tbuckley/cabot-search huggingface dataset:
Evidence based medicine: the Cochrane Collaboration.
Authors: W J Gillespie, None HandollH
Journal: British Journal of Sports Medicine (1997)

Evidence based medicine: the Cochrane CollaborationWhat is the Cochrane Collaboration?The Cochrane Collaboration is an international network of individuals and groups working in health care who are interested in developing and maintaining comprehensive, regularly updated, critical reviews of evidence from randomised controlled trials relevant to their specialty interests.Systematic review aims at reducing the biases that in the past have been evident in some of the reviews submitted to or commissioned by journals and publishing houses.Perhaps the greatest virtue of systematic review is that its methods are transparent as well as rigorous, and are clearly laid out.Reviews can be readily updated when new evidence becomes available, and can be corrected in response to comment and criticism.Systematic review includes a number of stages: * Definition of the primary objective of the review * Identification of all possible relevant trials by rigorous searching methods * Assessment of the quality of each trial that meets the entry criteria for the review * Extraction of data from each of these studies and contacting the authors if necessary for further infor- mation * Data synthesis; this may be qualitative or quantitative * Assessment of the implications for practice and further research.
Associations of Housing Mobility Interventions for Children in High-Poverty Neighborhoods With Subsequent Mental Disorders During Adolescence
Authors: Ronald C. Kessler, Greg J. Duncan, Lisa A. Gennetian, Lawrence F. Katz, Jeffrey R. Kling, Nancy A. Sampson, Lisa Sanbonmatsu, Alan M. Zaslavsky, Jens Ludwig
Journal: JAMA (2014)

<h3>Importance</h3> Youth in high-poverty neighborhoods have high rates of emotional problems. Understanding neighborhood influences on mental health is crucial for designing neighborhood-level interventions. <h3>Objective</h3> To perform an exploratory analysis of associations between housing mobility interventions for children in high-poverty neighborhoods and subsequent mental disorders during adolescence. <h3>Design, Setting, and Participants</h3> The Moving to Opportunity Demonstration from 1994 to 1998 randomized 4604 volunteer public housing families with 3689 children in high-poverty neighborhoods into 1 of 2 housing mobility intervention groups (a low-poverty voucher group vs a traditional voucher group) or a control group. The low-poverty voucher group (n=1430) received vouchers to move to low-poverty neighborhoods with enhanced mobility counseling. The traditional voucher group (n=1081) received geographically unrestricted vouchers. Controls (n=1178) received no intervention. Follow-up evaluation was performed 10 to 15 years later (June 2008-April 2010) with participants aged 13 to 19 years (0-8 years at randomization). Response rates were 86.9% to 92.9%. <h3>Main Outcomes and Measures</h3> Presence of mental disorders from the<i>Diagnostic and Statistical Manual of Mental Disorders</i>(Fourth Edition) within the past 12 months, including major depressive disorder, panic disorder, posttraumatic stress disorder (PTSD), oppositional-defiant disorder, intermittent explosive disorder, and conduct disorder, as assessed post hoc with a validated diagnostic interview. <h3>Results</h3> Of the 3689 adolescents randomized, 2872 were interviewed (1407 boys and 1465 girls). Compared with the control group, boys in the low-poverty voucher group had significantly increased rates of major depression (7.1% vs 3.5%; odds ratio (OR), 2.2 [95% CI, 1.2-3.9]), PTSD (6.2% vs 1.9%; OR, 3.4 [95% CI, 1.6-7.4]), and conduct disorder (6.4% vs 2.1%; OR, 3.1 [95% CI, 1.7-5.8]). Boys in the traditional voucher group had increased rates of PTSD compared with the control group (4.9% vs 1.9%, OR, 2.7 [95% CI, 1.2-5.8]). However, compared with the control group, girls in the traditional voucher group had a decreased rate of conduct disorder (0.3% vs 2.9%; OR, 0.1 [95% CI, 0.0-0.4]). <h3>Conclusions and Relevance</h3> Interventions to encourage moving out of high-poverty neighborhoods were associated with increased rates of depression, PTSD, and conduct disorder among boys and a reduced rate of conduct disorder among girls. Better understanding of interactions among individual, family, and neighborhood risk factors is needed to guide future public housing policy changes.
Heat Shock Protein 70 Enhances Vascular Bone Morphogenetic Protein-4 Signaling by Binding Matrix Gla Protein
Authors: Yucheng Yao, Andrew D. Watson, Sheng Ji, Kristina I. Boström
Journal: Circulation Research (2009)

