tbuckley/cabot-search huggingface dataset:
PWE-102 Elucidating The Role of Non JEJUNI/Coli-Campylobacter in The Development of Colorectal Cancer Utilising Comparative Genomics to Study Their Pathogenic Potential
Authors: I Mukhopadhya, T Hsu, H Nielsen, H Nielsen, S Berry, C Huttenhower, GL Hold
Journal: Gut (2016)

<h3>Introduction</h3> Emerging evidence links the gut microbiota to colonic inflammation and colorectal cancer (CRC). Studies have shown over-representation of oral bacterial species including <i>Campylobacter</i> spp. in CRC tissue and also njc-<i>Campylobacter </i>are over-represented in IBD wherein normal homeostasis has been lost. Understanding the role of njc<i>-Campylobacter</i> as an aetiological agent in CRC and elucidating their pathogenicity characteristics is of immense clinical importance. <h3>Aim</h3> To perform whole genome sequencing (WGS) of clinically derived njc-<i>Campylobacter</i> to compare/identify virulence traits potentially linked to disease presentation. <h3>Methods</h3> WGS of 21 unique clinically derived <i>Campylobacter</i> isolates was performed (7 <i>Campylobacter</i><i> showae</i>, 3 <i>Campylobacter</i><i> ureolyticus</i> and 11 <i>Campylobacter</i><i> concisus</i>) from biopsy/faecal samples of subjects with malignancy, acute enteritis and IBD. DNA was extracted using the QIAamp DNA Mini Kit. Libraries were prepared using Illumina Nextera XT DNA Library Prep Kit and Nextera XT Index Kit v2, multiplexed, and paired-end sequenced on the Illumina MiSeq. <i>De novo read </i>assembly used the A5-miseq pipeline with QUAST. Genome annotation was performed using the rapid prokaryotic genome annotation tool Prokka. <h3>Results</h3> Genome assembly of <i>C. showae </i>strains resulted in 8 to 59 contigs per strain (mean number = 21; average genome size 2,199,446 nucleotides); <i>C. concisus </i>isolates had an average contig number of 72 and average genome size of 1,982,586 nucleotides. <i>C. ureolyticus </i>strains average contig number was 134 and average genome size of 1,608,008 nucleotides. Through Prokka annotation, the average number of coding sequences was 2215 for <i>C. showae </i>isolates (range 2050–2368) with function predicted for ~71.3%. For <i>C. concisus </i>the average number of coding sequences was 1985 (range 1833–2087) with function predicted for ~ 71.9%. <i>C. ureolyticus </i>had a lower number of coding sequences (average 1613) with function predicted for ~72.6%. We focused on the VirB4/D10 operon homologs, which are components of the Type IV secretion system. Contrary to previously published sequence data from oral strains, the majority of colonic <i>C. showae </i>isolated and 2 <i>C</i><i>. concisus </i>strains possessed almost complete T4SS systems and additional virulence traits, including the exotoxin 9 gene. <h3>Conclusion</h3> The findings clearly demonstrate genetic differences among colonic <i>Campylobacter </i>isolates as compared to oral strains and sheds light on the pathogenic potential of these emerging colonic pathogens. The findings also further highlight the need for further sequencing studies to be undertaken. <h3>Disclosure of Interest</h3> None Declared
LNK (SH2B3) Synergizes with TP53 in Suppressing B-Precursor Acute Lymphoblastic Leukemia through IL-7 Receptor Signaling
Authors: Ying Cheng, Kudakwashe Chikwava, Chao Wu, Anchit Bhagat, John K. Choi, Wei Tong
Journal: Blood (2014)
Gulf War Veterans’ Health: A Comprehensive Medical Evaluation of a Population Based Cohort
Authors: S. Cohort, F. Eisen, D. Murthy, L. Toomey, R. Jackson, B. Alpern, Nancy G. Klimas, C. Hall, H. Pak, J. Hunter, J. Karlinsky, M. Battistone, M. Lyons
Journal: JAMA (2003)
Growth Factor Deprivation Combined with Prolonged Inhibition of BCR-ABL Does Not Eradicate Functional CML Stem Cells
Authors: Ashley Hamilton, Gudmundur V Helgason, Elaine Allan, Michael J. Alcorn, Franck E Nicolini, Allison Blair, Mirle Schemionek, Steffen Koschmieder, Valerie G Brunton, Tessa L Holyoake
Journal: Blood (2008)
Role of Type 2 Diabetes in Determining Retinal, Renal, and Cardiovascular Outcomes in Women With Previous Gestational Diabetes Mellitus
Authors: Ravi Retnakaran, Baiju R. Shah
Journal: Diabetes Care (2016)

