tbuckley/cabot-search huggingface dataset:
AB0026 Pathophysiological hypoxia affects both redox state and il-2 signaling of human cd4+ t cells and concomitantly impairs survival and proliferation
Authors: T. Gaber, C. L. Tran, S. Schellmann, M. Hahne, C. Strehl, M. Jakstadt, G.-R. Burmester, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease of diarthrodial joints, characterized by the infiltration of immune cells, alterations of cellular redox state and pathophysiological local tissue hypoxia (&lt;1% O<sub>2</sub>). <h3>Objectives</h3> We investigated the impact of different hypoxia levels on survival, proliferation, cytokine secretion, intracellular energy and redox state of quiescent and mitogen stimulated human CD4+ T cells. <h3>Methods</h3> Isolated human CD4+ T cells were exposed to normoxia (18% O<sub>2</sub>), physiological hypoxia (5% O<sub>2</sub>) and pathophysiological hypoxia (&lt;1% O<sub>2</sub>), respectively and cultured with or without PHA stimulation at defined periods of time (6h, 24, 48, and 72h). Cells were then analyzed by measuring IL-2R signaling (CD25 expression, phosphoSTAT5a), proliferation and the production of intracellular ROS (iROS) using flow cytometry. In addition, caspase-3/7 activity and ATP levels were determined by luminometric assays. Cellular oxidative damage and cytokine release were analyzed by ELISA based quantification of protein carbonylation (ROS damage) and IL2 production. <h3>Results</h3> We found pathophysiological hypoxia (&lt;1% O<sub>2</sub>) to decrease significantly CD4+ T cell survival after mitogenic stimulation. This effect was neither due to induced caspase-3/7-mediated apoptosis nor to increased ATP consumption or increased ATP depletion. However, the ability of stimulated T cells to proliferate was both delayed and suppressed under these hypoxic conditions, despite increased expression of CD25 and unchanged secreted IL-2 amounts. Hypoxia was also found to modify iROS levels in stimulated T cells over time, but without producing measurable effects on oxidative protein damage as compared to normoxia. In contrast, both normoxia (18% O<sub>2</sub>) and physiological hypoxia (5% O<sub>2</sub>) did not decrease CD4+ T cell survival and proliferation after mitogenic stimulation. <h3>Conclusions</h3> We conclude that pathophysiological hypoxia (&lt;1% O<sub>2</sub>) but not physiological hypoxia (5% O<sub>2</sub>) affects T cell proliferation and viability via disturbed IL-2R signaling downstream of STAT5a phosphorylation. However, the decreased T cell proliferation was not linked to an impaired cellular energy homeostasis. We suggest iROS links early events in T cell stimulation to the inhibition of the lymphoproliferative response under hypoxic conditions. The level of iROS may therefore act as a mediator of immune functions leading to down-regulation of long-term T cell activity in inflamed tissues. <h3>Disclosure of Interest</h3> None Declared
Abstract 5085: TopModel: An online resource for predictive models in cancer
Authors: Christopher W. Szeto, Artem Sokolov, Stephen Benz, Joshua Stuart, David Haussler
Journal: Cancer Research (2012)

Abstract One goal of characterizing the genome-wide landscape of cancer cells is to identify predictive signatures of onset, progression, and treatment outcomes. Many computational approaches have been developed to discover gene signatures with a range of success. The challenge still remains to identify the best approach that, when trained on one cohort, remains accurate in predicting outcomes on an unseen cohort. Thus far, no clear themes have emerged that might provide clues about which method works for a particular task. We have built a system called TopModel that facilitates the identification of top-performing machine-learning algorithms for a series of cancer-genomics challenges. The four components of the system include: 1) a benchmark that includes several cancer genomics datasets with outcome variables as targets to predict; 2) a database of results derived from the application of thousands of machine-learning and feature selection combinations; 3) a web interface that allows bioinformaticians to evaluate their own prediction results; and 4) a web interface that allows a biomedical researcher to upload data on a sample or set of samples in order to receive a report on the signatures predicted to exist in the sample(s). The cancer benchmark component provides a common ground for the development and evaluation of prediction methods for variables such as cancer subtype, drug response, survival, and others. Several datasets have been loaded including predicting survival in the TCGA cohorts, and the hundreds of drug sensitivities in several cancer cell line cohorts. We demonstrate the utility of the resource by comparing state-of-the art feature selection methods to a new approach that uses locality on a genetic interaction network. We evaluate the performance in terms of how well the features generalize across datasets as a trade-off to the accuracy of prediction. In addition to identifying high-value genome features, we explore the robustness of the cancer state in the absence of these features. We simulate gene knock outs by disconnecting these features in our pathway models, inferring the pathway interaction network in the absence of these features, and then reassessing using the top-performing predictive models of cancer. 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 5085. doi:1538-7445.AM2012-5085
Disseminated histoplasmosis presenting as colonic pseudotumor
Authors: J. Winn, S. Akbar, S. Theivanayagam, R. Lim, B. Odum, M. Bechtold, A. Diaz-Arias, M. Arif
Journal: Endoscopy (2013)

