| 1. |
- Aine, Mattias, et al.
(författare)
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Molecular analyses of triple-negative breast cancer in the young and elderly
- 2021
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer in young adults has been implicated with a worse outcome. Analyses of genomic traits associated with age have been heterogenous, likely because of an incomplete accounting for underlying molecular subtypes. We aimed to resolve whether triple-negative breast cancer (TNBC) in younger versus older patients represent similar or different molecular diseases in the context of genetic and transcriptional subtypes and immune cell infiltration.PATIENTS AND METHODS: In total, 237 patients from a reported population-based south Swedish TNBC cohort profiled by RNA sequencing and whole-genome sequencing (WGS) were included. Patients were binned in 10-year intervals. Complimentary PD-L1 and CD20 immunohistochemistry and estimation of tumor-infiltrating lymphocytes (TILs) were performed. Cases were analyzed for differences in patient outcome, genomic, transcriptional, and immune landscape features versus age at diagnosis. Additionally, 560 public WGS breast cancer profiles were used for validation.RESULTS: Median age at diagnosis was 62 years (range 26-91). Age was not associated with invasive disease-free survival or overall survival after adjuvant chemotherapy. Among the BRCA1-deficient cases (82/237), 90% were diagnosed before the age of 70 and were predominantly of the basal-like subtype. In the full TNBC cohort, reported associations of patient age with changes in Ki67 expression, PIK3CA mutations, and a luminal androgen receptor subtype were confirmed. Within DNA repair deficiency or gene expression defined molecular subgroups, age-related alterations in, e.g., overall gene expression, immune cell marker gene expression, genetic mutational and rearrangement signatures, amount of copy number alterations, and tumor mutational burden did, however, not appear distinct. Similar non-significant associations for genetic alterations with age were obtained for other breast cancer subgroups in public WGS data. Consistent with age-related immunosenescence, TIL counts decreased linearly with patient age across different genetic TNBC subtypes.CONCLUSIONS: Age-related alterations in TNBC, as well as breast cancer in general, need to be viewed in the context of underlying genomic phenotypes. Based on this notion, age at diagnosis alone does not appear to provide an additional layer of biological complexity above that of proposed genetic and transcriptional phenotypes of TNBC. Consequently, treatment decisions should be less influenced by age and more driven by tumor biology.
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| 2. |
- Glodzik, Dominik, et al.
(författare)
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Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Homologous recombination deficiency (HRD) is a defining characteristic in BRCA-deficient breast tumors caused by genetic or epigenetic alterations in key pathway genes. We investigated the frequency of BRCA1 promoter hypermethylation in 237 triple-negative breast cancers (TNBCs) from a population-based study using reported whole genome and RNA sequencing data, complemented with analyses of genetic, epigenetic, transcriptomic and immune infiltration phenotypes. We demonstrate that BRCA1 promoter hypermethylation is twice as frequent as BRCA1 pathogenic variants in early-stage TNBC and that hypermethylated and mutated cases have similarly improved prognosis after adjuvant chemotherapy. BRCA1 hypermethylation confers an HRD, immune cell type, genome-wide DNA methylation, and transcriptional phenotype similar to TNBC tumors with BRCA1-inactivating variants, and it can be observed in matched peripheral blood of patients with tumor hypermethylation. Hypermethylation may be an early event in tumor development that progress along a common pathway with BRCA1-mutated disease, representing a promising DNA-based biomarker for early-stage TNBC.
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| 3. |
- Borg, Farhana, Lektor, 1967-, et al.