OBJECTIVE Women who have gestational diabetes mellitus (GDM) have elevated lifetime risks for the development of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), compared with their peers. However, it is not known whether their risk of CVD is dependent upon the development of T2DM. Thus, we sought to evaluate the role of T2DM in determining vascular outcomes in women with previous GDM. RESEARCH DESIGN AND METHODS All women in Ontario, Canada, with a live-birth pregnancy between April 1994 and March 2014 (n = 1,515,079) were stratified into the following four groups: women with GDM in whom T2DM subsequently developed (n = 15,585, median age 32 years); those with GDM in whom T2DM did not develop (n = 41,299; median age 32 years); women who did not have GDM but in whom T2DM developed (n = 49,397; median age 31 years); and those with neither GDM nor T2DM (n = 1,408,798; median age 30 years). Women were followed over a median time of 10.0 years for the development of microvascular and macrovascular outcomes. RESULTS Among women who had GDM, only those in whom T2DM developed had an increased risk of vitrectomy/photocoagulation (hazard ratio [HR] 4.49, 95% CI 3.90–5.17), renal dialysis (HR 7.52, 5.24–10.81), and hospitalization for foot infection (HR 4.32, 3.42–5.46) (all P &amp;lt; 0.0001). However, for macrovascular outcomes, both women with GDM in whom T2DM developed and those in whom T2DM did not develop had increased risks of CVD (HR 2.82; 2.41–3.30; P &amp;lt; 0.0001; and HR 1.30; 1.07–1.59; P = 0.008, respectively) and coronary artery disease (HR 3.54; 2.96–4.23; P &amp;lt; 0.0001; and HR 1.41; 1.11–1.80; P = 0.005, respectively), although absolute event rates were very low. CONCLUSIONS Women with GDM have an elevated risk of cardiovascular outcomes, even in the absence of T2DM. In contrast, microvascular risk emerges only in those in whom T2DM develops.
PWE-021 Targets for Health Interventions for Inflammatory Bowel Disease-Fatigue
Authors: M Artom, C Norton, W Czuber-Dochan, J Sturt
Journal: Gut (2016)

<h3>Introduction</h3> Fatigue is a complex, multifactorial and multidimensional phenomenon. Recognition of modifiable correlates of fatigue can provide a further understanding of this phenomenon in patients with inflammatory bowel disease (IBD) and aid in the development of interventions tailored towards fatigue. The aim of the present review was to systematically search and synthesise available evidence on potentially modifiable factors contributing to IBD-fatigue and what advances in the management of fatigue in individuals with IBD have been made. <h3>Methods</h3> The review was comprised of a systematic search and a selective review. The process of selection of the retrieved citations was undertaken in two phases: i) systematic search for new studies published since the search of the previous review by Czuber-Dochan and colleagues in August 2012 (n = 21); ii) reselection of papers (n = 28) included in Czuber-Dochan and colleagues according to the aims of the current review. Seven databases were searched: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, the Cochrane Library and the British Nursing Index. The search included quantitative observational designs and experimental studies. <h3>Results</h3> Forty-three studies met the inclusion criteria, 27 cross-sectional studies, 7 longitudinal studies, 1 quantitative secondary data analysis, 7 RCTs and 1 open label pilot study. Studies were conducted in out-patient settings and with population-based cohorts. The quality of included papers was assessed using the Critical Appraisal Skills Programme. The studies were classified as high (n = 15), medium (n = 19) and low quality (n = 9), no studies were excluded on the basis of quality. IBD-fatigue was consistently associated with disease activity, depression, anxiety and sleep difficulties. However, most studies were cross-sectional thus the direction of causation remains unknown. The relationship between biochemical factors, such as anaemia and inflammation, and fatigue was inconsistent. Adding to the existing 5 interventions since the last review in 2013 only 3 interventions were tested to address IBD-fatigue. One assessed the effects of thiamine, one compared exercise advice, omega-3 oil fish oil, a dietary consultation and placebo and the last comparing solution focused therapy and care as usual. Findings from psychosocial and exercise interventions were promising. Nonetheless, interventions continue to be sparse, with methodological limitations and only short-term effects. <h3>Conclusion</h3> The review identified a number of psychosocial and physical factors, which could potentially be modified through targeted health interventions to improve fatigue in IBD. Research utilising prospective observational studies and RCT design is required to develop and test interventions to reduce fatigue, most likely within a biopsychosocial model of care. <h3>Disclosure of Interest</h3> None Declared
