tbuckley/cabot-search huggingface dataset:
PWE-029 Position Changes Among English Bcsp Colonoscopists: A Survey Of Practices: Abstract PWE-029 Table 1
Authors: A Ball, J Campbell, SA Riley
Journal: Gut (2014)

<h3>Introduction</h3> Studies suggest that modifying a patient’s position during colonoscope withdrawal may improve luminal distension and polyp detection. It is unclear whether this practice is widely adopted by endoscopists. <h3>Methods</h3> Colonoscopists within the English Bowel Cancer Screening Programme (BCSP) were invited to participate in a web-based survey assessing the use of position change during colonoscope withdrawal. Free text responses were assessed using thematic analysis. <h3>Results</h3> The survey was completed by 204/298 (68%) of English BCSP colonoscopists. 64.7% of respondents indicated that they almost always change a patient’s position, 16.7% usually, 13.7% sometimes, 3.4% occasionally and 1.5% rarely do so. 77% of those who almost always or usually changed a patient’s position did so as part of their routine, but 75.3% were less likely to change position in those with poor mobility and 75.3% would not change position if luminal distension was adequate. 93% of these respondents most often positioned patients supine while examining the transverse colon and nearly half examined the right and descending colon in a sub-optimal position (Table 1). Of those respondents who sometimes, occasionally or rarely changed a patient’s position, 42% were unconvinced that routine position change was beneficial. A further 21.1% felt it took too long, 7.8% felt it was inconvenient for the patient and 7.8% felt it was inconvenient for the endoscopist. These respondents were most likely to examine segments without changing patient position. Free text responses revealed that some endoscopists position patients differently during insertion and withdrawal and also use position change to optimise access during therapy. <h3>Conclusion</h3> Most BCSP colonoscopists change patients’ position during most colonoscope withdrawals, but the patient position is often sub-optimal. Increased awareness of the existing literature and further research assessing positioning strategy is warranted. <h3>Reference</h3> East JE <i>et al.</i><i>Gastrointest Endosc</i>. 2011 Mar;73(3):456–63 <h3>Disclosure of Interest</h3> None Declared.
P1183 VIRAL BREAKTHROUGH DURING TRIPLE THERAPY: CAUSES OF NON RESPONSE IN A MULTICENTRIC COHORT
Authors: J.L. Calleja Panero, J. Crespo, R. Rodríguez, M.A. Serra, J.M. Pascasio, R. Sola, R. Morillas, M. Romero, S. Lens, J. García Samaniego, B. Ruiz Antorán, J. Turnes
Journal: Journal of Hepatology (2014)
S116 Urge-to-cough intensity in chronic cough patients compared to asthmatics and healthy controls
Authors: E. C. Young, H. Sumner, A. Kelsall, A. A. Woodcock, J. A. Smith
Journal: Thorax (2010)

<h3>Background</h3> Healthy subjects inhaling increasing doses of capsaicin perceive an urge-to-cough (UTC) prior to initiating coughing. We compared subjective ratings of UTC intensity following inhalation of capsaicin in patients with chronic cough (CC), asthma (A) and healthy controls (HC). <h3>Methods</h3> A double-blind, randomised block design, capsaicin cough challenge was performed using single-breath inhalations, separated by 1 min, through a dosimeter (inspiratory flow rate limited). Seven individually pre-determined doses (0.48–1000 μMol; maximum dose inducing an average of at least five coughs) and one placebo dose were administered four times each, in four individually randomised blocks (Davenport <i>et al</i>), to reduce the bias associated with subjective UTC ratings. After each inhalation, UTC was rated on a modified Borg scale (0–10) and number of coughs in the first 15 s was recorded. Using Generalised Estimating Equations (GEE), we explored the effect of group and gender on average UTC intensity and average cough responses to increasing concentrations of capsaicin. <h3>Results</h3> We studied 20 treatment resistant CC, 18 stable mild/moderate A and 20 HC subjects, matched for gender (M:F 10:10, 9:9,10:10, respectively), age [mean (±SD) 57.1 years (±15.7), 51.7 years (±13.5), 58.8 years (±13.5); p=0.17], and lung function [3.02L (±0.98), 2.96L (±1.10), 3.20L (±0.99); p=0.72]. CC had significantly greater UTC intensity (p=0.006, see Abstract S116 Figure 1) and cough responses (p=0.002) compared to HC. Females had significantly greater UTC (p=0.001) and cough responses (p&lt;0.001) compared to males. There was no significant difference in UTC intensity (p=0.449) or cough responses (p=0.997) between A and HC. <h3>Conclusions</h3> In a randomised double-blind capsaicin cough challenge: Chronic cough patients perceive a more intense UTC sensation and also demonstrate a greater magnitude of cough response than healthy controls. Females perceive a more intense UTC sensation than males. These findings suggest both a heightened sensory experience in addition to an excessive motor response in patients with chronic cough. This data could be explained by sensitisation of afferent pathways (ie, peripheral and/or central sensitisation) but also by impaired inhibitory control mechanisms.
Re: Enigma of Fluorouracil and Levamisole
Authors: J. B. HEALY
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Re: Enigma of Fluorouracil and Levamisole Get access J. B. HEALY J. B. HEALY Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 19, 4 October 1995, Page 1486, https://doi.org/10.1093/jnci/87.19.1486 Published: 04 October 1995
Abstract 2992: Stringent analysis of large-scale siRNA screens identifies a kinase fusion oncogene.
Authors: Astrid A. Ruefli-Brasse, Cynthia Hart, Liza Fajardo, Elissa Swearingen, Linda Wong, Doreen Sakamoto, Kari Hale, Huanying Ge, Jeffery McDowell, Bharath Ramachandran, Elissa Cosgrove, J.E.Vivienne Watson, Seamus Ragan, Seamus Ragan, Paul Kassner, Paul Kassner, Kim Quon
Journal: Cancer Research (2013)

