| 1. |
- Alijagic, Andi, 1992-, et al.
(författare)
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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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| 2. |
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| 3. |
- Chandrasekaran, Venkatagaran, et al.
(författare)
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Cohesin-Mediated Chromatin Interactions and Autoimmunity
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Proper physiological functioning of any cell type requires ordered chromatin organization. In this context, cohesin complex performs important functions preventing premature separation of sister chromatids after DNA replication. In partnership with CCCTC-binding factor, it ensures insulator activity to organize enhancers and promoters within regulatory chromatin. Homozygous mutations and dysfunction of individual cohesin proteins are embryonically lethal in humans and mice, which limits in vivo research work to embryonic stem cells and progenitors. Conditional alleles of cohesin complex proteins have been generated to investigate their functional roles in greater detail at later developmental stages. Thus, genome regulation enabled by action of cohesin proteins is potentially crucial in lineage cell development, including immune homeostasis. In this review, we provide current knowledge on the role of cohesin complex in leukocyte maturation and adaptive immunity. Conditional knockout and shRNA-mediated inhibition of individual cohesin proteins in mice demonstrated their importance in haematopoiesis, adipogenesis and inflammation. Notably, these effects occur rather through changes in transcriptional gene regulation than through expected cell cycle defects. This positions cohesin at the crossroad of immune pathways including NF-kB, IL-6, and IFN gamma signaling. Cohesin proteins emerged as vital regulators at early developmental stages of thymocytes and B cells and after antigen challenge. Human genome-wide association studies are remarkably concordant with these findings and present associations between cohesin and rheumatoid arthritis, multiple sclerosis and HLA-B27 related chronic inflammatory conditions. Furthermore, bioinformatic prediction based on protein-protein interactions reveal a tight connection between the cohesin complex and immune relevant processes supporting the notion that cohesin will unearth new clues in regulation of autoimmunity.
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| 4. |
- Erlandsson, Malin, 1972, et al.
(författare)
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Survivin promotes a glycolytic switch in CD4+ T cells by suppressing the transcription of PFKFB3 in rheumatoid arthritis.
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:12
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explore the role of nuclear survivin in maintaining the effector phenotype of IFNγ-producing Tcells acting through the transcriptional control of glucose utilization. High expression of survivin in CD4+T cells was associated with IFNγ-dependent phenotype and anaerobic glycolysis. Transcriptome of CD4+ cells and sequencing of survivin-bound chromatin showed that nuclear survivin had a genome-wide and motif-specific binding to regulatory regions of the genes controlling cell metabolism. Survivin coprecipitates with transcription factors IRF1 and SMAD3, which repressed the transcription of the metabolic check-point enzyme phosphofructokinase 2 gene PFKFB3 and promoted anaerobic glycolysis. Combining transcriptome analyses of CD4+ cells and functional studies in glucose metabolism, we demonstrated that the inhibition of survivin reverted PFKFB3 production, inhibited glucose uptake, and reduces interferon effects in CD4+ cells. These results present a survivin-dependent mechanism in coordinating the metabolic adaptation of CD4+T cells and propose an attractive strategy to counteract IFNγ-dependent inflammation in autoimmunity.
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| 5. |
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| 6. |
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| 7. |
- Jarva, Erika, et al.
(författare)
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Aspects associated with health care professionals’ digital health competence development – a qualitative study
- 2022
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Ingår i: Finnish Journal of eHealth and eWelfare. - Joroinen : Sosiaali- ja Terveyshuollon Tietojenkaesittely / Finnish Social and Health Informatics Association. - 1798-0798. ; 14:1, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- Health care professionals need continuous education to maintain the competencies required to provide high-quality care; in today’s world, this means an understanding of digital health services. Insight into health care professionals’ experiences of which aspects influence their digital health competence development is therefore highly relevant.The objective of the study was to examine which aspects influence the digital health competence development of health care professionals (nursing workforce and allied health professionals).In-depth, semi-structured interviews were conducted with 20 health care professionals (Finland n=15, Sweden n=5) from various health care settings between May 2019 and July 2020. Interviews were audio-recorded, translated verbatim and analysed with inductive content analysis.Health care professionals perceive that digital health competence development is influenced by aspects related to digital health adoption, co-workers and the work community, their manager, and opportunities for continuous education and orientation.The participants agreed that digital health competence is an important part of a health care professional’s overall clinical competence. Continuous education geared towards digital health competence should be systematically designed, and potentially integrate the resources available on social media platforms. Additionally, managers and supervisors should take a stronger stance towards learning about digital health services so they can serve as role models to their employees and genuinely promote digital health competence development.
