Menetelmiä mielenkiintoisten solmujen löytämiseen verkostoista

With the increasing amount of graph-structured data available, finding interesting objects, i.e., nodes in graphs, becomes more and more important. In this thesis we focus on finding interesting nodes and sets of nodes in graphs or networks. We propose several definitions of node interestingness as well as different methods to find such nodes. Specifically, we propose to consider nodes as interesting based on their relevance and non-redundancy or representativeness w.r.t. the graph topology, as well as based on their characterisation for a class, such as a given node attribute value. Identifying nodes that are relevant, but non-redundant to each other is motivated by the need to get an overview of different pieces of information related to a set of given nodes. Finding representative nodes is of interest, e.g. when the user needs or wants to select a few nodes that abstract the large set of nodes. Discovering nodes characteristic for a class helps to understand the causes behind that class. Next, four methods are proposed to find a representative set of interesting nodes. The first one incrementally picks one interesting node after another. The second iteratively changes the set of nodes to improve its overall interestingness. The third method clusters nodes and picks a medoid node as a representative for each cluster. Finally, the fourth method contrasts diverse sets of nodes in order to select nodes characteristic for their class, even if the classes are not identical across the selected nodes. The first three methods are relatively simple and are based on the graph topology and a similarity or distance function for nodes. For the second and third, the user needs to specify one parameter, either an initial set of k nodes or k, the size of the set. The fourth method assumes attributes and class attributes for each node, a class-related interesting measure, and possible sets of nodes which the user wants to contrast, such as sets of nodes that represent different time points. All four methods are flexible and generic. They can, in principle, be applied on any weighted graph or network regardless of what nodes, edges, weights, or attributes represent. Application areas for the methods developed in this thesis include word co-occurrence networks, biological networks, social networks, data traffic networks, and the World Wide Web. As an illustrating example, consider a word co-occurrence network. There, finding terms (nodes in the graph) that are relevant to some given nodes, e.g. branch and root, may help to identify different, shared contexts such as botanics, mathematics, and linguistics. A real life application lies in biology where finding nodes (biological entities, e.g. biological processes or pathways) that are relevant to other, given nodes (e.g. some genes or proteins) may help in identifying biological mechanisms that are possibly shared by both the genes and proteins.Väitöskirja käsittelee verkostojen louhinnan menetelmiä. Sen tavoitteena on löytää mielenkiintoisia tietoja painotetuista verkoista. Painotettuna verkkona voi tarkastella esim. tekstiainestoja, biologisia ainestoja, ihmisten välisiä yhteyksiä tai internettiä. Tällaisissa verkoissa solmut edustavat käsitteitä (esim. sanoja, geenejä, ihmisiä tai internetsivuja) ja kaaret niiden välisiä suhteita (esim. kaksi sanaa esiintyy samassa lauseessa, geeni koodaa proteiinia, ihmisten ystävyyksiä tai internetsivu viittaa toiseen internetsivuun). Kaarten painot voivat vastata esimerkiksi yhteyden voimakuutta tai luotettavuutta. Väitöskirjassa esitetään erilaisia verkon rakenteeseen tai solmujen attribuutteihin perustuvia määritelmiä solmujen mielenkiintoisuudelle sekä useita menetelmiä mielenkiintoisten solmujen löytämiseksi. Mielenkiintoisuuden voi määritellä esim. merkityksellisyytenä suhteessa joihinkin annettuihin solmuihin ja toisaalta mielenkiintoisten solmujen keskinäisenä erilaisuutena. Esimerkiksi ns. ahneella menetelmällä voidaan löytää keskenään erilaisia solmuja yksi kerrallaan. Väitöskirjan tuloksia voidaan soveltaa esimerkiksi tekstiaineistoa käsittelemällä saatuun sanojen väliseen verkostoon, jossa kahden sanan välillä on sitä voimakkaampi yhteys mitä useammin ne tapaavat esiintyä keskenään samoissa lauseissa. Sanojen erilaisia käyttöyhteyksiä ja jopa merkityksiä voidaan nyt löytää automaattisesti. Jos kohdesanaksi otetaan vaikkapa "juuri", niin siihen liittyviä mutta keskenään toisiinsa liittymättömiä sanoja ovat "puu" (biologinen merkitys: kasvin juuri), "yhtälö" (matemaattinen merkitys: yhtälön ratkaisu eli juuri) sekä "indoeurooppalainen" (kielitieteellinen merkitys: sanan vartalo eli juuri). Tällaisia menetelmiä voidaan soveltaa esimerkiksi hakukoneessa: sanalla "juuri" tehtyihin hakutuloksiin sisällytetään tuloksia mahdollisimman erilaisista käyttöyhteyksistä, jotta käyttäjän tarkoittama merkitys tulisi todennäköisemmin katetuksi hakutuloksissa. Merkittävä sovelluskohde väitöskirjan menetelmille ovat biologiset verkot, joissa solmut edustavat biologisia käsitteitä (esim. geenejä, proteiineja tai sairauksia) ja kaaret niiden välisiä suhteita (esim. geeni koodaa proteiinia tai proteiini on aktiivinen tietyssä sairauksessa). Menetelmillä voidaan etsiä esimerkiksi sairauksiin vaikuttavia biologisia mekanismeja paikantamalla edustava joukko sairauteen ja siihen mahdollisesti liittyviin geeneihin verkostossa kytkeytyviä muita solmuja. Nämä voivat auttaa biologeja ymmärtämään geenien ja sairauden mahdollisia kytköksiä ja siten kohdentamaan jatkotutkimustaan lupaavimpiin geeneihin, proteiineihin tms. Väitöskirjassa esitetyt solmujen mielenkiintoisuuden määritelmät sekä niiden löytämiseen ehdotetut menetelmät ovat yleispäteviä ja niitä voi soveltaa periaatteessa mihin tahansa verkkoon riippumatta siitä, mitä solmut, kaaret tai painot edustavat. Kokeet erilaisilla verkoilla osoittavat että ne löytävät mielenkiintoisia solmuja

