tbuckley/cabot-search huggingface dataset:
Evaluation of direct-to-consumer low-volume lab tests in healthy adults
Authors: Brian A. Kidd, Gabriel Hoffman, Noah Zimmerman, Li Li, Joseph W. Morgan, Patricia K. Glowe, Gregory J. Botwin, Samir Parekh, Nikolina Babic, Matthew W. Doust, Gregory B. Stock, Eric E. Schadt, Joel T. Dudley
Journal: Journal of Clinical Investigation (2016)

BACKGROUND. Clinical laboratory tests are now being prescribed and made directly available to consumers through retail outlets in the USA. Concerns with these test have been raised regarding the uncertainty of testing methods used in these venues and a lack of open, scientific validation of the technical accuracy and clinical equivalency of results obtained through these services.
SAT0147 Clinical Associations of Cutaneous Vasculitis: Study of 817 Patients
Authors: J. Loricera, V. Calvo-Río, F. Ortiz-Sanjuán, H. Fernández-Llaca, M. A. González-López, L. Álvarez, M. C. González-Vela, D. González-Lamuño, C. Mata, J. Rueda-Gotor, V. M. Martínez-Taboada, M. Á. González-Gay, R. Blanco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cutaneous vasculitis (CV) includes a large and heterogeneous set of syndromes characterized by inflammation of the skin vessels. The most common clinical manifestation is palpable purpura with leukocytoclastic vasculitis in biopsy. <h3>Objectives</h3> Our aim was to study clinical associations of a large series of patients with CV. <h3>Methods</h3> Study of 817 consecutive and unselected patients with CV of the same university hospital. The diagnosis required histological confirmation except in obvious cases like Henoch-Schönlein Purpura (HSP) in childhood. Primary vasculitic syndromes were classified according to the classification of Chapel Hill <i>(Jennette J et al. Arthritis Rheum 1994; 37:187)</i>. Secondary vasculitis were considered those due to malignancies, major infections and connective tissue diseases. The different clinical associations were studied according to different age groups, considering adults patients older than 20 years (Michel et al. J Rheumatol 1992; 19:721-8). <h3>Results</h3> Of 817 patients (457 men/360 women), 459 were adults (mean age±SD, 55.3±17.5 years) and 358 children-young (mean age ± SD, 7.5 ± 4.2 years). Of the 358 children-young, 355 had primary VC: HSP (279 cases), cutaneous leukocytoclastic angiitis (CLA) (68) and urticarial vasculitis (8). Of the 459 adults, 369 had a primary CV: CLA (239), HSP(105), urticarial vasculitis (12) and mixed cryoglobulinemia (13 patients). The CV was a manifestation of a systemic necrotizing vasculitis in 13 adults; polyarteritis nodosa (3), microscopic polyangiitis (4), Wegener's disease (3) and Churg-Strauss syndrome (3). In addition, the CV was secondary to other processes in 77 adults: connective tissue diseases (34), severe infection (25), neoplasia (18). There were only three children-young patients, who had a secondary CV, a major infection (2 cases) and a connective tissue disease (1 case). Patients in which the CV was secondary to systemic necrotizing vasculitis, connective, serious infections or malignancies had clinical and laboratory data suggestive of this underlying disease. <h3>Conclusions</h3> CV in children in most cases (99.2%) is primary, usually HSP or CLA, and has a good prognosis. By contrast, in adults a 22.4% is due to malignancies, major infections, connective tissue diseases, systemic necrotizing vasculitis or cryoglobulinemic vasculitis. Therefore, clinical assotiations depends of age, being more serious in adults. <h3>Acknowledgements</h3> This study was supported by grants from "Fondo de Investigaciones Sanitarias" PI12/00193 (Spain). This work was also partially supported by RETICS Program, RD08/0075 (RIER) from "Instituto de Salud Carlos III" (ISCIII) (Spain). <h3>Disclosure of Interest</h3> None Declared
Recruitment of New Physicians, Part II
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2013)

