| 1. |
- Liu, Yang, et al.
(författare)
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Engineered human Diamond-Blackfan anemia disease model confirms therapeutic effects of clinically applicable lentiviral vector at single-cell resolution
- 2023
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Ingår i: Haematologica. - 1592-8721. ; 108:11, s. 3095-3109
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Tidskriftsartikel (refereegranskat)abstract
- Diamond-Blackfan anemia is a rare genetic bone marrow failure disorder which is usually caused by mutations in ribosomal protein genes. In the present study, we generated a traceable RPS19-deficient cell model using CRISPR-Cas9 and homology-directed repair to investigate the therapeutic effects of a clinically applicable lentiviral vector at single-cell resolution. We developed a gentle nanostraw delivery platform to edit RPS19 gene in primary human cord blood-derived CD34+ hematopoietic stem and progenitor cells. The edited cells showed expected impaired erythroid differentiation phenotype and a specific erythroid progenitor with abnormal cell cycle status accompanied by enrichment of TNFα/NF-κB and p53 signaling pathways was identified by single-cell RNA sequencing analysis. The therapeutic vector could rescue the abnormal erythropoiesis by activating cell cycle-related signaling pathways and promoted red blood cell production. Overall, these results establish nanostraws as a gentle option for CRISPR-Cas9-based gene editing in sensitive primary hematopoietic stem and progenitor cells, and provide support for future clinical investigations of the lentiviral gene therapy strategy.
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| 2. |
- Forsner, Maria, et al.
(författare)
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Mitt i informationsflödet om Covid 19 pandemin, en internationell webbenkätstudie till föräldrar och barn 7-12 år
- 2020
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Ingår i: State of Art- Covid 2019, Nationell digital konferens, Svenska läkarsällskpet.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Tidigt under våren 2020 drabbades Sverige av Covid 19 pandemin. Med pandemin följe en infodemi. Barn skolåldern och deras förälder hamnade mitt i detta informationsflöde. Syfte: Att undersöka hur barn får och tolkar information om Covid 19 pandemin. Metod: Anonymiserad webbenkät. 2 enkäter til barn, respektive föräldrar. Översatt till respektive språk. Deltagare 390 barn, 7-12 är (Sv 50) och 1234 föräldrar ( Sv 235). Insamling april – 1 juni ( Sv 22 maj-1 juni). Initierat av Lucy Bray med team, Edge Hills universitet Storbritannien. Omvårdnad forskare från Sverige, Kanada , Australien, Brasilien och Spanien. Resultat: Majoriteten av barn från andra länderna fick information från föräldrarna. Svaren från de svenska barnen speglade myndighetens rekommendationer. Utomhus skildrades som en positiv plats för de svenska barnen. Teckningar från Sverige visade i stor utsträckning munskydd på både människor och djur. Slutsats: De sveks barnen var medvetna om att coronaviruset kunde vara farligt, vikten av att hålla avstånd och tvätta händerna och skydda de äldre. Svaren från Sverige skiljde sig från de andra länderna med att skolan var främsta och önskade informationskällan. Utomhusaktiviteter uppskattades som önskvärt.
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| 3. |
- Jenholt Nolbris, Margaretha, 1956, et al.
(författare)
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Young children’s voices in an unlocked Sweden during the COVID-19 pandemic
- 2022
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Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 50:6, s. 693-702
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Tidskriftsartikel (refereegranskat)abstract
- Aims: During the COVID-19 pandemic, Sweden was one of the few countries that rejected lockdowns in favour of recommendations for restrictions, including careful hand hygiene and social distancing. Preschools and primary schools remained open. Several studies have shown negative impacts of the pandemic on children, particularly high levels of anxiety. The study aim was to explore how Swedish school-aged children aged 6–14 years, experienced the COVID-19 pandemic and their perceived anxiety.Methods: In total, 774 children aged 6–14 years and their guardians answered an online questionnaire containing 24 questions, along with two instruments measuring anxiety: the Children’s Anxiety Questionnaire and the Numerical Rating Scale. A convergent parallel mixed-methods design was used for analysing the quantitative and qualitative data. Each data source was first analysed separately, followed by a merged interpretative analysis.Results: The results showed generally low levels of anxiety, with no significant sex differences. Children who refrained from normal social activities or group activities (n=377) had significantly higher levels of anxiety. Most of the children were able to appreciate the bright side of life, despite the social distancing and refraining from activities, which prevented them from meeting and hugging their loved ones.Conclusions: These Swedish children generally experienced low levels of anxiety, except those who refrained from social activities. Life was nonetheless mostly experienced as normal, largely because schools remained open. Keeping life as normal as possible could be one important factor in preventing higher anxiety and depression levels in children during a pandemic.
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| 4. |
- Nilsson, Stefan, 1972, et al.
