tbuckley/cabot-search huggingface dataset:
Citrullination enhances the pro-inflammatory response to fibrin in rheumatoid arthritis synovial fibroblasts
Authors: Olga Sanchez-Pernaute, Maria Filkova, Antonio Gabucio, Martin Klein, Hanna Maciejewska-Rodrigues, Caroline Ospelt, Fabia Brentano, Beat A Michel, Renate E Gay, Gabriel Herrero-Beaumont, Steffen Gay, Michel Neidhart, Astrid Juengel
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Fibrin deposits are characteristic of the synovial tissues in rheumatoid arthritis (RA). Once citrullinated, fibrin becomes an autoantigen and is thought to contribute in this way to perpetuate the disease. Our study aimed to analyse the responses of RA synovial fibroblasts (RASF) to native and citrullinated fibrin. <h3>Methods</h3> The transcriptome induced by fibrin in RASF was approached with whole-genome-based gene expression arrays. The upregulation of selected pro-inflammatory genes by fibrin was confirmed in additional primary cell cultures using quantitative PCR and ELISA. Citrullination reactions were carried out with recombinant human peptidylarginine deiminases (PAD) 2 and 4. <h3>Results</h3> In the whole-genome array native fibrin was found to modulate the gene expression profile of RASF, particularly upregulating mRNA levels of several pro-inflammatory cytokines. The induction of interleukin (IL)-6 and IL-8 by fibrin was confirmed in additional samples at both the mRNA and the protein level. Blocking and knockdown experiments showed the participation of toll-like receptor (TLR)4 in the induction of both cytokines. As compared with the native macromolecule, PAD2-citrullinated fibrin induced significantly higher expression of the pro-inflammatory cytokines in these cells. <h3>Conclusions</h3> Our results suggest that fibrin mediates inflammatory responses in RASF via a TLR4 pathway. In this way, fibrin and particularly its citrullinated form may contribute to sustain the cytokine burst in RA.
Lung growth of pre-adolescent children
Authors: M Smeets, B Brunekreef, L Dijkstra, D Houthuijs
Journal: European Respiratory Journal (1990)

Lung growth was studied in 420 Dutch children aged 6-11 yrs. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) and maximal mid-expiratory flow (MMEF) were measured four times over a 2.5 yr period with a rolling-seal spirometer. In boys, pulmonary function increased with approximately the same velocity at all ages studied. In girls, however, the growth velocities of FVC and FEV1 increased markedly at age 10 yrs, and growth velocities of PEF and MMEF had increased already at age 9 yrs. The minimum pulmonary function growth velocity could not be determined from the available data in boys. In girls, the minimum pulmonary function growth velocities preceded the minimum height growth velocity at the onset of the pubertal growth spurt. All lung function growth rates were significantly associated with the growth rate of height. In girls, the growth rate of FVC was also associated with the weight growth rate. There was also some association between the growth rates of PEF and MMEF and age. In boys, there was a negative association between age and the growth rates of FVC and FEV1, after adjustment for the growth rate of height.
Runx3 specifies lineage commitment of innate lymphoid cells
Authors: Takashi Ebihara, Christina Song, Stacy H Ryu, Beatrice Plougastel-Douglas, Liping Yang, Ditsa Levanon, Yoram Groner, Michael D Bern, Thaddeus S Stappenbeck, Marco Colonna, Takeshi Egawa, Wayne M Yokoyama
Journal: Nature Immunology (2015)
Thromboembolism in inflammatory bowel disease: role of platelets.
Authors: M J Webberley, M T Hart, V Melikian
Journal: Gut (1993)

Patients with inflammatory bowel disease are susceptible to thromboembolism and recently small vessel thrombosis has been implicated as an aetiological factor in Crohn9s disease. This study therefore investigated platelet function in 104 patients with inflammatory bowel disease of whom eight had previous thromboembolism. Thirty five patients had reproducible spontaneous platelet aggregation of more than 30% (0 in controls) (p &lt; 0.0001). A further 20 patients showed hypersensitivity of platelets to low concentrations of aggregating agents (p &lt; 0.001). Plasma thromboxane B2 and beta thromboglobulin levels were significantly higher than controls (p &lt; 0.001 and p &lt; 0.001), but platelet lifespan studies were normal. There was no correlation with disease activity. Patients with inflammatory bowel disease have abnormal platelet activity, which may contribute to the inflammatory process.
When is enough enough? The integration of competing scientific agendas
Authors: Jozsef A. Toth
Journal: Behavioral and Brain Sciences (2002)

