tbuckley/cabot-search huggingface dataset:
The influence of the patients' participation in trials on the adherence to treatment in future
Authors: Andrii Sidorov, Yuriy Mostovoy, Nataliia Slepchenko
Journal: European Respiratory Journal (2012)

The aim of the study was to estimate the influence of participation in trials on the adherence of the patients to the treatment of chronic obstructive pulmonary disease (COPD) and concomitant arterial hypertension (AH) after the trial finishing.  43 patients (average age 51,5±6,5 years) with severe and very severe COPD and concomitant moderate AH were enrolled. On the each visit patients received information about the necessity of the regular taking of the basis therapy of the main and concomitant disease. The duration of the trial visits were 160±32 minutes instead of 21±5 minutes in case of routine ambulatory visits. Patients filled diaries concerning their knowledge about COPD and AH, taking of the basis therapy of both diseases. The statistical program SPSS 16.0 used for working with the data of study.  It was revealed that before the trial only 22 (51%) of the patients had basis therapy due to COPD and only 18 (42%) of them took antihypertensive therapy regularly. In the 6 months after the trial completing these data were 38 (88%) and 37 (86%) respectively. Patients answered that their knowledge about COPD and AH grows on 75±9%. The patients had 1,1±0,2 COPD exacerbations during the 6 months before the trial and during the next 6 months after the trial completing they had 0,7±0,1 COPD exacerbations (p=0,041). Perhaps, the improvement of the patients9 adherence to the treatment of COPD and AH connected with better cooperation between the patient and investigator than it was in routine clinical practice.  Conclusions. The participation in trial due to COPD improves the adherence of patients to the treatment of COPD on 37% and AH on 44% after the trial completion.
Crystals of monosodium urate monohydrate enhance lipopolysaccharide-induced release of interleukin 1β by mononuclear cells through a caspase 1-mediated process
Authors: E J Giamarellos-Bourboulis, M Mouktaroudi, E Bodar, J van der Ven, B-J Kullberg, M G Netea, J W M van der Meer
Journal: Annals of the Rheumatic Diseases (2008)

Objective: Recent studies suggest that crystals of monosodium urate (MSU), deposited in joints of patients with acute gouty arthritis, activate the NACHT domain, leucine-rich repeat and pyrin domain-containing protein (NALP)3 inflammasome. In the present study we have investigated whether production of proinflammatory cytokines by crystals was exacerbated during costimulation with Toll-like receptor (TLR) ligands. Methods: Mononuclear cells of 22 healthy donors were stimulated by various concentrations of MSU crystals in the absence or presence of lipopolysaccharide (LPS), Pam3Cys and flagellin. Production of tumour necrosis factor α (TNFα), interleukin (IL)1β and IL6, as well as the intracellular concentrations of proIL1β were measured by ELISA. mRNA transcripts of TNFα and IL1β were assessed by real-time PCR. Stimulation experiments were also performed with peripheral blood mononuclear cells (PBMCs) of one patient carrying a NALP3 mutation. Results: MSU induced a moderate release of IL1β and IL6, but not of TNFα. Urate crystals amplified IL1β production stimulated by the TLR4 ligand LPS, while no synergy was apparent for IL6 production. In addition, no synergy between urate crystals and Pam3Cys (TLR2 ligand) or flagellin (TLR5 ligand) was apparent. The synergy between urate crystals and LPS was directed at the level of the NALP3 inflammasome, as it was present only when active IL1β was measured, but not at the level of IL1 mRNA or proIL1β. The synergy between LPS and MSU crystals ceased to exist in the presence of a caspase 1 inhibitor. Conclusions: MSU crystals act in synergy with LPS for the induction of enhanced release of IL1β. Increased cleavage of proIL1β by urate-activated caspase 1 is proposed as the underlying mechanism.
Increased methylation variation in epigenetic domains across cancer types
Authors: Kasper Daniel Hansen, Winston Timp, Héctor Corrada Bravo, Sarven Sabunciyan, Benjamin Langmead, Oliver G McDonald, Bo Wen, Hao Wu, Yun Liu, Dinh Diep, Eirikur Briem, Kun Zhang, Rafael A Irizarry, Andrew P Feinberg
Journal: Nature Genetics (2011)
1079 INSULIN RESISTANCE CORRELATES WITH LOW DENSITY HEPATITIS C VIRUS PARTICLES IN GENOTYPE 1 INFECTION
Authors: S.H. Bridge, D.A. Sheridan, D.J. Felmlee, S.U. Nielsen, R.D.G. Neely, G.L. Toms, M.F. Bassendine
Journal: Journal of Hepatology (2010)
Repair of Infarcted Myocardium by Autologous Intracoronary Mononuclear Bone Marrow Cell Transplantation in Humans
Authors: Bodo E. Strauer, Michael Brehm, Tobias Zeus, Matthias Köstering, Anna Hernandez, Rüdiger V. Sorg, Gesine Kögler, Peter Wernet
Journal: Circulation (2002)

