bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitual Coffee Consumption and Risk of Heart Failure
Authors: Mostofsky Elizabeth , Rice Megan S. , Levitan Emily B. , Mittleman Murray A. 
Published: June 2012

Background—
There have been discrepant findings on the association between coffee consumption and risk of incident heart failure.

Methods and Results—
We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, Embase, and CINAHL) from January 1966 through December 2011, with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6522 heart failure events and 140 220 participants, were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared with no consumption, the strongest inverse association was seen for 4 servings/day and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of myocardial infarction or diabetes.

Conclusions—
Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.
Systematic Review and Cost–Benefit Analysis of Radial Artery Access for Coronary Angiography and Intervention
Authors: Mitchell Matthew D. , Hong Jaekyoung A. , Lee Bruce Y. , Umscheid Craig A. , Bartsch Sarah M. , Don Creighton W. 
Published: June 2012

Background—
Radial artery access for coronary angiography and interventions has been promoted for reducing hemostasis time and vascular complications compared with femoral access, yet it can take longer to perform and is not always successful, leading to concerns about its cost. We report a cost–benefit analysis of radial catheterization based on results from a systematic review of published randomized controlled trials.

Methods and Results—
The systematic review added 5 additional randomized controlled trials to a prior review, for a total of 14 studies. Meta-analyses, following Cochrane procedures, suggested that radial catheterization significantly increased catheterization failure (OR, 4.92; 95% CI, 2.69–8.98), but reduced major complications (OR, 0.32; 95% CI, 0.24–0.42), major bleeding (OR, 0.39; 95% CI, 0.27–0.57), and hematoma (OR, 0.36; 95% CI, 0.27–0.48) compared with femoral catheterization. It added approximately 1.4 minutes to procedure time (95% CI, −0.22 to 2.97) and reduced hemostasis time by approximately 13 minutes (95% CI, −2.30 to −23.90). There were no differences in procedure success rates or major adverse cardiovascular events. A stochastic simulation model of per-case costs took into account procedure and hemostasis time, costs of repeating the catheterization at the alternate site if the first catheterization failed, and the inpatient hospital costs associated with complications from the procedure. Using base-case estimates based on our meta-analysis results, we found the radial approach cost $275 (95% CI, −$374 to −$183) less per patient from the hospital perspective. Radial catheterization was favored over femoral catheterization under all conditions tested.

Conclusions—
Radial catheterization was favored over femoral catheterization in our cost–benefit analysis.
Histomorphometric and biochemical studies on the liver of rainbow trout (Oncorhynchus mykiss) after exposure to sublethal concentrations of phenol
Authors: Monfared Ali louei , Salati Amir Parviz 
Published: June 2012

Phenolic compounds are common water pollutants and include a wide variety of organic chemicals. The effects of three sublethal concentrations of phenol on liver histology and some biochemical parameters of Oncorhynchus mykiss after 8 weeks exposure were investigated in this study. A total of 80 rainbow trout ( O. mykiss) were randomly divided into four groups ( n = 20). Control group was kept in water without any add-on material, while experimental groups were exposed to the concentration of 0.6, 1.2 and 2.4 mg/L of phenol solution. At the end of the study period, the weight of liver, condition factor (CF) and hepatosomatic index (HSI) were measured. Tissue and blood samples were taken separately for histologic evaluation and serum biochemical parameters assay, respectively. In fish treated with phenol, significant reduction in liver weight, CF, HSI ratio, diameter of hepatocytes and hepatocytes nuclear diameter ( p < 0.05) was recorded. Total protein and albumin decreased significantly in treated fish in comparison with control ( p < 0.05), but levels of cholesterol, glucose, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in fish exposed to different concentrations of phenol showed a significant increase ( p < 0.05). These findings showed that phenol could cause its harmful impacts even in very low concentrations.
Absorption, Metabolism, and Excretion of [14C]‐Tivozanib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Male Participants: A Phase I, Open‐Label, Mass‐Balance Study
Authors: Cotreau Monette M. , Hale Christine L. , Jacobson Lindsey , Oelke Claudine S. , Strahs Andrew L. , Kochan Robert G. , Sanga Madhu , Slichenmyer William , Vargo Dennis L. 
Published: June 2012

