tbuckley/cabot-search huggingface dataset:
AB0797 Gait abnormalities in rheumatic patients with temporomandibular joint involvement.
Authors: D. Melchiorre, L. A. Rinaldi, M. Maresca, D. Simoni, V. Monaco, M. Di Bari, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The relationship between temporomandibular joint disorders (TMD) and alterations of posture and gait has been widely discussed in several investigations, reaching different and sometimes opposite conclusions <h3>Objectives</h3> To investigate whether TMD in early rheumatoid and psoriatic arthritis could influence gait pattern, assessed by computerized gait analysis with dual task (DT) paradigm. <h3>Methods</h3> Two groups of subjects were examined: a group of 30 patients with TMD in early rheumatoid or psoriatic arthritis without signs of involvement of other joints and a control group of 30 healthy subjects. Both temporomandibular joints were examined by ultrasound imaging in every subject. Gait analysis with a photogrammetric system during treadmill walking was performed. In DT procedure, treadmill walking was associated with a cognitive task. The coordination patterns thigh-leg, leg-foot and thigh-foot were analyzed. <h3>Results</h3> Sonographic findings showed joint effusion and alterations of condylar profile in all patients. Spatio-temporal parameters, during treadmill walking, did not show significant differences between controls and patients in single and dual task. Patients showed an asymmetric behavior of the coordination pattern leg-foot in DT procedure, during swing and stance phase of walking. In healthy subjects no significant difference of the coordination pattern leg-foot was observed. <h3>Conclusions</h3> DT procedure assessed the relationship between TMD and changes of the coordination pattern leg-foot during walking. DT shows that patients with TMD involvement develop an inadequate walking performance. These data focus the attention on the presence of postural abnormalities and gait alterations in patients with TMD, suggesting its evaluation in arthritides to obtain a timely correction of the gait modifications. <h3>Disclosure of Interest</h3> None Declared
Abstract 5482: Sun exposure and prostate cancer risk in New South Wales, Australia: A case control study
Authors: Visalini Nair-Shalliker, David P. Smith, Sam Egger, Ann Marie Hughes, Mark Clements, Anne Kricker, Bruce K. Armstrong
Journal: Cancer Research (2012)

Abstract Background Ultraviolet-B radiation in sunlight may influence risk of developing prostate cancer. Method We examined the relationship between individual solar UV exposure and risk for prostate cancer in a case control study combining the New South Wales (Australia) Prostate Cancer Care and Outcome (cases) and Non-Hodgkin Lymphoma (controls) studies. Results There was evidence that increasing solar UV exposure increased prostate cancer risk (adjusted OR for highest vs. lowest quartiles of average weekly, warmer months sun exposure 2.07 95% CI: 1.36-3.16) and that this increased risk was most evident with weekend sun exposure (adjusted OR 5.54 95%CI: 2.94-10.43). Increased sun sensitivity was also associated with increased risk of prostate cancer (adjusted OR 1.63 95% CI: 1.09-2.44 for very high sun sensitivity). Conclusion Our results suggest that increasing solar UV exposure increases prostate cancer risk in a high ambient solar UV environment. Impact Given that previous studies conducted mainly in low solar UV environments found either no evidence of an association or evidence of a negative association; our findings suggest the possibility of a U-shaped dose effect relationship between exposure to solar UV and prostate cancer. Further studies are needed to test the hypothesis that high solar UV exposure is a risk factor for prostate cancer and to explore possible mechanisms for such an association. 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 5482. doi:1538-7445.AM2012-5482
Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model
Authors: Keisuke Kitakaze, Yasumichi Mizutani, Eiji Sugiyama, Chikako Tasaki, Daisuke Tsuji, Nobuo Maita, Takatsugu Hirokawa, Daisuke Asanuma, Mako Kamiya, Kohei Sato, Mitsutoshi Setou, Yasuteru Urano, Tadayasu Togawa, Akira Otaka, Hitoshi Sakuraba, Kohji Itoh
Journal: Journal of Clinical Investigation (2016)

GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses.
