tbuckley/cabot-search huggingface dataset:
Defining disease activity states and clinically meaningful improvement in primary Sjögren's syndrome with EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI)
Authors: Raphaèle Seror, Hendrika Bootsma, Alain Saraux, Simon J Bowman, Elke Theander, Johan G Brun, Gabriel Baron, Véronique Le Guern, Valérie Devauchelle-Pensec, Manel Ramos-Casals, Valeria Valim, Thomas Dörner, Athanasios Tzioufas, Jacques-Eric Gottenberg, Roser Solans Laqué, Thomas Mandl, Eric Hachulla, Kathy L Sivils, Wan-Fai Ng, Anne-Laure Fauchais, Stefano Bombardieri, Roberta Priori, Elena Bartoloni, Vincent Goeb, Sonja Praprotnik, Takayuki Sumida, Sumusu Nishiyama, Roberto Caporali, Aike A Kruize, Cristina Vollenweider, Philippe Ravaud, Petra Meiners, Pilar Brito-Zerón, Claudio Vitali, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2014)

To define disease activity levels, minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) with the primary Sjögren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patient-reported index (ESSPRI).For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI.Low-activity (ESSDAI<5), moderate-activity (5≤ESSDAI≤13) and high-activity (ESSDAI≥14) levels were defined. MCII of ESSDAI was defined as an improvement of at least three points. The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15%.This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI≥5) and define response to treatment as an improvement of ESSDAI at least three points. For addressing patient-reported outcomes, inclusion of patients with unsatisfactory symptom state (ESSPRI≥5) and defining response as an improvement of ESSPRI at least one point or 15% seems reasonable.
"The unfriendly games"
Authors: P McCrory
Journal: British Journal of Sports Medicine (2002)

As I write this warm up, the 2002 Winter Olympics are in full flight at Salt Lake City, Utah. The media response has been rapid and savage. Already dubbed “the Unfriendly Games”, the overwhelming security at the venues and the infrastructure problems is making life extremely difficult by all accounts.1

Is this the shape of things to come? The thin end of the wedge and all that. Following the September 11 tragedy and the fear of terrorist …
Erratum to: Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens
Authors: Jian Feng, Matthew Wilkinson, Xiaochuan Liu, Immanuel Purushothaman, Deveroux Ferguson, Vincent Vialou, Ian Maze, Ningyi Shao, Pamela Kennedy, JaWook Koo, Caroline Dias, Benjamin Laitman, Victoria Stockman, Quincey LaPlant, Michael E Cahill, Eric J Nestler, Li Shen
Journal: Genome biology (2015)

The online version of the original article can be found under doi:10.1186/gb-2014-15-4-r65.
Radiotherapy in Older Women With Low-Risk Breast Cancer: Why Has Practice Not Changed?
Authors: Orit Kaidar-Person, Georgina Walker, David A.L. Morgan, Abraham Kuten
Journal: Journal of Clinical Oncology (2012)

TO THEEDITOR: The editorial 1 regarding the publication by Soulos et al 2 stated that some older women with breast cancer are being clearly overtreated. Most clinicians will agree with this statement. However, the author also indicated that “offering radiation therapy to a woman with a good-prognosis tumor and a life expectancy of less than 5 years does not seem indicated.” 1(p1578) Although this statement represents a publicly shared standard, 3,4 it is not supported by facts. Several studies have evaluated the role of adjuvant radiotherapy, and all indicated a benefit of radiotherapy in reducing locoregional recurrence rates. 5-11 The Toronto Breast Cancer Study indicated that the relapse rate was 1.2% with tamoxifen alone and decreased to 0% when tamoxifen was given with whole-breast irradiation (WBI). There were no significant differences in the distant recurrence rates, questioning the role of tamoxifen alone in controlling systemic disease in this subgroup of patients. 7 The Cancer and Leukemia Group B 9343 trial published in the same issue of New England Journal of Medicine concurred with the results of the Toronto group. In this study, women age 70 years with tumors 2 cm were assigned to tamoxifen either with or without WBI. The locoregional control recurrence rates were lower in the combined WBI-tamoxifen group (1% v 4%; P .001). 6 These results were supported in a later update abstract presented in 2010, where the only significantly different outcome was local recurrence with a difference of 2% in the irradiated group and 9% in those women who did not receive adjuvant radiotherapy. 5 In view of these facts, it is not clear why omitting radiotherapy in older patients with low-risk disease has become a publicly shared standard. Maybe it is because there were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or 5-year rates of overall survival. 3,5-7,12 Giordano 1 commented that older women with low-risk breast cancer treated with adjuvant radiotherapy are at risk for unnecessary adverse effects, inconvenience of treatment, and possibly increased personal costs for a treatment unlikely to offer them any benefit. This could also be applied to the endocrine treatment, as both classes of endocrine agents have their own recognized adverse effects and
Epigenome Mapping in Normal and Disease States
Authors: Alika K. Maunakea, Iouri Chepelev, Keji Zhao
Journal: Circulation Research (2010)

