bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways
Authors: Moon Changsuk , Han Jeong Ran , Park Hyun-Jung , Hah Jong Sik , Kang Jihee Lee 
Published: March 2009

AbstractBackgroundSynthetic peptides containing the RGD sequence inhibit integrin-related functions in different cell systems. Here, we investigated the effects of synthetic Arg-Gly-Asp-Ser (RGDS) peptide on key inflammatory responses to intratracheal (i.t.) lipopolysaccharide (LPS) treatment and on the integrin signaled mitogen-activated protein (MAP) kinase pathway during the development of acute lung injury.MethodsSaline or LPS (1.5 mg/kg) was administeredi.t.with or without a single dose of RGDS (1, 2.5, or 5 mg/kg, i.p.), anti-αvor anti-β3mAb (5 mg/kg, i.p.). Mice were sacrificed 4 or 24 h post-LPS.ResultsA pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-α and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL) fluid at 4 or 24 h post-LPS treatment. RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue. Importantly, the inhibition of the inflammatory responses and the kinase pathways were still evident when this peptide was administered 2 h after LPS treatment. Similarly, a blocking antibody against integrin αvsignificantly inhibited LPS-induced inflammatory cell migration into the lung, protein accumulation and proinflammatory mediator production in BAL fluid, at 4 or 24 h post-LPS. Anti-β3also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS.ConclusionThese results suggest that RGDS with high specificity for αvintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.
Finding evolutionarily conserved cis-regulatory modules with a universal set of motifs
Authors: Wilczynski Bartek , Dojer Norbert , Patelak Mateusz , Tiuryn Jerzy 
Published: March 2009

Abstract

Background
Finding functional regulatory elements in DNA sequences is a very important problem in computational biology and providing a reliable algorithm for this task would be a major step towards understanding regulatory mechanisms on genome-wide scale. Major obstacles in this respect are that the fact that the amount of non-coding DNA is vast, and that the methods for predicting functional transcription factor binding sites tend to produce results with a high percentage of false positives. This makes the problem of finding regions significantly enriched in binding sites difficult.

Results
We develop a novel method for predicting regulatory regions in DNA sequences, which is designed to exploit the evolutionary conservation of regulatory elements between species without assuming that the order of motifs is preserved across species. We have implemented our method and tested its predictive abilities on various datasets from different organisms.

Conclusion
We show that our approach enables us to find a majority of the known CRMs using only sequence information from different species together with currently publicly available motif data. Also, our method is robust enough to perform well in predicting CRMs, despite differences in tissue specificity and even across species, provided that the evolutionary distances between compared species do not change substantially. The complexity of the proposed algorithm is polynomial, and the observed running times show that it may be readily applied.
Euthanasia and other end-of-life decisions: a mortality follow-back study in Belgium
Authors: Van den Block Lieve , Deschepper Reginald , Bilsen Johan , Bossuyt Nathalie , Van Casteren Viviane , Deliens Luc 
Published: March 2009

Abstract

Background
This study compares prevalence and types of medical end-of-life decisions between the Dutch-speaking and French-speaking communities of Belgium. This is the first nationwide study that can make these comparisons and the first measurement after implementation of the euthanasia law (2002).

Methods
We performed a mortality follow-back study in 2005–2006. Data were collected via the nationwide Sentinel Network of General Practitioners, an epidemiological surveillance system representative of all Belgian GPs.
Weekly, all GPs reported the medical end-of-life decisions among all non-sudden deaths of patients in their practice. We compared the northern Dutch-speaking (60%) and southern French-speaking communities (40%) controlling for population differences.

Results
We analysed 1690 non-sudden deaths. An end-of-life decision with possible life-shortening effect was made in 50% of patients in the Dutch-speaking community and 41% of patients in the French-speaking community (OR 1.4; 95%CI, 1.2 to 1.8). Continuous deep sedation until death occurred in 8% and 15% respectively (OR 0.5; 95%CI, 0.4 to 0.7). Community differences regarding the prevalence of euthanasia or physician-assisted suicide were not significant.
Community differences were more present among home/care home than among hospital deaths: non-treatment decisions with explicit life-shortening intention were made more often in the Dutch-speaking than in the French-speaking community settings (OR 2.2; 95%CI, 1.2 to 3.9); while continuous deep sedation occurred less often in the Dutch-speaking community settings (OR 0.5; 95%CI, 0.3 to 0.9).