OP0208 High density fine mapping in rheumatoid arthritis indentifies 14 new loci:
Authors: S. Eyre, J. Bowes, D. Diogo, S. Raychaudhuri, E. Stahl, A. Zhernakova, L. Padyukov, C. Amos, R. Plenge, L. Klareskog, P. Gregersen, J. Worthington
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The advancement in genome wide association studies (GWAS) has brought the number of non-HLA loci associated with RA to 31. There is now the requirement to develop this genetic knowledge and translate it into clinical utility. One of the first steps towards this goal is to fine map these loci to better understand the genetic structure that underpins risk of developing disease. A major finding in the GWAS era has been the overlap of susceptibility loci in autoimmune diseases. This finding, coupled to the requirement to genetically fine map these loci in a wide range of autoimmune diseases, led to a pooling of resources and the development of a custom Illumina array by the Immunochip consortium. <h3>Objectives</h3> Fine map the 31 loci already associated with the RA at a genome-wide significance level, as well as investigate whether other novel associations to autoimmune loci on the immunochip array, or with SNPs included as a deep replication of RA GWAS results. <h3>Methods</h3> RA and control cohorts were available from 5 countries (UK, USA, Sweden, Spain and The Netherlands).We had 11,475 cases, of which 7,222 were ACPA positive (63%) and 3,339 were ACPA negative, and 15,870 controls for 163,081 polymorphic markers.Results of this analysis were added to non-overlapping samples of the previously best powered RA meta analysis to maximise the possibility of revealing novel loci associated with RA (1). <h3>Results</h3> We discovered a total of 14 novel RA loci confirmed at genome-wide significance (p&lt;5×10<sup>-8</sup>), 7 with immunochip data alone and a 7 when the additional GWAS meta analysis was added (Table 1), bringing the total of confirmed RA genetic susceptibility loci to 45. Genome-wide significance was also obtained, for the first time, for 2 loci in the ACPA negative analysis, those at HLA (P=2.92×10<sup>-15</sup>) and ANKRD55 (p=5.18×10<sup>-12</sup>). <h3>Conclusions</h3> Of the 39 confirmed RA loci densely mapped in this study, in more precisely mapping the association signal, we have localised to one gene in the LD defined region for 21 loci and discovered 18 SNPs within exonic regions that are in tight LD with the most associated signal.We present evidence for 14 new loci associated with the susceptibility to RA. These loci continue the theme of RA loci being strongly linked to immune function, and associated with other autoimmune loci. <h3>References</h3> Stahl EA, et al. Nat Genet 2010;42:508-14. <h3>Disclosure of Interest</h3> None Declared
OC-115 Comparison of screen detected and interval colorectal cancers in the bowel cancer screening programme: experience from the North East of England
Authors: M D Gill, M G Bramble, C J Rees, M Bradburn, T J Lee, S J Mills
Journal: Gut (2012)

<h3>Introduction</h3> The NHS Bowel Cancer Screening Programme (BCSP) commenced screening in North East England in February 2007. It offers biennial faecal occult blood testing (FOBt) followed by colonoscopy for those with a positive FOBt. All cases of colorectal cancer (CRC) known to the MDTs in this region are registered with the Northern Colorectal Cancer Audit Group (NORCCAG) database. <h3>Methods</h3> CRCs occurring in the screening population (aged 60–69 years) between April 2007 and March 2010 were identified from the NORCCAG database. Their screening history was obtained by cross-referencing this database with the regional BCSP database. Cases were classified into four groups: a control group (cancers diagnosed prior to first screening invite), screen detected, interval (cancers diagnosed between screening rounds after a negative FOBt) and non-uptake (patients who declined screening). Patient demographics, tumour characteristics and survival were compared between the four groups. <h3>Results</h3> 1336 CRCs were diagnosed in the screening population. 511 (38.2%) cancers were in the control group. 825 cancers (61.8%) were detected in individuals who had been invited for screening. 322 (39.0%) were screen detected, 311 (37.7%) were in the non-uptake group and 192 (23.3%) were interval cancers. All of the interval cancers followed a negative FOBt. Compared to both the control group and the interval cancer group, the proportion of males in the screen detected group was significantly higher (73.0% vs 62.4% &amp; 60.4%, χ<sup>2</sup>=9.88, p=0.002 and χ<sup>2</sup>=8.77, p=0.003 respectively). Screen detected cancers were more likely to be left sided than in the control or interval cancer groups (78.6% vs 70.1% &amp; 66.7%, χ<sup>2</sup>=7.32, p=0.007 &amp; χ<sup>2</sup>=8.89, p=0.003). Significantly more Dukes A and fewer Dukes D cancers were found in the screen detected group compared to the control and interval groups (p&lt;0.05). Screen detected cancers had a superior survival compared to interval cancers (χ<sup>2</sup>=50.36, p&lt;0.001) and the control group (χ<sup>2</sup>=53.62, p&lt;0.001). There was no difference in patient demographics, tumour location, stage of tumour nor survival between control and interval cancer groups. <h3>Conclusion</h3> This is one of the first studies that provides data on the performance of the BCSP in one region since its national implementation. The FOB test is better at detecting cancers in the left colon and in men. There are significant numbers of interval cancers, which were not found to have an improved outcome compared to the non-screened population as has previously been published. <h3>Competing interests</h3> None declared.
