390 research outputs found
Comparison of different pain scoring systems in critically ill patients in a general ICU
Background: Pain in critically ill patients in the intensive care unit (ICU) is common. However, pain assessment in critically ill patients often is complicated because these patients are unable to communicate effectively. Therefore, we designed a study (a) to determine the inter-rater reliability of the Numerical Rating Scale (NRS) and the Behavioral Pain Scale (BPS), (b) to compare pain scores of different observers and the patient, and (c) to compare NRS, BPS, and the Visual Analog Scale (VAS) for measuring pain in patients in the ICU. Methods: We performed a prospective observational study in 113 non-paralyzed critically ill patients. The attending nurses, two researchers, and the patient (when possible) obtained 371 independent observation series of NRS, BPS, and VAS. Data analyses were performed on the sample size of patients (n = 113). Results: Inter-rater reliability of the NRS and BPS proved to be adequate (kappa = 0.71 and 0.67, respectively). The level of agreement within one scale point between NRS rated by the patient and NRS scored by attending nurses was 73%. However, high patient scores (NRS ≥4) were underestimated by nurses (patients 33% versus nurses 18%). In responsive patients, a high correlation between NRS and VAS was found (rs= 0.84, P < 0.001). In ventilated patients, a moderate positive correlation was found between the NRS and the BPS (rs= 0.55, P < 0.001). However, whereas 6% of the observations were NRS of greater than or equal to 4, BPS scores were all very low (median 3.0, range 3.0 to 5.0). Conclusion: The different scales show a high reliability, but observer-based evaluation often underestimates the pain, particularly in the case of high NRS values (≥4) rated by the patient. Therefore, whenever this is possible, ICU patients should rate their pain. In unresponsive patients, primarily the attending nurse involved in daily care should score the patient's pain. In ventilated patients, the BPS should be used only in conjunction with the NRS nurse to measure pain levels in the absence of painful stimuli
Sentinel node procedure of the sigmoid using indocyanine green: feasibility study in a goat model
Detecting microRNA binding and siRNA off-target effects from expression data.
Sylamer is a method for detecting microRNA target and small interfering RNA off-target signals in 3' untranslated regions from a ranked gene list, sorted from upregulated to downregulated, after a microRNA perturbation or RNA interference experiment. The output is a landscape plot that tracks occurrence biases using hypergeometric P-values for all words across the gene ranking. We demonstrated the utility, speed and accuracy of this approach on several datasets
Lack of correlation between predicted and actual off-target effects of short-interfering RNAs targeting the human papillomavirus type 16 E7 oncogene.
BACKGROUND: When designing therapeutic short-interfering RNAs (siRNAs), off-target effects (OTEs) are usually predicted by computational quantification of messenger RNAs (mRNAs) that contain matches to the siRNA seed sequence in their 3' UTRs. It is assumed that the higher the number of predicted transcriptional OTEs, the greater the size of the actual OTE signature and the more detrimental the phenotypic consequences in target-negative cells. METHODS: We tested this general assumption by investigating the OTEs of potential therapeutic siRNAs targeting the human papillomavirus (HPV) type-16 E7 oncogene. We studied HPV-negative squamous epithelial cells, from normal cervix (NCx) and skin (HaCaT), which would be vulnerable to 'bystander' OTEs following transfection in vivo. RESULTS: We observed no correlation between the number of computationally predicted OTEs and the actual number of seed-dependent OTEs (P=0.76). On average only 20.5% of actual transcriptional OTEs were seed-dependent (i.e., predicted). The unpredicted OTEs included stimulation of innate immune pathways, as well as indirect (downstream) effects of other OTEs, which affected important cancer-associated pathways. Although most significant OTEs observed were seen in both NCx and HaCaT cells, only 0-5.9% of differentially expressed genes overlapped between the two cell types. CONCLUSION: These data do not support the assumption that actual OTEs correlate well with predicted OTEs
Parental Reports of Infant and Child Eating Behaviors are not Affected by Their Beliefs About Their Twins’ Zygosity
Parental perception of zygosity might bias heritability estimates derived from parent rated twin data. This is the first study to examine if similarities in parental reports of their young twins’ behavior were biased by beliefs about their zygosity. Data were from Gemini, a British birth cohort of 2402 twins born in 2007. Zygosity was assessed twice, using both DNA and a validated parent report questionnaire at 8 (SD = 2.1) and 29 months (SD = 3.3). 220/731 (8 months) and 119/453 (29 months) monozygotic (MZ) pairs were misclassified as dizygotic (DZ) by parents; whereas only 6/797 (8 months) and 2/445 (29 months) DZ pairs were misclassified as MZ. Intraclass correlations for parent reported eating behaviors (four measured at 8 months; five at 16 months) were of the same magnitude for correctly classified and misclassified MZ pairs, suggesting that parental zygosity perception does not influence reporting on eating behaviors of their young twins
SCPS: a fast implementation of a spectral method for detecting protein families on a genome-wide scale
