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  • Levin, A., et al. (author)
  • Novel insights into the disease transcriptome of human diabetic glomeruli and tubulointerstitium
  • 2020
  • In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:12, s. 2059-2072
  • Journal article (peer-reviewed)abstract
    • Background. Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, affecting similar to 30% of the rapidly growing diabetic population, and strongly associated with cardiovascular risk. Despite this, the molecular mechanisms of disease remain unknown. Methods. RNA sequencing (RNAseq) was performed on paired, micro-dissected glomerular and tubulointerstitial tissue from patients diagnosed with DN [n = 19, 15 males, median (range) age: 61 (30-85) years, chronic kidney disease stages 1-4] and living kidney donors [n = 20, 12 males, median (range) age: 56 (30-70) years]. Results. Principal component analysis showed a clear separation between glomeruli and tubulointerstitium transcriptomes. Differential expression analysis identified 1550 and 4530 differentially expressed genes, respectively (adjusted P < 0.01). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted activation of inflammation and extracellular matrix (ECM) organization pathways in glomeruli, and immune and apoptosis pathways in tubulointerstitium of DN patients. Specific gene modules were associated with renal function in weighted gene co-expression network analysis. Increased messengerRNA (mRNA) expression of renal damage markers lipocalin 2 (LCN) and hepatitis A virus cellular receptor1 (HAVCR1) in the tubulointerstitial fraction was observed alongside higher urinary concentrations of the corresponding proteins neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in DN patients. Conclusions. Here we present the first RNAseq experiment performed on paired glomerular and tubulointerstitial samples from DN patients. We show that prominent disease-specific changes occur in both compartments, including relevant cellular processes such as reorganization of ECM and inflammation (glomeruli) as well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher disease pathways and treatment targets in this high-risk patient population.
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  • Coath, W., et al. (author)
  • Operationalizing the centiloid scale for F-18 florbetapir PET studies on PET/MRI
  • 2023
  • In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:2
  • Journal article (peer-reviewed)abstract
    • INTRODUCTIONThe Centiloid scale aims to harmonize amyloid beta (A beta) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI). METHODSWe transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction. Gaussian-mixture-modelling-derived cutpoints for A beta PET positivity were converted. RESULTSThe Centiloid cutpoint was 14.2 for WC SUVRs. The relationship between WM and WC uptake differed between the calibration and testing datasets, producing implausibly low WM-based Centiloids. Linear adjustment produced a WM-based cutpoint of 18.1. DISCUSSIONTransformation of PET/MRI florbetapir data to Centiloids is valid. However, further understanding of the effects of acquisition or biological factors on the transformation using a WM reference is needed. HIGHLIGHTSCentiloid conversion of amyloid beta positron emission tomography (PET) data aims to standardize results.Centiloid values can be influenced by differences in acquisition.We converted florbetapir PET/magnetic resonance imaging data from a large birth cohort.Whole cerebellum referenced values could be reliably transformed to Centiloids. White matter referenced values may be less generalizable between datasets.
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  • Arheimer, Berit, et al. (author)
  • The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
  • 2024
  • In: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
  • Journal article (peer-reviewed)abstract
    • The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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  • Aulin, C., et al. (author)
  • The alarmins high mobility group box protein 1 and S100A8/A9 display different inflammatory profiles after acute knee injury
  • 2022
  • In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 30:9, s. 1198-1209
  • Journal article (peer-reviewed)abstract
    • Objective: To compare the concentrations of high mobility group box 1 protein (HMGB1) and S100A8/A9 in synovial fluid between patients with knee injuries and osteoarthritis (OA), and knee healthy subjects. To investigate associations of alarmin levels with different joint injuries and with biomarkers of inflammation, Wnt signaling, complement system, bone and cartilage degradation. Methods: HMGB1 and S100A8/A9 were measured in synovial fluid by immunoassays in patients with knee injuries, with OA and from knee healthy subjects, and were related to time from injury and with biomarkers obtained from previous studies. Hierarchical cluster and enrichment analyses of biomarkers associated to HMGB1 and S100A8/A9 were performed. Results: The synovial fluid HMGB1 and S100A8/A9 concentrations were increased early after knee injury; S100A8/A9 levels were negatively associated to time after injury and was lower in the old compared to recent injury group, while HMGB1 was not associated to time after injury. The S100A8/A9 levels were also increased in OA. The initial inflammatory response was similar between the alarmins, and HMGB1 and S100A8/A9 shared 9 out of 20 enriched pathways. The alarmins displayed distinct response profiles, HMGB1 being associated to cartilage biomarkers while S100A8/A9 was associated to proinflammatory cytokines. Conclusions: HMGB1 and S100A8/A9 are increased as an immediate response to knee trauma. While they share many features in inflammatory and immunoregulatory mechanisms, S100A8/A9 and HMGB1 are associated to different downstream responses, which may have impact on the OA progression after acute knee injuries.
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  • Bogren, Malin, 1970, et al. (author)
  • Health workforce perspectives of barriers inhibiting the provision of quality care in Nepal and Somalia : A qualitative study
  • 2020
  • In: Sexual and Reproductive Healthcare. - : Elsevier. - 1877-5756. ; 23
  • Journal article (peer-reviewed)abstract
    • ObjectiveIn this paper settings from Nepal and Somalia are used to focus on the perspectives of healthcare providers within two fragile health systems. The objective of this study was to describe barriers inhibiting quality healthcare in Nepal and Somalia from a health workforce perspective.MethodsData were collected through 19 semi-structured interviews with healthcare providers working in healthcare facilities. Ten interviews were conducted in Nepal and nine in Somalia.ResultsVarious structural barriers inhibiting the availability, accessibility, and acceptability of the quality care were similar in both countries. Barriers inhibiting the availability of quality care were linked to healthcare providers being overburdened with multiple concurrent jobs. Barriers inhibiting the accessibility to quality healthcare included long distances and the uncertain availability of transportation, and barriers to acceptability of quality healthcare was inhibited by a lack of respect from healthcare providers, characterised by neglect, verbal abuse, and lack of competence.ConclusionsInequality, poverty, traditional and cultural practices plus the heavy burden placed on healthcare providers are described as the underlying causes of the poor provision of quality care and the consequential shortcomings that emerge from it. In order to improve this situation adequate planning and policies that support the deployment and retention of the healthcare providers and its equitable distribution is required. Another important aspect is provision of training to equip healthcare providers with the ability to provide respectful quality care in order for the population to enjoy good standard of healthcare services.
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  • Chrysafi, Anna, et al. (author)
  • Quantifying Earth system interactions for sustainable food production via expert elicitation
  • 2022
  • In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 5:10, s. 830-842
  • Journal article (peer-reviewed)abstract
    • Several safe boundaries of critical Earth system processes have already been crossed due to human perturbations; not accounting for their interactions may further narrow the safe operating space for humanity. Using expert knowledge elicitation, we explored interactions among seven variables representing Earth system processes relevant to food production, identifying many interactions little explored in Earth system literature. We found that green water and land system change affect other Earth system processes strongly, while land, freshwater and ocean components of biosphere integrity are the most impacted by other Earth system processes, most notably blue water and biogeochemical flows. We also mapped a complex network of mechanisms mediating these interactions and created a future research prioritization scheme based on interaction strengths and existing knowledge gaps. Our study improves the understanding of Earth system interactions, with sustainability implications including improved Earth system modelling and more explicit biophysical limits for future food production.
