tbuckley/cabot-search huggingface dataset:
Topological and Functional Discovery in a Gene Coexpression Meta-Network of Gastric Cancer
Authors: Amit Aggarwal, Dong Li Guo, Yujin Hoshida, Siu Tsan Yuen, Kent-Man Chu, Samuel So, Alex Boussioutas, Xin Chen, David Bowtell, Hiroyuki Aburatani, Suet Yi Leung, Patrick Tan
Journal: Cancer Research (2006)

Abstract Gastric cancer is a leading cause of global cancer mortality, but comparatively little is known about the cellular pathways regulating different aspects of the gastric cancer phenotype. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we assembled and systematically analyzed a consensus gene coexpression meta-network of gastric cancer incorporating &amp;gt;300 tissue samples from four independent patient populations (the “gastrome”). We find that the gastrome exhibits a hierarchical scale-free architecture, with an internal structure comprising multiple deeply embedded modules associated with diverse cellular functions. Individual modules display distinct subtopologies, with some (cellular proliferation) being integrated within the primary network, and others (ribosomal biosynthesis) being relatively isolated. One module associated with intestinal differentiation exhibited a remarkably high degree of autonomy, raising the possibility that its specific topological features may contribute towards the frequent occurrence of intestinal metaplasia in gastric cancer. At the single-gene level, we discovered a novel conserved interaction between the PLA2G2A prognostic marker and the EphB2 receptor, and used tissue microarrays to validate the PLA2G2A/EphB2 association. Finally, because EphB2 is a known target of the Wnt signaling pathway, we tested and provide evidence that the Wnt pathway may also similarly regulate PLA2G2A. Many of these findings were not discernible by studying the single patient populations in isolation. Thus, besides enhancing our knowledge of gastric cancer, our results show the broad utility of applying meta-analytic approaches to genome-wide data for the purposes of biological discovery. (Cancer Res 2006; 66(1): 232-41)
Antihypertensive Medications and the Risk of Incident Type 2 Diabetes
Authors: E. N. Taylor
Journal: Diabetes Care (2006)

The purpose of this study was to examine the association between the use of different classes of antihypertensive medications and the risk of incident type 2 diabetes.We conducted a prospective study of three cohorts: the Nurses' Health Study (NHS) I and II and the Health Professionals Follow-up Study (HPFS). Antihypertensive medication use was ascertained by biennial questionnaires. After excluding participants who reported a history of diabetes at baseline, 41,193 older women (NHS I), 14,151 younger women (NHS II), and 19,472 men (HPFS), all with hypertension, were followed for 8, 10, and 16 years, respectively.We documented 3,589 incident cases of diabetes. After adjustment for age, BMI, physical activity, the use of other antihypertensive medications, and other risk factors, the multivariate relative risk (RR) of incident diabetes in participants taking a thiazide diuretic compared with those not taking a thiazide was 1.20 (95% CI 1.08-1.33) in older women, 1.45 (1.17-1.79) in younger women, and 1.36 (1.17-1.58) in men. The multivariate RR in participants taking a beta-blocker compared with those not taking a beta-blocker was 1.32 (1.20-1.46) in older women and 1.20 (1.05-1.38) in men. ACE inhibitors and calcium channel blockers were not associated with risk.Thiazide diuretic and beta-blocker use were independently associated with a higher risk of incident diabetes. Increased surveillance for diabetes in patients treated with these medications may be warranted.
Tempus fugit: competency assessment in Modernizing Medical Careers
Authors: D. A D Farmer
Journal: Journal of the Royal Society of Medicine (2007)

In the letter we call on Reed to cease all involvement in arms fairs.In particular we state that Reed's involvement in the arms trade 'is entirely at odds with the ethical and social obligations we have to promote the beneficial applications of our work and prevent its misuse, to anticipate and evaluate the possible unintended consequences of scientific and technological developments, and to consider at all times the moral responsibility we carry for our work.'
Ethics in health care and research in European transition countries: reality and future prospects
Authors: Ana Marušić
Journal: BMJ (2005)

