tbuckley/cabot-search huggingface dataset:
P14 Small-cell lung cancer in England: Trends in survival and therapy
Authors: A Khakwani, AL Rich, HA Powell, RA Stanley, DR Baldwin, RB Hubbard
Journal: Thorax (2013)

<h3>Background</h3> The purpose of this study was to identify trends in survival and chemotherapy use, during the duration of the National Lung Cancer Audit (NLCA), for individuals with small-cell lung cancer (SCLC) in England. <h3>Methods</h3> We used data from the NLCA database to identify people with histologically proven SCLC from 2004 to 2009. We used Hospital Episode Statistics (HES) database and NLCA to identify patients with codes of receiving chemotherapy, while NLCA was used to identify radiotherapy. We calculated the median survival by stage and observed the changing patient features of the cohort. We also looked at the proportions of patients with records of chemotherapy and/or radiotherapy over the years. <h3>Results</h3> 11,603 patients were diagnosed with SCLC in our cohort. The median survival was 6 months; 1 year for limited stage and 4 months for extensive stage. 70% received chemotherapy and this proportion did not change overtime. Patient features including sex, age and performance status remained stable throughout the years (χ<sup>2 </sup>p-value 0.25, 0.93 &amp; 0.08 respectively). There has been an increase in the proportion of patients that had a record of receiving chemotherapy and radiotherapy each year in both limited and extensive stage disease (from 19% to 36% in limited &amp; from 10% to 17% in extensive stage from 2004 to 2009) (table 1). Patients who had a record for chemotherapy and radiotherapy had better survival in days compared with those who received only chemotherapy or no treatment independent of stage (334 days for chemotherapy &amp; radiotherapy vs. 240 days for chemotherapy alone, 82 days for radiotherapy alone &amp; 25 days for no treatment). <h3>Conclusion</h3> Since 2004, when the NLCA was established, the recorded use of chemotherapy and survival in days has remained static. We have found an increasing trend in patients receiving chemotherapy &amp; radiotherapy which corresponds to better survival compared with other treatments. We were unable to see if these patients received these therapies for palliative or curative purpose; however the new chemotherapy and radiotherapy database soon to be linked with the NLCA would be better suitable to answer these questions.
1326 IMPROVEMENT OF PLASMA PARAMETERS LINKED TO NONALCOHOLIC FATTY LIVER DISEASE AFTER WEIGHT LOSS INDUCED BY PROXIMAL SMALL INTESTINAL EXCLUSION BY DUODENAL–JEJUNAL BYPASS LINER
Authors: C. de Jonge, S. Rensen, G. Koek, M. Joosten, W. Buurman, N. Bouvy, J.W. Greve
Journal: Journal of Hepatology (2013)
ANGI-04Olig2 REGULATES Wnt7b EXPRESSION AND VASCULATURE CHARACTERISTICS IN GLIOMA
Authors: Amelie Griveau, Samuel Shelton, An-Chi Tien, Giorgio Seano, Tracy Yuen, Jennifer Sabo, Jasmine Lau, Arman Jahangiri, Emmanuelle Huillard, Joanna Phillips, Anders Persson, Michael Oldham, William Weiss, Manish Aghi, Charles Stiles, Shwetal Mehta, Tracy Batchelor, Rakesh Jain, David Rowitch
Journal: Neuro-Oncology (2015)

Treatment of malignant gliomas has been a challenge due to their transient response to surgical resection and inhibitors of VEGF signaling. Recurrent tumors become resistant to anti-angiogenesis inhibitors and were proposed to convert to a mode of vessel “co-option” whereby they invade into brain parenchyma along the pre-existing vasculature. The genetic and signaling mechanisms that govern vascular co-option just recently started to be investigated and remain poorly understood. We have recently shown that immature oligodendrocyte precursors (OPCs) regulate angiogenesis in developing white matter through canonical Wnt7 signaling. In this study, we show that mRNA levels of OLIG2 and other OPC signature genes strongly correlate with WNT7B in human gliomas, especially oligodendroglioma. OLIG2+ oligodendroglial cells express high levels of WNT7A/B in close vicinity to vascular endothelial cells that express the Wnt target, LEF1. Furthermore, we demonstrate that Olig2 function regulates OPC-like features, Wnt7a/7b expression/activity and enhanced migration along a pre-existing vasculature in a p53-null murine glioma model. Conversely, Olig2-null tumors showed increased vascular density, VEGF expression and limited migration. We report that p53 acts as a direct repressor of the Wnt7b locus and that Olig2 promotes Wnt7b expression in a p53-mutant context. Intracranial administration of the Wnt inhibitor XAV939 with mouse oligodendroglioma cells significantly affected vessel density and migration of tumor cells. Finally, we observed selective upregulation of Wnt7b expression in a model of VEGF-resistant glioma. These findings indicate that OPC-like cells in glioma promote Wnt7b signaling providing an alternative pathway to VEGF signaling.