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| 8. |
- Jensen, Maja, 1978, et al.
(författare)
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Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27
- 2023
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Ingår i: Iscience. ; 26:7
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the role of survivin in epigenetic control of gene transcription through interaction with the polycomb repressive complex 2 (PRC2). PRC2 is responsible for silencing gene expression by trimethylating lysine 27 on histone 3. We observed differential expression of PRC2 subunits in CD4(+) T cells with varying levels of survivin expression, and ChIP-seq results indicated that survivin colocalizes with PRC2 along DNA. Inhibition of survivin resulted in a significant increase in H3K27 trimethylation, implying that survivin prevents PRC2 from functioning. Peptide microarray showed that survivin interacts with peptides from PRC2 subunits, and machine learning revealed that amino acid composition contains relevant information for predicting survivin interaction. NMR and BLI experiments supported the interaction of survivin with PRC2 subunit EZH2. Finally, protein-protein docking revealed that the survivin-EZH2 interaction interface overlaps with catalytic residues of EZH2, potentially inhibiting its H3K27 methylation activity. These findings suggest that survivin inhibits PRC2 function.
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| 9. |
- Järlskog, Ida, 1991, et al.
(författare)
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Traffic-related microplastic particles, metals, and organic pollutants in an urban area under reconstruction
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 774
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Tidskriftsartikel (refereegranskat)abstract
- In urban environments, particularly areas under reconstruction, metals, organic pollutants (OP), and microplastics (MP), are released in large amounts due to heavy traffic. Road runoff, a major transport route for urban pollutants, contributes significantly to a deteriorated water quality in receiving waters. This study was conducted in Gothenburg, Sweden, and is unique because it simultaneously investigates the occurrence of OP, metals, and MP on roads and in stormwater from an urban area under reconstruction. Correlations between the various pollutants were also explored. The study was carried out by collecting washwater and sweepsand generated from street sweeping, road surface sampling, and flow-proportional stormwater sampling on several occasions. The liquid and solid samples were analyzed for metals, polycyclic aromatic hydrocarbons (PAH), oxy-PAH, aliphatics, aromatics, phthalates, and MP. The occurrence of OP was also analyzed with a non-target screening method of selected samples. Microplastics, i.e. plastic fragments/fibers, paint fragments, tire wear particles (TWP) and bitumen, were analyzed with a method based on density separation with sodium iodide and identification with a stereo microscope, melt-tests, and tactile identification. MP concentrations amounted to 1500 particles/L in stormwater, 51,000 particles/L in washwater, and 2.6 × 106 particles/kg dw in sweepsand. In stormwater, washwater and sweepsand, MP ≥20 μm were found to be dominated by TWP (38%, 83% and 78%, respectively). The results confirm traffic as an important source to MP, OP, and metal emissions. Concentrations exceeding water and sediment quality guidelines for metals (e.g. Cu and Zn), PAH, phthalates, and aliphatic hydrocarbons in the C16–C35 fraction were found in most samples. The results show that the street sweeper collects large amounts of polluted materials and thereby prevents further spread of the pollutants to the receiving stormwater.
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| 10. |
- Wadell, M., et al.