Finding representative nodes in probabilistic graphs

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A Model for Mining Relevant and Non-redundant Information

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Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial

Background Early cognitive intervention is the only routine therapeutic approach used for amelioration of intellectual deficits in individuals with Down's syndrome, but its effects are limited. We hypothesised that administration of a green tea extract containing epigallocatechin-3-gallate (EGCG) would improve the effects of non-pharmacological cognitive rehabilitation in young adults with Down's syndrome.; Methods We enrolled adults (aged 16-34 years) with Down's syndrome from outpatient settings in Catalonia, Spain, with any of the Down's syndrome genetic variations (trisomy 21, partial trisomy, mosaic, or translocation) in a double-blind, placebo-controlled, phase 2, single centre trial (TESDAD). Participants were randomly assigned at the IMIM-Hospital del Mar Medical Research Institute to receive EGCG (9 mg/kg per day) or placebo and cognitive training for 12 months. We followed up participants for 6 months after treatment discontinuation. We randomly assigned participants using random-number tables and balanced allocation by sex and intellectual quotient. Participants, families, and researchers assessing the participants were masked to treatment allocation. The primary endpoint was cognitive improvement assessed by neuropsychologists with a battery of cognitive tests for episodic memory, executive function, and functional measurements. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01699711.; Findings The study was done between June 5, 2012, and June 6, 2014. 84 of 87 participants with Down's syndrome were included in the intention-to-treat analysis at 12 months (43 in the EGCG and cognitive training group and 41 in the placebo and cognitive training group). Differences between the groups were not significant on 13 of 15 tests in the TESDAD battery and eight of nine adaptive skills in the Adaptive Behavior Assessment System II (ABAS-II). At 12 months, participants treated with EGCG and cognitive training had significantly higher scores in visual recognition memory (Pattern Recognition Memory test immediate recall, adjusted mean difference: 6.23 percentage points [95% CI 0.31 to 12.14], p=0.039; d 0.4 [0.05 to 0.84]), inhibitory control (Cats and Dogs total score, adjusted mean difference: 0.48 [0.02 to 0.93], p=0.041; d 0.28 [0.19 to 0.74]; Cats and Dogs total response time, adjusted mean difference: -4.58 s [-8.54 to -0.62], p=0.024; d -0.27 [-0.72 to -0.20]), and adaptive behaviour (ABAS-II functional academics score, adjusted mean difference: 5.49 [2.13 to 8.86], p=0.002; d 0.39 [-0.06 to 0.84]). No differences were noted in adverse effects between the two treatment groups.; Interpretation EGCG and cognitive training for 12 months was significantly more effective than placebo and cognitive training at improving visual recognition memory, inhibitory control, and adaptive behaviour. Phase 3 trials with a larger population of individuals with Down's syndrome will be needed to assess and confirm the long-term efficacy of EGCG and cognitive training.; Funding Jerome Lejeune Foundation, Instituto de Salud Carlos III FEDER, MINECO, Generalitat de Catalunya.Peer ReviewedPostprint (author's final draft

