bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bias in error estimation when using cross-validation for model selection
Authors: Varma Sudhir , Simon Richard 
Published: February 2006

Abstract

Background
Cross-validation (CV) is an effective method for estimating the prediction error of a classifier. Some recent articles have proposed methods for optimizing classifiers by choosing classifier parameter values that minimize the CV error estimate. We have evaluated the validity of using the CV error estimate of the optimized classifier as an estimate of the true error expected on independent data.

Results
We used CV to optimize the classification parameters for two kinds of classifiers; Shrunken Centroids and Support Vector Machines (SVM). Random training datasets were created, with no difference in the distribution of the features between the two classes. Using these "null" datasets, we selected classifier parameter values that minimized the CV error estimate. 10-fold CV was used for Shrunken Centroids while Leave-One-Out-CV (LOOCV) was used for the SVM. Independent test data was created to estimate the true error. With "null" and "non null" (with differential expression between the classes) data, we also tested a nested CV procedure, where an inner CV loop is used to perform the tuning of the parameters while an outer CV is used to compute an estimate of the error.
The CV error estimate for the classifier with the optimal parameters was found to be a substantially biased estimate of the true error that the classifier would incur on independent data. Even though there is no real difference between the two classes for the "null" datasets, the CV error estimate for the Shrunken Centroid with the optimal parameters was less than 30% on 18.5% of simulated training data-sets. For SVM with optimal parameters the estimated error rate was less than 30% on 38% of "null" data-sets. Performance of the optimized classifiers on the independent test set was no better than chance.
The nested CV procedure reduces the bias considerably and gives an estimate of the error that is very close to that obtained on the independent testing set for both Shrunken Centroids and SVM classifiers for "null" and "non-null" data distributions.

Conclusion
We show that using CV to compute an error estimate for a classifier that has itself been tuned using CV gives a significantly biased estimate of the true error. Proper use of CV for estimating true error of a classifier developed using a well defined algorithm requires that all steps of the algorithm, including classifier parameter tuning, be repeated in each CV loop. A nested CV procedure provides an almost unbiased estimate of the true error.
Multiscale Hy3S: Hybrid stochastic simulation for supercomputers
Authors: Salis Howard , Sotiropoulos Vassilios , Kaznessis Yiannis N 
Published: February 2006

Abstract

Background
Stochastic simulation has become a useful tool to both study natural biological systems and design new synthetic ones. By capturing the intrinsic molecular fluctuations of "small" systems, these simulations produce a more accurate picture of single cell dynamics, including interesting phenomena missed by deterministic methods, such as noise-induced oscillations and transitions between stable states. However, the computational cost of the original stochastic simulation algorithm can be high, motivating the use of hybrid stochastic methods. Hybrid stochastic methods partition the system into multiple subsets and describe each subset as a different representation, such as a jump Markov, Poisson, continuous Markov, or deterministic process. By applying valid approximations and self-consistently merging disparate descriptions, a method can be considerably faster, while retaining accuracy. In this paper, we describe Hy3S, a collection of multiscale simulation programs.

Results
Building on our previous work on developing novel hybrid stochastic algorithms, we have created the Hy3S software package to enable scientists and engineers to both study and design extremely large well-mixed biological systems with many thousands of reactions and chemical species. We have added adaptive stochastic numerical integrators to permit the robust simulation of dynamically stiff biological systems. In addition, Hy3S has many useful features, including embarrassingly parallelized simulations with MPI; special discrete events, such as transcriptional and translation elongation and cell division; mid-simulation perturbations in both the number of molecules of species and reaction kinetic parameters; combinatorial variation of both initial conditions and kinetic parameters to enable sensitivity analysis; use of NetCDF optimized binary format to quickly read and write large datasets; and a simple graphical user interface, written in Matlab, to help users create biological systems and analyze data. We demonstrate the accuracy and efficiency of Hy3S with examples, including a large-scale system benchmark and a complex bistable biochemical network with positive feedback. The software itself is open-sourced under the GPL license and is modular, allowing users to modify it for their own purposes.

Conclusion
Hy3S is a powerful suite of simulation programs for simulating the stochastic dynamics of networks of biochemical reactions. Its first public version enables computational biologists to more efficiently investigate the dynamics of realistic biological systems.
Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes
Authors: Morris Gerard AJ , Lowe Christopher E , Cooper Jason D , Payne Felicity , Vella Adrian , Godfrey Lisa , Hulme John S , Walker Neil M , Healy Barry C , Lam Alex C , Lyons Paul A , Todd John A 
Published: February 2006

Abstract

Background
The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1).

Results
We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families.