Matrix Gla protein (MGP) is a calcification inhibitor, which binds and inhibits bone morphogenetic protein (BMP)-2 and -4.The objective was to determine whether MGP also binds other proteins, which could interfere with its function.We transfected bovine aortic endothelial cells with N-terminally FLAG-tagged MGP and used immunoprecipitation and liquid chromatographic-tandem mass spectrometric analysis to identify MGP-binding proteins. Heat shock protein (HSP)70, a stress-induced protein expressed in atherosclerotic lesions and soluble in serum, was identified as a novel MGP-binding protein. The interaction between MGP and HSP70 was confirmed by coimmunoprecipitation and chemical crosslinking, and blocked the interaction between MGP and BMP-4. In endothelial cells, HSP70 enhanced BMP-4-induced proliferation and tube formation, and in calcifying vascular cells, HSP70 enhanced BMP-induced calcium deposition. In addition, HSP70 mediated the procalcific effect of interleukin-6 on calcifying vascular cells. In apolipoprotein E-null mice, a model for atherosclerosis, levels of BMP-4, HSP70, MGP, and interleukin-6 were elevated in the aortic wall. Levels of BMP-4, HSP70, and interleukin-6 were also elevated in serum, and anti-HSP70 antibodies diminished its procalcific effect on calcifying vascular cells.HSP70 binds MGP and enhances BMP activity, thereby functioning as a potential link between cellular stress, inflammation, and BMP signaling.
Reduced recruitment of inflammatory cells in a contact hypersensitivity response in P-selectin-deficient mice.
Authors: M Subramaniam, S Saffaripour, S R Watson, T N Mayadas, R O Hynes, D D Wagner
Journal: The Journal of Experimental Medicine (1995)

The inflammatory response at sites of contact hypersensitivity induced by oxazolone was examined in the ears of P-selectin-deficient and wild-type mice. Accumulation of CD4+ T lymphocytes, monocytes, and neutrophils was reduced significantly in the mutant mice, as well as mast cell degranulation. In contrast, there was no significant difference in vascular permeability or edema between the two genotypes. The results demonstrate a role for P-selectin in recruitment of CD4+ T lymphocytes and show that P-selectin plays a role in long-term inflammation as well as in acute responses.
The evaluation of pulmonary involvement pattern in high resolution computerized tomography of patients with rheumatoid arthritis in Iran from 2010-2011
Authors: Kazem Navari, Reza Farokhsersht, Mohamadreza Masoodi, Shahram Zare, Najmen Ziaee
Journal: European Respiratory Journal (2012)

