Browsing by Subject "VERSION"

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  • Iqbal, Sumaiya; Perez-Palma, Eduardo; Jespersen, Jakob B.; May, Patrick; Hoksza, David; Heyne, Henrike O.; Ahmed, Shehab S.; Rifat, Zaara T.; Rahman, M. Sohel; Lage, Kasper; Palotie, Aarno; Cottrell, Jeffrey R.; Wagner, Florence F.; Daly, Mark J.; Campbell, Arthur J.; Lal, Dennis (2020)
    Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variations on protein structure and function being especially challenging. Here we characterize the three-dimensional (3D) amino acid positions affected in pathogenic and population variants from 1,330 disease-associated genes using over 14,000 experimentally solved human protein structures. By measuring the statistical burden of variations (i.e., point mutations) from all genes on 40 3D protein features, accounting for the structural, chemical, and functional context of the variations' positions, we identify features that are generally associated with pathogenic and population missense variants. We then perform the same amino acid-level analysis individually for 24 protein functional classes, which reveals unique characteristics of the positions of the altered amino acids: We observe up to 46% divergence of the class-specific features from the general characteristics obtained by the analysis on all genes, which is consistent with the structural diversity of essential regions across different protein classes. We demonstrate that the function-specific 3D features of the variants match the readouts of mutagenesis experiments for BRCA1 and PTEN, and positively correlate with an independent set of clinically interpreted pathogenic and benign missense variants. Finally, we make our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step toward translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the variants' pathogenicity in terms of the perturbed molecular mechanisms.
  • Svedholm-Häkkinen, Annika M.; Halme, Saara; Lindeman, Marjaana (2018)
    Background/Objective: Empathizing-Systemizing Theory suggests that low empathizing and high systemizing are linked to autistic traits in the general population. Evidence from autistic individuals is convincing, but more research in the normal population is needed. Method: We conducted two surveys (N=3,345) investigating the relationships between empathizing, systemizing and autistic traits in the general population, using a large variety of self-report instruments and direct performance tests. Results: Strong connections between autistic symptoms, empathizing, and systemizing were found using commonly used measures (Autism Quotient, Systemizing Quotient and Empathizing Quotient). Other measures on empathizing and systemizing found the connections that E-S-theory predicts, but the correlations were a lot more modest. Weak empathizing was related to autism's social difficulties, while systemizing was linked to non-social aspects of autism. Conclusions: The present results support the main tenets of empathizing-systemizing theory, but suggest that earlier findings might be inflated due to overlapping items in the most common assessment instruments. (c) 2017 Asociacion Espanola de Psicologia Conductual. Published by Elsevier Espana, S.L.U.
  • Tolokonnikov, S. V.; Borzov, I. N.; Kortelainen, Markus; Lutostansky, Yu. S.; Saperstein, E. E. (2016)
    Fayans energy density functional (EDF) FaNDF(0) has been applied to the nuclei around uranium region. Ground state characteristics of the Th, U and Pu isotopic chains, up to the two-neutron drip line, are found and compared with predictions from several Skyrme EDFs. The two-neutron drip line is found for FaNDF(0), SLy4 and SkM* EDFs for a set of elements with even proton number, from Pb up to Fm.
  • Konstantinou, Despoina; Popin, Rafael; Fewer, David P.; Sivonen, Kaarina; Gkelis, Spyros (2021)
    Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products.
  • Simonsen, Nina; Koponen, Anne M.; Suominen, Sakari (2018)
    Background: To meet the challenges of the rising prevalence of chronic diseases, such as type 2 diabetes, new approaches to healthcare delivery have been initiated; among these the influential Chronic Care Model (CCM). Valid instruments are needed to evaluate the public health impact of these frameworks in different countries. The Patient Assessment of Chronic Illness Care (PACIC) is a 20-item quality of care measure that, from the perspective of the patient, measures the extent to which care is congruent with the CCM. The aim of this study was to evaluate the psychometric properties of the Finnish translation of the PACIC questionnaire, in terms of validity and reliability, in a large register-based sample of patients with type 2 diabetes. Method: The PACIC items were translated into Finnish in a standardized forward-backward procedure, followed by a cross-sectional survey among patients with type 2 diabetes (response rate 56%; n = 2866). We assessed the Finnish version of the PACIC scale for the following psychometric properties: content validity, internal consistency reliability, convergent and construct validity. We also present descriptive data on total scale as well as predetermined subscale levels. Results: The item-response on the PACIC scale was high with only small numbers of missing data (0.5-1.1%). Ceiling effects were low (0.3-5.3%) whereas floor effects were over 20% for two of the predetermined subscales (problem solving and follow-up/coordination). The total PACIC scale showed a reasonable distribution and excellent internal consistency (alpha 0.94) while the internal consistency of the subscales were at least acceptable (0.74-0.86). The principal component analysis identified a two-or three-factor solution instead of the proposed five-dimensional. In other respects, the PACIC scale showed the hypothesized relationships with quality of care and outcome measures, thus demonstrating convergent and construct validity. Conclusion: A Finnish version of the PACIC scale is now validated in the primary care setting among patients with type 2 diabetes. The findings suggest comparable psychometric properties of the Finnish scale as of the original English instrument and earlier translations, and reasonable levels of validity and reliability.
