| 1. |
- Backman, Max, et al.
(author)
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Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
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In: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
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Journal article (peer-reviewed)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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| 2. |
- Backman, Max, 1987-, et al.
(author)
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Spatial immunophenotyping of the tumor microenvironment in non-small cell lung cancer
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Other publication (other academic/artistic)abstract
- Introduction: Immune cells in the tumor microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterize the spatial immune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence multispectral imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4 Eff), CD4 regulatory cells (CD4 Treg), CD8 effector cells (CD8 Eff), CD8 regulatory cells (CD8 Treg), B-cells, NK-cells, NKT-cells, M1 macrophages (M1), CD163+ myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs). Results: CD4 Eff cells, CD8 Eff cells, and M1 macrophages were the most abundant immune cells invading the tumor cell compartment and indicated a patient group with a favorable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4 Eff, CD4 Treg, CD8 Treg, and B-cells), as well as pDCs, were independently associated with longer survival. However, when these immune cells were located close to CD8 Treg cells, the favorable impact was attenuated. In the multivariate Cox regression model including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8 Treg–B-cells, CD8 Eff–cancer cells, and B-cells–CD4 Treg) demonstrated positive prognostic impact, while short M2–M1 distances were prognostically unfavorable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is also crucial for diagnostic use.
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| 3. |
- Backman, Max, 1987-, et al.
(author)
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Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer
- 2023
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 185, s. 40-52
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Journal article (peer-reviewed)abstract
- Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial im-mune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163 thorn myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs).Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use.
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| 4. |
- Bernhard, M., et al.
(author)
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Institutionalising electoral uncertainty and authoritarian regime survival
- 2020
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In: European Journal of Political Research. - : Wiley. - 0304-4130 .- 1475-6765. ; 59:2, s. 465-487
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Journal article (peer-reviewed)abstract
- Authoritarian incumbents routinely use democratic emulation as a strategy to extend their tenure in power. Yet, there is also evidence that multiparty competition makes electoral authoritarianism more vulnerable to failure. Proceeding from the assumption that the outcomes of authoritarian electoral openings are inherently uncertain, it is argued in this article that the institutionalisation of elections determines whether electoral authoritarianism promotes stability or vulnerability. By 'institutionalisation', it is meant the ability of authoritarian regimes to reduce uncertainty over outcomes as they regularly hold multiparty elections. Using discrete-time event-history models for competing risks, the effects of sequences of multiparty elections on patterns of regime survival and failure in 262 authoritarian regimes from 1946 to 2010 are assessed, conditioned on their degree of competitiveness. The findings suggest that the institutionalisation of electoral uncertainty enhances authoritarian regime survival. However, for competitive electoral authoritarian regimes this entails substantial risk. The first three elections substantially increase the probability of democratisation, with the danger subsequently diminishing. This suggests that convoking multiparty competition is a risky game with potentially high rewards for autocrats who manage to institutionalise elections. Yet, only a small number of authoritarian regimes survive as competitive beyond the first few elections, suggesting that truly competitive authoritarianism is hard to institutionalise. The study thus finds that the question of whether elections are dangerous or stabilising for authoritarianism is dependent on differences between the ability of competitive and hegemonic forms of electoral authoritarianism to reduce electoral uncertainty.
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| 5. |
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| 6. |
- Boese, Vanessa Alexandra, et al.
(author)
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Deterring Dictatorship: Explaining Democratic Resilience since 1900
- 2020
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In: SSRN Electronic Journal. - Göteborg : Göteborgs universitet. - 1556-5068.