RA is a chronic systemic disease Pulmonary involvement is the most frequent manifestations of rheumatoid arthritis. The goal of this study was to assess pulmonary involvement pattern in patients with RA by HRCT Scan in Bandar-abbas.  Methods: In this prospective study fifty patients with RA referred to rheumatology clinic in Bandar abbas were evaluated. Data were obtained included: age, sex, duration of disease, methotroxate usage, smoking, pulmonary chronic disease, clinical symptoms of pulmonary involvement and patient self assessment. After clinical and laboratory investigations, HRCT were performed.  Results: Mean age of 49.3 years. Three patients with respiratory symptoms and 47 patients without pulmonary complaint. The most frequent pulmonary involvement in HRCT findings sub pleural fibrosis (26%) and followed by air trapping and mosaic pattern (20%), pleural thickening (14%), honey combing (10%), pulmonary nodules (8%), pribronchial thickening (8%), ground glass pattern (8%). Bronchiectasis (8%), Alveolar (2%) and reticular pattern (2%). There was no statistically significant relationship between lung involvement pattern and, rheumatoid factor positivity, Anti ccp and methotroxate usage but correlation between HRCT findings and age, duration of the disease, disease activity (DAS 28) and respiratory symptoms was significant (P  Conclusion: The results of our study indicate HRCT was useful for evaluation of pulmonary involvement in patients with RA although these patients had no respiratory symptoms. Larger and prospective studies are needed to assess of lung involvement pattern in HRCT in asymptomatic RA patients.
ASAS/EULAR recommendations for the management of ankylosing spondylitis
Authors: J Zochling
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. <b>Methods:</b> Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. <b>Results:</b> The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I–IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. <b>Conclusion:</b> Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.
Prolongation of Transgene Expression by Coexpression of Cytokine Response Modifier A in Rodent Liver after Adenoviral Gene Transfer
Authors: Xiao-Kang Li, Motomichi Kosuga, Keisuke Tokieda, Arihiko Kanaji, Yasuyuki Fukuhara, Mitsuhiro Hashimoto, Keiko Okabe, Hiroyuki Yaginuma, Masao Yamada, Seiichi Suzuki, Torayuki Okuyama
Journal: Molecular Therapy (2002)

The short duration of expression of the transgenes is a major barrier to the clinical application of adenovirus-mediated gene therapy for hepatic enzyme deficiencies. Previous reports show that Fas-mediated apoptosis has a pivotal role in the rapid elimination of adenovirus-infected hepatocytes. After considering this result and our recent observation that murine hepatocytes can be protected from Fas-mediated apoptosis by expressing cytokine response modifier A (CrmA) in vivo, we hypothesized that CrmA coexpression could also prevent adenovirus-infected hepatocytes from rapid elimination and that this would make prolonged transgene expression achievable in vivo. To examine this, mice with congenital deficiency of lysosomal beta-glucuronidase (GUSB) were infected with recombinant adenoviruses expressing both CrmA and GUSB, and the duration of transgene expression was evaluated. The serum GUSB activity in the mice injected with a recombinant adenovirus expressing GUSB only became undetectable 60 days after the injection, whereas higher than normal GUSB activity was observed for at least 120 days in mice injected with adenoviruses expressing both GUSB and CrmA. Furthermore, we showed that exogenous CrmA expression could prevent the adenovirus-infected hepatocytes from cell death induced by cytotoxic T lymphocytes in vitro. These observations indicate that transgene expression after administration of E1-deleted adenovirus is prolonged by coexpression of the antiapoptotic protein CrmA.
Alternative Splicing of a Cancer-Associated Intronic Variant of TG-FBR1 in Cancer Cell Lines
Authors: Michael P. Markey, Jeremy R. Graff, Julia H. Carter, Taiping Chen
Journal: Cancer Research (2006)