A careful, expertly done recruitment process is very important in having a successful group. Selecting a search committee, deciding what characteristics the group wants in a new person, evaluating the candidate's curriculum vitae, speaking to the individual on the phone or during a meeting, and calling references are important steps in selecting the top candidates for a group. The interview at the practice site is the next step, and it is critical. Many tips for planning and conducting a successful interview are given in this article.
SERIAL GALECTIN-3 AND FUTURE CARDIOVASCULAR DISEASE IN THE GENERAL POPULATION: DATA OF PREVEND
Authors: Allart Rogier van der Velde, Wouter Meijers, Jennifer Ho, Frank Brouwers, Michiel Rienstra, Stephan Bakker, Anneke Muller Kobold, Dirk van Veldhuisen, Wiek van Gilst, Pim van der Harst, Rudolf De Boer
Journal: Journal of the American College of Cardiology (2016)
Abstract 3897: Design and preclinical evaluation of single agents with antitubulin and antiangiogenic activity as antitumor agents
Authors: Aleem Gangjee, Roheeth Kumar Pavana, Xin Zhang, Michael Ihnat, Ernest Hamel
Journal: Cancer Research (2012)

Abstract Agents that interfere with microtubules are important antitumor agents. Tumor angiogenic mechanisms that are vital for tumor growth and metastasis are targeted by antiangiogenic agents. Antiangiogenic agents are usually not tumoricidal but are mainly cytostatic. Combination chemotherapy with antiangiogenic and cytotoxic agents has shown significant promise, and several studies with such combinations are in progress in the clinic. Single agents with both antiangiogenic activities and cytotoxicity could afford single agents that would circumvent the pharmacokinetic problems of multiple agents, avoid drug-drug interactions, be used at lower doses to alleviate toxicity, be devoid of overlapping toxicities, and delay or prevent tumor cell resistance. We have designed, synthesized and evaluated two novel compounds, AG119 and AG425, that inhibit both vascular endothelial growth factor receptor-2 (VEGFR-2) for antiangiogenic effects and tubulin for cytotoxic effects in single agents. Both compounds have comparable potency as sunitinib and semaxinib against cell lines overexpressing VEGFR-2 and were equipotent with semaxinib on VEGFR-2 mediated endothelial cell proliferation, indicating a functional effect of these agents on VEGFR-2 inhibition (IC50: semaxanib 68.2 ± 4.2 µM, AG119: 60.2 ± 2.4 µM, AG425: 52.3 ± 3.8 µM). The novel compounds are effective and potent inhibitors (comparable to combretastatin A-4) of bovine brain tubulin assembly (IC50: combretastatin A-4 1.2 ± 0.01 µM, AG119: 3.5 µM, AG425: 1.9 ± 0.1 µM). The compounds were potent inhibitors of [3H]colchicine binding to tubulin, indicating that these compounds, particularly AG425, bind at the colchicine site. These agents cause microtubule depolymerization, arrest cells in late G2/M phase and trigger apoptotic cell death. Moreover, AG119 and AG425 are potent anticancer compounds in aggressive basal like breast cancer (BLBC) and triple negative breast cancer (TNBC) cell lines. The novel compounds showed sensitivity in taxol resistant cells, indicating that they are unlikely to be Pgp or MRP substrates [unlike taxol], and these compounds possess relative selectivity of kill on tumor versus normal cell types. In vivo these agents reduce tumor size and vascularity in two flank xenograft models [the BLBC MDA-MB-435 model and U251 glioma model] in immunodeficient mice, superior to docetaxel and sunitinib, without overt toxicity to the animals. 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 3897. doi:1538-7445.AM2012-3897
Case 2-2016
Authors: Ellen K. Roh, Mohammed Ali, Michael T. Lu, Scott H. Bradshaw
Journal: New England Journal of Medicine (2016)

An 84-year-old woman was admitted to the hospital because of chest pain, respiratory distress, and a purpuric rash. Initial chest imaging showed bilateral patchy and confluent opacities, a finding consistent with pulmonary edema. A diagnostic procedure was performed.
HIGH-THROUGHPUT SCREENING OF GLIOMA STEM CELL LINES FOR DRUG STRUCTURE- AND GENOTYPE-CORRELATED SENSITIVITY TO A PANEL OF TYROSINE KINASE INHIBITORS
Authors: J. de Groot, C. Thomas, Y. Piao, N. Nguyen, D. Drewry, B. Zuercher, R. Verhaak, C. Stephan, E. P. Sulman, F. Lang, A. Yung
Journal: Neuro-Oncology (2014)