Abstract 253: The cancer testis antigen MAGED2 protects human melanoma cells from TRAIL-induced apoptosis by suppressing TRAIL-R2 expression
Authors: Hsin-Yi Tseng, Li Hua Chen, Yan Ye, Chen Chen Jiang, Peter Hersey, Xu Dong Zhang
Journal: Cancer Research (2012)

Abstract Melanoma-associated antigen D2 (MAGED2), a member of the MAGE-II cancer testis antigen family, is expressed by almost all normal tissues and many different cancer tissues. Although it has been reported that MAGE proteins have a pro-survival role in cancer cells such as malignant mast cells, the potential biological significance of MAGE proteins in melanoma remains to be established. Here, we show that MAGED2 is involved in the protection of melanoma cells against apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL) through suppressing the expression of TRAIL-R2, the major TRAIL death receptor that mediates TRAIL-induced apoptosis in melanoma. siRNA knockdown of MAGED2 sensitised melanoma cells to apoptosis induced by TRAIL. This was associated with enhanced activation of the caspase cascade and formation of the TRAIL death-inducing signalling complex (DISC), suggesting that MAGED2 acts at or above the DISC to protect melanoma cells against TRAIL-induced apoptosis. Indeed, inhibition of MAGED2 by siRNA resulted in up-regulation of TRAIL-R2 on the melanoma cell surface, which appeared to be specific, because knockdown of MAGED2 did not impinge on the expression of other TNF receptor family members, nor did it up-regulate TRAIL-R2 in melanocytes. Up-regulation of TRAIL-R2 by inhibition of MAGED2 was mediated by a p53-responsive transcriptional increase, in that p53 was also up-regulated in melanoma cells with MAGED2 knocked down, and that knockdown of MAGED2 did not up-regulate TRAIL-R2 in melanoma cells deficient in p53. In summary, our results identify MAGED2 as an important mechanism that suppresses TRAIL-R2 expression, thus protecting melanoma cells from TRAIL-induced apoptosis. 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 253. doi:1538-7445.AM2012-253
THU0357 Predictive value of exercise stress test (24h test&amp;re-test) and coghealth© in differential diagnosis of chronic fatigue syndrome vs. fibromyalgia:
Authors: S. Garcia-Blanco, V. Poca-Dias, C. Santos, A. Cuscό-Segarra, V. Torrente-Segarra, F.J. Garcia-Fructuoso
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Determining the discriminating value of the test CogHealth© and its relation with the dual exercise stress test (test re-test 24 hours) in the differential diagnosis between the chronic fatigue syndrome (CFS/ME) and fibromyalgia (FM) <h3>Methods</h3> 57 patients were included, 42 diagnosed of FM (32 women, 10 men) and 15 of CFS/ME (women). Were applied the neurocognitive CogHealth© test and a double stress test (ST) in treadmill (Bruce protocol) with 24 hours of difference, measuring the METS value (metabolic equivalents) through the formula MET VO2/3.5 and the percentage of maximum theoretician heart rate (MTHR), had to be greather 70% in both proofs to be considerate valid. The data were analysed according to the SPSS program: comparison between groups of patients in ST and CogHealth© test was performed using T-Student and General Linear Model for repeated measures, and principal component factor analysis and discriminant analysis for relationship between both diseases <h3>Results</h3> The results of ST show significative differences between CFS/ME and FM patients. We observe an increment in the HTHR values and a sensible decrease of the METS in the patients with CFS/ME in the second ST, being higher and keeping constant the values of the group FM (table 1). We observe significative differences between CFS/ME and FM patients in the CogHealth© results. The results of the CogHealth© test in the total scale and in the sub-scales, are outside of normal in all the cases with CFS/ME and normal in all the patients with FM (table 1). There are a significative relation between second ST and the CogHealth© test results. Two components can explain more of 50% of the variation found in the patients. First is defined by the variables of the CogHealth© and it would explain the 36,55% of the total variation. The variables of the CogHealth that allow to classify 100% of patients correctly would be: CogHealth detection2, CogHealth Associated Learning, CogHealth Monitoring, CogHealth One Back, CogHealth One Card Learning. The predictive value does not increase if we add variables of the ST although there are significative (p=0,000). <h3>Conclusions</h3> The CogHealth© test and a double ST are a valid tool to discriminate between CFS/ME and the FM. <h3>Disclosure of Interest</h3> None Declared
Cardiac-Specific Troponin I Levels to Predict the Risk of Mortality in Patients with Acute Coronary Syndromes
Authors: Elliott M. Antman, Milenko J. Tanasijevic, Bruce Thompson, Mark Schactman, Carolyn H. McCabe, Christopher P. Cannon, George A. Fischer, Anthony Y. Fung, Christopher Thompson, Donald Wybenga, Eugene Braunwald
Journal: New England Journal of Medicine (1996)

In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. We studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non–Q-wave myocardial infarction.
