65 research outputs found

    Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor

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    Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to α-, β-, and γ-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA–induced reduction of PCDHG@ encoded proteins leads to elevated β-catenin protein, increased β-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses β-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling

    Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

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    We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

    Artificial intelligence (AI): multidisciplinary perspectives on emerging challenges, opportunities, and agenda for research and practice

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    As far back as the industrial revolution, great leaps in technical innovation succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision making engendering new opportunities for continued innovation. The impact of AI is significant, with industries ranging from: finance, retail, healthcare, manufacturing, supply chain and logistics all set to be disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: technological, business and management, science and technology, government and public sector. The research offers significant and timely insight to AI technology and its impact on the future of industry and society in general

    ANION RECOGNITION BY NOVEL RUTHENIUM(II) BIPYRIDYL CALIX[4]ARENE RECEPTOR MOLECULES

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    Exotic calix[4]arene mono- and di-topic anion receptors containing one and two ruthenium(II) bipyridyl moieties have been prepared and shown by 1H NMR and CV to bind and electrochemically recognise halide, dihydrogen phosphate and hydrogen sulphate anions. The monotopic calix[4]arene anion receptor 8 selectively electrochemically recognises H2PO 4 - in the presence of tenfold excess amounts of HSO 4 - and Cl-

    Novel arenavirus isolates from Namaqua rock mice, Namibia, Southern Africa

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    CITATION: Witkowski, P. T. et al. 2015. Novel arenavirus isolates from Namaqua rock mice, Namibia, Southern Africa. Emerging Infectious Diseases, 21(7):1213-1216, doi: 10.3201/eid2107.141341.The original publication is available at http://wwwnc.cdc.gov/eidArenaviruses are feared as agents that cause viral hemorrhagic fevers. We report the identification, isolation, and genetic characterization of 2 novel arenaviruses from Namaqua rock mice in Namibia. These findings extend knowledge of the distribution and diversity of arenaviruses in Africa.http://wwwnc.cdc.gov/eid/article/21/7/14-1341_articlePublishers' versio

    Measurement accuracy of prototype non-contrast, compressed sensing-based, respiratory motion-resolved whole heart cardiovascular magnetic resonance angiography for the assessment of thoracic aortic dilatation: comparison with computed tomography angiography.

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    Patients with thoracic aortic dilatation who undergo annual computed tomography angiography (CTA) are subject to repeated radiation and contrast exposure. The purpose of this study was to evaluate the feasibility of a non-contrast, respiratory motion-resolved whole-heart cardiovascular magnetic resonance angiography (CMRA) technique against reference standard CTA, for the quantitative assessment of cardiovascular anatomy and monitoring of disease progression in patients with thoracic aortic dilatation. METHODS: Twenty-four patients (68.6 ± 9.8 years) with thoracic aortic dilatation prospectively underwent clinical CTA and research 1.5T CMRA between July 2017 and November 2018. Scans were repeated in 15 patients 1 year later. A prototype free-breathing 3D radial balanced steady-state free-precession whole-heart CMRA sequence was used in combination with compressed sensing-based reconstruction. Area, circumference, and diameter measurements were obtained at seven aortic levels by two experienced and two inexperienced readers. In addition, area and diameter measurements of the cardiac chambers, pulmonary arteries and pulmonary veins were also obtained. Agreement between the two modalities was assessed with intraclass correlation coefficient (ICC) analysis, Bland-Altman plots and scatter plots. Area, circumference and diameter measurements on a per-level analysis showed good or excellent agreement between CTA and CMRA (ICCs > 0.84). Means of differences on Bland-Altman plots were: area 0.0 cm <sup>2</sup> [- 1.7; 1.6]; circumference 1.0 mm [- 10.0; 12.0], and diameter 0.6 mm [- 2.6; 3.6]. Area and diameter measurements of the left cardiac chambers showed good agreement (ICCs > 0.80), while moderate to good agreement was observed for the right chambers (all ICCs > 0.56). Similar good to excellent inter-modality agreement was shown for the pulmonary arteries and veins (ICC range 0.79-0.93), with the exception of the left lower pulmonary vein (ICC < 0.51). Inter-reader assessment demonstrated mostly good or excellent agreement for both CTA and CMRA measurements on a per-level analysis (ICCs > 0.64). Difference in maximum aortic diameter measurements at baseline vs follow up showed excellent agreement between CMRA and CTA (ICC = 0.91). The radial whole-heart CMRA technique combined with respiratory motion-resolved reconstruction provides comparable anatomical measurements of the thoracic aorta and cardiac structures as the reference standard CTA. It could potentially be used to diagnose and monitor patients with thoracic aortic dilatation without exposing them to radiation or contrast media

    Low-kV coronary artery calcium scoring with tin filtration using a kV-independent reconstruction algorithm.

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    PURPOSE: To investigate the accuracy of Agatston scoring and potential for radiation dose reduction of a coronary artery calcium scoring (CACS) CT protocol at 100 kV with tin filtration (Sn100kV) and kV-independent iterative reconstruction, compared to standard 120 kV acquisitions. MATERIALS AND METHODS: With IRB approval and in HIPAA compliance, 114 patients (61.8 \ub1 9.6 years; 66 men) underwent CACS using a standard 120 kV protocol and an additional Sn100kV CACS scan. The two datasets were reconstructed using a medium sharp convolution algorithm and in addition the Sn100kV scans were reconstructed iteratively based on a kV-independent algorithm. Agatston scores and radiation dose values were compared between the Sn100kV and the standard 120 kV protocol. RESULTS: Median Agatston scores derived from the Sn100kV protocol with the kV-independent algorithm and the standard 120 kV were 21.4 (IQR, 0-173.8) and 24.7 (IQR, 0-171.1) respectively, with no significant differences (p=0.18). Agatston scores derived from the two different protocols had an excellent correlation (r = 0.99). The dose-length-product was 11.5 \ub1 4.1 mGy 7 cm using Sn100kV and 50.4 \ub1 24.9 mGy 7 cm using the standard 120 kV protocol (p < 0.01), resulting in a significantly lower (77%) effective dose at Sn100kV (0.16 \ub1 0.06 mSv vs. 0.71 \ub1 0.35 mSv, p < 0.01). Additionally, 99% of the patients were classified into the same risk category (0, 1-10, 11-100, 101-400, or >400) using the Sn100kV protocol. CONCLUSION: CACS at Sn100kV using the kV-independent iterative algorithm is feasible and provides high accuracy when compared to standard 120 kV scanning. Furthermore, radiation dose can be significantly reduced for this screening application in a priori healthy individuals
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