tbuckley/cabot-search huggingface dataset:
Open-label, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study
Authors: D. E Furst, N. Gaylis, V. Bray, E. Olech, D. Yocum, J. Ritter, M. Weisman, D. J Wallace, J. Crues, D. Khanna, G. Eckel, N. Yeilding, P. Callegari, S. Visvanathan, J. Rojas, R. Hegedus, L. George, K. Mamun, K. Gilmer, O. Troum
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To incorporate a new trial design to examine clinical response, cytokine expression and joint imaging in patients with rheumatoid arthritis (RA) switching from etanercept to infliximab treatment. <b>Methods:</b> A randomised, open-label, clinical trial of 28 patients with an inadequate response to etanercept was conducted. Eligible patients received background methotrexate and were randomised 1:1 to discontinue etanercept and receive infliximab 3 mg/kg at weeks 0, 2, 6, 14 and 22, or to continue etanercept 25 mg twice weekly. Data were analysed for clinical response, serum biomarker levels, radiographic progression, MRI and adverse events. <b>Results:</b> At week 16, 62% of infliximab-treated patients achieved American College of Rheumatology 20% criteria for improvement in RA (ACR20) responses compared with 29% of etanercept-treated patients. A 30.8% decrease from baseline in Disease Activity Score 28 was observed in patients receiving infliximab, compared with a 16.0% decrease in patients receiving etanercept. ACR20 and American College of Rheumatology 50% criteria for improvement in RA responses correlated at least minimally with intracellular adhesion molecule-1 and interleukin 8 in patients receiving infliximab. 38% of patients who were switched to infliximab showed reductions in Health Assessment Questionnaire scores (&gt;0.4), compared with 0% of patients receiving etanercept. MRI analyses were inconclusive. Both drugs were well tolerated; 54% of infliximab-treated patients and 50% of etanercept-treated patients reported adverse events. <b>Conclusions:</b> In this exploratory, open-label trial (with single-blind evaluator), patients were randomised to continue with etanercept or switch to infliximab. The small sample size of this hypothesis-generating study was underpowered to show statistical differences between groups. There was a numerical trend favouring patients who switched to infliximab, therefore warranting further study with a more rigorous design.
Sternal sinus following Teflon reconstruction of the right ventricular outflow tract
Authors: P. B. Deverall, G. H. Wooler
Journal: Thorax (1968)

A case of chronic sternal sinus is described in which exploration revealed a loose patch of Teflon felt which had been used three years earlier in reconstructing the outflow tract of the right ventricle in a case of congenital pulmonary stenosis. Teflon, a synthetic polymer of low biological reactivity, while being suitable in its solid sheet form for use in plastic reconstructive surgery, is not ideally suited to cardiovascular work. The properties of such an ideal material are defined. The low reactivity and porosity of Teflon, by reducing fibroblastic invasion, lessens the likelihood of the material being incorporated by host tissues. From experimental and clinical evidence we no longer regard Teflon felt as a suitable prosthetic material for use in intracardiac or vascular work or in reconstruction of the right ventricular outflow tract.
Analysis of a prospectively randomized comparison of doxorubicin versus 5-fluorouracil, doxorubicin, and BCNU in advanced gastric cancer: implications for future studies.
Authors: J A Levi, R M Fox, M H Tattersall, R L Woods, D Thomson, G Gill
Journal: Journal of Clinical Oncology (1986)