AbstractObjective: To evaluate the absorption, metabolism, and excretion of tivozanib, a new investigational drug for renal cell carcinoma and solid malignancies. Methods: Eight healthy male participants received a single 1.5‐mg (˜160 μCi) dose of oral [14C]‐tivozanib. Whole blood, serum, urine, and feces were evaluated up to 28 days postdose for pharmacokinetics, radioanalysis, and metabolites. Adverse events were recorded throughout the study. Results: [14C]‐tivozanib concentration peaked at 10.9 ± 5.84 hours. The mean serum half‐life for [14C]‐tivozanib was 89.3 ± 23.5 hours. The maximum concentration and area under the curve for [14C]‐tivozanib were 12.1 ± 5.67 ng/mL and 1084 ± 417.0 ng·h/mL, respectively. Mean recovery of total radioactivity was 91.0% ± 11.0%; 79.3% ± 8.82% of the radioactivity was recovered in feces both as unchanged tivozanib and metabolites. In the urine, 11.8% ± 4.59% was recovered only as metabolites. No unchanged tivozanib was found in the urine. Conclusion: Tivozanib had a long half‐life with no major circulating metabolite, was well tolerated as a single dose, and was primarily eliminated via feces with no unchanged tivozanib found in urine. These pharmacokinetic data of [14C]‐tivozanib are consistent with previous studies of unlabeled tivozanib.
A Single‐Dose Bioequivalence and Food Effect Study With Aprepitant and Fosaprepitant Dimeglumine in Healthy Young Adult Subjects
Authors: Shadle Craig R. , Murphy M. Gail , Liu Yang , Ho Maureen , Tatosian Daniel , Li Susie (Xiujiang) , Blum Robert A. 
Published: June 2012

AbstractFosaprepitant dimeglumine, a lyophilized prodrug, is rapidly converted to aprepitant, a substance P/neurokinin 1 (NK1) receptor antagonist. Intravenous (IV) fosaprepitant and oral aprepitant are used in combination with other antiemetics to prevent chemotherapy‐induced nausea and vomiting. This randomized, phase 1 study was designed to assess the aprepitant area under the curve (AUC0‐∞) equivalence of a single, oral 165‐mg or 185‐mg dose of aprepitant to a single 150‐mg fosaprepitant IV dose infused over 20 minutes, and to evaluate the effect of food on the bioavailability of the oral 165‐mg and 185‐mg aprepitant doses. Plasma samples were analyzed for aprepitant, and linear mixed‐effects models were applied to natural log‐transformed aprepitant AUC data. A 2 one‐sided tests procedure was used to evaluate bioequivalence; the adjusted P values for the AUC0‐∞ of both oral doses versus the IV dose were < .05, supporting the hypothesis that each single, oral dose of aprepitant is equivalent to the AUC0‐∞ of a single IV infusion of fosaprepitant. Food effect results suggest that dose adjustment would not be necessary with a single oral dose of aprepitant. Single‐dose administration of oral 165 mg and 185 mg aprepitant and IV 150 mg fosaprepitant was generally well tolerated.
Dynamics based alignment of proteins: an alternative approach to quantify dynamic similarity
Authors: Münz Márton , Lyngsø Rune , Hein Jotun , Biggin Philip C 
Published: June 2012

Abstract

Background
The dynamic motions of many proteins are central to their function. It therefore follows that the dynamic requirements of a protein are evolutionary constrained. In order to assess and quantify this, one needs to compare the dynamic motions of different proteins. Comparing the dynamics of distinct proteins may also provide insight into how protein motions are modified by variations in sequence and, consequently, by structure. The optimal way of comparing complex molecular motions is, however, far from trivial. The majority of comparative molecular dynamics studies performed to date relied upon prior sequence or structural alignment to define which residues were equivalent in 3-dimensional space.

Results
Here we discuss an alternative methodology for comparative molecular dynamics that does not require any prior alignment information. We show it is possible to align proteins based solely on their dynamics and that we can use these dynamics-based alignments to quantify the dynamic similarity of proteins. Our method was tested on 10 representative members of the PDZ domain family.

Conclusions
As a result of creating pair-wise dynamics-based alignments of PDZ domains, we have found evolutionarily conserved patterns in their backbone dynamics. The dynamic similarity of PDZ domains is highly correlated with their structural similarity as calculated with Dali. However, significant differences in their dynamics can be detected indicating that sequence has a more refined role to play in protein dynamics than just dictating the overall fold. We suggest that the method should be generally applicable.
MLPAinter for MLPA interpretation: an integrated approach for the analysis, visualisation and data management of Multiplex Ligation-dependent Probe Amplification
Authors: van Eijk Ronald , Eilers Paul HC , Natté Remco , Cleton-Jansen Anne-Marie , Morreau Hans , van Wezel Tom , Oosting Jan 
Published: June 2012

Abstract

Background
Multiplex Ligation-Dependent Probe Amplification (MLPA) is an application that can be used for the detection of multiple chromosomal aberrations in a single experiment. In one reaction, up to 50 different genomic sequences can be analysed. For a reliable work-flow, tools are needed for administrative support, data management, normalisation, visualisation, reporting and interpretation.

