tbuckley/cabot-search huggingface dataset:
HG-11 * INTEGRATIVE MOLECULAR META-ANALYSIS OF 700 PEDIATRIC HIGH GRADE GLIOMA AND DIPG DEFINES WIDESPREAD INTER- AND INTRA-TUMORAL HETEROGENEITY
Authors: A. Mackay, M. Vinci, A. Burford, L. Bjerke, K. Taylor, M. Nandhabalan, L. Marshall, V. Molinari, S. Popov, W. Ingram, A. Moore, S. Trabelsi, D. Hmida, K. Mu, L. Bidinotto, R. Reis, H. K. Ng, A. von Bueren, M. Baudis, C. Jones
Journal: Neuro-Oncology (2015)

Recent molecular profiling studies of paediatric high grade (pHGG) and diffuse intrinsic pontine glioma (DIPG) have refined these tumours into age- and location-based subgroups driven by unique genetic and epigenetic alterations, however individual studies are underpowered to investigate subgroup-specific events. We have retrieved publicly available genome-wide data from ∼560 pHGG/DIPG samples and combined this with ∼140 unpublished cases including young adults up to the age of 30 years. We have integrated multiple array-based and sequencing platforms to produce DNA copy number profiles from ∼700 tumours, ∼500 with clinicopathological and histone H3 annotation, and >300 of which have full somatic sequence information. We identified subgroup-specific genetic alterations co-segregating, or mutually exclusive, with known driving histone mutations. H3.3G34R/V cerebral hemispheric tumours harbour significantly more CNAs and SNVs than other subgroups. These included novel amplified loci at 1p13.3 (KCNA) and a histone cluster at 6p22.2, though lacked key amplified loci such as MYC/MYCN. H3.1K27M DIPG were distinct from H3.3K27M primarily on the basis of whole arm chromosomal changes (enriched +2, -16q; reduced -17p and a lack of TP53 mutations). H3.3K27M tumours harboured specifically enriched known (7q31.2;MET) and novel amplicons (17p11.2;TOP3A). Integration with mutation data identified subgroup-independent, non-overlapping pathway-level recurrent alterations, such as RTK-PI3K-mTOR, dysregulated in 55% cases and conferring shorter survival in hemispheric, but not other locations. As well as inter-tumoral differences, deeper interrogation of the sequencing data also reveals substantial intra-tumoral heterogeneity. Whilst driving histone H3 mutations were found to be present in 100% of cells, mutations in genes such as PDGFRA and PIK3CA were predominantly found at subclonal levels, and tumours from all locations were inferred to be comprised of multiple subclonal populations, with H3.3G34R/V the most genetically diverse. These data improve our understanding of the underlying biology of pHGG/DIPG, and will provide rational targets for subgroup-specific and –independent therapies.
PCPT Update: Enrollment Mounts, but Minority Participation Lags
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article PCPT Update: Enrollment Mounts, but Minority Participation Lags Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 20, 19 October 1994, Pages 1500–1501, https://doi.org/10.1093/jnci/86.20.1500 Published: 19 October 1994
Hyperinsulinism and Hyperammonemia in Infants with Regulatory Mutations of the Glutamate Dehydrogenase Gene
Authors: Charles A. Stanley, Yen K. Lieu, Betty Y.L. Hsu, Alberto B. Burlina, Cheryl R. Greenberg, Nancy J. Hopwood, Kusiel Perlman, Barry H. Rich, Enrico Zammarchi, Mortimer Poncz
Journal: New England Journal of Medicine (1998)

A new form of congenital hyperinsulinism characterized by hypoglycemia and hyperammonemia was described recently. We hypothesized that this syndrome of hyperinsulinism and hyperammonemia was caused by excessive activity of glutamate dehydrogenase, which oxidizes glutamate to α-ketoglutarate and which is a potential regulator of insulin secretion in pancreatic beta cells and of ureagenesis in the liver.
Hodgkin's Disease, Tonsillectomy and Family Size
Authors: Nancy Gutensohn, Frederick P. Li, Ralph E. Johnson, Philip Cole
Journal: New England Journal of Medicine (1975)

The association of tonsillectomy and Hodgkin's disease was investigated by comparison of 136 young adult patients with their 315 siblings and 78 spouses. On the basis of a case-spouse comparison, the risk ratio of Hodgkin's disease among tonsillectomized persons was 3.1 (1.5 to 7.7, 95 per cent confidence limits); on the basis of a case-sibling comparison it was 1.4 (0.8-2.6). The case-sibling analysis was repeated according to sibship size, and increased risk of disease was associated with tonsillectomy only within the 37 sibships of size two. A similar variation of risk ratio with sibship size was found in data from a prior study. The range of the association implies that the relation beteeen tonsillectomy and Hodgkin's disease either is noncausal or is complex and modified by family size. Risk of Hodgkin's disease was found to increase as a sibship size decreased, suggesting that a cause of Hodgkin's disease is correlated with childhood social class.