increasingly migrates to health systems, imposing lower costs on sponsors or researchers, hospitals have strong incentives to take on research projects that may not be in the best interests of the patients or the institution as a whole.Yet it is far from clear that the resources of clinical ethics are particularly apt for addressing these kinds of problems of structural adjustment or professional "deformation." 4 The language of ethics risks being used to ratify decisions made for reasons of pragmatism or expediency.Institutions may find it more useful to set up ethics committees more to satisfy foreign partners' or research sponsors' requirements, rather than to address problems of concern to patients.Ethics committees can serve many useful functions: education, dispute resolution, regulation, policy development.To be genuinely useful to clinicians and patients, and to be morally legitimate, ethics committees need to have both a clear sense of purpose and a clear sense of how best to achieve that purpose.Medical ethics scholars must take up the challenge of addressing the moral problems of social transition, otherwise they will be merely a moral figleaf covering the structural violence in countries in transition. 5
Effects of distance to treatment centre and case load upon tuberculosis treatment completion
Authors: I.R. Lake, N.R. Jones, L. Bradshaw, I. Abubakar
Journal: European Respiratory Journal (2011)

To the Editors:

The prompt identification and adequate treatment of tuberculosis (TB) cases are key components of the global control effort [1]. In many high-income countries, TB is relatively uncommon, implying that many clinicians do not have regular and continuing experience of managing TB. To address this, a policy response is a trend towards small numbers of centralised treatment facilities where individuals may receive better and more complete treatment [2, 3]. This centralising trend is the opposite to many low-income countries, where there is a move towards larger numbers of more decentralised TB services to facilitate patient access [4]. The difference is that such countries have sufficient cases to allow clinical staff to maintain their expertise, even in rural areas.

If TB services become more centralised, then patients may experience greater difficulty in accessing TB services due to increasing the distance between the home and treatment centre. There is little research on how distance affects TB completion, but rural residence is a known risk factor associated with a delay in the diagnosis and treatment of TB [5] and may therefore affect treatment completion. However, most of this evidence comes from low-income countries. In contrast, in high-income countries, good transport links and reasonable social security systems imply that such barriers may not exist.

This epidemiological study examined whether treatment centre case load (annual number of TB patients seen) and healthcare accessibility (proximity of patient residence to TB treatment centre) have an influence upon the completion of TB treatment in England and Wales, UK.

The study was based upon a sample of 21,954 patients reported to the national enhanced TB surveillance system (ETS) from 2001 to 2006 in England and Wales. These TB patients all had …
Enhanced development of atherosclerosis in cholesterol-fed rabbits by suppression of cell-mediated immunity.
Authors: S E Roselaar, G Schonfeld, A Daugherty
Journal: Journal of Clinical Investigation (1995)

T lymphocytes are present in atherosclerotic lesions, but the role of this cell type in the disease process has not been determined. To determine whether cell-mediated immunity influences atherogenesis, New Zealand White rabbits fed a cholesterol-supplemented diet (0.5% wt/wt) were treated with cyclosporin A (n = 20) or vehicle alone (n = 16) for 12 wk. The dose of cyclosporin A was adjusted so that a blood concentration between 100 and 200 ng/ml was maintained to achieve a selective action T-lymphocytes. Effectiveness of immunosuppression in cyclosporin A-treated rabbits was confirmed by allogeneic skin graft survival. Cyclosporin A administration did not affect total plasma lipid concentrations, body weight, or renal function. Percentage of aortic intimal area covered with atherosclerotic lesions was increased significantly by immunosuppression in both the arch region (75 +/- 3% [mean +/- SEM] compared with 60 +/- 5% in controls; P < 0.01) and the thoracic region (47 +/- 7% vs 27 +/- 6%; P = 0.04). Enhanced atherogenesis was not associated with diminished numbers of T lymphocytes in lesions, changes in T lymphocyte subtype, or any discernible change in cellular composition. Humoral immune responses to oxidized LDL were similar in the two groups: serum titres of autoantibodies against malondialdehyde-modified LDL were equivalent. These data demonstrate that cyclosporin A-induced suppression of cell-mediated immunity increased the development of macrophage-rich atherosclerotic lesions in cholesterol-fed rabbits.
Signaling and Functions of Angiopoietin-1 in Vascular Protection
Authors: Nicholas P.J. Brindle, Pipsa Saharinen, Kari Alitalo
Journal: Circulation Research (2006)