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  • Erlandsson, Kerstin, 1961-, et al. (author)
  • Half-time evaluation of a new 4-year Ph.D. program in nursing and midwifery at the University of Gondar, Ethiopia
  • 2021
  • In: Global Health Action. - : Taylor and Francis Ltd.. - 1654-9716 .- 1654-9880. ; 14:1
  • Journal article (peer-reviewed)abstract
    • A new four-year Ph.D. programme in nursing and midwifery, the first of its kind in Ethiopia, was started in 2018/2019 at the University of Gondar when eight doctoral students in nursing and midwifery entered the program. We who have been involved see this as an appropriate time to evaluate what has been accomplished to date and to look toward future possibilities. Our aim in carrying out such an evaluation and presenting our findings is in part to determine if similar programs might be developed in other similar settings and in part to learn what modifications to the present program might be considered. The key elements of a questionnaire survey with closed and open response alternatives were based on the content, structure and learning outcomes of the home university Ph.D. programme as described in the curriculum. The questionnaire responses captured changes that would be needed to maintain a fully satisfactory programme that blends onsite instruction and online access to faculty resulting in a twenty-first century blended Ph.D. programme. Improved dialogue between the home university faculty and the external supervisors is needed. The programme can provide a career pathway that midwifery and nursing educators can follow in their own country rather than having to leave to study in another country. The findings provide insight into the feasibility of extending similar Ph.D. programmes to other parts of East Africa and with the SDG 5 in mind with an increased focus on women leadership. The justification for this initiative is to meet the need for more nursing and midwifery faculty who can provide quality midwifery and nursing education in East African countries. Retention of these professionals will help to deal with the shortage of healthcare personnel and will provide better care for the general population. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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  • Erlandsson, Kerstin, 1961-, et al. (author)
  • Implementing an internet-based capacity building program for interdisciplinary midwifery-lead teams in Ethiopia, Kenya Malawi and Somalia
  • 2021
  • In: Sexual & Reproductive HealthCare. - : Elsevier B.V.. - 1877-5756 .- 1877-5764. ; 30
  • Journal article (peer-reviewed)abstract
    • The Swedish care model MIDWIZE defined as midwife-led interdisciplinary care and zero separation between mother and newborn, was implemented in 2020–21 in Ethiopia, Kenya, Malawi, and Somalia in a capacity building programme funded by the Swedish Institute. Objective: To determine the feasibility of using an internet-based capacity building programme contributing to effective midwifery practices in the labour rooms through implementation of dynamic birthing positions, delayed umbilical cord clamping and skin-to-skin care of newborns in the immediate postnatal period. Methods: The design is inspired by process evaluation. Focus group discussions with policy leaders, academicians, and clinicians who participated in the capacity building programme were carried out. Before and after the intervention, the numbers for dynamic birthing positions, delayed umbilical cord clamping and skin-to-skin care of the newborn in the immediate postnatal period were detected. Results: Participants believed the internet-based programme was appropriate for their countries’ contexts based on their need for improved leadership and collaboration, the need for strengthened human resources, and the vast need for improved outcomes of maternal and newborn health. Conclusion: The findings provide insight into the feasibility to expand similar online capacity building programmes in collaboration with onsite policy leaders, academicians, and clinicians in sub-Saharan African countries with an agenda for improvements in maternal and child health. © 2021
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  • Erlandsson, M, et al. (author)
  • TRANSCRIPTIONAL ACTIVITY OF SURVIVIN CONTRIBUTES TO MATURATION AND FUNCTION OF THE INTERFERON-GAMMA PRODUCING T CELLS IN RHEUMATOID ARTHRITIS
  • 2020
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 83-84
  • Conference paper (other academic/artistic)abstract
    • Interferon gamma (IFNg) signalling and downstream effects make important contribution in pathogenesis of rheumatoid arthritis (RA). Here, we propose a mechanism by which oncoprotein survivin participates in development of IFN-dependent repertoire of T cells in RA patients.Objectives:We study the role of survivin in the phenotype of CD4 T cells of RA patients.Methods:CD4 cells of RA patients and healthy controls were purified from blood, activated and subjected to RNAseq, ChIPseq with antibodies to survivin (BIRC5) was performed on CD4+ cells. Histone H3 ChIPseq was performed using antibodies to H3K27ac, H3K27me3 and H3K4me3. Statistical analysis was performed In R-studio using the Bioconductor package DESeq2, clustering using Spearman and Ward.D2.Results:Unsupervised clustering of CD4 samples by expression of 48 core Th cell markers identified subsets of CD28hiCD27hiIFNnegcentral memory cells (Tcm), CD28loCD27loIFNloeffector memory cells (Tem) and CD28nullCD27nullIFNhiterminal effector cells (Tte). Tte cells showed classical features of Th1 cells including high levels of TBX21, TNFa and IL32 and signs of activation in IFN signalling machinery. Interestingly, they combined the features of peripheral Tregs CD25hiFoxp3hiIKZF2negand IL10 producing cells together with type 1 regulatory cells, which rely on transcription factors BATF and IRF1 for the differentiation and produced high amounts of perforin and granzyme B. Importantly, Tte CD4 cells had also high transcription of BIRC5 (p=1.15e-18).To study if BIRC5 is a part of IFN signalling, CD4 cells were cultured with survivin inhibitor YM155 and activated with IFNg. RNAseq analysis revealed 2033 (FC<2.0, n=336) differentially expressed genes in the IFN stimulated cultures. Interestingly, a substantial number of these IFN-dependent genes was significantly reduced in the survivin-deficient cultures and included among others CD28, FoxP3, IKZF2, ICOS, BATF, PRDM1, CXCR3, IRF4 and IRF8. Analysis of the peak sequences identified enrichment for composite motifs for IRFs (ETS:IRF, p1.0e-124; bZIP:IRF, p=1.0e-640), indicating that survivin is important for IFNg signalling. Numerically, the peaks containing ETS:IRF motifs were most prevalent and identified in total within 49.7% of all survivin-ChIP peaks. Frequent was co-localisation of the IRF:bZIP and IRF:ETS motifs within the survivin peaks. Among the IRF motifs dominated those suitable for IRF1 (p=1,0e-127) and IRF8 (p=1,0e-84). However, the DNA binding motifs of these two are alike.Encouraged by the survivin ChIPseq results, we wanted to know its relation to histone marks. We observed that 50% of survivin peaks containing both IRF:bZIP and IRF:ETS motifs are co-localized with the H3K27ac marks. In total, 16 of 48 core Th cell markers used for patients clustering were identified by survivin ChIPseq, co-localized with IRF composite motifs and histone marks. They were also dependent of survivin for expression.Conclusion:his study showed that survivin binds to DNA and regulates the core gene expression contributing to maturation and function of the IFNg producing Th1 cells.References:-Disclosure of Interests:Malin Erlandsson: None declared, Karin ME Andersson: None declared, Nisha Nair: None declared, Anastasius Damdimopoulos: None declared, Sofia Töyrä Silfverswärd: None declared, Rille Pullerits: None declared, Anne Barton Consultant of: AbbVie, Maria I Bokarewa: None declared
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  • Agalave, Nilesh M., et al. (author)
  • Sex-dependent role of microglia in disulfide high mobility group box 1 protein-mediated mechanical hypersensitivity
  • 2021
  • In: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 162:2, s. 446-458
  • Journal article (peer-reviewed)abstract
    • High mobility group box 1 protein (HMGB1) is increasingly regarded as an important player in the spinal regulation of chronic pain. Although it has been reported that HMGB1 induces spinal glial activation in a Toll-like receptor (TLR)4-dependent fashion, the aspect of sexual dimorphisms has not been thoroughly addressed. Here, we examined whether the action of TLR4-activating, partially reduced disulfide HMGB1 on microglia induces nociceptive behaviors in a sex-dependent manner. We found disulfide HMGB1 to equally increase microglial Iba1 immunoreactivity in lumbar spinal dorsal horn in male and female mice, but evoke higher cytokine and chemokine expression in primary microglial culture derived from males compared to females. Interestingly, TLR4 ablation in myeloid-derived cells, which include microglia, only protected male mice from developing HMGB1-induced mechanical hypersensitivity. Spinal administration of the glial inhibitor, minocycline, with disulfide HMGB1 also prevented pain-like behavior in male mice. To further explore sex difference, we examined the global spinal protein expression using liquid chromatography-mass spectrometry and found several antinociceptive and anti-inflammatory proteins to be upregulated in only male mice subjected to minocycline. One of the proteins elevated, alpha-1-antitrypsin, partially protected males but not females from developing HMGB1-induced pain. Targeting downstream proteins of alpha-1-antitrypsin failed to produce robust sex differences in pain-like behavior, suggesting that several proteins identified by liquid chromatography-mass spectrometry are required to modulate the effects. Taken together, the current study highlights the importance of mapping sex dimorphisms in pain mechanisms and point to processes potentially involved in the spinal antinociceptive effect of microglial inhibition in male mice.