False Impression of Positive Meckel’s Scintigraphy Caused by Ectopic Cross-Fused Kidneys
Authors: VOLKAN BEYLERGIL, PINAR OZGEN KIRATLI
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine, Hacettepe University Medical School, Ankara, Turkey Received for publication August 2, 2000. Revision accepted January 22, 2001. Reprint requests: Hacettepe University Medical School, Department of Nuclear Medicine, 06100 Sıhhıye Ankara, Turkey. CLINICAL NUCLEAR MEDICINE publishes in each issue a section of references to articles of interest to its readers taken from the world medical literature. Articles below were selected from listings received through August 15, 2001. Slavic and Oriental language articles have English summaries unless marked with an asterisk after language abbreviation.
AB0289 Can cd11c expression successfully predict response to etanercept in rheumatoid arthritis patients?
Authors: S. L. Smith, D. Plant, S. Eyre, A. Yarwood, K. L. Hyrich, A. W. Morgan, A. G. Wilson, J. D. Isaacs, A. Barton
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The treatment of rheumatoid arthritis (RA) with biologic drugs such as anti-tumor necrosis factor alpha (TNF) has significantly improved the clinical outcome in patients; however, 30-40% of patients fail to experience a satisfactory response. In an ideal scenario, an effective drug which is unlikely to induce serious adverse events would be selected for each patient prior to treatment, based on an algorithm including a variety of predictive markers which would include demographic data. CD11c (ITGAX) is an integrin molecule involved in the chemotaxis of immune cells and cell adhesion. Expression of CD11c in monocytes has been correlated with treatment response in RA patients receiving adalimumab monotherapy with a sensitivity of 100% and specificity of 91.7%. Whether this observation solely applies to adalimumab or whether this observation encompasses other anti-TNF drugs has yet to be investigated. <h3>Objectives</h3> To assess pre-treatment levels of CD11c expression in RNA to determine whether expression levels can differentiate future responder and non-responder patients as assessed by the 28-joint disease activity (DAS28) score in etanercept treated patients with RA. <h3>Methods</h3> Total RNA was extracted from pre-treatment whole blood samples of fifty patients (25 responders and 25 non-responders; defined using EULAR criteria at 3-month follow-up) from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) longitudinal cohort. RNA was subsequently converted to high quality single stranded cDNA for use in gene expression profiling using the QuantStudio™ 12K Flex real-time qPCR system in order to measure CD11c, GAPDH and ACTB mRNA transcripts. The comparative C<sub>T</sub> method was then used to relatively quantify CD11c against the geometric average of the two housekeeping genes GAPDH and ACTB. <h3>Results</h3> Etanercept responder and non-responder patients showed similar baseline CD11c expression levels when normalised against a geometric average of the two housekeeping genes. Slightly higher levels of expression were seen in the pre-treatment samples taken from future responders yielding a fold-change of 0.493 as compared to non-responders (p-value = 0.81). <h3>Conclusions</h3> CD11c expression was not correlated with treatment outcome in etanercept treated RA patients. However, it cannot be excluded as a potential biomarker as this marker may only be specific to adalimumab and not other classes of anti-TNFs. Another possibility is that CD11c expression may be wholly cell-type specific resulting in masked signals which would be missed in whole blood RNA samples. Further experiments with specific cell populations and different biologics will be needed to confirm this hypothesis. <h3>Disclosure of Interest</h3> None Declared
THE TENDYNE EARLY FEASIBILITY TRIAL OF TRANSCATHETER MITRAL VALVE IMPLANTATION
Authors: David W.M. Muller, Paul Jansz, Marty Shaw, Paul Sorajja, Wesley Pedersen, Richard Bae, Robert Farivar, Jeffrey Popma, Philipp Blanke, Jonathon Leipsic
Journal: Journal of the American College of Cardiology (2016)
Antagonistic Roles of Thymic Stromal Lymphopoietin (TSLP) and Surfactant Protein-D (SP-D) in Dendritic Cell Regulation During Ozone-Induced Exacerbation of Allergic Airway Inflammation in Mice
Authors: Angela Haczku, Blerina Kokalari, Moyar Q. Ge, Cynthia Koziol-White, Imre Redai, Martine Loubeau, Carla Bauer, Christopher Stevenson, Lisa R. Forbes
Journal: Journal of Allergy and Clinical Immunology (2013)
RESPONSE TO EXERCISE TRAINING AND OUTCOMES IN HEART FAILURE PATIENTS WITH DIABETES MELLITUS: INSIGHTS FROM HF-ACTION
Authors: Adam Z. Banks, Robert Mentz, Amanda Stebbins, Catherine Mikus, Phillip Schulte, Jerome Fleg, Lawton Cooper, Steven Keteyian, Ileana Pina, Dalane Kitzman, Mona Fiuzat, David Whellan, William Kraus, Christopher O’Connor
