1,720,954 research outputs found
Proteomic predictors of Cardiovascular events in Type 1 Diabetes
No full textType 1 diabetes (T1D) is an autoimmune disease caused by the loss of insulin secretion in the pancreas, resulting to increased blood sugar levels. T1D increases the risk of various micro- and macrovascular complications, which decrease both quality of life and life expectancy. Cardiovascular disease (CVD), which affects the blood circulation and the heart, is one of the most severe complications as it is the leading cause of mortality and morbidity in T1D, often occurring at a younger age than in the general population. Despite the well-known elevated CVD risk in T1D, the biological mechanisms remain poorly understood. Proteomics, a large-scale study of proteins, offer a possibility to analyze molecular changes associated with the disease progression and prediction. This thesis aimed to identify proteins that predict the increased risk of CVD in T1D, providing new insights into the disease mechanisms.
We analysed 5,420 proteins, using the Olink Explore HT® platform, in 830 participants from the Finnish Diabetic Nephropathy (FinnDiane) T1D cohort, followed up to a median 15.5 years. We studied four separate CVD outcomes: coronary artery disease (CAD), stroke, CVD, and major adverse cardiac event (MACE), to determine whether different complications are associated with distinct proteomic signatures and biological mechanisms. First, we conducted differential expression analysis (DEA) to identify proteins that are differentially expressed between cases and controls. Second, to assess the predictive value of the proteins, we used a survival model to test associations with incident CVD events. We further adjusted the DEA and survival analysis for the estimated glomerular filtration rate (eGFR) to examine the potential impact of kidney function on these associations, given its known link to CVD. Lastly, an enrichment analysis was performed to identify functions and pathways enriched among the proteins identified with survival analysis to provide further insight into underlying biological mechanisms.
From the survival analysis we identified 1,315 proteins associated with the increased risk of MACE, 1,230 with CVD, 1,060 with CAD and 389 with stroke, after correction for multiple testing. While most of these proteins were also differentially expressed in DEA, those associated with the highest event risk in survival analysis showed only modest changes in the expression levels, suggesting that large expression shifts may not directly correlate with the increased risk of cardiovascular events. Alpha-1-microglobulin/bikunin precursor (AMBP) showed the highest risk for MACE (6.9-fold increase), CVD (6.4-fold increase) and CAD (5.5-fold increase), while follistatin-like 1 (FSTL1) conferred the highest risk for stroke (4.5-fold increase). Adjusting previously used models with kidney function decreased the number of significant findings, suggesting that some proteins increase the CVD risk indirectly through kidney function. Enrichment analysis results showed that CVD related pathways, i.e., vascular dysfunction and inflammatory response, were enriched among the proteins associated with the incidence of the studied CVD events. These findings highlight the potential of proteomics to predict cardiovascular events in T1D and provide insights into the underlying biological mechanisms.
Future studies are needed to explore the causality of the proteomic associations, assess the influence of known CVD risk factors (i.e. obesity, hypertension, smoking), and replicate the results in other cohorts, including the general population and individuals with type 2 diabetes, to inspect whether these findings are diabetes-specific or more general
The gut microbiome in the development of Alzheimer’s disease
No full textAlzheimerin tauti (AD) on neurodegeneratiivinen sairaus, jonka tyypillisiä oireita ovat kognition ja muistin heikentyminen. AD:n tyypillisiin patologisiin muutoksiin kuuluvat esimerkiksi proteiinikertymien muodostuminen ja krooninen neuroinflammaatio. AD:n kehittymiseen liittyy paljon kysymyksiä, sillä AD:n patologia ja molekulaariset reitit eivät ole vielä täysin tiedossa. Tuoreimmat tutkimukset ovat osoittaneet suolistomikrobiomin olevan vuorovaikutuksessa aivojen kanssa. Tämän yhteyden häiriöiden uskotaan vaikuttavan esimerkiksi AD:ssa. Suolistomikrobiomin ja AD:n välisen yhteyden tutkiminen mahdollistaa AD:n patologian paremman ymmärtämisen sekä mahdollisesti uusien hoito- ja ehkäisymenetelmien löytämisen.
Suolistomikrobiomin dysbioosi tarkoittaa suolistomikrobiomin monimuotoisuuden muutoksia. Monimuotoisuuden muutokset tapahtuvat pääjakso-, suku- ja lajitasolla. Dysbioosissa suolistomikrobiomin rakenne muuttuu inflammaatiota estävän sijasta inflammaatiota edistäväksi. Suolistomikrobiomin dysbioosi on yhdistetty AD:n patologisiin muutoksiin, esimerkiksi neuroinflammaatioon, proteiinikertymien muodostumiseen sekä aivoveriesteen heikentymiseen. Patologiset muutokset lisäävät AD-potilaan kognitiivista heikentymistä ja muiden oireiden vakavuutta. Suolistomikrobiomin ja AD:n välinen yhteys on suhteellisen uusi tutkimusaihe, mutta se on herättänyt tutkijoiden mielenkiinnon ja tutkimukset aiheesta lisääntyvät jatkuvasti.
AD on etenkin ikääntyneiden ihmisten sairaus ja sen määrän oletetaan lisääntyvät tulevaisuudessa, sillä ikääntyvien määrä kasvaa globaalisti jatkuvasti. Siksi olisikin erityisen tärkeää, että AD:n patologiaa ymmärrettäisiin paremmin. Parempi patologian ymmärtäminen avaa uusia hoito- sekä ehkäisymenetelmiä ja auttaa aikaisempaan AD:n diagnosointiin, mikä auttaisi vähentämään vakavasti sairastuneiden määrää. Suolistomikrobiomin ja AD:n välisen suhteen löytämisen myötä uusia AD:n hoito- ja ehkäisymenetelmiä on kohdistettu suolistomikrobiomiin. Suolistomikrobiomiin kohdistetut hoitomekanismit ylläpitävät tai palauttavat suolistomikrobiomin tasapainon, jonka avulla ehkäistään AD:n progressiota ja varhaisessa vaiheessa sairauden kehittymistä. Suolistomikrobiomiin kohdistettuina hoitomenetelminä voisi toimia esimerkiksi pro- ja prebiootit, ulosteensiirto sekä suolistomikrobiomiin kohdistuvat AD-lääkkeet
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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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