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  • Andersson, KM, et al. (author)
  • SURVIVIN INHIBITS TRANSCRIPTION OF PBX1 AND SUPPORTS THE EFFECTOR PHENOTYPE OF THE MEMORY CD4 T CELLS IN RHEUMATOID ARTHRITIS
  • 2020
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 227-228
  • Conference paper (other academic/artistic)abstract
    • The oncogenic protein survivin is a marker of severe rheumatoid arthritis (RA). High serum levels of Survivin predict progressive joint damage1and poor treatment response2.Objectives:To study the role of survivin in the transcriptional regulation of phenotype in CD4+T cells.Methods:CD4+T cells of RA female patients were isolated from the perpheral blood. Activated CD4+cells were treated with survivin inhibitor YM155. Transcriptional analysis was done by RNAseq (Illumina) and conventional qPCR. Chromatin of CD4 cells was immunoprecipitated using polyclonal antibodies to survivin and subjected to deep sequencing (survivin ChIPseq, Hiseq2000, Illumina) and aligned to GRCh38. Statistical analysis of differentially expressed genes (DEG) was done in R-studio using Benjamini-Hochberg adjustment for multiple testing (Bioconductor, DESeq2 package).Results:Survivin ChIPseq of the activated CD4+T cells was enriched with the genes engaged in regulatory transcription factor specific DNA binding (GO:0000987, adj p=0.0005) and RNA polymerase II regulatory transcription (GO:0000978, adj p = 0.0004). Among survivin targets were the genes of HOX-B cluster and TALE family proteins MEIS, PKNOX and PBX1 controlling early leukopoesis and T cell maturation. Inhibition of survivin in PBMC resulted in significant upregulation of PBX1 (p=0.023), MEIS3 (p=0.0036), similar tendency was observed for HOXB6 and HOXC4 genes. RNAseq analysis CD4 cells of RA patients with different transcription of PBX1, identified 1636 genes (adj p<10-5). BIRC5, coding for survivin, was 8.3 folds higher in CD4+cells with low PBX1 (p=0.0005). Among the core transcription factors of T helper cell differentiation, we identifed NF-kB1 and NF-kB2, TBX21, IRF4, IRF8 and STAT3, BATF and BATF3. This followed by significantly higher TNF, IFNg and IL17A and IL17F in PBX1lo CD4 T cells. The pathway enrichment analysis of DEG identified strong over-representation of cytokine-specific genes (GO:005125, GO:0005126, GO:0048018, GO:0030545, FDR q-values 10-12-10-9). The genes of IL4, IL5, IL13, IL9, IL3 and CSF2 located within the chromosome 5 were common for all GO-lists, and were higher in PBX1lo, but none of those genes was identified by survivin-ChIPseq or PBX1-ChIPseq. Analysis of ChIPseq data identified the genes of STAT3, IRF4, IRF8 and BATF as common targets for PBX1 and survivin.Conclusion:This genome-wide analysis indicates that survivin regulates transcription of the TALE family protein PBX1 in CD4+ T cells, which has essential effect for differentiation and phenotype of Th subsets. Low PBX1 in RA patients is associated with terminally differentiated effector CD4+ T cells.References:[1]Svensson, B.et.al.Smoking in combination with antibodies to cyclic citrullinated peptides is associated with persistently high levels of survivin in early rheumatoid arthritis: a prospective cohort study.Arthritis Res Ther16, R12 (2014).[2]Levitsky, A.et.al.Serum survivin predicts responses to treatment in active rheumatoid arthritis: a post hoc analysis from the SWEFOT trial.BMC Med13, 247 (2015).Disclosure of Interests:None declared
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  • Andersson, Per A, 1986- (author)
  • Norms in Prosocial Decisions : The Role of Observability, Avoidance, and Conditionality
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Prosocial behaviors benefit other people and range from donations to charity to behavior limiting the spread of disease, such as masking and vaccination. The overarching purpose of this thesis was to contribute to our understanding of how social norms and conformity affect prosocial behavior. Here, three norm-related factors that affect such prosocial behavior were investigated: observability, avoidance and conditionality. Observability concerns whether a person is being observed during prosocial decisions, which can typically increase conformity to norms. Avoidance concerns whether a person avoids or seeks out knowledge about prosocial norms. Conditionality concerns the conditional nature of when behavior shifts occur in relation to others behavior. For instance, a person may want to follow a prosocial norm only if a very large majority adheres to it, or only if the goal of the norm is realistic to attain. Paper I focused on observability of prosocial decisions. Making decisions while knowing they would be shown to others increased prosocial behavior in the form of cooperation in a Public Goods Game, and preferences for deontological choices in moral dilemmas, but not donations given to charity. Paper II examined the existence of avoidance behavior regarding social norm about donations. Such norm avoiders appeared to be comprised of both prosocial and less prosocial individuals. Paper III investigated the interplay between descriptive (what people do) and injunctive (what one should do) norms in regards to masking during COVID-19. Paper IV then explored how varying the goal set for a prosocial norm affects willingness to try to achieve the goal, in the context of thresholds for herd immunity and vaccines for COVID-19. Some individuals were demotivated by seeing a higher goal as harder to achieve and others were motivated by believing a higher goal to lead to more people getting vaccinated. Taken together, these papers point to the inherent complexity of how norms relate to prosocial behavior, and suggest relevant aspects to consider when wanting to promote prosocial behavior. 
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  • Andersson, Per A, 1986-, et al. (author)
  • Prosocial and moral behavior under decision reveal in a public environment
  • 2020
  • In: Journal of Behavioral and Experimental Economics. - : Elsevier. - 2214-8043 .- 2214-8051. ; 87
  • Journal article (peer-reviewed)abstract
    • People may act differently in public environments due to actual reputation concerns, or due to the mere presence of others. Unlike previous studies on the influence of observability on prosocial behavior we control for the latter while manipulating the former, i.e. we control for implicit reputation concerns while manipulating explicit. We show that revealing decisions in public did not affect altruistic behavior, while it increased cooperation and made subjects less likely to make utilitarian judgments in sacrificial dilemmas (i.e., harming one to save many). Our findings are in line with theoretical models suggesting that people, at large, are averse to standing out in both positive and negative ways when it comes to altruistic giving. This "wallflower effect" does however not seem to extend to decisions on cooperation and moral judgments made in public.