Gastrointestinal histoplasmosis may be a rare initial manifestation in immunocompromised patients. We present a case of colonic histoplasmosis in a patient with human immunodeficiency virus (HIV), disseminated disease, and an unusual presentation.
Abstract 1737: Lipocalin-2/NGAL expression is associated with poor prognostic variables in human mammary, endometrial and ovarian carcinomas
Authors: Jeffrey S. Ross, Christine E. Sheehan, Bhaskar V.S. Kallakury
Journal: Cancer Research (2010)

Abstract BACKGROUND: Recent literature has shown that lipocalin-2, a lipophilic ligand transporter member of the lipocalin family has a possible role as a biomarker and a modulator of human cancers. Elevated levels of lipocalin-2 have been demonstrated in several types of human cancer. However, its role as a prognostic biomarker has not been widely reported. DESIGN: Formalin-fixed, paraffin-embedded tissue sections from 146 invasive mammary, 124 endometrial and 59 ovarian carcinomas were immunostained by automated method (Ventana Medical Systems Inc., Tucson, AZ) using rat monoclonal lipocalin-2/NGAL (R&amp;D Systems, Minneapolis, MN). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables. RESULTS: Cytoplasmic lipocalin-2 overexpression was observed in 78/146 (53%) of invasive mammary carcinomas and correlated with PR positive status [63% PR positive versus 41% PR negative, p=0.012] and disease recurrence [69% recurrent versus 48% non-recurrent, p=0.021). On multivariate analysis, advanced stage, lipocalin-2 overexpression, ER negative status, metastatic disease at diagnosis and positive node status were independent predictors of disease recurrence; while advanced stage, metastatic disease at diagnosis and positive node status were independent predictors of shortened survival. In endometrial carcinomas, cytoplasmic lipocalin-2 overexpression was observed in 47/124 (38%) tumors, and correlated with tumor grade (52% grade 3 vs. 43% grade 2 vs. 21% grade 1, p=0.045) and with ER negative status [52% ER negative vs 28% ER positive, p=0.049]. There was no correlation with disease recurrence or overall survival. In invasive ovarian carcinomas, cytoplasmic lipocalin-2 overexpression correlated with tumor grade (0% grade 1 vs. 40% grade 2 vs. 67% grade 3, p=0.006) and advanced tumor stage (32% stage I vs. 65% stage III vs. 100% stage IV, p=0.018). Lipocalin-2 expression did not correlate with patient survival. CONCLUSION: Lipocalin-2 overexpression correlates with varying markers of biologic aggressiveness in human mammary, endometrial and ovarian carcinomas warranting further study. 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 1737.
Abstract 1302: Targeting mTORC1 by epidermal overexpression of PRAS40(T246A) suppresses TPA-induced epidermal hyperplasia during tumor promotion.
Authors: Okkyung Rho, John DiGiovanni
Journal: Cancer Research (2013)

