tbuckley/cabot-search huggingface dataset:
Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus
Authors: Jennifer A. Bartlett, Shyam Ramachandran, Christine L. Wohlford-Lenane, Carrie K. Barker, Alejandro A. Pezzulo, Joseph Zabner, Michael J. Welsh, David K. Meyerholz, David A. Stoltz, Paul B. McCray
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Studies suggest that inappropriate responses to proinflammatory stimuli might contribute to inflammation in cystic fibrosis (CF) lungs. However, technical challenges have made it difficult to distinguish whether altered responses in CF airways are an intrinsic defect or a secondary effect of chronic disease in their tissue of origin. The CF pig model provides an opportunity to study the inflammatory responses of CF airways at birth, before the onset of infection and inflammation.Objectives: To test the hypothesis that acute inflammatory responses are perturbed in porcine CF airways.Methods: We investigated the inflammatory responses of newborn CF and non-CF pig airways following a 4-hour exposure to heat-killed Staphylococcus aureus, in vivo and in vitro.Measurements and Main Results: Following an in vivo S. aureus challenge, markers of inflammation were similar between CF and littermate control animals through evaluation of bronchoalveolar lavage and tissues. However, transcriptome analysis revealed genotype-dependent differences as CF pigs showed a diminished host defense response compared with their non-CF counterparts. Furthermore, CF pig airways exhibited an increase in apoptotic pathways and a suppression of ciliary and flagellar biosynthetic pathways. Similar differences were observed in cultured airway epithelia from CF and non-CF pigs exposed to the stimulus.Conclusions: Transcriptome profiling suggests that acute inflammatory responses are dysregulated in the airways of newborn CF pigs.
Loss of Heterozygosity on Chromosomes 1p and 11p in Sporadic Pheochromocytoma
Authors: M. Tsutsumi, J. Yokota, T. Kakizoe, K. Koiso, T. Sugimura, M. Terada
Journal: JNCI Journal of the National Cancer Institute (1989)

We used 29 polymorphic DNA markers to analyze tumor DNA samples from six patients with sporadic pheochromocytoma for possible loss of chromosomal heterozygosity; four had benign disease and two had malignant disease. Loss of heterozygosity was observed on four chromosomes: 1p (three of four patients), 2p (one of one), 5q (two of six), and 11p (three of five). Chromosomes 1p and 11p frequently had allelic deletions in these tumors, and these deletions may play an important role in the development of pheochromocytoma.
ED-32 * OUTCOMES OF PEDIATRIC BRAINSTEM LOW GRADE GLIOMAS: A SINGLE INSTITUTION SERIES
Authors: S. Upadhyaya, K. Muraszko, H. Garton, C. Maher, P. Robertson
Journal: Neuro-Oncology (2014)

BACKGROUND: Brainstem tumors constitute 10% of primary CNS tumor of children; 80% are malignant pontine gliomas, but 20% are low grade gliomas (LGG) with a more indolent course. Since advances in imaging & neurosurgical techniques, surgical resection is the initial treatment of choice for some of these tumors. However, optimal therapy for those which are incompletely resected or which relapse after surgery is uncertain. METHODS: We reviewed the clinical characteristics, therapy and outcomes of all children with non-tectal brainstem LGGs treated with surgical resection, chemotherapy (CT-carboplatin/VCR or thioguanine/procarbazine/CCNU/VCR), or radiation therapy (RT), at the University of Michigan Mott Children's Hospital over a 20 year period (1993-2013). RESULTS: Median age at diagnosis was 6 years; Histopathologic diagnosis was confirmed in 23/25 tumors; 61% were pilocytic astrocytoma, most often in cervicomedullary brainstem. Twenty one patients underwent initial tumor resection (11 GTR/NTR, 6 STR, 4 PR); 14 of these received no other therapy; 7 received adjuvant therapy (3-CT, 2-RT, 2 CT + RT) after surgery; 6 initially-resected tumors received CT at the time of local tumor relapse, to which all had partial or complete radiographic responses. Among 4 patients who underwent no initial surgical resection, 3 received RT at diagnosis, and 1 has stable disease, untreated for 2 years. All 25 patients are alive in remission with either stable disease or no evidence of disease, at a median follow-up of 12 years. Ten year relapse-free survival is 61 % and overall survival, 100%. DISCUSSION: This single institution retrospective study demonstrates excellent survival rates for children with brainstem LGG, with initial surgery +/- CT or RT, and effective salvage with CT. The efficacy of the well-tolerated chemotherapy in this series supports its role in the treatment of unresectable brainstem LGG, or in those which progress after initial surgical management.
Abstract 3682: Differential effect of withaferin A treatment on activation of Notch1 and Notch2 in human breast cancer cells.
Authors: Joomin Lee, Anuradha Sehrawat, Shivendra V. Singh
Journal: Cancer Research (2013)