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  • Blomgren, Johanna, et al. (author)
  • Maternal health leaders' perceptions of barriers to midwife-led care in Ethiopia, Kenya, Malawi, Somalia, and Uganda
  • 2023
  • In: Midwifery. - 0266-6138 .- 1532-3099. ; 124, s. 103734-
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To identify and examine barriers to midwife-led care in Eastern Africa and how these barriers can be reduced DESIGN: A qualitative inductive study with online focus group discussions and semi-structured interviews using content analysis SETTING: The study examines midwife-led care in Ethiopia, Malawi, Kenya, Somalia, and Uganda -five African countries with an unmet need for midwives and a need to improve maternal and neonatal health outcomes.PARTICIPANTS: Twenty-five participants with a health care profession background and current position as a maternal and child health leader from one of the five study countries.FINDINGS: The findings demonstrate barriers to midwife-led care connected to organisational structures, traditional hierarchies, gender disparities, and inadequate leadership. Societal and gendered norms, organisational traditions, and differences in power and authority between professions are some factors explaining why the barriers persist. A focus on intra- and multisectoral collaborations, the inclusion of midwife leaders, and providing midwives with role models to leverage their empowerment are examples of how to reduce the barriers.KEY CONCLUSIONS: This study provides new knowledge on midwife-led care from the perspectives of health leaders in five African countries. Transforming outdated structures to ensure midwives are empowered to deliver midwife-led care at all healthcare system levels is crucial to moving forward.IMPLICATIONS FOR PRACTISE: This knowledge is important as enhancing the midwife-led care provision is associated with substantially improved maternal and neonatal health outcomes, higher satisfaction of care, and enhanced utilisation of health system resources. Nevertheless, the model of care is not adequately integrated into the five countries' health systems. Future studies are warranted to further explore how reducing barriers to midwife-led care can be adapted at a broader level.
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  • Chandrasekaran, V, et al. (author)
  • AGGREGATED SURVIVIN BINDING AROUND HISTONE H3 EPIGENETIC MODIFICATIONS IN RISK LOCI ASSOCIATED WITH RHEUMATOID ARTHRITIS
  • 2021
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 428-428
  • Conference paper (other academic/artistic)abstract
    • Survivin is an integral part of the Chromosomal Passenger Complex (CPC) which plays a vital role in mitosis. Experiments have demonstrated that survivin can physically bind to DNA. Crystallographic studies show that survivin binds to Threonine-3 of histone H3. In patients with autoimmune diseases, increased survivin expression contributes to an aggravated disease phenotype. Thus, functional, and mechanistic data point to a potential chromatin regulatory role for survivin, possibly in combination with the established gene regulatory function carried out by histone epigenetic modifications (EM).Objectives:The objective of the study was to analyse the co-localization of chromatin bound survivin with three histone H3 epigenetic modifications – acetylated lysine 27 (K27ac) and trimethylated lysine 4 (K4me3) and lysine-27 (K27me3). The second objective was to analyse if survivin-bound DNA sequences overlapped with sequences in the vicinity of 106 GWAS SNPs that are associated with a risk of developing rheumatoid arthritis (RA).Methods:Chromatin from CD4 T cells of 14 female subjects was immunoprecipitated with survivin antibodies and each of the histone H3 antibodies, and coupled with sequencing (ChIPseq, Hiseq2000, Illumina). After mapping the annotations of sequenced regions to the human reference genome hg38, enriched peaks were identified through Homer software. The identified survivin ChIP peaks were analysed for colocalization with peaks of the three histone H3 EMs and with RA risk loci, using the Bioconductor package ‘ChIPPeakAnno’ through RStudio.Results:Among the total of ~13,000 individual survivin ChIP-peaks, 33% colocalized with histone H3 EM peaks. The overlapping peaks show a linear increase in average peak size compared with the peaks showing no colocalization with any H3 EM peak. A maximum of 5.5-fold increase in average peak size was observed when survivin bound peaks overlap with peaks of all three H3 EMs. A major proportion (86%) of top RA risk SNPs was associated with either binding of survivin or H3 EMs. In this subset, 63% of RA risk SNPs were found within an area of 100 kilobases from survivin ChIP-peaks, with preferential enrichment of high-scoring peaks when survivin colocalizes with all 3 H3 EMs. Survivin was bound to risk SNPs annotated to, among others, the major immunological genes CD83, IRF4, CD28, ICOS and IL2RAConclusion:This study presents experimental evidence that survivin binding to DNA preferentially occurred in regions with high density of histone EMs. The increased aggregation of survivin around histone H3 EMs point to its potential regulatory function in gene transcription. Since regions around RA risk SNPs overlap with survivin peaks, survivin’s nuclear function could have immunologically important effects in mechanisms of autoimmune diseases.Disclosure of Interests:None declared
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  • Chandrasekaran, V, et al. (author)
  • FUNCTIONAL ROLE OF SURVIVIN IN ORGANIZATION OF BIVALENT CHROMATIN REGIONS AND CONSEQUENCE FOR ARTHRITIS-RELEVANT GENE EXPRESSION
  • 2022
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 231-231
  • Conference paper (other academic/artistic)abstract
    • Bivalent chromatin (BvCR) is characterized by the presence of simultaneous active and repressive modifications on histone H3 proteins. Influencing expression of the genes, BvCR determine cell fate and direct differentiation and lineage commitment in primary T cells and contribute to autoimmunity. Survivin is highly expressed during cell division and in effector Th1 cells contributing to aggravation of autoimmune inflammation. Survivin can physically bind to DNA, specifically to Threonine-3 of histone H3 (1). Thus, functional, and mechanistic data point to a potential chromatin regulatory role for survivin, potentially acting in combination with histone epigenetic modifications (EMs).ObjectivesThe goal of our study is to establish the colocalization of survivin with BvCRs and to deduce functional effects of this collaboration on chromatin organization and gene expression.MethodsChromatin from CD4+ T cells of 14 female subjects was immunoprecipitated with survivin antibodies and histone H3K27ac, H3K27me3, H3K4me3 antibodies, and coupled with DNA sequencing (ChIPseq, Hiseq2000, Illumina). BvCR were identified as exact overlaps of the three histone EM peaks and the overlapping regions were searched for co-localization with survivin using the ‘ChIPPeakAnno’ Bioconductor package. Tag counts K27me3>K27ac were defined as inactive/poised BvCR, while tag count K27me3<K27ac were identified asactive BvCR. Motif search was done through the MEME tool, and high/moderate complexity motifs with E-value >10e-5 were selected and scanned through the HOCOMOCO database to identify consensus transcription factor (TF) motifs. TFs co-localized with the BvCD were identified through ReMap database. To identify survivin sensitive genes, CD4+ T cells were treated with survivin inhibitor YM155 and a list of reproducible DEG (log2FC>[0.4], >1 experiment) was mapped and analysed for clustering with BvCR.ResultsCo-localization of survivin ChIP peaks with individual H3-peaks was significantly less frequent compared to overlap with all three (a3)-H3 BvCR (7.1 vs 29.8%, p=8.9e-13). Overlap of a3-H3 peaks not containing survivin was less frequent (34%) compared to those which contained survivin (66%). Notably, survivin peak size was 5.5-fold higher when colocalized with a3-H3 peaks, compared to no, or any single H3 (p<2.2e-16). In contrast, no size difference for any of the H3 EM peaks was found.Further analysis of two non-redundant groups of BvCR that contain (survivin-a3H3, n=4085), and not containing survivin (a3H3noSurv, n = 2131) demonstrated that survivin was mostly associated with inactive BvCR (OR1.29, p=6.6e-6), while no such specificity was found for BvCR with no survivin. Additionally, survivin containing BvCR contained abundant binding sites matching known consensus TF motifs. No sequence-specific motifs were identified in BvCR with no survivin. Comparison of results obtained through HOCOMOCO and ReMap databases resulted in a list of 68 unique TFs. Many of those are key regulators of adaptive immune responses, cellular metabolism, and pluripotency. Differentially expressed genes mapped to BvCR demonstrated enrichment for cellular hormone metabolic processes, regeneration and DNA biosynthesis.ConclusionThis study provides experimental evidence that survivin defines binding specificity in bivalent chromatin regions being associated with regulation of cellular metabolism and renewal of CD4+ T cells that are functionally important to resist autoimmunity.References[1]Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B Science. 2010 Oct 8; 330(6001): 235–239.Disclosure of InterestsNone declared
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24.