This commentary asks the reader to examine Pylyshyn's target article and the imagery debate at four levels of analysis – institutional, programmatic, empirical, and individual. It is proposed that the debate follows somewhat generic patterns of discourse at all four levels, but the discourse associated with one side of the debate may or may not be expressible and evaluated in terms of the other. The different sides of the debate might better serve cognitive science if they proceed as separate research programs in their respective sub-disciplines. A more inclusive program could result, however, if the opposing approaches could somehow unite.
PTU-046 A Retrospective Comparison of Plastic, Uncovered and fully Covered Metal Stents in the Management of Distal Malignant Biliary Strictures
Authors: F Sampaziotis, J Evans, A King, B Macfarlane, A Leahy
Journal: Gut (2013)

<h3>Introduction</h3> Uncovered self expanding metal stents (USEMS) are associated with longer patency and reduced complication rates compared to polyethylene stents (PS), for the management of distal malignant biliary strictures (DMBS) [1]. However, PS are used for unstaged tumours, due to difficulties in operative USEMS removal. Fully covered self expanding metal stents (FCSEMS) can be easily removed before or during surgical resection. Recent data supports their use as first line management of DMBS, regardless of resectability status [2]. The current study provides the first retrospective comparison of survival, patency and complication rates between PS, USEMS and FCSEMS in the context of DMBS. <h3>Methods</h3> The records of all patients, who underwent endoscopic retrograde cholangiopancreatography and stent placement for newly diagnosed DMBS in our centre, between February 2007 and August 2012 were reviewed. Patients who subsequently underwent surgical resection were excluded from the patient survival estimation. The stent patency period was calculated as the period between stent insertion and occlusion; death or surgical resection with a patent stent. Cumulative patient survival and stent patency were estimated using the Kaplan Meier method. The log-rank test was used for comparison between groups. Fisher’s exact test was used for comparison of complication rates. The statistical analysis software used was IBM SPSS Statistics 20. <h3>Results</h3> 87 cases were identified: 37 PS (8.5 or 10 Ff), 26 USEMS (wallstent/wallflex) and 24 FCSEMS (wallflex). 7 patients proceeded to surgical resection. Stent occlusion occurred in 54%, 23% and 4.2% of the patients in the PS, USEMS and FCSEMS group respectively, with a mean patency period of 87, 144 and 196 days. Cumulative patency was higher in the FCSEMS vs USEMS group (p = 0.028) and higher in both groups compared to the PS group (p &lt; 0.001 and p = 0.007 respectively) [Fig15]. No statistically significant difference was observed in survival or complications between the 3 groups. However, 6 episodes of cholangitis occured in the PS group vs 1 episode in each of the FCSEMS and USEMS groups; 2 episodes of pancreatitis were noted in the FCSEMS group vs none in the other groups. <h3>Conclusion</h3> The use of FCSEMS as first line management for DMBS is associated with longer patency and similar complication rates compared to USEMS and PS. However, the risk of pancreatitis requires further assessment. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Lammer J, <i>et al.</i> Common bile duct obstruction due to malignancy: Treatment with plastic versus metal stents. Radiology 1996; 201:167–72. Siddiqui AA, <i>et al.</i> Fully covered self-expandable metal stents are effective and safe to treat distal malignant biliary strictures, irrespective of surgical resectability status. J Clin Gastroenterol. 2011; 45:824–7.
Prevalence of and Risk Factors for Hepatic Steatosis and Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: the Edinburgh Type 2 Diabetes Study
Authors: Rachel M. Williamson, Jackie F. Price, Stephen Glancy, Elisa Perry, Lisa D. Nee, Peter C. Hayes, Brian M. Frier, Liesbeth A.F. Van Look, Geoffrey I. Johnston, Rebecca M. Reynolds, Mark W.J. Strachan
Journal: Diabetes Care (2011)

