1,721,066 research outputs found
Extended Text for "Potential for diagnosis of infectious disease from the 100,000 Genomes Project Metagenomic Dataset: Recommendations for reporting results"
No full textExtended Text for "Potential for diagnosis of infectious disease from the 100,000 Genomes Project Metagenomic Dataset: Recommendations for reporting results" submitted to Wellcome Open Researc
Prolonged cardiac monitoring for stroke prevention: A systematic review and meta-analysis of randomized-controlled clinical trials
No full textIntroduction: Prolonged cardiac monitoring (PCM) substantially improves the detection of subclinical atrial fibrillation (AF) among patients with history of ischemic stroke (IS), leading to prompt initiation of anticoagulants. However, whether PCM may lead to IS prevention remains equivocal. Patients and methods: In this systematic review and meta-analysis, randomized-controlled clinical trials (RCTs) reporting IS rates among patients with known cardiovascular risk factors, including but not limited to history of IS, who received PCM for more than 7 days versus more conservative cardiac rhythm monitoring methods were pooled. Results: Seven RCTs were included comprising a total of 9048 patients with at least one known cardiovascular risk factor that underwent cardiac rhythm monitoring. PCM was associated with reduction of IS occurrence compared to conventional monitoring (Risk Ratio: 0.76; 95% CI: 0.59–0.96; I 2 = 0%). This association was also significant in the subgroup of RCTs investigating implantable cardiac monitoring (Risk Ratio: 0.75; 95% CI: 0.58–0.97; I 2 = 0%). However, when RCTs assessing PCM in both primary and secondary prevention settings were excluded or when RCTs investigating PCM with a duration of 7 days or less were included, the association between PCM and reduction of IS did not retain its statistical significance. Regarding the secondary outcomes, PCM was related to higher likelihood for AF detection and anticoagulant initiation. No association was documented between PCM and IS/transient ischemic attack occurrence, all-cause mortality, intracranial hemorrhage, or major bleeding. Conclusion: PCM may represent an effective stroke prevention strategy in selected patients. Additional RCTs are warranted to validate the robustness of the reported associations
Compilation of all known HERV-K HML-2 proviral integrations
No full textHuman endogenous retroviruses (HERVs) occupy 8% of the human genome. Although most HERV integrations are severely degenerated by mutations, the most recently integrated proviruses, such as members of the HERV-K HML-2 subfamily, partially retain regulatory and protein-coding capacity. The precise number of HML-2 proviral copies in the modern human population is constantly changing in literature, as new integrations are being uncovered. The first comprehensive list of HML-2 proviral loci was compiled in 2011, including a total of 91 proviruses. Since then, multiple articles published additions and modifications to that list, mainly in the form of new polymorphic proviral sites, updated chromosomal band characterizations or the correspondence of coordinates in the new version of the published human reference genome. In the present study, we systematically searched the literature for lists of HML-2 proviruses and their coordinates and cross-examined every proviral locus information, also against the human genome. We gathered all available data about all HML-2 proviral integrations identified to date and updated, corrected and refined the coordinates in both human genome assemblies currently used in research, to incorporate the whole provirus in each case. Thereby we present an exhaustive (to date) catalogue of all known HML-2 proviruses and their respective coordinates, as a powerful tool for studies aiming to decipher HERV role in health and disease, especially for high-throughput data analyses, which could lead to the discovery of links between specific HERV integrations and biological mechanisms or medical disorders. © The Author(s) 2025
Transcriptional modulation of human endogenous retroviruses in primary CD4<sup>+</sup> T cells following vorinostat treatment
No full textThe greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A "shock and kill" approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs) are used to "shock" the silent provirus into active replication to permit "killing" by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC) inhibitor-vorinostat. Potentially, pathological off-target effects of vorinostat may result from the activation of human endogenous retroviruses (HERVs), which share common ancestry with exogenous retroviruses including HIV. To explore the effects of HDAC inhibition on HERV transcription, an unbiased pharmacogenomics approach (total RNA-Seq) was used to evaluate HERV expression following the exposure of primary CD4+ T cells to a high dose of vorinostat. Over 2,000 individual HERV elements were found to be significantly modulated by vorinostat, whereby elements belonging to the ERVL family (e.g., LTR16C and LTR33) were predominantly downregulated, in contrast to LTR12 elements of the HERV-9 family, which exhibited the greatest signal, with the upregulation of 140 distinct elements. The modulation of three different LTR12 elements by vorinostat was confirmed by droplet digital PCR along a dose-response curve. The monitoring of LTR12 expression during clinical trials with vorinostat may be indicated to assess the impact of this HERV on the human genome and host immunity.</p