Abstract Withaferin A (WA), a constituent of the Ayurvedic medicine plant Withania somnifera, exhibits in vivo efficacy against human breast cancer xenografts in athymic mice as well as spontaneous mammary cancer development in MMTV-neu transgenic mice. However, the mechanism underlying anticancer effect of WA is not fully understood. The present study was undertaken to determine the role of Notch family of transcription factors in anticancer effects of WA using human breast cancer cells as a model. Notch activation is linked to mammary carcinogenesis as evidenced by the following observations: (a) overexpression of activated Notch1 and Notch3 in transgenic mice blocks mammary gland development but induces tumorigenesis of the breast; (b) high level expression of Notch1 and its ligands is associated with poor outcome in breast cancer; (c) expression of Notch ligand Jagged1 is associated with recurrence in lymph node-negative breast cancer; and (d) Notch1 is involved in migration and invasion of human breast cancer cells. The present study reveals differential effect of WA treatment on activation of Notch1 versus Notch2 in human breast cancer cells. Exposure of MDA-MB-231 (an estrogen-independent cell line with mutant p53) and MCF-7 (an estrogen-responsive cell line with wild-type p53) human breast cancer cells to pharmacological concentrations of WA (2 and 4 μM) resulted in cleavage (suggesting activation) of Notch2, which was accompanied by transcriptional activation of Notch as evidenced by RBP-Jk, HES-1A/B, and HEY-1 luciferase reporter assays. On the other hand, WA treatment caused a decrease in levels of both transmembrane and cleaved (active) Notch1. The WA-mediated activation of Notch2 was associated with induction of γ-secretase complex components presenilin1 and/or nicastrin. Inhibition of MDA-MB-231 and MDA-MB-468 cell migration resulting from WA exposure was statistically significantly augmented by knockdown of Notch2 using siRNA and shRNA. Activation of Notch2 was not observed in cells treated with withanone or withanolide A, which are structural analogs of WA. Moreover, withanone and withanolide A were practically inactive against MDA-MB-231 cell migration. The results of the present study suggest that anti-metastatic effect of WA may be augmented in the presence of Notch2 inhibitors. This study was supported by the grant CA142604 awarded by the National Cancer Institute. Citation Format: Joomin Lee, Anuradha Sehrawat, Shivendra V. Singh. Differential effect of withaferin A treatment on activation of Notch1 and Notch2 in human breast cancer cells. [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 3682. doi:10.1158/1538-7445.AM2013-3682
Effects of chrysotile co-exposure on BaP binding in normal human fibroblasts.
Authors: M J Chang, N P Singh, R W Hart
Journal: Environmental Health Perspectives (1983)

