tbuckley/cabot-search huggingface dataset:
AB1036 Misclassification of patients with osteoporosis according to the used reference curve:
Authors: N. Hammoumraoui, M. El Rakaawi, C. Haouichat, D. Hanoune, S. Abrouk, F. Sadouki, R. Allat, H. Djoudi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Differences between populations in bone mineral density reference curve are widely reported. The use of a reference other than its own may lead to an excessive osteoporosis diagnosis. <h3>Objectives</h3> The purpose of this study is to determine the prevalence of misclassified post-menopausal women regarding their bone density status according to different reference peak bone masses. <h3>Methods</h3> This is a population-based study, carried out in Douera city (50 000 inhabitants town near Algiers). One thousand two hundred and fifty five (1255) post-menopausal women were randomly selected. For all of them a bone mineral density was obtained using a Hologic QDR 2000 apparatus. Both hip and spine sites were measured. Patients were classified (normal, osteopenia or osteoporosis) according to the world health organization osteoporosis classification. For the calculation of the T-score we used the peak bone mass of a local study and the OFELY (osteoporose femme deLyon) one. The percentage of misclassified subjects for different bone status stages is calculated. <h3>Results</h3> The mean study population age is: 61.7 years. The number of misclassified women was nearly the same at both the hip and the spine sites. When classifying the subjects by taking in account the lowest site (international society for clinical densitometry recommendation) 9% of women are misclassified. These results are summarized in the following table. <h3>Conclusions</h3> This study showed that there are a great number of misclassified women. This leads to prescribe an unnecessary expensive treatment for women who have osteoporosis but who have actually osteopenia. <h3>Disclosure of Interest</h3> None Declared
SC-28 * NOVEL INHIBITORS ON HEDGEHOG PATHWAY TO PREVENT MEDULLOBLASTOMA RELAPSE
Authors: J. Rodriguez-Blanco, L. Bin, V. Martin, E. Lee, C. Rodriguez, A. Capobianco, D. J. Robbins
Journal: Neuro-Oncology (2014)

Medulloblastoma (MB) is a highly malignant brain tumor affecting predominantly children. MB arises from cerebella stem cells that do not respond to cellular cues to stop dividing, resulting in them becoming Cancer Stem Cells (CSC). These CSCs are resistant to most conventional chemotherapies, and thus ultimately become the source of tumor relapse. One sub-type of MB harbors a constitutively active Hedgehog (HH) signaling pathway. Recently a large number of HH-inhibitors, mostly that target Smoothened (SMO) have been developed for MB treatment. Unfortunately, one of these inhibitors (vismodegib) also revealed a rapid selection for resistant cells and aggressive relapses likely driven by CSCs. We are focused on alternative targets to SMO for MB- through CSCs eradication. We use mice that spontaneously develop MB: PTCH1+/-p53+/-. It has been described that CSCs isolated from MBs developed on these mice become enriched for genes related to HH signaling. PTCH1+/-p53+/- MB CSCs grown in culture show neuronal stem cells markers, self-renewal, are multipotent and tumorigenic in vivo. We isolated CSCs from these tumors and treated them with a panel of putative inhibitors to identify those that affect CSC survival and self-renewal in vitro, and tumor initiation in vivo. A number of these inhibitors also affect survival of the CD15+ population within the CSCs culture, and abolish its ability to self-renew. Novel drugs acting on HH dependent MB, which do not target SMO, would allow the clinical oncologist to bypass the mechanism of tumor resistance observed in response to SMO antagonists.
