1,721,014 research outputs found
Child migration: from social determinants of health to the development agenda and beyond
No full textThis is an Accepted Manuscript of an article published by Taylor & Francis in 'Medicine, Conflict and Survival' on 2016-07-02, available online: https://www.tandfonline.com/10.1080/13623699.2016.1258806. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing [email protected]
Rare biochemical & genetic conditions: clues for broader mechanistic insights
No full textRare disorders often represent a molecular deviation from hi-fidelity genomic integrity networks and are often perceived as too difficult or unimportant for further mechanistic studies. Here, we synthesize evidence demonstrating how valuable knowledge of biochemical pathways related to rare disorders can be for biomedicine. To this end, we describe several rare congenital lipid, protein, organic acid, and glycan metabolism disorders and discuss how rare phenotypes (such as "extreme responders") and case reports (such as the lenalidomide cases) have provided clues for drug discovery or repurposing. We also discuss how rare disorders such as Gaucher disease and ultra-rare genetic syndromes can provide insights into cancer and mTOR-driven metabolism, respectively. Our discussion highlights the continued value of biochemical pathways and studies in understanding human pathophysiology and drug discovery even in the genomics era. © 2025. The Author(s)
Διερεύνηση των γενετικών, μικροβιακών-ιογενών και άλλων περιβαλλοντικών παραγόντων σε νευροφλεγμονώδεις και νευροεκφυλιστικές νόσους του ΚΝΣ μέσω προσεγγίσεων «-ομικής» ή «μετα-έρευνας»
No full textNeurological disorders represent a major component of the global disease burden. Nonetheless, in contrast to cancer and heart disorders, two broad disease categories which have been extensively studied in the last three decades, neurological disorders have been understudied. As a result, their underlying causes, and the potential contribution of genetic and non-genetic (also described as environmental) factors remain underexplored. To address this hovering research gap, and in light of an increasing body of studies in the field, I aimed to study the contribution of several genetic and non-genetic risk factors in neurodegenerative and neuroinflammatory disorders, harnessing Alzheimer’s & Parkinson’s diseases, and Multiple Sclerosis as exemplars, respectively. By applying both -omics and meta-research (i.e., secondary research) approaches, my analyses suggest that: a) the approach of meta-umbrella systematic review can provide valuable insights into non-genetic protective and risk factors, and represents a third-generation meta-research approach, preceded by umbrella and systematic reviews; b) APOE4/APOE4 (the chief genetic risk factor of Alzheimer’s disease) may be implicated in regulating the recently discovered meningeal lymphatic vessels by causing lymphosclerosis, the lymphatic equivalent of atherosclerosis, and in turn, meningeal and brain lymphedema, thus collectively impeding the flux of CSF toxic metabolites from the brain to the cervix and potentially leading to accumulation of amyloid-beta and tau in the brain; c) On the single-microbe level, the gut microbe Helicobacter pylori may be associated with increased risk for Parkinson’s disease, whose clinical scores such as the Unified Parkinson's Disease Rating Scale (UPDRS) may be reduced following Helicobacter pylori’s eradication; and, d) On the microbiome level, the CSF may not be devoid of the presence of viruses, for which our advanced bioinformatic analysis indicated separate clustering of CSF virome in Multiple Sclerosis patients versus controls. In parallel to the above data-intensive approaches, and to justify the historic(al) roots of a Ph.D. thesis as Doctor Philosophicus, I also present a critical analysis of the so-called ELSI (Ethical, Legal, and Societal Implications) of Neurological Research. In doing so, I argue that: a) the research niches of countries with limited resources for research (yet often classified as wealthy) can be regarded as hidden pearls that can boost local research pipelines in times of austerity, and to this end, I provide specific examples from patient population and biotechnological resources in Greece; b) the post-CRISPR/Cas9 genome editing