARD naive sub-sample, there was a significant effect of 'Cohort', and a significant 'Calendar year by Cohort' interaction indicating the rate of change in DAS28 scores over time differed between cohorts. Calendar year of assessment was not a significant predictor of HAQ scores for the total sample (adjß=0.0002, 95% CI -0.0002, 0.001), and was also a significant predictor of increased HAQ scores for the sub-sample who met the ACR/EULAR 2010 RA criteria, indicating no improvement in functional disability over time. <h3>Conclusions</h3> Baseline disease activity has decreased over time and may not be solely attributable to the increased use of DMARDs. However, there has been no improvement in levels of functional disability. <h3>Acknowledgements</h3> Funded by Arthritis UK and GlaxoSmithKline <h3>Disclosure of Interest</h3> None Declared
Abstract 1068: Keratinocyte-specific deletion in mice reveals gene dose-dependent function of SIRT1 in tumorigenesis.
Authors: Mei Ming, Keyoumars Soltani, Christopher R. Shea, Xiaoling Li, Yu-ying He
Journal: Cancer Research (2013)

Abstract The protein deacetylase SIRT1, a mammalian counterpart of the yeast silent information regulator 2 (Sir2) and a proto member of the sirtuin family, regulates various pathways in metabolism, DNA repair, and cell survival. However, the role of SIRT1 in cancer is still under debate. Here we show that the role of SIRT1 in skin cancer development induced by the human skin carcinogen UVB radiation is dependent on its gene dose. Keratinocyte-specific heterozygous deletion of SIRT1 increases UVB-induced skin tumorigenesis, whereas homozygous deletion of SIRT1 decreases skin tumorigenesis. In mouse skin, SIRT1 is haploinsufficient for DNA repair and the expression of xeroderma pigmentosum C (XPC), a protein critical for repairing UVB-induced DNA damage. Similar to homozygous SIRT1 deletion, heterozygous SIRT1 deletion reduces the XPC protein levels and UVB-induced DNA damage repair. As compared with normal human skin, down-regulation of SIRT1 is in parallel with down-regulation of XPC in human cutaneous squamous cell carcinoma at both the protein and mRNA levels. In contrast, homozygous SIRT1 deletion in mouse skin augments p53 acetylation, and the expression of its transcriptional target Noxa, and sensitizes epidermis to UVB-induced apoptosis in vivo, while heterozygous SIRT1 deletion has no effect. Although mice with homozygous SIRT1 deletion do not develop tumors, these mice suffer severe sunburn. The gene dose-dependent function of SIRT1 in DNA repair and cell survival is consistent with its role in UVB-induced skin tumorigenesis and injury. Taken together, our results indicate that, depending on the SIRT1 levels, SIRT1 acts as a tumor suppressor and as an oncogene. Citation Format: Mei Ming, Keyoumars Soltani, Christopher R. Shea, Xiaoling Li, Yu-ying He. Keratinocyte-specific deletion in mice reveals gene dose-dependent function of SIRT1 in tumorigenesis. [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 1068. doi:10.1158/1538-7445.AM2013-1068
T-Cell Lymphomas Containing Epstein–Barr Viral DNA in Patients with Chronic Epstein–Barr Virus Infections
Authors: J F Jones, S Shurin, C Abramowsky, R R Tubbs, C G Sciotto, R Wahl, J Sands, D Gottman, B Z Katz, J Sklar
Journal: New England Journal of Medicine (1988)

Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein–Barr virus (EBV) capsid antigen (>10,000) and early antigen (>640) but low titers to the EBV nuclear antigen (≤40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95–8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell–receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections. (N Engl J Med 1988; 318:733–41.)
Abstract 4953: Interaction of vitamin E compounds with docosahexaenoic acid on induction of apoptosis in human triple negative breast cancer cells
Authors: Ailian Xiong, Weiping Yu, Bob Sanders, Kimberly Kline
Journal: Cancer Research (2012)

Abstract Successful treatment of triple negative (ER-, PR-, HER2-) breast cancers (TNBC) remains elusive because of the limitations of currently available chemotherapeutic agents for TNBC, drug resistance and drug toxicities. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has been shown to exhibit anticancer actions both in vitro and in vivo in a variety of cancers, including human breast cancer. Here, we report that DHA induces apoptosis in TNBC cell lines, which is associated with cleavage of caspase-8 and -9. DHA induces endoplasmic reticulum (ER) stress evidenced by the increased levels of ER stress markers, GRP78, CHOP, and spliced XBP-1, and induced increased levels of death receptor DR5 protein expression. siRNAs to CHOP and DR5 blocked DHA-induced apoptosis and siRNA to CHOP blocked DHA-induced upregulation of DR5, indicating that DHA induces ER stress mediated death receptor dependent apoptosis in TNBC cells via CHOP. Furthermore, our data show that DHA mediated increases in levels of reactive oxygen species (ROS), apoptosis and ER stress can be blocked by antioxidants; N-Acetyl Cysteine (NAC) and alpha-tocopherol (αT) indicating that ROS plays a critical role in DHA-induced apoptosis and ER stress. In contrast to αT, gamma-tocotrienol (γT3), another form of vitamin E, cooperated with DHA to induce apoptosis and ER stress in TNBC cells. siRNAs to CHOP and DR5 blocked the combination effects mediated by DHA + γT3 on induction of apoptosis and ER stress. Taken together, our data, for the first time, demonstrate that DHA induces apoptosis in TNBC cells via activation of an ER stress mediated DR5 dependent pro-apoptotic pathway. Our data also show that different forms of vitamin E exhibit different combinational effects on DHA-induced apoptosis; namely, blockage by αT and enhancement by γT3. (Funding for these studies was provided by the Clayton Foundation for Research). 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 4953. doi:1538-7445.AM2012-4953
352 FOLLICLE-STIMULATING HORMONE INDUCES CHOLANGIOCYTES GROWTH IN COURSE OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: R. Mancinelli, A. Franchitto, P. Onori, G. Carpino, S. Brozzetti, D. Jefferson, J. Venter, H. Francis, G. Alpini, E. Gaudio
Journal: Journal of Hepatology (2012)
Antitumor Activity of Imexon
Authors: P. SAGASTER, E. M. KOKOSCHKA, O. KOKRON, M. MICKSCHE
Journal: JNCI Journal of the National Cancer Institute (1995)