AB1081-HPR Pharmacological Adherence To Conventional or Biological Therapy in Patients with Rheumatoid Arthritis in A Colombian Specialized Rheumatology Center
Authors: N. Palacio, P. Santos-Moreno, L. Villarreal, G. Ballesteros, J. Bello, E. Castillo, R. Giraldo, D. Gomez, A. Aza, A. Lopez, A. Cardozo, C. Castro, D. Buitrago-Garcia
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The lack of pharmacological adherence and consecutive therapeutic failure is a prevalent and relevant problem in clinical practice, especially in the treatment of chronic diseases such as rheumatoid arthritis (RA). In the context of chronic diseases, World Health Organization considers lack of adherence like a public health priority because represents negative consequences like: therapy failures, higher rates of hospitalization and increased costs of health care. <h3>Objectives</h3> The aim of this observational study was determine adherence to treatment in patients with RA, their demographic characteristics and clinical variables. <h3>Methods</h3> An observational, descriptive cross sectional study conducted in a non-probability sample of convenience in patients with RA who consult to rheumatology institution specialized in RA patients. Descriptive epidemiology was applied for continuous variables, measures of central tendency and dispersion for categorical and qualitative variables (averages/percentages); we used Pearson9s chi-squared test (χ<sup>2</sup>) and T student test to evaluate bivariate correlation. <h3>Results</h3> 356 patients were included, 186 (52%) received DMARDs therapy and 170 (48%) biological therapy. 309 (86%) were female and 47 (43%) were male meanDAS28 was 2.5 ± 1 HAQ was 0.87 ± 1.3. The most frequent comorbidity was osteoporosis 145 (40%) and hypertension 135 (37%). 103 (28%) participants suspended the medication when they felt polimedicated. In the group using DMARDs 71 (38%) suspended the medication due to an adverse event and in the biological therapy group 55 (32%). 71 (38%) patients in the group with DMARDs referred administrative difficulties while in the group with biological therapy 56 (32%) referred the same issue. When we explored the adherence, regarding age the group where we found fewer adherence in the group between 40 and 60 years this correlation was not statistically significative. When patients suspended the medication when they felt medicated with many drugs mean DAS28–2.6 higher than who did not suspend medication mean DAS28–2.4. When the medication due to an adverse event was suspended mean DAS28–2.57 higher than those who did not suspend the medication (DAS28–2.46) and was statistically significative. <h3>Conclusions</h3> This study shows that most of patients (two thirds) are adherent to conventional or biological treatment; however a important number remains non-adherent with a higher DAS28 score with clinical and economical implications. <h3>Disclosure of Interest</h3> None declared
PWE-091 Limited Impact on Colorectal Cancer Detection and Mortality Rates with Complete Colonoscopy Examination Despite Poor Bowel Preparation
Authors: A Masding, Z Cargill, N Aveyard, S Musa, A Alisa, K Tang
Journal: Gut (2016)

<h3>Introduction</h3> Achieving key quality indicators of colonoscopy are recognised to be associated with quality of bowel cleansing.<sup>1</sup> However, the impact of bowel preparation quality on colorectal cancer (CRC) detection and associated mortality rates is unclear. Limited published studies report conflicting results correlating detection of pre-malignant lesions with quality of bowel preparation and do not report on colorectal mortality.<sup>2</sup> Current guidelines suggest that if bowel preparation is poor, colonoscopy should be repeated within 1 year.<sup>3</sup> Aim: To determine the prevalence of poor bowel preparation in patients achieving complete colonoscopy, and its association with polyp detection, CRC, and mortality rates within a large district general hospital. <h3>Methods</h3> All patients with poor bowel preparation (Boston Bowel Preparation Scale &lt;5) undergoing colonoscopy by a single endoscopist were identified using the UNISOFT database over 5 years (2006–2010). Electronic records were analysed to identify indication for colonoscopy, completion rates, adenoma detection rate (ADR), diagnosis, 1 and 5 year mortality rates, and number of repeat colonoscopies/completion CT colonography. <h3>Results</h3> 990 colonoscopies were performed (ADR 26%). 