Type 2 diabetes is an established risk factor for development of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and clinical correlates of these conditions in a large cohort of people with type 2 diabetes.A total of 939 participants, aged 61-76 years, from the Edinburgh Type 2 Diabetes Study (ET2DS)-a large, randomly selected population of people with type 2 diabetes-underwent liver ultrasonography. Ultrasound gradings of steatosis were compared with magnetic resonance spectroscopy in a subgroup. NAFLD was defined as hepatic steatosis in the absence of a secondary cause (screened by questionnaire assessing alcohol and hepatotoxic medication use, plasma hepatitis serology, autoantibodies and ferritin, and record linkage to determine prior diagnoses of liver disease). Binary logistic regression was used to analyze independent associations of characteristics with NAFLD.Hepatic steatosis was present in 56.9% of participants. After excluding those with a secondary cause for steatosis, the prevalence of NAFLD in the study population was 42.6%. Independent predictors of NAFLD were BMI, lesser duration of diabetes, HbA(1c), triglycerides, and metformin use. These remained unchanged after exclusion of participants with evidence of hepatic fibrosis from the group with no hepatic steatosis.Prevalences of hepatic steatosis and NAFLD were high in this unselected population of older people with type 2 diabetes, but lower than in studies in which ultrasound gradings were not compared with a gold standard. Associations with features of the metabolic syndrome could be used to target screening for this condition.
Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis
Authors: A Pastor, R Menendez, MJ Cremades, V Pastor, R Llopis, J Aznar
Journal: European Respiratory Journal (1997)

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.
Insulin Response in Relation to Insulin Sensitivity
Authors: Julia H. Goedecke, Joel A. Dave, Mirjam V. Faulenbach, Kristina M. Utzschneider, Estelle V. Lambert, Sacha West, Malcolm Collins, Tommy Olsson, Brian R. Walker, Jonathan R. Seckl, Steven E. Kahn, Naomi S. Levitt
Journal: Diabetes Care (2009)

OBJECTIVE The purpose of this study was to characterize differences in the acute insulin response to glucose (AIRg) relative to insulin sensitivity (SI) in black and white premenopausal normoglycemic South African women matched for body fatness. RESEARCH DESIGN AND METHODS Cross-sectional analysis including 57 black and white South African women matched for BMI, SI, AIRg, and the disposition index (AIRg × SI) were performed using a frequently sampled intravenous glucose tolerance test with minimal model analysis, and similar measures were analyzed using an oral glucose tolerance test (OGTT). Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography. RESULTS S I was significantly lower (4.4 ± 0.8 vs. 9.4 ± 0.8 and 2.9 ± 0.8 vs. 6.0 ± 0. 8 × 10−5 min−1/[pmol/l], P &amp;lt; 0.001) and AIRg was significantly higher (1,028 ± 255 vs. 352 ± 246 and 1,968 ± 229 vs. 469 ± 246 pmol/l, P &amp;lt; 0.001), despite similar body fatness (30.9 ± 1.4 vs. 29.7 ± 1.3 and 46.8 ± 1.2 vs. 44.4 ± 1.3%) in the normal-weight and obese black women compared with their white counterparts, respectively. Disposition index, a marker of β-cell function, was not different between ethnic groups (3,811 ± 538 vs. 2,966 ± 518 and 3,646 ± 485 vs. 2,353 ± 518 × 10−5 min, P = 0.10). Similar results were obtained for the OGTT-derived measures. CONCLUSIONS Black South African women are more insulin resistant than their white counterparts but compensate by increasing their insulin response to maintain normal glucose levels, suggesting an appropriate β-cell response for the level of insulin sensitivity.
Challenging the spliceosome machine.
Authors: Michael Weir, Matthew Eaton, Michael Rice
Journal: Genome biology (2006)

