tbuckley/cabot-search huggingface dataset:
OP0222 (Collagen Specific-)T Cell Related Parameters Provide Information for the Management of Rheumatoid Arthritis Patients
Authors: G. Di Sante, C. Nicolò, A.L. Fedele, E. Gremese, B. Tolusso, A. Carbonella, M.R. Gigante, S.L. Bosello, F. Ria, G. Ferraccioli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The developmental risk of Rheumatoid Arthritis (RA) is strongly linked to HLA-DRB1*04 (DR4) and *01 (DR1). In RA, activated immune cells, as CD4+T cells, B cells, dendritic cells and macrophages infiltrate the synovial tissue. In a previous work, we found that huCollp261-273-specific T cell repertoire analyzed in peripheral blood of DR4+ RA patients was restricted to a limited number of TCR rearrangements. This collagen-specific repertoire appears modulated by disease activity (1). The two most used TCR-beta chains were TRBV25-TRBJ2.2 and TRBV6-4-TRBJ2-3. <h3>Objectives</h3> To examine the frequency and the distribution of huCollp261-273-specific T cells and the role of DR alleles in RA patients in order to find new biomarker for the management of the disease. <h3>Methods</h3> HLA genotyping was performed using the Innogenetics® kit, following the manufacturer9s protocol. TCR repertoire analysis: Peripheral blood mononuclear cells (PBMCs) were purified from whole blood and TCR BV-JB analysis was performed as previously described. (1) Patients: we analyzed 100 samples from RA patients, 57 with a high disease activity (DAS &gt;3.7) and 43 with a low disease activity (DAS≤2.4). <h3>Results</h3> The presence of TRBV25-TRBJ2.2 and TRBV6-4-TRBJ2-3 in T cells was significantly associated with disease activity in the group of DR4+ RA patients. The usage of these two receptors described two non-overlapping groups of RA patients, with subjects using TRBV6-4+ displaying a significantly higher disease activity. The combination of TCR usage in DR4+ subjects and of DR haplotypes in RA patients described four distinct responses to treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and biologic agents. Fifty percent of DR4+ TRBV25- patients responded to DMARDs and the remaining responded well to biologic agents; DR4+ TRBV25+ patients failed to respond to DMARDs but displayed a good response to biologic agents and this latter group might therefore be candidate to treatment with biologic agents. In the group of DR4-, DR1- or DR7-patients, the DR11 allele appeared highly enriched in subjects displaying a high disease activity. Accordingly, within the group of DR4-, DR1- DR7- RA patients, we observed that 50% of all patients achieved a good response after DMARDs treatment; among patients non-responder to DMARDs, however, it appeared that DR11+ subjects responded to a lesser extent than DR11- patients to biologic agents. <h3>Conclusions</h3> These findings showed that the analysis of collagen specific T cells repertoire and HLA-DR haplotype can provide useful information to a personalized treatment in RA patients. <h3>References</h3> Ria F., et al. Arthritis Research &amp; Therapy, 2008. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4311
Graceful degradation and conceptual development
Authors: Frank Keil
Journal: Behavioral and Brain Sciences (2011)

Abstract In this book, Carey gives cognitive science a detailed account of the origins of concepts and an explanation of how origins stories are essential to understanding what concepts are and how we use them. At the same time, this book's details help highlight the challenge of explaining how conceptual change works with real-world concepts that often have heavily degraded internal content.
Complete mucosal healing defined by endoscopic Mayo subscore still demonstrates abnormalities by novel high definition colonoscopy and refined histological gradings
Authors: Marietta Iacucci, Miriam Fort Gasia, Cesare Hassan, Remo Panaccione, Gilaad Kaplan, Subrata Ghosh, Xianyong Gui
Journal: Endoscopy (2015)