Conclusion
We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.
Molecular targets for rapid identification of Brucella spp
Authors: Ratushna Vladyslava G , Sturgill David M , Ramamoorthy Sheela , Reichow Sherry A , He Yongqun , Lathigra Raju , Sriranganathan Nammalwar , Halling Shirley M , Boyle Stephen M , Gibas Cynthia J 
Published: February 2006

Abstract

Background

Brucella is an intracellular pathogen capable of infecting animals and humans. There are six recognized species of Brucella that differ in their host preference. The genomes of the three Brucella species have been recently sequenced. Comparison of the three revealed over 98% sequence similarity at the protein level and enabled computational identification of common and differentiating genes. We validated these computational predictions and examined the expression patterns of the putative unique and differentiating genes, using genomic and reverse transcription PCR. We then screened a set of differentiating genes against classical Brucella biovars and showed the applicability of these regions in the design of diagnostic tests.

Results
We have identified and tested set of molecular targets that are associated in unique patterns with each of the sequenced Brucella spp. A comprehensive comparison was made among the published genome sequences of B. abortus, B. melitensis and B. suis. The comparison confirmed published differences between the three Brucella genomes, and identified subsets of features that were predicted to be of interest in a functional comparison of B. melitensis and B. suis to B. abortus. Differentiating sequence regions from B. abortus, B. melitensis and B. suis were used to develop PCR primers to test for the existence and in vitro transcription of these genes in these species. Only B. suis is found to have a significant number of unique genes, but combinations of genes and regions that exist in only two out of three genomes and are therefore useful for diagnostics were identified and confirmed.

Conclusion
Although not all of the differentiating genes identified were transcribed under steady state conditions, a group of genes sufficient to discriminate unambiguously between B. suis, B. melitensis, and B. abortus was identified. We present an overview of these genomic differences and the use of these features to discriminate among a number of Brucella biovars.
Expression of hemagglutinin protein from the avian influenza virus H5N1 in a baculovirus/insect cell system significantly enhanced by suspension culture
Authors: Nwe Nitar , He Qigai , Damrongwatanapokin Sudarat , Du Qingyun , Manopo Ivanus , Limlamthong Yukol , Fenner Beau James , Spencer Lynn , Kwang Jimmy 
Published: February 2006

Abstract

Background
Prevention of a possible avian influenza pandemic necessitates the development of rapid diagnostic tests and the eventual production of a vaccine.

Results
For vaccine production, hemagglutinin (HA1) from avian influenza H5N1 was expressed from a recombinant baculovirus. Recombinant HA1 was expressed in monolayer or suspension culture insect cells by infection with the recombinant baculovirus. The yield of rHA1 from the suspension culture was 68 mg/l, compared to 6 mg/l from the monolayer culture. Immunization of guinea pigs with 50 μg of rHA1 yielded hemagglutinin inhibition and virus neutralization titers of 1:160 after two times vaccination with rHA1 protein.

Conclusion
Thus, the production of rHA1 using an insect suspension cell system provides a promising basis for economical production of a H5 antigen.
Use of flow cytometry for the adhesion analysis of Streptococcus pyogenes mutant strains to epithelial cells: investigation of the possible role of surface pullulanase and cysteine protease, and the transcriptional regulator Rgg
Authors: Hytönen Jukka , Haataja Sauli , Finne Jukka 
Published: February 2006

Abstract

Background
Flow cytometry based adherence assay is a potentially powerful but little used method in the study of bacterial binding to host structures. We have previously characterized a glycoprotein-binding activity in Streptococcus pyogenes called 'strepadhesin' binding to thyroglobulin, submaxillar mucin, fetuin and asialofetuin. We have identified surface-associated pullulanase (PulA) and cysteine protease (SpeB) as carriers of strepadhesin activity. In the present paper, we investigated the use of flow cytometry as a method to study the binding of Rgg, SpeB and PulA knock-out strains to cultured human epithelial cells.

Results
Streptococcal mutants were readily labelled with CFDA-SE and their binding to epithelial cells could be effectively studied by flow cytometry. A strain deficient in Rgg expression showed increased binding to the analyzed epithelial cell lines of various origin. Inactivation of SpeB had no effect on the adhesion, while PulA knock-out strains displayed decreased binding to the cell lines.