Tc-99m Dicarboxypropane Diphosphonate Uptake in Ovarian Fibrothecoma
Authors: ROBERTA DANIELI, NEVENKA MONCILOVIC, GIANFRANCO PESCE, MICHELLE REINER, JACQUES BERNIER
Journal: Clinical Nuclear Medicine (2000)

A 76-year-old woman had a palpable mass in the lower abdomen. Computed tomography showed an abnormal pelvic mass with necrotic areas, probably of ovarian origin. A Tc-99m dicarboxypropane diphosphonate whole-body scan performed to evaluate the extent of the disease (i.e., the presence of bone metastases) revealed only diffuse uptake of the tracer in the pelvis. Histopathologic analysis after surgical excision of the mass revealed a fibrothecoma of the right ovary, which is a benign tumor composed of cells derived from the ovarian stroma and, in some instances, resembles the thecal element of the follicle.
Abstract 4468: Pre-diagnostic steroid hormone levels and risk of testicular germ cell tumors
Authors: Katherine A. McGlynn, Victoria M. Chia, Britton Trabert, Michael B. Cook, Sabah Quraishi, Frank Z. Stanczyk, Nader Rifai, Gary Bradwin, Mark V. Rubertone, Barry I. Graubard, Ralph L. Erickson
Journal: Cancer Research (2012)

Abstract Background: Testicular germ cell tumors (TGCT), the most commonly occurring cancer among young men in the U.S., are thought to be endocrine-related tumors. The relationship between steroid hormone levels and development of TGCT, however, has been difficult to study given the rarity of the tumor in the general population and the paucity of pre-diagnostic serum from young men. The U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study, however, was able to overcome these obstacles by enrolling military servicemen who had previously donated serum specimens to the Department of Defense Serum Repository. Methods: STEED participants were enrolled between 2002 and 2005. The associations between TGCT risk and log-transformed serum concentrations of testosterone, free testosterone, estradiol, free estradiol, 3α-androstanediol glucuronide (3α-diol-G), an indicator of peripheral androgen action, and sex hormone-binding globulin (SHBG) were examined in 517 case and 790 control participants. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, adjusting for date of serum donation, age, race/ethnicity, family history of testicular cancer, history of cryptorchidism, height, and body mass index. Results: The analysis found that while testosterone was not significantly associated with TGCT risk, there was an inverse association between 3α-diol-G and risk (OR=0.80, 95%CI=0.63-0.99). In addition, there was a significant inverse association with TGCT and the ratio of 3α-diol-G to testosterone (OR=0.76, 95%CI=0.61-0.93). There was also a significant direct association between estradiol and TGCT risk (OR=1.41, 95%CI=1.06-1.87). The relationships between the free forms of testosterone and estradiol and risk were the same as the relationships between the total forms of each hormone and risk. There was no association between TGCT and SHBG. Conclusion: These results suggest that the hormone metabolism of men who subsequently develop TGCT may vary from that of other men. In men who develop TGCT, more testosterone may be converted to estradiol and less to dihydrotestosterone, the most potent form of androgen, than in men who do not develop TGCT. Further examination of metabolites, both upstream and downstream in the steroid hormone pathway, may help elucidate the mechanism by which these exposures are related to development of TGCT. 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 4468. doi:1538-7445.AM2012-4468
AB0769 Decrease in voicing of critical view in rheumatology journals
Authors: E. Ataç, S. Celik, K. E. Tascilar, H. Yazici
