| 1. |
- Clark, M. S., et al.
(author)
-
Multi-omics for studying and understanding polar life
- 2023
-
In: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14
-
Journal article (peer-reviewed)abstract
- Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss ‘omics’ approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.
|
|
| 2. |
- Pilheden, M., et al.
(author)
-
Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia
- 2022
-
In: Hemasphere. - : Ovid Technologies (Wolters Kluwer Health). - 2572-9241. ; 6:10
-
Journal article (peer-reviewed)abstract
- Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3(D835H) or NRAS(G13D/G12S) mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
|
|
| 3. |
- Arad-Cohen, Nira, et al.
(author)
-
Supportive care in pediatric acute myeloid leukemia:Expert-based recommendations of the NOPHO-DB-SHIP consortium
- 2022
-
In: Expert Review of Anticancer Therapy. - : Taylor & Francis Group. - 1473-7140 .- 1744-8328. ; 22:11, s. 1183-1196
-
Research review (peer-reviewed)abstract
- Introduction Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. Area covered The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. Expert opinion Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome.
|
|
| 4. |
- Cooke, Audrey, et al.
(author)
-
Identifying the nonverbal mathematical exploration in preverbal children playing with a commercial toy
- 2022
-
In: Bringing Nordic mathematics education into the future. - : Svensk förening för MatematikDidaktisk Forskning - SMDF. ; , s. 33-40
-
Conference paper (peer-reviewed)abstract
- Young children often engage with commercial toys, many of which are now connected to a television or online video program that the children (and their caregivers) can watch. Children who are preverbal are often engaged (and targeted) with these toys, benefitting with a range of learnings and demonstrations of understandings. This paper uses 360-degree videos to explore the learnings and understandings demonstrated when a preverbal child engages with a commercial toy with an educator. The 360-degree video shows the preverbal child’s behaviours, both in response to the educator’s speech and actions and self-initiated. Children were observed engaged in events, made up of behaviours that were delineated into actions to help the researchers identify what mathematical exploration and understandings each child may demonstrate. Of particular interest is the mathematical understandings and exploration that the child may demonstrated via their actions.
|
|
| 5. |
- Enshaei, Amir, et al.
(author)
-
A validated novel continuous prognostic index to deliver stratified medicine in pediatric acute lymphoblastic leukemia
- 2020
-
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 135:17, s. 1438-1446
-
Journal article (peer-reviewed)abstract
- Risk stratification is essential for the delivery of optimal treatment in childhood acute lymphoblastic leukemia. However, current risk stratification algorithms dichotomize variables and apply risk factors independently, which may incorrectly assume identical associations across biologically heterogeneous subsets and reduce statistical power. Accordingly, we developed and validated a prognostic index (PIUKALL) that integrates multiple risk factors and uses continuous data. We created discovery (n = 2405) and validation (n = 2313) cohorts using data from 4 recent trials (UKALL2003, COALL-03, DCOG-ALL10, and NOPHO-ALL2008). Using the discovery cohort, multivariate Cox regression modeling defined a minimal model including white cell count at diagnosis, pretreatment cytogenetics, and end-of-induction minimal residual disease. Using this model, we defined PIUKALL as a continuous variable that assigns personalized risk scores. PIUKALL correlated with risk of relapse and was validated in an independent cohort. Using PIUKALL to risk stratify patients improved the concordance index for all end points compared with traditional algorithms. We used PIUKALL to define 4 clinically relevant risk groups that had differential relapse rates at 5 years and were similar between the 2 cohorts (discovery: low, 3% [95% confidence interval (CI), 2%-4%]; standard, 8% [95% CI, 6%-10%]; intermediate, 17% [95% CI, 14%-21%]; and high, 48% [95% CI, 36%-60%; validation: low, 4% [95% CI, 3%-6%]; standard, 9% [95% CI, 6%-12%]; intermediate, 17% [95% CI, 14%-21%]; and high, 35% [95% CI, 24%-48%]). Analysis of the area under the curve confirmed the PIUKALL groups were significantly better at predicting outcome than algorithms employed in each trial. PIUKALL provides an accurate method for predicting outcome and more flexible method for defining risk groups in future studies.
|
|
| 6. |
- Hasselgren, Malin, et al.
(author)
-
Genomic and fitness consequences of inbreeding in an endangered carnivore
- 2021
-
In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:12, s. 2790-2799
-
Journal article (peer-reviewed)abstract
- Reduced fitness through genetic drift and inbreeding is a major threat to small and isolated populations. Although previous studies have generally used genetically verified pedigrees to document effects of inbreeding and gene flow, these often fail to capture the whole inbreeding history of the species. By assembling a draft arctic fox (Vulpes lagopus) genome and resequencing complete genomes of 23 additional foxes born before and after a well-documented immigration event in Scandinavia, we here look into the genomic consequences of inbreeding and genetic rescue. We found a difference in genome-wide diversity, with 18% higher heterozygosity and 81% lower F-ROH in immigrant F1 compared to native individuals. However, more distant descendants of immigrants (F2, F3) did not show the same pattern. We also found that foxes with lower inbreeding had higher probability to survive their first year of life. Our results demonstrate the important link between genetic variation and fitness as well as the transient nature of genetic rescue. Moreover, our results have implications in conservation biology as they demonstrate that inbreeding depression can effectively be detected in the wild by a genomic approach.
|
|
| 7. |
|
|
| 8. |
- Karlsson, Lene, et al.
(author)
-
Characteristics and outcome of primary resistant disease in paediatric acute myeloid leukaemia
- 2023
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 201:4, s. 757-765
-
Journal article (peer-reviewed)abstract
- A significant proportion of events in paediatric acute myeloid leukaemia (AML) are caused by resistant disease (RD). We investigated clinical and biological characteristics in 66 patients with RD from 1013 children with AML registered and treated according to the NOPHO-AML 93, NOPHO-AML 2004, DB AML-01 and NOPHO-DBH AML 2012 protocols. Risk factors for RD were age10 years or older and a white-blood-cell count (WBC) of 100 x 10(9)/L or more at diagnosis. The five-year overall survival (OS) was 38% (95% confidence interval [CI]: 28%-52%). Of the 63 children that received salvage therapy with chemotherapy, 59% (N = 37) achieved complete remission (CR) with OS 57% (95% CI: 42%-75%) compared to 12% (95% CI: 4%-35%) for children that did not achieve CR. Giving more than two salvage chemotherapy courses did not increase CR rates. OS for all 43 patients receiving allogeneic haematopoietic stem cell transplantation (HSCT) was 49% (95% CI: 36%-66%). Those achieving CR and proceeding to HSCT had an OS of 56% (95% CI: 41%-77%, N = 30). This study showed that almost 40% of children with primary resistant AML can be cured with salvage therapy followed by HSCT. Children that did not achieve CR after two salvage courses with chemotherapy did not benefit from additional chemotherapy.
|
|
| 9. |
- Modvig, S, et al.
(author)
-
Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.
- 2021
-
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35, s. 1894-1906
-
Journal article (peer-reviewed)abstract
- PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p<0.0001), 29 (HzR 2.7, p<0.0001), and 79 (HzR 3.5, p<0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4×10-2 versus 5.2×10-3, p<0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y=3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD>10-4 associated with a CIR5y=22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
|
|
| 10. |
- Norén Nilsson, Astrid, et al.
(author)
-
Civil Society Leadership
- 2023
-
In: Routledge Handbook of Civil and Uncivil Society in Southeast Asia. - 9780367422080 ; , s. 175-189
-
Book chapter (peer-reviewed)
|
|