Abstract 294: Protein interactions of PTEN and its cancer-associated G20E mutant compared by SILAC-based parallel affinity purification and mass spectrometry
Authors: Jayantha Gunaratne, Mei Xian Goh, Swa Lee Foon, Fen Yee Lee, Emma Sanford, Loke Meng Wong, Kelly Hogue, Walter Blackstock, Koichi Okumura
Journal: Cancer Research (2010)

Abstract The tumor suppressor PTEN (phosphatase and tensin homologue) negatively regulates the phosphatidyl-inositol-3-kinase (PI3K) pathway through its lipid phosphatase activity and is one of the most commonly lost tumor suppressors in human cancers. Though the tumor suppressive function involves PTEN's lipid phosphatase-dependent and -independent activities, the mechanism leading to the phosphatase independent function of PTEN is poorly understood. Some PTEN mutants have lipid phosphatase activity but fail to suppress cell growth. Here we use a cancer associated mutant, G20E, to gain insight on the phosphatase independent function of PTEN by investigating protein-protein interactions using stable isotope labeling by amino acids in cell culture (SILAC). A strategy named parallel affinity purification (PAP) and mass spectrometry (MS) has been developed to allow prioritizing interactors acquired from SILAC pull-downs and the comparison of the interactions between wild-type and G20E PTEN. Liquid chromatography-MS analysis of tryptic digested SILAC-PAP pull-downs revealed known and new interactors. Hierarchical clustering of the heat map generated from the proteins with elevated SILAC ratios from PAP-MS analysis show three distinct clusters: 1) wild-type specific interactors, 2) those unique to the G20E mutant and 3) proteins common to wild-type and mutant. Pathway analyses indicate that the new interactors can be subdivided into apoptosis, cell migration, polarity and the Ca2+ signaling network. These finding contribute to a better understanding of the novel mechanisms of PTEN's phosphatase dependent and independent functions. 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 294.
Abstract 1181: Association between DNA methylation profile and neo-adjuvant treatment response in breast cancer patients.
Authors: Ji-Yeob Choi, Taehyun Kim
Journal: Cancer Research (2013)

Abstract Epigenetic alterations are common in breast cancer, yet how these modifications contribute to chemotherapy response is poorly understood. This study aimed to define a DNA methylation profile associated with response to neo-adjuvant treatment in breast cancer and to identify possible candidate genes associated with resistance as predictors. Eleven pre-treatment and 12 post-treatment serum samples with 6 pairs of FFPE tissues were collected in neo-adjuvant chemotherapy with operable and locally advanced breast cancer. Illumina HumanMethylation450K BeadChip technology for serum DNA and Roche Nimblegen Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Arrays, MeDIP-chip technology for FFPE DNA were used for simultaneous analysis of 450,000 CpG sites for serum DNA and 27,728 for FFPE DNA, respectively. Genes generated from pre-treatment samples were compared with those genes obtained from post-treatment samples, which showed differential modulation following neo-adjuvant chemotherapy. Association on 11 pre-treatment serum DNA highlighted 102 genes significantly related to Ki67 level change as the treatment response (p =0.2) after excluding genes changed by neo-adjuvant chemotherapy. Among them, 16 genes showed consistent methylation levels between serum and tissue (hypermethylation including ITIH3, p-value=0.0015, 8.9 fold-change; hypomethylation including ARID3A, p-value=0.0037, 1.4 fold-change). Hypomethylation of DBH, PRDM16, SLC12A7 and VSX2 in pre-treatment serum and tissue DNA were also predicted to another response surrogate measured by the changes of tumor size (p =0.2). Our study suggests that testing for methylation levels of genes identified in this study may be beneficial in predicting individual patient response to neo-adjuvant therapies. Citation Format: Ji-Yeob Choi, Taehyun Kim. Association between DNA methylation profile and neo-adjuvant treatment response in breast cancer patients. [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 1181. doi:10.1158/1538-7445.AM2013-1181
SP0151 Improving risk communication in RA
Authors: L. Fraenkel
Journal: Annals of the Rheumatic Diseases (2013)