Abstract: Epigenomes are comprised, in part, of all genome-wide chromatin modifications, including DNA methylation and histone modifications. Unlike the genome, epigenomes are dynamic during development and differentiation to establish and maintain cell type–specific gene expression states that underlie cellular identity and function. Chromatin modifications are particularly labile, providing a mechanism for organisms to respond and adapt to environmental cues. Results from studies in animal models clearly demonstrate that epigenomic variability leads to phenotypic variability, including susceptibility to disease that is not recognized at the DNA sequence level. Thus, capturing epigenomic information is invaluable for comprehensively understanding development, differentiation, and disease. Herein, we provide a brief overview of epigenetic processes, how they are relevant to human health, and review studies using technologies that enable epigenome mapping. We conclude by describing feasible applications of epigenome mapping, focusing on epigenome-wide association studies (eGWAS), which have the potential to revolutionize current studies of human diseases and will likely promote the discovery of novel diagnostic, preventative, and treatment strategies.
Joint effects of preinfarction angina and development of collateral vessels on outcome in patients with acute myocardial infarction who underwent primary coronary intervention
Authors: Kunihiro Kinio, Hiroshi Sato, Hideyuki Sato, Issei Shiotani, Yozo Ohnishi, Daisaku Nakatani, Hiroya Mizuno, Eiji Hishida, Naokazu Kinoshita, Kenshi Fujii, Masatsugu Hori
Journal: Journal of the American College of Cardiology (2002)
Mitochondrial haplogroups associated with elite Japanese athlete status
Authors: Eri Mikami, Noriyuki Fuku, Hideyuki Takahashi, Nao Ohiwa, Robert A Scott, Yannis P Pitsiladis, Mitsuru Higuchi, Takashi Kawahara, Masashi Tanaka
Journal: British Journal of Sports Medicine (2010)

Purpose It has been hypothesised that certain mitochondrial haplogroups, which are defined by the presence of a characteristic cluster of tightly linked mitochondrial DNA polymorphisms, would be associated with elite Japanese athlete status. To examine this hypothesis, the frequencies of mitochondrial haplogroups found in elite Japanese athletes were compared with those in the general Japanese population. Methods Subjects comprised 139 Olympic athletes (79 endurance/middle-power athletes (EMA), 60 sprint/power athletes (SPA)) and 672 controls (CON). Two mitochondrial DNA fragments containing the hypervariable sequence I (m16024–m16383) of the major non-coding region and the polymorphic site at m.5178C&gt;A within the NADH dehydrogenase subunit 2 gene were sequenced, and subjects were classified into 12 major mitochondrial haplogroups (ie, F, B, A, N9a, N9b, M7a, M7b, M*, G2, G1, D5 or D4). The mitochondrial haplogroup frequency differences among EMA, SPA and CON were then examined. Results EMA showed an excess of haplogroup G1 (OR 2.52, 95% CI 1.05 to 6.02, p=0.032), with 8.9% compared with 3.7% in CON, whereas SPA displayed a greater proportion of haplogroup F (OR 2.79, 95% CI 1.28 to 6.07, p=0.007), with 15.0% compared with 6.0% in CON. Conclusions The results suggest that mitochondrial haplogroups G1 and F are associated with elite EMA and SPA status in Japanese athletes, respectively.
Aspergillus fumigatus allergen I, a major IgE-binding protein, is a member of the mitogillin family of cytotoxins.
Authors: L K Arruda, T A Platts-Mills, J W Fox, M D Chapman
Journal: The Journal of Experimental Medicine (1990)

A major 18-kD IgE-binding protein from Aspergillus fumigatus (Asp fI) has been purified. Partial amino acid sequencing of Asp f I showed extensive sequence homology (95%) between Asp fI and a cytotoxin (mitogillin) produced by A. restrictus. Crossinhibition radioimmunoassay using murine monoclonal antibody and human IgG and IgE antibodies showed that Asp fI and mitogillin were antigenically indistinguishable. Furthermore, both proteins inhibited protein synthesis in vitro by greater than 90%. Asp fI was expressed in A. fumigatus but not in seven other Aspergillus species. The results suggest that Asp fI could play a dual role in the pathogenesis of A. fumigatus-related diseases by promoting colonization through cytotoxic activity and by causing inflammatory reactions involving IgE antibodies.
Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors
Authors: Thomas E. Merchant, Susan R. Rose, Christina Bosley, Shengjie Wu, Xiaoping Xiong, Robert H. Lustig
Journal: Journal of Clinical Oncology (2011)

Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors.Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n = 51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor types, n = 2) underwent provocative testing of GH secretion by using the secretogogues arginine and L-dopa before and after (6, 12, 36, and 60 months) conformal radiation therapy (CRT). A total of 664 arginine/l-dopa test procedures were performed.Baseline testing revealed preirradiation GHD in 22.9% of tested patients. On the basis of data from 118 patients, peak GH was modeled as an exponential function of time after CRT and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of the time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 to 30 Gy; and 60 months and 15 to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of GHD at 5 years (TD(50/5)).GH secretion after CRT can be predicted on the basis of dose and time after irradiation in pediatric patients with localized brain tumors. These findings provide an objective radiation dose constraint for the hypothalamus.
Association of African-American Ethnic Background With Survival in Men With Metastatic Prostate Cancer
Authors: I. M. Thompson, C. M. Tangen, A. Tolcher, E. D. Crawford, M. Eisenberger, C. M. Moinpour
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: African-American men have earlier onset of prostate cancer, higher prostate-specific antigen (PSA) levels, more advanced stage at diagnosis, and higher mortality than white men. It is not known whether the poorer survival of African-American men with prostate cancer reflects their later stage at diagnosis or differences in the basic biology of their disease. To evaluate this question, we examined outcomes of African-American and white men with metastatic prostate cancer in the context of a randomized clinical trial. Methods: Southwest Oncology Group Study 8894 was a randomized phase III trial that compared orchiectomy with or without flutamide in men with metastatic prostate cancer. Using data from 288 African-American and 975 white men in the trial, we conducted a proportional hazards regression analysis to determine if ethnicity was an independent predictor of survival. All statistical tests were two-sided. Results: African-American men were more likely than white men to have extensive disease and bone pain and had poorer performance status, younger age at study entry, higher Gleason score, and higher PSA levels. After adjustment for these prognostic variables, the hazard ratio (HR) for all-cause mortality for African-American men relative to white men was 1.23 (P = .018). Further adjustment for initial quality-of-life assessments also resulted in higher HRs associated with African-American ethnicity relative to white ethnicity (HR = 1.39; P = .007). Conclusions: African-American men with metastatic prostate cancer have a statistically significantly worse prognosis than white men that cannot be explained by the prognostic variables explored in this study. These data should give increased impetus for efforts to detect the disease early in African-American men and for the development of more effective therapies based on potential biologic differences in this ethnic group.
Elution of cytomegalovirus antibodies from adenocarcinoma of the colon.
Authors: A Grail, M Norval
Journal: Gut (1985)

Eluates were prepared by high salt extraction from normal colonic mucosa and adenocarcinomatous tissue from 28 patients, eight more from unmatched colonic tissue and five from patients with other gastrointestinal disease. Immunoglobulins were detected by ELISA: IgG was present in 24% eluates from normal colon and 21% from carcinomas; IgA in 55% eluates from normal colon and 39% from carcinomas; IgM in 55% from normal colon and 37% from carcinomas. Cytomegalovirus-specific antibody was found in 15% eluates from normal colon and in 18% carcinomas. Out of the 28 matched specimens, cytomegalovirus-specific IgG was detected in one normal and four tumour eluates, specific IgA in two normal and four tumour eluates, and specific IgM in two normal and two tumour eluates. In two instances cytomegalovirus-specific antibody was present in the eluates prepared from the normal and tumour tissue of the same patient. Of those eluates which contained cytomegalovirus-specific antibodies by ELISA, two were positive by anti-complement immunofluorescence of human embryo fibroblasts infected with cytomegalovirus strain AD-169. It seems possible, therefore, that cytomegalovirus antigens on colonic cells may be masked by complexing with anti-cytomegalovirus antibodies, and may not therefore be detected by techniques such as immunofluorescence.
Abnormal transcription factor induction through the surface immunoglobulin M receptor of B-1 lymphocytes.
Authors: D L Morris, T L Rothstein
Journal: The Journal of Experimental Medicine (1993)