BACKGROUND: There is substantial genetic heterogeneity among glioblastoma tumors from different patients. To develop an accurate depiction of the molecular determinants of response to therapy, we used a large collection of glioma stem cell lines (GSCs) to study the impact of this heterogeneity on response to tyrosine kinase inhibition. Twelve glioma stem cell (GSC) lines, which are representative of TCGA molecular subtypes, were utilized in a high-throughput compound-screening assay to identify drug sensitivities to over 350 tyrosine kinase inhibitors (GSK PKIS1) with varying cellular targets and mechanisms of kinase inhibition. METHODS: Cells were screened in 384-well plates at a density of 1000 cells/well with drug concentrations of either 5 or 0.5 µM. Cell viability measurements were taken using Cell-Titer Glo five days after drug treatment and compared to control wells. Compounds were defined as highly active (>90 % inhibition at 5 µM; >50% inhibition at 0.5 µM), moderately active (>70% inhibition at 5 µM; >30% inhibition at 0.5 µM), or weakly active (>50% inhibition at 5 µM; >15% inhibition at 0.5 µM.) Compounds used in the screen were analyzed for inhibition efficacy against 220 kinases (NanoSyn). RESULTS: Structure-activity relationship analysis identified three compounds that were highly active against eleven cell lines, three more compounds that were highly effective against at least seven cell lines, and seven additional compounds that were highly effective against at least four cell lines. Kinases identified as potential high value targets in selective cell lines include AKT1, PLK1, and IGF1R. Limited responses were seen to EGFR inhibitors. A separate set of compounds targeting TGF-beta, STAT3, PI3K and Notch were used for comparison of drug efficacy. Differential kinase activity amongst the effective compounds has been utilized to identify novel kinases for further study. Ongoing experiments are being performed to correlate the molecular phenotypes of the GSC's by analyzing RNAseq, whole exome, proteomic, DNA methylation, and copy number variation data with drug sensitivity. CONCLUSIONS: Integrating drug sensitivity and molecular phenotype will allow us to provide a complete picture of the underlying molecular determinants of GSC sensitivity and resistance to a panel of targeted kinases with the objective of ultimately designing personalized clinical trials for patients with glioblastoma. SECONDARY CATEGORY: n/a.
Abstract 2119: DDB2 and XPC influence ATR and ATM recruitment and regulate DNA damage response upon UV irradiation
Authors: Alo Ray, Keisha Milum, Aruna Battu, Altaf Wani
Journal: Cancer Research (2012)