<b>Background and study aims:</b> A novel high definition colonoscopy imaging technique (i-Scan) can characterize, in detail, colonic mucosa in patients with ulcerative colitis, and may provide additional information about mucosal healing. The aim of this study was to create a more refined histological and endoscopic criteria based on this novel technique in order to redefine inflammatory activity and mucosal healing. <b>Patients and methods:</b> A total of 78 patients with ulcerative colitis were assessed by high definition colonoscopy as well as by white light endoscopy (WLE). Mayo endoscopic subscores were assigned to patients according to WLE findings. Mucosal and vascular patterns on high definition colonoscopy were each graded from 1 – 4. A histological scoring system (ECAP system) was designed to reflect all histological changes in ulcerative colitis. <b>Results:</b> The overall high definition imaging scores (mucosal and vascular patterns) were significantly correlated with Mayo endoscopic subscores (rs = 0.86, 95 % confidence interval [CI] 0.79 – 0.91; <i>P</i> < 0.0001). Of those with Mayo endoscopic subscore of 0, 30.4 % had an abnormal mucosal pattern and 73.9 % of them had an abnormal vascular pattern on high definition colonoscopy; a score of 6 or less had a sensitivity of 95.8 % (95 %CI 85.7 % – 99.3 %) and specificity of 75.9 % (95 %CI 56.5 % – 90.0 %) to detect mucosal healing as defined by Mayo endoscopy subscore of 0 or 1. Furthermore, mucosal and vascular pattern scores were also significantly correlated with most parameters of the proposed ECAP score. <b>Conclusion:</b> The subtle histological abnormalities underlying the apparently healed mucosa in ulcerative colitis could be detected using high definition colonoscopy and the refined ECAP histology scoring system. These techniques detect residual abnormalities in the majority of patients with seemingly complete mucosal healing by conventional Mayo criteria.
OP0196 An Alteration in Circulating CXCR5+CD4+ T Cell Subsets in RA Patients is Associated with Increased Circulating Plasmablasts
Authors: I. Arroyo-Villa, M.-B. Bautista-Caro, A. Balsa, P. Aguado, A. Villalba, C. Plasencia, E. Martín-Mola, M.-E. Miranda-Carus
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RA is an autoimmune condition characterized by chronic joint inflammation. Tfh cells, a recently described Th subset localized in lymphoid organs, help B cell differentiation and function. Circulating central memory CD4 T cells expressing CXCR5 can be subdivided into three different subpopulations based on the combined expression of surface CXCR5 with or without CCR6 and/or CXCR3: CXCR5+CXCR3+CCR6- (Tfh-Th1), CXCR5+CXCR3-CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 cells have been demonstrated to display functional properties of Tfh cells; in contrast Tfh-Th1 cells are unable to provide B cell help. An altered proportion of these subpopulations has been associated with autoimmune diseases. <h3>Objectives</h3> To study the frequency of circulating CXCR5+CD4+ T cell subsets together with the frequency of circulating plasmablasts (CD19+CD20-CD27+CD38high B cells) in patients with RA. <h3>Methods</h3> Peripheral blood was drawn from healthy controls (n=27) and RA patients (n=27). After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CXCR5, CCR6, CXCR3, CD19, CD20, CD27, and CD38, and examined by flow cytometry. The percentages of CXCR5+CXCR3+CCR6- (Tfh-Th1), CXCR5+CXCR3-CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh/Th2) cells were calculated after gating for CD3, CD4 and CXCR5+. The percentage of CD20-CD38high cells was calculated after gating for CD19+ and CD27+. <h3>Results</h3> The frequency of circulating CXCR5+ cells gated for CD4+ T cells was not different among the studied groups. In contrast, in RA patients, the frequency of Tfh-Th1 cells was significantly decreased and the frequency of Tfh-Th17 and Tfh-Th2 cells was significantly increased as compared with controls. Subsequently, the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1 was increased in RA patients. That is, RA patients demonstrate a higher proportion of Tfh cells bearing a phenotype associated with B cell helping capacity. At the same time, the frequency of circulating plasmablasts was increased in RA patients as compared with controls. Interestingly, there was a significantly positive correlation between the percentage of circulating plasmablasts and the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1, together with a significantly negative correlation between the percentage of circulating plasmablasts and the percentage of circulating Tfh-Th1 cells. <h3>Conclusions</h3> RA patients demonstrate altered proportions of circulating Tfh subpopulations, with overrepresentation of subsets bearing a phenotype associated with B cell helping capacity. At the same time, an increased proportion of circulating plasmablasts is apparent in RA patients. <h3>Disclosure of Interest</h3> None Declared
Cost Effectiveness of Bone Marrow Transplantation in Acute Nonlymphocytic Leukemia
Authors: H. Gilbert Welch, Eric B. Larson
Journal: New England Journal of Medicine (1989)

