| 1. |
- Häfner, Sophia J., et al.
(author)
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Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions
- 2023
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In: Developmental Cell. - 1534-5807. ; 58:17, s. 9-1609
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Journal article (peer-reviewed)abstract
- Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms. 2′-O-methylation (2′-O-me) of rRNA represents an important source of heterogeneity, where site-specific alteration of methylation levels can modulate translation. Here, we examine changes in rRNA 2′-O-me during mouse brain development and tri-lineage differentiation of human embryonic stem cells (hESCs). We find distinct alterations between brain regions, as well as clear dynamics during cortex development and germ layer differentiation. We identify a methylation site impacting neuronal differentiation. Modulation of its methylation levels affects ribosome association of the fragile X mental retardation protein (FMRP) and is accompanied by an altered translation of WNT pathway-related mRNAs. Together, these data identify ribosome heterogeneity through rRNA 2′-O-me during early development and differentiation and suggest a direct role for ribosomes in regulating translation during cell fate acquisition.
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| 2. |
- Knudsen, Gitte M, et al.
(author)
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Guidelines for the content and format of PET brain data in publications and archives : A consensus paper
- 2020
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In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 40:8, s. 1576-1585
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Journal article (peer-reviewed)abstract
- It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis.
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| 3. |
- Bergfelt Lennmyr, Emma, 1984-
(author)
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Registry-Based Studies in Adult Acute Lymphoblastic Leukemia in Sweden : Survival and Quality of Life
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Acute lymphoblastic leukemia (ALL), a common child malignancy, also constitutes a minor fraction of adult cancer with approximately 50 new cases per year in Sweden. While the five-year overall survival (OS) in pediatric ALL is more than 90%, the prognosis in adults is dismal. Using the Swedish ALL quality registry, this thesis investigates treatment and outcome of adult ALL according to national guidelines. In addition, the introduction of patient-reported outcome in the ALL and Acute Myeloid Leukemia registries is evaluated. In Paper I, measurement of minimal residual disease by flow cytometry was found to be feasible but not consistently applied in the 35 patients with Philadelphia (Ph)-negative B-ALL investigated. In Paper II, treatment, toxicity and outcome of 155 patients, 55-85 years (y) with ALL diagnosis between 2005 and 2012 were studied in detail by patient charts review. An age-adopted protocol recommended from 2009 did not result in better outcome. In Paper III, disease recurrence in the same cohort as Paper II was studied. The median overall survival (OS) after ALL relapse was 3.6 months. In Paper IV, the whole ALL registry was studied and OS was estimated in 930 adult patients diagnosed in the periods 1997-2006 and 2007-2015. Five year OS improved in patients 18-45y from 50% to 65%, in patients 46-65y from 25% to 46%, and in patients >65y from 7% to 11%. This demonstrates that young patients have the best prognosis, in part due to the introduction of a dose-intense “pediatric-like” chemotherapy protocol. Compared to women, middle-aged men were found to have a worse outcome.Historically, Philadelphia-positive (Ph-pos) ALL has a poor prognosis compared to Ph-negative ALL. In this material, the frequency of Ph-pos ALL was 34% of examined B-ALL. Analysis of the whole registry revealed that in 2007-2015, i.e. after the introduction of the tyrosine kinase inhibitor imatinib, Ph-pos ALL was no longer associated with inferior OS. In Paper V, ALL and Acute Myeloid Leukemia patients, six months after diagnosis, completed a web or paper questionnaire regarding quality of life, symptoms and experience with care. The response rate was 64%. Depression symptoms were frequent (18%), especially in young women who reported worrying about fertility.In summary, although OS in adult ALL has improved, more effective and less toxic therapies in upfront treatment are highly warranted. Collection of patient-reported outcome in a national quality registry is feasible and can add important aspects of cancer care that are not usually addressed.
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| 4. |
- Jacobsen, Ramune, et al.
(author)
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Online and Blended Learning Courses for Healthcare Professionals and Policymakers on Patients' Perspectives on Medicine : A Project Report.
- 2022
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In: Pharmacy. - : MDPI AG. - 2226-4787. ; 10:2
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Journal article (peer-reviewed)abstract
- In order for healthcare professionals to better engage with patients, they need to understand and integrate the perspectives of patients into their daily work. In this project, we developed two courses for healthcare professionals on patients' perspectives on medicine. One course was an online course that introduced the patients' perspectives on medicine and explained its importance for healthcare and health policy. The second course was a blended learning course, consisting of online modules and face-to-face webinars, which specified how to explore patients' perspectives in qualitative interviews, and how to develop implementation plans. Patients participated in the development, execution, and evaluation of both courses. Overall, more than 2000 healthcare professionals enrolled in the first course and, in just over a year, 191 participants completed the online course; 57 healthcare professionals registered in the second blended learning course and six participants completed both components of the course. The relevance of knowledge gained was positively evaluated. Participants especially appreciated the participation of patients. Based on the feedback, the second blended learning course was adapted to run online and both courses continue to be freely available to all interested healthcare professionals on the Coursera platform.
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| 5. |
- Nørgaard, Jesper, et al.
(author)
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Absence of Large-Scale Ice Masses in Central Northeast Siberia During the Late Pleistocene
- 2023
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 50:10
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Journal article (peer-reviewed)abstract
- Ongoing speculation regarding the existence of large Late Pleistocene ice masses in Northeast Eurasia reflects the dearth of age constraints on glaciations across this vast region. Here, we report the first dates from the central part of Northeast Siberia, consisting of 22 cosmogenic 10Be exposure ages from boulders deriving from a sequence of three moraines in the Chersky Range. The dated moraine sequence indicates progressive contraction of maximum glacier extent from Marine Isotope Stage 6 to the Last Glacial Maximum, while the remotely-sensed mapping indicates an older, more expansive glaciation in the region yet undated. Our results show that Late Pleistocene glaciations were limited to the highlands, and Northeast Siberia did not host a large, coalescent ice sheet during the Last Glacial Maximum or Marine Isotope Stage 6.
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