Experimental data suggest that bone marrow-derived cells may contribute to the healing of myocardial infarction (MI). For this reason, we analyzed 10 patients who were treated by intracoronary transplantation of autologous, mononuclear bone marrow cells (BMCs) in addition to standard therapy after MI.After standard therapy for acute MI, 10 patients were transplanted with autologous mononuclear BMCs via a balloon catheter placed into the infarct-related artery during balloon dilatation (percutaneous transluminal coronary angioplasty). Another 10 patients with acute MI were treated by standard therapy alone. After 3 months of follow-up, the infarct region (determined by left ventriculography) had decreased significantly within the cell therapy group (from 30+/-13 to 12+/-7%, P=0.005) and was also significantly smaller compared with the standard therapy group (P=0.04). Likewise, infarction wall movement velocity increased significantly only in the cell therapy group (from 2.0+/-1.1 to 4.0+/-2.6 cm/s, P=0.028). Further cardiac examinations (dobutamine stress echocardiography, radionuclide ventriculography, and catheterization of the right heart) were performed for the cell therapy group and showed significant improvement in stroke volume index, left ventricular end-systolic volume and contractility (ratio of systolic pressure and end-systolic volume), and myocardial perfusion of the infarct region.These results demonstrate for the first time that selective intracoronary transplantation of autologous, mononuclear BMCs is safe and seems to be effective under clinical conditions. The marked therapeutic effect may be attributed to BMC-associated myocardial regeneration and neovascularization.
Hypertonic saline for acute viral bronchiolitis: take the evidence with a grain of salt
Authors: Jürg Barben, Claudia E. Kuehni
Journal: European Respiratory Journal (2014)

We can improve future studies by agreeing on a definition of acute viral bronchiolitis for large, multicentre RCTs http://ow.ly/zrZhPFifty years ago, REYNOLDS and COOK [1] wrote, ''Oxygen is vitally important in bronchiolitis and there is little convincing evidence that any other therapy is consistently or even occasionally useful.''Their claim is once again supported by the new trial on hypertonic saline published in this issue of the European Respiratory Journal (ERJ) [2].Acute viral bronchiolitis (AVB) is the most common lower respiratory tract infection in infancy.It is caused by respiratory viruses, typically by respiratory syncytial virus [3].Although only 1-2% of children are hospitalised, AVB accounts for a large proportion of paediatric emergency visits and hospitalisations during winter months [4].An effective treatment would reduce the number of hospitalisations, hospital length of stay (LOS) and their corresponding health costs.Over the past half century, no therapy for AVB has shown a convincing effect, though many have been tested.Among those treatments ruled out are b 2 -agonists, anticholinergics, inhaled or oral corticosteroids and chest physiotherapy [5][6][7][8].Adrenaline might slightly improve short-term outcomes in outpatients but does not seem to reduce LOS in in-patients [9].Current management recommendations and guidelines thus focus on supportive treatment with supplemental oxygen, fluid management, nasal douche with normal saline and/or nasal decongestants and respiratory support as needed, and avoiding unnecessary handling [10][11][12][13][14].Recently, studies have investigated the effectiveness of nebulised hypertonic saline.The first results looked promising [15][16][17][18].A Cochrane review, which included papers indexed in medical databases until May 2013 [15-25], concluded that nebulised 3% hypertonic saline may reduce LOS among infants with nonsevere acute bronchiolitis, and improves clinical severity scores among in-and outpatients [26].Unfortunately, the studies included in the review are heterogeneous and sample sizes are generally small.The type of interventions varied: some inhaled hypertonic saline only once or twice [19,25] while others used repeated inhalation until discharge.Intervals between inhalations varied from 4 to 8 h; inhaled volumes varied between 2 and 5 mL.Type of nebuliser [15,16,21,22,25] and mass median aerodynamic diameter [15,16] were rarely mentioned.Only a few studies tested hypertonic saline as a monotherapy.Most added other drugs regularly or on demand, including adrenaline [15, 16, 18-20, 24, 25] or b 2 -agonists [17,18,21,23,25].Criteria for hospital admission, oxygen requirement and discharge differed between studies, and oxygen saturation cut-off varied.All but one study [18] came from a single centre.Some focused on in-patients
Social determinants of health, universal health coverage, and sustainable development: case studies from Latin American countries
Authors: Luiz Odorico Monteiro de Andrade, Alberto Pellegrini Filho, Orielle Solar, Félix Rígoli, Lígia Malagon de Salazar, Pastor Castell-Florit Serrate, Kelen Gomes Ribeiro, Theadora Swift Koller, Fernanda Natasha Bravo Cruz, Rifat Atun
Journal: The Lancet (2014)
Some Immunological Considerations in Liver Transplantation
Authors: Paul S. Russell
Journal: Hepatology (1984)