(författare)
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Challenges imposed by the COVID-19 pandemic on the Obstetrics and Gynecology residency program: a mixed-methods Swedish survey in the COPE Staff cohort study
- 2022
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To outline how the training program and work situation of residents in Obstetrics and Gynecology (OB-GYN) was affected by the pandemic and to illuminate how residents experienced these changes. Methods As part of the COVID-19 in Pregnancy and Early Childhood Staff (COPE Staff) cohort study, between January and May 2021, all participating residents were invited to answer a 28-question online Resident Survey focusing on their specialist education, work situation and experiences during the COVID-19 pandemic. Descriptive statistics were given in percentages for categorical variables and means and standard deviations (SD) for continuous variables. Univariate comparative analyses were performed with the use of the Pearson's Chi-2-test for dichotomous data. The association between residents' worry about the quality and length of their specialist training, with extra clinical hours and transfer to other healthcare institutions were assessed by multivariate logistic regression. Free text responses were analyzed by content analysis. Results Of the 162 participating OB-GYN residents, 69% expressed concern that the pandemic would have a negative impact on their training. Ninety-five (95%) reported cancellation/postponement of educational activities, 70% performed fewer surgeries and 27% had been transferred to other healthcare institutions where about half reported having gained more general knowledge as a physician. Working extra clinical hours was reported by 69% (7.4 +/- 5.3 hours per week) and 14% had considered changing their profession due to the pandemic. Senior residents, compared to junior residents, more often experienced cancelled/postponed clinical rotations (30% vs 15%, P=0.02) and reported performing fewer surgeries (P=0.02). The qualitative analysis highlighted the lack of surgical procedural training as a major concern for residents. Conclusion The COVID-19 pandemic has strongly impacted the training program and work situation of OB-GYN residents in Sweden. Residents were concerned over the negative impact of the pandemic on their training program and senior residents reported more missed educational opportunities as compared to junior residents. Program directors, head of institutions and clinical supervisors can use the problem areas pinpointed by this study to support residents and compensate for missed educational opportunities. While hands-on-training and operating time cannot be compensated for, the authors hope that the findings of the study can help develop new strategies to minimize the negative impact of the current and future pandemics on resident education and work situation.
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| 11. |
- Åkerström, Magnus, 1981, et al.
(författare)
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The COPE Staff study : Study description and initial report regarding job satisfaction, work-life conflicts, stress, and burnout among Swedish maternal and neonatal healthcare workers during the COVID-19 pandemic
- 2023
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Ingår i: International Journal of Gynecology & Obstetrics. - : John Wiley & Sons. - 0020-7292 .- 1879-3479. ; 162:3, s. 989-997
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo describe the study design of the COPE Staff cohort study on working conditions for maternal and neonatal healthcare workers (MNHCWs), and present baseline data regarding job satisfaction, work-life conflicts, stress, and burnout. MethodsBetween January and April 2021, 957 MNHCWs (administrative and medical staff) completed a baseline survey. Average levels of job satisfaction, work-life conflicts, stress, and burnout, and associations to perceived workload were assessed. ResultsThe average levels of job satisfaction, work-life conflicts, stress, and burnout were 68.6 (95% confidence interval [CI] 64.3-72.8), 42.6 (95% CI 37.3-48.0), 42.0 (95% CI 37.7-46.3), and 1.9 (95% CI 1.6-2.2), respectively. The respondents scoring above critical values indicating clinical burnout ranged between 3% and 18%, respectively, for the four burnout sub-dimensions. Women reported significantly higher levels of stress and burnout. Younger participants had lower job satisfaction and higher levels of work-life conflicts, stress, and burnout. Higher perceived workload was significantly associated with lower job satisfaction levels and higher levels of work-life conflicts, stress, and burnout. ConclusionsOur results indicate associations between MNHCWs perceived workload and job satisfaction, work-life conflicts, stress, and burnout during the COVID-19 pandemic. Eighteen percent scored above critical values for exhaustion.
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| 12. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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| 13. |
- Andersson, Edvin K. W., et al.
(författare)
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Initial SEI formation in LiBOB-, LiDFOB- and LiBF4-containing PEO electrolytes
- 2024
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 12:15, s. 9184-9199
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Tidskriftsartikel (refereegranskat)abstract
- A limiting factor for solid polymer electrolyte (SPE)-based Li-batteries is the functionality of the electrolyte decomposition layer that is spontaneously formed at the Li metal anode. A deeper understanding of this layer will facilitate its improvement. This study investigates three SPEs – polyethylene oxide:lithium tetrafluoroborate (PEO:LiBF4), polyethylene oxide:lithium bis(oxalate)borate (PEO:LiBOB), and polyethylene oxide:lithium difluoro(oxalato)borate (PEO:LiDFOB) – using a combination of electrochemical impedance spectroscopy (EIS), galvanostatic cycling, in situ Li deposition photoelectron spectroscopy (PES), and ab initio molecular dynamics (AIMD) simulations. Through this combination, the cell performance of PEO:LiDFOB can be connected to the initial SPE decomposition at the anode interface. It is found that PEO:LiDFOB had the highest capacity retention, which is correlated to having the least decomposition at the interface. This indicates that the lower SPE decomposition at the interface still creates a more effective decomposition layer, which is capable of preventing further electrolyte decomposition. Moreover, the PES results indicate formation of polyethylene in the SEI in cells based on PEO electrolytes. This is supported by AIMD that shows a polyethylene formation pathway through free-radical polymerization of ethylene.