A multi-institutional cooperative study of patients with locally advanced, recurrent, or metastatic gastric adenocarcinoma who had not previously received chemotherapy was conducted, prospectively randomizing patients to receive either doxorubicin or the three-drug combination, 5-fluorouracil (5-FU), doxorubicin (Adriamycin; Adria Laboratories, Columbus, Ohio), and BCNU (FAB). The 187 evaluable patients were initially stratified according to the presence of measurable or evaluable disease and performance status. There was a significantly higher response rate observed for FAB (40%) compared with doxorubicin (13%) among the 145 measurable-disease patients. Duration of response and survival were significantly longer for FAB in the measurable-disease group, but for the total patient population an early advantage for FAB in time to disease progression and survival was lost with continued follow-up. Median survival was 33 weeks for patients receiving FAB and 19 weeks for those receiving doxorubicin. Significant pretreatment factors adversely affecting survival included poor performance status, weight loss of greater than 10%, and more than two sites of metastases. Toxicity was not severe in either treatment arm, and only thrombocytopenia occurred significantly more often with FAB. It is contended that in the treatment of advanced gastric cancer, chemotherapy only exerts a relatively short-term and modest beneficial effect, most apparent in patients with intermediate tumor bulk. 5-FU remains the most active single agent, and combination chemotherapy has not yet proven its overall worth. Further studies are indicated comparing the most active combinations with 5-FU using optimal doses and schedules, and consideration must be given to the incorporation of no-treatment controls.
Deliberate Deceit of Family Members: A Challenge to Providers of Clinical Genetics Services
Authors: Jennifer T. Loud, Nancy E. Weissman, June A. Peters, Ruthann M. Giusti, Benjamin S. Wilfond, Wylie Burke, Mark H. Greene
Journal: Journal of Clinical Oncology (2006)

The proband was a 55-year-old white female who sought pretest counseling when she learned that her father was a BRCA1 mutation carrier. Her father is 85 years old, in good health, and is a brother of a woman who died as a result of ovarian cancer at the age of 35. He learned his mutation status as a participant in a National Cancer Institute research study of familial breast and ovarian cancer. He encouraged all of his children to enroll onto the study and to consider testing. The proband and her siblings (two sisters ages 40 and 48, and a brother age 38, all unaffected) decided to obtain pretest counseling and consider genetic testing. During pretest counseling, the proband revealed her preference that information related to a positive mutation test, in either herself or her siblings, be withheld from her parents. Her rationale was to protect her father from the guilt of having passed a mutation on to an offspring. She stated that her test results “were her own,” and that she would not disclose results to her relatives, whether she tested negative or positive. She also indicated that she would attempt to influence how her siblings communicated their personal test results within the family, by encouraging them to withhold their results, should they learn that they were mutation carriers. All four siblings chose to be tested and their results were disclosed in individual sessions on the same day. The proband, one sister, and her brother had the same mutation that had been identified in their father; the other sister tested negative. The proband was assured that the research team would preserve the confidentiality of her information. She stated that she clearly understood the implications of her test results for her children, that she would “take care of them,” promising that they would be informed of the test results when it “was appropriate.” The proband’s siblings shared their mutation results with family members in the waiting room following their disclosure session. However, in the presence of several members of the research team, the proband lied to her family members about her test results, informing her family that she had tested negative for the BRCA1 mutation.
Hypoxia-Inducible Factor 1–Dependent Induction of Intestinal Trefoil Factor Protects Barrier Function during Hypoxia
Authors: Glenn T. Furuta, Jerrold R. Turner, Cormac T. Taylor, Robert M. Hershberg, Katrina Comerford, Sailaja Narravula, Daniel K. Podolsky, Sean P. Colgan
Journal: The Journal of Experimental Medicine (2001)

Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, the intestine, and particularly barrier-protective epithelial cells, are susceptible to damage related to diminished blood flow and concomitant tissue hypoxia. We sought to identify compensatory mechanisms that protect epithelial barrier during episodes of intestinal hypoxia. Initial studies examining T84 colonic epithelial cells revealed that barrier function is uniquely resistant to changes elicited by hypoxia. A search for intestinal-specific, barrier-protective factors revealed that the human intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA binding activity, and loading cells with antisense oligonucleotides directed against the α chain of HIF-1 resulted in a loss of ITF hypoxia inducibility. Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in epithelial cells exposed to hypoxia, and the addition of recombinant human ITF to vascular endothelial cells partially protected endothelial cells from hypoxia-elicited barrier disruption. Extensions of these studies in vivo revealed prominent hypoxia-elicited increases in intestinal permeability in ITF null mice. HIF-1–dependent induction of ITF may provide an adaptive link for maintenance of barrier function during hypoxia.
Scleroderma in childhood.
Authors: B M Ansell, G A Nasseh, E G Bywaters
Journal: Annals of the Rheumatic Diseases (1976)