2479   Transforming growth factor beta (TGF-β) is a multifunctional protein controlling a broad spectrum of cellular activities ranging from proliferation and differentiation to apoptosis. Tumor suppressor and apoptotic activities of TGF-β are mediated through activation of Smad 2/3 and Smad 4 pathways. Negative regulation of this pathway occurs through the inhibitory feedback loop imposed by Smad 7. Disturbances in Smad signaling are frequently observed in many cancer types including pancreatic cancer and are associated with the loss of sensitivity of tumor cells to growth inhibition by TGF-β. Recent studies have identified number of TGF-β-inducible proteins that play an important role in Smad-mediated signaling. Here we focused on one of them, TIEG2 (KLF11), a TGF-β effector protein that has been shown to potentiate TGF-β signaling by terminating the inhibitory function of Smad 7. TIEG2 in association with mSin3a represses the expression of Smad7 resulting in the activation of TGF-β signaling pathway. We show that the treatment of the Capan-1 pancreatic carcinoma cells with proteosomal inhibitor (velcade) and prolyl-hydroxylase inhibitor (desferroxamine) down-regulate Smad7 expression, suggesting that TGF-β signaling pathway could be regulated in oxygen-dependent manner. It is well known that pancreatic tumors are hypoxic, and one of the primary effects of radiotherapy is reoxygenation. Interestingly, we found a common consensus PHD hydroxylation and pVHL binding domain in the primary structure of TIEG2. TGF-β treatment caused an increase in the protein levels of TIEG2 in the presence of either velcade or desferroxamineRadiation induced the protein levels of the TIEG2 and Smad 7, however, in combination with velcade or desferroxamine treatment the levels of Smad7 expression remained unchanged. Here we demonstrate that the mutations in the TIEG2 hydroxylation domain down-regulate Smad7-driven luciferase reporter activity and the mutation in the second leucine of the PHD domain (TIEG2L369I) was most effective in inhibiting Smad 7 activity. Mutations in 4 consensus Erk phosphorylation sites in combination with mutations in TIEG2 PHD domain resulted in enhanced repression of the Smad7-luc reporter activity. We hypothesize that irradiation in addition to the induction of the TGF-β also induces Erk MAP kinase which could phosphorylate TIEG2 leading to its dissociation from its corepressor mSin3a and loss of repression of Smad7 gene expression. In summary, we conclude that the interplay between the oxygen-dependent TIEG2 stability and Smad7 function could modulate TGF-β signaling in response to irradiation.
The hazards of smoking in women: results from the Million Women Study
Authors: Laurence Si Chong Lok
Journal: Thorax (2013)

The hazards of smoking in women: results from the Million Women Study Smoking is associated with many diseases and remains a major cause of mortality.The Million Women Study is a large UK prospective cohort study of women born in the second quarter of the 20th century, collecting data for a broad range of health issues.Women were recruited and sent questionnaires that included lifestyle factors such as smoking at baseline, 3 years and 8 years.After excluding women with previous smoking-associated diseases, 1.2 million invited participants were followed up for mortality for a mean of 12 years via national mortality records.Current smokers had a threefold increase in mortality compared with never-smokers, with adjusted mortality rate ratio increasing almost linearly with the number of cigarettes smoked at baseline.Relative risks were highest for deaths due to chronic lung disease and lung cancer.Ex-smokers had lower but still raised relative risks.Applying their results to a hypothetical population, the authors calculated that smokers lose 11 years of life span.The large sample size would minimise any selection bias of the Million Women Study, which recruited volunteers within the UK breast screening programme.With an average starting age of 19 years, this cohort is felt to represent the first generation of women in the UK where the long-term effects of smoking throughout adult life can be observed.The authors provided figures on the proportional reduction in mortality by stopping smoking before certain ages; used in the appropriate context, these data may be a useful tool for smoking cessation advice.
Capsulotomy for Refractory Anxiety Disorders: Long-Term Follow-Up of 26 Patients
Authors: Christian Rück, Sergej Andréewitch, Karin Flyckt, Gunnar Edman, Håkan Nyman, Björn A. Meyerson, Bodo E. Lippitz, Tomas Hindmarsh, Pär Svanborg, Per Mindus, Marie Åsberg
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The objective of the present study was to evaluate the long-term efficacy and safety of capsulotomy in patients with anxiety disorders. METHOD: Twenty-six patients who had undergone bilateral thermocapsulotomy were followed up 1 year after the procedure and after a mean of 13 years. Primary diagnoses were generalized anxiety disorder (N=13), panic disorder (N=8), and social phobia (N=5). Measures of psychiatric status included symptom rating scales and neuropsychological testing. Ratings were done by psychiatrists not involved in patient selection or postoperative treatment. A quantitative magnetic resonance imaging (MRI) evaluation was conducted to search for common anatomic denominators. Seventeen of the 23 patients who were alive at long-term follow-up were followed up in person, and one was interviewed by telephone; the relatives of these 18 patients were interviewed. RESULTS: The reduction in anxiety ratings was significant both at 1-year and long-term follow-up. Seven patients, however, were rated as having substantial adverse symptoms; the most prominent adverse symptoms were apathy and dysexecutive behavior. Neuropsychological performance was significantly worse in the patients with adverse symptoms. No common anatomic denominator could be found in responders in the analysis of MRI scans. CONCLUSIONS: Thermocapsulotomy is an effective treatment for selected cases of nonobsessive anxiety but may carry a significant risk of adverse symptoms indicating impairment of frontal lobe functioning. These findings underscore the importance of face-to-face assessments of adverse symptoms.
Proteasome-mediated degradation of IκBα and processing of p105 in Crohn disease and ulcerative colitis
Authors: Alexander Visekruna, Thorsten Joeris, Daniel Seidel, Anjo Kroesen, Christoph Loddenkemper, Martin Zeitz, Stefan H.E. Kaufmann, Ruth Schmidt-Ullrich, Ulrich Steinhoff
Journal: Journal of Clinical Investigation (2006)