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There has been concern that medical journals do not provide adequate space for letters to the editor sections.<sup>1</sup> We had the impression that rheumatology journals, similarly, were not giving due importance to letters, hence to the dissenting voice. To this end we decided to survey the changes in frequency of letters and the other types of publications in 3 widely read rheumatology journals within the last 25 years. <h3>Methods</h3> Ann Rheum Dis, Arthritis Rheum and Rheumatology were hand searched at 11 time points within the last 25 years for the total number of letters and other manuscripts. The number of letters or other types of manuscripts were tabulated for each calendar year for the 3 journals combined, between 1985 and 2010. Supplements were excluded. For qualitative analysis of letter content, the frequency of rebuttal letters (letters with any degree of negative criticism of published manuscripts in the journals surveyed) was determined. Such rebuttal letters were further scored (1-3) according to their degree of criticism with 3 being the most critical. For this purpose, samples of rebuttal letters with separate degrees of criticism were initially discussed at a training session. The eLetters section of Ann Rheum Dis was also hand searched at 12 time points within the last 12 years for the number of letters and replies. <h3>Results</h3> Figure 1 shows the number of letters and the other kinds of manuscripts for each calendar year. The mean ratio of letters to all manuscripts for the 11 time points was 0.18 (0.16–0.20, 95% CI). There was a significant change (p ≤ 0,0001) in the ratio of letters to the total number of manuscripts within the 11 time points and the latest ratio of 0.11 was definitely outside the 95% confidence intervals for all times given above. Meanwhile only 26% (range: 17%&gt;33%) of all letters surveyed were rebuttals of published work. In turn, the 3rd degree rebuttal letters constituted 25% (range: 12%&gt;39%) of all rebuttals. That is, only 6% of all letters were about serious criticism. In the eLetters section of Ann Rheum Dis, there were 224 letters, almost all of which were about moderate to serious criticism, but there were only 30 replies. <h3>Image/graph</h3> <h3>Conclusions</h3> The frequency of letters –the places of dissenting voice- in our leading rheumatology journals has decreased in the last 25 years. Furthermore only a minor fraction of these letters voice serious criticisms. <h3>References</h3> Christopher Baethge, Gabriele Seger. Our readers' voice. Dtsch Arztebl Int. 2009;106(12):207-9 <h3>Disclosure of Interest</h3> None Declared
IRON OXIDE LABELING OF HUMAN EMBRYONIC STEM CELL-DERIVED CARDIOVASCULAR CELLS: A NOVEL METHOD OF TRACKING STEM CELLS IN VIVO
Authors: Shone Almeida, Rhys Skelton, Stanislas Rapacchi, Peng Zhao, Peng Hu, David Elliot, Reza Ardehali
Journal: Journal of the American College of Cardiology (2015)
Abstract 3821: Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines
Authors: Miyako Kitazono, Yuichi Takiguch, Satoru Kitazono, Hironori Ashinuma, Atsushi Kitamura, Yuji Tada, Katsushi Kurosu, Emiko Sakaida, Ikuo Sekine, Nobuhiro Tanabe, Masatoshi Tagawa, Koichiro Tatsumi
Journal: Cancer Research (2012)

Abstract Background: Malignant pleural mesothelioma (MPM) is one of the most lethal cancers with a rapidly increasing incidence worldwide. Although cisplatin and pemetrexed are recognized as key drugs, and their combination chemotherapy is a standard therapy for MPM, their drug-to-drug interactions, cross-resistance, and resistance mechanisms are not well understood. Methods: The interaction between cisplatin and pemetrexed was evaluated by colonogenic assays followed by isobologram analysis in 4 human MPM cell lines. The cell lines were exposed to the agents using a stepwise dose-escalation method to establish drug-resistant sublines. Thymidylate synthase (TS) mRNA expression was evaluated by RT-PCR, and gene expression profiles were assessed by cDNA microarray analysis and gene ontology analysis using Ingenuity Pathway Analisis (IPA) in the drug-resistant