  • Ahlberg, Mats Steinholtz; Adami, Hans-Olov; Beckmann, Kerri; Bertilsson, Helena; Bratt, Ola; Cahill, Declan; Egevad, Lars; Garmo, Hans; Holmberg, Lars; Johansson, Eva; Rannikko, Antti; Van Hemelrijck, Mieke; Jäderling, Fredrik; Wassberg, Cecilia; Åberg, Ulrika W. N.; Bill-Axelson, Anna (2019)
    Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, 0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.
  • Wailan, Alexander M.; Coll, Francesc; Heinz, Eva; Tonkin-Hill, Gerry; Corander, Jukka; Feasey, Nicholas A.; Thomson, Nicholas R. (2019)
    The ability to distinguish different circulating pathogen clones from each other is a fundamental requirement to understand the epidemiology of infectious diseases. Phylogenetic analysis of genomic data can provide a powerful platform to identify lineages within bacterial populations, and thus inform outbreak investigation and transmission dynamics. However, resolving differences between pathogens associated with low-variant (LV) populations carrying low median pairwise single nucleotide variant (SNV) distances remains a major challenge. Here we present rPinecone, an R package designed to define sub-lineages within closely related LV populations. rPinecone uses a root-to-tip directional approach to define sub-lineages within a phylogenetic tree according to SNV distance from the ancestral node. The utility of this software was demonstrated using both simulated outbreaks and real genomic data of two LV populations: a hospital outbreak of methicillin-resistant Staphylococcus aureus and endemic Salmonella Typhi from rural Cambodia. rPinecone identified the transmission branches of the hospital outbreak and geographically confined lineages in Cambodia. Sub-lineages identified by rPinecone in both analyses were phylogenetically robust. It is anticipated that rPinecone can be used to discriminate between lineages of bacteria from LV populations where other methods fail, enabling a deeper understanding of infectious disease epidemiology for public health purposes.
  • Oshukova, Svetlana; Kaltiala-Heino, Riittakerttu; Hillege, Sanne; de Ruiter, Corine; Joffe, Grigori; Miettunen, Jouko; Marttila, Riikka; Marttunen, Mauri; Kaivosoja, Matti; Lindberg, Nina (2016)
    Background: Culture-related differences in psychopathic traits have been reported for adults, but for adolescents such knowledge is lacking. The aim of this cross-national study was to compare self-reported psychopathic traits between Finnish and Dutch samples of mid-adolescent community youth. Methods: The Youth Psychopathic traits Inventory (YPI) was filled in by 372 Finnish and 474 Dutch 15- to 16-year-old pupils. As gender-specific differences exist in psychopathic traits, we analyzed the data separately for boys and girls. Results: Dutch boys scored significantly higher than Finnish boys on total and all dimensional scores of the YPI as well as on most sub-dimensional scores. Dutch girls scored significantly higher than Finnish girls on the Affective dimension and on the two corresponding sub-dimensions: remorselessness and callousness. Finnish girls scored significantly higher on grandiosity, which loads to the Interpersonal dimension of the YPI. Conclusions: Our findings suggest that culture influences the manifestation of psychopathic traits already in adolescence and that this relation is more prominent in boys.