To compare the cost effectiveness of bone marrow transplantation and conventional chemotherapy, we evaluated the resources used in the care of adult patients with acute nonlymphocytic leukemia who were enrolled in a prospective trial and received induction chemotherapy at a single university hospital. Nineteen patients were subsequently treated with chemotherapy and 17 with transplantation. Cost accounting began with induction chemotherapy and extended over a five-year period. Costs were estimated by means of a resource-based, multivariate prediction model. The transplantation and chemotherapy groups had virtually equivalent use of resources (hospital days, laboratory tests, blood products, and radiologic and operative procedures) over five years, except for a 10-fold increase in the use of the intensive care unit for the patients who underwent transplantation (P less than 0.001). The total costs over five years were estimated at $193,000 per patient for transplantation and $136,000 per patient for chemotherapy (P = 0.02). At five years, the costs per year of life saved ("life-year") were nearly equal ($62,500 per life-year for transplantation vs. $64,000 per life-year for chemotherapy) because of the better rate of disease-free survival in patients who underwent bone marrow transplantation. We conclude that the cost effectiveness of bone marrow transplantation to treat acute nonlymphocytic leukemia compares favorably with that of chemotherapy and could be further enhanced if intensive care resources were used more selectively.
Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression
Authors: Virissa Lenters, Lützen Portengen, Anna Rignell-Hydbom, Bo A.G. Jönsson, Christian H. Lindh, Aldert H. Piersma, Gunnar Toft, Jens Peter Bonde, Dick Heederik, Lars Rylander, Roel Vermeulen
Journal: Environmental Health Perspectives (2015)

BackgroundSome legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures.ObjectivesWe assessed associations between multiple correlated biomarkers of environmental exposure and birth weight.MethodsWe evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models.ResultsTwo phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL).ConclusionsThis study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.CitationLenters V, Portengen L, Rignell-Hydbom A, Jönsson BA, Lindh CH, Piersma AH, Toft G, Bonde JP, Heederik D, Rylander L, Vermeulen R. 2016. Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts: multi-pollutant models based on elastic net regression. Environ Health Perspect 124:365–372; http://dx.doi.org/10.1289/ehp.1408933
Regulatory Reply to the ATMOSPHERE Data Monitoring Committee
Authors: Tomas Salmonson, Heidi Janssen, Thomas Sudhop, Elke Stahl
Journal: New England Journal of Medicine (2016)

To the Editor: We agree with Swedberg et al.,1 whose Sounding Board article is now published in the Journal, regarding the role and responsibilities of the data monitoring committee. We also agree that the data monitoring committee should be allowed to act independently during the progress of a trial. The committee’s role is to provide continuous safety monitoring of the trial and to make recommendations on further trial conduct.2 Regulators such as the European Medicines Agency (EMA) must also act in line with their responsibilities regarding the safety of medicines. It is their role to continuously review any new information . . .
FDA Approval is Not the End: Getting the Most Out of Taxol
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article FDA Approval is Not the End: Getting the Most Out of Taxol Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 3, 3 February 1993, Pages 181–182, https://doi.org/10.1093/jnci/85.3.181 Published: 03 February 1993
Abstract 4514: Proteasome inhibition causes regression of leukemia in part through regulation of forkhead tumor suppressors
Authors: Amrik Singh, Min Ye, Keli Song, Octavian Bucur, Roya Khosravi-Far
Journal: Cancer Research (2010)

Abstract BCR-ABL plays an essential role in the pathogenesis of chronic myeloid leukemia (CML) and some cases of acute lymphocytic leukemia (ALL). Although ABL kinase inhibitors have shown great promise in the treatment of CML, the persistence of residual disease and the occurrence of resistance have prompted investigations into the molecular effectors of BCR-ABL. Here, we show that BCR-ABL stimulates the proteasome-dependent degradation of members of the forkhead family of tumor suppressors in vitro, in an in vivo animal model, and in samples from patients with BCR-ABL-positive CML or ALL. As several downstream mediators of BCR-ABL are regulated by the proteasome degradation pathway, we also show that inhibition of this pathway, using bortezomib, causes regression of CML-like disease. Bortezomib treatment led to inhibition of BCR-ABL-induced suppression of FoxO proteins and their proapoptotic targets, tumor necrosis factor-related apoptosis-inducing ligand and BIM, thereby providing novel insights into the molecular effects of proteasome inhibitor therapy. We additionally show sensitivity of imatinib-resistant BCR-ABL T315I cells to bortezomib. Our data delineate the involvement of FoxO proteins in BCR-ABL-induced evasion of apoptosis and provide evidence that bortezomib is a candidate therapeutic in the treatment of BCR-ABL-induced leukemia. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4514.
Cryospectrophotometric Determination of Tumor Intravascular Oxyhemoglobin Saturations: Dependence on Vascular Geometry and Tumor Growth
Authors: B M Fenton, E K Rofstad, F L Degner, R M Sutherland
Journal: JNCI Journal of the National Cancer Institute (1988)

