Benefit of Apabetalone on Plasma Proteins in Renal Disease.

Introduction:Apabetalone, a small molecule inhibitor, targets epigenetic readers termed BET proteins that contribute to gene dysregulation in human disorders. Apabetalone has in vitro and in vivo anti-inflammatory and antiatherosclerotic properties. In phase 2 clinical trials, this drug reduced the incidence of major adverse cardiac events in patients with cardiovascular disease. Chronic kidney disease is associated with a progressive loss of renal function and a high risk of cardiovascular disease. We studied the impact of apabetalone on the plasma proteome in patients with impaired kidney function. Methods:Subjects with stage 4 or 5 chronic kidney disease and matched controls received a single dose of apabetalone. Plasma was collected for pharmacokinetic analysis and for proteomics profiling using the SOMAscan 1.3k platform. Proteomics data were analyzed with Ingenuity Pathway Analysis to identify dysregulated pathways in diseased patients, which were targeted by apabetalone. Results:At baseline, 169 plasma proteins (adjusted P value <0.05) were differentially enriched in renally impaired patients versus control subjects, including cystatin C and β2 microglobulin, which correlate with renal function. Bioinformatics analysis of the plasma proteome revealed a significant activation of 42 pathways that control immunity and inflammation, oxidative stress, endothelial dysfunction, vascular calcification, and coagulation. At 12 hours postdose, apabetalone countered the activation of pathways associated with renal disease and reduced the abundance of disease markers, including interleukin-6, plasminogen activator inhibitor-1, and osteopontin. Conclusion:These data demonstrated plasma proteome dysregulation in renally impaired patients and the beneficial impact of apabetalone on pathways linked to chronic kidney disease and its cardiovascular complications

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Categorizing facial expressions : a comparison of computational models

The original publication is available at www.springerlink.com Copyright SpringerRecognizing expressions is a key part of human social interaction, and processing of facial expression information is largely automatic for humans, but it is a non-trivial task for a computational system. The purpose of this work is to develop computational models capable of differentiating between a range of human facial expressions. Raw face images are examples of high-dimensional data, so here we use two dimensionality reduction techniques: principal component analysis and curvilinear component analysis. We also preprocess the images with a bank of Gabor filters, so that important features in the face images may be identified. Subsequently, the faces are classified using a support vector machine. We show that it is possible to differentiate faces with a prototypical expression from the neutral expression. Moreover, we can achieve this with data that has been massively reduced in size: in the best case the original images are reduced to just 5 components. We also investigate the effect size on face images, a concept which has not been reported previously on faces. This enables us to identify those areas of the face that are involved in the production of a facial expression.Peer reviewe

Effects of oxygenation and/or SOD on addition to St. Thomas' Hospital cardioplegic solution

博士（医学）神戸大

Discrepant outcomes in two Brazilian patients with Bloom syndrome and Wilms’ tumor: two case reports

Abstract\ud \ud Introduction\ud Bloom syndrome is a rare, autosomal recessive, chromosomal instability disorder caused by mutations in the BLM gene that increase the risk of developing neoplasias, particularly lymphomas and leukemias, at an early age.\ud \ud \ud Case presentation\ud Case 1 was a 10-year-old Brazilian girl, the third child of a non-consanguineous non-Jewish family, who was born at 36 weeks of gestation and presented with severe intrauterine growth restriction. She had Bloom syndrome and was diagnosed with a unilateral Wilms’ tumor at the age of 3.5 years. She responded well to oncological treatment and has remained disease-free for the last 17 years. Case 2 was a 2-year-old Brazilian girl born to non-Jewish first-degree cousins. Her gestation was marked by intrauterine growth restriction. She had Bloom syndrome; a unilateral stage II Wilms’ tumor was diagnosed at the age of 4 years after the evaluation of a sudden onset abdominal mass. Surgical removal, neoadjuvant chemotherapy and radiotherapy were not sufficient to control the neoplasia. The tumor recurred after 8 months and she died from clinical complications.\ud \ud \ud Conclusion\ud Our study reports the importance of rapid diagnostics and clinical follow-up of these patients.CAPE

e-MIR2: a public online inventory of medical informatics resources

Background. Over the last years, the number of available informatics resources in medicine has grown exponentially. While specific inventories of such resources have already begun to be developed for Bioinformatics (BI), comparable inventories are as yet not available for Medical Informatics (MI) field, so that locating and accessing them currently remains a hard and time-consuming task. Description. We have created a repository of MI resources from the scientific literature, providing free access to its contents through a web-based service. Relevant information describing the resources is automatically extracted from manuscripts published in top-ranked MI journals. We used a pattern matching approach to detect the resources? names and their main features. Detected resources are classified according to three different criteria: functionality, resource type and domain. To facilitate these tasks, we have built three different taxonomies by following a novel approach based on folksonomies and social tagging. We adopted the terminology most frequently used by MI researchers in their publications to create the concepts and hierarchical relationships belonging to the taxonomies. The classification algorithm identifies the categories associated to resources and annotates them accordingly. The database is then populated with this data after manual curation and validation. Conclusions. We have created an online repository of MI resources to assist researchers in locating and accessing the most suitable resources to perform specific tasks. The database contained 282 resources at the time of writing. We are continuing to expand the number of available resources by taking into account further publications as well as suggestions from users and resource developers

Copy number variation in Williams-Beuren syndrome: suitable diagnostic strategy for developing countries

<p>Abstract</p> <p>Background</p> <p>Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis (SVAS), mental retardation, and overfriendliness comprise typical symptoms of WBS. Although fluorescence in situ hybridization (FISH) is considered the gold standard technique, the microsatellite DNA markers and multiplex ligation-dependent probe amplification (MLPA) could be used for to confirm the diagnosis of WBS.</p> <p>Results</p> <p>We have evaluated a total cohort of 88 patients with a suspicion clinical diagnosis of WBS using a collection of five markers (D7S1870, D7S489, D7S613, D7S2476, and D7S489_A) and a commercial MLPA kit (P029). The microdeletion was present in 64 (72.7%) patients and absent in 24 (27.3%) patients. The parental origin of deletion was maternal in 36 of 64 patients (56.3%) paternal in 28 of 64 patients (43.7%). The deletion size was 1.55 Mb in 57 of 64 patients (89.1%) and 1.84 Mb in 7 of 64 patients (10.9%). The results were concordant using both techniques, except for four patients whose microsatellite markers were uninformative. There were no clinical differences in relation to either the size or parental origin of the deletion.</p> <p>Conclusion</p> <p>MLPA was considered a faster and more economical method in a single assay, whereas the microsatellite markers could determine both the size and parental origin of the deletion in WBS. The microsatellite marker and MLPA techniques are effective in deletion detection in WBS, and both methods provide a useful diagnostic strategy mainly for developing countries.</p