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25.
  • Dai, L, et al. (author)
  • Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study
  • 2021
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2, s. e0247623-
  • Journal article (peer-reviewed)abstract
    • Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01–1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01–1.48 and 1.27, 1.01–1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.
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26.
  • de la Vega, Maria Pagnon, et al. (author)
  • The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation
  • 2021
  • In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:606
  • Journal article (peer-reviewed)abstract
    • Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.
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27.
  • Erlandsson, Arvid, et al. (author)
  • Moral preferences in helping dilemmas expressed by matching and forced choice
  • 2020
  • In: Judgment and Decision Making. - Tallahassee, FL, United States : SOC JUDGMENT & DECISION MAKING. - 1930-2975. ; 15:4, s. 452-475
  • Journal article (peer-reviewed)abstract
    • This paper asks whether moral preferences in eight medical dilemmas change as a function of how preferences are expressed, and how people choose when they are faced with two equally attractive help projects. In two large-scale studies, participants first read dilemmas where they "matched" two suggested helping projects (which varied on a single attribute) so that they became equally attractive. They did this by filling in a missing number (e.g., how many male patients must Project M save in order to be equally attractive as Project F which can save 100 female patients). Later, the same participants were asked to choose between the two equally attractive projects. We found robust evidence that people do not choose randomly, but instead tend to choose projects that help female (vs. male), children (vs. adult), innocent (vs. non-innocent), in group (vs. outgroup) and existing (vs. future) patients, and imply no (vs. some) risk of a harmful side-effect, even when these projects have been matched as equally attractive as, and save fewer patients than the contrasting project. We also found that some moral preferences are hidden when expressed with matching but apparent when expressed with forced choice. For example, 88-95% of the participants expressed that female and male patients are equally valuable when doing the matching task, but over 80% of them helped female patients in the choice task.
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28.
  • Erlandsson, Arvid, 1982-, et al. (author)
  • Type and amount of help as predictors for impression of helpers
  • 2020
  • In: PLOS ONE. - San Francisco, CA, United States : Public Library of Science. - 1932-6203. ; 15:12
  • Journal article (peer-reviewed)abstract
    • Impression of helpers can vary as a function of the magnitude of helping (amount of help) and of situational and motivational aspects (type of help). Over three studies conducted in Sweden and the US, we manipulated both the amount and the type of help in ten diverse vignettes and measured participants’ impressions of the described helpers. Impressions were almost unaffected when increasing the amount of help by 500%, but clearly affected by several type of help-manipulations. Particularly, helpers were less positively evaluated if they had mixed motives for helping, did not experience intense emotions or empathy, or if helping involved no personal sacrifice. In line with the person-centered theory of moral judgment, people seem to form impressions of helpers primarily based on the presumed underlying processes and motives of prosociality rather than its consequences.
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29.
  • Faithfull, Carolyn (author)
  • Ekosystemtjänstanalyser som stöd för en regional ekosystembaserad havsförvaltning : Erfarenheter från tre pilotområden: 8-fjordar, Stockholms skärgård och Södra Bottenhavet
  • 2024
  • Reports (other academic/artistic)abstract
    • Kartläggning och analys av ekosystemtjänster är viktiga verktyg för att synliggöra människans relation till och beroende av ekosystemet. De kan till exempel påvisa samband mellan processer i ekosystemet och samhället, och användas som underlag för att diskutera avvägningar mellan olika mål och intressen. I ekosystembaserad havsförvaltning kan diskussioner om ekosystemtjänster öka aktörers förståelse för ekosystemet som grund för vårt nyttjande av havet. De kan också stödja åtgärdsarbete och strategisk planering. Här presenterar vi analyser av ekosystemtjänster som tagits fram som underlag för en regional ekosystembaserad havsförvaltning i Södra Bottenhavet, Stockholms skärgård och området 8+fjordar i Bohuslän. Vi har dels använt två olika metoder för att kartlägga utbredningen av ekosystemtjänster och associerade nyttigheter i pilotområden - en naturbaserad metod som utgår från utbredningen av ekosystemkomponenter och en öppen GIS-metod för att samla in lokal kunskap om ekosystemtjänster från intressenter och allmänhet.Den naturbaserade kartläggningen gjordes för Södra Bottenhavet och Stockholms skärgård. Studien hade som mål att utveckla och testa en metod för att kartlägga kustnära ekosystemtjänster utifrån kartor av arter och livsmiljöer och utvärdera hur metoden kan användas för ekosystembaserad planering. Vi har gjort en bedömning av vilka ekosystemtjänster som är relevanta att kartlägga med metoden i dessa områden och vilka arter och livsmiljöer som främst kan förväntas bidra till dessa tjänster. För att lätt kunna dela resultaten har vi utvecklat en app som tillåter en användare att ta fram potentiella ekosystemtjänstkartor utifrån kartor över arter och livsmiljöer. Som nästa steg behöver appen utvärderas tillsammans med användare, för att testa användbarhet och vidare utvecklingsbehov.Öppen-GIS-analysen gjordes inom projektet 8+fjordar, där intressenter och allmänhet bjöds in till workshops för att beskriva sin syn på områdets värden och vad som påverkar miljön i området. De resulterande GIS-lagren ger en bild av hur användare av det lokala ekosystemet uppfattar sin närmiljö och vilka ekosystemtjänster de värdesätter och nyttjar. En initial utvärdering visar att resultaten kan användas till exempel för att identifiera platser där det finns konflikter mellan olika användningar av havet och peka ut behov av åtgärder för att lösa dessa konflikter. Processen att ta fram underlagen bidrog dessutom till ett gemensamt lärande inom projektet.Den tredje metoden som vi har använt är en enkät- och intervjustudie för att undersöka markägares attityder och preferenser i samband med åtgärdsarbete i Stockholms skärgård. Den här studien fokuserade på vilka ekosystemtjänster och nyttigheter markägare värdesätter i naturtypen grunda havsvikar. Resultatet kompletterar kunskapen om människans förhållande till denna naturtyp och lägger en viktig grund för att inkludera sociala mål och indikatorer i arbetet för att skydda och restaurera grunda havsvikar.Ekosystemtjänster är fortfarande ett abstrakt begrepp för många och rapporten syftar till att genom exempel synliggöra hur ekosystemtjänster kan användas för att stödja en långsiktigt hållbar förvaltning av kustområden. Att ta hänsyn till det komplexa samspelet mellan människa och natur är en central del av ekosystembaserad förvaltning. Våra tre exempel fyller delvis olika syften inom denna komplexitet. De kan användas individuellt för särskilda ändamål eller komplettera varandra. I samtliga fall är det viktigt att arbeta nära aktörer för att tydligt definiera behov, syften, och säkerställa att de slutliga resultaten blir lokalt användbara.