The effects of chrysotile and benzo(a)pyrene (BaP) co-exposure on uptake, metabolism and BaP binding to nucleic acids were investigated in normal human fibroblasts. A significant enhancement in these parameters was found when co-exposure was carried out under serum-free conditions. In the presence of serum, only a slight enhancement of BaP uptake was detected, while metabolism and binding to nucleic acids were not affected over the 8-hr incubation period studied.
SP0017 Lipoplex-Containing Sirna to Modulate Monocyte Inflammatory Response: Application to Arthritis
Authors: F. Apparailly
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> RNA interference (RNAi) is one of the most exciting and important discoveries of the past few decades. Small interfering RNAs (siRNAs) can silence gene activity and be used to interfere with pathophysiological processes. Substantial research has focused on introducing 9drug-like9 properties to RNAi molecules, and clinical trials have been initiated. Despite initial success, the current challenge that remains is to develop vehicles that efficiently deliver the therapeutic siRNA to specific cell types. As for many other diseases, siRNA-based therapy is also emerging as a promising approach for the treatment of rheumatoid arthritis (RA). Although the pathogenesis of RA is complex, identification of candidate genes able to influence inflammatory response has been successful. As for the cell population to target for RNAi-mediated anti-inflammatory intervention in RA, monocytes display optimal features. Indeed, due to their capacity to differentiate into dendritic cells (DC), M1/M2 macrophages as well as osteoclasts (OC), monocytes control both inflammation and bone turnover, two hallmarks of RA. There are however functionally distinct subsets of monocytes that control homeostatic and inflammatory processes. Excessive and prolonged activation of monocytes – and especially Ly6C<sup>high</sup> "inflammatory" monocytes in the mouse – is a hallmark of chronic inflammation. Precise targeting of this cell subset could be therapeutically beneficial while sparing other subsets and leukocytes. We will present strategies developed to target Ly6C<sup>high</sup> monocytes with optimized lipid-based formulations as well as therapeutic siRNAs used to silence inflammation in mouse. We will also discuss potential applications of siRNA therapeutics in clinical trials for RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6277
Abstract 2830: Energy balance and breast cancer risk among sisters pairs in the Breast Cancer Family Registry Study
Authors: Fang Fang Zhang, Esther M. John, Dee W. West, Julia Knight, Irene Andrulis, Saundra Buys, Mary Daly, Beth Stearman, Manleen Kaur, Jamboor Vishwanatha, Alfredo Morabia, Mary Beth Terry
Journal: Cancer Research (2010)