Immunological considerations of special interest in liver transplantation are examined. It is concluded that liver transplants between human beings generate typical rejection reactions although they may, overall, be somewhat more mild than those encountered in transplanted kidneys and hearts. This is the case in some animals for reasons which are not yet clear. There is evidence that the transplanted liver can suffer immune attack better than other organs. Whether graft-vs.-host activity is of clinical importance is uncertain. The advent of cyclosporin immunosuppression has improved the outlook for liver recipients but multiple complications of immunosuppression will still occur and demand skillful management.
Transmission of Papovavirus by Cryotherapy Applicator
Authors: C. Robert Charles
Journal: JAMA (1971)

To the Editor.—  The literature of the past 80 years abounds with evidence that the human papovavirus is transmitted from man to man, both through direct contact with wart tissue and indirectly through contact with wart-contaminated objects. The following case reports show the possibility of transmission of the papovavirus indirectly by cotton-tipped applicators used in dermatologic cryotherapy.  Report of Cases.—Case 1.—  A 57-year-old white woman complained of multiple tumors on the trunk of several years' duration. One of these lesions was particularly large and unsightly and she wished it removed. The skin showed many yellowbrown, greasy macules and papules with the typical structure of seborrheic keratoses. The lesion the patient wished removed was located on the upper part of the back and measured 1X1 cm. It had a friable, easily removed verrucous surface and was clinically a typical seborrheic keratosis. It was subsequently frozen with liquid nitrogen using
STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer
Authors: Cristina Peña, María Virtudes Céspedes, Maja Bradic Lindh, Sara Kiflemariam, Artur Mezheyeuski, Per-Henrik Edqvist, Christina Hägglöf, Helgi Birgisson, Linda Bojmar, Karin Jirström, Per Sandström, Eleonor Olsson, Srinivas Veerla, Alberto Gallardo, Tobias Sjöblom, Andy C.-M. Chang, Roger R. Reddel, Ramón Mangues, Martin Augsten, Arne Östman
Journal: Cancer Research (2012)

Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis.
Lymph flow regulates collecting lymphatic vessel maturation in vivo
Authors: Daniel T. Sweet, Juan M. Jiménez, Jeremy Chang, Paul R. Hess, Patricia Mericko-Ishizuka, Jianxin Fu, Lijun Xia, Peter F. Davies, Mark L. Kahn
Journal: Journal of Clinical Investigation (2015)