(författare)
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A whole (pre)school approach to sustainability in eco- and non-eco-certified preschools in Sweden : Principals’ views and attitudes
- 2023
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Ingår i: Konferens i pedagogiskt arbete, 2023. - Linköping : Linköping University Electronic Press. - 9789180752831 - 9789180752848 ; , s. 22-23
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Konferensbidrag (refereegranskat)abstract
- Although a whole school approach (WSA) to sustainability has been described as one of the most meaningful education approaches, the concept of WSA has not yet been widely explored within the context of preschool education, where the play, learning, and care are preconditions for a wholeness in childhood. The concept of the WSA considers raising quality and standard across entire education institution (Henderson & Tilbury, 2004). This approach also emphasizes the needs for (pre)school to engage children, teachers, parents, and the wider community in sustainability (Mogren, Gericke & Scherp, 2019). The principals have important roles to play in reforming and prioritizing preschools activities towards sustainability (Borg & Vinterek, 2020). This paper explores 50 principals’ views and attitudes towards sustainability from a WSA perspective. Using randomized sampling, the principals were selected from 25 eco-certified and 25 non-eco-certified preschools in 25 municipalities in Sweden, out of 290. A questionnaire was utilized to collect demographic information about the preschools, number of children, number of qualified teachers, principals’ attitudes towards preschool’s activities with sustainability, and also an open-ended question about how the principals themselves integrate sustainability in their planning of preschool activities and what they actually do. The qualitative data was analyzed by using Wals and Mathie’s (2022) six component Whole School Approach Flower Model. The components are: 1. Vision, ethos, leadership and coordination; 2. Institutional practices; 3. Pedagogy and learning; 4. Curriculum; 5. Community connections; and 6. Capacity building. The components were adapted and operationalized within a preschool context. The quantitative data was analyzed by principal component analysis (PCA) in the SIMCA statistical software (Umetrics 2020). This study is a part of a project, “Eco-certified preschools and children’s learning for sustainability: Researching holistic outcomes of preschool education for sustainability (HOPES)” (Swedish Research Council, Dnr. 2018-04445). The analyses will be completed by June, 2023. ReferencesBorg, F., & Vinterek, M. (2020). Principals´ Views on and Descriptions of Preschool Education for Sustainable Development. Journal of Applied Technical and Educational Sciences, 10(2), 18-40. doi:10.24368/jates.v10i2.170Henderson, K., & Tilbury, D. (2004). Whole school approaches to sustainability: An international review of sustainable school programs. Report prepared by Macquarie University for the Australian Government Department of the Environment and Heritage. Sydney.Mogren, A., Gericke, N., & Scherp, H.-Å. (2019). Whole school approaches to education for sustainable development: a model that links to school improvement. Environmental Education Research, 25(4), 508-531. https://doi:10.1080/13504622.2018.1455074 Umetrics. (2020). SIMCA-P+. In (Version 16.0) [Computer software]. Sartorius Stedim Inc. https://www.sartorius.com/en/products/process-analytical-technology/data-analytics-software/mvda-software/simca?gclid=Cj0KCQiAvvKBBhCXARIsACTePW-oD9sm_Ng1dgNBivHH9GFSApdp5wo2G0EDOydryNnzZQ-20Xoj_vIaApIwEALw_wcB
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| 4. |
- Borg, Farhana, Lektor, 1967-, et al.
(författare)
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Methodological and ethical issues when interviewing preschool children : Experiences from a study on sustainability in Sweden
- 2023
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Ingår i: 31st EECERA ANNUAL CONFERENCE. Children’s Curiosity, Agency and Participation: Challenges for Professional Action and Development. ; , s. 135-135
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Konferensbidrag (refereegranskat)abstract
- To contribute to the methodological and ethical discourse on children’sparticipation in research on complex issues, this case-study critically discusses experiences from a large-scale randomized interview study about preschool education for sustainability in Sweden. Young children’s ability to express their views has been subject to debate, resulting in them often being excluded asresearch participants. Hence, age-appropriate methodological approaches are needed to ensure their participation.This study draws from Josefsson and Wall’s(2020) concept of children’s “empowered inclusion” and Lundy’s (2007) model of voice, space, audience, and influence.Employing a qualitative case-studyapproach, methodological approaches and ethical considerations and experiences of a randomized study are scrutinized. A total of 403 children from 50 preschools were interviewed about sustainability using illustrations. An interview instrument was developed and pretested in two iterations. Data were analyzed thematically. The Swedish Ethical Review Authority did not raise any objection to the interview study. Consent to participate was collected from parents and children.They were informed that the children could withdraw at any time if they wanted. The findings demonstrate that research with young children can be undertaken in an ethically acceptable manner. The use of illustrations was helpful in creating a friendly environment and supporting children’s understanding of complex issues. Individual and pair interviews were effective while group interviews were problematic. Children’s attention dropped after 12-15 minutes. These findings suggest that preschool children can express their views on important matters under ethically acceptable and methodologically appropriate conditions.