SP0030 Pediatric neuropsychiatric lupus
Authors: T. Avcin
Journal: Annals of the Rheumatic Diseases (2013)

Neuropsychiatric involvement is one of the most common features of childhood-onset systemic lupus erythematosus (cSLE) occurring in 20 to 95% of patients. The large variation in frequency of neuropsychiatric manifestations reported in cSLE is the result of differing case definitions and the methods used for evaluation. The majority of patients with neuropsychiatric involvement have the initial signs and symptoms early in the course of the disease and approximately 25% develop initial neuropsychiatric manifestations more than 2 years after disease onset. There have been few comprehensive studies evaluating neuropsychiatric disease in cSLE. In general, central nervous system involvement appears to be more severe in children than in adults and cSLE is associated with higher accrual of permanent organ damage. The most common neuropsychiatric manifestation in cSLE is headache occurring in approximately 50% of patients. Neurocognitive deficits in cSLE ranges from concentration difficulties, a decrease in school performance to frank confusion and coma. Since there are no validated clinical or research neuropsychological testing for children, it is particularly difficult to determine subtle neurocognitive impairment in cSLE. Cerebrovascular disease occurs in up to 30% of patients with neuropsychiatric involvement and is usually associated with the presence of antiphospholipid antibodies. Antiphospholipid antibodies have been associated also with other neuropsychiatric manifestations, in particular movement disorders (chorea), seizures, psychosis and transverse myelopathy. These latter manifestations are likely the result of a nonthrombotic, immune-mediated mechanism rather than thrombosis. Involvement of peripheral nervous system has been infrequently described in cSLE, mainly as isolated case reports only. The diagnosis of neuropsychiatric involvement in cSLE is often difficult, as both focal and diffuse manifestations may occur and there is no gold standard for diagnosis. A high index of clinical suspicion, in addition to laboratory and neuroimaging findings may support the diagnosis. It is important to exclude other causes such as infection, hypertension or metabolic abnormalities associated with neuropsychiatric signs and symptoms. The management of patients with neuropsychiatric cSLE requires interdisciplinary approach and includes symptomatic and immunosuppressive medications. In patients with severe neuropsychiatric involvement a combination therapy with high-dose steroids and cyclophosphamide is usually required. Psychotropic medications and supportive non-pharmacological approaches are frequently required in patients with psychiatric disorders and cognitive dysfunction. In the future, it is expected that novel biomarkers and advanced neuroimaging modalities will provide better understanding of the underlying mechanisms of neuropsychiatric involvement in cSLE and help guide therapeutic decisions. <h3>Disclosure of Interest</h3> None Declared
Abstract 4764: Targeting formin autoinhibition to construct cell infrastructure
Authors: Leanne Lash-VanWhye, Susan Kitchen-Goosen, Arthur S. Alberts
Journal: Cancer Research (2012)

Abstract Rho small GTP-binding proteins locally manage Diaphanous-related formins as they construct the cytoskeletal infrastructure that supports essential changes in cell morphology. Rho binding unlatches formin intramolecular autoinhibition. The autoinhibition is mediated by the Dia-inhibitory and -autoregulatory domains (DID &amp; DAD) which flank the formin homology-2 (FH2) domain. The free FH2 domain guides the assembly of the linear actin and microtubule structures required for adhesion, migration, division, and polarity establishment. Microtubule stabilization is already known to be an effective anti-cancer strategy. Combined with the knowledge that formins can act as haploinsufficient tumor suppressor genes, a screen was conducted for agents that could impair autoinhibition in order to activate formins for therapeutic benefit. We have focused on two of the primary “hits” for development. VARI01 and VARI02 are nearly identical thioamide inhibitors of DID-DAD binding (IC50 values ≤ 140 nM). Exposure of cultured tumor cells to either compound triggered the expected changes in cell structure and signaling that were consistent with formin activation. These included microtubule stabilization, F-actin assembly, the activation of the transcription factor SRF, cell-cycle arrest, and eventual apoptosis. SRF senses changes in actin dynamics to activate the expression of genes that reinforce cell structure and monitor genome integrity. VARI01 and VARI02 both exhibit anti-tumor activity in xenograft studies. Ongoing studies are aimed at identifying VARI01/VARI02-sensitive tumor types and to define other potential therapeutic applications. Significance: Microtubule stabilization by taxol has proven to be an effective anti-cancer strategy, but it has significant deleterious side effects. Small-molecule formin activation serve as a novel class of anti-cancer agents that may provide tools for unlocking the biological roles of formins in signalling and disease. 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 4764. doi:1538-7445.AM2012-4764
