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641.
Peter H. Gann Ryan Deaton Anup Amatya Mahesh Mohnani Erika Enk Rueter Yirong Yang Viju Ananthanarayanan 《PloS one》2013,8(7)
Background
Our objective was to develop and validate a multi-feature nuclear score based on image analysis of direct DNA staining, and to test its association with field effects and subsequent detection of prostate cancer (PCa) in benign biopsies.Methods
Tissue sections from 39 prostatectomies were Feulgen-stained and digitally scanned (400×), providing maps of DNA content per pixel. PCa and benign epithelial nuclei were randomly selected for measurement of 52 basic morphometric features. Logistic regression models discriminating benign from PCa nuclei, and benign from malignant nuclear populations, were built and cross-validated by AUC analysis. Nuclear populations were randomly collected <1 mm or >5 mm from cancer foci, and from cancer-free prostates, HGPIN, and PCa Gleason grade 3–5. Nuclei also were collected from negative biopsy subjects who had a subsequent diagnosis of PCa and age-matched cancer-free controls (20 pairs).Results
A multi-feature nuclear score discriminated cancer from benign cell populations with AUCs of 0.91 and 0.79, respectively, in training and validation sets of patients. In prostatectomy samples, both nuclear- and population-level models revealed cancer-like features in benign nuclei adjacent to PCa, compared to nuclei that were more distant or from PCa-free glands. In negative biopsies, a validated model with 5 variance features yielded significantly higher scores in cases than controls (P = 0.026).Conclusions
A multifeature nuclear morphometric score, obtained by automated digital analysis, was validated for discrimination of benign from cancer nuclei. This score demonstrated field effects in benign epithelial nuclei at varying distance from PCa lesions, and was associated with subsequent PCa detection in negative biopsies.Impact
This nuclear score shows promise as a risk predictor among men with negative biopsies and as an intermediate biomarker in Phase II chemoprevention trials. The results also suggest that subvisual disturbances in nuclear structure precede the development of pre-neoplastic lesions. 相似文献642.
Dietrich Rebholz-Schuhmann Jee-Hyub Kim Ying Yan Abhishek Dixit Caroline Friteyre Robert Hoehndorf Rolf Backofen Ian Lewin 《PloS one》2013,8(10)
Motivation
Biomedical entities, their identifiers and names, are essential in the representation of biomedical facts and knowledge. In the same way, the complete set of biomedical and chemical terms, i.e. the biomedical “term space” (the “Lexeome”), forms a key resource to achieve the full integration of the scientific literature with biomedical data resources: any identified named entity can immediately be normalized to the correct database entry. This goal does not only require that we are aware of all existing terms, but would also profit from knowing all their senses and their semantic interpretation (ambiguities, nestedness).Result
This study compiles a resource for lexical terms of biomedical interest in a standard format (called “LexEBI”), determines the overall number of terms, their reuse in different resources and the nestedness of terms. LexEBI comprises references for protein and gene entries and their term variants and chemical entities amongst other terms. In addition, disease terms have been identified from Medline and PubmedCentral and added to LexEBI. Our analysis demonstrates that the baseforms of terms from the different semantic types show only little polysemous use. Nonetheless, the term variants of protein and gene names (PGNs) frequently contain species mentions, which should have been avoided according to protein annotation guidelines. Furthermore, the protein and gene entities as well as the chemical entities, both do comprise enzymes leading to hierarchical polysemy, and a large portion of PGNs make reference to a chemical entity. Altogether, according to our analysis based on the Medline distribution, 401,869 unique PGNs in the documents contain a reference to 25,022 chemical entities, 3,125 disease terms or 1,576 species mentions.Conclusion
LexEBI delivers the complete biomedical and chemical Lexeome in a standardized representation (http://www.ebi.ac.uk/Rebholz-srv/LexEBI/). The resource provides the disease terms as open source content, and fully interlinks terms across resources. 相似文献643.
Gopal Krushna Pal Chandrasekaran Adithan Palghat Hariharan Ananthanarayanan Pravati Pal Nivedita Nanda Thiyagarajan Durgadevi Venugopal Lalitha Avupati Naga Syamsunder Tarun Kumar Dutta 《PloS one》2013,8(11)
Background
Though cardiovascular (CV) risks are reported in first-degree relatives (FDR) of type 2 diabetics, the pathophysiological mechanisms contributing to these risks are not known. We investigated the association of sympathovagal imbalance (SVI) with CV risks in these subjects.Subjects and Methods
Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate-pressure product (RPP), spectral indices of heart rate variability (HRV), autonomic function tests, insulin resistance (HOMA-IR), lipid profile, inflammatory markers, oxidative stress (OS) marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72) and control group (subjects with no family history of diabetes, n = 104).Results
BMI, BP, BHR, HOMA-IR, lipid profile, inflammatory and OS markers, renin, LF-HF (ratio of low-frequency to high-frequency power of HRV, a sensitive marker of SVI) were significantly increased (p<0.0001) in study group compared to the control group. SVI in study group was due to concomitant sympathetic activation and vagal inhibition. There was significant correlation and independent contribution of markers of insulin resistance, dyslipidemia, inflammation and OS to LF-HF ratio. Multiple-regression analysis demonstrated an independent contribution of LF-HF ratio to prehypertension status (standardized beta 0.415, p<0.001) and bivariate logistic-regression showed significant prediction (OR 2.40, CI 1.128–5.326, p = 0.002) of LF-HF ratio of HRV to increased RPP, the marker of CV risk, in study group.Conclusion
SVI in FDR of type 2 diabetics occurs due to sympathetic activation and vagal withdrawal. The SVI contributes to prehypertension status and CV risks caused by insulin resistance, dyslipidemia, inflammation and oxidative stress in FDR of type 2 diabetics. 相似文献644.