Decision support tools are frequently developed for preference-sensitive decisions in which there are no clear dominant choices (e.g. treatment of early stage prostate cancer). Less attention has been paid to supporting patient decision making for situations in which evidence-based guidelines strongly recommend a specific treatment approach that is likely to significantly benefit most, if not all, patients. A notable example is the underuse of disease modifying drugs in patients with rheumatoid arthritis (RA). American and European guidelines strongly recommend treat-to-target strategies to minimize inflammation based on strong evidence that patients treated according to these protocols have a substantially reduced risk of future disability and morbidity. Nonetheless, many patients are undertreated. Recent studies suggest that this may be, in part, due to ineffective risk communication and poor patient-physician communication. Risk communication is particularly challenging in this situation because of the large number of risks to disclose, the difficulty of explaining the risks of extremely rare, but dreaded, adverse events, and the tendency for people to discount future benefits. We developed a web-based decision support tool to effectively inform patients and promote high quality decision making in RA patients. The content and formatting of the tool were developed based on Fuzzy-trace theory (FTT) principles. FTT provides an evidence-based approach to help patients extract the central gist (essential bottom line) of available options and retrieve and apply relevant values in order to make value-concordant decisions. In a pre-post test study, using the tool resulted in improved knowledge, improved values clarity, and increased willingness to escalate care. Most importantly, the tool significantly increased the likelihood of making an informed, value-concordant choice. <h3>Disclosure of Interest</h3> None Declared
P01.19 * A GENOME-WIDE RNAI SYNTHETIC LETHAL SCREEN FOR SENSITIZERS OF GLIOBLASTOMA MULTIFORME TO TEMOZOLOMIDE
Authors: T. A. Johannessen, A. Grudic, T. Sundstrom, J. K. Varughese, M. Lund-Johansen, R. Bjerkvig, L. Prestegarden
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is highly resistant to therapy and carries a dismal prognosis. Standard of care includes surgery followed by radiotherapy (RT) with concurrent and adjuvant chemotherapy with temozolomide (TMZ). The addition of TMZ to RT increases the overall survival by approximately 3 months compared to RT alone, but there are virtually no long-term survivors. In this work we sought to identify small-molecule sensitizers to TMZ in GBM by integrating a genome-wide lentiviral shRNA library screen with the Connectivity Map database. We first transfected the human GBM cell line U87 with a pooled RNAi library targeting approximately 5000 genes, and incubated the cells at three sub-lethal TMZ concentrations or in control medium. DNA was extracted from both treated and untreated cells at 12 days. Barcodes identifying each shRNA were amplified by PCR and quantified using next-generation sequencing. Individual silencing of 292 genes lead to significantly reduced cell growth in the treated population while silencing of 414 genes increased cellular viability compared to the control group. The Connectivity Map database was then interrogated using these results to identify small-molecule inhibitors that would induce analogous changes in gene expression. This integrated high-throughput approach identified a broad range of compounds with potential cytotoxic activity such as the anti-psychotic thioridazine, the phytoestrogen resveratrol, the antibiotic furazolidone, and the proteasomal inhibitor MG-262. Upon validation in low-throughput cytotoxicity assays, we found these compounds effective as single-agent therapies, but also synergistic with concomitant TMZ therapy. Several of these compounds have previously been implicated in anti-cancer therapy, but not as synthetic lethal partners of chemotherapeutic drugs. Interestingly, we found a prominent cytotoxic effect of the dopamine receptor antagonist thioridazine when given as monotherapy and as combination therapy with TMZ. The therapeutic potential of thioridazine and concomitant TMZ in vivo is currently being explored in a clinically relevant intracranial GBM animal model.