ResponseWe welcome Dr. Waldum's comment on neuroendocrine origin of diffuse gastric carcinomas.In our study, the data on cancer incidence were obtained from the family history.The majority of family members with gastric carcinoma were deceased, and their diagnoses were confirmed by death certificates.We had little success obtaining medical records of deceased family members, and death certificates are not specific enough regarding the subtype of cancer.The examination of gastric cancer subtypes should certainly be considered in prospective studies of genetic epidemiology of Ewing's sarcoma family of tumors.
Abstract 5370: Potentiation of the novel topoisomerase I inhibitor indenoisoquinoline NSC743400 by Chk1/2 inhibitors in p53-deficient cells
Authors: Sheena M. Aris, Yves Pommier
Journal: Cancer Research (2010)

Abstract Clincally available camptothecin derivatives, though highly effective against a broad range tumors, are limited by their chemical instability, solubility, ABCG2-mediated efflux and reversibility of Top1-DNA complexes. Indenoisoquinolines were identified as topoisomerase I (Top1) inhibitors by the COMPARE analysis of the NCI drug screen database. Although structurally similar to camptothecin, idenoisoquinolines are chemically stable, able to overcome ABCG2 efflux while forming more persistent Top1-DNA complexes and maintaining potent antitumor activity. The potential for indenoisoquinoline derivatives as possible clinical agents is further aided by the synergistic effect observed between camptothecin and Chk1/2 inhibitors. Chk1/2 kinases regulate cell cycle, DNA damage response via ATM, ATR and DNA-PK, which are activated by genomic instability. Previous studies have shown Chk1/2 inhibitors, such as UCN-01, can potentiate camptothecin-mediated cytotoxicity in p53 mutant cells by eliminating the DNA replication checkpoint. Further synthesis has led to the water-soluble indenoisoquinoline derivative, NSC743400 for clinical development. Current checkpoint kinase inhibitors, like PV1019 or AZD7762, offer a higher level of specificity than their predecessors that can be exploited by combination with indenoisoquinolines. Checkpoint inhibition showed synergistic antiproliferative activity with NSC743400 in human colon carcinoma HT-29 cells. Furthermore, AZD7762 was able to abrogate the late S-phase arrest induced by NSC743400 as early as 3h post treatment. Inhibition of checkpoint kinases also abrogated the DNA replication fork progression response to NSC743400. The effect of these inhibitors on the autophosphorylation of both Chk1 and Chk2 post NSC743400 was examined by Western blot. These results further substantiate the idea that checkpoint inhibition is a viable strategy in enhancing the antiproliferative effect of novel non-camptothecinn inhibitors such as the indenoisoquinolines. 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 5370.
AB0299 The Five-Year Radiological Course and the Development of Functional Disorders in Patients with Early Rheumatoid Arthritis
Authors: Y.A. Ermakova, D.E. Karateev, E.L. Luchikhina, N.V. Demidova, A.V. Smirnov, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The functional status in rheumatoid arthritis (RA) has reversible and irreversible components. The irreversible component includes the structural changes in joints. The study of the radiological progression is especially important for a long time. <h3>Objectives</h3> To investigate the radiological course of the disease and to study the influence of the joint destruction on the functional status in patients with early RA. <h3>Methods</h3> We used the data of long-term Russian project "RADICAL" (Early Arthritis: Diagnostic, Clinical, Aggressive Treatment). A total of 193 patients with early RA (diagnosed for less than two year) according to American College of Rheumatology criteria included in the study from 2003 to 2007 (67,5% RF (+); 57% ACCP (+), 86,5% women, age of 49 [40-58]). Patients were followed prospectively for 5 years. They were treated DMARDs, including the biologic therapy - Infliximab, Rituximab, Adalimumab (24%), according the "tight-control" principle. The radiological investigation of hands and feet with the evolution of Sharp/van der Heijde Score (SHS), HAQ, DAS28 were performed every 12 months. <h3>Results</h3> At the beginning of the observation 16% patients had joint erosions. The erosive arthritis has been verified at years 1-5 of follow-up in 27,5%, 38,5%, 49,5%, 58%, 73% of cases, respectively. Baseline median [25th percentile, 75th percentile] of SHS was 0 [0-0]. From 1 to 5 years - 0 [0-10], 0 [0-4], 1 [0-8], 3 [0-12], 6 [0-14], respectively. Baseline median of HAQ was 1,125 [0,625-1,75]. From 1 to 5 years the median HAQ changed to 0,5 [0,125-1,0], 0,5 [0-1,0], 0,5 [0-1,0], 0,5 [0-1,0], 0,75 [0,125-1,125], respectively. We found weak but significant correlation between SHS and HAQ. Baseline Pearson correlation coefficient was 0,17, from 1 to 5 years – 0,25, 0,29, 0,36, 0,37, 0,39, respectively. <h3>Conclusions</h3> During the first 5 years of RA the erosive process in joints increased. However, the most of patients had only minimal or moderate radiological damage (SHS). The functional impairment was on minimal level during the total 5 years follow-up period. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4512