Angiopoietin-1 (Ang1) has powerful vascular protective effects: suppressing plasma leakage, inhibiting vascular inflammation, and preventing endothelial death. Preclinical studies indicate that Ang1 may be therapeutically useful in a number of situations, including treatment of edema, endotoxemia, and transplant arteriosclerosis. However, the ligand has also been implicated in vessel remodeling, induction of angiogenesis and pulmonary hypertension, indicating that strategies to minimize any deleterious effects while optimizing vessel protection are likely to be needed. This review surveys the published data on vascular protective effects of Ang1 and highlights the therapeutic potential of this ligand, as well as possible limitations to its use. We also consider the data on Ang1 receptors and speculate on how to maximize therapeutic benefit by targeting the Tie receptors.
The pattern of use of asthma medication in adolescents and young adults: A nationwide study on 2.2 million people
Authors: Lars Pedersen, Emil Fosbøl, Gunnar Gislason, Fredrik Folke, Casper Lund-Andersen, Christian Torp-Pedersen, Backer Vibeke
Journal: European Respiratory Journal (2011)

Pharmacological treatment of asthma is highly effective in controlling symptoms and improving quality of life. Within the last 15 years new drugs such as combinations of ICS and long-acting beta-2-agonists (LABA) and leukotriene modifiers for treating asthma has been introduced on the Danish market. Studies have shown that these drugs have changed the pattern of prescription, but most studies on prescription pattern of asthma medication have studied selected populations or population samples.

The study aimed to identify patterns of use of asthma medication in adolescents and young adults in an unselected population.

The study population comprised all Danish individuals aged 10-40 years at January 1 1996 (2,213,264 individuals). The population was followed until the end of 2006. From the national Danish prescription registry we collected data on all asthma medication (ATC code R03) claimed by the study population.

At every year in the study period, beta-2-agonists were the most commonly claimed drug both in number of users and number of prescriptions. The first years of the study, there was an increasing use of LABA, but after the introduction of combined ICS and LABA, the use of LABA decreased whereas there was a steady increase in use of ICS and LABA in fixed combinations. When leukotriene modifiers were introduced in 1998, usage increased rapidly the first two years and then plateaued with only a small yearly increase. The use of theophyllines more than halved during the study.

This study on the use of asthma medication in an unselected population shows a shift in the use of asthma medication, but short-acting beta-2-agonists remained the most frequently used drug.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Stewart Sell, P. G. H. Gell
Journal: The Journal of Experimental Medicine (1965)

Lymphocytes from the peripheral blood of newborn rabbits heterozygous for IgG allotypes As4 and As5, or As5 and As6, obtained at an age when only the maternal allotypic determinants are detectable in the serum, may be stimulated in vitro to transform into "blast" cells with antiallotype sera directed against the determinants contolled both by the maternal and by the paternal chromosomes. This result rules out the possibility that allotypic specificity is conferred upon lymphocytes by environmental IgG and suggests that the lymphocytes of newborn rabbits have the potential to synthesize IgG determinants either in the form of intact IgG molecules or constituent polypeptide chains.
Republished research: Effects of circuit training as alternative to usual physiotherapy after stroke: randomised controlled trial
Authors: Ingrid G L van de Port, Lotte E G Wevers, Eline Lindeman, Gert Kwakkel
Journal: British Journal of Sports Medicine (2013)

▸ This article is an abridged version of a paper that was published on bmj.com. Cite this article as: BMJ 2012; 344 :e2672

Study question What is the effect of task oriented circuit training compared with usual physiotherapy in terms of self reported walking competency for patients with stroke discharged from a rehabilitation centre to their own home?

Summary answer Task oriented circuit training started in the first six months is as effective as individually tailored physiotherapy for patients with moderate to mild stroke and allows patients to exercise more intensively with a lower ratio of staff to patients.

