tbuckley/cabot-search huggingface dataset:
OP0089 The Expresion of Tumor Necrosis Factor Related Apoptosis Inducing Ligand in Muscle Tissue of Polymyositis/Dermatomyositis
Authors: H. Zhou, G. Wang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To analyze the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in muscle tissue from patients with polymyositis/dermatomyositis (PM/DM) and the effects of TRAIL on apoptosis of human skeletal muscle cells. To analyze the correlated clinical significance by testing the serum tumor necrosis factor–related apoptosis-inducing ligand (sTRAIL) level of patients with polymyositis/dermatomyositis. <h3>Methods</h3> Muscle biopsy samples and blood samples were selected from 40 PM/DM patients and 20 healthy volunteers. The expression of TRAIL in the muscle tissue was detected by immunohistochemistry. The human skeletal muscle cells were treated with different concentrations of TRAIL (0, 1, 5, 10, 50 ng/mL) in primary culture. The apoptotic rates of primary cultured human skeletal muscle cells were measured by flow cytometry. The level of serum TRAIL was tested by enzyme-linked immunosorbent assay (ELISA). <h3>Results</h3> The expression of TRAIL was found in muscle tissue samples from the PM/DM patients and healthy controls. The expression of TRAIL in the muscle tissue from the PM/DM patients was significantly higher than those from healthy controls (P&lt;0.05). The skeletal muscle cells from PM/DM patients had significantly higher apoptosis rate (%) than healthy volunteers. After 24 hours stimulated by different concentration of TRAIL (0, 1, 5, 10, 50 ng/mL), the apoptosis rate (%) in PM/DM group are:13.72±11.52, 31.23±14.05, 40.09±9.15, 39.91±13.38, 31.32±9.07,respectively.The apoptosis rates in PM/DM group are significantly higher than in control group in same stimulated concentration of TRAIL (P&lt;0.05). And the 5ng/mL stimulated concentration made the highest apoptosis rate. The serum level of sTRAIL in PM/DM patients was 1380.71±126.49 ng/L, which significantly higher than healthy control group9s 493.89±33.32 ng/L (P&lt;0.05). And the serum levels of sTRAIL in PM/DM patients with dysphagia was 1775.76±321.95 ng/L, which was significantly higher than 958.24±155.66 ng/L (P&lt;0.05) from patients without dysphagia. There were no differences between sTRAIL from patients with or without interstitial lung disease (P&gt;0.05). The serum levels of sTRAIL in Jo-1 positive group was 562.36±52.99 ng/L, which was significantly lower than in Jo-1 negative group9s 1334.57±181.21 ng/L (P&lt;0.05). Spearman rank correlation analysis showed that level of sTRAIL was negatively correlated with lactic dehydrogenase (LDH) (r=-4.03, P&lt;0.05). <h3>Conclusions</h3> TRAIL plays a important role in pathogenesis of polymyositis/dermatomyositis and its abnormal expression is closely related to PM/DM patients9 clinical features. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2643
Noninvasive Prenatal DNA Testing: The Vanguard of Genomic Medicine
Authors: Lisa Hui, Diana W. Bianchi
Journal: Annual Review of Medicine (2016)