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| 14. |
- Andree, Maria, et al.
(författare)
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Knowledge Products from Close-To-Practice Research
- 2024
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Ingår i: Round table presentation at the NERA-conference, 6-8 March, Malmö University.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- ‘Close-to-practice research’ has received increased attention across the Nordic countries. Following the British Education Research Association (BERA), the notion of ‘close-to-practice research’ is used to refer to educational research that is based on problems in practice, often involves researchers working in partnership with practitioners in schools and addresses issues of relevance to practitioners. This roundtable focuses on how close-to-practice research can contribute to the knowledge base of the teaching profession by bringing together perspectives from didactics, school improvement and educational policy. More specifically, the interest is directed toward what characterizes the knowledge produced through practice-based research that may have significance for teachers' professional knowledge base and practice. The roundtable conversation builds on a previous analysis of what kinds of knowledge products are generated in didactic close-to-practice research where teachers and researchers work together within the research environment Stockholm Teaching & Learning Studies. As a result of this analysis a typology of knowledge products was proposed including: (i) descriptions of knowing, (ii) teaching design, (iii) didactic examples and (iv) methodological tools. It has been proposed that additional knowledge products may be developed, such as artifacts to be used in teaching (e.g. lesson plans, visual representations). The roundtable will include the following points of discussion: 1) a brief presentation of the typology, 2) challenging and developing the typology of knowledge products proposed by previous research by investigating different cases of close-to-practice research from traditions of action research and practice-developing research within subject-didactics, and 3) discussing how the notion of knowledge products may contribute to advancing the conversation on cumulativity in the field of educational research in general, and in relation to syntheses of close-to-practice research in particular. The participants will be engaged in conversations on the desirability and feasibility of striving towards cumulativity.
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| 15. |
- Båth, Petra, 1988, et al.
(författare)
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Lipidic cubic phase serial femtosecond crystallography structure of a photosynthetic reaction centre
- 2022
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Ingår i: Acta Crystallographica Section D-Structural Biology. - : International Union of Crystallography (IUCr). - 2059-7983. ; 78, s. 698-708
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Tidskriftsartikel (refereegranskat)abstract
- Serial crystallography is a rapidly growing method that can yield structural insights from microcrystals that were previously considered to be too small to be useful in conventional X-ray crystallography. Here, conditions for growing microcrystals of the photosynthetic reaction centre of Blastochloris viridis within a lipidic cubic phase (LCP) crystallization matrix that employ a seeding protocol utilizing detergent-grown crystals with a different crystal packing are described. LCP microcrystals diffracted to 2.25 angstrom resolution when exposed to XFEL radiation, which is an improvement of 0.15 angstrom over previous microcrystal forms. Ubiquinone was incorporated into the LCP crystallization media and the resulting electron density within the mobile Q(B) pocket is comparable to that of other cofactors within the structure. As such, LCP microcrystallization conditions will facilitate time-resolved diffraction studies of electron-transfer reactions to the mobile quinone, potentially allowing the observation of structural changes associated with the two electron-transfer reactions leading to complete reduction of the ubiquinone ligand.
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| 16. |
- Dolatabadi, Soheila, et al.
(författare)
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FUS-DDIT3 Fusion Oncoprotein Expression Affects JAK-STAT Signaling in Myxoid Liposarcoma
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma is one of the most common sarcoma entities characterized by FET fusion oncogenes. Despite a generally favorable prognosis of myxoid liposarcoma, chemotherapy resistance remains a clinical problem. This cancer stem cell property is associated with JAK-STAT signaling, but the link to the myxoid-liposarcoma-specific FET fusion oncogene FUS-DDIT3 is not known. Here, we show that ectopic expression of FUS-DDIT3 resulted in elevated levels of STAT3 and phosphorylated STAT3. RNA sequencing identified 126 genes that were regulated by both FUS-DDIT3 expression and JAK1/2 inhibition using ruxolitinib. Sixty-six of these genes were connected in a protein interaction network. Fifty-three and 29 of these genes were confirmed as FUS-DDIT3 and STAT3 targets, respectively, using public chromatin immunoprecipitation sequencing data sets. Enriched gene sets among the 126 regulated genes included processes related to cytokine signaling, adipocytokine signaling, and chromatin remodeling. We validated CD44 as a target gene of JAK1/2 inhibition and as a potential cancer stem cell marker in myxoid liposarcoma. Finally, we showed that FUS-DDIT3 interacted with phosphorylated STAT3 in association with subunits of the SWI/SNF chromatin remodeling complex and PRC2 repressive complex. Our data show that the function of FUS-DDIT3 is closely connected to JAK-STAT signaling. Detailed deciphering of molecular mechanisms behind tumor progression opens up new avenues for targeted therapies in sarcomas and leukemia characterized by FET fusion oncogenes.