What is …
Antihypertensive Effect of Clonidine
Authors: G. ONESTI, A. B. SCHWARTZ, K. E. KIM, V. PAZ-MARTINEZ, C. SWARTZ
Journal: Circulation Research (1971)

Clonidine hydrochloride is a sympathetic inhibitor with central site of action. The antihypertensive effect in man in the supine position is associated with a decrease in cardiac output and no cons...
Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1
Authors: Tihamer Orban, Jay M. Sosenko, David Cuthbertson, Jeffrey P. Krischer, Jay S. Skyler, Richard Jackson, Liping Yu, Jerry P. Palmer, Desmond Schatz, George Eisenbarth
Journal: Diabetes Care (2009)

OBJECTIVE There is limited information from large-scale prospective studies regarding the prediction of type 1 diabetes by specific types of pancreatic islet autoantibodies, either alone or in combination. Thus, we studied the extent to which specific autoantibodies are predictive of type 1 diabetes. RESEARCH DESIGN AND METHODS Two cohorts were derived from the first screening for islet cell autoantibodies (ICAs) in the Diabetes Prevention Trial–Type 1 (DPT-1). Autoantibodies to GAD 65 (GAD65), insulinoma-associated antigen-2 (ICA512), and insulin (micro-IAA [mIAA]) were also measured. Participants were followed for the occurrence of type 1 diabetes. One cohort (Questionnaire) included those who did not enter the DPT-1 trials, but responded to questionnaires (n = 28,507, 2.4% ICA+). The other cohort (Trials) included DPT-1 participants (n = 528, 83.3% ICA+). RESULTS In both cohorts autoantibody number was highly predictive of type 1 diabetes (P &amp;lt; 0.001). The Questionnaire cohort was used to assess prediction according to the type of autoantibody. As single autoantibodies, ICA (3.9%), GAD65 (4.4%), and ICA512 (4.6%) were similarly predictive of type 1 diabetes in proportional hazards models (P &amp;lt; 0.001 for all). However, no subjects with mIAA as single autoantibodies developed type 1 diabetes. As second autoantibodies, all except mIAA added significantly (P &amp;lt; 0.001) to the prediction of type 1 diabetes. Within the positive range, GAD65 and ICA autoantibody titers were predictive of type 1 diabetes. CONCLUSIONS The data indicate that the number of autoantibodies is predictive of type 1 diabetes. However, mIAA is less predictive of type 1 diabetes than other autoantibodies. Autoantibody number, type of autoantibody, and autoantibody titer must be carefully considered in planning prevention trials for type 1 diabetes.
Diagnostic and prognostic significance of genetic regional heterogeneity in meningiomas
Authors: Wolfgang K. Pfisterer, Nicole C. Hank, Mark C. Preul, William P. Hendricks, Jeanette Pueschel, Stephen W. Coons, Adrienne C. Scheck
Journal: Neuro-Oncology (2004)

We analyzed the frequency and regional distribution of cells with genetic abnormalities of chromosomes 1, 14, and 22 in meningiomas. This data was evaluated for correlation to the clinical outcome of the patients. Eight defined areas of each of 77 paraffin-embedded meningioma samples (59 grade I, 13 grade II, and 5 grade III) were analyzed by fluorescent in situ hybridization using bacterial artificial chromosome probes localized to chromosomes 1p36.32, 1q25.3, 14q13.3, 14q32.12, 22q11.2, and 22q12.1-3. Chromosome deletion was considered to be regionally heterogeneous if <7 regions showed cells with chromosome deletions. Deletion of 1p occurred in 35% of the grade I tumors. Distribution of cells with 1p deletion was regionally heterogeneous in 25% and homogeneous in 10% of grade I tumors. Distribution of cells with deletion of 1p was regionally heterogeneous in 23% and homogeneous in 69% of the grade II tumors. All grade III meningiomas had homogeneous distribution of cells with deletion of chromosome 1p. Distribution of cells with deletion of 14q was regionally heterogeneous in 27% and homogeneous in 2% of the grade I meningiomas, heterogeneous in 31% and homogeneous in 62% of the grade II tumors, and heterogeneous in 40% and homogeneous in 60% of the grade III meningiomas. Distribution of cells with deletion of 22q was regionally heterogeneous in 15% and homogeneous in 3% of the grade I tumors, heterogeneous in 15% and homogeneous in 31% of grade II tumors, and homogeneous in 20% of the grade III meningiomas. Distribution of cells with trisomy 22q was regionally heterogeneous in 10% of grade I tumors, heterogeneous in 23% of grade II, and homogeneous in 80% of grade III meningiomas. The proportion of patients with a deletion of 22q (either homogeneous or heterogeneous) who had recurrence was greater than the proportion of those without 22q deletion who had recurrence, and deletion of 22q was significantly associated with radiologically detected recurrence (P < 0.05). We conclude that the appearance of chromosomal aberrations in different areas of the tumor demonstrates the importance of regional heterogeneity in the biological behavior of meningiomas.
Isolation of Mycoplasma pneumoniae from the synovial fluid of a hypogrammaglobulinaemic patient in a survey of patients with inflammatory polyarthritis.
Authors: D Taylor-Robinson, J M Gumpel, A Hill, A J Swannell
Journal: Annals of the Rheumatic Diseases (1978)