Abstract Animal models have shown strong evidence that energy restriction inhibits mammary tumor development. Nevertheless, epidemiologic studies in humans generally do not support an association between energy intake and breast cancer risk. Failure to take into consideration the integrated effect of energy intake, physical activity and body size may obscure the true effect of energy intake on breast cancer risk. We analyzed the combined effects of energy intake, body size and physical activity on the risk of breast cancer among 4,564 women diagnosed with breast cancer between 1995 and 2006 and 3,411 of their unaffected sisters enrolled in the Breast Cancer Family Registry. Dietary data were collected using the food frequency questionnaire developed for the Hawaii-Los Angeles Multiethnic Cohort. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). We observed an overall 50% increased risk of breast cancer among women in the highest quartile of energy intake compared to those in the lowest quartile (OR=1.5, 95% CI: 1.1-2.2, ptrend &amp;lt; 0.01). The association with energy intake was limited to women with lower levels of strenuous physical activity (OR=1.9, 95% CI: 1.3-2.9 for &amp;lt; 1.75 hours/week during the past three years), and was stronger among women with higher body mass index (BMI) (OR=2.2, 95% CI: 0.6-7.7 for BMI ≥ 30; OR=1.5, 95% CI: 0.6-3.7 for BMI 25-29; OR=1.3, 95% CI: 0.7-2.5 for BMI &amp;lt; 25 kg/m2). Our results suggest that higher total energy intake in adulthood is associated with a 50% increase in breast cancer risk compared to sisters with lower energy intake in adulthood; these associations are stronger among less active and obese women. 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 2830.
AB1075 Seronegative arthropathies: Value of dual-energy CT for differential diagnosis
Authors: M. Mustak, J. Boltuch-Sherif, M. Kasper, G. Minimair, G. Strau, L. Erlacher
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Seronegative Oligo/Polyarthritis combines a set of diseases including gout as a possible differential diagnosis. The identification of monosodium urate crystals is the gold standard for the proof of gout. However, the puncture of small finger and toe joints maybe a challenge and is therefore often not applicable. <h3>Methods</h3> A retrospective analysis of 49 patients was used to investigate the value of Dual-Energy CT for differential diagnosis in patients with seronegative arthropathies. Puncture and analysis of the joint fluid was possible in 15 patients, whereas Dual-Energy CT without puncture could be performed in the remaining 34 patients. <h3>Results</h3> In the first group of patients (n=15), where a crystal analysis was available, urate crystals could be indentified in 14 and Dual-Energy CT investigation confirmed monosodium urate depositions in 11 of these patients.In 3 cases with positive urate crystal detection in joint fluid gout-CT was negative.In one case pyrophosphate crystals were identified and no urate depositions in gout-CT could be detected. In the second group (n=34) joint puncture could not be performed as the affected joints were small finger and toe joints.21 of these patients revealed urate depositions in Dual-Energy CT. In these cases the diagnosis of gout was confirmed and appropriate therapy could be started. 17 out of these 21 patients had elevated uric acid levels. <h3>Conclusions</h3> Dual-Energy CT can be applied as a tool for diagnosing gout in patients with seronegative inflammatory arthropathy especially in the case of polyarticular joint involvement and no possibility of joint puncture. <h3>References</h3> W Zhang, M Doherty, E Pascual et al. Eular evidence based recommendations for gout. Part I: Diagnosis.Report of a task force of the standing committee for international clinical studies including therapeutics/ESCISIT). Ann Rheum Dis 2006;65:1301-1311 W Zhang, M Doherty, T Bardin et al. Eular evidence based recommendations for gout. Part II: Management.Report of a task force of the standing committee for international clinical studies including therapeutics/ESCISIT). Ann Rheum Dis 2006;65:1312-1324 N Dalbeth, B Clark, K Gregory et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis 2009; 68:1290-1295 RGThiele,N Schlesinger. Diagnosis of gout by ultrasound. Rheumatology 2007;46:1116-1121 JC Gerster, M Landry, G Rivier. Computes Tomographic Imaging of Subcutaneous Gouty Tophi. Clin Rheumatol 1998;17:62-64 S Nicolaou, CJ Yong-Hing, S Galea-Soler. Dual Energy CT as a Potential New Diagnostic Tool in the Management of Gout in the Acute Setting. AJR 2010;194:1072-1078 G.Strau, M. Mustak, M Kasper. Dual-Energy-Computertomografie (article in German). Jatros Orthopädie &amp; Rheumatologie 5/2011 <h3>Disclosure of Interest</h3> None Declared
P975 DYNAMIC CHANGES OF THE INFLAMMATION BASED INDEX (IBI) AS A PREDICTOR OF MORTALITY FOLLOWING TRANS-ARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA
Authors: D.J. Pinato, G. Karamanakos, A. Goyal, D. Adjogatse, A.B. Siegel, J.L. Weintraub, J. Stebbing, J.W. Jang, R. Sharma
Journal: Journal of Hepatology (2014)
The Hairy Eyeball — Limbal Dermoid
Authors: Ali Mahdavi Fard, Leili Pourafkari
Journal: New England Journal of Medicine (2013)

A 19-year-old man presented with a mass in his right eye that had been present since birth but had gradually increased in size. The mass caused vision defects, mild discomfort on blinking, and the intermittent sensation of the presence of a foreign body.
Abstract 30: Identification of genomic and epigenetic features of tumor suppressors and oncogenes in ovarian cancer
Authors: Kazimierz O. Wrzeszczynski, Vinay Varadan, Sitharthan Kamalakaran, Douglas A. Levine, Nevenka Dimitrova, Michael Q. Zhang, Robert Lucito
Journal: Cancer Research (2011)

Abstract The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 42 primary ovarian cancer samples using our MOMA-ROMA technology and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both datasets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogene and tumor suppressor candidates by integrating these multiple genomic and epigenetic data types. Genes with a strong correlation for methylation dependent expression exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. Moreover, well characterized tumor suppressors and oncogenes exhibit varying CNV, methylation and expression features within cancers. We therefore compared significant copy number variation and methylation effects on expression for many known tumor suppressors, oncogenes and cancer related genes in order to identify altered gene function properties specific to primary ovarian tumors. Here, we present the analysis of multiple genomic modalities from two primary ovarian tumor datasets for the identification of candidate genes. We predict genes with epigenetic and genomic tumor suppressor and oncogenic properties having both analyzed and identified known validated ovarian cancer genes and identifying new candidates. 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 30. doi:10.1158/1538-7445.AM2011-30
Higher-Complexity ED Billing Codes — Sicker Patients, More Intensive Practice, or Improper Payments?
Authors: Stephen R. Pitts
Journal: New England Journal of Medicine (2012)