208/990 (21%) had poor bowel preparation (M:F 103:105, mean age 62 years). Of these, 197/208 (95%) had complete colonoscopy to the terminal ileum, caecum or anastomosis and 51/208 (25%) underwent repeat colonoscopy/CT colonography. 86/208 (41%) had indications of anaemia, previous polyps, previous CRC and abnormal imaging. Of these, 9% (n = 8/86) were found to have CRC. There was a 3/86 (3.5%) 1 year mortality rate, and 24/86 (28%) 5 year mortality rate, none from CRC. In a comparison group with the same indications for colonoscopy and good bowel preparation (n = 69), 1 and 5 year mortality rates were 2.9% (2/69) and 7.3% (n = 5/69), respectively, 1 of which resulted from CRC. <h3>Conclusion</h3> The quality of bowel preparation does not significantly impact on CRC detection or mortality rates if complete colonoscopy examination is achieved. Early repeat colonoscopy/CT colonography within 1 year may not be necessary and subsequent examination could be at the standard recommended surveillance interval. <h3>References</h3> 1 Hassan, <i>et al</i>. Bowel preparation for colonoscopy: ESGE Guideline. <i>Endoscopy</i> 2013;<b>45</b>:142–150. 2 Wong, <i>et al</i>. Determinants of Bowel Preparation Quality and Its Association With Adenoma Detection. <i>Medicine (Baltimore)</i> 2016;<b>95</b>(2). 3 Lieberman, <i>et al</i>. 2012. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the us multi-society task force on colorectal cancer. <i>Gastroenterology</i><b>143</b>(3):844–57. <h3>Disclosure of Interest</h3> None Declared
Abstract 5324: Selective Inhibition of HDAC6 regulates preferential cytotoxicity in cancer cells by modulating p53 and Hsp90 stability
Authors: So Hee Kwon
Journal: Cancer Research (2015)

Abstract A HDAC6-selective inhibitor is a promising new therapeutic agent for cancer treatment, but its precise mechanisms of actions are not well understood. In particular, the relevance of p53 for HDAC6 inhibitor-induced effects has not been fully elucidated. Here, we show that a γ-lactam based HDAC inhibitor A452 selectively inhibits HDAC6 catalytic activity in vivo and in vitro. A452 causes cell death as well as growth inhibition of transformed cells not observed in normal cells. A452 exhibits differential cytotoxicity for wild-type (wt) and mutant p53 (mutp53) human colorectal cancer cells. Interestingly, A452 shows different mechanisms of action of modulating p53 in cancer cells. A452 increases wtp53 by destabilizing MDM2 and MDMX. In contrast, A452 causes mutp53 destabilization by inhibiting complex formation between Hsp90 and hyperstable mutp53, which is a hallmark of p53 mutation and cancer cell-specific. A452 also chemosensitizes cancer cells differing in p53 status for chemotherapy due to its ability to degrade mutp53 and stabilize wtp53. Intriguingly, acetylation of Hsp90 by A452 results in its degradation as well as inactivation of its chaperone activity. Furthermore, A452 effectively suppresses cell migration and invasion. These results demonstrate that A452 is a specific HDAC6 inhibitor and requires for p53 and Hsp90 for inducing anticancer action. Therefore, these results suggest that therapeutic targeting of HDAC6 may represent a new way to treat cancers expressing mutant forms of p53. Citation Format: So Hee Kwon. Selective Inhibition of HDAC6 regulates preferential cytotoxicity in cancer cells by modulating p53 and Hsp90 stability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5324. doi:10.1158/1538-7445.AM2015-5324
Prognostic Value of Interim PET/CT in Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL). Experience of the Spanish Geltamo Group
Authors: Mónica Coronado, Emilia Pardal, Rosa Couto, Fatima de la Cruz, Carlos Panizo, Carlos Grande, Reyes Arranz, María José Ramirez, Roberto Hernández, Alejandro Martin, Dolores Caballero
Journal: Blood (2012)
Studies of BP-1-102, a Novel Direct Small-Molecule Inhibitor of Stat3 Demonstrates Substantial Anti-Myeloma Pre-Clinical Activity
Authors: Victor H Jimenez-Zepeda, Zhi Hua Li, Brent DG Page, Seda Zeng, Ellen Wei, Chungyee Leung-Hagesteijn, James Turkson, Patrick T. Gunning, Suzanne Trudel
Journal: Blood (2010)
Use of Recombinant Factor VIIa (rFVIIa) for Acute Bleeding Episodes in Acquired Hemophilia: Final Analysis From the Hemostasis and Thrombosis Research Society (HTRS) Registry AH Study
Authors: Alice D. Ma, Craig M. Kessler, Hamid A B Al-Mondhiry, Margaret Fisher, Robert Z. Gut, David L. Cooper
Journal: Blood (2012)
