tbuckley/cabot-search huggingface dataset:
Integration of subclassification strategies in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for non-specific chronic low back pain: a systematic review
Authors: K V Fersum, W Dankaerts, P B O'Sullivan, J Maes, J S Skouen, J M Bjordal, A Kvåle
Journal: British Journal of Sports Medicine (2009)

There is lack of evidence for specific treatment interventions for patients with non-specific chronic low back pain (NSCLBP) despite the substantial amount of randomised controlled clinical trials evaluating treatment outcome for this disorder.It has been hypothesised that this vacuum of evidence is caused by the lack of subclassification of the heterogeneous population of patients with chronic low back pain for outcome research.A systematic review.A systematic review with a meta-analysis was undertaken to determine the integration of subclassification strategies with matched interventions in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for NSCLBP. A structured search for relevant studies in Embase, Cinahl, Medline, PEDro and the Cochrane Trials Register database, followed by hand searching all relevant studies in English up to December 2008.Only 5 of 68 studies (7.4%) subclassified patients beyond applying general inclusion and exclusion criteria. In the few studies where classification and matched interventions have been used, our meta-analysis showed a statistical difference in favour of the classification-based intervention for reductions in pain (p=0.004) and disability (p=0.0005), both for short-term and long-term reduction in pain (p=0.001). Effect sizes ranged from moderate (0.43) for short term to minimal (0.14) for long term.A better integration of subclassification strategies in NSCLBP outcome research is needed. We propose the development of explicit recommendations for the use of subclassification strategies and evaluation of targeted interventions in future research evaluating NSCLBP.
Rapid Evaluation of Least-Squares and Minimum-Evolution Criteria on Phylogenetic Trees
Authors: D. Bryant, P. Waddell
Journal: Molecular Biology and Evolution (1998)

We present fast new algorithms for evaluating trees with respect to least squares and minimum evolution (ME), the most commonly used criteria for inferring phylogenetic trees from distance data. These include: an optimal O(N2 ) time algorithm for calculating the branch (edge) lengths on a tree according to ordinary or unweighted least squares (OLS); an O(N3) time algorithm for edge lengths under weighted least squares (WLS) and the FitchMargoliash method; and an optimal O(N4) time algorithm for generalised least squares edge lengths. The Minimum Evolution criterion is based on the sum of edge lengths. Consequently, the edge lengths algorithms presented here lead directly to O(N2), O(N3) and O(N4) time algorithms for ME under OLS, WLS and GLS respectively. These algorithms are substantially faster than all those previously published, and the algorithms for OLS and GLS are the fastest possible (with respect to order of computational complexity). An optimal algorithm for determining path lengths in a tree with given edge lengths is also developed. This leads to an optimal O(N ) algorithm for OLS sums of squares evaluation and corresponding O(N3 ) and O(N4) time algorithms for WLS and GLS sums of squares, respectively. The GLS algorithm is time optimal if the covariance matrix is already inverted. The considerable increases in speed enable far more extensive tree searches and statistical evaluations (e.g. bootstrap, parametric bootstrap or jackknife). Hopefully, the fast algorithms for WLS and GLS will encourage their use for evaluating trees and their edge lengths ( e.g. for approximate divergence time estimates), since they should be more statistically efficient than OLS.
Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus.
Authors: N S van Oers, B L Cohen, R A Murgita
Journal: The Journal of Experimental Medicine (1989)

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.
Fair prices for new direct-acting antiviral agents (DAAs) to make treatment for all affordable
Authors: Sylvie Deuffic-Burban, Yazdan Yazdanpanah
Journal: Gut (2015)

Until 2011, the combination of pegylated interferon (pINF) and ribavirin (RBV) for 24 or 48 weeks was the approved treatment for chronic hepatitis C (CHC). Telaprevir and boceprevir, licensed in 2011 for use in patients infected with HCV genotype 1, were the first direct-acting antiviral agents (DAAs). With combinations including these agents, higher sustained viral response (SVR) rates were achieved compared with pINF+RBV, but also higher side effects. In 2013, sofosbuvir (SOF) was approved for use in HCV-infected patients with genotypes 2 and 3 in combination with RBV, and in those with genotypes 1 and 4, in combination with pINF and RBV with SVR rates >90%.1 ,2 With approval of other oral DAAs such as simeprevir and daclatasvir, now highly efficacious interferon-free regimens are also prescribed, particularly in genotypes 1 and 4.3 ,4 Moreover, last week, the European Commission granted marketing authorisation for the SOF–ledipasvir combination (Harvoni), the first single-tablet interferon-free regimen to treat HCV-infected patients with genotypes 1 and 4.5 