Between 2001 and 2010, billing for level 5 emergency department visits increased from 27% to 48% of Medicare discharges. Some blame up-coding facilitated by EHRs, but other factors are changes in demographics, practice patterns, and the emergency department's role.
P986 MANAGEMENT OF HCC BY TRANSARTERIAL CHEMOEMBOLIZATION CONVENTIONAL AND BEADS DOXORUBICIN
Authors: V. Ciria, M.T. Ferrer, Á. Giraldez, J.M. Sousa, V. Nacarino, Á. Iglesias, J. Peiró, J.M. Pascasio
Journal: Journal of Hepatology (2014)
OC-092 Alteration in Mucosal Keratin 8 Level, Phosphorylation and Relative Ratio to Vimentin Associate with development of Colitis-Associated Cancer
Authors: D Majumdar, C Evans, B Corfe, A Lobo
Journal: Gut (2013)

<h3>Introduction</h3> Intermediate filament(IF) proteins keratin(K) and vimentin(VIM) are cellular cytoskeleton components. Mutations of K8 gene associated with inefficient IF assembly is seen in subset of IBD patients. VIM a marker of epithelial-mesenchymal transformation is associated with aggressive colorectal cancer(CRC). We have previously shown alterations in mucosal IF proteins on mass spectrometry(MS) in UC patients at differing risk of CRC. We aimed to validate changes noted on MS and additionally investigate post-translational modifications in K8. <h3>Methods</h3> Rectal biopsies were studied from the following groups of patients with UC: quiescent long standing pancolitis(LSPC-20–40years); inactive recent onset UC(ROUC &lt; 5 years), UC with primary sclerosing cholangitis(PSC), pancolitis with dysplasia (DR), distal active colitis (ACT) &amp; controls(CON). Biopsies were also taken from dysplastic lesions(DT) and un-inflamed proximal colonic mucosa(INACT) in ACT group(to investigate proteomic changes due to inflammation in same group of patients). Western immunoblotting was undertaken using antibodies to K8, K18, K19, VIM, and K8 phosphorylated at Ser23, Ser73 and Ser431. Individual band intensities were quantified by densitometric analyses of the blots. <h3>Results</h3> Multiple K8 forms were noted; relative to CON, low K8 levels &amp; molecular weight(MW) forms (37kDa) was seen in ROUC and DT (Fig A). Similar to MS results, in ACT there was reduction in K8, K18, K19 &amp; VIM levels with low MW K8 forms (FigB). Vimentin was increased in LSPC, PSC, DR &amp; DT compared to CON (Fig A); progressive increase in VIM:K8 ratio was noted (DT &gt; DR &gt; PSC &gt; LSPC &gt; ROUC- Fig C). K8 phosphorylation was reduced or absent in ACT and ROUC (Fig A&amp;B), with diminished levels noted in PSC, DR and DT compared to LSPC. K8pS23 levels relative to total K8, was comparable in CON and LSPC but showed a reduced ratio in ROUC &amp; dysplasia(Fig D). <h3>Conclusion</h3> K8 levels and phosphorylation are reduced in acute inflammation and restore/overcompensate in longstanding quiescent disease. This restoration is not apparent in recently inflamed mucosa (ROUC) despite endoscopic and histological remission; with similar changes seen in more aggressive disease. Recurrent bouts of acute inflammation in the mucosa with associated failure of restoration of K8 integrity may be associated with increased colon cancer risk. An altered VIM:K8 ratio may in addition be a surrogate mucosal marker of disease progression. <h3>Disclosure of Interest</h3> None Declared