Fluid shear forces have established roles in blood vascular development and function, but whether such forces similarly influence the low-flow lymphatic system is unknown. It has been difficult to test the contribution of fluid forces in vivo because mechanical or genetic perturbations that alter flow often have direct effects on vessel growth. Here, we investigated the functional role of flow in lymphatic vessel development using mice deficient for the platelet-specific receptor C-type lectin–like receptor 2 (CLEC2) as blood backfills the lymphatic network and blocks lymph flow in these animals. CLEC2-deficient animals exhibited normal growth of the primary mesenteric lymphatic plexus but failed to form valves in these vessels or remodel them into a structured, hierarchical network. Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic vessels was both premature and excessive, a phenotype identical to that observed with loss of the lymphatic endothelial transcription factor FOXC2. In vitro evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing shear stress is sufficient to induce expression of genes required for lymphatic valve development and identified GATA2 as an upstream transcriptional regulator of FOXC2 and the lymphatic valve genetic program. These studies reveal that lymph flow initiates and regulates many of the key steps in collecting lymphatic vessel maturation and development.
Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis
Authors: A Walther, R Houlston, I Tomlinson
Journal: Gut (2008)

<h3>Background:</h3> Several studies have suggested that microsatellite instability (MSI) resulting from defective DNA mismatch repair confers a better prognosis in colorectal cancer (CRC). Recently, however, data have suggested this is secondary to the effects of ploidy/chromosomal instability (CIN). To estimate the prognostic significance of CIN for survival, data from published studies have been reviewed and pooled. <h3>Methods:</h3> Studies stratifying survival in CRC by CIN status were identified by searching PubMed and hand-searching bibliographies of identified studies. Two reviewers confirmed study eligibility and extracted data independently, and data were pooled using a fixed-effects model. The principal outcome measure was the HR for death. <h3>Results:</h3> 63 eligible studies reported outcome in 10 126 patients, 60.0% of whom had CIN+ (aneuploid/polyploid) tumours. The overall HR associated with CIN was 1.45 (95% CI 1.35 to 1.55, p&lt;0.001). In patients with stage II–III CRCs, the HR was 1.45 (95% CI 1.27 to 1.65, p&lt;0.001). The effect was similar for progression-free survival (HR = 1.71, 95% CI 1.51 to 1.94, p&lt;0.001). There was no evidence of significant interstudy heterogeneity. <h3>Conclusion:</h3> CIN is associated with a worse prognosis in CRC, and should be evaluated as a prognostic marker, together with MSI status, in all clinical trials, particularly those involving adjuvant therapies.
Spermatozoal nuclear determinants of reproductive outcome: implications for ART
Authors: Emre Seli, Denny Sakkas
Journal: Human Reproduction Update (2005)

A male factor is implicated in more than 50% of couples treated with IVF. However, neither the routine testing of male fertility potential nor its treatment address the specific mechanisms by which spermatozoal factors may impact upon reproductive outcome. An important function of spermatozoa is to deliver the paternal genome to the oocyte. Recently, a number of acquired spermatozoal nuclear factors that may have implications on reproductive outcome have been described. These include non-specific DNA strand breaks, numerical abnormalities in spermatozoal chromosome content, Y chromosome microdeletions and alterations in the epigenetic regulation of paternal genome. The exact mechanisms by which these factors affect reproduction are unknown and their implications for assisted reproduction technology outcome need to be further investigated. These recent findings point to the need for novel and more personalized approaches to test and treat male factor infertility.
De subitaneis mortibus. XXX. Observations on the pathophysiology of the long QT syndromes with special reference to the neuropathology of the heart.
Authors: T N James, P Froggatt, W J Atkinson, P R Lurie, D G McNamara, W W Miller, G T Schloss, J F Carroll, R L North
Journal: Circulation (1978)

Eight patients (different families) with syncopal attacks and a long QT interval in the ECG died suddenly. Five heard normally and three were born deaf. At postmortem examination of all eight hearts the single consistent abnormality was focal neuritis and neural degeneration within the sinus node, A-V node, His bundle and ventricular myocardium. Although the etiology of this intracardiac neural disease is uncertain, a chronic viral infection or some noninfectious degenerative process are among the plausible causes discussed. If intracardiac neuritis and neural degeneration prove to be a prevalent finding among other victims dying from the long QT syndromes, further consideration should be given to whether there is any genuine hereditary component in the pathogenesis. Because of the asymmetrical and focal distribution of the cardioneural lesions, the response to present forms of medical or surgical treatment of the lung QT syndromes may vary from benefit to harm. Until more is known of the true etiology of the neural disease, treatment will probably remain empirical in nature and should be conducted with cautious clinical observation.
Genetic linkage between serum levels of the third component of complement and the H-2 complex.
Authors: A Ferreira, V Nussenzweig
Journal: The Journal of Experimental Medicine (1975)