Noninvasive prenatal DNA testing is the vanguard of genomic medicine. In only four years, this screening test has revolutionized prenatal care globally and opened up new prospects for personalized medicine for the fetus. There are widespread implications for increasing the scope of human genetic variation that can be detected before birth, and for discovering more about maternofetal and placental biology. These include an urgent need to develop pretest education for all pregnant women and consistent post-test management recommendations for those with discordant test results. The reduction in invasive testing has had downstream effects on specialist training and caused many countries to re-examine their national approaches to prenatal screening. Finally, the accumulating datasets of genomic information on pregnant women and their fetuses raise ethical issues regarding consent for future data mining and intellectual property.
AB0930 Non-Response to Colchicine in FMF Should BE Identified Accuratly
Authors: M. Alkan Melikoglu, K. Senel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Colchicine prophylaxis is the single most important factor in ameliorating FMF for the prevention of both attacks and secondary amyloidosis. It is known that some cases donot respond to colchicine prophylaxis. <h3>Objectives</h3> The aim of the present study was to evaluate the exact proportion of those patients who do not respond to the colchicine and to characterize their demographic, sociodemographic and clinical aspects. <h3>Methods</h3> 108 patients with FMF were included in our study. The demographic (age, gender), socioeconomic (education level, employment stataus, economic income level) and clinical features (age at onset of FMF, age at FMF diagnosis, family history of FMF, mean duration of colchicine use and mean daily colchicine dose) of the patients were evaluated. The patients unresponsive to colchicine therapy according to their statement were recorded. Also with another question, patient9s routine colchicines-consuming habits were asked in a self-answering format. Data were analysed with the chi-square test and Fisher9s exact test. <h3>Results</h3> There were 50 female and 58 male patients with a mean age of 42.4±11.3 years. The mean age at FMF onset and at FMF diagnosis were found as 14.3±10.5 and 19.1±12.9 years respectively. % 16 of the patients defined themselves as "suffering from attacks inspite of regular colchicine". Irregular colchicine usage was determined in % 11 of the patients who were considered as "unresponsive to colchicine therapy" according to their statements. In spite of regular colchicine regimen, attacks were present in 5% of the patients in our study. Although there was no difference in demographic and clinical aspects, patients with irregular colchicine usage were found to be from lower socioeconomic backgrounds, had less education and more unemployment (p&lt;0.001). <h3>Conclusions</h3> In conclusion, regular colchicine usage anemnesis may be misleading in the first evaluation and this risk seems to be higher in patients with lower socioeconomic backgounds. Routine colchicine consuming habits should be detailed in patients with FMF before claiming its failure. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2313
Abstract 3145: Smyd3 catalyzes a novel methylation mark and regulates cancer cell proliferation
Authors: Glenn S. VanAller, Nicolas Reynoird, Olena Barbash, Michael J. Huddleston, BaoChau Le, Roland S. Annan, Ben A. Garcia, Peter J. Tummino, Or Gozani, Ryan G. Kruger
Journal: Cancer Research (2012)

Abstract SET and MYND domain-containing protein 3 (Smyd3) is a lysine methyltransferase over-expressed in liver, breast and rectal carcinomas. We have shown that knockdown of Smyd3 has an anti-proliferative effect in cancer cell lines and that this effect can be rescued with wild type but not catalytically inactive Smyd3, directly linking Smyd3 catalytic activity to proliferation. Published reports indicate Smyd3 methylates lysine 4 of histone H3, lysine 20 of histone H4 and VEGFR1. However, activity testing of a peptide library and intact recombinant nucleosomes indicate that a unique methylation mark is catalyzed by Smyd3. LC-MS/MS analysis of in vitro reaction products have identified the location of this novel site of methylation. The existence of this novel mark and its dependence on Smyd3 activity was confirmed in cancer cells and mouse embryonic fibroblasts. We speculate that overexpression of Smyd3 causes aberrant methylation and plays an important role in the deregulation of gene expression leading to uncontrolled cellular proliferation in cancer making Smyd3 a promising target for anti-cancer 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 3145. doi:1538-7445.AM2012-3145
Abstract 1080: Molecular and cellular pharmacology of BI 811283, a potent inhibitor of Aurora B kinase
Authors: Ulrike Tontsch-Grunt, Ulrich Gürtler, Stephan K. Zahn, Guido Boehmelt, Marc Jarvis, Guenther R. Adolf, Flavio Solca
Journal: Cancer Research (2010)

