| 1. |
- Franco, Irene, et al.
(författare)
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Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
- 2019
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer. Results: To analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions. Conclusions: Our analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
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| 2. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Rationale for a Swedish cohort consortium
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.
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| 3. |
- Östh, J, et al.
(författare)
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Keeping Track of My Drinking : Patient Perceptions of Using Smartphone Applications as a Treatment Complement for Alcohol Dependence
- 2024
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Ingår i: Substance Use & Misuse. - : Taylor & Francis. - 1082-6084 .- 1532-2491. ; 59:2, s. 291-299
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol dependence is common, yet highly undertreated. Smartphone applications (apps) have potential to enhance treatment accessibility and effectiveness, however evidence is limited, especially studies focussing on user experiences. The aim was to describe patient perceptions on the usability and acceptability of self-monitoring apps provided as treatment complement for alcohol dependence.Methods: Individual semi-structured interviews were conducted through video or phone calls with 21 participants, recruited from a randomized controlled trial at a dependency clinic in Stockholm. The participants had used two specific apps for self-monitoring consumption ("Glasklart" and "iBAC") during 12 wk prior to the interviews. Data was analyzed using Qualitative Content Analysis.Results: Two domains were identified: 1) Smartphone applications as facilitators to treatment, and 2) Barriers to smartphone application use. Using apps within the treatment context was believed to increase the accuracy of the reported consumption. Participants became more aware of their alcohol problem and described the apps as reinforcers that could increase both the motivation to change and the focus on the problem and commitment to treatment. The apps were further described as helpful to control alcohol consumption. However, app usage was constrained by technical problems, unfit app-specific features and procedures, and alcohol-related shame and stigma.Discussion and Conclusions: Self-monitoring alcohol apps have several beneficial features that can help assess, track, and control alcohol consumption, and improve communication with clinicians. The results indicate they can be useful complements to treatment for patients with alcohol dependence, but their use can be limited by different, foremost technical, issues. Smartphone applications for self-monitoring of alcohol consumption may help provide accurate data, increase consumption awareness, focus, motivation, and perceived control; Smartphone applications for self-monitoring of alcohol consumption are considered helpful complements to alcohol treatment; The use of smartphone applications for self-monitoring of alcohol consumption can be constrained by technical problems, and unfit app-specific features and procedures.
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