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30.
  • Ferede, A. J., et al. (author)
  • Patients’ perceptions of caring behaviors at referral hospitals in Ethiopia : A cross-sectional survey
  • 2023
  • In: International Journal of Nursing Sciences. - : Chinese Nursing Association. - 2352-0132. ; 10:3, s. 391-397
  • Journal article (peer-reviewed)abstract
    • Objective: The purpose of this study was to determine patients’ perceptions of nurse caring behaviors and to identify factors associated with these perceptions. Methods: A cross-sectional study was conducted at three referral hospitals in Ethiopia. A consecutive sample of male and female patients (n = 652, response rate 98.8%) was interviewed using the Amharic version of the Caring Behaviors Inventory-16 (CBI-16, including four subscales: Assurance, Knowledge and skill, Respectful, and Connectedness) and the Patient Satisfaction Instrument (PSI). Socio-demographic and clinical factors associated with perceptions of caring behaviors were identified using multiple linear regression analysis. Results: Patients’ perceptions of nurse caring behaviors were high (total Mean = 4.86, SD = 0.72). Behaviors related to the Assurance subscale were rated the highest. The multiple linear regression analysis result showed several socio-demographic and clinical factors statistically significantly associated with patients’ perceptions of caring behaviors (total mean scores). Patients who were 40–49 years (B = −0.19, P = 0.012) and single (B = −0.13, P = 0.03) scored lower on total CBI-16 scores. Whereas, patients who had a higher educational level (B = 0.35, P = 0.001), cared for at surgery units (B = 0.11, P = 0.027), and reported having spent more time with a nurse in the past 8-h shift (B = 0.16, P < 0.001) were more likely to have higher perceptions of the care they received. The CBI-16 was positively correlated with satisfaction with received care, as measured with the Patient Satisfaction Instrument (r = 0.62, P < 0.001). Conclusion: Hospitalized patients in Ethiopia have overall high perceptions of nurse caring behaviors, especially with regard to physical-based caring, while their expectations of emotional-focused care are lower. We identified patients who were in need of care, patients aged 40–49 years and single. The time spent with nurses plays a pivotal role in patients’ perceptions of nurse caring behaviors. © 2023 The Authors
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31.
  • Gleeson, Tom, et al. (author)
  • Illuminating water cycle modifications and Earth system resilience in the Anthropocene
  • 2020
  • In: Water resources research. - 0043-1397 .- 1944-7973. ; 56:4
  • Journal article (peer-reviewed)abstract
    • Fresh water—the bloodstream of the biosphere—is at the center of the planetary drama of the Anthropocene. Water fluxes and stores regulate the Earth's climate and are essential for thriving aquatic and terrestrial ecosystems, as well as water, food, and energy security. But the water cycle is also being modified by humans at an unprecedented scale and rate. A holistic understanding of freshwater's role for Earth system resilience and the detection and monitoring of anthropogenic water cycle modifications across scales is urgent, yet existing methods and frameworks are not well suited for this. In this paper we highlight four core Earth system functions of water (hydroclimatic regulation, hydroecological regulation, storage, and transport) and key related processes. Building on systems and resilience theory, we review the evidence of regional‐scale regime shifts and disruptions of the Earth system functions of water. We then propose a framework for detecting, monitoring, and establishing safe limits to water cycle modifications and identify four possible spatially explicit methods for their quantification. In sum, this paper presents an ambitious scientific and policy grand challenge that could substantially improve our understanding of the role of water in the Earth system and cross‐scale management of water cycle modifications that would be a complementary approach to existing water management tools.
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32.
  • Görür, Yunus Can, et al. (author)
  • Rapidly Prepared Nanocellulose Hybrids as Gas Barrier, Flame Retardant, and Energy Storage Materials
  • 2022
  • In: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 5:7, s. 9188-9200
  • Journal article (peer-reviewed)abstract
    • Cellulose nanofibril (CNF) hybrid materials show great promise as sustainable alternatives to oil-based plastics owing to their abundance and renewability. Nonetheless, despite the enormous success achieved in preparing CNF hybrids at the laboratory scale, feasible implementation of these materials remains a major challenge due to the time-consuming and energy-intensive extraction and processing of CNFs. Here, we describe a scalable materials processing platform for rapid preparation (<10 min) of homogeneously distributed functional CNF-gibbsite and CNF-graphite hybrids through a pH-responsive self-assembly mechanism, followed by their application in gas barrier, flame retardancy, and energy storage materials. Incorporation of 5 wt % gibbsite results in strong, transparent, and oxygen barrier CNF-gibbsite hybrid films in 9 min. Increasing the gibbsite content to 20 wt % affords them self-extinguishing properties, while further lowering their dewatering time to 5 min. The strategy described herein also allows for the preparation of freestanding CNF-graphite hybrids (90 wt % graphite) that match the energy storage performance (330 mA h/g at low cycling rates) and processing speed (3 min dewatering) of commercial graphite anodes. Furthermore, these ecofriendly electrodes can be fully recycled, reformed, and reused while maintaining their initial performance. Overall, this versatile concept combines a green outlook with high processing speed and material performance, paving the way toward scalable processing of advanced ecofriendly hybrid materials. 
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33.
  • Jawak, Shridhar D., et al. (author)
  • SIOS's Earth Observation (EO), Remote Sensing (RS), and Operational Activities in Response to COVID-19
  • 2021
  • In: Remote Sensing. - : MDPI. - 2072-4292. ; 13:4
  • Journal article (peer-reviewed)abstract
    • Svalbard Integrated Arctic Earth Observing System (SIOS) is an international partnership of research institutions studying the environment and climate in and around Svalbard. SIOS is developing an efficient observing system, where researchers share technology, experience, and data, work together to close knowledge gaps, and decrease the environmental footprint of science. SIOS maintains and facilitates various scientific activities such as the State of the Environmental Science in Svalbard (SESS) report, international access to research infrastructure in Svalbard, Earth observation and remote sensing services, training courses for the Arctic science community, and open access to data. This perspective paper highlights the activities of SIOS Knowledge Centre, the central hub of SIOS, and the SIOS Remote Sensing Working Group (RSWG) in response to the unprecedented situation imposed by the global pandemic coronavirus (SARS-CoV-2) disease 2019 (COVID-19). The pandemic has affected Svalbard research in several ways. When Norway declared a nationwide lockdown to decrease the rate of spread of the COVID-19 in the community, even more strict measures were taken to protect the Svalbard community from the potential spread of the disease. Due to the lockdown, travel restrictions, and quarantine regulations declared by many nations, most physical meetings, training courses, conferences, and workshops worldwide were cancelled by the first week of March 2020. The resumption of physical scientific meetings is still uncertain in the foreseeable future. Additionally, field campaigns to polar regions, including Svalbard, were and remain severely affected. In response to this changing situation, SIOS initiated several operational activities suitable to mitigate the new challenges resulting from the pandemic. This article provides an extensive overview of SIOS's Earth observation (EO), remote sensing (RS) and other operational activities strengthened and developed in response to COVID-19 to support the Svalbard scientific community in times of cancelled/postponed field campaigns in Svalbard. These include (1) an initiative to patch up field data (in situ) with RS observations, (2) a logistics sharing notice board for effective coordinating field activities in the pandemic times, (3) a monthly webinar series and panel discussion on EO talks, (4) an online conference on EO and RS, (5) the SIOS's special issue in the Remote Sensing (MDPI) journal, (6) the conversion of a terrestrial remote sensing training course into an online edition, and (7) the announcement of opportunity (AO) in airborne remote sensing for filling the data gaps using aerial imagery and hyperspectral data. As SIOS is a consortium of 24 research institutions from 9 nations, this paper also presents an extensive overview of the activities from a few research institutes in pandemic times and highlights our upcoming activities for the next year 2021. Finally, we provide a critical perspective on our overall response, possible broader impacts, relevance to other observing systems, and future directions. We hope that our practical services, experiences, and activities implemented in these difficult times will motivate other similar monitoring programs and observing systems when responding to future challenging situations. With a broad scientific audience in mind, we present our perspective paper on activities in Svalbard as a case study.