Abstract Akt activation is an important event during the early stages of skin tumor promotion by diverse tumor promoting stimuli. Transgenic mice overexpressing either wild-type Akt1 (Aktwt) or a constitutively active form of Akt1 (Aktmyr) exhibit dramatically enhanced susceptibility to two-stage skin carcinogenesis and skin tumor promotion. Several downstream Akt targets are modulated (i.e., increased phosphorylation) in keratinocytes during tumor promotion, including the mammalian target of rapamycin (mTORC1). Recent experiments show that inhibiting mTORC1 by using topical rapamycin in both wild-type and BK5.Aktwt transgenic mice can effectively block TPA-induced activation of mTORC1 signaling, epidermal hyperproliferation and skin tumor promotion in a dose-dependent manner. Treatment with rapamycin also inhibited TPA-induced proliferation and migration of labeling retaining cells (LRCs) of the bulge region from the hair follicles to upper epidermal compartments. To further examine the importance of mTORC1 signaling in epithelial carcinogenesis, we generated BK5.PRAS40mt (PRAS40T246A) mice using the BK5 vector that targets expression to the basal layer of epidermis. PRAS40 was originally identified as a novel Akt substrate with a phosphorylation site at Thr246 and acts as a negative regulator when bound to mTORC1. PRAS40T246A expressed in BK5.PRAS40mt mice remained bound to raptor even after TPA treatment as determined by immunoprecipitation analysis. BK5.PRAS40mt mice displayed reduced phosphorylation of both S6K (T389) and 4EBP1 (S65) in epidermis following treatment with TPA. Furthermore, these transgenic mice were significantly less sensitive to TPA-induced epidermal proliferation (measured by both epidermal thickness and labeling index) compared to nontransgenic siblings. TPA-mediated migration and proliferation of LRCs was also inhibited in BK5.PRAS40mt mice. BK5.PRAS40mt mice also expressed lower levels of cell cycle proteins in epidermis after TPA treatment. Collectively, the current data further support the hypothesis that downstream signaling pathways through mTORC1 contribute significantly to the process of skin tumor promotion through effects on proliferation. Supported by CA37111 and 129409. Citation Format: Okkyung Rho, John DiGiovanni. Targeting mTORC1 by epidermal overexpression of PRAS40(T246A) suppresses TPA-induced epidermal hyperplasia during tumor promotion. [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 1302. doi:10.1158/1538-7445.AM2013-1302
George Duncan Stewart Beechey Vincent Jerome Boyce Alfred McKillop ("Mac") Simpson-Brass Leslie Turner Geoffrey Herbert Watson
Authors: W R Almond, A. D Weeks, A G. Cameron, A. Turner, R. Patel, I. Watson
Journal: BMJ (1999)

# George Duncan Stewart Beechey {#article-title-2}

Former general practitioner Chorley, Lancashire ( b Missoorie, India, 1910; q Glasgow 1938), died after a cerebral vascular accident on 13 January 1999. Duncan had a degree in forestry from Oxford, intending to join his father in the colonial service, but after working on the Kielder forest in Northumbria he pursued his true vocation. He joined the Royal Navy when war broke out, but was invalided out when Portsmouth dockyard was bombed, and he joined a practice in Chorley where he remained for over 40 years. Duncan was a popular and intuitive doctor with a sometimes unconventional approach to helping his patients. Outside medicine his interests included tracing and writing about the careers of his talented ancestors, sculpture, wood carving, and gardening. In later years he learnt to read and write Chinese. Predeceased by his wife, Mabel (Moulie), he leaves a daughter and a grandson and a granddaughter.

# Vincent Jerome Boyce {#article-title-3}

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Registrar in obstetrics and gynaecology Scunthorpe General …

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PTU-196 Long-term results of laparoscopic Heller's cardiomyotomy for achalasia cardia
Authors: M Stavrou, L Martin, F El-Madani, S Gupta
Journal: Gut (2012)

<h3>Introduction</h3> To review the long-term efficacy of Laparoscopic Heller9s Cardiomyotomy in patients with Achalasia Cardia at a large UK District General Hospital. <h3>Methods</h3> A structured postal survey was undertaken on 40 consecutive patients with clinical, radiologic, endoscopic and manometric diagnosis of Achalasia Cardia who underwent Laparoscopic Cardiomyotomy by a single surgeon at our unit between 1996 and 2011. The procedure was supplemented by Anterior Fundoplication on all the patients. <h3>Results</h3> The average age of the 40 patients in the study group was 49 years (range 18–80 years) with an equal sex distribution. Mean follow-up since surgery was 34 months (3–88 months). Dysphagia scores improved in all the patients (100%). Thirteen patients (33%) had complete remission from dysphagia whereas 24 (60%) experienced occasional dysphagia only. Despite the improvement in dysphagia, three patients (7%) continued to have regular dysphagic symptoms. Although only seven patients (17%) had regular reflux symptoms, fifteen patients (37%) were on regular acid-suppressing drugs. Results were further stratified into excellent (38%), good (37%), fair (25%) and poor (0%), based on a previously described classification.<sup>1</sup> All patients (100%) reported overall improvement in their health-related quality of life as evaluated by relief of gastrointestinal symptoms (dysphagia and reflux) and patient satisfaction. Patient satisfaction was considerably high largely due to the absence of dysphagia and undeterred by the presence of reflux symptoms. <h3>Conclusion</h3> Laparoscopic Cardiomyotomy with Anterior Fundoplication achieves excellent long-term relief from dysphagia for most of the patients with Achalasia. Despite the fundoplication, acid reflux is a frequent post-operative complication. However anti-acid medications minimise its clinical significance. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Vantrappen G</b>, Hellmans J. Treatment of achalasia and related motor disorders. <i>Gastroenterology</i> 1980;<b>79</b>:144–5.
Atrial Arrhythmia after Surgical Closure of Atrial Septal Defects in Adults
Authors: M A Gatzoulis, M A Freeman, S C Siu, G D Webb, L Harris
Journal: New England Journal of Medicine (1999)