The Incidence of Primary Cardiac Arrest during Vigorous Exercise
Authors: David S. Siscovick, Noel S. Weiss, Robert H. Fletcher, Tamar Lasky
Journal: New England Journal of Medicine (1984)

To examine the risk of primary cardiac arrest during vigorous exercise, we interviewed the wives of 133 men without known prior heart disease who had had primary cardiac arrest. Cases were classified according to their activity at the time of cardiac arrest and the amount of their habitual vigorous activity. From interviews with wives of a random sample of healthy men, we estimated the amount of time members of the community spent in vigorous activity. Among men with low levels of habitual activity, the relative risk of cardiac arrest during exercise compared with that at other times was 56 (95 per cent confidence limits, 23 to 131). The risk during exercise among men at the highest level of habitual activity was also elevated, but only by a factor of 5 (95 per cent confidence limits, 2 to 14). However, among the habitually vigorous men, the overall risk of cardiac arrest--i.e., during and not during vigorous activity--was only 40 per cent that of the sedentary men (95 per cent confidence limits, 0.23 to 0.67). Although the risk of primary cardiac arrest is transiently increased during vigorous exercise, habitual vigorous exercise is associated with an overall decreased risk of primary cardiac arrest.The risk of cardiac arrest during vigorous exercise is examined in the context of the relationship between the risk of cardiac arrest and vigorous exercise in general. The data concern 133 men who had primary cardiac arrest in Washington State between 1979 and 1981 and a control group of healthy men. The data were obtained through interviews with the men's wives. The results indicate that the risk of cardiac arrest during exercise is higher than at other times, especially among those with low levels of habitual activity; however, among habitually vigorous men, the overall risk of cardiac arrest (during and not during vigorous activity) is only 40 percent that of sedentary men.
Lymphocytic Bronchitis Associated with Graft-versus-Host Disease in Recipients of Bone-Marrow Transplants
Authors: William E. Beschorner, Rein Saral, Grover M. Hutchins, Peter J. Tutschka, George W. Santos
Journal: New England Journal of Medicine (1978)

Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.
Abstract 3202: Universal detection of protein phosphorylation based on multi-functionalized soluble nanopolymers
Authors: Anton Iliuk, Li Pan, Shawn Liu, Juan Martinez, Mark Hall, Xiaoqi Liu, Andy Tao
Journal: Cancer Research (2012)

Abstract Protein phosphorylation, as the most common covalent modification of proteins, plays a critical role in the regulation of many cellular functions. Irregularities in phosphorylation network are a major cause of onset and progression of many diseases, most notably cancer. Consequently, detection of protein phosphorylation is essential in further understanding of cellular signaling pathways and mechanisms of cell growth and proliferation. To assist in effective phosphorylation analyses, we introduce here a novel technique based on soluble nanopolymers with excellent solubility, compact spherical shape and chemical homogeneity. Soluble nanopolymers functionalized with Ti(IV) ions have shown highly versatility and allow for highly efficient analyses of phosphorylation and signaling pathways. We devise here a novel strategy, termed pIMAGO (phospho-imaging), for effective detection of phosphoproteins on a membrane (Western Blot format) or in a 96-well plate (ELISA format). Unlike antibody-based strategies, the new method is capable of selectively binding a phosphorylated residue independent of amino acid microenvironment. It shows no preference for either of the phosphosites, and thus holds great promise in biological analyses where the site of phosphorylation is not known or its specific antibody is not available. Using this technique, the phosphorylation levels of proteins of interest under physiological conditions can be readily detected as part of a standard Western Blot or ELISA procedures without the need for radioactivity or expensive phosphosite-specific antibodies. The utility of the approach has been demonstrated using standard mixtures of proteins, by in vitro kinase and phosphatase assays, as well as with kinase inhibitor screening and enzyme profiling. In addition, multiplexing capabilities of pIMAGO are presented, a feature often unavailable during antibodies-based detection. Finally, we further confirmed that the technique is sensitive and specific enough to detect endogenous phosphorylation changes by analyzing physiological signaling in number of endogenous protein complexes isolated directly from cells. 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 3202. doi:1538-7445.AM2012-3202
SAT0259 ASAS Classification Criteria for Axial Spa Were Superior to ESSG and Amor Criteria in Distinguishing Spa Patients Among Patients with Chronic Back Pain: Results of a Two-Year Follow-Up Study From China