Conclusion
These results suggest that the flow cytometric assay is a valuable tool in the analysis of S. pyogenes adherence to host cells. It appears to be an efficient and sensitive tool for the characterization of interactions between the bacteria and the host at the molecular level. The results also suggest a role for Rgg regulated surface molecules, like PulA, in the adhesion of S. pyogenes to host cells.
Can electronic search engines optimize screening of search results in systematic reviews: an empirical study
Authors: Sampson Margaret , Barrowman Nicholas J , Moher David , Clifford Tammy J , Platt Robert W , Morrison Andra , Klassen Terry P , Zhang Li 
Published: February 2006

Abstract

Background
Most electronic search efforts directed at identifying primary studies for inclusion in systematic reviews rely on the optimal Boolean search features of search interfaces such as DIALOG® and Ovid™. Our objective is to test the ability of an Ultraseek® search engine to rank MEDLINE® records of the included studies of Cochrane reviews within the top half of all the records retrieved by the Boolean MEDLINE search used by the reviewers.

Methods
Collections were created using the MEDLINE bibliographic records of included and excluded studies listed in the review and all records retrieved by the MEDLINE search. Records were converted to individual HTML files. Collections of records were indexed and searched through a statistical search engine, Ultraseek, using review-specific search terms. Our data sources, systematic reviews published in the Cochrane library, were included if they reported using at least one phase of the Cochrane Highly Sensitive Search Strategy (HSSS), provided citations for both included and excluded studies and conducted a meta-analysis using a binary outcome measure. Reviews were selected if they yielded between 1000–6000 records when the MEDLINE search strategy was replicated.

Results
Nine Cochrane reviews were included. Included studies within the Cochrane reviews were found within the first 500 retrieved studies more often than would be expected by chance. Across all reviews, recall of included studies into the top 500 was 0.70. There was no statistically significant difference in ranking when comparing included studies with just the subset of excluded studies listed as excluded in the published review.

Conclusion
The relevance ranking provided by the search engine was better than expected by chance and shows promise for the preliminary evaluation of large results from Boolean searches. A statistical search engine does not appear to be able to make fine discriminations concerning the relevance of bibliographic records that have been pre-screened by systematic reviewers.
Q fever endocarditis masquerading as Mixed cryoglobulinemia type II. A case report and review of the literature
Authors: Rafailidis Petros I , Dourakis Spiros P , Fourlas Christos A 
Published: February 2006

Abstract

Background
The clinical manifestations of Q fever endocarditis are protean in nature. Mixed cryoglobulinemia type II is rarely a facet of the presenting clinical manifestations of Q fever endocarditis.

Case presentation
We report a case of a 65-year-old pensioner with such an association and review the literature. As transesophageal echocardiograms are usually normal and blood cultures are usually negative in Q fever endocarditis, many of the manifestations (fever, rash, glomerulonephritis/evidence of renal disease, low serum C4 complement component, presence of mixed type II cryoglobulin, constitutional symptoms as arthralgias and fatigue) can be attributed to Mixed cryoglobulinemia type II per se. The use of Classic Duke Endocarditis Service criteria does not always suffice for the diagnosis of Q fever.

Conclusion
The application of the modified criteria proposed by Fournier et al for the improvement of the diagnosis of Q fever endocarditis will help to reach the diagnosis earlier and thus reduce the high mortality of the disease. We would like to stress the importance of ruling out the diagnosis of Q fever endocarditis in cases of mixed type II cryoglobulinemia.
Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma
Authors: Snoussi Kaouther , Strosberg A Donny , Bouaouina Noureddine , Ahmed Slim Ben , Helal A Noureddine , Chouchane Lotfi 
Published: February 2006

Abstract

Background
Leptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in
LEP
and
LEPR
have implications for susceptibility to and prognosis in breast carcinoma.

Methods
We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the
LEP
and
LEPR
genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses.

Results
A significantly increased risk of breast carcinoma was associated with heterozygous
LEP (-2548) GA
(OR = 1.45; P = 0.04) and homozygous
LEP (-2548) AA
(OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous
LEPR 223QR
genotype (OR = 1.68; P = 0.007) or homozygous
LEPR 223RR
genotype (OR = 2.26; P = 0.001) and breast carcinoma.
Moreover, the presence of the
LEP (-2548) A
allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the
LEPR 223R
allele showed a significant association with decreased overall survival.

Conclusion
Our results indicated that the polymorphisms in
LEP
and
LEPR
genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis.
A reference frame for blood volume in children and adolescents
Authors: Raes Ann , Van Aken Sarah , Craen Margarita , Donckerwolcke Raymond , Walle Johan Vande 
Published: February 2006

Abstract

Background
Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter.

Methods
Plasma volume (PV) and red cell volume (RCV) were measured and F-cell ratio was calculated in 77 children with idiopathic nephrotic syndrome in drug-free remission (mean age, 9.8 ± 4.6 y). BV was calculated as the sum of PV and RCV. Due to the dependence of these values on age, size and sex, all data were normalised for body size parameters.