Conclusion
Even though legal and general healthcare systems are the same for the whole country, there are considerable variations between the communities in type and prevalence of certain end-of-life decisions, even after controlling for population differences.
Glycerol: An unexpected major metabolite of energy metabolism by the human malaria parasite
Authors: Lian Lu-Yun , Al-Helal Mohammed , Roslaini Abd Majid , Fisher Nicholas , Bray Patrick G , Ward Stephen A , Biagini Giancarlo A 
Published: March 2009

Abstract

Background
Malaria is a global health emergency, and yet our understanding of the energy metabolism of the principle causative agent of this devastating disease, Plasmodium falciparum, remains rather basic. Glucose was shown to be an essential nutritional requirement nearly 100 years ago and since this original observation, much of the current knowledge of Plasmodium energy metabolism is based on early biochemical work, performed using basic analytical techniques (e.g. paper chromatography), carried out almost exclusively on avian and rodent malaria. Data derived from malaria parasite genome and transcriptome studies suggest that the energy metabolism of the parasite may be more complex than hitherto anticipated. This study was undertaken in order to further characterize the fate of glucose catabolism in the human malaria parasite, P. falciparum.

Methods
Products of glucose catabolism were determined by incubating erythrocyte-freed parasites with D-[1-13C] glucose under controlled conditions and metabolites were identified using 13C-NMR spectroscopy.

Results
Following a 2 h incubation of freed-P. falciparum parasites with 25 mM D-[1-13C] glucose (n = 4), the major metabolites identified included; [3-13C] lactate, [1,3-13C] glycerol, [3-13C] pyruvate, [3-13C] alanine and [3-13C] glycerol-3-phosphate. Control experiments performed with uninfected erythrocytes incubated under identical conditions did not show any metabolism of D-[1-13C] glucose to glycerol or glycerol-3-phosphate.

Discussion
The identification of glycerol as a major glucose metabolite confirms the view that energy metabolism in this parasite is more complex than previously proposed. It is hypothesized here that glycerol production by the malaria parasite is the result of a metabolic adaptation to growth in O2-limited (and CO2 elevated) conditions by the operation of a glycerol-3-phosphate shuttle for the re-oxidation of assimilatory NADH. Similar metabolic adaptations have been reported previously for other microaerobic/anaerobic organisms, such as yeast, rumen protozoa and human parasitic protozoa.

Conclusion
These data highlight the need to re-evaluate the carbon and redox balance of this important human pathogen, ultimately leading to a better understanding of how the parasite is able to adapt to the variable environments encountered during parasite development and disease progression.
A MT1-MMP/NF-κB signaling axis as a checkpoint controller of COX-2 expression in CD133(+) U87 glioblastoma cells
Authors: Annabi Borhane , Laflamme Carl , Sina Asmaa , Lachambre Marie-Paule , Béliveau Richard 
Published: March 2009

Abstract

Background
The CD133(+) stem cell population in recurrent gliomas is associated with clinical features such as therapy resistance, blood-brain barrier disruption and, hence, tumor infiltration. Screening of a large panel of glioma samples increasing histological grade demonstrated frequencies of CD133(+) cells which correlated with high expression of cyclooxygenase (COX)-2 and of membrane type-1 matrix metalloproteinase (MT1-MMP).

Methods
We used qRT-PCR and immunoblotting to examine the molecular interplay between MT1-MMP and COX-2 gene and protein expression in parental, CD133(+), and neurospheres U87 glioma cell cultures.

Results
We found that CD133, COX-2 and MT1-MMP expression were enhanced when glioma cells were cultured in neurosphere conditions. A CD133(+)-enriched U87 glioma cell population, isolated from parental U87 cells with magnetic cell sorting technology, also grew as neurospheres and showed enhanced COX-2 expression. MT1-MMP gene silencing antagonized COX-2 expression in neurospheres, while overexpression of recombinant MT1-MMP directly triggered COX-2 expression in U87 cells independent from MT1-MMP's catalytic function. COX-2 induction by MT1-MMP was also validated in wild-type and in NF-κB p65-/- mutant mouse embryonic fibroblasts, but was abrogated in NF-κB1 (p50-/-) mutant cells.