Extraction, thin-layer chromatography and gas chromatography–mass spectrophotometry analyses revealed the presence of 12, 13, and 12 fatty acids in young, mature, and senescent leaves of Momordica charantia L., representing 87.30, 95.25, and 83.11 % of the total fatty acids, respectively. The proportion of saturated fatty acids was highest in senescent leaves (78.60 %) followed by young leaves (69.42 %) and mature leaves (48.92 %), with the balance accounted for by unsaturated fatty acids. Palmitic acid was the predominant saturated fatty acid in the three types of leaves, whereas alpha-linolenic acid was the predominant unsaturated fatty acid. The fatty acids from young, mature, and senescent leaves followed by the application of a synthetic mixture of fatty acids that was comparable to the natural fatty acids found in the three types of leaves, elicited the attraction of the female insect Epilachna dodecastigma (Coleoptera: Coccinellidae) at 50–200, 50–200, and 100–200 μg/ml concentrations, respectively, in a Y-shaped glass tube olfactometer bioassay. Individual synthetic fatty acids were also evaluated by the olfactometer bioassay at concentrations comparable to the proportions detected in the three types of leaves. Individual synthetic palmitic acid, stearic acid, oleic acid, linoleic acid, and alpha-linolenic acid at 58.24, 13.96, 29.40, 30.31, and 29.76 μg, respectively, attracted the insect. A synthetic blend of 79.13, 10.57, 29.40, 30.31, and 36.33 μg of palmitic, stearic, oleic, linoleic, and alpha-linolenic acids, respectively, which is the proportion present in a 200 μg/ml concentration of fatty acids of mature leaves, or of 116.49, 13.96, and 29.76 μg of palmitic, stearic and alpha-linolenic acids, respectively, which is the proportion present in a 200 μg/ml concentration of natural fatty acids of young leaves, served as attractants for E. dodecastigma. 相似文献
645.
646.
647.
648.
Abhishek Abhishek Sally Doherty Rose Maciewicz Kenneth Muir Weiya Zhang Michael Doherty Anna M Valdes 《Arthritis research & therapy》2014,16(1):R25
Introduction
Chondrocalcinosis (CC) most commonly results from calcium pyrophosphate crystal deposition (CPPD). The objective of this study is to examine the association between candidate single-nucleotide polymorphisms (SNPs) and radiographic CC.Methods
SNPs in ankylosis human (ANKH), high ferritin (HFE), tissue non-specific alkaline phosphatase (TNAP), ecto-neucleotide pyrophosphatase 1 (ENPP1), and transferrin (TE) genes were genotyped in participants of the Genetics of Osteoarthritis and Lifestyle (GOAL) and Nottingham Osteoarthritis Case-Control studies. Adjusted genotype odds ratio (aORGENOTYPE), the OR for association between one additional minor allele and CC, was calculated and adjusted for age, gender, body mass index (BMI), and osteoarthritis (OA) by using binary logistic regression. Statistical significance was set at P ≤0.003 after Bonferroni correction for multiple tests.Results
The -4bpG > A polymorphism in the 5′ untranslated region (5′ UTR) of ANKH associated with CC after Bonferroni correction. This was independent of age, gender, OA, and BMI; aORGENOTYPE (95% confidence interval, or CI) was 1.39 (1.14-1.69) (P = 0.001). rs3045 and rs875525, two other SNPs in ANKH, associated with CC; aORGENOTYPE (95% CI) values were 1.31 (1.09-1.58) (P = 0.005) and 1.18 (1.03-1.35) (P = 0.015), respectively; however, this was non-significant after Bonferroni correction.Conclusions
This study validates the association between a functional polymorphism in the 5′ UTR of ANKH and CC and shows for the first time that this is independent of age and OA – the two key risk factors for CC. It shows that other SNPs in ANKH may also associate with CC. This supports the role of extracellular inorganic pyrophosphate in the pathogenesis of CC. The findings of this hospital-based study require replication in a community-based population. 相似文献649.
650.
Medhavi Sudarshan Toolika Singh Abhishek Kumar Singh Ankita Chourasia Bhawana Singh Mary E. Wilson Jaya Chakravarty Shyam Sundar 《PLoS neglected tropical diseases》2014,8(12)