Results
Here, we developed a data management system, MLPAInter for MLPA interpretation, that is windows executable and has a stand-alone database for monitoring and interpreting the MLPA data stream that is generated from the experimental setup to analysis, quality control and visualisation. A statistical approach is applied for the normalisation and analysis of large series of MLPA traces, making use of multiple control samples and internal controls.

Conclusions

MLPAinter visualises MLPA data in plots with information about sample replicates, normalisation settings, and sample characteristics. This integrated approach helps in the automated handling of large series of MLPA data and guarantees a quick and streamlined dataflow from the beginning of an experiment to an authorised report.
Detecting sequence dependent transcriptional pauses from RNA and protein number time series
Authors: Emmert-Streib Frank , Häkkinen Antti , Ribeiro Andre S 
Published: June 2012

AbstractBackgroundEvidence suggests that in prokaryotes sequence-dependent transcriptional pauses affect the dynamics of transcription and translation, as well as of small genetic circuits. So far, a few pause-prone sequences have been identified from in vitro measurements of transcription elongation kinetics.ResultsUsing a stochastic model of gene expression at the nucleotide and codon levels with realistic parameter values, we investigate three different but related questions and present statistical methods for their analysis. First, we show that information from in vivo RNA and protein temporal numbers is sufficient to discriminate between models with and without a pause site in their coding sequence. Second, we demonstrate that it is possible to separate a large variety of models from each other with pauses of various durations and locations in the template by means of a hierarchical clustering and arandom forestclassifier. Third, we introduce anapproximate likelihood functionthat allows to estimate the location of a pause site.ConclusionsThis method can aid in detecting unknown pause-prone sequences from temporal measurements of RNA and protein numbers at a genome-wide scale and thus elucidate possible roles that these sequences play in the dynamics of genetic networks and phenotype.
Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits
Authors: Cánovas Angela , Quintanilla Raquel , Amills Marcel , Pena Ramona N 
Published: June 2012

Abstract

Background
Selection for increasing intramuscular fat content would definitively improve the palatability and juiciness of pig meat as well as the sensorial and organoleptic properties of cured products. However, evidences obtained in human and model organisms suggest that high levels of intramuscular fat might alter muscle lipid and carbohydrate metabolism. We have analysed this issue by determining the transcriptomic profiles of Duroc pigs with divergent phenotypes for 13 fatness traits. The strong aptitude of Duroc pigs to have high levels of intramuscular fat makes them a valuable model to analyse the mechanisms that regulate muscle lipid metabolism, an issue with evident implications in the elucidation of the genetic basis of human metabolic diseases such as obesity and insulin resistance.

Results
Muscle gene expression profiles of 68 Duroc pigs belonging to two groups (HIGH and LOW) with extreme phenotypes for lipid deposition and composition traits have been analysed. Microarray and quantitative PCR analysis showed that genes related to fatty acid uptake, lipogenesis and triacylglycerol synthesis were upregulated in the muscle tissue of HIGH pigs, which are fatter and have higher amounts of intramuscular fat than their LOW counterparts. Paradoxically, lipolytic genes also showed increased mRNA levels in the HIGH group suggesting the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Several genes related to the insulin-signalling pathway, that is usually impaired in obese humans, were also upregulated. Finally, genes related to antigen-processing and presentation were downregulated in the HIGH group.

Conclusion
Our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the cell would be needed to to elucidate the effects of lipid deposition on muscle metabolism in pigs.
Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion
Authors: Zheng Dongling , Kille Peter , Feeney Graham P , Cunningham Phil , Handy Richard D , Hogstrand Christer 
Published: June 2012

Abstract

Background
Zinc deficiency is detrimental to organisms, highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within the zebrafish gill. This tissue represents a model system for studying ion absorption across polarised epithelial cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals.