Conclusion
We provide evidence for enhanced COX-2 expression in CD133(+) glioma cells, and direct cell-based evidence of NF-κB-mediated COX-2 regulation by MT1-MMP. The biological significance of such checkpoint control may account for COX-2-dependent mechanisms of inflammatory balance responsible of therapy resistance phenotype of cancer stem cells.
Bisulfite-based epityping on pooled genomic DNA provides an accurate estimate of average group DNA methylation
Authors: Docherty Sophia J , Davis Oliver SP , Haworth Claire MA , Plomin Robert , Mill Jonathan 
Published: March 2009

Abstract

Background
DNA methylation plays a vital role in normal cellular function, with aberrant methylation signatures being implicated in a growing number of human pathologies and complex human traits. Methods based on the modification of genomic DNA with sodium bisulfite are considered the 'gold-standard' for DNA methylation profiling on genomic DNA; however, they require relatively large amounts of DNA and may be prohibitively expensive when used on the large sample sizes necessary to detect small effects. We propose that a high-throughput DNA pooling approach will facilitate the use of emerging methylomic profiling techniques in large samples.

Results
Compared with data generated from 89 individual samples, our analysis of 205 CpG sites spanning nine independent regions of the genome demonstrates that DNA pools can be used to provide an accurate and reliable quantitative estimate of average group DNA methylation. Comparison of data generated from the pooled DNA samples with results averaged across the individual samples comprising each pool revealed highly significant correlations for individual CpG sites across all nine regions, with an average overall correlation across all regions and pools of 0.95 (95% bootstrapped confidence intervals: 0.94 to 0.96).

Conclusion
In this study we demonstrate the validity of using pooled DNA samples to accurately assess group DNA methylation averages. Such an approach can be readily applied to the assessment of disease phenotypes reducing the time, cost and amount of DNA starting material required for large-scale epigenetic analyses.
Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis
Authors: Giles Jon T , Szklo Moyses , Post Wendy , Petri Michelle , Blumenthal Roger S , Lam Gordon , Gelber Allan C , Detrano Robert , Scott William W , Kronmal Richard A , Bathon Joan M 
Published: March 2009

Abstract
Introduction
Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.

Methods
Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.

Results
The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.

Conclusions
Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.
Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis: a cross-sectional study
Authors: Elkan Ann-Charlotte , Håkansson Niclas , Frostegård Johan , Cederholm Tommy , Hafström Ingiäld 
Published: March 2009

Abstract
Introduction
Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA.

Methods
A total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined.

Results
The mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001).

Conclusions
About one in five patients with low-active RA displayed rheumatoid cachexia. This condition was associated with high levels of LDL cholesterol, low levels of atheroprotective anti-PC and high frequency of hypertension, which is of interest in the context of CVD in RA. The cachexia could not be related to diet fat intake. However, patients on a Mediterranean-like diet had high anti-PC levels in spite of similar frequency of cachexia. High anti-PC levels may provide some protection against CVD.
Role of [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in the Follow-Up of Lymphoma
Authors: Luigi Zinzani Pier , Stefoni Vittorio , Tani Monica , Fanti Stefano , Musuraca Gerardo , Castellucci Paolo , Marchi Enrica , Fina Mariapaola , Ambrosini Valentina , Pellegrini Cinzia , Alinari Lapo , Derenzini Enrico , Montini Giancarlo , Broccoli Alessandro , Bacci Francesco , Pileri Stefano , Baccarani Michele 
Published: March 2009