Authors: Z. Liao, Z. Lin, Q. Li, J. Huang, Y. Pan, T. Li, Z. Hu, O. Jin, Y. Zhang, M. Yang, Y. Wu, J. Gu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In 2009 the Assessment of SpondyloArthritis international Society (ASAS) developed the new classification criteria for axial spondyloarthritis in a large cohort of patients with recent-onset low back pain. <h3>Objectives</h3> To evaluated the value of ASAS criteria in distinguishing axial SpA patients from other back pain patients in a 2-year following-up study, comparing to ESSG criteria and Amor criteria. <h3>Methods</h3> Patients with chronic back pain ≥3 months and age at onset before 45 were enrolled and clinical parameters were collected, especially the SpA features. On the first visit, patients were divided into two groups of fulfilling the ESSG criteria, Amor criteria or ASAS classification criteria or not. Final diagnosis of axial SpA and non-SpA were confirmed by rheumatologists after 2-year follow-up. Chi-square test was performed to test the association between the expert’s opinion and each set of classification criteria, respectively. P&lt;0.05 was considered to be significantly difference. <h3>Results</h3> Eight hundred and sixty-seven patients with chronic back pain were enrolled and diagnosed as 455 axial SpA patients and 412 non-SpA patients after 2-year follow-up. On the first visit, the ASAS criteria could distinguish more SpA patients than ESSG criteria and Amor criteria, and more non-SpA patients than ESSG criteria and Amor criteria. Chi-square test showed the ASAS criteria had better distinguishing coincidence (Kappa=0.7593) than both ESSG criteria (Kappa=0.5926) and Amor criteria (Kappa=0.6469). <h3>Conclusions</h3> ASAS axial SpA classification criteria showed superior value to ESSG criteria and Amor criteria on diagnosing axial SpA patients from Chinese patients with chronic back pain. <h3>Acknowledgements</h3> The study was supported by the grants of clinical subject (2007) of Ministry of public health of China and 5010 Subject of Sun Yat-sen University. <h3>Disclosure of Interest</h3> None Declared
PTH-027 Anaesthesia-led Propofol Sedation For Complex Endoscopy: Climbing Higher: Abstract PTH-027 Table 1
Authors: C Quarterman, M Davies, HL Smart, N Taggart, S Sarkar
Journal: Gut (2014)

<h3>Introduction</h3> NHS indicators for quality improvement (QI) are divided into key domains - safety, experience, outcome and effectiveness. Patient experience has been shown to be positively related to clinical effectiveness and safety and should not be overlooked when assessing the effectiveness of a service. The introduction of a new Anaesthesia-Led Propofol Sedation (ALPS) service in 2012 was pivotal in managing patients undergoing complex endoscopic procedures. Our aim was to establish a continuous quality improvement programme to take an already successful service and pursue excellence. <h3>Methods</h3> Measures and scores were agreed within the domains of patient optimisation, outcome and experience, and service efficiency. A composite score was used as an Excellence Score. All patient episodes were scored by the same anaesthetist using a 3-point qualitative scale; fully (&gt;95% complete, 2 points), largely (75–95% complete, 1 point) and partially/not achieved (&lt;75% complete, 0 points). Individual domain scores and the Excellence Score were presented as a percentage, in terms of the current service and “What If” scores to show the impact of changing practice. Patient experience was measured indirectly and with a telephone questionnaire at one-week post-discharge. Results were discussed in an MDT focus group, interventions instigated and the data recollected three months later and re-discussed. <h3>Results</h3> 40 consecutive patients attending for complex endoscopic procedures from January to June 2013 were reviewed. Table 1 shows scores during the first three months and the influence of implemented changes. Across all scores, improvement was seen, particularly in the Efficiency Score which increased by 22%. A patient optimisation score reflected a guideline-compliant service, but was initially low due to a lack of pre-assessment and individualised patient preparation, and sporadic use of an adapted WHO Surgical Safety Checklist. A “What If” score of 82% was presented, showing the potential service gains in the presence of these additions. Consequently managers agreed to fund use of the Hospital Preoperative Assessment Service and clinical staff agreed to implement regular use of an adapted WHO Safe Surgery Checklist. <h3>Conclusion</h3> Achieving excellence depends upon acknowledging weaknesses in practice that may already be very good. This study has shown the value of a quality improvement programme in improving a new, innovative service. Often adoption of care elements used routinely elsewhere within the hospital setting can lead to significant improvements in patient care and the efficiency of the service. <h3>Disclosure of Interest</h3> None Declared.