Abstract The interpretation of RNAi knockdown experiments can be challenging due to the extensive off-target effects exhibited by siRNAs and shRNAs. This has led to the reporting of results that cannot be independently verified, or to the identification of putative cancer targets that are insufficiently robust to support industrial drug discovery efforts. The problems associated with off target effects are particularly acute in high throughput RNAi screens, whose results often differ wildly between laboratories using different experimental platforms. As a result, the validity of published large-scale RNAi screens has recently been called into question. Here we report results from large scale RNAi screens to identify genes essential for the proliferation or survival of cancer cells. To overcome the inherent liabilities of RNAi screens, we have increased the experimental power by using typically 8, and up to 20 RNAi triggers per gene, and have developed novel statistical algorithms that exploit this increased power. Importantly, this approach allows the calculation of a false discovery rate (FDR) that accurately predicts the ability of results to be confirmed by independent labs using independent reagents, solving a key issue of such screens. Using a stringent FDR cutoff of 5%, known essential genes and driver oncogenes such as KRAS, ERBB2 and BRAF are readily identified, demonstrating the robustness and power of the method. We have also identified a number of novel cancer targets. We present the identification and genetic and pharmacological validation of one of these targets, a kinase present as a fusion partner in multiple fusion oncogenes in primary tumors. Our data demonstrate that large-scale RNAi screens can be a robust and independently verifiable tool to uncover previously unknown cancer vulnerabilities which have yet to be characterized despite extensive genomic sequencing efforts. Citation Format: Astrid A. Ruefli-Brasse, Cynthia Hart, Liza Fajardo, Elissa Swearingen, Linda Wong, Doreen Sakamoto, Kari Hale, Huanying Ge, Jeffery McDowell, Bharath Ramachandran, Elissa Cosgrove, J.E.Vivienne Watson, Seamus Ragan, Seamus Ragan, Paul Kassner, Paul Kassner, Kim Quon. Stringent analysis of large-scale siRNA screens identifies a kinase fusion oncogene. [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 2992. doi:10.1158/1538-7445.AM2013-2992
PWE-093 Screening with Holotranscobalamin is Superior to Serum B12 in Identifying Vitamin B12 Deficiency in Patients with Crohn’S Disease
Authors: M G Ward, V C Kariyawasam, P A Blaker, K V Patel, R M Goel, A Sobczynska-Malefora, A Ajaegbu, D J Harrington, S H Anderson, J D Sanderson, P M Irving
Journal: Gut (2013)