sublines. Results: Cisplatin and pemetrexed had synergistic effects in 3 cell lines and an additive effect in the fourth cell line. The former 3 cell lines showed similar sensitivity to pemetrexed in the parental cells and their cisplatin-resistant sublines, whereas the fourth cell line exhibited cross-resistance. In contrast, cisplatin had diverse effects on pemetrexed-resistant sublines. High TS expression did not correlate with natural pemetrexed resistance and its elevatedexpression correlated with acquired pemetrexed resistance in 2 sublines. Microarray analysis disclosed that the genes which related to “cellular development”,” small molecule biochemistry,” “cellular movement,” “cell death, and “cellular growth and proliferation” affected drug-resistant mechanisms deeply, and that this tendency was common to cisplatin-resistant sublines and pemetrexed-resistant sublines. Conclusion: Cisplatin and pemetrexed showed synergistic activity and no cross-resistance in 3 of the 4 MPM cell lines, suggesting the clinical relevance of their combination chemotherapy. TS expression did not necessarily correlate with pemetrexed resistance. Multiple mechanisms of molecular and cellular functions may underlie acquired resistance to cisplatin and pemetrexed in MPM. 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 3821. doi:1538-7445.AM2012-3821
Abstract 85: RUNX1 and ELK1 directly regulate the transcription of EVI1 during megakaryocytic differentiation
Authors: Miren Maicas, Iria Vazquez, Carmen Vicente, Xabier Cortes-Lavaud, Nerea Marcotegui, Leyre Urquiza, Maria J. Calasanz, Maria D. Odero
Journal: Cancer Research (2012)

Abstract High expression of EVI1 is a negative prognostic indicator of survival in patients with acute myeloid leukemia (AML). The EVI1 gene (3q26) codes for a transcription factor indispensable for the proliferation and self-renewal of HSCs during embryogenesis and in the adult, and is downregulated upon differentiation; however, the regulation of EVI1 in megakaryocytic differentiation should be different, as it is highly expressed in megakaryocytes and platelets, but not in other committed hematopoietic cells. Our aim was to identify transcription factors involved in the regulation of EVI1. Site-directed mutagenesis and ChIP assays identified RUNX1 and ELK1 as putative transcription factors of EVI1. Furthermore, knockdown of RUNX1 and ELK1 led to EVI1 downregulation, and their overexpression to upregulation of EVI1. Of note, in a series of patient samples with AML at diagnosis (n=46), we found a significant positive correlation between EVI1 and RUNX1, and EVI1 and ELK1 mRNA expression levels. RUNX1 has been reported as a key transcription factor in megakaryocytic development. To investigate whether RUNX1 could regulate EVI1 in this process, we treated K562 cells with TPA. After the treatment, we observed an increase in RUNX1, as previously described, and in ELK1 and EVI1. Knockdown of RUNX1 resulted in a marked decrease of the megakaryocytic markers ITGA2B and ITGB3, and of EVI1. Moreover, EVI1 knockdown led to the same effects by blocking the differentiation process, suggesting that the role of EVI1 in megakaryocytic differentiation would be through RUNX1. Interestingly, chromatin immunoprecipitation assay (ChIP) showed that RUNX1 regulates the transcription of EVI1 by acetylation of the histone H3 on its promoter region. In conclusion, we demonstrate that RUNX1 and ELK1, two proteins with essential functions in hematopoiesis, regulate EVI1 in AML. Moreover, our results suggest that these transcription factors could regulate EVI1 expression during megakaryocytic differentiation, and that RUNX1 would activate EVI1 expression through acetylation of the histone H3 on its promoter region. This study opens new directions to further understand the mechanisms of EVI1 overexpressing leukemias. 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 85. doi:1538-7445.AM2012-85