Journal: Journal of the American College of Cardiology (2015)
Efficacité du système "over-the-scope clip" (OTSC®) dans le traitement des fistules gastriques après chirurgie bariatrique de type "Sleeve Gastectomy"
Authors: G Rahmi, E Samaha, G Malamut, B Landi, JM Canard, JM Chevallier, C Cellier
Journal: Endoscopy (2012)

Le traitement de la fistule gastrique après "Sleeve Gastrectomy" est difficile avec des récidives fréquentes. Le nouveau système de clips "over-the-scope" (OTSC®, Ovesco Endoscopy GmbH, Tuebingen, Allemagne) a une force occlusive importante (envergure de 9mm ou 11mm).
CARACTERIZACIÓN DE LA EFICACIA DE LA ENTEROSCOPIA DE DOBLE BALÓN MEDIANTE UN MODELO PORCINO
Authors: F Soria, O López Albors, E Pérez Cuadrado, E Morcillo, C Martín, FM Sánchez, P Esteban, LF Carballo Alvarez, R Latorre-Reveriego
Journal: Endoscopy (2011)

Introducción: El principal factor limitante de la enteroscopia de doble balón (EDB) es la pérdida progresiva de eficacia en el avance. Esto condiciona tanto la distancia máxima explorable como su duración. La caracterización de la dinámica de esta exploración mediante un modelo experimental aportaría un conocimiento más objetivo para programar EDB.
OP0004 Cardiovascular Risk in Intensively Treated Rheumatoid Arthritis: Comparison to an Osteoarthritis Population. First Prospective Analysis of the Act-CVD Cohort
Authors: I. Meek, H. E. Vonkeman, M. A. van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality. This association is thought to be due to the chronic inflammatory disease process, clustering of lifestyle associated CV risk factors, as well as the use of medication such as non steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in patients with RA. Most studies on CV risk in patients with RA were performed before the introduction of modern powerful anti-inflammatory therapies and intensive treatment strategies aiming at remission. It is important to obtain more information on CV risk in intensively treated RA. <h3>Objectives</h3> To evaluate CV event risk and its predictors in intensively treated RA compared to an OA population. <h3>Methods</h3> First prospective analysis of occurrence of CV events (myocardial infarction, acute coronary syndrome, coronary intervention, acute heart failure, acute cardiac death) in a cohort of consecutive patients attending the Arthritis Centre Twente (ACT-CVD). All patients with a diagnosis of RA (n=495) or OA (n=208) without previous CV events were included in this study. Inclusion took place between February 2009 and November 2011, follow up data for this analysis were collected onto November 2012. Incidence of CV events in RA and OA groups was compared by Kaplan Meier survival analysis, potential CV event risk factors (age, sex, atherogenic index, current smoking, ESR, IgM RF, DAS28 RA disease activity and RA erosions) within groups were evaluated by logistic regression. <h3>Results</h3> At baseline RA and OA groups did not differ in sex (% female; RA=72, OA=78), age (mean years; RA=59, OA=59) and 10-year risk of CV death (mean %; RA=5.7, OA=5.5). The RA group (mean disease duration 7.5 years, 50 % IgM RF positive) was characterized by low disease activity (mean DAS28 2.5, 66% DAS28 remission). After a median follow up of 36 months 46 events had occurred (RA=29, OA=17, p=0.25, figure 1 ). Age, systolic blood pressure and presence of erosions significantly contributed to CV event risk in RA, whereas in age and current smoking significantly contributed to OA associated CV risk. <h3>Image/graph</h3> <h3>Conclusions</h3> These preliminary data suggest that CV event risk in intensively treated RA equals CV event risk in OA. Factors contributing to CV event risk in rheumatic diseases may be disease specific. Disclosure of Interest: None Declared
P694The induction of homeobox genes by disturbed flow limits inflammation at atherosusceptible sites
Authors: I Gauci
Journal: Cardiovascular Research (2014)

Atherosclerosis develops at branches and bends of arteries that are exposed to disturbed blood, whereas regions exposed to uniform flow are protected. Disturbed flow generates low, oscillatory wall shear stress (WSS) which promotes atherosclerosis by inducing EC expression of inflammatory molecules. Conversely, high unidirectional WSS is protective. We studied the transcriptome at low and high WSS regions in the porcine aorta using micro arrays and observed differential expression of multiple Homeobox (Hox) genes. These transcription factors regulate embryonic development and morphogenesis. We hypothesize that Hox genes also influence EC responses to WSS. This project aims to: (1) assess the influence of WSS on Hox gene expression, (2) assess the effects of Hox genes on inflammatory activation in sheared EC.