Abstract Background Using cDNA copies of transcripts and corresponding genomic sequences from the Berkeley Drosophila Genome Project, a set of 24,753 donor and acceptor splice sites were computed with a scanning algorithm that tested for single nucleotide insertion, deletion and substitution polymorphisms. Using this dataset, we developed a progressive partitioning approach to examining the effects of challenging the spliceosome system. Results Our analysis shows that information content increases near splice sites flanking progressively longer introns and exons, suggesting that longer splice elements require stronger binding of spliceosome components. Information also increases at splice sites near very short introns and exons, suggesting that short splice elements have crowding problems. We observe that the information found at individual splice sites depends upon a balance of splice element lengths in the vicinity, including both flanking and non-adjacent introns and exons. Conclusion These results suggest an interdependence of multiple splicing events along the pre-mRNA, which may have implications for how the macromolecular spliceosome machine processes sets of neighboring splice sites.
A Type VI Secretion System of Pseudomonas aeruginosa Targets a Toxin to Bacteria
Authors: Rachel D. Hood, Pragya Singh, FoSheng Hsu, Tüzün Güvener, Mike A. Carl, Rex R.S. Trinidad, Julie M. Silverman, Brooks B. Ohlson, Kevin G. Hicks, Rachael L. Plemel, Mo Li, Sandra Schwarz, Wenzhuo Y. Wang, Alexey J. Merz, David R. Goodlett, Joseph D. Mougous
Journal: Cell Host & Microbe (2010)
T cell derived cytokines in psoriatic arthritis synovial fluids
Authors: G. Partsch, E. Wagner, B. F Leeb, H. Broll, A. Dunky, J. S Smolen
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> The aim of this study was to investigate the concentrations of T cell derived cytokines in the synovial fluids (SFs) of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA). <h3>METHODS</h3> Th1 type cytokines (interleukin 2 (IL2), tumour necrosis factor β (TNFβ), and interferon γ (INFγ)) and Th2 type cytokines (IL4, IL10) were measured by means of enzyme linked immunosorbent assays. <h3>RESULTS</h3> IL2 was usually not detectable in any of the disease groups. TNFβ was found in 3 of 31 PsA SFs (mean (SEM) 11.1 (2.3) pg/ml) and in a significantly lower concentration than in 20 of the 40 RA SFs (42.2 (15.6) pg/ml; p &lt; 0.002). INFγ was measurable in 2 of 10 PsA and 6 of 16 RA SFs (p &gt; 0.05). IL4 was present at low concentrations in 4 of 22 PsA SFs (0.41 (0.8) pg/ml), and in 15 of 20 RA SFs (0.63 (0.09) pg/ml; p &lt; 0.01). IL10 was found in 4 of 27 PsA SFs (12.3 (0.9) pg/ml) and in 27 of 32 RA SFs (37.3 (4.9) pg/ml; p &lt; 0.0001). In all OA SFs cytokine concentrations were below the limit of detection. <h3>CONCLUSION</h3> The pattern of T cell derived cytokines in PsA SFs was similar to that of RA SFs. However, both the frequency and the concentrations of cytokines were lower in PsA SFs than in RA SFs, while OA SFs generally lacked any detectable T cell cytokines altogether. The presence of Th1 and Th2 cell derived cytokines in PsA SFs suggests the presence of activated T cells in the inflamed joint tissues and their participation in the immunoinflammatory events.
Recovering Population Parameters from a Single Gene Genealogy: An Unbiased Estimator of the Growth Rate
Authors: Yosef E. Maruvka, Nadav M. Shnerb, Yaneer Bar-Yam, John Wakeley
Journal: Molecular Biology and Evolution (2010)