<p>Abstract</p> <p>Background</p> <p>An important problem in genomics is the automatic inference of groups of homologous proteins from pairwise sequence similarities. Several approaches have been proposed for this task which are "local" in the sense that they assign a protein to a cluster based only on the distances between that protein and the other proteins in the set. It was shown recently that global methods such as spectral clustering have better performance on a wide variety of datasets. However, currently available implementations of spectral clustering methods mostly consist of a few loosely coupled Matlab scripts that assume a fair amount of familiarity with Matlab programming and hence they are inaccessible for large parts of the research community.</p> <p>Results</p> <p>SCPS (Spectral Clustering of Protein Sequences) is an efficient and user-friendly implementation of a spectral method for inferring protein families. The method uses only pairwise sequence similarities, and is therefore practical when only sequence information is available. SCPS was tested on difficult sets of proteins whose relationships were extracted from the SCOP database, and its results were extensively compared with those obtained using other popular protein clustering algorithms such as TribeMCL, hierarchical clustering and connected component analysis. We show that SCPS is able to identify many of the family/superfamily relationships correctly and that the quality of the obtained clusters as indicated by their F-scores is consistently better than all the other methods we compared it with. We also demonstrate the scalability of SCPS by clustering the entire SCOP database (14,183 sequences) and the complete genome of the yeast <it>Saccharomyces cerevisiae </it>(6,690 sequences).</p> <p>Conclusions</p> <p>Besides the spectral method, SCPS also implements connected component analysis and hierarchical clustering, it integrates TribeMCL, it provides different cluster quality tools, it can extract human-readable protein descriptions using GI numbers from NCBI, it interfaces with external tools such as BLAST and Cytoscape, and it can produce publication-quality graphical representations of the clusters obtained, thus constituting a comprehensive and effective tool for practical research in computational biology. Source code and precompiled executables for Windows, Linux and Mac OS X are freely available at <url>http://www.paccanarolab.org/software/scps</url>.</p
An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.
Progressive hearing loss is common in the human population, but little is known about the molecular basis. We report a new N-ethyl-N-nitrosurea (ENU)-induced mouse mutant, diminuendo, with a single base change in the seed region of Mirn96. Heterozygotes show progressive loss of hearing and hair cell anomalies, whereas homozygotes have no cochlear responses. Most microRNAs are believed to downregulate target genes by binding to specific sites on their mRNAs, so mutation of the seed should lead to target gene upregulation. Microarray analysis revealed 96 transcripts with significantly altered expression in homozygotes; notably, Slc26a5, Ocm, Gfi1, Ptprq and Pitpnm1 were downregulated. Hypergeometric P-value analysis showed that hundreds of genes were upregulated in mutants. Different genes, with target sites complementary to the mutant seed, were downregulated. This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally
clusterMaker: a multi-algorithm clustering plugin for Cytoscape
<p>Abstract</p> <p>Background</p> <p>In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present <it>clusterMaker</it>, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. <it>clusterMaker </it>is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view), k-means, k-medoid, SCPS, AutoSOME, and native (Java) MCL.</p> <p>Results</p> <p>Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast <it>Saccharomyces cerevisiae</it>; and the cluster analysis of the vicinal oxygen chelate (VOC) enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section.</p> <p>Conclusions</p> <p>The Cytoscape plugin <it>clusterMaker </it>provides a number of clustering algorithms and visualizations that can be used independently or in combination for analysis and visualization of biological data sets, and for confirming or generating hypotheses about biological function. Several of these visualizations and algorithms are only available to Cytoscape users through the <it>clusterMaker </it>plugin. <it>clusterMaker </it>is available via the Cytoscape plugin manager.</p
A framework for protein structure classification and identification of novel protein structures
BACKGROUND: Protein structure classification plays a central role in understanding the function of a protein molecule with respect to all known proteins in a structure database. With the rapid increase in the number of new protein structures, the need for automated and accurate methods for protein classification is increasingly important. RESULTS: In this paper we present a unified framework for protein structure classification and identification of novel protein structures. The framework consists of a set of components for comparing, classifying, and clustering protein structures. These components allow us to accurately classify proteins into known folds, to detect new protein folds, and to provide a way of clustering the new folds. In our evaluation with SCOP 1.69, our method correctly classifies 86.0%, 87.7%, and 90.5% of new domains at family, superfamily, and fold levels. Furthermore, for protein domains that belong to new domain families, our method is able to produce clusters that closely correspond to the new families in SCOP 1.69. As a result, our method can also be used to suggest new classification groups that contain novel folds. CONCLUSION: We have developed a method called proCC for automatically classifying and clustering domains. The method is effective in classifying new domains and suggesting new domain families, and it is also very efficient. A web site offering access to proCC is freely available a
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