Abstract Background. The serine/threonine kinase Aurora B is involved in the regulation of several mitotic processes, including chromosome condensation, congression and segregation as well as cytokinesis. These essential functions of Aurora B and its overexpression in many cancer types render this protein kinase an attractive target for anticancer drug development. Methods. BI 811283 was profiled in enzymatic kinase assays as well as in proliferation assays on various human cancer cell lines. Cell cycle status was assessed by DNA content analysis (Cellomics ArrayScan, FACScalibur). Histone H3 phosphorylation was determined by immunofluorescence (Cellomics ArrayScan). Apoptosis was detected by Western blotting for cleaved PARP and microscopic enumeration of DAPI-stained cells showing nuclear fragmentation. Senescent cells were identified by staining for SA-ß-Gal activity. Results. BI 811283 inhibited human Aurora B kinase activity with an IC50 value of 9 nM, Aurora A and C kinases with 70 nM and 17 nM, respectively. In a panel of 46 additional kinases representative of the human kinome, BI 811283 at 1000 nM inhibited 7/46 kinases by more than 50%. EC50 values for inhibition of proliferation of &amp;gt;20 human cancer cell lines were in the range of 2 to 14 nM. In the non-small cell lung cancer cell line NCI-H460, treatment with BI 811283 resulted in a rapid (&amp;lt;1 h) inhibition of histone H3 phosphorylation. Within 48 h of treatment, the fraction of polyploid cells increased from &amp;lt;5% to &amp;gt;80%, paralleled by a marked increase in cell volume. An increase of cleaved poly (ADP-ribose) polymerase and a concomitant increase in the fraction of cells with nuclear fragmentation from &amp;lt;1% to 7% was observed after 72 h and 96 h of treatment. Within 96 h, the fraction of senescent cells markedly increased from &amp;lt;3% to 25% of the population. Conclusions. BI 811283 is a potent and selective Aurora kinase inhibitor that inhibits proliferation of cancer cells independent of tissue origin or oncogenome status. Treated cells exhibit a polyploid phenotype characteristic for Aurora B inhibition and show hallmarks of senescence as well as a slow onset of apoptosis in a small fraction of cells. In vivo activity of BI 811283 has been demonstrated in multiple cancer xenograft models in nude mice (see accompanying poster). Phase I clinical trials are ongoing. 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 1080.
Specific support needed for marginalised groups
Authors: G Karmi
Journal: BMJ (1994)

The debate on race and racism is a prominent feature of our time. And it is this which forms the most appropriate context for a discussion of separate associations for doctors from ethnic minority backgrounds. Several organisations of this type exist. The Overseas Doctors Association is probably the best known, but there are also associations for Pakistani, Afro-Caribbean, Greek, and Palestinian doctors. Though a commonality of culture, language, and ethnic origin is a clear rationale for establishing such associations, in some cases …
Bus fare discounts for senior citizens should be taken and used
Authors: Anthony A Laverty
Journal: BMJ (2016)

As a 32 year old full bus fare payer, I am heartened to read Clarfield’s concern over whether benefits for his generation are dooming the rest of us.1 But he need not give himself such a hard time, and I hope that data from the English free bus pass scheme for older people offer him some comfort.

Free bus travel …
PWE-110 Acceptance and Adjustment in a District General Cohort of Inflammatory Bowel Disease Patients: Findings and Implications
Authors: N Swart, D Wellsted, K Lithgo, T Price, M W Johnson
Journal: Gut (2013)

<h3>Introduction</h3> 'Acceptance' refers to the patient's willingness to engage with their illness. Poor acceptance implies the avoidance or denial of an illness and the accompanying somatic experiences. A lack of acceptance highlights an unwillingness to make the necessary behavioural changes that are required to manage a disease effectively (e.g. missing clinical appointments, medication adherence, bad diet, poor coping strategies). This can have serious ramifications for long-term conditions such as inflammatory bowel disease (IBD). <h3>Objective</h3> To assess the prevalence of poor acceptance within our IBD patients. <h3>Methods</h3> 2400 patients with IBD in the Luton &amp; Dunstable catchment area were invited to participate in a web-based quality of life assessment, with the option to request a paper copy. Eligibility required patients to be between 18 and 90 years of age, with no serious learning difficulties or pre-existing mental disorders. The 7-item self-report "Acceptance and Adjustment Questionnaire" (AAQ-II; Bond <i>et al</i> 2011) was used. AAQ-II scoring ranges from 7 to 49. A bimodal distribution suggested two groups of patients (Good and Poor Acceptance) separated by a cut-off score of 18. Logistic regression was used to identify predictors of acceptance and adjustment. <h3>Results</h3> 245 patients completed the assessment (43% male; mean age = 53, SD = 17). Approximately 37% of patients fell in the Poor Acceptance group. Significant predictors of Poor Acceptance were found in Anxiety, Depression, Emotional Illness Perception and Socio-Economic Deprivation. Anxiety levels were scored on a scale from 0 to 21 using the GAD-7. Depression levels were scored on a scale from 0 to 27 using the PHQ-9. Emotional Illness Perception on a scale from 3 to 21 using the Brief Illness Perception Questionnaire. Deprivation based on postcode area was expressed as percentile ranks. For each one point increase in Anxiety, Depression and Emotional Illness Perception scores the likelihood of Poor Acceptance increased by 22%, 21% and 27% respectively. Greater deprivation increased the likelihood of Poor Acceptance by 2% per percentile rank. <h3>Conclusion</h3> Predictors of Poor Acceptance may be grouped into Mood and Deprivation. Education through self-management programmes may tackle some of the problems caused by deprivation. To optimise treatment success in IBD, we would advocate further research into a mood-orientated approach using screening tools, coupled with clinical judgement and targeted psychological interventions such as Acceptance and Commitment Therapy (ACT), which is based upon Acceptance and Adjustment Theory. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3927: Distinct roles of hMLH1-hMRE11 in homologous recombination and heteroduplex DNA repair at a single chromosomal locus
Authors: Chengtao Her, Keqian Xu, Joshua D. Tompkins, Xiling Wu
Journal: Cancer Research (2010)

