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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 4. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 5. |
- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 6. |
- Buli, Benti Geleta
(författare)
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Mental health problems among adolescents in Sweden : Analysis of trends, developmental trajectories, and associated factors
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to investigate trends and trajectories of mental health problems and associated factors among adolescents in Sweden. The project consisted of four studies, with the first presenting trends and the subsequent ones exploring influencing factors. The first two studies used data from SALVe, repeated cross-sectional surveys from 2004 – 2020, while the third used national HBSC data from 2002 – 2018. Study IV was based on data from SALVe cohorts conducted among young people born in 1997 and 1999 where data were collected in four waves every three years from 2012 – 2021. Study I investigated trends in mental health problems among adolescents in Västmanland County, revealing an overall decrease but disparities based on socioeconomic status (SES) and sex. Higher SES was associated with reduced mental health problems, while lower SES showed an increase. Girls exhibited a more pronounced decrease in depressive symptoms and suicidal ideations than boys. Study II, using the same dataset, confirmed these trends and identified school-related factors influencing mental health problems, with improvements correlating with reduced problems in the high SES group. Study III found a significant increase in PSS over time, higher in girls, and linked to lifestyle factors, particularly alcohol drunkenness among high SES adolescents. Study IV focused on cohorts born in 1997 and 1999, exploring the impact of family and peer relationships on depressive and anxiety symptoms among young people.The results indicate that intermediary factors, including school-related factors, lifestyle choices, and social relationships, which vary across SES gradients, are linked to adolescent mental health problems. The associations between these intermediary factors and the mental health problems were, in most cases, influenced by a group of factors, including SES, sex, country of origin, and birth cohort, collectively named structural determinants. These determinants discriminated results between boys and girls, high SES and low SES, Nordic and non-Nordic origin, and the 1997 and 1999 cohorts. This underscores the need for at least two-tiered policy intervention. The first involves an immediate to mid-term response, targeting these intermediary factors with a special focus on the low SES group, girls, and young people with foreign backgrounds. The second entails a long-term policy intervention to narrow the divide.
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| 7. |
- Buli, Benti Geleta, et al.
(författare)
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Trends in adolescent mental health problems 2004–2020 : do sex and socioeconomic status play any role?
- 2023
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Ingår i: Scandinavian Journal of Public Health. - 1403-4948 .- 1651-1905.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aims to investigate trends in four types of adolescent mental health problems; that is, psychosomatic symptoms, depressive symptoms, suicidal ideations, and suicide attempts 2004–2020. A second aim is to investigate the moderating roles of socioeconomic status and sex in these trends.Methods: The analysis is based on repeated cross-sectional data 2004–2020 among grade 9 students in secondary schools in a Swedish county. In total, data from 19,873 students were included in the analysis. We fitted linear and logistic regression equations and used survey-years’ coefficients to estimate the trends. We also estimated the moderating effects of socioeconomic status and sex using interactions between survey year and socioeconomic status and sex, respectively.Results: The trends in all mental health problems declined over time. Through its interaction with survey year, socioeconomic status moderated the trends; psychosomatic symptoms (B = −0.115, P<0.001), depressive symptoms (B = −0.084, P<0.001) and suicidal ideations (odds ratio 0.953, confidence interval 0.924–0.983) significantly declined over time among those with high socioeconomic status. However, socioeconomic status did not have an association with the trend in suicide attempts. Interaction between sex and year of survey was associated with significant decreasing trends in depressive symptoms and suicidal ideations only among girls.Conclusions: Adolescent mental health problems have decreased over time, but only for adolescents with high socioeconomic status, or only in depressive symptoms and suicidal ideations for girls. The results shed light on the growing inequalities in health outcomes across levels of socioeconomic status.
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| 8. |
- Buli, Benti Geleta, et al.
(författare)
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Trends in adolescent mental health problems and the role of lifestyle factors
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background:Adolescent mental health problems are on the rise globally, including in Sweden. One indicator is an increase in psychosomatic symptoms (PSS) over time. Lifestyle factors such as physical activity (PA), diet, smoking, and alcohol consumption may influence the trends in PSS. However, we found limited research on such associations.Methods:This study is based on data collected every four years from nationally representative samples of 15-year-old boys and girls in Sweden (N = 9,196, 50.5% girls), as part of the Health Behavior in School-aged Children (HBSC) study. PSS was measured using a scale developed from the HBSC symptom checklist. We analyzed the trends in PSS from 2002 to 2018 and fitted models to investigate the associations between the trends and lifestyle factors. We included interaction terms between time and each lifestyle factor and fitted separate models for the high and low socioeconomic status (SES) groups.ResultsIn general, the mean scores for PSS increased from 2.26 in 2002 to 2.49 in 2018 (p<.001). Compared to the average mean scores during preceding years, the changes in PSS mean scores at each survey year were also significant in all years except 2010. More frequent breakfast intake, daily consumption of fruits and vegetables, and higher PA were associated with lower PSS mean scores while smoking and alcohol consumption had the opposite association. The only significant interaction (B = .050; CI: .015, ¬ .085; p<.01) was observed in the high SES group, indicating that the increasing trend in PSS was stronger among those who had been drunk once or more in a lifetime, compared to those who had never been drunk.ConclusionsThe results indicate increasing trends in mental health problems among young people in Sweden. Furthermore, the study revealed that alcohol drunkenness was associated with a more substantial rise in PSS over time among those in the high SES group. Further research is needed to understand the reasons behind these findings.
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| 9. |
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| 10. |
- Buli, Benti Geleta, et al.
(författare)
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Trends in mental health problems among Swedish adolescents : Do school-related factors play a role?
- 2024
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Ingår i: PLOS ONE. - 1932-6203. ; 19:3
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Tidskriftsartikel (refereegranskat)abstract
- AimThe aim of this study is to investigate the extent to which school-related factors, such as school liking, participation in decision-making, school-related parental support, teachers’ support, and school physical environment, explain trends in mental health problems. The problems considered are psychosomatic symptoms (PSS), depressive symptoms (DS), suicidal ideations (SI), and suicide attempts (SA) among Swedish adolescents of varying socioeconomic status (SES) from 2004 to 2020.MethodsWe analyzed data collected through repeated cross-sectional surveys from 19,873 15-year-old students at schools in a county in Sweden. Boys and girls each constituted 50% of the participants. We fitted linear and logistic regression models to investigate associations between the school-related factors and trends in mental health problems.ResultsIncreased school-related parental support and school liking were cross-sectionally associated with decreased PSS, DS and SI, with school liking also associated with decreased SA. Conducive school physical environment was also found to be cross-sectionally associated with lower PSS and DS scores. Over time, mental health problems have shown a general increase among adolescents in the low SES group and a decrease among those in the high SES group. While school-related factors explained the improvement in mental health in the high SES group, we found such association only between parental support trends in PSS and DS, along with participation and trends in SA over time among adolescents in the low SES group.ConclusionsThe results show that school-related factors play significant roles in influencing adolescent mental health. The influence, however, varied across SES gradients over time. This suggests that working against inequities in school-related factors would help address inequities in mental health.
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