A Phase II Study Using Post-Transplant Cyclophosphamide (PTC) As Graft Versus Host Disease (GVHD) Prophylaxis in Patients Undergoing HLA Matched Sibling Donor Stem Cell Transplant (SCT) for Severe Aplastic Anemia (SAA)
Authors: Biju George, Vikram Mathews, Kavitha M Lakshmi, Rayaz Ahmed, Aby Abraham, Alok Srivastava
Journal: Blood (2012)
SAT0625 Challenges of Disease-Related Communication in The Daily Lives of Persons with Rheumatic and Musculoskeletal Diseases. Results of A Participatory Research Project
Authors: W. Mau, J. Lamprecht, A.C. Schöpf, M. Schlöffel, E. Farin-Glattacker, A. Thyrolf
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> At least every ninth person with rheumatic and musculoskeletal diseases (RMDs) reports severe limitations of social participation due to multiple health problems and reduced resources [1]. Reduced participation is frequently associated with social interactions and communication around the subject of disease-related problems [2]. These conversations may be necessary for the patients in order to follow their interests or reach certain goals. If the patients experience difficulties in these situations, low communication skills may be significant barriers to social participation. <h3>Objectives</h3> To identify significant factors of disease-related everyday communication of persons with RMDs in a nationwide project funded by the Deutsche Rheumaliga Bundesverband e.V. (DRL). Based on the results, a training to enhance the communication skills of persons with RMDs in various situations significant for social participation will be developed. <h3>Methods</h3> An online questionnaire addressing context, content, difficulties, and burden of the disease-related everyday communication was answered by 1.015 persons with RMDs (87% females, mean age 55 (SD 12) years, mean disease duration 16 (SD 12) years). Communication skills were recorded by the short version of the Insecurity Questionnaire [3]. In this participatory research project four persons with RMDs are involved throughout the project. <h3>Results</h3> More than half of the participants report difficulties in disease-related conversations across various situations. The majority of these persons suffer from this experience as a burden particularly in conversations at the work place or in civil services. Compared to men, women report difficulties more frequently in the private environment and with representatives of public authorities and they feel a higher burden due to difficult conversations in all situations. In comparison with population samples the communication skills of persons with RMDs are lower with higher scores of the scales "fear-of-failure/criticism", "fear-of-contact", and "inability-to-say no" of the Insecurity Questionnaire. <h3>Conclusions</h3> The project offers new insight into the disease-related communication of persons with RMDs. The subsequent training ("KOKOS-Rheuma") will include difficult and strenuous conversations especially at the work place or in civil services. Persons with RMDs will be given exercises for typical situations that require saying no, adequate arguing, and giving feedback in order to reduce fear of failure and criticism. <h3>References</h3> Mattukat, K. &amp; Thyrolf, A., Z Rheumatol 2014;73:2–8. Farin, E., Ullrich, A. &amp; Nagl, M., Health Education Research 2013;28:1080–1091. Albani, C. et al., Psychother Psych Med 2006;56:18–127. <h3>Disclosure of Interest</h3> None declared
Risk Factors For Clonal Evolution Of Acquired Bone Marrow Failure After Immunosuppressive Therapy In Children
Authors: Asahito Hama, Hideki Muramatsu, Masafumi Ito, Yoshiyuki Kosaka, Masahiro Tsuchida, Yoshiyuki Takahashi, Ryoji Kobayashi, Etsuro Ito, Hiromasa Yabe, Shouichi Ohga, Akira Ohara, Seiji Kojima
Journal: Blood (2013)
Induction Chemotherapy Followed Immediately by Busulfan-Based Reduced Conditioning and Allografting in Elderly Patients with Advanced MDS or sAML.
Authors: Nicolaus Kröger, Tatjana Zabelina, Christine Wolschke, Heinrich Lellek, Thomas Stübig, Maite Lestin, Haefaa Alchalby, Francis Ayuk, Ulrike Bacher, Boris Fehse, Axel R. Zander
Journal: Blood (2009)
Searching for Amplification of Chromosome 5 Segments by Molecular Cytogenetics in 9 Myelodysplastic Syndromes/Acute Myeloid Leukemia (MDS)/(AML) Patients with Apparent Monosomy 5
Authors: Paolo Bernasconi, Irene Dambruoso, Marina Boni, Rita Zappatore, Paola Maria Cavigliano, Ilaria Giardini, Marilena Caresa, Cesare Astori, Carlo Castagnola, Mario Lazzarino
Journal: Blood (2008)