(författare)
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To be or not to be vaccinated against COVID-19 - The adolescents' perspective - A mixed-methods study in Sweden.
- 2021
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Ingår i: Vaccine: X. - : Elsevier BV. - 2590-1362. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination of the population seems to be an important strategy in halting the COVID-19 pandemic in both local and global society. The aim of this study was to explore Swedish adolescents' willingness to be vaccinated against COVID-19 and its association with sociodemographic and other possible factors. A survey was distributed in Sweden between 7 July and 8 November 2020. The main qualitative question concerned adolescents' thoughts on vaccination against COVID-19 and evaluated whether the adolescents would like to be vaccinated when a COVID-19 vaccine is made available. In total, 702 adolescents aged between 15 and 19 responded to the questionnaire. A convergent parallel mixed-methods design was used. The results showed that nearly one in three adolescents had not decided if they wanted to get a COVID-19 vaccine, i.e. 30.5%: n = 214. Of the participants 54.3% (n = 381) were willing to be vaccinated. Girls had higher levels of anxiety about the vaccine compared to boys. In addition, high levels of anxiety impacted on the participants' willingness to be vaccinated. One reason for being undecided about the vaccine was that participants felt they did not know enough about it. Practising social distancing increased willingness to be vaccinated, as reflected in the qualitative results which showed participants wanted to be vaccinated to protect others. The results impart important knowledge to healthcare professionals and contribute to their communication with adolescents about vaccine hesitancy.
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| 5. |
- Rydström, Anna, et al.
(författare)
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Functional and molecular profiling of hematopoietic stem cells during regeneration
- 2023
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Ingår i: Experimental Hematology. - 0301-472X .- 1873-2399. ; 127, s. 40-51
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) enable hematopoietic stem cell transplantation (HCT) through their ability to replenish the entire blood system. Proliferation of HSCs is linked to decreased reconstitution potential, and a precise regulation of actively dividing HSCs is thus essential to ensure long-term functionality. This regulation becomes important in the transplantation setting where HSCs undergo proliferation followed by a gradual transition to quiescence and homeostasis. Although mouse HSCs have been well studied under homeostatic conditions, the mechanisms regulating HSC activation under stress remain unclear. Here, we analyzed the different phases of regeneration after transplantation. We isolated bone marrow from mice at 8 time points after transplantation and examined the reconstitution dynamics and transcriptional profiles of stem and progenitor populations. We found that regenerating HSCs initially produced rapidly expanding progenitors and displayed distinct changes in fatty acid metabolism and glycolysis. Moreover, we observed molecular changes in cell cycle, MYC and mTOR signaling in both HSCs, and progenitor subsets. We used a decay rate model to fit the temporal transcription profiles of regenerating HSCs and identified genes with progressively decreased or increased expression after transplantation. These genes overlapped to a large extent with published gene sets associated with key aspects of HSC function, demonstrating the potential of this data set as a resource for identification of novel HSC regulators. Taken together, our study provides a detailed functional and molecular characterization of HSCs at different phases of regeneration and identifies a gene set associated with the transition from proliferation to quiescence.
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| 6. |
- Warsi, Sarah, et al.
(författare)
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Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells
- 2022
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 107:12, s. 2884-2896
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Tidskriftsartikel (refereegranskat)abstract
- Even though hematopoietic stem cells (HSC) are characterized by their ability to self-renew and differentiate, they primarily reside in quiescence. Despite the immense importance of this quiescent state, its maintenance and regulation is still incompletely understood. Schlafen2 (Slfn2) is a cytoplasmic protein known to be involved in cell proliferation, differentiation, quiescence, interferon response, and regulation of the immune system. Interestingly, Slfn2 is highly expressed in primitive hematopoietic cells. In order to investigate the role of Slfn2 in the regulation of HSC we have studied HSC function in the elektra mouse model, where the elektra allele of the Slfn2 gene contains a point mutation causing loss of function of the Slfn2 protein. We found that homozygosity for the elektra allele caused a decrease of primitive hematopoietic compartments in murine bone marrow. We further found that transplantation of elektra bone marrow and purified HSC resulted in a significantly reduced regenerative capacity of HSC in competitive transplantation settings. Importantly, we found that a significantly higher fraction of elektra HSC (as compared to wild-type HSC) were actively cycling, suggesting that the mutation in Slfn2 increases HSC proliferation. This additionally caused an increased amount of apoptotic stem and progenitor cells. Taken together, our findings demonstrate that dysregulation of Slfn2 results in a functional deficiency of primitive hematopoietic cells, which is particularly reflected by a drastically impaired ability to reconstitute the hematopoietic system following transplantation and an increase in HSC proliferation. This study thus identifies Slfn2 as a novel and critical regulator of adult HSC and HSC quiescence.
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