Mycoplasmas were not isolated from synovial fluid or membrane specimens taken from 41 patients suffering from inflammatory polyarthritis. However, Mycoplasma pneumoniae was isolated in two laboratories and on two occasions from the knee joint of a hypogammaglobulinaemic patient with a chronic polyarthritis.
Pro-atrial natriuretic peptide and pro-vasopressin to predict severity and prognosis in community-acquired pneumonia
Authors: Stefan Krüger, Jana Papassotiriou, Reinhard Marre, Klaus Richter, Christian Schumann, Heike von Baum, Nils G. Morgenthaler, Norbert Suttorp, Tobias Welte
Journal: Intensive Care Medicine (2007)
Evaluation of beta-cell secretory capacity using glucagon-like peptide 1.
Authors: T Vilsbøll, M B Toft-Nielsen, T Krarup, S Madsbad, B Dinesen, J J Holst
Journal: Diabetes Care (2000)

OBJECTIVE: Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first compared the effects of intravenous bolus injections of 2.5, 5, 15, and 25 nmol GLP-1 with glucagon (1 mg intravenous) and a standard meal (566 kcal) in 6 type 2 diabetic patients and 6 matched control subjects. Next, we studied another 6 patients and 6 control subjects and, in addition to the above procedure, performed a combined glucose plus GLP-1 stimulation, where plasma glucose was increased to 15 mmol/l before injection of 2.5 nmol GLP-1. Finally, we compared the insulin response to glucose plus GLP-1 stimulation with that observed during a hyperglycemic arginine clamp (30 mmol/l) in 8 patients and 8 control subjects. RESULTS: Peak insulin and C-peptide concentrations were similar after the meal, after 2.5 nmol GLP-1, and after glucagon. Side effects were less with GLP-1 than with glucagon. Peak insulin and C-peptide concentrations were as follows (C-peptide concentrations are given in parentheses): for patients (n = 12): meal, 277 +/- 42 pmol/l (2,181 +/- 261 pmol/l); GLP-1 (2.5 nmol), 390 +/- 74 pmol/l (2,144 +/- 254 pmol/l); glucagon, 329 +/- 50 pmol/l (1,780 +/- 160 pmol/l); glucose plus GLP-1, 465 +/- 87 pmol/l (2,384 +/- 299 pmol/l); for control subjects (n = 12): meal, 543 +/- 89 pmol/l (2,873 +/- 210 pmol/l); GLP-1, 356 +/- 51 pmol/l (2,001 +/- 130 pmol/l); glucagon, 420 +/- 61 pmol/l (1,995 +/- 99 pmol/l); glucose plus GLP-1, 1,412 +/- 187 pmol/l (4,391 +/- 416 pmol/l). Peak insulin and C-peptide concentrations during the hyperglycemic arginine clamp and during glucose plus GLP-1 injection were as follows: for patients: 475 +/- 141 pmol/l (2,295 +/- 379 pmol/l) and 816 +/- 268 pmol/l (3,043 +/- 508 pmol/l), respectively; for control subjects: 1,403 +/- 308 pmol/l (4,053 +/- 533 pmol/l) and 2,384 +/- 452 pmol/l (6,047 +/- 652 pmol/l), respectively. CONCLUSIONS: GLP-1 (2.5 nmol = 9 microg) elicits similar secretory responses to 1 mg glucagon (but has fewer side effects) and a standard meal. Additional elevation of plasma glucose to 15 mmol/l did not enhance the response further. The incremental response was similar to that elicited by arginine, but hyperglycemia had an additional effect on the response to arginine.