Molecular evolution of human viruses and application in molecular epidemiology
No full textThe purpose of this PhD thesis was the application of phylogenetic methodology on virus’ molecular data in order to make epidemiological inferences. For this reason three viruses were studied, the Human Immunodeficiency Virus (HIV), the Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV) and the Hepatitis C Virus (HCV). For HIV we studied the distribution of recombination frequency and the distribution of phylogenetic information. More specifically we found that recombination was not randomly distributed across the genome and more specifically it was associated with genetic similarity. Moreover we found that: a) the phylogenetic information is not uniformly distributed across the genome, b) recombination disrupts the phylogenetic information content and c) there is a relationship between phylogenetic information and genetic similarity. For SARS-CoV we studied the taxonomy and we tested for the scenario of recombinant origin. More specifically we found that the virus was phylogenetically closer to Group II and that there is no evidence of recent recombination intergroup event. For HCV we studied recombination and the origin of the genotypes. More specifically we found that there is closer relationship between genotypes 1 and 4, which might be related to the similar resistance of these genotypes in ribavirininterferon therapy. Moreover we studied the molecular clock of the virus and we found that the virus is evolving faster than it was previously thought and that it fits the strict clock only for the E2-P7-NS2 region, but not for NS5B. Finally we studied the expansion of the epidemic in Greece for subtypes 1a, 1b, 3a and 4a and we estimated that the introductions happened in 1927, 1950, 1970 and 1940 respectively.Η παρούσα διδακτορική διατριβή έχει ως σκοπό την εφαρμογή μεθόδων φυλογενετικής συμπερασματολογίας σε μοριακά δεδομένα ιών που προσβάλλουν τον άνθρωπο με σκοπό την εξαγωγή επιδημιολογικών συμπερασμάτων. Στα πλαίσια της διατριβής μελετήθηκαν τρεις ιοί, ο ιός της ανθρώπινης ανοσοανεπάρκειας (HIV), ο κοροναϊός του οξέως αναπνευστικού συνδρόμου (SARS-CoV) και o ιός της Ηπατίτιδας C (HCV). Στον ιό της ανθρώπινης ανοσοανεπάρκειας μελετήθηκε ο ανασυνδυασμός και η φυλογενετική πληροφορία. Πιο συγκεκριμένα βρέθηκε ότι ο ανασυνδυασμός δε συμβαίνει τυχαία κατά μήκους του γονιδιώματος του HIV και ότι σχετίζεται με τη γενετική ομοιότητα. Επίσης βρέθηκε ότι: α) η φυλογενετική πληροφορία δεν κατανέμεται ομοιόμορφα κατά μήκους του γονιδιώματος, β) ο ανασυνδυασμός εκφυλίζει τη φυλογενετική πληροφορία και γ) ότι η φυλογενετική πληροφορία σχετίζεται με τη γενετική ομοιότητα. Στον ιό του οξέως αναπνευστικού συνδρόμου μελετήθηκε η ταξινόμησή του και ελέγχθηκε το σενάριο του ανασυνδυασμού. Συγκεκριμένα βρέθηκε ότι ταξινομικά είναι πλησιέστερα στην Ομάδα ΙΙ των κοροναϊών, ενώ δε φαίνεται κάποιο πρόσφατο γεγονός δια-ομαδικού ανασυνδυασμού. Στον ιό της Ηπατίτιδας C μελετήθηκε ο ανασυνδυασμός και η καταγωγή των γονότυπων. Συγκεκριμένα βρέθηκε πιο κοντινή σχέση μεταξύ των γονότυπων 1 και 4, γεγονός που μπορεί να σχετίζεται με την παρόμοια αντοχή τους στη θεραπευτική αγωγή ριμπαβιρίνης ιντερφερόνης. Επιπλέον μελετήθηκε το μοριακό ρολόι του ιού και βρέθηκε ότι ο ιός εξελίσσεται ταχύτερα από ότι είχε θεωρηθεί αρχικά και ότι ακολουθεί το σταθερό ρολόι στην περιοχή E2-P7-NS2, αλλά όχι στην NS5B. Τέλος, μελετήθηκε η επέκταση της επιδημίας στην Ελλάδα για τους υπότυπους 1a, 1b, 3a και 4a και εκτιμήθηκε ότι οι εισαγωγές τους έγιναν το 1927, το 1950, το 1970 και το 1940 αντίστοιχα
A novel method for the multiplexed target enrichment of MinION next generation sequencing libraries using PCR-generated baits
Full text linkThe enrichment of targeted regions within complex next generation sequencing libraries commonly uses biotinylated baits to capture the desired sequences. This method results in high read coverage over the targets and their flanking regions. Oxford Nanopore Technologies recently released an USB3.0-interfaced sequencer, the MinION. To date no particular method for enriching MinION libraries has been standardized. Here, using biotinylated PCR-generated baits in a novel approach, we describe a simple and efficient way for multiplexed enrichment of MinION libraries, overcoming technical limitations related with the chemistry of the sequencing-adapters and the length of the DNA fragments. Using Phage Lambda and Escherichia coli as models we selectively enrich for specific targets, significantly increasing the corresponding read-coverage, eliminating unwanted regions. We show that by capturing genomic fragments, which contain the target sequences, we recover reads extending targeted regions and thus can be used for the determination of potentially unknown flanking sequences. By pooling enriched libraries derived from two distinct E. coli strains and analyzing them in parallel, we demonstrate the efficiency of this method in multiplexed format. Crucially we evaluated the optimal bait size for large fragment libraries and we describe for the first time a standardized method for target enrichment in MinION platform
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
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