This new wave of antiviral therapy for CHC holds great promise with SVR rates >90%, better tolerability and shorter treatment duration. However, they are also accompanied by a significant increase in the cost of treatment regimens. As resources are limited, particularly in the time of crisis, it is important to assess, along with the already proven efficacy, the cost-effectiveness of these new drugs to treat CHC. The cost-effectiveness analysis allows us to explicitly consider whether the additional benefit from a more effective but more expensive strategy is ‘worth’ the additional cost. …
Does MOVES move the needle?
Authors: Robert Meyer
Journal: Annals of the Rheumatic Diseases (2015)

Osteoarthritis (OA) of the knee is a common and vexing condition. Additional safe and effective modalities to treat this chronic condition are badly needed.

The article by Hochberg et al 1 summarises the findings from the Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) study and concludes that the combination of glucosamine and chondroitin has equal efficacy to celecoxib, based on a 6-month, non-inferiority design using the change in the Western Ontario and McMaster osteoarthritis index (WOMAC) score as the assessment. Indeed, the combination …
Hypoxia in lung vascular biology and disease.
Authors: N WEISSMANN, F GRIMMINGER, W SEEGER
Journal: Cardiovascular Research (2006)

See reviews in the series by Weissmann et al.  [3]  (pages 620–629), Weir and Olschewski  [4]  (pages 630–641), and Fandrey et al.  [6]  (pages 642–651) in this issue and by Ghohani et al.  [7]  and Maggiorini  [8]  in next month's issue. 

With the evolution of photosynthesis, organisms had to cope with a dramatic environmental change: the presence of oxygen. Despite the initial toxicity of this gas, the presence of molecular oxygen offered a more effective energy metabolism. As a result, animals and humans require oxygen to survive, and a shortage of oxygen, hypoxia , can evoke life-threatening conditions. To maintain an optimal energy supply for the body, the lung is the first-line organ functioning as an interface between the body and the environment. This organ is the focus of an overview of the various aspects of “ Hypoxia in the Pulmonary Circulation ” in this Review Focus Series .

The lung structure is designed to achieve a very rapid and effective gas exchange. This is accomplished by two components, a large gas exchange surface and an extremely thin diffusion barrier between the alveolar gas and the blood [1]. The large capillary surface and the fragile diffusion barrier require a low blood pressure in the lung compared to the systemic circulation. In fact, pulmonary arterial blood pressure ranges <20 mmHg in healthy humans to prevent the risk of lung oedema and bleeding. In addition …
Ultrastructure and viability of isolated bovine preantral follicles
Authors: R van den Hurk
Journal: Human Reproduction Update (1998)

Techniques for the isolation of ovarian follicles and maturation of oocytes in vitro have enormous reproductive potential. Preservation of normal tissue function is vital. This study emphasizes the ultrastructure and viability of mechanically isolated bovine small (diameter 40-100 μm) preantral and large (140-450 μm) preantral/early antral follicles. Viability studies were performed for small preantral follicles. The presence of esterase activity, active mitochondria and dead cells served as parameters of oocyte and granulosa cell viability. After 1 day of culture, all follicles had a viable granulosa, displaying active mitochondria and/or esterase activity in all their cells, although a few (generally <5) dead granulosa cells were present in 17% of the follicles. Of the oocytes, 35 and 80% had esterase activity and active mitochondria respectively, whereas 8% appeared dead. The percentages of oocytes showing esterase activity and active mitochondria decreased during culture, whereas the percentage of follicles with dead oocytes or dead granulosa cells strongly increased. More than 90% of the isolated small follicles showed a poor ultrastructure, especially of their oocyte, which points to a negative selective isolation of poor follicles in the present study and/or an isolation procedure-induced damage of follicles. With respect to large preantral follicles, 42% of those distributed in the cortex and 64% of those isolated and cultured for 1 day had a poor ultrastructure. In contrast with the small ones, the percentage of ultrastructurally poor large preantral follicles had decreased to 27% after 5 days of culture, possibly due to better isolation and culture conditions. It is recommended to use ultrastructural and/or viability cell markers for in-vitro grown follicles to evaluate their quality, and particularly that of their oocytes.
Is the Failing Heart Energy Starved?
Authors: Joanne S. Ingwall, Robert G. Weiss
Journal: Circulation Research (2004)