SP0204 Treatment of Early Undifferentiated Arthritis in 2014
Authors: A. Van Der Helm-Van Mil
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> A considerable proportion of patients presenting with early arthritis have a disease that cannot be classified directly; this is called undifferentiated arthritis (UA). UA patients are heterogeneous in several aspects. This is reflected by the diverse outcomes: one third of the patients progresses to rheumatoid arthritis (RA), one third remains unclassified and one third remits spontaneously. In this presentation the heterogeneity will be evaluated and questions that are relevant for clinical practice will be addressed. Which UA patients will progress towards RA in case untreated? What is the disease outcome? When should treatment be initiated?, What drugs to choose? This presentation is based on the currently available literature; the randomized clinical trials in UA will be explored to provide answers that are helpful for daily clinical care. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6144
Relationship Between Nuclear Pockets in Bovine Peripheral Blood Lymphocytes and C-Type Virus Particles in Cultures of These Cells 2 3
Authors: A. Weber, M. Fahning, R. H. Hemmer, C. Jessen
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Relationship Between Nuclear Pockets in Bovine Peripheral Blood Lymphocytes and C-Type Virus Particles in Cultures of These Cells Get access A. Weber, A. Weber College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55101; and International Cryobiolgical Services, Inc., 1935 West County Road 82, St. Paul, Minnesota 55113 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Fahning, M. Fahning College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55101; and International Cryobiolgical Services, Inc., 1935 West County Road 82, St. Paul, Minnesota 55113 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. H. Hemmer, R. H. Hemmer College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55101; and International Cryobiolgical Services, Inc., 1935 West County Road 82, St. Paul, Minnesota 55113 Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Jessen C. Jessen College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55101; and International Cryobiolgical Services, Inc., 1935 West County Road 82, St. Paul, Minnesota 55113 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 81–88, https://doi.org/10.1093/jnci/51.1.81 Published: 01 July 1973 Article history Received: 16 August 1971 Accepted: 21 February 1973 Published: 01 July 1973
OP0210-HPR Increase in Knee Muscle Strength is Associated with A Decrease in Activity Limitations in Patients with Established Knee Osteoarthritis: A 2 Years Follow-Up Study in the AMS-OA Cohort
Authors: D.C. Sanchez-Ramirez, M. van der Leeden, M. van der Esch, L. Roorda, S. Verschueren, J. van Dieen, J. Dekker, W. Lems
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Osteoarthritis (OA) is considered a major cause of pain and activity limitations. Activity limitations are defined as difficulties in performing daily activities. Previous studies have shown a slow increase in activity limitations over time in patients with OA, while others have found no change or even a decrease in activity limitations in this group of patients. Nevertheless, there is a high between-patients variability in the course of activity limitations in patients with OA which needs to be further explained. <h3>Objectives</h3> To examine the longitudinal association between knee muscle strength and activity limitations in patients with established knee osteoarthritis (OA), over two years. <h3>Methods</h3> Data from 186 patients with knee OA part of the Amsterdam Osteoarthritis cohort were gathered at baseline and at two-year follow up. Knee extensor and knee flexor muscle strength were assessed using an isokinetic dynamometer. Activity limitations were assessed using Western Ontario and McMaster University Osteoarthritis Index (WOMAC) - Physical Function subscale, Get Up and Go test (GUG) and the stairs test. Uni- and multivariate linear regression analyses were used to assess the association between changes in muscle strength and changes in activity limitations, adjusting for relevant confounders and baseline activity limitations. <h3>Results</h3> There was an overall 16% increase in mean knee muscle strength (p&lt;0.001), 19% increase in knee extensor muscle strength (p&lt;0.001) and 17% increase in knee flexor muscle strength (p&lt;0.001), over two years. Increased average knee muscle strength and knee flexor muscle strength were associated with better self-reported physical function (WOMAC) (b=-5.7, p=0.03 and b=-6.2, p=0.05), decreased time performing the GUG (b=-1.2, p=0.003 and b=-1.4, p=0.05) and decreased time performing the stairs test (b=-4.4, p&lt;0.001 and b=-6.6, p&lt;0.001). Increased extensor muscle strength was only associated with decreased time performing the stairs test (b=-2.7, p&lt;0.001). <h3>Conclusions</h3> The increase of knee muscle strength is associated with decreased activity limitations in patients with knee OA, over two years. These results suggest that muscle strength partially explains the between-patients variability in activity limitations. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1360