We show that the number of lineages ancestral to a sample, as a function of time back into the past, which we call the number of lineages as a function of time (NLFT), is a nearly deterministic property of large-sample gene genealogies. We obtain analytic expressions for the NLFT for both constant-sized and exponentially growing populations. The low level of stochastic variation associated with the NLFT of a large sample suggests using the NLFT to make estimates of population parameters. Based on this, we develop a new computational method of inferring the size and growth rate of a population from a large sample of DNA sequences at a single locus. We apply our method first to a sample of 1,212 mitochondrial DNA (mtDNA) sequences from China, confirming a pattern of recent population growth previously identified using other techniques, but with much smaller confidence intervals for past population sizes due to the low variation of the NLFT. We further analyze a set of 63 mtDNA sequences from blue whales (BWs), concluding that the population grew in the past. This calls for reevaluation of previous studies that were based on the assumption that the BW population was fixed.
Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial
Authors: H K Genant, C G Peterfy, R Westhovens, J-C Becker, R Aranda, G Vratsanos, J Teng, J M Kremer
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Assess the effect of abatacept on progression of structural damage over 2 years in patients with rheumatoid arthritis who had an inadequate response to methotrexate. <h3>Methods:</h3> 539 patients entered an open-label extension of the AIM (Abatacept in Inadequate responders to Methotrexate) trial and received abatacept. Radiographic assessment of the hands and feet was performed at baseline, year 1 and year 2. At year 2, each patient's radiographs were scored for progression blinded to sequence and treatment allocation. <h3>Results:</h3> In patients treated with abatacept for 2 years, greater reduction in progression of structural damage was observed in year 2 than in year 1. The mean change in total Genant-modified Sharp scores was reduced from 1.07 units in year 1 to 0.46 units in year 2. Similar reductions were observed in erosion and joint space narrowing scores. Following 2 years of treatment with abatacept, 50% of patients had no progression of structural damage as defined by a change in the total score of ⩽0 compared with baseline. 56% of patients treated with abatacept had no progression during the first year compared with 45% of patients treated with placebo. In their second year of treatment with abatacept, more patients had no progression than in the first year (66% vs 56%). <h3>Conclusions:</h3> Abatacept has a sustained effect that inhibits progression of structural damage. Furthermore, the mean change in radiographic progression in patients treated with abatacept for 2 years was significantly lower in year 2 versus year 1, suggesting that abatacept may have an increasing disease-modifying effect on structural damage over time.
T cell costimulatory pathways
Authors: M H Sayegh, L A Turka
Journal: Journal of the American Society of Nephrology (1995)

It is now accepted that T cells need two signals for full activation. The first is the foreign antigen itself presented by self-major histocompatibility complex and thus provides antigen specificity to the immune response. The second is a "costimulatory" signal, the best-characterized of which is provided through the T cell accessory molecule CD28. In vitro, the blockade of costimulatory signals inhibits T cell activation and induces a state of antigen-specific unresponsiveness. In vivo, agents that block CD28-mediated costimulation have proved extremely effective in inhibiting the immune response in experimental models of transplantation and autoimmune disease, providing novel strategies for use in clinical trials in the near future.
Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse
Authors: S. Jain, J. Cohen, M.M. Ward, N. Kornhauser, E. Chuang, T. Cigler, A. Moore, D. Donovan, C. Lam, M.V. Cobham, S. Schneider, S.M. Hurtado Rúa, S. Benkert, C. Mathijsen Greenwood, R. Zelkowitz, J.D. Warren, M.E. Lane, V. Mittal, S. Rafii, L.T. Vahdat
Journal: Annals of Oncology (2013)
Letrozole, a new oral non-steroidal aromastase inhibitor in treating postmenopausal patients with advanced breast cancer. A pilot study
Authors: G. Bisagni, G. Cocconi, F. Scaglione, F. Fraschini, Ch. Pfister, P.F. Trunet
Journal: Annals of Oncology (1996)

To evaluate the endocrine effects as well as the pharmacokinetic parameters, efficacy and safety of letrozole, a new fourth-generation non-steroidal aromatase inhibitor.Fourteen postmenopausal women with progressive metastatic breast cancer, previously treated with endocrine therapy and/or chemotherapy for advanced disease, were treated with 0.5 mg daily doses of letrozole, orally. Endocrine and pharmacokinetic measurements were made before treatment and on days 14, 28, 56, and 84 of therapy.Letrozole induced a >86% decrease in plasma estrone and a approximately 67% reduction in circulating estradiol from day 14 on. There was a statistically significant decrease in plasma cortisol, which appeared clinically irrelevant since all values remained within the normal range. No significant changes in aldosterone concentration were noted. One patient achieved a complete response (CR) and 4 patients a partial response (PR), with an objective response rate of 36% (95% CI 13% to 65%). Median duration of response was 24 months, ranging from 4 to 44 months. No toxic effects attributable to letrozole were noted in any patient.Letrozole appears to be a very promising new antiaromatase drug. The characteristics of the patients more likely to respond, taking into account prior systemic treatment, should be defined by future studies. Further phase II and phase III studies comparing letrozole to other available second or even first-line endocrine-therapy agents, are warranted.