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| 17. |
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| 18. |
- Gøtzsche-Astrup, Oluf, et al.
(författare)
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Trust in interagency collaboration: The role of institutional logics and hybrid professionals
- 2023
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Ingår i: Journal of Professions and Organization. - : Oxford University Press (OUP). - 2051-8803 .- 2051-8811. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Interagency collaboration among social workers, teachers, and police is key to countering violent extremism in the Nordic countries by securing comprehensive assessment of cases of concern. Yet, previous research indicates that different institutional logics—perceptions of fundamental goals, strategies, and grounds for attention in efforts to counter violent extremists—exist across professions and challenge collaboration and trust building in practice. In this article, we empirically investigate these claims across social workers (n=1,105), teachers (n=1,387), and police (n=1,053) in four Nordic countries: Denmark, Sweden, Norway, and Finland. Using results from online surveys with professionals, we investigate the distribution of a ‘societal security logic’ and a ‘social care logic’ across professions and the degree to which these institutional logics translate into mutual trust. Through a comparison of institutional logics among practitioners with and without practical experience of interagency collaboration, we investigate whether and how institutional logics tend to mix and merge in hybrid organizational spaces. We conclude that differences in institutional logics across professions are differences in degree rather than in kind, but that such differences are important in shaping mutual trust and that experiences of interagency collaboration are correlated with a convergence toward a ‘social care logic’ conception of countering violent extremism.
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| 19. |
- Hendry, Alexandra, et al.
(författare)
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Inhibitory control and problem solving in early childhood : Exploring the burdens and benefits of high self-control
- 2022
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Ingår i: Infant and Child Development. - : John Wiley & Sons. - 1522-7227 .- 1522-7219. ; 31:3
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Tidskriftsartikel (refereegranskat)abstract
- Low inhibitory control (IC) is sometimes associated with enhanced problem-solving amongst adults, yet for young children high IC is primarily framed as inherently better than low IC. Here, we explore associations between IC and performance on a novel problem-solving task, amongst 102 English 2- and 3-year-olds (Study 1) and 84 Swedish children, seen at 18-months and 4-years (Study 2). Generativity during problem-solving was negatively associated with IC, as measured by prohibition-compliance (Study 1, both ages, Study 2 longitudinally from 18-months). High parent-reported IC was associated with poorer overall problem-solving success, and greater perseveration (Study 1, 3-year-olds only). Benefits of high parent-reported IC on persistence could be accounted for by developmental level. No concurrent association was observed between problem-solving performance and IC as measured with a Delay-of-Gratification task (Study 2, concurrent associations at 4-years). We suggest that, for young children, high IC may confer burden on insight- and analytic-aspects of problem-solving.
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| 20. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 21. |
- Hultqvist, Sara, 1977-, et al.
(författare)
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Conditions for uptake of evidence-based knowledge in municipal care for older people in Sweden : a developmental evaluation
- 2022
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Ingår i: BMC Research Notes. - London : BioMed Central. - 1756-0500. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this paper is to describe the initial phase of a long-term collaboration initiative between a municipality and the Faculty of Medicine at a university in Sweden. The overall ambition of the collaboration is to strengthen the quality of care for older people. The concrete goal is to equip academically trained registered health care professionals (HCP) with tools for transferring evidence-based knowledge into practice. As municipal healthcare for older people is mainly carried out by staff lacking academic education, reg. HCP are key actors to bring in and consolidate an evidence-based approach in this setting. Developmental evaluation (DE) has been used to evaluate four separate activities in the initial phase. The activities where sequenced in a cumulative design to provide knowledge for further development of adequate tools.Results: The cumulative design originally planned did not fit the internal logic of the municipality. Therefore, workflow and pace adjustments were made to proceed towards the joint ambition; the creation of fruitful conditions for the uptake of evidence-based knowledge. Long-term collaboration between academia and organizations outside academia demands a sensitive and flexible research approach, recognizing that collaboration implies mutuality and restricts the sovereignty of academia in designing research.