AB0370 Association of Clinical Efficacy with Serum Level of Adalimumab (ADA) and Anti- Adalimumab Antibody Levels in Patients with Early Rheumatoid Arthritis (RA)
Authors: A.S. Avdeeva, E.N. Aleksandrova, A.A. Novikov, D.E. Karateev, E.L. Luchihina, M.V. Cherkasova, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> ADA is effective and safe drug for the treatment of RA. Application of ADA can be accompanied by formation anti-adalimumab antibody (anti-ADA Ab) influencing on efficiency of therapy and the development of adverse events <h3>Objectives</h3> To evaluated the correlation of serum levels of ADA and anti-ADA Ab in relation to clinical response in patients (pts) with early RA <h3>Methods</h3> Serum levels of ADA (μg/ml) and anti-ADA Ab (positive/negative result) was determined by ELISA in 25 pts with early RA (15 women, mean age – 54,0; 47,0-58,0 years, mean disease duration - 8,0; 5,0-25,0 months, mean DAS 28 – 5,8; 4,9-7,5, SDAI 34,3; 22,8-54,2, CDAI 32,0; 21,7-48,4) baseline and then after 12 and 24 weeks of treatment. All patients received disease-modifying antirheumatic drugs (DMARDs) (100%&gt;methotrexate) and ADA 40mg every 2 weeks. For all patients the ADA was the first biologic <h3>Results</h3> On the 12-th week of therapy values [Me; interquartile range] DAS 28 were 3,5 (3,2-4,4); SDAI-13,0 (7,0-16,6); CDAI - 10,8 (7,0-16, 0), 6 pts achieved a good EULAR response, 14- moderate response. On the 24-th week of treatment the value DAS 28 were 3,5 (3,1-4,4), SDAI-11,7 (7,4-17,5) and CDAI - 10,5 (6,2-16, 3), a good response was noted at 7 patients, moderate response - at 9 pts. The pts was distributed in two groups from serum levels of ADA: &lt;3,0 (the first group n=7) and ≥3,0 (second group n=13). There were no differences between the groups on disease activity, level of acute-phase reactants by the 12th week of therapy (p&gt;0,05). Higher disease activity and also the level of acute-phase reactants were marked out among pts of the first group (DAS 28 – 4,5; 3,3-4,9, ESR – 44; 18-57 mm/h, CRP -10,1; 4,9-34,5 mg/ml) compared with pts of the second group (3,5; 2,9-3,9, 15,0; 6,0-17,0 mm/h, 1,9; 0,75-6,7 mg/ml, respectively, p&lt;0,05) by the 24th week of therapy. Also on the 24th week negative correlation was found with level of ADA and DAS 28 (r= -0,46; p=0,04), CRP (r= -0,54; p=0,02) and ESR (r= -0,5; p=0,02). Anti-ADA Ab was found in 3 (12,5%) pts at week 12 and in 2 (10%) pts at week 24. By 24th week of treatment at 100% of pts with presence of anti-ADA Ab was absence of clinical effect (ΔDAS28 = -1,36; -3,1-0,4). In the group of pts without anti-ADA Ab we found fewer of "no respondents" (11%) and identified positive dynamics DAS 28 (ΔDAS28=2,5; 1,66-2,9) (p&lt;0,05) <h3>Conclusions</h3> Low drug level (&lt;3,0 μg/ml) in serum is associated with a high clinical and laboratory disease activity at pts with early RA receiving the ADA therapy. By 12-24 weeks of ADA therapy anti-ADA Ab is found in 10-12,5% of pts, it9s formation is accompanied of decrease in efficacy of therapy <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2266
Abstract 5089: Evaluation of BMP4 and BMP7 induced gene expression changes in breast cancer cells reveals time-dependent transcription patterns and a common synexpression group of genes
Authors: Alejandra Rodriguez-Martinez, Emma-Leena Alarmo, Lilli Saarinen, Johanna Ketolainen, Kari Nousiainen, Sampsa Hautaniemi, Anne H. Kallioniemi
Journal: Cancer Research (2012)

