ROBOUT: a conditional outlier detection methodology for high-dimensional data

This paper presents a methodology, called ROBOUT, to identify outliers conditional on a high-dimensional noisy information set. In particular, ROBOUT is able to identify observations with outlying conditional mean or variance when the dataset contains multivariate outliers in or besides the predictors, multi-collinearity, and a large variable dimension compared to the sample size. ROBOUT entails a pre-processing step, a preliminary robust imputation procedure that prevents anomalous instances from corrupting predictor recovery, a selection stage of the statistically relevant predictors (through cross-validated LASSO-penalized Huber loss regression), the estimation of a robust regression model based on the selected predictors (via MM regression), and a criterion to identify conditional outliers. We conduct a comprehensive simulation study in which the proposed algorithm is tested under a wide range of perturbation scenarios. The combination formed by LASSO-penalized Huber loss and MM regression turns out to be the best in terms of conditional outlier detection under the above described perturbed conditions, also compared to existing integrated methodologies like Sparse Least Trimmed Squares and Robust Least Angle Regression. Furthermore, the proposed methodology is applied to a granular supervisory banking dataset collected by the European Central Bank, in order to model the total assets of euro area banks

Wilms’ Tumor in a 37-Year-Old

Wilms’ tumor is rare in adults. Though the approach to diagnosis and treatment of adult Wilms’ tumor (AWT) is closely modeled on recommendations for childhood Wilms’ tumor, views differ on how aggressive the treatment should be. We report a case of a 37-year-old with Stage III favorable histology AWT. A radical nephrectomy was performed and the patient was due for chemotherapy. Recent advances, controversies and current recommendations in the treatment of AWT are discussed

Repurposing existing drugs for the treatment of COVID-19

The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by SARS-CoV-2 viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist, thus development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and anti-inflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date only dexamethasone and remedesivir have been shown to be effective, but several other promising candidates are in trials

ArrayExpress—a public database of microarray experiments and gene expression profiles

ArrayExpress is a public database for high throughput functional genomics data. ArrayExpress consists of two parts—the ArrayExpress Repository, which is a MIAME supportive public archive of microarray data, and the ArrayExpress Data Warehouse, which is a database of gene expression profiles selected from the repository and consistently re-annotated. Archived experiments can be queried by experiment attributes, such as keywords, species, array platform, authors, journals or accession numbers. Gene expression profiles can be queried by gene names and properties, such as Gene Ontology terms and gene expression profiles can be visualized. ArrayExpress is a rapidly growing database, currently it contains data from >50 000 hybridizations and >1 500 000 individual expression profiles. ArrayExpress supports community standards, including MIAME, MAGE-ML and more recently the proposal for a spreadsheet based data exchange format: MAGE-TAB. Availability:

Stressful life events are associated with low secretion rates of immunoglobulin A in saliva in the middle aged and elderly

Whether chronic stress experience is related to down-regulation of secretory immunoglobulin A (S-IgA) was tested in two substantial cohorts, one middle-aged (N = 640) and one elderly (N = 582), comprising similar numbers of men (N = 556) and women (N = 666) and manual (N = 606) and non-manual (N = 602) workers. Participants indicated from a list of major stressful life events up to six they had experienced in the previous two years. They also rated how disruptive and stressful the events were, at the time and now, as well as their perceived seriousness; the products of these impact values and event frequency were adopted as measures of stress load. From unstimulated 2-minute saliva samples, saliva volume and S-IgA concentration were measured, and S-IgA secretion rate determined as their product. There was a negative association between the stress load measures and S-IgA secretion rate, still evident following adjustment for such variables as smoking and saliva volume. The associations also withstood adjustment for sex, cohort, and household occupational status. Although these associations are small in terms of the amount of variance explained, they nonetheless suggest that chronic stress experience either decreases IgA production by the local plasma cells or reduces the efficiency with which S-IgA is transported from the glandular interstitium into saliva. Given the importance of S-IgA in immune defence at mucosal surfaces and the frequency with which infections are initiated at these surfaces, S-IgA down-regulation could be a means by which chronic stress increases susceptibility to upper respiratory tract infection

Functional characterization of two novel mutations in scn5a associated with brugada syndrome identified in Italian patients

Background. Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by “coved type” ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20–30% of BrS cases and is considered clinically relevant. Methods. Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. Results. Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. Conclusions. Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention

Using a Stick Does Not Necessarily Alter Judged Distances or Reachability

Background It has been reported that participants judge an object to be closer after a stick has been used to touch it than after touching it with the hand. In this study we try to find out why this is so. Methodology We showed six participants a cylindrical object on a table. On separate trials (randomly intermixed) participants either estimated verbally how far the object is from their body or they touched a remembered location. Touching was done either with the hand or with a stick (in separate blocks). In three different sessions, participants touched either the object location or the location halfway to the object location. Verbal judgments were given either in centimeters or in terms of whether the object would be reachable with the hand. No differences in verbal distance judgments or touching responses were found between the blocks in which the stick or the hand was used. Conclusion Instead of finding out why the judged distance changes when using a tool, we found that using a stick does not necessarily alter judged distances or judgments about the reachability of objects

ArrayExpress—a public repository for microarray gene expression data at the EBI

ArrayExpress is a public repository for microarray data that supports the MIAME (Minimum Informa-tion About a Microarray Experiment) requirements and stores well-annotated raw and normalized data. As of November 2004, ArrayExpress contains data from ∼12 000 hybridizations covering 35 species. Data can be submitted online or directly from local databases or LIMS in a standard format, and password-protected access to prepublication data is provided for reviewers and authors. The data can be retrieved by accession number or queried by vari-ous parameters such as species, author and array platform. A facility to query experiments by gene and sample properties is provided for a growing subset of curated data that is loaded in to the ArrayExpress data warehouse. Data can be visualized and analysed using Expression Profiler, the integrated data analysis tool. ArrayExpress is available at http://www.ebi.ac.uk/arrayexpress

ArrayExpress update—an archive of microarray and high-throughput sequencing-based functional genomics experiments

The ArrayExpress Archive (http://www.ebi.ac.uk/arrayexpress) is one of the three international public repositories of functional genomics data supporting publications. It includes data generated by sequencing or array-based technologies. Data are submitted by users and imported directly from the NCBI Gene Expression Omnibus. The ArrayExpress Archive is closely integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Advanced queries provided via ontology enabled interfaces include queries based on technology and sample attributes such as disease, cell types and anatomy

Gene Expression Atlas update—a value-added database of microarray and sequencing-based functional genomics experiments

Gene Expression Atlas (http://www.ebi.ac.uk/gxa) is an added-value database providing information about gene expression in different cell types, organism parts, developmental stages, disease states, sample treatments and other biological/experimental conditions. The content of this database derives from curation, re-annotation and statistical analysis of selected data from the ArrayExpress Archive and the European Nucleotide Archive. A simple interface allows the user to query for differential gene expression either by gene names or attributes or by biological conditions, e.g. diseases, organism parts or cell types. Since our previous report we made 20 monthly releases and, as of Release 11.08 (August 2011), the database supports 19 species, which contains expression data measured for 19 014 biological conditions in 136 551 assays from 5598 independent studies