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| 22. |
- Jarl, Maria, 1973, et al.
(författare)
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Organizational characteristics of successful and failing schools: a theoretical framework for explaining variation in student achievement
- 2021
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Ingår i: School Effectiveness and School Improvement. - : Informa UK Limited. - 0924-3453 .- 1744-5124. ; 32:3, s. 448-464
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Tidskriftsartikel (refereegranskat)abstract
- Why do some schools bring forth high achievement levels, whereas others do not? To understand the mechanisms behind school success, one must examine schools as organizations and the social relations and interactions among their members. By integrating the literature on educational effectiveness and sociological institutionalism, this article presents a study of four successful and four failing schools in Sweden regarding the impact of schools’ internal organization on student achievement. The results demonstrate that the two types of schools have distinct organizational characteristics, which show significant stability over time. Linking organizational characteristics and student outcomes, we argue that (a) the varying social reality of teachers and principals among the two types of schools fosters different types of actions and beliefs among teachers and principals, which (b) causes different learning environments for students that subsequently lead to variations in their learning trajectories.
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| 23. |
- Jarva, Erika, et al.
(författare)
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Healthcare professionals' perceptions of digital health competence : A qualitative descriptive study
- 2022
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Ingår i: Nursing Open. - Chichester : Wiley-Blackwell Publishing Inc.. - 2054-1058. ; 9:2, s. 1379-1393
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Tidskriftsartikel (refereegranskat)abstract
- Aims and objectives: This study aims to provide insight into healthcare professionals' lived experiences of digital health competence with the objective of improving the knowledge of how digital health competence is perceived by healthcare professionals.Background: Healthcare professionals need to adjust to the digital era to provide quality and ethical care. Previous research has rarely adopted a healthcare professional's standpoint to describe their perceptions of digital health competence, even though their perspective in how new care practices are designed and implemented is vital.Design: A qualitative descriptive study.Methods: Healthcare professionals (nurses and allied health professionals) from versatile healthcare settings were recruited for individual semi-structured interviews in Sweden (n= 5) and Finland (n= 15) (spring 2019-summer 2020). Purposive and convenience sampling was used. Participants' backgrounds were in the public and private sectors. The interviews were transcribed for inductive content analysis. The SRQR guideline guided the study process.Results: Healthcare professionals' perceptions of digital health competence are connected to competence to provide patient-centric care through digital channels, using technology and digital health systems, interacting with the patient through digital means, evaluating what digital health is and combining digital and traditional methods. Professionals' perceptions of their own digital health competence were divided, with the participants either reporting sufficient competence or perceiving a lack of skills in some specific areas.Conclusions: Healthcare professionals' perceptions of digital health competence focus on the ability to provide patient-centric care by evaluating the need and possibilities for using digital health services jointly with more traditional methods. This study provides a sound basis for digital health research, but future studies should focus on elucidating factors which affect digital health competence and competence development.Relevance to clinical practice: The results of this study can guide healthcare practices and digital health implementation, as well as function as a basis for instrument or theory development. Health care and nursing leaders should enable the resources to hybrid practices in patient-centric care provision. © 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.
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| 24. |
- Labori, Knut Jørgen, et al.
(författare)
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Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial
- 2024
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Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 9:3, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma.Methods: NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing.Findings: Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event.Interpretation: This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.
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| 25. |
- Luna Santa-María, Manuel, 1995, et al.
(författare)
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Digital RNA sequencing using unique molecular identifiers enables ultrasensitive RNA mutation analysis
- 2024
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Mutation analysis is typically performed at the DNA level since most technical approaches are developed for DNA analysis. However, some applications, like transcriptional mutagenesis, RNA editing and gene expression analysis, require RNA analysis. Here, we combine reverse transcription and digital DNA sequencing to enable low error digital RNA sequencing. We evaluate yield, reproducibility, dynamic range and error correction rate for seven different reverse transcription conditions using multiplexed assays. The yield, reproducibility and error rate vary substantially between the specific conditions, where the yield differs 9.9-fold between the best and worst performing condition. Next, we show that error rates similar to DNA sequencing can be achieved for RNA using appropriate reverse transcription conditions, enabling detection of mutant allele frequencies <0.1% at RNA level. We also detect mutations at both DNA and RNA levels in tumor tissue using a breast cancer panel. Finally, we demonstrate that digital RNA sequencing can be applied to liquid biopsies, analyzing cell-free gene transcripts. In conclusion, we demonstrate that digital RNA sequencing is suitable for ultrasensitive RNA mutation analysis, enabling several basic research and clinical applications.