Abstract Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta superfamily of growth factors. They are well-known for their key roles in the regulation of various developmental processes and bone formation, but in recent years, evidence has also accumulated of their crucial contribution in tumor biology. In particular, BMP4 and BMP7 have been implicated in breast cancer pathogenesis. However, little is known about BMP target genes in the context of tumor cells. Here, we used whole-genome microarrays to explore the effects of BMP4 and BMP7 treatment on global gene expression levels in seven breast cancer cell lines during a 6-point time series. Several complementary methods, including hierarchical clustering of differentially expressed genes, gene ontology enrichment analyses and model based clustering of temporal data, were used for data analysis. Both BMP ligands had a strong influence on gene expression levels, although the response to BMP4 treatment was more pronounced as compared to BMP7. As might have been expected, the cellular functions most strongly affected by the stimulation of BMP signaling were regulation of transcription and development. The observed transcriptional response, as well as its functional outcome, followed a temporal sequence, where the regulation of gene expression and signal transduction was followed by changes in transcripts involved in metabolism and cell proliferation. Hierarchical clustering analysis revealed distinct differences in the response of individual cell lines to BMPs, but also underlined a common synexpression group of genes for both ligands. Remarkably, the majority of the genes within these synexpression groups were shared by the two ligands, and thus these genes are likely to represent the core molecular responses common to BMP4 and BMP7 signaling pathways. Taken together, our data demonstrate that BMP signaling has a substantial effect on gene transcription in breast cancer cells and that the cellular functions affected follow a logical temporal pattern. Our results also reveal components of the cellular transcriptional response that are common to BMP4 and BMP7. Finally, our study provides a list of putative novel BMP target genes relevant in breast cancer. 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 5089. doi:1538-7445.AM2012-5089
Successful Gene Therapy Has Researchers Looking for the Bystander Effect
Authors: L. Seachrist
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Successful Gene Therapy Has Researchers Looking for the Bystander Effect Get access Lisa Seachrist Lisa Seachrist Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Pages 82–83, https://doi.org/10.1093/jnci/86.2.82 Published: 19 January 1994
Maternal opioid dose is associated with neonatal abstinence syndrome in children born to women with sickle cell disease
Authors: Tyler Shirel, Collin P. Hubler, Rena Shah, Amy B. Mager, Kathryn L. Koch, Darshita Sheth, Michael R. Uhing, Cresta W. Jones, Joshua J. Field
Journal: American Journal of Hematology (2016)

The objective of this study was to test the hypothesis that higher daily opioid dose is associated with the presence and severity of neonatal abstinence syndrome (NAS) in pregnant women with sickle cell disease (SCD). This was a retrospective study of pregnant women with SCD who required opioids. NAS was evaluated using the Finnegan scoring system and classified as none, mild, and severe. Severe NAS was defined as a Finnegan score ≥ 8 on 3 consecutive tests. Thirty-four pregnancies were examined in 30 women with SCD. Higher daily morphine dose was associated with a higher percentage of days in the hospital during pregnancy (P < 0.001). Hospital days contributed disproportionately to daily morphine dose as larger amounts of opioids were administered in the hospital compared to home (P = 0.002). Median maternal oral morphine dose was 416 mg for infants with severe NAS compared with 139 mg for those with mild NAS (P = 0.04). For infants with no NAS, median maternal morphine was 4 mg, significantly less than those with mild NAS (P < 0.001). Infants born to women who used on average >200 mg/day of oral morphine equivalent in the last month of pregnancy had a 13-fold increased risk of severe NAS compared with those who used <200 mg/day. These data demonstrate that higher median daily opioid dose is associated with progressively more severe NAS in pregnant women with SCD. Strategies to decrease pain and avoid hospitalizations are needed to reduce opioid use and NAS.