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- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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| 3. |
- Dimdins, Girts, et al.
(författare)
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Worldviews and Values as Bases for Political Orientations
- 2023
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Ingår i: International Review of Social Psychology (IRSP). - : Ubiquity Press, Ltd.. - 2397-8570. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- This study used structural equation modelling to test how political orientations (self-reported placement on socially liberal-conservative and economically left-right continuums) could be predicted from basic worldviews (a generally humanistic vs. normativistic orientation) and basic personal values (concepts pertaining to desirable end states or behaviors) in conjunction with core political values (normative principles about functioning of society) in a population sample from Sweden. In general, political orientation was much more strongly predicted by social-focus values (conservation and self-transcendence), and only weakly predicted by personal-focus values (self-enhancement and openness to change). The results also showed that basic personal values in conjunction with core political values mediated the relationship between basic worldviews and political orientation.
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| 5. |
- Sandgren, Maria, 1963-
(författare)
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How modes of instrumental practice are distributed in three musical genres and among vocalists and instrumentalists at music colleges
- 2019
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Ingår i: Psychology of Music. - : Sage Publications. - 0305-7356 .- 1741-3087. ; 47:5, s. 767-778
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigates whether past and present instrumental practices differ across musical genres (jazz, folk music, classical music) and vocalists in relation to instrumentalists ( N = 108). New findings were that vocalists and instrumentalists differed significantly in all practice experiences ( p < .05–.001), whereas fewer differences were found across genres. In line with previous research, classical musicians engaged more in solitary practice than folk music and jazz musicians did ( p < .001), yet jazz and folk music students practiced more in ensemble compared to classical musicians ( p < .05). In addition, the results contrasted with the general view of solitary practice as a demanding and unpleasant activity, as all groups of music students found solitary practice to be a more positive than negative experience. Future studies are warranted to more closely and empirically investigate vocalists’ practice habits, and to examine how emotions are related to instrumental practicing in music education.
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| 6. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.
- 2023
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Ingår i: JCO Precision Oncology (JCO PO). - : American Society of Clinical Oncology. - 2473-4284. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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