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| 7. |
- Christiansen, Ditte M., 1990-, et al.
(författare)
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High-resolution data are necessary to understand the effects of climate on plant population dynamics of a forest herb
- 2024
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Ingår i: Ecology. - 0012-9658 .- 1939-9170. ; 105:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate is assumed to strongly influence species distribution and abundance. Although the performance of many organisms is influenced by the climate in their immediate proximity, the climate data used to model their distributions often have a coarse spatial resolution. This is problematic because the local climate experienced by individuals might deviate substantially from the regional average. This problem is likely to be particularly important for sessile organisms like plants and in environments where small-scale variation in climate is large. To quantify the effect of local temperature on vital rates and population growth rates, we used temperature values measured at the local scale (in situ logger measures) and integral projection models with demographic data from 37 populations of the forest herb Lathyrus vernus across a wide latitudinal gradient in Sweden. To assess how the spatial resolution of temperature data influences assessments of climate effects, we compared effects from models using local data with models using regionally aggregated temperature data at several spatial resolutions (≥1 km). Using local temperature data, we found that spring frost reduced the asymptotic population growth rate in the first of two annual transitions and influenced survival in both transitions. Only one of the four regional estimates showed a similar negative effect of spring frost on population growth rate. Our results for a perennial forest herb show that analyses using regionally aggregated data often fail to identify the effects of climate on population dynamics. This emphasizes the importance of using organism-relevant estimates of climate when examining effects on individual performance and population dynamics, as well as when modeling species distributions. For sessile organisms that experience the environment over small spatial scales, this will require climate data at high spatial resolutions.
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| 8. |
- Dihge, Looket, et al.
(författare)
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Prediction of lymph node metastasis in breast cancer by gene expression and clinicopathological models: Development and validation within a population based cohort.
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 25:21, s. 6368-6381
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: More than 70% of patients with breast cancer present with node-negative disease, yet all undergo surgical axillary staging. We aimed to define predictors of nodal metastasis using clinicopathological characteristics (CLINICAL), gene expression data (GEX), and mixed features (MIXED) and to identify patients at low risk of metastasis who might be spared sentinel lymph node biopsy (SLNB).Experimental Design: Breast tumors (n = 3,023) from the population-based Sweden Cancerome Analysis Network–Breast initiative were profiled by RNA sequencing and linked to clinicopathologic characteristics. Seven machine-learning models present the discriminative ability of N0/N+ in development (n = 2,278) and independent validation cohorts (n = 745) stratified as ER+HER2−, HER2+, and TNBC. Possible SLNB reduction rates are proposed by applying CLINICAL and MIXED predictors.Results: In the validation cohort, the MIXED predictor showed the highest area under ROC curves to assess nodal metastasis; AUC = 0.72. For the subgroups, the AUCs for MIXED, CLINICAL, and GEX predictors ranged from 0.66 to 0.72, 0.65 to 0.73, and 0.58 to 0.67, respectively. Enriched proliferation metagene and luminal B features were noticed in node-positive ER+HER2− and HER2+ tumors, while upregulated basal-like features were observed in node-negative TNBC tumors. The SLNB reduction rates in patients with ER+HER2− tumors were 6% to 7% higher for the MIXED predictor compared with the CLINICAL predictor accepting false negative rates of 5% to 10%.Conclusions: Although CLINICAL and MIXED predictors of nodal metastasis had comparable accuracy, the MIXED predictor identified more node-negative patients. This translational approach holds promise for development of classifiers to reduce the rates of SLNB for patients at low risk of nodal involvement.
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