Detection of atrial fibrillation episodes in long-term heart rhythm signals using a support vector machine

Atrial fibrillation (AF) is a serious heart arrhythmia leading to a significant increase of the risk for occurrence of ischemic stroke. Clinically, the AF episode is recognized in an electrocardiogram. However, detection of asymptomatic AF, which requires a long-term monitoring, is more efficient when based on irregularity of beat-to-beat intervals estimated by the heart rate (HR) features. Automated classification of heartbeats into AF and non-AF by means of the Lagrangian Support Vector Machine has been proposed. The classifier input vector consisted of sixteen features, including four coefficients very sensitive to beat-to-beat heart changes, taken from the fetal heart rate analysis in perinatal medicine. Effectiveness of the proposed classifier has been verified on the MIT-BIH Atrial Fibrillation Database. Designing of the LSVM classifier using very large number of feature vectors requires extreme computational efforts. Therefore, an original approach has been proposed to determine a training set of the smallest possible size that still would guarantee a high quality of AF detection. It enables to obtain satisfactory results using only 1.39% of all heartbeats as the training data. Post-processing stage based on aggregation of classified heartbeats into AF episodes has been applied to provide more reliable information on patient risk. Results obtained during the testing phase showed the sensitivity of 98.94%, positive predictive value of 98.39%, and classification accuracy of 98.86%.Web of Science203art. no. 76

GAPDH mediates drug resistance and metabolism in Plasmodium falciparum malaria parasites

Efforts to control the global malaria health crisis are undermined by antimalarial resistance. Identifying mechanisms of resistance will uncover the underlying biology of the Plasmodium falciparum malaria parasites that allow evasion of our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor of plastidial isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway. We have thus identified an unusual metabolic regulation scheme in the malaria parasite through the essential glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Two parallel genetic screens converged on independent but functionally analogous resistance alleles in GAPDH. Metabolic profiling of FSM-resistant gapdh mutant parasites indicates that neither of these mutations disrupt overall glycolytic output. While FSM-resistant GAPDH variant proteins are catalytically active, they have reduced assembly into the homotetrameric state favored by wild-type GAPDH. Disrupted oligomerization of FSM-resistant GAPDH variant proteins is accompanied by altered enzymatic cooperativity and reduced susceptibility to inhibition by free heme. Together, our data identifies a new genetic biomarker of FSM-resistance and reveals the central role of GAPDH in MEP pathway control and antimalarial sensitivity

De novo Assembly and Analysis of the Northern Leopard Frog Rana pipiens Transcriptome

The northern leopard frog Rana (Lithobates) pipiens is an important animal model, being used extensively in cancer, neurology, physiology, and biomechanical studies. R. pipiens is a native North American frog whose range extends from northern Canada to southwest United States, but over the past few decades its populations have declined significantly and is now considered uncommon in large portions of the United States and Canada. To aid in the study and conservation of R. pipiens, this paper describes the first R. pipiens transcriptome. The R. pipiens transcriptome was annotated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Eukaryotic Orthologous Groups (KOG). Differential expression analysis revealed universal and tissue specific genes, and endocrine-related genes were identified. Transcriptome assemblies and other sequence data are available for download

CDH1 mutation distribution and type suggests genetic differences between the etiology of orofacial clefting and gastric cancer

Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least ‘likely pathogenic’, and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants

Knowledge Transfer and Exchange Processes for Environmental Health Issues in Canadian Aboriginal Communities

Within Canadian Aboriginal communities, the process for utilizing environmental health research evidence in the development of policies and programs is not well understood. This fundamental qualitative descriptive study explored the perceptions of 28 environmental health researchers, senior external decision-makers and decision-makers working within Aboriginal communities about factors influencing knowledge transfer and exchange, beliefs about research evidence and Traditional Knowledge and the preferred communication channels for disseminating and receiving evidence. The results indicate that collaborative relationships between researchers and decision-makers, initiated early and maintained throughout a research project, promote both the efficient conduct of a study and increase the likelihood of knowledge transfer and exchange. Participants identified that empirical research findings and Traditional Knowledge are different and distinct types of evidence that should be equally valued and used where possible to provide a holistic understanding of environmental issues and support decisions in Aboriginal communities. To facilitate the dissemination of research findings within Aboriginal communities, participants described the elements required for successfully crafting key messages, locating and using credible messengers to deliver the messages, strategies for using cultural brokers and identifying the communication channels commonly used to disseminate and receive this type of information