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34.
  • Jensen, Maja, 1978, et al. (author)
  • Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27
  • 2023
  • In: Iscience. ; 26:7
  • Journal article (peer-reviewed)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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35.
  • Kelemu, Tsehayneh, et al. (author)
  • Polymorphism in killer cell immunoglobulin-like receptors and human leukocyte antigen-c and predisposition to preeclampsia in Ethiopian pregnant women population
  • 2020
  • In: Journal of Reproductive Immunology. - : Elsevier BV. - 0165-0378. ; 141
  • Journal article (peer-reviewed)abstract
    • Introduction: Preeclampsia (PE) is a human specific pregnancy-related syndrome of unknown etiology that affects 2–8 % of pregnancies. Polymorphism in maternal Killer Cell Immunoglobulin-like Receptors (KIRs) and the ligand fetal Human Leukocyte Antigen-C (HLA-C) may predispose pregnant mothers for PE due to defective trophoblast invasion into the maternal decidua. Our study aimed to investigate the association between maternal KIR and fetal HLA-C polymorphism and PE in Ethiopian pregnant women. Methods: We included a total of 288 (157 controls and 131 PE cases) in a case-controls study at Adama Regional Referral Hospital, Ethiopia. The KIR and HLA-C genotyping was done using traditional polymerase chain reaction on genomic DNA extracted form maternal venous and cord blood followed by 2% agarose gel electrophoresis. Results: The statistical associations between variables were evaluated using Pearson's Chi-square test. P < 0.05, with 95 % confidence interval was considered statistically significant. A significant association was observed between the KIR2DS1 and PE, with a higher frequency (60.5 %) of the gene in the control group. Similarly, a significant association was observed between KIR AA genotype and PE, with a higher frequency (38.2 %) of this genotype in the PE group. Ethiopians share the same risk genotype for PE as seen in previous African and European studies, namely homozygosity of a maternal KIR AA genotype. However, Ethiopians differ from other East African populations by sharing the same protective KIR2DS1 gene as Europeans.
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36.
  • Kiragu, J. M., et al. (author)
  • Costs and intermediate outcomes for the implementation of evidence-based practices of midwifery under a MIDWIZE framework in an urban health facility in Nairobi, Kenya
  • 2023
  • In: Sexual & Reproductive HealthCare. - : Elsevier. - 1877-5756 .- 1877-5764. ; 37
  • Journal article (peer-reviewed)abstract
    • Background: Three evidence-based midwife-led care practices: dynamic birth positions (DBP), immediate skin-to-skin contact (SSC) with zero separation between mother and newborn, and delayed cord clamping (DCC), were implemented in four sub-Saharan African countries after an internet-based capacity building program for midwifery leadership in quality improvement (QI). Knowledge on costs of this QI initiative can inform resource mobilization for scale up and sustainability. Methods: We estimated the costs and intermediate outcomes from the implementation of the three evidence-based practices under the midwife-led care (MIDWIZE) framework in a single facility in Kenya through a pre- and post-test implementation design. Daily observations for the level of practice on DBP, SSC and DCC was done at baseline for 1 week and continued during the 11 weeks of the training intervention. Three cost scenarios from the health facility perspective included: scenario 1; staff participation time costs ($515 USD), scenario 2; staff participation time costs plus hired trainer time costs, training material and logistical costs ($1318 USD) and scenario 3; staff participation time costs plus total program costs for the head trainer as the QI leader from the capacity building midwifery program ($8548 USD). Results: At baseline, the level of DBP and SSC practices per the guidelines was at 0 % while that of DCC was at 80 %. After 11 weeks, we observed an adoption of DBP practice of 36 % (N = 111 births), SSC practice of 79 % (N = 241 births), and no change in DCC practice. Major cost driver(s) were midwives’ participation time costs (56 %) for scenario 1 (collaborative), trainers’ material and logistic costs (55 %) in scenario 2(collaborative) and capacity building program costs for the trainer (QI lead) (94 %) in scenario 3 (programmatic). Costs per intermediate outcome were $2.3 USD per birth and $0.5 USD per birth adopting DBP and SSC respectively in Scenario 1; $6.0 USD per birth adopting DBP and $1.4 USD per birth adopting SSC in Scenario 2; $38.5 USD per birth adopting DBP and $8.8 USD per birth adopting SSC in scenario 3. The average hourly wage of the facility midwife was $4.7 USD. Conclusion: Improving adoption of DBP and SSC practices can be done at reasonable facility costs under a collaborative MIDWIZE QI approach. In a programmatic approach, higher facility costs would be needed. This can inform resource mobilization for future QI in similar resource-constrained settings. © 2023
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37.
  • Lafage, Denis, et al. (author)
  • A new primer for metabarcoding of spider gut contents
  • 2020
  • In: Environmental DNA. - : Wiley-Blackwell. - 2637-4943. ; 2:2, s. 234-243
  • Journal article (peer-reviewed)abstract
    • Abstract As a key predator group, spiders have received a lot of attention by food web ecologists. The difficulty involved in studying their diet has led to the use of new technologies such as metabarcoding of gut contents. The amplification of a broad range of spider prey without amplifying spiders themselves is challenging. Until now, an efficient universal primer for this purpose was not available. We developed a novel forward primer (NoSpi2) targeting the COI gene. The primer was designed not to amplify spiders of Pardosa genus while amplifying most other invertebrates. NoSpi2 was tested together with the reverse primer BR2 in silico, in vitro on single specimens of prey and spiders, on mock and malaise trap communities, and in an ecological application. In silico evaluation predicted high primer bias for Pardosa species and more generally for spiders of the oval calamistrum clade (Lycosidae and closely related species) and low bias for other invertebrates. These results were confirmed by in vitro tests. Additionally, some spider families were not amplified contrary to our expectations. We demonstrated a high efficiency for the primer pair NoSpi2/BR2 which recovered 94% of taxa in the mock community and 85% of the taxa detected by the best invertebrate primer pair known for the malaise trap community. The field experiment showed that Lycosidae (Hygrolycosa, Pardosa, Piratula, Trochosa) DNA is not amplified by NoSpi2/BR2. It demonstrated a broad range of detectable prey species (12 orders, 67 families, 117 species). The ability of NoSpi2/BR2 primer to reliably amplify prey species, without amplifying any predator DNA, makes it an ideal choice for gut content analysis for lycosid species and related species, even enabling the homogenization of entire specimens without dissection. Given that the detected prey species included other spiders and carabid beetles, this primer could be also used to study intraguild predation.
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38.