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| 26. |
- Lundquist, Patrik, et al.
(författare)
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Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- 2022
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Tidskriftsartikel (refereegranskat)abstract
- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
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| 27. |
- Lyngfelt, Lovisa, et al.
(författare)
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Impact of the Uncoupling Protein 1 on Cardiovascular Risk in Patients with Rheumatoid Arthritis
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Adiposity is strongly associated with cardiovascular (CV) morbidity. Uncoupling protein 1 (UCP1) increases energy expenditure in adipocytes and may counteract adiposity. Our objective was to investigate a connection between UCP1 expression and cardiovascular health in patients with rheumatoid arthritis (RA) in a longitudinal observational study. Transcription of UCP1 was measured by qPCR in the subcutaneous adipose tissue of 125 female RA patients and analyzed with respect to clinical parameters and the estimated CV risk. Development of new CV events and diabetes mellitus was followed for five years. Transcription of UCP1 was identified in 89 (71%) patients. UCP1 positive patients had often active RA disease (p = 0.017), high serum levels of IL6 (p = 0.0025) and were frequently overweight (p = 0.015). IL-6(hi)BMI(hi) patients and patients treated with IL6 receptor inhibitor tocilizumab had significantly higher levels of UCP1 compared to other RA patients (p < 0.0001, p = 0.032, respectively). Both UCP1(hi) groups displayed unfavorable metabolic profiles with high plasma glucose levels and high triglyceride-to-HDL ratios, which indicated insulin resistance. Prospective follow-up revealed no significant difference in the incidence of new CV and metabolic events in the UCP1(hi) groups and remaining RA patients. The study shows that high transcription of UCP1 in adipose tissue is related to IL6-driven processes and reflects primarily metabolic CV risk in female RA patients.
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| 28. |
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| 29. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 30. |
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| 31. |
- Tarvis, Maria, 1963-, et al.
(författare)
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From chaos to a new normal—the COVID-19 pandemic as experienced by municipal health and social care providers in Sweden : A qualitative study
- 2023
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Ingår i: Nordic journal of nursing research. - London : Sage Publications. - 2057-1585 .- 2057-1593. ; 43:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- When the COVID-19 pandemic began to spread around the world, Swedish municipalities were unprepared. Different guidelines on how to act in relation to the disease varied and protective equipment was lacking. This study aims to describe the experiences of health and social care providers of working at municipality level during the COVID-19 pandemic. A total of 12 assistant nurses, 13 registered nurses, and three physicians were interviewed, individually or in groups, between fall 2020 and spring 2021. The interviews were semi-structured and were analyzed using thematic analysis, utilizing a design following the COREQ-checklist. Three main themes were identified as follows: ‘Initial chaotic situation and uncertainty regarding how to deal with the pandemic’; ‘Continuous changes in organization and work routines’, and ‘Management of the pandemic has become the new normal’. Though health and social care workers eventually managed to embed dealing with COVID-19 as a routine feature of their daily work, municipalities must prepare for future crises.
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| 32. |
- Wu, Liang-Ting, et al.
(författare)
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A method for modelling polymer electrolyte decomposition during the Li-nucleation process in Li-metal batteries
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Elucidating the complex degradation pathways and formed decomposition products of the electrolytes in Li-metal batteries remains challenging. So far, computational studies have been dominated by studying the reactions at inert Li-metal surfaces. In contrast, this study combines DFT and AIMD calculations to explore the Li-nucleation process for studying interfacial reactions during Li-plating by introducing Li-atoms close to the metal surface. These Li-atoms were added into the PEO polymer electrolytes in three stages to simulate the spontaneous reactions. It is found that the highly reactive Li-atoms added during the simulated nucleation contribute to PEO decomposition, and the resulting SEI components in this calculation include lithium alkoxide, ethylene, and lithium ethylene complexes. Meanwhile, the analysis of atomic charge provides a reliable guideline for XPS spectrum fitting in these complicated multicomponent systems. This work gives new insights into the Li-nucleation process, and experimental XPS data supporting this computational strategy. The AIMD/DFT approach combined with surface XPS spectra can thus help efficiently screen potential polymer materials for solid-state battery polymer electrolytes.
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