  • Moseholm, Ellen; Fetters, Micheal D.; Aho, Inka; Mellgren, Åsa; Johansen, Isik S.; Storgaard, Merete; Pedersen, Gitte; Katzenstein, Terese L.; Weis, Nina (2019)
    Introduction The success of combination antiretroviral therapy has decreased the risk of perinatal HIV transmission and normalised pregnancy in women living with HIV (WLWH). Despite these advances, WLWH still face complex medical and psychosocial issues during pregnancy and postpartum, and there is a gap of knowledge on the experiences of becoming and being a mother living with HIV in today's context. The overall aim of this study is to investigate psychosocial outcomes and experiences of WLWH in Scandinavia during pregnancy and early motherhood. Methods and analysis This is a multicentre longitudinal convergent mixed methods study consisting of a quantitative survey study, a qualitative interview study and a mixed methods analysis. The survey study aims to examine psychosocial outcomes of WLWH across the pregnancy - postpartum trajectory. Participants are pregnant WLWH living in Scandinavia. Two control groups of HIV-negative pregnant women and non-pregnant WLWH are also included. Data is collected in the third trimester, 3 and 6 months postpartum using standardised questionnaires. Statistical analysis will assess changes over time and identify predictors of adverse outcomes. The interview study seeks to understand experiences of pregnancy and becoming a mother while living with HIV. Pregnant WLWH who are enrolled in the survey study will be asked to participate in individual interviews in the third trimester and 6 months postpartum. Data will be analysed using narrative analysis. The survey and interview results will be merged in a mixed methods analysis to assess confirmation, expansion or discordance between the data sets. Ethics and dissemination Approval from the Danish Data Protection Agency (VD-2018-253), and the Finnish and Swedish Ethics Committees have been obtained (HUS/1330/2019 and Dnr: 2019-04451, respectively). Study results will be disseminated to patient organisations, through publications in peer-reviewed journals and at scientific conferences.
  • Mustelin, Linda; Kärkkäinen, Ulla; Kaprio, Jaakko; Keski-Rahkonen, Anna (2016)
    Background: We assessed whether the Eating Disorder Inventory (EDI) is suitable for screening binge eating disorder (BED) in young women. Method: Young women (N = 2825) from the 1975-79 birth cohorts of Finnish twins were assessed by questionnaires, including subscales of the EDI. For a subset of women (N = 548), we established DSM-5 diagnoses of BED; 16 women had lifetime BED. We compared screening properties of the EDI scales using receiver operating characteristic (ROC) analysis, determined optimal cutoff points, and calculated sensitivities and specificities. Results: The best screen for DSM-5 BED was the global score of three subscales (Bulimia, Drive for Thinness, Body Dissatisfaction) with an area under the curve (AUC) of 0.86. Its sensitivity was 87% and specificity 76% at cutoff >= 21. Three individual subscales had acceptable screening properties: Bulimia (AUC 0.83; sensitivity 80%, specificity 78% at cutoff >= 2), Drive For Thinness (AUC 0.82; sensitivity 87%, specificity 72% at cutoff >= 7), and Body Dissatisfaction (AUC 0.81; sensitivity 93%, specificity 60% at cutoff >= 8). Conclusion: The EDI performed well as a screening tool for BED in our community-based sample of young twin women. Future studies should assess its value in other populations and in clinical settings. (C) 2016 Elsevier Ltd. All rights reserved.
  • Kotanen, Petra; Kainu, Annette; Brander, Pirkko; Bergman, Paula; Lehtomäki, Anu; Kreivi, Hanna-Riikka (2020)
    Abstract Introduction Chronic respiratory insufficiency impacts patients? lives and reduces quality of life. The Severe Respiratory Insufficiency (SRI) questionnaire examines health-related quality of life and is designed specifically for patients receiving home mechanical ventilation (HMV) for chronic respiratory failure (CRF). Objectives The aim of this study was to validate the Finnish version of the SRI and study its reproducibility in patients with CRF. Methods Our 74 patients receiving HMV or long-term oxygen treatment for CRF or both completed the SRI and St George?s Respiratory questionnaires (SGRQ) three times (at baseline, and then one week and one month later). Reliability and validity of the questionnaires was analyzed with Cronbach?s alpha and intraclass correlation coefficient. Patients were prospectively followed-up for five years, with data collected on their use of hospital services and mortality. Results Cronbach?s alpha in the SRI ranged from 0.67 to 0.88 and was >0.7 on all subscales except the ?attendant symptoms and sleep?. On four subscales, Cronbach?s alpha was >0.8, and on the summary scale, 0.95. The SRI showed high correlation with SGRQ. Both tests showed good reproducibility. During the five-year follow-up, 27 (36%) patients died. Conclusions The Finnish SRI proved valid, reliable, and reproducible. Its psychometric properties were good and similar to those of the original questionnaire and of other validation studies.