Abstract Increasing evidence indicates that the mismatch repair protein hMLH1 and DNA double-strand break (DSB) repair protein hMRE11 play multifunctional roles in various processes of DNA repair and damage response in human cells. Our previous studies have revealed a physical interaction between these two proteins and have suggested a role for hMRE11 in heteroduplex DNA repair and hMLH1-dependent DNA damage-induced G2 arrest. Here, we analyzed the effects of hMLH1-hMRE11 on homologous recombinational repair of an induced DSB and consequential heteroduplex repair at a single chromosomal locus by a newly developed reporter system. The results of these studies indicate that hMLH1 and hMRE11 display a synergistic anti-recombination effect and the hMLH1-mediated anti-recombination is at least partially dependent on its interaction with hMRE11, whereas the repair of heteroduplex DNA requires functional hMLH1 and hMRE11. Consistent with these results, chromatin immunoprecipitation (ChIP) analysis of the reporter locus demonstrates that DSB triggers the loading of hMLH1 and hMRE11 proteins to both the proximal region and the site containing heteroduplex DNA. However, in contrast to the proximal regions, loading of hMLH1-hMRE11 at the site of heteroduplex DNA also requires hMSH2, suggesting the involvement of DNA mismatch repair. In summary, our studies have provided evidence to suggest that, in addition to DNA damage response, hMLH1-hMRE11 are involved in at least two other DNA damage repair processes: anti-recombination and heteroduplex DNA repair. Our results implicate that mutations impairing the hMLH1-hMRE11 interaction might promote spontaneous chromosomal recombination between ectopic repetitive sequences and thereby increasing gene conversion and genomic instability. 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 3927.
AB1437-HPR Measurement issues in the evaluation of arthritis self-management interventions
Authors: S. Nolte, S. Newman, G.R. Elsworth, R.H. Osborne
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interventions aimed at delivering self-management support and education for people with chronic conditions have long been recognized as an important aspect of chronic disease management. However, current evidence regarding program effectiveness is mixed, in particular for people with arthritis. <h3>Objectives</h3> To provide an in-depth analysis of outcome measures used in the evaluation of chronic disease self-management programs consistent with the Stanford curricula. <h3>Methods</h3> Based on a systematic review on self-management programs, standardized effect sizes derived from reported outcome measures are categorized according to the quality of life appraisal model developed by Schwartz and Rapkin which polarizes outcomes from performance-based measures (e.g., clinical outcomes) to evaluation-based measures (e.g., emotional well-being). <h3>Results</h3> The majority of outcomes assessed in self-management trials are based on evaluative methods. Overall, effects on knowledge – the only performance-based measure observed in selected trials – are generally medium to large. In contrast, substantially more inconsistent results are found for both perception- and evaluation-based measures that mostly range between nil and small positive effects. <h3>Conclusions</h3> Effectiveness of self-management interventions, especially those aimed at people with arthritis, and resulting recommendations for health policy makers are most frequently derived from highly variable evaluation-based measures, i.e. types of outcomes that potentially carry a substantial amount of measurement error and/or bias. Therefore, decisions regarding the value and efficacy of self-management programs need to be interpreted with care. Researchers and practitioners should apply caution when selecting the range of outcome measures in self-management program evaluation. <h3>Disclosure of Interest</h3> None Declared
Parkes Weber Syndrome
Authors: Stefan Stefanov-Kiuri, Alvaro Fernandez-Heredero
Journal: New England Journal of Medicine (2014)