Abstract DNA damage response (DDR) pathways control the activation of DNA repair mechanisms, the activation and eventual release of cell cycle checkpoints to prevent replication of damaged DNA, and apoptosis as a last resort. These processes suggest the coordination of numerous proteins required to preserve genomic integrity. ATR and ATM kinases are central to checkpoint activation in response to DNA damage and replication stress. Activated ATR and ATM phosphorylate several proteins involved in DNA repair and cell cycle arrest. The nature of the signal, which activates ATR and ATM in response to UV damage, is not clear. Here, we showed that DDB2 and XPC, two early damage recognition factors, promote ATR and ATM recruitment and phosphorylation. ATR and ATM localize to the damage site and physically interact with XPC and DDB2. ATR and ATM recruitment and their phosphorylation are affected in cells defective in DDB2 and XPC function. In contrast, ATR- and ATM-deficiency do not regulate DDB2 and XPC recruitment to the damage site. Consequently, phosphorylation of ATR and ATM substrates Chk1, Chk2, H2AX, and BRCA1 was significantly reduced or abrogated in mutated cells, indicating that defective DDB2 and XPC function impair checkpoint signal transduction cascade in response to UV damage. Furthermore, DDB2 and XPC also regulate BRCA1 and Rad51 recruitment to the damage site, implicating their role in homologous recombination-mediated DNA repair pathway. Collectively, these data showed that ATR and ATM are present in the preincision complex with XPC, and influence DNA repair and checkpoint signaling pathways. In support of this, we revealed that depletion of ATR and ATM influence NER efficiency. These results are consistent with a model in which DDB2 and XPC cross-talk with ATR and ATM during maintenance of genomic integrity. 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 2119. doi:1538-7445.AM2012-2119
OP0237-HPR Upper Limb Exercise, Education and Self Management in Early Rheumatoid Arthritis (The Extra Programme)- Results from a Randomised Controlled Trial
Authors: V. Manning, M. Hurley, D. L. Scott, E. Choy, L. Bearne
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Upper limb dysfunction occurs early in people with rheumatoid arthritis (RA) and deteriorates as disease progresses, impacting on independence. Exercise is a key component in the management of upper limb disability but studies focus on the hand in isolation and do not address proximal motor deficits. Tailored home exercise regimens are needed to address global upper limb dysfunction which, if completed long term, could encourage self management. <h3>Objectives</h3> To evaluate the effect of a brief, supervised education, self management and upper limb exercise programme, (Education and eXercise Training in early Rheumatoid Arthritis (EXTRA)) programme supplementing a home exercise regimen on upper limb disability. <h3>Methods</h3> 108 adults with RA for &lt;5 years (26 males, age mean (SD) 55 (15) years, disease duration 20 (19) months) were randomized to receive either Usual Care (n= 52) or the EXTRA programme (n=56). This programme comprised of 4 group, supervised upper limb exercise, education and self management sessions, aimed at improving self efficacy and disease self management (2 sessions/ week for the first 2 weeks, 1 hour/ session, 4-6 participants per group) supplementing a tailored functional home exercise regimen. Upper limb disability (Disability of Arm, Shoulder, Hand questionnaire (DASH)), function (Grip Ability Test (GAT)), self efficacy (Arthritis Self Efficacy Scale - pain subscale (PSE)) and disease activity (Disease Activity Score (DAS 28)) were assessed at baseline, 3 and 9 months. Intention to treat analysis using full factorial mixed Analysis of Variance (ANOVA) (treatment, time and treatment x time interaction) adjusted for baseline disease duration, disease activity and disability, and corrected for multiple comparisons, were used to determine between group differences,. Significance was accepted at P&lt;0.05. <h3>Results</h3> Compared to the usual care group, participants who completed the EXTRA programme had improved disability, function and self efficacy with no adverse effects on disease activity. <h3>Conclusions</h3> The EXTRA programme improves upper limb disability, self efficacy and function in people with early RA with no detrimental effects on disease activity and may be easily implemented into practice. <h3>Acknowledgements</h3> The authors would like to thank the patients and staff at King's, Lewisham, Guy's and St Thomas' NHS Foundation Trusts and the Physiotherapy Research Foundation, UK for their financial support. <h3>Disclosure of Interest</h3> V. Manning Grant/research support from: Physiotherapy Research Foundation, M. Hurley: None Declared, D. Scott: None Declared, E. Choy: None Declared, L. Bearne Grant/research support from: Physiotherapy Research Foundation
The dominance of the individual in intergroup relations research: Understanding social change requires psychological theories of collective and structural phenomena
Authors: Elizabeth Levy Paluck
Journal: Behavioral and Brain Sciences (2012)

Abstract Dixon et al. suggest that the psychological literature on intergroup relations should shift from theorizing “prejudice reduction” to “social change.” A focus on social change exposes the importance of psychological theories involving collective phenomena like social norms and institutions. Individuals' attitudes and emotions may follow, rather than cause, changes in social norms and institutional arrangements.
Abstract 902: Role of ABCC10 in taxane mediated resistance in non-small cell lung carcinoma.
Authors: Janet Wangari-Talbot, Bruce Zhang, Elizabeth Hopper-Borge
Journal: Cancer Research (2013)