Atrial flutter and atrial fibrillation are causes of morbidity in adults with an atrial septal defect. In this study, we attempted to identify risk factors for atrial flutter and fibrillation both before and after the surgical closure of an atrial septal defect.
Case 24-2014
Authors: Michael Mannstadt, Angela E. Lin, Long P. Le
Journal: New England Journal of Medicine (2014)

A 27-year-old man ‎was seen in the outpatient endocrinology clinic because of severe osteoporosis and multiple bone fractures since childhood. He had had mild cognitive impairment, delayed speech, and pale blue sclerae during childhood. Diagnostic tests were performed.
AB1348 Heterogeneity of patients with anticentromere antibodies
Authors: L. Belloli, C. Crotti, N. Ughi, M. Massarotti, B. Marasini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anticentromere antibody (ACA) are considered a serological marker of systemic sclerosis (SSc), in particular of its limited form (lcSSc). They are rarely observed in other connective tissue diseases, but seldom are found associated with primary biliary cirrhosis (PBC). <h3>Objectives</h3> To evaluate the clinical heterogeneity of patients with anticentromere antibodies (ACA). <h3>Methods</h3> One hundred of patients sent to our Center because of ACA positivity, were retrospectively analyzed. There were 99 females with a follow-up period of at least 5 years. <h3>Results</h3> All patients had an autoimmune disease. Eighty-four had systemic sclerosis (SSc): 71 had lcSSc, 8 diffuse SSc (dcSSc) and 5 SSc sine scleroderma. In 17 patients (20.2%) SSc was associated with other autoimmune diseases, mostly with PBC (12 patients, 9 with lcSSc) and autoimmune thyroiditis (7 patients, 6 lcSSc). Two patients had SSc in overlap with rheumatoid arthritis (RA) and Sjögren's syndrome (SS), respectively. Sixteen patients did not have SSc, but other rheumatic diseases: 9 had Undifferentiated Connective Tissue Disease, 2 Systemic Lupus Erythematosus, 2 SS and 2 RA in overlap with SS. <h3>Conclusions</h3> The presence of ACA does indicate an autoimmune disorder, mainly lcSSc, often in overlap with PBC. Therefore, the presence of ACA should deserve further examination, because marker of autoimmune disease. <h3>Disclosure of Interest</h3> None Declared
THU0349 Assessment of dry eye symptoms in primary fbromyalgia
Authors: M. Antivalle, M. Battellino, A. Batticciotto, M.C. Ditto, A. Mutti, V. Varisco, F. Atzeni, P. Sarzi-Puttini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> While dry eye symptoms and signs have been frequently reported in fibromyalgia patients, no study so far has specifically investigated the concordance between subjective symptoms and objective findings in this population. <h3>Objectives</h3> Aim of this study was to assess to whether, in FM patients, dry eye subjective symptoms are correlated to a real reduction of tear production, or mainly reflect a state of altered perception. <h3>Methods</h3> 158 patients were studied, 66 with fibromyalgia (FM: 62 F, 4 M, mean age 41.83 yrs) and 92 control subjects affected by miscellaneous rheumatic diseases (Controls: 81 F, 11 M, mean age 42.26 yrs). All patients completed the questionnaire used in the diagnosis of Sjögren's syndrome (SQ) (1), and the McMonnies dry eye questionnaire (McM) (2). Schirmer's I test (ST) was performed, and a result ≤5 mm after 5 minutes was defined as positive. The impact of FM was assessed by tender points (TP) count, the Widespread Pain Index (WPI), and the Symptom Severity score (SS) (3). <h3>Results</h3> ST was positive in 91 patients (FM 11/66 (16.7%); Controls 32/92 (34.8%), p=0.009). 91 patients answered affirmatively to at least one of the three questions related to dry eye of the SQ (FM 54/66 (81.8%); Controls 37/92 (40.2%)), including 56 patients with negative ST (FM 43/55 (78.2%); Controls 13/60 (21.7%), p=0.000) (fig 1). By McM, 72 patients (FM: 35/45 (77.8%); Controls 37/82 (45.1%)) were classified as having dry eye, including 46 with negative ST (FM 27/36 (75.0%); Controls 19/53 (35.8%)). SQ and McM questionnaires were fairly well correlated (k =0.760, p=0.000). Logistic regression showed that for both SQ and McM, dry eye symptoms were correlated to age, actual ST results, and to the presence of FM (p&lt;0.000). In FM, dry eye symptoms were correlated to the burden of FM (fig 2). <h3>Conclusions</h3> This is the first study addressing the concordance between subjective symptoms and objective findings in the assessment of dry eye in FM. Our results show that dry eye symptoms are extremely frequent in FM, but are related to the severity of FM symptoms rather than to the results of Schirmer's test. <h3>References</h3> Vitali C, Ann Rheum Dis 2002 Nichols KK, Cornea 2004 Wolfe F, Arthritis Care Res. 2010 <h3>Disclosure of Interest</h3> None Declared
ED-25 * SOCIOECONOMIC STATUS MODIFIES THE IMPACT OF RACE/ETHNICITY ON GLIOBLASTOMA PROGNOSIS
Authors: A. Porter, D. Johnson
Journal: Neuro-Oncology (2014)