<h3>Introduction</h3> Risk factors for vitamin B12 deficiency in patients with Crohn’s disease (CD) include ileal disease and previous ileal resections. Screening for B12 deficiency is traditionally through serum B12 which is relatively insensitive. Holotranscobalamin (holoTC) is a test that measures the metabolically active fraction of B12 available for cellular uptake and has been shown to perform better than traditional testing in identifying patients with functional B12 deficiency. We hypothesised that holoTC would identify B12 deficiency in patients with CD deemed to be B12 replete on traditional testing and sought to identify prevalence and risk factors within this population. <h3>Methods</h3> Prospective study of consecutive patients with CD. Patients receiving B12 supplementation were excluded. Patients underwent paired serum B12 and HoloTC testing. Serum B12 &lt; 107pmol/L or HoloTC &lt; 25pmol/L was defined as B12 deficient. Intermediate HoloTC values between 25pmol/L and 50pmol/L underwent further assessment with methylmalonic acid (MMA), considered the gold standard in metabolic B12 deficiency. MMA &gt; 280nmol/L in patients &lt; 65 years of age and &gt; 360nmol/L in patients &gt; 65 years of age confirmed B12 deficiency. Risk factors for B12 deficiency were examined including Montreal classification, surgical history and the presence of ileal inflammation or stricture. <h3>Results</h3> 70 patients who were not receiving B12 supplementation were included, (37 (53%) male, median age 37.5 years (IQR 28–47)). Disease location was ileal in 19 (27%), colonic in 19 (27%), ileocolonic in 32 (46%). 27 (39%) had undergone surgery, 22 (31%) an ileal resection. 18 (26%) were B12 deficient using HoloTC; 8 (11.5%) on HoloTC alone and 10 (14.5%) after MMA analysis on intermediate HoloTC results. Serum B12 testing identified 4 (5.7%) patients with B12 deficiency; 2 were functionally B12 deficient with HoloTC alone and 2 were replete when assessed by MMA. Ileal resection length &gt; 30cm (OR 5.3, 95% CI 2.6–10.8, p &lt; 0.0001), ileal inflammation (OR 11.3, 95% CI 3.48–36.9, p &lt; 0.0001), ileal stricture (OR 6.1, 95% CI 2.8–13.7, p &lt; 0.0001) and ileal resection (OR 5.0, 95% CI 2.3–10.7, p &lt; 0.0001) were significant predictors of B12 deficiency on univariate analysis. <h3>Conclusion</h3> HoloTC identifies vitamin B12 deficiency in a significant percentage of patients with CD otherwise considered replete on traditional testing. In addition serum B12 testing identifies patients who are not functionally deficient. Active ileal disease, ileal resection and ileal resection &gt; 30cm were significant predictors of vitamin B12 deficiency. <h3>Disclosure of Interest</h3> None Declared.
Abstract 5225: Correlation between αvβ3 integrin expression, paclitaxel resistance and RGD-bearing conjugate efficacy
Authors: Anat Eldar-Boock, Joaquin Sanchis, Ruth Lupu, Maria J. Vicent, Ronit Satchi-Fainaro
Journal: Cancer Research (2012)

Abstract Overcoming drug resistance, emerging either on recurring cancer or metastasis, is a major target of cancer treatments. The combination of anti-angiogenic therapy with cytotoxic therapy offers a promising therapeutic approach. Paclitaxel (PTX) is a widely-used potent cytotoxic drug, which also exhibits anti-angiogenic activity at low doses. The use of the hydrophobic PTX to its full potential is limited by severe side effects, caused by the drug and its solubilizing agents. Integrins play a key role in cell matrix interactions. The highly restricted expression of integrin αvβ3, overexpressed on tumor endothelial and some epithelial cells, during tumor growth, invasion, and metastasis present an interesting molecular target for metastatic breast tumors. In addition, PTX acquired resistance correlated with integrin αvβ3 overexpression on breast cancer cells. We designed and synthesized a novel polyglutamic acid (PGA)-PTX-E-[c(RGDfK)2] nano-scaled conjugate. Polymer conjugation converted PTX to a water-soluble macromolecule, which passively targeted the tumor tissue exploiting the enhanced permeability and retention (EPR) effect, while extravasating via the leaky tumor neovasculature. The E-[c(RGDfK)2] enhanced the effects previously seen for PGA-PTX alone, utilizing the additional active targeting to the αvβ3 integrin. PGA is enzymatically-degradable by cathepsin B, leading to PTX release. PGA-PTX-E-[c(RGDfK)2] displayed a potent anti-angiogenic therapy, determined by several, well-established, in vitro assays. Mice bearing orthotopic mammary tumors demonstrated preferential tumor accumulation of the RGD-bearing conjugate, leading to enhanced antitumor efficacy and a marked decreased in toxicity compared with free PTX. The correlation between αvβ3 integrin expression on tumor cells and acquired PTX-resistance was determined by in vitro manipulation of αvβ3 overexpressing-cells and by examining subsets of primary versus metastatic or recurring tumors of PTX-treated patients as well as free and conjugated-PTX-treated tumor-bearing mice. Taken together, our conjugate alters the pharmacokinetics of free PTX. Inclusion of an active targeting moiety to integrin expressing-cells, have the potential to manipulate and overcome acquired drug resistance, which will hopefully warrant it as a novel targeted, anti-angiogenic and anticancer therapy. 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 5225. doi:1538-7445.AM2012-5225
Abstract P4-06-07: PI3K Mutations Are More Common in Low Grade DCIS
Authors: R Sakr, S Chandarlapaty, V Andrade, D Giri, S Muhsen, P Wooyul, M Morrow, N Rosen, T. King
Journal: Cancer Research (2010)