Enhanced NF-kappaB activity is involved in the pathology of both forms of inflammatory bowel disease (IBD), Crohn disease (CD) and ulcerative colitis (UC). Here we analyzed the mechanism of proteasome-mediated NF-kappaB activation in CD and UC. Our studies demonstrate that the subunit composition and the proteolytic function of proteasomes differ between UC and CD. High expression of the immunoproteasome subunits beta1i and beta2i is characteristic of the inflamed mucosa of CD. In line with this, we found enhanced processing of NF-kappaB precursor p105 and degradation of inhibitor of NF-kappaB, IkappaBalpha, by immunoproteasomes isolated from the mucosa of CD patients. In comparison with healthy controls and CD patients, UC patients exhibited an intermediate phenotype regarding the proteasome-mediated processing/degradation of NF-kappaB components. Finally, increased expression of the NF-kappaB family member c-Rel in the inflamed mucosa of CD patients suggests that p50/c-Rel is important for IFN-gamma-mediated induction of immunoproteasomes via IL-12-driven Th1 responses. These findings suggest that distinct proteasome subunits influence the intensity of NF-kappaB-mediated inflammation in IBD patients.
A STABLE HEMOLYSIN-LEUCOCIDIN AND ITS CRYSTAL-LINE DERIVATIVE ISOLATED FROM BETA HEMOLYTIC STREPTOCOCCI
Authors: E. J. Czarnetzky, Isabel M. Morgan, Stuart Mudd
Journal: The Journal of Experimental Medicine (1938)

1. A chemically pure hemolysin-leucocidin has been isolated from beta hemolytic streptococci, but not from other species of bacteria studied. 2. It does not give rise to antibodies, but precipitates immune sera against hemolytic streptococci, and is therefore a hapten. 3. A highly purified sample of S. H. up to a dilution of 1:128,000 hemolyzes red blood cells. Its hemolytic activity is not specifically neutralized by antiserum versus beta hemolytic streptococci. It is leucocidic in that it inhibits the reduction of methylene blue by leucocytes. 4. The hemolysin-leucocidin is stable to oxygen, to heat and to moderate changes in hydrogen ion concentration. Its chemical structure has been determined in part. Its molecular weight is 2260. 5. A crystalline derivative has been isolated as the sodium salt from the hemolysin-leucocidin. As the free acid it has a molecular weight of 720. Its hemolytic and leucocidic activity parallels that of S. H., although it is not serologically active. It possesses a high degree of toxicity for mice and rabbits.
Controlling collateral development: the difficult task of mimicking mother nature
Authors: L Gonçalves
Journal: Cardiovascular Research (2001)

in the heart and in the peripherical circulation, can be [7] Fulton WFM.Arterial anastomoses in the coronary circulation.I. achieved through administration of angiogenic growth Anatomical features in normal and diseased hearts demonstrated by factors.However, it is premature to gauge if the exciting stereoarteriography.