| 1. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 2. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 3. |
- van Atteveld, Jenneke E., et al.
(författare)
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Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors : evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
- 2021
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:9, s. 622-637
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Tidskriftsartikel (refereegranskat)abstract
- Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dualenergy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > -1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.
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| 4. |
- Grahn, Petra, et al.
(författare)
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Early disc degeneration in radiotherapy-treated childhood brain tumor survivors
- 2023
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls.MethodsIn this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5-33.1), 67 survivors (mean age 28.4, range 16.2-43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration.ResultsChildhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05).ConclusionsSigns of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.
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| 5. |
- Kaasinen, E, et al.
(författare)
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Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
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Tidskriftsartikel (refereegranskat)abstract
- Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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| 10. |
- Karppinen, J, et al.
(författare)
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Serum biomarkers for Modic changes in patients with chronic low back pain
- 2021
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Ingår i: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. - : Springer Science and Business Media LLC. - 1432-0932. ; 30:64, s. 1018-1027
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Mannisto, J, et al.
(författare)
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In Reply
- 2017
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Ingår i: Obstetrics and gynecology. - 1873-233X. ; 129:5, s. 944-945
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| 22. |
- Toksvang, LN, et al.
(författare)
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Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol
- 2022
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22:1, s. 483-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM) trial investigates a novel strategy for ALL maintenance.MethodsTEAM is a randomized phase 3 sub-protocol to the ALLTogether1 trial, which includes patients 0–45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5–12.5 mg/m2/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m2/day. A total of 778 patients will be included in TEAM during ~ 5 years. The study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse, TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients.DiscussionTEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms.Trial registrationEudraCT, 2018–001795-38. Registered 2020-05-15,Clinicaltrials.gov,NCT04307576. Registered 2020-03-13,https://clinicaltrials.gov/ct2/show/NCT04307576
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| 23. |
- Koivisto, K, et al.
(författare)
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The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging
- 2019
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Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini–Hochberg (B–H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP-10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.
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| 30. |
- Beilina, Larisa, 1970, et al.
(författare)
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Optimization approach for the simultaneous reconstruction of the dielectric permittivity and magnetic permeability functions from limited observations
- 2015
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Ingår i: Inverse Problems and Imaging. - : American Institute of Mathematical Sciences (AIMS). - 1930-8337 .- 1930-8345. ; 9:1, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- We consider the inverse problem of the simultaneous reconstruction of the dielectric permittivity and magnetic permeability functions of the Maxwell's system in 3D with limited boundary observations of the electric field. The theoretical stability for the problem is provided by the Carleman estimates. For the numerical computations the problem is formulated as an optimization problem and hybrid finite element/difference method is used to solve the parameter identification problem.
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| 31. |
- Egnell, C, et al.
(författare)
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Erratum
- 2022
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 198:3, s. 610-610
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 32. |
- Groth, Camilla, et al.
(författare)
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Conditions for experiential knowledge exchange in collaborative research across the sciences and creative practice
- 2020
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Ingår i: Codesign-International Journal of Cocreation in Design and the Arts. - : Informa UK Limited. - 1571-0882. ; 16:4, s. 328-344
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Tidskriftsartikel (refereegranskat)abstract
- Interdisciplinary research across the sciences and creative practice offers potential to explore new areas of knowledge previously hidden between disciplines. However, diverging epistemology and expectations make collaboration difficult. We interviewed 11 researchers working in projects that combined scientific and creative practice research, to investigate how they dealt with different epistemological approaches. In some cases, the discrepancies that were first experienced as hindrances turned into enablers, opening up new vistas for learning. Our findings show that the prerequisites for experiential knowledge transfer need to be built consciously by engaging in hands-on practices and shared cognitive activities that may extend beyond the personal comfort zone. Furthermore, the common goals and research questions need to be motivating for all involved. Although academic research funding agents encourage interdisciplinary research, funding alone is not sufficient to motivate people to work and truly learn together. By combining different types of knowledge in co-creation processes, participants are able to better share each other's views and construct a multifaceted understanding. An analysis of the interviews suggests how a conscious development of interdisciplinary practice helps educate thinkers and makers to feel comfortable in the unsettling zone between disciplinary boundaries, and thus contribute to innovative research.
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| 33. |
- Hakkarainen, M, et al.
(författare)
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The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
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Tidskriftsartikel (refereegranskat)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
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| 35. |
- Oskarsson, T., et al.
(författare)
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Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
- 2018
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S693-S694
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objectives: Children and adolescents undergoing treatment for cancer are exposed to multiple factors that impact the development of peak bone mass and bone quality. The aims of this study were to examine the risks and cumulative incidence of osteoporotic fractures in childhood cancer survivors and identify subgroups at higher risk.Design/Methods: In the national cancer registries of Denmark, Finland, Iceland and Sweden we identified patients diagnosed with cancer before 20 years of age from the start of registration in the 1940s and 1950s through 2008. We compared 26.334 one‐year survivors with a cohort of 162.372 age‐ and sex‐matched population comparison subjects selected from the national population registries. With data derived from national hospital registries we estimated the standardized hospitalization rate ratios (SHRR) and the mean cumulative count (MCC) of hospital admissions for osteoporotic fractures. To identify subgroups at risk we used Cox regression models to generate hazard ratios (HR) for osteoporotic fractures. Death and new cancer were treated as competing risks.Results: The estimated SHRR for the first osteoporotic fracture was 1.41 (95% CI; 1.27‐1.58) but the MCC for recurrent osteoporotic fractures did not differ between the survivors and the comparison group. The SHRR for isolated hip fractures was 2.90 (2.32‐3.63). The adjusted HR for osteoporotic fracture as the first event was 1.53 (1.09‐2.16) if cancer was diagnosed 15‐19 years and 2.10 (1.48‐2.98) for long‐term survivors of CNS tumors. Survivors 15‐19 years at cancer diagnosis and long‐term survivors of CNS tumors were also at higher risk of experiencing a second fracture, HR 3.29 (1.65‐6.55) and HR 2.71 (1.45‐5.05), respectively.Conclusions: Childhood cancer survivors are at higher risk of being hospitalized for osteoporotic fractures but the burden of recurrent fractures is not higher. For subgroups at risk, surveillance of bone health and measures to increase bone strength and prevent fractures should be encouraged.
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