Abstract Background: DCIS is a non-obligate precursor to invasive breast cancer yet it remains difficult to predict which lesions will progress or over what time interval. Factors associated with a higher risk of progression include high histologic grade and HER2 amplification. HER2 signaling via the PI3K pathway is associated with accelerated invasiveness in laboratory models and mutations in the helical domain of PI3K have been associated with a worse prognosis in invasive cancer. We hypothesized that PI3K pathway mutations are associated with higher risk of progression in DCIS and therefore would be more common in high grade DCIS. Methods: 195 cases of pure DCIS were identified from the MSKCC breast service database (1999-2003). All cases were reviewed by a single pathologist to assign histologic grade. Sections were obtained from archived formalin-fixed paraffin embedded (FFPE) blocks for manual microdissection to isolate pure DCIS lesions for DNA extraction. Multiplex array (Sequenom®) genotyping for PIK3CA was performed on prePCR amplified DNA. Comparisons were made between high and low grade DCIS using Fisher's exact test. Results: Among 195 pure DCIS cases, 89 were classified as high grade and 106 as low grade. Sequenom® analysis was informative in all cases. PIK3CA mutations were identified in 4/89 (4%) cases of high grade DCIS and in 24/106 (23%) cases of low grade DCIS (p=0.000). All 4 mutations in high grade DCIS were located in the kinase domain, whereas in low grade DCIS, 9/24 (37%) mutations were in the kinase domain (H1047R) and 15/24 (67%) mutations were in the helical domain (E542K, E545K, N345K). Conclusion: PI3K mutations were relatively uncommon in pure high grade DCIS as compared to low grade DCIS. PI3K mutations in low grade DCIS were observed in both the kinase and helical domain. These findings support the hypothesis that breast tumorigenesis differs by grade and PI3K mutations may be more prominent in low grade carcinogenesis. The significance of helical domain mutations in low grade lesions requires further investigation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-07.
AI-13 * CIRCULATING ENDOTHELIAL PROGENITOR CELLS IN GLIOBLASTOMA PATIENTS EXPRESS INCREASED LEVELS OF c-Kit AND SCF
Authors: K. Huizer, A. Sacchetti, D. Mustafa, M. van der Weiden, M. Kros
Journal: Neuro-Oncology (2014)

Current treatment options for glioblastoma patients have modest effects on survival. Since GBMs are one of the most vascularized tumors, treatment targeting GBM vessels has recently been introduced; clinical improvement, however, is limited. Endothelial progenitor cells are bone-marrow derived cells that home to ischemic tissue, guided by chemoattractants, where they differentiate under the influence of the microenvironment, and stimulate angiogenesis by secreting proangiogenic factors. As such, EPCs play an important role in neovascularization, including in GBMs. While changes in gene expression in EPCs once they arrive at their target location are well-established, little is known about the expression of proangiogenic factors in EPCs that are circulating in the blood. Since important factors from the GBM microenvironment also enter the bloodstream, we hypothesized that changes in gene expression could already be present in circulating EPCs from GBM patients. In order to test this hypothesis, we isolated EPCs (CD34 + CD133 + CD45dim) by FACS from blood of healthy controls (HC) and GBM patients. We determined the expression of a panel of 54 genes involved in angiogenesis by RT-PCR. The amount of circulating EPCs were similar between HC and GBM patients. Several genes, however, were differentially expressed; EPCs from GBM patients expressed both c-kit and SCF at a higher level than HC EPCs. In GBM, SCF is an important proangiogenic factor, which binds to its receptor c-kit. Both SCF and c-kit are expressed by subsets of endothelial cells in GBMs. We are currently investigating whether EPC c-kit and SCF expression correlates with tumor endothelial cell expression, and plan to do functional studies to determine the significance of our findings in GBM neovascularization. Our findings suggests that GBMs are capable of influencing gene expression in EPCs while they are still in the circulation. Influencing circulating EPCs in GBM patients could represent a novel type of antiangiogenic therapy.
Extraskeletal Accumulation of Bone-Seeking Agent Mimicking Diaphragmatic Uptake
Authors: YUSUKE INOUE, TOHRU OHTAKE, JUNICHI NISHIKAWA, KOHKI YOSHIKAWA, YASUHITO SASAKI
Journal: Clinical Nuclear Medicine (1998)

