1,517 research outputs found
Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics
Background:
Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer.
Methodology/Principal Findings:
Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer.
Conclusions/Significance:
Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy
Development and Validation of a Composite Programmatic Assessment Tool for HIV Therapy
Background
We developed and validated a new and simple metric, the Programmatic Compliance Score (PCS), based on the IAS-USA antiretroviral therapy management guidelines for HIV-infected adults, as a predictor of all-cause mortality, at a program-wide level. We hypothesized that non-compliance would be associated with the highest probability of mortality.
Methods and Findings
3543 antiretroviral-naive HIV-infected patients aged ≥19 years who initiated antiretroviral therapy between January 1, 2000 and August 31, 2009 in British Columbia (BC), Canada, were followed until August 31, 2010. The PCS is composed by six non-performance indicators based on the IAS-USA guidelines: (1) having <3 CD4 count tests in the first year after starting antiretroviral therapy; (2) having <3 plasma viral load tests in the first year after starting antiretroviral therapy; (3) not having drug resistance testing done prior to starting antiretroviral therapy; (4) starting on a non-recommended antiretroviral therapy regimen; (5) starting therapy with CD4 <200 cells/mm3; and (6) not achieving viral suppression within 6 months since antiretroviral therapy initiation. The sum of these six indicators was used to develop the PCS score - higher score indicates poorer performance. The main outcome was all-cause mortality. Each PCS component was independently associated with mortality. In the mortality analysis, the odds ratio (OR) for PCS ≥4 versus 0 was 22.37 (95% CI 10.46–47.84).
Conclusions
PCS was strongly associated with all-cause mortality. These results lend independent validation to the IAS-USA treatment guidelines for HIV-infected adults. Further efforts are warranted to enhance the PCS as a means to further improve clinical outcomes. These should be specifically evaluated and targeted at healthcare providers and patients
Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages
OBJECTIVE
Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+).
METHODS
Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale.
RESULTS
In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN.
CONCLUSIONS
This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages
Grammar-based distance in progressive multiple sequence alignment
Background: We propose a multiple sequence alignment (MSA) algorithm and compare the alignment-quality and execution-time of the proposed algorithm with that of existing algorithms. The proposed progressive alignment algorithm uses a grammar-based distance metric to determine the order in which biological sequences are to be pairwise aligned. The progressive alignment occurs via pairwise aligning new sequences with an ensemble of the sequences previously aligned. Results: The performance of the proposed algorithm is validated via comparison to popular progressive multiple alignment approaches, ClustalW and T-Coffee, and to the more recently developed algorithms MAFFT, MUSCLE, Kalign, and PSAlign using the BAliBASE 3.0 database of amino acid alignment files and a set of longer sequences generated by Rose software. The proposed algorithm has successfully built multiple alignments comparable to other programs with significant improvements in running time. The results are especially striking for large datasets. Conclusion: We introduce a computationally efficient progressive alignment algorithm using a grammar based sequence distance particularly useful in aligning large datasets
Compensatory ingestion upon dietary restriction in Drosophila melanogaster
Dietary restriction extends the lifespan of numerous, evolutionarily diverse species. In D. melanogaster, a prominent model for research on the interaction between nutrition and longevity, dietary restriction is typically based on medium dilution, with possible compensatory ingestion commonly being neglected. Possible problems with this approach are revealed by using a method for direct monitoring of D. melanogaster feeding behavior. This demonstrates that dietary restriction elicits robust compensatory changes in food consumption. As a result, the effect of medium dilution is overestimated and, in certain cases, even fully compensated for. Our results strongly indicate that feeding behavior and nutritional composition act concertedly to determine fly lifespan. Feeding behavior thus emerges as a central element in D. melanogaster aging
High-Fat Diet with Acyl-Ghrelin Treatment Leads to Weight Gain with Low Inflammation, High Oxidative Capacity and Normal Triglycerides in Rat Muscle
Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity
Observation of an Exotic Baryon in Exclusive Photoproduction from the Deuteron
In an exclusive measurement of the reaction , a
narrow peak that can be attributed to an exotic baryon with strangeness
is seen in the invariant mass spectrum. The peak is at
GeV/c with a measured width of 0.021 GeV/c FWHM, which is largely
determined by experimental mass resolution. The statistical significance of the
peak is . The mass and width of the observed peak are
consistent with recent reports of a narrow baryon by other experimental
groups.Comment: 5 pages, 5 figure
Measurement of Beam-Spin Asymmetries for Deep Inelastic Electroproduction
We report the first evidence for a non-zero beam-spin azimuthal asymmetry in
the electroproduction of positive pions in the deep-inelastic region. Data have
been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector
at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of
the modulation increases with the momentum of the pion relative to
the virtual photon, , with an average amplitude of for range.Comment: 5 pages, RevTEX4, 3 figures, 2 table
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n
We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic
range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c)
peaks where two nucleons each have 20% or less, and the third nucleon has most
of the transferred energy. These fast pp and pn pairs are back-to-back with
little momentum along the three-momentum transfer, indicating that they are
spectators. Experimental and theoretical evidence indicates that we have
measured distorted two-nucleon momentum distributions by striking the third
nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR
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