Scleroderma in childhood is a rare but confusing disorder. Systemic and diffuse disease do occur but are uncommon. Much more common are local lesions of different types which can be multiple; these are often associated with joint symptoms and the development of joint contractures and tendon contractures due to nodule formation. In such circumstances the condition mimics juvenile chronic polyarthritis (Still's disease). A third, rare variant, sclerodermatous fasciitis, has also been described in one young patient.
Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.
Authors: S Slavin, Z Fuks, H S Kaplan, S Strober
Journal: The Journal of Experimental Medicine (1978)

Bone marrow (BM) and skin allografts from C57BL/Ka (H-2b/b) mice were transplanted to BALB/c (H-2d/d) recipients treated with total lymphoid irradiation (TLI), whole-body irradiation (WBI), or fractionated thymic irradiation TLI prolonged skin allograft survival about five times as long as that in untreated controls, and allowed for permanent engraftment of BM cells in approximately equal to 90% of recipients. None of the BM recipients showed clinical signs of graft-versus-host disease (GVHD) (diarrhea, weight loss, hunched back, etc.). On the other hand, recipients given WBI and allogeneic BM cells developed severe clinical GVHD. The majority of the latter recipients died within 12 days after BM transplantation, and 95% died within 61 days. Although TLI protected BALB/c mice against GVHD induced by BM cells, all recipients given TLI and allogeneic spleen cells developed lethal GVHD. Thymic irradiation alone marginally prolonged skin allograft survival, and did not allow for allogeneic BM engraftment. These results suggest that TLI may be a useful regimen in clinical BM transplantation, since this form of radiotherapy is used extensively in humans and has few severe side effects.
Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study
Authors: Umberto Veronesi, Giovanni Paganelli, Giuseppe Viale, Alberto Luini, Stefano Zurrida, Viviana Galimberti, Mattia Intra, Paolo Veronesi, Patrick Maisonneuve, Giovanna Gatti, Giovanni Mazzarol, Concetta De Cicco, Gianfranco Manfredi, Julia Rodríguez Fernández
Journal: The Lancet Oncology (2006)
Bone Marrow Fibrosis In Immune Thrombocytopenia (ITP) Patients Treated With Thrombopoietin Receptor Agonists (TRA) – a Single Center Long-Term Follow-Up
Authors: Waleed Ghanima, Julia Turbiner Geyer, Christina Soo Lee, Attilio Orazi, Leonardo Boiocchi, Allison Imahiyerobo, James B. Bussel
Journal: Blood (2013)
Plasmacytoid Dendritic Cells Induce CD8+ Regulatory T Cells In Human Ovarian Carcinoma
Authors: Shuang Wei, Ilona Kryczek, Linhua Zou, Ben Daniel, Pui Cheng, Peter Mottram, Tyler Curiel, Andrzej Lange, Weiping Zou
Journal: Cancer Research (2005)