The requirement of chemical energy in the form of ATP to support systolic and diastolic work of the heart is absolute. Because of its central role in cardiac metabolism and performance, the subject of this review on energetics in the failing heart is ATP. We briefly review the basics of myocardial ATP metabolism and describe how this changes in the failing heart. We present an analysis of what is now known about the causes and consequences of these energetic changes and conclude by commenting on unsolved problems and opportunities for future basic and clinical research.
Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema
Authors: K S Thomas
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. <b>Design:</b> Randomised, double blind, parallel group study of 18 weeks9 duration. <b>Setting:</b> 13 general practices and a teaching hospital in the Nottingham area. <b>Participants:</b> 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. <b>Interventions:</b> 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. <b>Main outcome measures:</b> Primary outcomes were total number of scratch-free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children9s life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. <b>Results:</b> No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch-free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval −2.0 to 4.0, P=0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. <b>Conclusion:</b> A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children. <h3>What is already known on this topic</h3> Topical corticosteroids have been used to control atopic eczema for 40 years No studies have compared short bursts of a potent preparation with prolonged use of a weak preparation for controlling mild or moderate disease <h3>What this study adds</h3> A short burst of a potent topical steroid is as effective and safe as prolonged use of a weak preparation for mild or moderate atopic eczema The type of preparation is immaterial provided that the dosage is adequate
Histochemical demonstration of sinusoidal γ-glutamyltransferase activity by substrate protection fixation: Comparative studies in rat and guinea pig liver
Authors: António José Lanca, Yedy Israel
Journal: Hepatology (1991)

Most histochemical methods for the detection of an enzymatic activity are preceded by tissue fixation with chemical agents that partially inactivate the enzymes. It is well known that substrates exert a marked protection against fixative-induced inactivation. The conventional histochemical methods for the demonstration of hepatic γ-glutamyltransferase activity have not been successful in detecting the activity of the enzyme on the sinusoidal side of the hepatocytes despite mounting biochemical evidence for its presence on that pole of the hepatocyte. Under conventional fixation the enzymatic activity in hepatocytes is only seen on the bile canalicular side. This may be the result of a preferential protective effect of γ-glutamyltransferase by its normal substrate, glutathione, present in the bile canaliculus at concentrations 500 times higher than in the sinusoidal lumen (8 mmol/L vs. 10 to 20 mmol/L). To test this hypothesis and to reduce the degree of fixative-induced inhibition of the enzyme activity, glutathione was either incorporated in the fixative solution or the livers were perfused with high concentrations of glutathione (10 mmol/L) before fixation. Our results histochemically demonstrate, in the normal adult rat liver, the existence of γ-glutamyl-transferase activity not only on the bile canalicular pole but also on the sinusoidal pole of the hepatocytes. Visualization of the enzyme activity on the sinusoidal pole is dependent on glutathione protection. Guinea pig livers, which present a 10-fold higher γ-glutamyltransferase activity than rat livers (similar to that in human beings), showed marked sinusoidal γ-glutamyltransferase activity even in the absence of glutathione protection. Glutathione protection further increased this sinusoidal activity. Histochemical data in the guinea pig paralleled the biochemical findings indicating that in a single pass guinea pig liver can remove considerably higher amounts (more than two thirds) of circulating glutathione than rat liver. The histochemical demonstration of γ-glutamyl-transferase activity in the sinusoidal pole of the hepatocyte in normal adult rat and guinea pig liver adds further evidence to the biochemical data supporting the existence of a sinusoidal γ-glutamyltransferase ectoactivity capable of removing glutathione from the circulation. (Hepatology 1991;14:857-863).
Molecular Evidence for Hierarchical Transcriptional Lineage Priming in Fetal and Adult Stem Cells and Multipotent Progenitors
Authors: Robert Månsson, Anne Hultquist, Sidinh Luc, Liping Yang, Kristina Anderson, Shabnam Kharazi, Suleiman Al-Hashmi, Karina Liuba, Lina Thorén, Jörgen Adolfsson, Natalija Buza-Vidas, Hong Qian, Shamit Soneji, Tariq Enver, Mikael Sigvardsson, Sten Eirik W. Jacobsen
Journal: Immunity (2007)
Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study
Authors: A G Semb, T K Kvien, A H Aastveit, I Jungner, T R Pedersen, G Walldius, I Holme
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To examine the rates of acute myocardial infarction (AMI) and ischaemic stroke (IS) and to examine the predictive value of total cholesterol (TC) and triglycerides (TG) for AMI and IS in patients with rheumatoid arthritis (RA) and people without RA. Methods In the Apolipoprotein MOrtality RISk (AMORIS) Study 480 406 people (including 1779 with RA, of whom 214 had an AMI and 165 an IS) were followed for 11.8 (range 7–17) years. Cox regression analysis was used to calculate HR per SD increase in TC or TG with 95% CI. All values were adjusted for age, diabetes and hypertension. Results The levels of TC and TG were significantly lower in patients with RA than in people without RA. Despite this, the rate of AMI and IS per 1000 years was at least 1.6 times higher in RA than non-RA. TC was nearly significantly predictive for AMI (HR/SD 1.13 (95% CI 0.99 to 1.29), p=0.07) and significantly predictive for future IS in RA (HR/SD 1.20 (95% CI 1.03 to 1.40), p=0.02). TG had no relationship to development of AMI (1.07, 0.94 to 1.21, p=0.29), but was weakly related to IS (1.13, 0.99 to 1.27, p=0.06). In contrast, both TC and TG were significant predictors of AMI and IS in people without RA. Conclusions Patients with RA had 1.6 times higher rate of AMI and IS than people without RA. TC and TG were significant predictors of AMI and IS in people without RA, whereas the predictive value in RA was not consistent.
Antivascular Actions of Microtubule-Binding Drugs
Authors: Edward L. Schwartz
Journal: Clinical Cancer Research (2009)