Purpose In lymphoma, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. However, there are no prospective studies investigating the value of serial FDG-PET over time in patients in complete remission. Patients and Methods All patients with lymphoma who achieved the first complete remission were prospectively enrolled onto the study and scheduled for serial FDG-PET scans at 6, 12, 18, and 24 months; further scans were then carried out on an annual basis. Overall, the population included 421 patients (160 patients with Hodgkin's lymphoma [HL], 183 patients with aggressive non-Hodgkin's lymphoma [NHL], and 78 patients with indolent follicular NHL). All patients had a regular follow-up evaluation, including complete clinical and laboratory evaluation, and final assessment of any suspect FDG-PET findings using other imaging procedures (computed tomography [CT] scan) and/or biopsy and/or clinical evolution. FDG-PET findings were reported as positive for relapse, inconclusive (when equivocal), or negative for relapse. Results PET enabled documentation of lymphoma relapse in 41 cases at 6 months, in 30 cases at 12 months, in 26 cases at 18 months, in 10 cases at 24 months, and in 11 cases at more than 36 months. All 36 patients with inconclusive positive PET underwent biopsy; only 12 (33%) of 36 patients had a concomitant suggestion of positivity on CT. A lymphoma relapse was diagnosed in 24 (66%) of 36 patients. Conclusion Our results confirm FDG-PET as a valid tool for follow-up of patients with HL and NHL. In patients with inconclusive positive results, histologic confirmation plays an important role in identifying true relapse.
Prospective, Randomized Trial of Two Different Modalities of Flushing Central Venous Catheters in Pediatric Patients With Cancer
Authors: Cesaro Simone , Tridello Gloria , Cavaliere Mara , Magagna Laura , Gavin Patrizia , Cusinato Riccardo , Zadra Nicola , Franco Zanon Giovanni , Zanesco Luigi , Carli Modesto 
Published: March 2009

Purpose There are limited prospective data on whether the method of flushing affects the complication rate of tunnelled central venous catheters (CVCs). Patients and Methods During a 25-month period, 203 pediatric patients who had newly placed Broviac-Hickman CVCs were randomly assigned to standard flushing with heparin solution or to experimental flushing with normal saline via a positive-pressure cap. Results Two hundred twenty-one complications were recorded among 75,249 CVC-days (2.94 per 1,000 CVC-days). A higher incidence of CVC occlusion (83 v 41 episodes; P = .0002) and bacteremia (24 v 9; P = .01) were found in the experimental arm. The cumulative probability of developing at least one CVC complication was higher in the experimental arm than in the standard arm (65.1% [95% CI, 55% to 75%] v 43.8% [95% CI, 34% to 54%], respectively; P = .01). No difference was found in either the cause or the frequency of premature removal of CVCs between the two study arms. After a median follow-up of 360 days (range, 4 to 1,073), CVC survival was similar: 77% (95% CI, 66% to 84%) for the experimental arm and 69% (95% CI, 53% to 80%) for the standard arm (P = .7). The factors associated with the occurrence of CVC complication were a diagnosis of leukemia/lymphoma, double-lumen CVC, and experimental flushing. The only factor significantly associated with premature removal of a CVC was a diagnosis of leukemia/lymphoma (hazard rate, 2.3; 95% CI, 1.1 to 4.7). Conclusion An increased complication rate was found with normal saline flushing, but additional investigation is warranted to clarify whether it is related to saline use or to once-a-week flushing.
A prospective examination of perceived stress as a mediator of the relationship between life‐events and QOL following breast cancer
Authors: Beatty Lisa , Lee Christina , Wade Tracey D. 
Published: March 2009

Objectives This study prospectively investigated the relationship between life‐events, perceived stress, and quality of life (QOL) following breast cancer diagnosis, using the bio‐behavioural model of cancer stress as a framework.Design A longitudinal, self‐report design was used.Methods Three waves of data from 10,543 mid‐aged Australian women (aged 45–50 at Survey 1) were collected over 5 years as part of a population‐based survey. From this group a subsample (N=140) were identified who did not have breast cancer at Survey 1, but who subsequently developed breast cancer. Random regression growth curve analyses were used to investigate whether perceived stress mediated the relationship between initial life‐events and change in QOL functioning overtime.Results Prospective evidence was generated for each of the three criteria for testing mediation. As the number of life‐events before breast cancer increased, women were significantly more likely to experience corresponding increases in perceived stress over the 5‐year period. As the level of perceived stress before breast cancer increased, women were more likely to experience deteriorations overtime in role emotional, role physical, vitality, bodily pain, physical functioning, and social functioning. As the number of life‐events before breast cancer increased, women were at significant risk of experiencing deteriorations overtime in bodily pain, social functioning, role emotional, and vitality. Mediational analyses revealed that perceived stress fully mediated the relationship between initial life‐events and two QOL domains; role‐emotional and social functioning.Conclusion Results partially supported the bio‐behavioural model of cancer stress, but the model does not appear to fit the data as well as predicted, and may require revision.