To directly dissect the role of each immune component in human tumor immunopathogenesis, we have studied the interaction between dendritic cells and T cells in the tumor environment of patients with ovarian carcinoma. We previously reported that functional plasmacytoid dendritic cells, but not functionally mature myeloid dendritic cells, accumulated in tumor microenvironments. We now show that tumor ascites macrophage-derived dendritic cells induced tumor-associated antigen-specific CD8+ T cells with effector functions. Strikingly, tumor ascites plasmacytoid dendritic cells induced interleukin-10+ CCR7+ CD45RO+ CD8+ regulatory T cells. Four characteristics have been identified in tumor plasmacytoid dendritic cell-induced CD8+ regulatory T cells: (a) induction of CD8+ regulatory T cells is independent of CD4+ CD25+ T cells; (b) CD8+ regulatory T cells significantly suppress myeloid dendritic cell-mediated tumor-associated antigen-specific T cell effector functions through interleukin-10; (c) repetitive myeloid dendritic cell stimulation can recover CD8+ regulatory T cell-mediated poor T cell proliferation, but not T cell effector function; (d) CD8+ regulatory T cells express functional CCR7, and efficiently migrate with lymphoid homing chemokine MIP-3beta. Primary suppressive CCR7+ CD45RO+ CD8+ T cells are found in the tumor environment of patients with ovarian cancers. Thus, tumor-associated plasmacytoid dendritic cells contribute to the tumor environmental immunosuppressive network. Collectively, tumors manipulate tumor microenvironmental dendritic cell subset distribution and function to subvert tumor immunity. The data are relevant to understanding tumor immunopathology as well as reevaluating tumor immunotherapeutic strategies.
Biennial Versus Annual Mammography and the Risk of Late-Stage Breast Cancer
Authors: E. White, D. L. Miglioretti, B. C. Yankaskas, B. M. Geller, R. D. Rosenberg, K. Kerlikowske, L. Saba, P. M. Vacek, P. A. Carney, D. S. M. Buist, N. Oestreicher, W. Barlow, R. Ballard-Barbash, S. H. Taplin
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Mammography screening may reduce breast cancer mortality by detecting cancers at an earlier stage. However, certain questions remain, including the ideal interval between mammograms. Methods: We conducted an observational study using information collected by seven mammography registries across the United States to investigate whether women diagnosed with breast cancer after having screening mammograms separated by a 2-year interval (n = 2440) are more likely to be diagnosed with late-stage disease (positive lymph nodes or metastases) than women diagnosed with breast cancer after having screening mammograms separated by a 1-year interval (n = 5400). Analyses were stratified by age and breast density to clarify whether groups that have the poorest mammography sensitivity (i.e., women under age 50 years and those with mammographically dense breasts) would benefit most from annual screening. The subjects were women diagnosed with breast cancer between 1996 and 2001 who were 40–89 years old at their index mammographic examination (i.e., the most recent screen at or before breast cancer diagnosis). Data were analyzed by logistic regression, adjusting for race, ethnicity, family history of breast cancer, and mammography registry. Results: Among women age 40–49 years at the index mammogram, those with a 2-year screening interval were more likely to have late-stage disease at diagnosis than those with a 1-year screening interval (28% versus 21%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.01 to 1.81). There was no increase in late-stage disease for women 50 years or older with a 2-year versus a 1-year screening interval (women age 50–59 years at index mammogram: OR = 0.97, 95% CI = 0.75 to 1.25; women age 60–69 years at index mammogram: OR = 0.99, 95% CI = 0.72 to 1.35; women age 70 years or older at index mammogram: OR = 0.88, 95% CI = 0.64 to 1.19). There was no indication that women with dense breasts would benefit more from a 1-year versus 2-year screening interval than women with fatty breasts. Conclusion: These findings may be useful for policy decisions about appropriate screening intervals and for use in statistical models that estimate the costs and benefits of mammography by age and screening interval.
Thomsen-Friedenreich and Tn Antigens in Nipple Fluid: Carbohydrate Biomarkers for Breast Cancer Detection
Authors: Senthil R. Kumar, Edward R. Sauter, Thomas P. Quinn, Susan L. Deutscher
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Novel biomarkers would facilitate early and accurate diagnosis of breast cancer. The Thomsen-Freidenreich (TF) and Tn antigens are aberrantly glycosylated carbohydrate cancer-associated antigens found in ∼80% of adenocarcinomas. Both TF and Tn are expressed on cell-surface glycoproteins and glycolipids. Nipple aspirate fluid (NAF) is concentrated in secreted proteins and lipids from cells that give rise to cancer. The objective of this study was to determine if NAF from breasts with cancer contains elevated levels of TF and Tn compared with NAF from normal breasts. A sensitive and specific antigen capture immunoassay for TF and Tn detection in NAF was developed for this purpose. Experimental Design: Fifty NAF samples, 25 from breasts with cancer and 25 from normal breasts, were examined. Antigen capture immunoassays were done on the samples using monoclonal antibodies that specifically recognized either TF or Tn antigen in NAF. These antibodies captured serially diluted NAF samples, and the concentration of TF or Tn was determined by comparing absorbance values against a standard curve generated from standard sources of TF or Tn. Results: TF and Tn were detected in 19 of 25 and 20 of 25 NAF samples from breasts with cancer, respectively, compared with 0 of 25 and 1 of 25 NAF samples from breasts without cancer (P &amp;lt; 0.001 for both TF and Tn). In 92% of the cancerous breast NAF samples tested, either TF or Tn was found. Conclusions: Simultaneous measurement of TF and Tn in NAF may facilitate the noninvasive detection of breast cancer and warrants further study.
AT-46 * VORINOSTAT AND BEVACIZUMAB FOR RECURRENT HIGH-GRADE GLIOMA: INTERIM ANALYSIS OF A PHASE II CLINICAL TRIAL
Authors: K. Peters, D. Reardon, D. Randazzo, S. Dutton, A. Edwards, E. Lipp, J. Herndon, F. McSherry, A. Desjardins, T. Ranjan, G. Vlahovic, H. Friedman
Journal: Neuro-Oncology (2014)