Results
BV normalised for lean body mass (LBM) did not differ significantly by sex (p < 0.376) or pubertal stage (p < 0.180), in contrast to normalisation for the other anthropometric parameters. There was no significant difference between reference values for children and adults.

Conclusion
LBM was the anthropometric index most closely correlated to vascular fluid volumes, independent of age, gender and pubertal stage.
Screening for antimicrobial activity of ten medicinal plants used in Colombian folkloric medicine: A possible alternative in the treatment of non-nosocomial infections
Authors: Rojas Jhon J , Ochoa Veronica J , Ocampo Saul A , Muñoz John F 
Published: February 2006

Abstract

Background
The antimicrobial activity and Minimal Inhibitory Concentration (MIC) of the extracts of Bidens pilosa L., Bixa orellana L., Cecropia peltata L., Cinchona officinalis L., Gliricidia sepium H.B. & K, Jacaranda mimosifolia D.Don, Justicia secunda Vahl., Piper pulchrum C.DC, P. paniculata L. and Spilanthes americana Hieron were evaluated against five bacteria (Staphylococcus aureus, Streptococcus β hemolític, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli), and one yeast (Candida albicans). These plants are used in Colombian folk medicine to treat infections of microbial origin.

Methods
Plants were collected by farmers and traditional healers. The ethanol, hexane and water extracts were obtained by standard methods. The antimicrobial activity was found by using a modified agar well diffusion method. All microorganisms were obtained from the American Type Culture Collection (ATCC). MIC was determined in the plant extracts that showed some efficacy against the tested microorganisms. Gentamycin sulfate (1.0 μg/ml), clindamycin (0.3 μg/ml) and nystatin (1.0 μg/ml) were used as positive controls.

Results
The water extracts of Bidens pilosa L., Jacaranda mimosifolia D.Don, and Piper pulchrum C.DC showed a higher activity against Bacillus cereus and Escherichia coli than gentamycin sulfate. Similarly, the ethanol extracts of all species were active against Staphylococcus aureus except for Justicia secunda. Furthermore, Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC presented the lowest MICs against Escherichia coli (0.8, 0.6 and 0.6 μg/ml, respectively) compared to gentamycin sulfate (0.9 8g/ml). Likewise, Justicia secunda and Piper pulchrum C.DC showed an analogous MIC against Candida albicans (0.5 and 0.6 μg/ml, respectively) compared to nystatin (0.6 μg/ml). Bixa orellana L, exhibited a better MIC against Bacillus cereus (0.2 μg/ml) than gentamycin sulfate (0.5 μg/ml).

Conclusion
This in vitro study corroborated the antimicrobial activity of the selected plants used in folkloric medicine. All these plants were effective against three or more of the pathogenic microorganisms. However, they were ineffective against Streptococcus β hemolytic and Pseudomonas aeruginosa. Their medicinal use in infections associated with these two species is not recommended. This study also showed that Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC could be potential sources of new antimicrobial agents.
Selection of optimal recording sites for limited lead body surface potential mapping: A sequential selection based approach
Authors: Finlay Dewar D , Nugent Chris D , Donnelly Mark P , Lux Robert L , McCullagh Paul J , Black Norman D 
Published: February 2006

Abstract

Background
In this study we propose the development of a new algorithm for selecting optimal recording sites for limited lead body surface potential mapping. The proposed algorithm differs from previously reported methods in that it is based upon a simple and intuitive data driven technique that does not make any presumptions about deterministic characteristics of the data. It uses a forward selection based search technique to find the best combination of electrocardiographic leads.

Methods
The study was conducted using a dataset consisting of body surface potential maps (BSPM) recorded from 116 subjects which included 59 normals and 57 subjects exhibiting evidence of old Myocardial Infarction (MI). The performance of the algorithm was evaluated using spatial RMS voltage error and correlation coefficient to compare original and reconstructed map frames.

Results
In all, three configurations of the algorithm were evaluated and it was concluded that there was little difference in the performance of the various configurations. In addition to observing the performance of the selection algorithm, several lead subsets of 32 electrodes as chosen by the various configurations of the algorithm were evaluated. The rationale for choosing this number of recording sites was to allow comparison with a previous study that used a different algorithm, where 32 leads were deemed to provide an acceptable level of reconstruction performance.

Conclusion
It was observed that although the lead configurations suggested in this study were not identical to that suggested in the previous work, the systems did bear similar characteristics in that recording sites were chosen with greatest density in the precordial region.