Entropy-based gene ranking without selection bias for the predictive classification of microarray data

Background

We describe the E-RFE method for gene ranking, which is useful for the identification of markers in the predictive classification of array data. The method supports a practical modeling scheme designed to avoid the construction of classification rules based on the selection of too small gene subsets (an effect known as the selection bias, in which the estimated predictive errors are too optimistic due to testing on samples already considered in the feature selection process).

Results

With E-RFE, we speed up the recursive feature elimination (RFE) with SVM classifiers by eliminating chunks of uninteresting genes using an entropy measure of the SVM weights distribution. An optimal subset of genes is selected according to a two-strata model evaluation procedure: modeling is replicated by an external stratified-partition resampling scheme, and, within each run, an internal K-fold cross-validation is used for E-RFE ranking. Also, the optimal number of genes can be estimated according to the saturation of Zipf's law profiles.

Conclusions

Without a decrease of classification accuracy, E-RFE allows a speed-up factor of 100 with respect to standard RFE, while improving on alternative parametric RFE reduction strategies. Thus, a process for gene selection and error estimation is made practical, ensuring control of the selection bias, and providing additional diagnostic indicators of gene importance.

     

Apolipoprotein A-I(Milano): current perspectives

PURPOSE OF REVIEW: Strategies to increase HDL are among the major targets of clinical research in atherosclerosis prevention. The mutant apolipoprotein A-I(Milano) has been associated with a reduced incidence of coronary disease in carriers. Furthermore, recombinant apolipoprotein A-I(Milano) has displayed remarkable atheroprotective activities and the possibility of directly reducing the burden of atherosclerosis in experimental models. This review is aimed at providing an update on the experimental studies in which apolipoprotein A-I(Milano), produced as a recombinant protein, has displayed important effects in the treatment of vascular diseases. RECENT FINDINGS: In the past year, two reports have appeared, indicating that a single-dose administration of recombinant apolipoprotein A-I(Milano) dimers formulated into liposomes can reduce atheromas in models such as the apolipoprotein E-deficient mice and a rabbit model of carotid focal lesion, in which a direct 90 min infusion of the product reduced atheroma up to 30%. This finding was associated with an increase in HDL free cholesterol and the permanence of the recombinant product in the lesion for over 72 h. SUMMARY: Recombinant apolipoprotein A-I(Milano), formulated as synthetic HDL with phospholipids, appears to exert a direct removing effect on arterial cholesterol. This is well evident in experimental animals and, more recently in clinical findings, as indicated by a dramatic increase in HDL free cholesterol after the infusion of different doses of the agent. As the product appears to be well tolerated and non-immunogenic, ongoing phase II studies in patients are being awaited with interest to obtain a 'proof of principle' for 'HDL therapy'.     

The satisfaction with the removable partial denture therapy in the Croatian adult population

Little is known about the outcomes of treatment and patient's satisfaction with removable partial dentures in adult Croatian population. Therefore patient's satisfaction with their partial dentures in relation to some socio-economic variables was studied. Patient's satisfaction with denture retention, speech, aesthetics, comfort of wearing dentures, chewing ability was also studied in relation to different denture classification, construction, material, denture base shape (major connectors), denture support and the number of missing teeth. A total of 165 patients, 59 males and 105 females between 38 and 87 years took part in this study. A questionnaire, devised for a purpose of the study, was divided into three parts. In the first part, patients answered questions about age, gender, marital status, education, general health, socio-economic status, self-supporting life, period of tooth loss and number of previous denture experiences and in the second part, patients graded their partial dentures, depending on the level of satisfaction, by using a scale from 1 to 5. In the third part a dentist determined Kennedy classification and their modifications, denture material and denture support, denture base shape and the number of missing teeth and graded a denture construction. Influence of these factors on patient's satisfaction was analyzed. A majority of the examined patients were satisfied with the partial prosthesis, but a small amount of dissatisfaction existed. More then half of them scored all the examined parameters to the best score category. Considering chewing with lower partial dentures, women were more satisfied than men (p < 0.05). Patients with more missing teeth gave lower grades for the comfort of wearing dentures (p < 0.05). Patients of higher education gave lower grades (p < 0.05) for the aesthetics. Patients were not satisfied with speech if the dentist graded a construction of a lower partial denture low (p < 0.05). Dissatisfaction was related to mastication, aesthetics, number of missing teeth and ability of speech. These findings can aid a clinician in discussing a treatment plan and help a patient understand the risk of dissatisfaction in the presence of certain factors.     

Biochemical, electrophoretic and immunohistochemical aspects of malate dehydrogenase in truffles (Ascomycotina)

The malate dehydrogenase (MDH; EC 1.1.1.37; L-malate-NAD(+)-oxidoreductase) activities of truffles of the genus Tuber (Tuber melanosporum Vittad., Tuber brumale Vittad., Tuber aestivum Vittad., Tuber magnatum Pico, Tuber rufum Pico) have been characterized with regard to the K(m) and V(max) values in the direct and reverse reactions. The isoelectrofocusing has revealed bands showing pI values ranging from pH 5.85 to 7.8. The MDH of T. melanosporum has been partially purified by hydroxyapatite treatment, DEAE-cellulose and Sephadex G-75 columns. With the partially purified T. melanosporum MDH activity polyclonal anti-T. melanosporum MDH antibodies have been prepared and used to localize MDH in the mycorrhizae and ascocarps of T. melanosporum. These antibodies inhibit T. melanosporum MDH activity as well as that of T. magnatum but not that of rabbit liver; this supports the specificity of the MDH antibodies used to localize MDH in truffle tissues.     