BACKGROUND: Demographic factors, most prominently age but also race and marital status, are associated with glioblastoma prognosis. Likewise, treatment-related factors, such as surgery type and radiation therapy, significantly impact survival. Socioeconomic status (SES) is associated both with demographic factors and access to health care in the USA. Analyses of glioblastoma patient survival which include SES will provide new insight into the relationship between demographics, treatment received, and ultimately survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program tracks cancer incidence and survival in the United States. We obtained a custom SEER data set containing demographic and treatment information regarding patients with GBM diagnosed from 2000 to 2010, including information on SES based on the census tract. Predictors of GBM treatment and survival were evaluated via Kaplan-Meier analyses as well as Cox proportional hazards regression models. RESULTS: A total of 26,481 patients with glioblastoma were evaluated. In the final model, age, marital status, race/ethnicity, SES quintile, radiation use, and surgery type were all associated with survival. Notably, race/ethnicity was not a predictor of survival in models controlling for age alone, but in multivariable models including SES, White Non-Hispanic patients (ref) had poorer survival than White Hispanics [RR 0.90 (95% CI 0.86-0.95)], Blacks [RR 0.87 (95% CI 0.81-0.92)], and All Others [RR 0.85 (95% CI 0.80-0.91)]. With regard to treatment, greater SES was associated with higher gross total resection rate and higher utilization of radiation (p < 0.001 for each comparison). CONCLUSION: Higher SES is associated with both more aggressive treatment of glioblastoma and longer survival. Previously known demographic prognostic factors, including age and marital status, remain significant when SES is also considered. White Non-Hispanic individuals had poorer survival than other racial/ethnic groups when controlling for demographic and treatment factors, a finding that stands in contrast to previous analyses and warrants further evaluation.
Primary T-Prolymphocytic Leukemia (T-PLL) Cells Are Sensitive To BCL-2 and HDAC Inhibitors: Results From High-Throughput Ex Vivo Drug Testing
Authors: Emma I Andersson, Tea Pemovska, Samuli Eldfors, Anneli Lauhio, Paavo Pietarinen, Edgar Faber, Olli Kallioniemi, Krister Wennerberg, Caroline Heckman, Kimmo Porkka, Satu Mustjoki
Journal: Blood (2013)
Bone Scintigraphy in Polyostotic Fibrous Dysplasia
Authors: N Fukumitsu, M Dohi, K Midda, N Nakada, Y Sunagawa, J Harada, M Uchiyama, Y Mori, K Ishibasi, K Fukuda
Journal: Clinical Nuclear Medicine (1999)

The authors describe a patient with polyostotic fibrous dysplasia. A 21-year-old woman with a history of left coxodynia had exacerbation of her symptoms. Bone scintigraphy showed multiple areas of increased accumulation in the left side of the limbs. Plain radiographs showed multifocal bony lesions with some bone expansion and mixed osteolytic and ground-glass opacities. The findings are those of polyostotic fibrous dysplasia, which tends to involve one side of the body.