  • Malm, Mari-Cristin, et al. (author)
  • Somaliland women’s perception of stillbirth : a descriptive survey study
  • 2021
  • In: Somali Health Action Journal. - Umeå : Umeå University Library. - 2004-1985. ; 1:1
  • Journal article (peer-reviewed)abstract
    • Background: Somali women, not only those living in Somaliland but also those living abroad as asylum seekers and refugees, are highly vulnerable in terms of perinatal health outcomes. Respectful and supportive care is critical for all women when stillbirth occurs and improving bereavement care and reducing the stigma that surrounds stillbirth are global priorities. Culturally- and context-specific approaches that build on an understanding of the needs of women giving birth to a stillborn baby, no matter where or why, are required.Objective: This study aims to investigate and analyze Somali women’s experiences of stillbirth, including their perceived reasons for losing their unborn baby, the premonitions they had before giving birth and their experiences of psychosocial support from healthcare professionals and relatives.Methods: A descriptive retrospective study was conducted at the Borama regional hospital in Somaliland. A study-specific questionnaire was developed that gathered personal information and data on topics related to women’s experiences of stillbirth. Women who had either experienced a stillbirth at the hospital or had been referred there after a stillbirth 2015 were approached and 75 women agreed to participate in the study.Results: Most of the women were multiparas and had experienced a previous stillbirth. Before having it confirmed that their baby was no longer alive most of the woman reported that they had felt no fetal movements and had a premonition that something was wrong. The most common perceived cause of stillbirth that the women reported was prolonged labour followed by a ‘big baby’. Thirty-three women (44%) felt it was important to know the cause of the stillbirth and eight reported feeling angry or disappointed (11 %) with the health care providers who assisted them during labour, birth, or post-partum, although 41 women (55%) were satisfied with their treatment. A third of the women blamed themselves for their stillbirth and a majority spoke to others about it.Conclusions: Our results show that women in Somaliland share similar perceptions of stillbirth as women in high income countries. This raises important implications for antenatal care and preventive interventions and stressed the need to respond to women’s concerns regardless of background, context or setting. A maternal healthcare approach that is equal in its global application must be established to enable health care providers to give relevant information and care both in the cultural setting of Somaliland and elsewhere in the world where Somali-born women live and give birth.
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  • Oparina, N, et al. (author)
  • COMPLEX LANDSCAPE OF BIRC5/SURVIVIN GENOME BINDING IN HUMAN CD4+T CELLS
  • 2021
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 410-410
  • Conference paper (other academic/artistic)abstract
    • Survivin, coded by BIRC5 gene, is a multitasking protein essential for cell renewal and homeostasis. In autoimmune conditions as rheumatoid and psoriasis arthritis, survivin was associated with inflammation severity and joint damage. Importantly, inhibition of survivin alleviated experimental arthritis in mice. We have recently shown survivin to be essential for T cell differentiation and micro-RNA processing. The known anti-apoptotic and proliferation facilitating functions of survivin does not explain the nuclear localization of survivin in interphase.Objectives:We aimed to uncover nuclear functions of BIRC5/survivin in CD4 cell of RA patients and healthy.Methods:CD4 T cells were isolated from the peripheral blood using positive selection on magnetic beads (EasySep) and activated for 48h with ConA+LPS. Chromatin immunoprecipitation (ChIP) with polyclonal anti-survivin antibodies was done in four independent samples of healthy donors (n=5), healthy smokers (n=3), rheumatoid arthritis (n=3) and breast cancer (n=2). Pooled libraries were constructed for each group and ChIPseq was carried out (Illumina). For comparative RNAseq analysis, activated CD4 T cells were incubated with or without survivin inhibitor (YM155) for 24h. State-of-the-art bioinformatics pipelines were applied for NGS data and the survivin-binding peaks were used for comparison with genes, chromatin state annotation and functional gene- and regulatory regions-based functional analysis. Co-localization of peaks in the whole genome and in vicinity of the differentially expressed genes (DEG) was done using ReMap integrated ChIPseq datasets for all human cells and tissues.Results:We identified 13 thousands non-overlapping survivin ChIP-peaks (>3000 peaks were present in at least 3 samples). Survivin-bound regions were enriched near the genes and promoters (p=e-30 and p=e-8), which implied that survivin role in transcription could be mediated by known transcription factors. Thus, we analyzed survivin peaks vs binding regions of 1135 transcription regulators (TR) available in ReMap.Potential partner proteins of survivin were selected based on the enrichment of the overlapping peaks in the whole genome and in CD4-active regulatory areas. Both, strict overlaps and location within 10 and 100kb survivin peak vicinity were analyzed. This approach allowed us to select >150 TRs enriched in all tests. The enriched TRs were involved in immunity and RA-relevant pathways including cytokine response and production, JAK-STAT signaling, etc. Among the TRs co-localized with survivin were CHD8, MAX, EP300, BRD2, CTCF and RAD21, all responsible for chromatin architecture. Several TRs were massively enriched in the vicinity of DEGs after survivin depletion including MAX, AR, CTCF, MYC and IRF1. Search for TR binding motifs in survivin peaks supported over-representation of binding sites for IRFs (p=e-5) and several proteins of the bZIP-family (p=e-5).Conclusion:Analysis of the survivin bound DNA in CD4 cells demonstrated the nonrandom distribution with specific enrichment within the regulatory elements of the genes and co-localizeation with protein partners to regulate their transcription.Disclosure of Interests:None declared
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  • Roth, Nina, et al. (author)
  • A call for consistency with the terms ‘wetter’ and ‘drier’ in climate change studies
  • 2021
  • In: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 10
  • Research review (peer-reviewed)abstract
    • Ongoing and future hydroclimatic changes have large environmental and societal impacts. In terrestrial ecosystems, these changes are usually described with the terms ‘wetter’ and ‘drier’, which refer to the change in the quantity and/or presence of water, either as water fluxes or stocks. We conducted a literature review of almost 500 recent climate change studies to quantitatively investigate the consistency of the use of these terms across disciplines, regarding the hydroclimatic variables they are related to. We found that although precipitation is prevalently used to describe ‘wetter’ and ‘drier’ conditions, many other variables are also used to refer to changes in water availability between research fields, pointing to a varied perspective on the use of these terms. Some studies do not define the terms at all. In order to facilitate meta-analyses across disciplines, we therefore highlight the need to explicitly state which hydroclimatic variables authors are referring to. In this way, we hope that the terms ‘wetter’ and ‘drier’ used in scientific studies are easier to relate to hydroclimatic processes, which should facilitate the application by authorities and policy makers.
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45.
  • Staal, Arie, et al. (author)
  • Hysteresis of tropical forests in the 21st century
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Tropical forests modify the conditions they depend on through feedbacks at different spatial scales. These feedbacks shape the hysteresis (history-dependence) of tropical forests, thus controlling their resilience to deforestation and response to climate change. Here, we determine the emergent hysteresis from local-scale tipping points and regional-scale forest-rainfall feedbacks across the tropics under the recent climate and a severe climate-change scenario. By integrating remote sensing, a global hydrological model, and detailed atmospheric moisture tracking simulations, we find that forest-rainfall feedback expands the geographic range of possible forest distributions, especially in the Amazon. The Amazon forest could partially recover from complete deforestation, but may lose that resilience later this century. The Congo forest currently lacks resilience, but is predicted to gain it under climate change, whereas forests in Australasia are resilient under both current and future climates. Our results show how tropical forests shape their own distributions and create the climatic conditions that enable them. Tropical rainforests partly create their own climatic conditions by promoting precipitation, therefore rainforest losses may trigger dramatic shifts. Here the authors combine remote sensing, hydrological modelling, and atmospheric moisture tracking simulations to assess forest-rainfall feedbacks in three major tropical rainforest regions on Earth and simulate potential changes under a severe climate change scenario.
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