Populations of murine peritoneal B-1 and splenic B-2 cells, highly purified by negative selection techniques, were used to demonstrate that B-1 cells completely fail to enter cell cycle in response to surface immunoglobulin M (sIgM) crosslinking without any decrease in cell number or viability. This failure of B-1 cell responsiveness appears to represent a specific defect in sIgM-derived signaling inasmuch as stimulation to enter S phase occurs normally in response to activated and fixed T cells, and to lipopolysaccharide (LPS). The level at which sIgM signaling fails was determined by evaluating the nuclear expression of the transcription factor complex, NF-kappa B, whose sIgM-mediated induction in B-2 cells is dependent on protein kinase C (PKC) activation but is independent of protein synthesis. There was no induction of nuclear NF-kappa B in B-1 cells stimulated by sIgM crosslinking, although NF-kappa B was stimulated by phorbol myristate acetate and by LPS. In contrast, NF-kappa B was induced in B-2 cells by all three stimuli. Thus, in B-1 cells, the sIgM-mediated induction of a transcription factor that is substantially stimulated by anti-IgM in B-2 cells is blocked. However, all sIgM-derived signaling in B-1 cells was not impaired inasmuch as anti-IgM increased I-A antigen expression. These results strongly suggest that sIgM receptor-mediated signaling in B-1 cells is interrupted early in the signal transduction pathway, at a point proximal to the activation of PKC. These results further demonstrate that transcription factor induction can be used to analyze the level at which receptor-mediated signaling is blocked.
<i>Child Guidance.</i>By Smiley Blanton, B. S., M. D. (Cornell), and Margaret Gray Blanton, authors of<i>"Speech Training for Children,"</i>etc. Introduction by Thomas W. Salmon, M. D., Columbia University. (<i>New York, The Century Company, 1927.</i>)
Authors: Harry Stack Sullivan
Journal: American Journal of Psychiatry (1927)
Impaired detection of Mycobacterium tuberculosis immunity in patients using high levels of immunosuppressive drugs
Authors: U. Sester, H. Wilkens, K. van Bentum, M. Singh, G. W. Sybrecht, H-J. Schäfers, M. Sester
Journal: European Respiratory Journal (2009)

We have previously shown, in renal transplant recipients on maintenance immunosuppression, that a whole-blood assay was superior in detecting immunity towards purified protein derivative (PPD) compared with skin testing. As blood tests may have limitations during high-dose immunosuppression therapy, the present study was aimed at characterising the effect of high immunosuppressive drug levels on PPD-specific T-cell immunity. PPD-reactive CD4 T-cells from 13 renal transplant recipients were longitudinally quantified by the induction of cytokines using flow cytometry. To further address the effect of high and low maintenance immunosuppression, drug effects were studied in vitro and in 49 age-matched lung transplant recipients and 49 renal transplant recipients. Maintenance immunosuppression after renal transplantation did not affect PPD-specific T-cell detection (median T-cell frequencies 0.55% before and 0.46% &gt;12 months after transplantation), whereas specific T-cell frequencies were significantly lower 3 months after transplantation (0.15%; p = 0.0002). Likewise, high-level maintenance immunosuppression after lung transplantation was associated with a significantly lower prevalence in PPD-specific T-cell reactivity compared with renal transplant recipients (16.7% versus 52.1%; p = 0.0005). In line with the observations made in vivo , calcineurin inhibitors analysed in vitro led to a dose-dependent decrease in antigen-specific T-cell reactivity. The flow cytometric assay is not adversely affected by low drug doses. In contrast, decreased levels of PPD-specific T-cells early after transplantation and low prevalence of PPD-reactivity in lung transplant recipients suggest a reduced sensitivity of in vitro testing during high-level immunosuppression.
Increased Incidence of Hodgkin's Disease After Allogeneic Bone Marrow Transplantation
Authors: Philip A. Rowlings, Rochelle E. Curtis, Jakob R. Passweg, H. Joachim Deeg, Gérard Socié, Lois B. Travis, Douglas W. Kingma, Elaine S. Jaffe, Kathleen A. Sobocinski, Mary M. Horowitz
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Immune dysregulation associated with allogeneic bone marrow transplantation (BMT) is linked to an increased risk of posttransplant lymphoproliferative disorders (PTLD); however, reports of Hodgkin's disease (HD) after transplantation are rare. PATIENTS AND METHODS: We evaluated the risk of HD among 18,531 persons receiving allogeneic BMT between 1964 and 1992 at 235 centers. The number of HD cases was compared with that expected in the general population. Risk factors were identified using Poisson regression and a nested case-control study. RESULTS: Risk of HD was increased in the postBMT population compared with the general population with an observed-to-expected incidence ratio (O/E) of 6.2 (observed cases, n = 8; 95% confidence interval [CI], 2.7 to 12). A significantly increased risk of HD remained after excluding two human immunodeficiency virus–positive patients (observed cases, n = 6; O/E = 4.7, 95% CI, 1.7 to 10.3). Mixed cellularity subtype predominated (five of eight cases, 63%). Five of six assessable cases contained Epstein-Barr virus (EBV) genome. Posttransplant HD differed from PTLD by later onset (&gt; 2.5 years) and lack of association with established risk factors (such as T-cell depletion and HLA disparity). Patients with HD were more likely than matched controls to have had grade 2 to 4 acute graft-versus-host disease (GVHD), required therapy for chronic GVHD, or both (P = .002), although analysis included small numbers of patients. CONCLUSION: The increased incidence of HD among BMT recipients adds support to current theories which link overstimulation of cell-mediated immunity and exposure to EBV with various subtypes of HD. The long latency of HD after transplant and lack of association with risk factors for PTLD is noteworthy and should be explored further for possible insights into pathogenesis.