Effect of epigallocatechin gallate on the body composition and lipid profile of down syndrome individuals: implications for clinical management

© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Peer ReviewedPostprint (author's final draft

Health Related Quality of Life and Return to Work After Minor Extremity Injuries: a Longitudinal Study Comparing Upper Versus Lower Extremity Injuries

Purpose: To investigate the impact on health related quality of life (HRQL) during the first year after minor extremity injury and to determine whether there is a difference in recovery patterns and return to work between upper extremity injuries (UEI) and lower extremity injuries (LEI). Method: A total of 181 adults’ age 18 years or older randomly selected from patients admitted to an emergency department with minor injuries were studied. HRQL was measured using the Functional Status Questionnaire (FSQ) at 1–2 weeks, 3, 6, and 12-months post-injury. Pre-injury FSQ scores were measured retrospectively at admission. A quasi-least square (QLS) model was constructed to examine differences of FSQ scores at each measuring point for UEI and LEI. Results: Fractures of the knee/lower leg (25%) were the most frequently injured body area. Slips or falls (57%) and traffic-related events (22%) were the most common injury causes. The mean ISS was 4.2 (SD 0.86). Both groups had significant declines in the FSQ scores physical and social functioning at 1–2 weeks after injury. Patients with UEI made larger improvements in the first 3 months post-injury versus patients with LEI whose improvements extended over the first 6 months. None of the groups reached the pre-injury FSQ scores during the first post-injury year except in the subscale work performance where UEI exceeded the pre-injury scores. At 12 months post-injury, significant lower FSQ scores remained in the LEI group compared to the UEI group in intermediate activities of daily living (p = 0.036, d 0.4) and work performance (p = 0.004, d 0.7). The return to work at 3 months and 12 months were 76% and 88% for UEI and 58% and 77% for LEI. No significant differences were found between groups in the FSQ scale mental health and social interaction. Conclusions: LEI had the highest impact on HRQL and return to work during the first year which exceeded the consequences of UEI. These findings contribute to the information about the consequences of injury in order to give sufficient prognostic information to patients and different stakeholders. Future investigations should aim to investigate specific minor extremity injuries and identify factors that facilitate recovery and return to work

Semantic Verbal Fluency Pattern, Dementia Rating Scores and Adaptive Behavior Correlate With Plasma Aβ Concentrations in Down Syndrome Young Adults

Down syndrome (DS) is an intellectual disability (ID) disorder in which language and specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer's disease (AD), including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong AD predictor being the semantic verbal fluency task (SVFT) a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP) and the biological amyloidosis markers in DS. In the current study, we used the SVFT in young adults with DS to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR), the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and plasma levels of Aβ peptides (Aβ and Aβ), as a potent biomarker of AD. In DS, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ concentrations, a higher DMR score and impaired communication skills (ABAS-II). The total word production and switching ability in SVFT were good indicators of plasma Aβ concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with DS

SegMine workflows for semantic microarray data analysis in Orange4WS

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Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study)

Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics