1,721,006 research outputs found
Precision medicine for pandemics: stratification of COVID-19 molecular phenotypes defined by topological analysis of global blood gene expression.
No full textPrecision medicine offers a promising avenue for better therapeutic responses to pandemics such as COVID-19. This study leverages independent patient cohorts in Florence and Liège gathered under the umbrella of the DRAGON consortium for the stratification of molecular phenotypes associated with COVID-19 using topological analysis of global blood gene expression. Whole blood from 173 patients was collected and RNA was sequenced on the Novaseq platform. Molecular phenotypes were defined through topological analysis of gene expression relative to the biological network using the TopMD algorithm. The two cohorts from Florence and Liège allowed for independent validation of the findings in this study. Clustering of the topological maps of differential pathway activation revealed three distinct molecular phenotypes of COVID-19 in the Florence patient cohort, which were also observed in the Liège cohort.Cluster 1 was characterised by high activation of pathways associated with ESC pluripotency, NRF2, and TGF-β receptor signalling. Cluster 2 displayed high activation of pathways including focal adhesion-PI3K-Akt-mTOR signalling and type I interferon induction and signalling, while Cluster 3 exhibited low IRF7-related pathway activation. TopMD was also used with the Drug-Gene Interaction Database (DGIdb), revealing pharmaceutical interventions targeting mechanisms across multiple phenotypes and individuals.The data illustrates the utility of molecular phenotyping from topological analysis of blood gene expression, and holds promise for informing personalised therapeutic strategies not only for COVID-19 but also for Disease X. Its potential transferability across multiple diseases highlights the value in pandemic response efforts, offering insights before large-scale clinical studies are initiated
Understanding severe coronavirus disease in humans from the analysis of clinical samples with RNA sequencing
Get PDFCoronaviruses in humans have been of concern since the emergence of SARS-CoV, MERS-CoV and SARS-CoV-2 over the past two decades. Coronavirus disease in humans can range from asymptomatic to mild or severe where symptomatic disease is associated with fever, cough, and respiratory symptoms. Next generation sequencing and phylogeny studies can provide insight into viral evolution due to the nucleotide polymorphisms which arise due to the inherent error rates. Nanopore sequencing can facilitate these studies rapidly and are therefore a useful public health tool for genome surveillance. MERS-CoV emerged in Saudi Arabia in 2012 and is associated with sporadic outbreaks. To facilitate rapid genomic surveillance of MERS-CoV in Saudi Arabia, a PCR amplification sequencing method compatible with Nanopore was designed. This approach is useful as data derived from this methodology can be used for phylogeny and variant analysis which supports investigation into transmission events and viral evolution. Upon the emergence of SARS-CoV-2 in late 2019, this approach was then repurposed and utilised on a subset of patients from the UK. Alternative viral genome sequencing approaches were then employed to assess the tissue tropism of SARS-CoV-2 in fatal COVID-19 cases, where tropism was widespread, while inflammation was exclusive to pulmonary tissues. To complement the analysis conducted on the tissue of fatal COVID-19 patients, blood from patients at point of care were utilised for blood transcriptomics analysis. Both illumina and nanopore sequencing methodologies were employed to assess differences in transcript abundance in these patients. Transcriptomic profiles from COVID-19 patients were compared to profiles from Influenza patients and healthy controls, in addition to fatal and non-fatal COVID-19 cases. The key finding from this analysis was that immunoglobulin domains transcripts exhibited altered abundance when comparing COVID and Influenza patients, as well as between fatal and non-fatal COVID-19 cases. From this insight, it is hypothesised that an early adaptive immune response is associated with survival, or a delayed adaptive response is associated with fatality. As it is challenging to control variables from patient data, an hACE2 mice model was utilised to explore the host response against Influenza A virus and SARS-CoV-2 as independent and sequential infections using lung tissue. Transcriptomic analysis revealed a sustained cytokine and interferon response in coinfected mice. Transcripts changing in abundance in both human blood and mice lungs were compared to generate a subset of transcripts that may be essential to the response to SARS-CoV-2 infection. In summary, the results described within this thesis provide insights into the novel coronavirus SARS-CoV-2 and COVID-19 disease in humans. Additionally, the outputs of this thesis provide a foundation for further investigation and development of Nanopore sequencing methodologies as a prognostic tool
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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