To delineate the complex relationships between overall tumor oxygenation and vascular configuration, intravascular oxyhemoglobin (HbO2) saturation distributions were measured with cryospectrophotometric techniques. Four factors related to vascular morphometry and tumor growth were evaluated: a) vessel diameter, b) distance of vessel from the tumor surface, c) tumor volume, and d) vascular density. To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized. In contrast to skeletal muscle, a preponderance of very low HbO2 saturations was observed for both large and small tumors of all lines. Saturations up to about 90% were also generally present, however, even in very large tumors. Variations in vascular configuration were predominantly tumor-line dependent rather than due to inherent characteristics of the host vasculature, and widely disparate HbO2 distributions were found for alternate lines implanted in identical host mice. Although peripheral saturations remained fairly constant with tumor growth, HbO2 values were markedly lower for vessels nearer the tumor center and further decreased with increasing tumor volume. HbO2 satuations did not change substantially with increasing vascular density (except for KHT tumors), although density did decrease with increasing distance from tumor surface. Combined effects of vessel diameter, tumor volume, and vessel location on HbO2 saturations were complex and varied markedly with both tumor line and vessel class. For specific classes, HbO2 distributions correlated closely with radiobiological hypoxic fractions, i.e., for tumor lines in which hypoxic fraction increased substantially with tumor volume, corresponding HbO2 values decreased, while for lines in which hypoxic fraction remained constant, HbO2 values also were unchanged. Although these trends may also be a function of differing oxygen consumption rates between tumor lines, functional alterations in the rapidly expanding tumor vasculature undoubtedly play a primary role in explaining spatial oxygenation heterogeneities.
PREDICTORS OF IN-HOSPITAL GASTROINTESTINAL BLEEDING FOLLOWING PERCUTANEOUS CORONARY INTERVENTION IN THE UNITED STATES
Authors: Dhaval Pau, Nileshkumar Patel, Nikhil Nalluri, Hafiz Khan, Ritesh Kanotra, Kanishk Agnihotri, Nilay Patel, Shilpkumar Arora, Azfar Sheikh, Moiz Ahmed, Marc Bogin, James Lafferty
Journal: Journal of the American College of Cardiology (2016)
Abstract P2-13-01: Effects of 12-Week Resistance Training on Strength, Fatigue Syndrome and Quality of Life with Breast Cancer Patients during Chemotherapy
Authors: FT Baumann, A Leskaroski, A Knicker, H Krakowski-Roosen, W Bloch, N. Harbeck
Journal: Cancer Research (2010)

Abstract Introduction: Up to 100% of all breast cancer patients are suffering from fatigue during chemotherapy [Mock 2001, Jacobsson 1998, Irvine 1994]. Causality as well as the treatment of this non-uniform symptom complex is yet unclear. Exercising studies show a positive effect of endurance training on the development of fatigue [Dimeo 2003]. The study situation regarding feasibility and efficiency of pure resistance training with breast cancer patients with fatigue is still unsatisfactory [De Backer 2009, Courneya 2007]. Methods: In this prospective, controlled, randomized study 32 female patients were recruited 6 weeks after operation. 20 probands (IG) accomplished a 12-week resistance training (2 x per week, 60 min each with 75% of the maximum voluntary capacity) during adjuvant chemotherapy. The control group (CG, n=12) did not train. The measurements took place before and after the intervention and maximally isometric and isocinetic strength was tested with the Isomed 2000. Quality of life was evaluated with the EORTC QLQ-C30 inclusive module BR23 and fatigue symptoms by the MFI questionnaires. Results: No exacerbations could be observed during the study. Strength (p=0.029), fatigue (p=0.048) and different ranges of the quality of life significantly improved in IG, while in CG fatigue and quality of life worsened. 4 out of 5 ranges of the fatigue diagnostic (f.e. General Fatigue, p=0.01) as well as nearly all ranges of the quality of life evaluation were significantly different between IG and KG. In addition, muscle strength (of the arm concerned) showed significant differences between the groups (p=0.032). Discussion: It could be shown for the first time, that maximum strength testing as well as resistance training with breast cancer patients were feasible already 6 weeks post-OP. Positively, the increase in muscle power, the reduction of fatigue symptoms and the improvement of the quality of life occurred despite concurrent cytotoxic treatment. We rate the high acceptance of the training program as a success. Based on the positive results and the past studies [De Backer 2009, Courneya 2007] we recommend the integration of strength training into the early rehabilitation of breast cancer patients. We note that this study will be completed by December 2010 yet further studies have to be conducted, in order to better understand the effects of different training intensities. Literature: Courneya et al.: JCO 2007; 25: 4396-4404 Dimeo et al.: Sup Care in Canc 2003; 11:S623-628 Irvine et al. Cancer Nurs 1994; 17: 367-378 Jacobsson et al. J Pain Symptom Manage 1999;18 (4): 233-242 Mock V. Cancer Suppl 2001; 92 (6): 1699-1707 Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-13-01.