Prognosis for recurrent glioblastoma remains poor with progression-free survival at six months (PFS6) of 9-15%, but with the addition of bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A (VEGF-A), studies have shown PFS6 improved to 40-50%. Vorinostat, a small molecule inhibitor of histone deactylase (HDAC), has anti-tumor activity directly through HDAC inhibition and indirectly by promoting anti-angiogenesis. Its good oral bioavailability and favorable toxicity profile make it a promising additive agent. We designed a clinical trial to examine the addition of vorinostat and bevacizumab (BEV) in recurrent GBM. This was a phase II open-label, single arm study. Primary endpoint was PFS6. Secondary endpoints were safety/tolerability, radiographic response, progression-free survival, and overall survival. Chief eligibility criteria included age ≥ 18 years, KPS ≥ 70, time interval ≥4 wks from last treatment, and ≤2 prior progressions. Dosing regimen was BEV 10 mg/kg iv q2wks, and vorinostat 400 mg po for 7 days on then 7 days off in a 28 day cycle. To date, 38 of 40 recurrent GBM patients have been enrolled. Most common treatment-related grade 2 and above toxicities were lymphopenia (50%), leukopenia (34%), neutropenia (26%), and hypertension (22%). There were two grade 4 toxicities (sinus bradycardia and pulmonary embolism) and no treatment-related grade 5 toxicities. With a median follow-up of 5.7 months (95% CI: 3.4, 8.8 months), PFS6 was 22.6% (95% CI: 8.9-40.1). Best radiographic responses included 4 partial responses, 30 stable responses, 1 radiographic progression, 2 too early to assess and 1 termination due to toxicity without follow-up imaging. In initial interim analysis, the combination of voriniostat and BEV did not improve PFS6 in comparison to historical controls on BEV alone, but median follow-up is only 5.7 months. Additional data will be presented with a longer follow-up time for analysis.
The cultural evolution of emergent group-level traits
Authors: Paul E. Smaldino
Journal: Behavioral and Brain Sciences (2014)

Abstract Many of the most important properties of human groups – including properties that may give one group an evolutionary advantage over another – are properly defined only at the level of group organization. Yet at present, most work on the evolution of culture has focused solely on the transmission of individual-level traits. I propose a conceptual extension of the theory of cultural evolution, particularly related to the evolutionary competition between cultural groups. The key concept in this extension is the emergent group-level trait. This type of trait is characterized by the structured organization of differentiated individuals and constitutes a unit of selection that is qualitatively different from selection on groups as defined by traditional multilevel selection (MLS) theory. As a corollary, I argue that the traditional focus on cooperation as the defining feature of human societies has missed an essential feature of cooperative groups. Traditional models of cooperation assume that interacting with one cooperator is equivalent to interacting with any other. However, human groups involve differential roles, meaning that receiving aid from one individual is often preferred to receiving aid from another. In this target article, I discuss the emergence and evolution of group-level traits and the implications for the theory of cultural evolution, including ramifications for the evolution of human cooperation, technology, and cultural institutions, and for the equivalency of multilevel selection and inclusive fitness approaches.