Tc-99m MDP bone imaging of a 64-year-old woman with uterine corpus carcinoma showed no evidence of bone metastases. Extraskeletal accumulation was noted in the pelvis and right upper abdomen. Accumulation in the right upper abdomen was curvilinear and resembled the diaphragm. CT demonstrated metastatic involvement in the omentum and right subphrenic area, which was considered to be the cause of the extraskeletal accumulation.
Prenatal Diagnosis of Fetal RhD Status by Molecular Analysis of Maternal Plasma
Authors: Y.M. Dennis Lo, N. Magnus Hjelm, Carrie Fidler, Ian L. Sargent, Michael F. Murphy, Paul F. Chamberlain, Priscilla M.K. Poon, Christopher W.G. Redman, James S. Wainscoat
Journal: New England Journal of Medicine (1998)

The ability to determine fetal RhD status noninvasively is useful in the treatment of RhD-sensitized pregnant women whose partners are heterozygous for the RhD gene. The recent demonstration of fetal DNA in maternal plasma raises the possibility that fetal RhD genotyping may be possible with the use of maternal plasma.
A1.09 S100-damps in IL-1RA<sup>-/-</sup>mice, a serum biomarker and<i>in vivo</i>imaging tool to assess joint inflammation and destruction in experimental seronegative arthritis
Authors: EJW Geven, S Abdollahi-Roodsaz, A Sloetjes, MI Koenders, D Foell, J Roth, T Vogl, PLEM van Lent
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Seronegative joint diseases are characterised by the lack of autoantibodies and rheumatoid factor, potent biomarkers for disease activity in seropositive arthritis. Promising alternative biomarkers in seronegative arthritis are the Damage Associated Molecular Patterns (DAMPs), S100A8 and S100A9, proteins specifically expressed by infiltrating phagocytes. In this study we explore the biomarker potential of S100A8/S100A9 to asses joint inflammation and damage in IL-1Ra<sup>-/-</sup> mice, a mouse model for seronegative arthritis in which serum autoantibodies are not correlated to disease activity. <h3>Materials and methods</h3> Serum of IL-1Ra<sup>-/-</sup> and BALB/c mice was collected every two weeks and swelling in the hind paws was macroscopically scored. Serum levels of IL-1β, IL-6 and TNFα were measured by Luminex technology and S100A8/A9 complex levels by ELISA. Hind paws were isolated and histologically scored for cell influx, cartilage damage and bone erosion, sections were also stained for S100A9 expression. Synovial S100A8 was imaged by injection of anti-S100A8-Cy7 antibody and 24 h p.i. fluorescent images were acquired in the IVIS Lumina optical imaging system. <h3>Results</h3> Starting at week 8 up to week 16, serum levels of S100A8/A9 in IL-1Ra<sup>-/-</sup> mice were significantly increased (1640 ± 1008 ng/ml) compared to BALB/c mice (429 ± 191 ng/ml, P = 0.005) and strongly correlated to joint swelling (r = 0.740, P &lt; 0.0001) and microscopic parameters for joint pathology (r = 0.672–0.770, P &lt; 0.0001), in contrast to levels of IL-1β, IL-6, and TNFα. Serum S100A8/A9 levels already correlated to joint swelling (r = 0.410, P = 0.047) as early as week 8 and high serum levels at week 10 were predictive for increased joint swelling at week 16 (r = 0.563, P = 0.004). Local expression of S100A9 within the synovium correlated to joint damage and serum S100A8/A9 levels and imaging of S100A8 using specific anti-S100A8-Cy7 antibody showed a specific targeting in inflamed joints of IL-1Ra<sup>-/-</sup> mice when compared to a control isotype (P = 0.044). <h3>Conclusions</h3> High levels of serum S100A8/A9 correlate to joint inflammation and destruction in experimental seronegative arthritis and local synovial expression of S100-DAMPs can be monitored <i>in vivo</i> by molecular imaging. These findings underline the potential of S100-DAMPs as a serum and imaging biomarker for disease severity in seronegative arthritis.
Dilatation endoscopique et achalasie: facteurs prédictifs de mauvaise réponse
Authors: D Gargouri, M Sabbah, A Ouakaa-Kchaou, A Kochlef, N Bibani, H Elloumi, J Kharrat, A Ghorbel
Journal: Endoscopy (2012)

La dilatation pneumatique endoscopique est un traitement efficace de l'achalasie. La récidive des symptômes nécessite parfois de nouvelles séances de dilatation endoscopique ou même le recours à la chirurgie. Le but de ce travail est d'identifier les facteurs prédictifs de mauvaise réponse à la dilatation endoscopique au cours de l'achalasie.