Results
Zebrafish were treated with either zinc-depleted (water = 2.61 μg L-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μg L-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array. Of the genes represented the expression of a total of 333 transcripts showed differential regulation by zinc depletion (having a fold-change greater than 1.8 and an adjusted P-value less than 0.1, controlling for a 10% False Discovery Rate). Down-regulation was dominant at most time points and distinct sets of genes were regulated at different stages. Annotation enrichment analysis revealed that 'Developmental Process' was the most significantly overrepresented Biological Process GO term (P = 0.0006), involving 26% of all regulated genes. There was also significant bias for annotations relating to development, cell cycle, cell differentiation, gene regulation, butanoate metabolism, lysine degradation, protein tyrosin phosphatases, nucleobase, nucleoside and nucleotide metabolism, and cellular metabolic processes. Within these groupings genes associated with diabetes, bone/cartilage development, and ionocyte proliferation were especially notable. Network analysis of the temporal expression profile indicated that transcription factors foxl1, wt1, nr5a1, nr6a1, and especially, hnf4a may be key coordinators of the homeostatic response to zinc depletion.

Conclusions
The study revealed the complex regulatory pathways that allow the organism to subtly respond to the low-zinc condition. Many of the processes affected reflected a fundamental restructuring of the gill epithelium through reactivation of developmental programs leading to stem cell differentiation. The specific regulation of genes known to be involved in development of diabetes provides new molecular links between zinc deficiency and this disease. The present study demonstrates the importance of including the time-dimension in microarray studies.
Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth
Authors: Bolpetti Aline , Silva João S , Villa Luisa L , Lepique Ana Paula 
Published: June 2012

AbstractBackgroundHuman Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like, induce T cell regulatory phenotype and play an important role in tumor growth. M2 macrophages secrete several cytokines, among them IL-10, which has been shown to play a role in T cell suppression by tumor macrophages in other tumor models. In this work, we sought to establish if IL-10 is part of the mechanism by which HPV tumor associated macrophages induce T cell regulatory phenotype, inhibiting anti-tumor activity and facilitating tumor growth.ResultsTC-1 tumor cells do not express or respond to IL-10, but recruit leukocytes which, within the tumor environment, produce this cytokine. Using IL-10 deficient mice or blocking IL-10 signaling with neutralizing antibodies, we observed a significant reduction in tumor growth, an increase in tumor infiltration by HPV16 E7 specific CD8 lymphocytes, including a population positive for Granzyme B and Perforin expression, and a decrease in the percentage of HPV specific regulatory T cells in the lymph nodes.ConclusionsOur data shows that in the HPV16 TC-1 tumor mouse model, IL-10 produced by tumor macrophages induce regulatory phenotype on T cells, an immune escape mechanism that facilitates tumor growth. Our results point to a possible mechanism behind the epidemiologic data that correlates higher IL-10 expression with risk of cervical cancer development in HPV infected women.
Filifactor alocis - involvement in periodontal biofilms
Authors: Schlafer Sebastian , Riep Birgit , Griffen Ann L , Petrich Annett , Hübner Julia , Berning Moritz , Friedmann Anton , Göbel Ulf B , Moter Annette 
Published: June 2012

Abstract

Background
Bacteria in periodontal pockets develop complex sessile communities that attach to the tooth surface. These highly dynamic microfloral environments challenge both clinicians and researchers alike. The exploration of structural organisation and bacterial interactions within these biofilms is critically important for a thorough understanding of periodontal disease. In recent years, Filifactor alocis, a fastidious, Gram-positive, obligately anaerobic rod was repeatedly identified in periodontal lesions using DNA-based methods. It has been suggested to be a marker for periodontal deterioration. The present study investigated the epidemiology of F. alocis in periodontal pockets and analysed the spatial arrangement and architectural role of the organism in in vivo grown subgingival biofilms.

Results
A species-specific oligonucleotide probe, FIAL, was designed and evaluated. A total of 490 subgingival plaque samples were submitted to PCR and subsequent dot blot hybridization to compare the prevalence of F. alocis in patients suffering from generalized aggressive periodontitis (GAP), chronic periodontitis (CP), and control subjects resistant to periodontitis. Moreover, a specially designed carrier system was used to collect in vivo grown subgingival biofilms from GAP patients. Subsequent topographic analysis was performed using fluorescence in situ hybridization.
While the majority of patients suffering from GAP or CP harboured F. alocis, it was rarely detected in the control group. In the examined carrier-borne biofilms the organism predominantly colonized apical parts of the pocket in close proximity to the soft tissues and was involved in numerous structures that constitute characteristic architectural features of subgingival periodontal biofilms.

Conclusions

F. alocis is likely to make a relevant contribution to the pathogenetic structure of biofilms accounting for periodontal inflammation and can be considered an excellent marker organism for periodontal disease.