10,104 research outputs found

    An automated retinal image quality grading algorithm

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    This paper introduces an algorithm for the automated assessment of retinal fundus image quality grade. Retinal image quality grading assesses whether the quality of the image is sufficient to allow diagnostic procedures to be applied. Automated quality analysis is an important preprocessing step in algorithmic diagnosis, as it is necessary to ensure that images are sufficiently clear to allow pathologies to be visible. The algorithm is based on standard recommendations for quality analysis by human screeners, examining the clarity of retinal vessels within the macula region. An evaluation against a reference standard data-set is given; it is shown that the algorithm's performance correlates closely with that of clinicians manually grading image quality. © 2011 IEEE.</p

    Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads

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    A library of hybrid molecules is developed based on the common chemical features shared by clemastine and tamoxifen both of which are well known for their antileishmanial activities. In the initial screening against Leishmania major and L. amazonensis promastigotes, as well as cytotoxicity assays using HepG2 cells, several hybrids showed submicromolar activity against the parasite and no toxicity against human cells. The compounds with an EC50 10 were further characterized against intracellular amastigotes as well as promastigotes of species that cause both visceral and cutaneous leishmaniasis, such as L. infantum and L. braziliensis, respectively. These sequential screenings revealed the high pan-activity of this class of molecules against these species, with several compounds displaying an EC50 ≤ 2 μM against both promastigotes and intracellular amastigotes. Two of them were identified as the potential templates for lead optimization of this series having shown the highest activities against all species in both stages of parasite. The present findings can serve as a good starting point in the search for novel antileishmanial compounds that are easy to access and highly active

    Automated diagnosis of referable maculopathy in diabetic retinopathy screening

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    This paper introduces an algorithm for the automated diagnosis of referable maculopathy in retinal images for diabetic retinopathy screening. Referable maculopathy is a potentially sight-threatening condition requiring immediate referral to an ophthalmologist from the screening service, and therefore accurate referral is extremely important. The algorithm uses a pipeline of detection and filtering of peak points with strong local contrast, segmentation of candidate lesions, extraction of features and classification by a multilayer perceptron. The optic nerve head and fovea are detected, so that the macula region can be identified and scanned. The algorithm is assessed against a reference standard database drawn from the Birmingham City Hospital (UK) diabetic retinopathy screening programme, against two possible modes of use: independent screening, and pre-filtering to reduce human screener workload.</p

    Raw data.

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    Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T. cruzi. Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major, for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T. cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L. major IPCS. However, disruption of the T. cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T. cruzi IPCS null mutants are unable to establish an infection in vivo, even in immune deficient mice.</div

    Variant counts per gene from the MUSC cohort.

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    Adult-onset progressive hearing loss is a common, complex disease with a strong genetic component. Although to date over 150 genes have been identified as contributing to human hearing loss, many more remain to be discovered, as does most of the underlying genetic diversity. Many different variants have been found to underlie adult-onset hearing loss, but they tend to be rare variants with a high impact upon the gene product. It is likely that combinations of more common, lower impact variants also play a role in the prevalence of the disease. Here we present our exome study of hearing loss in a cohort of 532 older adult volunteers with extensive phenotypic data, including 99 older adults with normal hearing, an important control set. Firstly, we carried out an outlier analysis to identify genes with a high variant load in older adults with hearing loss compared to those with normal hearing. Secondly, we used audiometric threshold data to identify individual variants which appear to contribute to different threshold values. We followed up these analyses in a second cohort. Using these approaches, we identified genes and variants linked to better hearing as well as those linked to worse hearing. These analyses identified some known deafness genes, demonstrating proof of principle of our approach. However, most of the candidate genes are novel associations with hearing loss. While the results support the suggestion that genes responsible for severe deafness may also be involved in milder hearing loss, they also suggest that there are many more genes involved in hearing which remain to be identified. Our candidate gene lists may provide useful starting points for improved diagnosis and drug development.</div

    Not many genes are shared between male and female Metabolic and Sensory gene lists.

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    The Venn diagram shows the overlap of genes identified as having a high variant load in Metabolic or Sensory hearing loss in all, male and female participants in the MUSC cohort. The shaded circles show the high variant load gene counts identified in all participants.</p