AKR/J (H-2kk) mice have higher serum C3 levels than DBA/2J (H-2dd). The F1 hybrids have intermediate levels. Analysis of the progeny of backcrosses at 21 days of age shows that C3 levels in mice of H-2dk type are significantly higher than those with H-2dd type and lower than those with H-2kk type. In addition, mice of H-2kk, H-2dk, and H-2dd types have C3 levels not significantly different from those of AKR/J, AKD2F1, and DBA/2J respectively. These findings demonstrate linkage between a gene controlling C3 levels and the H-2 complex.
Effects of chronic amiodarone treatment on human myocardial adrenoceptor density and adenylate cyclase response
Authors: R. Bjornerheim, T. Froysaker, V. Hansson
Journal: Cardiovascular Research (1991)

Study objective — The aim of the study was to evaluate the effect of chronic treatment by amiodarone on β adrenoceptor density and adenylate cyclase response in human myocardium. Design — Density of β1 and β2 adrenoceptors was measured by radioligand binding assay. β Adrenoceptor stimulated production of cAMP was measured by adenylate cyclase assay. Experimental material — Right auricular tissue from five patients on chronic amiodarone treatment was compared with that from nine patients in similar clinical and haemodynamic state undergoing coronary bypass surgery. Measurements and main results — β1 and β2 adrenoceptor subtypes were quantified using the highly β1 selective antagonist Sandoz 204 545. The total β adrenoceptor density was 28% lower in the amiodarone treated group than in the controls (42.0 v 58.3 fmol·mg−1 protein, p<0.02), β1 adrenoceptors were 25% lower (33.1 v 44.3 fmol·mg−1 protein, p<0.02), and β2 adrenoceptors were 36% lower (8.9 v 14.0 fmol·mg−1 protein, p<0.02). The cAMP production following non-selective β adrenoceptor stimulation (isoprenaline 5 μmol·litre−1) was reduced by 38% in the amiodarone treated group (14.2 to 8.7 pmol·min−1·mg−1 protein, p = 0.05). Terbutaline stimulated cAMP production was reduced by 49% (8.3 to 4.3 pmol·min−1·mg−1 protein, p = 0.03). Fluoride stimulated cAMP production was not significantly different (9.4 v 8.4 pmol·min−1·mg−1 protein, p = 0.15). Conclusions — Chronic treatment with amiodarone is associated with a non-selective downregulation of β adrenoceptors, β Adrenoceptor stimulated cAMP production was also reduced. The “β blocking like effect” of amiodarone is probably related to downregulation of β adrenoceptors.
Systematic CpG Islands Methylation Profiling of Genes in the Wnt Pathway in Epithelial Ovarian Cancer Identifies Biomarkers of Progression-Free Survival
Authors: Wei Dai, Jens M. Teodoridis, Constanze Zeller, Janet Graham, Jenny Hersey, James M. Flanagan, Euan Stronach, David W. Millan, Nadeem Siddiqui, Jim Paul, Robert Brown
Journal: Clinical Cancer Research (2011)

Wnt pathways control key biological processes that potentially impact on tumor progression and patient survival. We aimed to evaluate DNA methylation at promoter CpG islands (CGI) of Wnt pathway genes in ovarian tumors at presentation and identify biomarkers of patient progression-free survival (PFS).
MPs demand urgent action to tackle social care's many shortcomings
Authors: A. O'Dowd
Journal: BMJ (2010)

All political parties must tackle the multiple shortcomings of social care provision in England, which has a complicated and difficult relationship with the NHS, says an influential group of MPs.

The parliamentary health select committee called for fundamental reform of the social care system in England and said political point scoring must end. The committee, publishing a report from its inquiry into social care, said all political parties should work together to map out sustainable reform instead of indulging in “pre-election politicking” over this issue.

It was referring to the recent failure of talks between the three main political parties and relevant charities to agree a deal on funding of …