Abstract Microtubule-binding drugs (MBD) are widely used in cancer chemotherapy and also have clinically relevant antiangiogenic and vascular-disrupting properties. These antivascular actions are due in part to direct effects on endothelial cells, and all MBDs (both microtubule-stabilizing and microtubule-destabilizing) inhibit endothelial cell proliferation, migration, and tube formation in vitro, actions that are thought to correspond to therapeutic antiangiogenic actions. In addition, the microtubule-destabilizing agents cause prominent changes in endothelial cell morphology, an action associated with rapid vascular collapse in vivo. The effects on endothelial cells occur in vitro at low drug concentrations, which do not affect microtubule gross morphology, do not cause microtubule bundling or microtubule loss and do not induce cell cycle arrest, apoptosis, or cell death. Rather, it has been hypothesized that, at low concentrations, MBDs produce more subtle effects on microtubule dynamics, block critical cell signaling pathways, and prevent the microtubules from properly interacting with transient subcellular assemblies (focal adhesions and adherens junctions) whose subsequent stabilization and/or maturation are required for cell motility and cell-cell interactions. This review will focus on recent studies to define the molecular mechanisms for the antivascular actions of the MBDs, information that could be useful in the identification or design of agents whose actions more selectively target the tumor vasculature.
Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer: a retrospective study
Authors: Ana Ramírez de Molina, Jacinto Sarmentero-Estrada, Cristóbal Belda-Iniesta, Miquel Tarón, Victor Ramírez de Molina, Paloma Cejas, Marcin Skrzypski, David Gallego-Ortega, Javier de Castro, Enrique Casado, Miguel Angel García-Cabezas, Jose Javier Sánchez, Manuel Nistal, Rafael Rosell, Manuel González-Barón, Juan Carlos Lacal
Journal: The Lancet Oncology (2007)
A Novel β-Oxa Polyunsaturated Fatty Acid Downregulates the Activation of the IκB Kinase/Nuclear Factor κB Pathway, Inhibits Expression of Endothelial Cell Adhesion Molecules, and Depresses Inflammation
Authors: Antonio Ferrante, Brenton S. Robinson, Harmeet Singh, Hubertus P.A. Jersmann, Judith V. Ferrante, Zhi H. Huang, Neil A. Trout, Michael J. Pitt, Deborah A. Rathjen, Christopher J. Easton, Alf Poulos, Rolf H. Prager, Frank S. Lee, Charles S.T. Hii
Journal: Circulation Research (2006)

Several novel polyunsaturated fatty acids (PUFAs) that contain either an oxygen or sulfur atom in the beta-position were found to exhibit more selective antiinflammatory properties than their natural PUFA counterparts. One of these, beta-oxa-23:4n-6, unlike natural PUFAs, lacked ability to stimulate oxygen radical production in neutrophils but caused marked inhibition of agonist-induced upregulation of leukocyte adhesion to cultured human umbilical vein endothelial cells (HUVEC) and E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression. In addition, beta-oxa-23:4n-6 inhibited acute and chronic inflammatory responses in mice as well as the upregulation of adhesion molecule expression in arterial endothelium. This action of beta-oxa-23:4n-6 required a functional 12- but not 5-lipoxygenase or cyclooxygenases, consistent with its metabolism via the 12-lipoxygenase pathway. Whereas beta-oxa-23:4n-6 did not affect the activation of mitogen-activated protein kinases by tumor necrosis factor, activation of the IkappaB kinase/nuclear factor kappaB pathway was selectively inhibited. These novel PUFAs could form the basis for a potential new class of pharmaceuticals for treating inflammatory diseases, including atherosclerosis.