Effects of vitamin E and prostaglandin E2 on expression of CREB1 and CREB2 proteins by human T lymphocytes

Both prostaglandins (PGs) and vitamin E are known to deeply affect immune responses. It is shown here that they both influence T cell-mediated immunity through reciprocal interference on the expression of cyclic-AMP responsive element binding (CREB) family proteins. CREB1 protein of human T lymphocytes was significantly modulated by a brief treatment of 5 to 10 min with PGE2. On the contrary, vitamin E appeared to be ineffective on the CREB1 behavior, while it abolished the PGE2-induced modulation of this protein. The CREB2 protein expression was also affected by PGE2 treatment, but a longer period of incubation (>20 min) was needed to observe these changes. Vitamin E showed a strong enhancing effect on CREB2 that was partially reversed by the subsequent treatment with PGE2. Our results support the idea that there is reciprocal interference between PGE2 and vitamin E on PGE2-induced signals in T lymphocytes. These data are in agreement with the reports concerning different cell systems and experimental conditions.     

Mitochondrial Membrane Potential and DNA Stainability in Human Sperm Cells: A Flow Cytometry Analysis with Implications for Male Infertility

Sperm cells from control donors of proven fertility and men from barren couples were studied by conventional procedures, i.e., light microscopy as well as flow cytometry. Light microscopy analysis of semen included the measurement of spermatozoa concentration, morphology, and motility. All the men from barren couples were asthenozoospermic at the conventional analysis of semen samples. Flow cytometry was applied to study two important parameters of sperm cells: mitochondrial membrane potential (MMP) assessed by the cationic dye JC-1 and DNA stainability with propidium iodide (PI). JC-1 staining was more reliable than the classical procedure used for this purpose, i.e., rhodamine 123 (Rh123) staining, and allowed us to show a positive correlation between MMP and spermatozoa motility. Regarding DNA analysis, a higher relative percentage of immature spermatozoa, showing a high accessibility of DNA to the intercalating PI fluorochrome, was found in men from barren couples compared to donors of proven fertility. The relative percentage of immature spermatozoa was significantly higher in semen from oligoasthenozoospermic subjects. Moreover, a positive correlation was found between immature spermatozoa, as evaluated by PI staining, and cells with depolarized mitochondria, as evaluated by JC-1 staining, suggesting that spermatozoa defective for nuclear maturity could be functionally defective cells. No correlation between immature spermatozoa determined by FCM and immature spermatozoa determined by light microscopy was found, suggesting that these two techniques assess sperm cell maturity at different levels.     

Improved Estimation of Cardiac Function Parameters Using a Combination of Independent Automated Segmentation Results in Cardiovascular Magnetic Resonance Imaging

This work aimed at combining different segmentation approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by estimating six cardiac function parameters resulting from the left ventricle contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations and five automated methods, were considered, and sixteen combinations of the automated methods using STAPLE were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates than individual automated segmentation methods. Overall, combining different automated segmentation methods improved the reliability of the segmentation result compared to that obtained using an individual method and could achieve the accuracy of an expert.     

Treatment of Solitary Painful Osseous Metastases with Radiotherapy,Cryoablation or Combined Therapy: Propensity Matching Analysis in 175 Patients

Purpose

aim of this study was to identify outcomes in pain relief and quality of life in patients with a solitary painful osseous metastasis treated by radiotherapy, cryoablation or the combination using a propensity score matching study design.

Materials and Methods

175 patients with painful bone metastases were included in the study. Twenty-five of them underwent a radiation course (20 Gy in five daily fractions) 15 days after the cryoablation. These subjects were retrospectively matched by propensity analysis with a group of subjects treated by radiotherapy (125 subjects) and with a group treated byCryoablation (25 subjects). The pain relief in terms of complete response, rate of subjects requiring analgesics after treatments and the changes in self-rated quality of life were measured. Informed consent was obtained from the subject and the study was approved by the local Ethical Committee.

Results

An higher proportion of subjects treated by cryoablation (32%) or cryoablation followed by RT (72%;) experienced a complete response compared with patients treated by radiotherapy alone (11.2%). After Bonferroni correction strategy, the addition of radiotherapy to cryoablation significantly improved the rate of complete response compared with cryoablation alone (p = 0.011) and this paralleled with an improved self-rated quality of life. Seventeen subjects (13.6%) of patients in the radiotherapy group, 9 (36%) in the cryoablation group, and 19 (76)% in the cryoablation- radiotherapy group did not require narcotic medications.

Conclusions

The addition of radiotherapy to cryoablation favorably impacts on perceived pain, with a favorable toxicity profile. However, our data should be interpreted with caution and could serve as a framework around which to design future trials.