era represents a tremendous opportunity as potential therapeutic armamentarium even for complex disorders with neurological manifestations, such as Down’s syndrome (Trisomy 21); however, rigorous bioethics regulations should be set prior to clinical trials, especially if the latter are applied during the embryological stage of patients with Down’s syndrome; and c) stronger public advocacy is needed for syndromes with neuropsychiatric manifestations, such as the Imposter syndrome, whose high prevalence and psychological burden has had a huge impact in societally underrepresented groups. Collectively, my Ph.D. thesis aims to shed some light into the causality of certain neurological disorders, anticipating that the results and conclusions presented here will open an avenue to future research questions.Οι νευρολογικές διαταραχές αντιπροσωπεύουν ένα σημαντικό ποσοστό του παγκόσμιου φορτίου ασθενειών. Ωστόσο, σε αντίθεση με τον καρκίνο και τις καρδιακές διαταραχές, δύο ευρείες κατηγορίες ασθενειών που έχουν μελετηθεί εκτενώς τις τελευταίες τρεις δεκαετίες, οι νευρολογικές και νευροψυχιατρικές διαταραχές έχουν υπομελετηθεί. Ως αποτέλεσμα, οι υποκείμενες αιτίες των νευρολογικών και νευροψυχιατρικών διαταραχών και η πιθανή συμβολή γενετικών και μη-γενετικών παραγόντων (περιγράφονται επίσης ως περιβαλλοντικοί παράγοντες) παραμένουν, σε μεγάλο βαθμό, ανεξερεύνητες. Για την αντιμετώπιση αυτού του αιωρούμενου ερευνητικού «κενού» και υπό το φως ενός αυξανόμενου αριθμού μελετών στον τομέα, ο στόχος της παρούσας διατριβής ήταν να μελετηθεί η συμβολή πολλών γενετικών και μη-γενετικών παραγόντων κινδύνου σε νευροεκφυλιστικές, νευροψυχιατρικές, και νευροεφλεγμονώδεις διαταραχές, χρησιμοποιώντας τις νόσους του Alzheimer & Parkinson και τη Σκλήρυνση κατά Πλάκας ως πρότυπα παραδείγματα των ασθενειών αυτών. Εφαρμόζοντας προσεγγίσεις τόσο της «-ομικής» όσο και της «μετα-έρευνας», η παρούσα διατριβή υπογραμμίζει ότι: α) η προσέγγιση τύπου «meta-umbrella συστηματική ανασκόπηση», που εισάγεται για πρώτη φορά στη βιβλιογραφία, μπορεί να παράσχει πολύτιμες πληροφορίες για τους μη-γενετικούς παράγοντες κινδύνου αλλά και προστατευτικούς παράγοντες. β) Το APOE4 γονίδιο / APOE4 πρωτεΐνη (ο κύριος παράγοντας γενετικού κινδύνου της νόσου του Αλτσχάιμερ) μπορεί να εμπλέκεται στη ρύθμιση των πρόσφατα ανακαλυφθέντων μηνιγγικών λεμφικών αγγείων προκαλώντας «λεμφοσκλήρωση», νοούμενη ως το λεμφικό ισοδύναμο της αθηροσκλήρωσης και, με τη σειρά της, μηνιγγικό και εγκεφαλικό λεμφοίδημα, εμποδίζοντας έτσι την παροχέτευση των τοξικών μεταβολιτών του εγκεφαλονωτιαίου υγρού (ΕΝΥ) από τον εγκέφαλο στον τράχηλο, και πιθανώς οδηγώντας σε συσσώρευση αμυλοειδούς βήτα και tau στον εγκέφαλο. γ) Σε επίπεδο μονήρους μικροβίου, το μικρόβιο του στομάχου Helicobacter pylori μπορεί να σχετίζεται με αυξημένο κίνδυνο για τη νόσο του Parkinson, του οποίου οι κλινικές βαθμολογίες όπως το Unified Parkinson Disease Rating Scale (UPDRS) μπορεί να μειωθούν μετά την εκρίζωση του Helicobacter pylori. δ) Σε επίπεδο πολλαπλών μικροβίων, το ΕΝΥ μπορεί να μην στερείται της παρουσίας ιών, για τους οποίους η προηγμένη βιοπληροφορική ανάλυσή μας έδειξε ξεχωριστή συσσώρευση ιών στο ΕΝΥ ασθενών με Σκλήρυνση κατά Πλάκας έναντι των υγιών μαρτύρων. Παράλληλα στην παρούσα διατριβή παρουσιάζεται μία κριτική ανάλυση των λεγόμενων ELSI (Ethical, Legal and Societal Implications) της έρευνας πάνω στη νευρολογία, εστιάζοντας α) στις χώρες με περιορισμένους πόρους για έρευνα και το πώς μπορεί να ενισχύσουν τους τοπικούς ερευνητικούς φορείς σε περιόδους λιτότητας, παρέχοντας συγκεκριμένα παραδείγματα από την Ελλάδα, β) στην τροποποίηση του γονιδιώματος μέσω του «μοριακού ψαλιδιού» CRISPR / Cas9 ως πιθανό θεραπευτικό οπλισμό για σύνθετες διαταραχές με νευρολογικές εκδηλώσεις, όπως το σύνδρομο Down (Trisomy 21) αλλά και την ανάγκη τήρησης αυστηρών κανόνων βιοηθικής, γ) στο «σύνδρομο του απατεώνα» του οποίου η ψυχολογική επιβάρυνση έχει τεράστιο αντίκτυπο σε κοινωνικά ευάλωτες ομάδες. Συνολικά, η παρούσα διατριβή στοχεύει να διερευνήσει την αιτιοπαθογένεια πρότυπων νευρολογικών και νευροψυχιατρικών διαταραχών, ευελπιστώντας ότι τα αποτελέσματα και τα συμπεράσματα που παρουσιάζονται εδώ θα ανοίξουν έναν δρόμο για μελλοντικά ερευνητικά ερωτήματα
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
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