A 77-year-old woman presented with fingertip ulcers and arteriovenous malformation of the left arm that had been present since childhood. Physical examination revealed hypertrophy, with a giant arteriovenous malformation involving her fingers, forearm, elbow, and upper arm.
EVEREST II REALISM - A CONTINUED ACCESS STUDY TO EVALUATE THE SAFETY AND EFFECTIVENESS OF THE MITRACLIP DEVICE: ANALYSIS OF RESULTS THROUGH 1 YEAR
Authors: Ted Feldman, Scott Lim, Peter Fail, Brian Whisenant, Michael Rinaldi, Paul Grayburn, Richard Smalling, Elyse Foster, Neil Weissman, Saibal Kar
Journal: Journal of the American College of Cardiology (2015)
Breast Cancer Survival of Elderly Women in the Netherlands (1994-2005).
Authors: E. Bastiaannet, A. de Craen, G. Liefers, L. van der Geest, R. Westendorp, C. van de Velde
Journal: Cancer Research (2009)

Abstract Purpose of the study: Breast cancer is the most commonly diagnosed malignancy in elderly women. With an increasing life expectancy of Western populations and increasing incidence of breast cancer, it is one of the major health concerns in the geriatric population. Aim of this study was to assess time trends in relative survival of elderly breast cancer patients in the Netherlands as compared to the younger patients and compare expected and observed mortality in the Dutch population.Methods: Female breast cancer patients 15 years and older, diagnosed with their first primary breast cancer from 1994-2005, were selected from the Netherlands Cancer Registry (NCR). Relative survival was calculated by the Hakulinen method as the ratio of the survival observed among the cancer patients and the survival that would have been expected based on the corresponding (age and year) general population. National life tables were used to estimate expected survival. Relative Excess Risks of death (RER) over time according to age were estimated using a multivariate generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times.Results: Overall, 127 805 patients were included. Relative survival (5-years) declined from 87.1% for 15-65 years old to 86.1% (65-74), 74.7% (75-84) and 68.4% for 85 years and older. From 1995-2005 relative survival did increase for the young patients (RER corrected for stage, histology, treatment and grade 0.93; p&amp;lt;0.001) and for 65-69 (RER 0.93; p&amp;lt;0.001), 70-74 (RER 0.97; p=0.005) and 75-79 (0.98; p=0.03) years old. However, relative survival did not increase significantly for elderly patients of 80 years and older. Relative survival was higher for patients younger than 70 years and the difference in (corrected) RER for elderly versus young patients did increase over the years from 1.22 to 1.69 (p&amp;lt;0.001). Stratified for stage the differences were most striking in the higher stages. Differences between observed and expected mortality decreased with increasing age.Conclusion(s): The gap in breast cancer survival between young and elderly (&amp;gt;70) patients has increased in the Netherlands and survival for patients of 80 years and older has not improved. Despite growing degree of interest, internationally agreed evidence-based guidelines for the elderly with breast cancer do not exist. The aim of the FOCUS study that recently started in the Netherlands is to develop clinical guidelines for the elderly females with breast cancer using population-based, clinical trial and molecular data. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2052.
SEX-RELATED VARIATIONS IN IN-HOSPITAL OUTCOMES IN PATIENTS WITH HEART FAILURE RECEIVING LEFT VENTRICULAR ASSIST DEVICES: FINDINGS FROM NATIONWIDE INPATIENT SAMPLE STUDY 2002-2012
Authors: Marjan Mujib, Nabila K. Mazumder, Wilbert Aronow, Dhaval Kolte, Sahil Khera, Tanush Gupta, Prakash Harikrishnan, Sachin Sule, Diwakar Jain, Gregg Lanier, Ali Ahmed, Gregg Fonarow, Howard Cooper, Alan Gass, William Frishman, Sumanth Prabhu, Julio Panza
Journal: Journal of the American College of Cardiology (2016)