Abstract Lung cancer is the leading cause of cancer deaths worldwide with non-small cell lung cancer (NSCLC) accounting for ∼85% of diagnosed cases. The 5 year survival rate for NSCLC is ∼15% with less than 7% of the patients alive 10 years after initial diagnosis. The taxanes, docetaxel and paclitaxel are potent chemotherapeutic drugs which result in cell cycle arrest and apoptosis through inhibition of microtubule depolymerization and are fundamental in cancer treatment regimens and are used as first line agents in NSCLC. Chemoresistance is a major obstacle in the treatment of NSCLC, an observation attributed in part to the drug efflux activity of the ATP Binding Cassette (ABC) transporter family proteins. ABCC10, a member of the ABC transporter family has been shown to confer resistance to various anti-neoplastic agents including docetaxel and paclitaxel in vitro. More importantly, Abcc10 null mice have been shown to exhibit increased tissue sensitivity to paclitaxel in vivo. Thus, ABCC10 may be an ideal target for investigation as a factor involved in reducing taxane efficacy. Here, we investigate whether ABCC10 has a role in taxane resistance in non-small cell lung carcinoma. Human NSCLC cell lines were examined for ABCC10 expression by western immunoblots ABCC10 expression was then targeted for suppression using short-hairpin RNAs in the NSCLC cell lines A549 and H1299. Our results show that ABCC10 is expressed at varying levels in human NSCLC cell lines. Furthermore, suppression of ABCC10 in NSCLC cell lines resulted in increased cellular accumulation of docetaxel as well as a reduction in the efflux of the drug out of the cells. Further studies are needed to assess effects of ABCC10 in vivo on docetaxel sensitivity as well as the mechanisms involved in regulating ABCC10 activity. Citation Format: Janet Wangari-Talbot, Bruce Zhang, Elizabeth Hopper-Borge. Role of ABCC10 in taxane mediated resistance in non-small cell lung carcinoma. [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 902. doi:10.1158/1538-7445.AM2013-902
LEFT VENTRICULAR LAYER FUNCTION IN HYPERTENSION ASSESSED BY STRAIN RATE USING THE NOVEL ONE-BEAT REAL-TIME 3-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY WITH HIGH VOLUME RATES
Authors: Tai Kojima, Masanori Kawasaki, Ryuhei Tanaka, Shingo Minatoguchi, Maki Saeki, Maki Nagaya, Noriaki Sato, Koji Ono, Maya Ishiguro, Takashi Yoshizane, Takatomo Watanabe, Shunichiro Warita, Makoto Iwama, Toshiyuki Noda, Sachiro Watanabe, Shinya Minatoguchi
Journal: Journal of the American College of Cardiology (2015)
Turning science into clinical practice – the case of carbon dioxide insufflation
Authors: M. Bretthauer
Journal: Endoscopy (2010)

Insufflation of gas (most often room air) is required during all endoscopic procedures. The volume of insufflated gas far exceeds that naturally occurring in the physiologic environment of the gastrointestinal tract. For instance, between 8 and 14 L of gas are insufflated during colonoscopy [1] [2], whereas the physiologic gas volume in the gastrointestinal tract is estimated to be only 0.1 – 1.0 L [3]. Thus, it is not surprising that many patients undergoing endoscopy experience considerable discomfort due to retained gas in the gastrointestinal tract.
SP0112 Lymphoid tissue inducer cells are sufficient for memory CD4 T cell survival
Authors: D. Withers
Journal: Annals of the Rheumatic Diseases (2013)

Maintaining memory T cells is critical to the success of vaccination and T cell survival is heavily influenced by costimulatory molecules, amongst which, the tumour necrosis factor super family members OX40 and CD30 are clearly important for CD4 T cells. Since lymphoid tissue inducer (LTi) cells, the key hematopoietic cell type responsible for lymph node formation, constitutively express high levels of both OX40L and CD30L in the adult, but not the embryo (when lymph nodes form), we investigated whether these cells were involved in memory CD4 T cell survival in vivo. Mice deficient in RORg, which lack LTi cells, were unable to generate memory antibody responses upon challenge. Furthermore, antigen-specific memory CD4 T cells failed to survive in RORg<sup>-/-</sup> mice. To specifically test whether LTi cells were the RORg-dependent population required, memory CD4 T cells were transferred into chimeric mice comparable except for the presence or absence of LTi cells. The survival of these memory CD4 T cells was entirely LTi cell dependent. Whilst naive CD4 T cell survival was unaffected by the absence of LTi cells, the persistence of memory phenotype cells arising from homeostatic proliferation, was also LTi-dependent. Agonistic anti-OX40 Abs could rescue memory T cell survival in the absence of LTi cells, indicating that provision of OX40L is one mechanism by which LTi cells support CD4 T cell survival. In summary, we demonstrate that LTi cells support memory CD4 T cells in vivo identifying a novel and important role for these innate lymphoid cells. <h3>Disclosure of Interest</h3> None Declared
ASSESSMENT OF THE EFFECT OF A MEAL ON THE ABSORPTION KINETICS OF THEOPHYLLINE WITH Tc-99m-DTPA LABELED TABLETS.
Authors: Jean C. Maublant, M. Sournac, J. M. Aiache, A. Veyre
Journal: Clinical Nuclear Medicine (1988)

Centre Jean Perrin, INSERM U71 and Faculté de Médecine, Clermont-Ferrand, and Centre de Recherche Pierre Fabre Medicament, Castres, France.