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Other publication (other academic/artistic)abstract
- Democracy is under threat globally from democratically elected leaders engaging in erosion of media freedom, civil society, and the rule of law. What distinguishes democracies that prevail against the forces of autocratization? This article breaks new ground by conceptualizing democratic resilience as a two-stage process, whereby democracies first exhibit resilience by avoiding autocratization altogether and second, by avoiding democratic breakdown given that autocratization has occurred. To model this two-stage process, we introduce the Episodes of Regime Transformation (ERT) dataset tracking autocratization since 1900. These data demonstrate the extraordinary nature of the current wave of autocratization: Fifty-nine (61%) episodes of democratic regression in the ERT began after 1992. Since then, autocratization episodes have killed an unprecedented 36 democratic regimes. Using a selection-model, we simultaneously test for factors that make democracies more prone to experience democratic regression and, given this, factors that explain democratic breakdown. Results from the explanatory analysis suggest that constraints on the executive are positively associated with a reduced risk of autocratization. Once autocratization is ongoing, we find that a long history of democratic institutions, durable judicial constraints on the executive, and more democratic neighbours are factors that make democracy more likely to prevail.
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| 7. |
- Boese, Vanessa Alexandra, et al.
(author)
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How democracies prevail: democratic resilience as a two-stage process
- 2021
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In: Democratization. - : Informa UK Limited. - 1351-0347 .- 1743-890X. ; 28:5, s. 885-907
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Journal article (peer-reviewed)abstract
- This article introduces a novel conceptualization of democratic resilience - a two-stage process where democracies avoid democratic declines altogether or avert democratic breakdown given that such autocratization is ongoing. Drawing on the Episodes of Regime Transformation (ERT) dataset, we find that democracies have had a high level of resilience to onset of autocratization since 1900. Nevertheless, democratic resilience has become substantially weaker since the end of the Cold War. Fifty-nine episodes of sustained and substantial declines in democratic practices have occurred since 1993, leading to the unprecedented breakdown of 36 democratic regimes. Ominously, we find that once autocratization begins, only one in five democracies manage to avert breakdown. We also analyse which factors are associated with each stage of democratic resilience. The results suggest that democracies are more resilient when strong judicial constraints on the executive are present and democratic institutions were strong in the past. Conversely and adding nuance to the literature, economic development is only associated with resilience to onset of autocratization, not to resilience against breakdown once autocratization has begun.
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| 8. |
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| 9. |
- Edgell, Amanda B, et al.
(author)
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Establishing Pathways to Democracy Using Domination Analysis
- 2020
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In: SSRN Electronic Journal. - Göteborg : Göteborgs universitet. - 1556-5068.
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Other publication (other academic/artistic)abstract
- How does the order in which liberalization unfolds affect the likelihood for a successful democratic transition? Dahl was among the first to argue that the sequence matters for the outcome when it comes to democratization. This paper builds upon his work and empirically analyzes pathways to democracy employing the newly developed method of domination analysis. We are the first to demonstrate three key findings: 1) There is a clear structure in terms of order of how most episodes of liberalization from authoritarian rule develop; 2) Such sequences are different in key respects for failed and successful episodes of liberalization; and 3) Clean election elements - in the capacity of electoral management bodies - stand out as developing earlier in episodes that successfully lead to democracy.
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| 10. |
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| 11. |
- Elfving, Hedvig, et al.
(author)
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Spatial distribution of tertiary lymphoid structures in the molecular and clinical context of non-small cell lung cancer.
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Other publication (other academic/artistic)abstract
- Tertiary lymphoid structures (TLS) are lymphocyte aggregates resembling secondary lymphoid organs and are pivotal in cancer immunity. The ambiguous morphological definition of TLS makes it challenging to ascertain their clinical impact on patient survival and response to immunotherapy. This study aimed to characterize TLS in hematoxylin-eosin tissue sections from lung cancer patients, assessing their occurrence in relation to the local immune environment, mutational background, and patient outcome.Two pathologists evaluated one whole tissue section from each resection specimen of 680 NSCLC patients. TLS were spatially quantified within the tumor area or periphery and further categorized based on the presence of germinal centers (mature TLS). Metrics were integrated with immune cell counts, genomic and transcriptomic data, and correlated with clinical parameters.Out of 536 evaluable cases, TLS were present in 86% of tumor samples, predominantly in the tumor periphery, with a median of eight TLS per case. TLS with germinal centers were found in 24% of cases. TLS presence correlated positively with increased plasma cell (CD138+) and lymphocytic cell (CD3+, CD8+, FOXP3+) infiltration. Tumors with higher tumor mutational burden (TMB) exhibited higher periphery TLS numbers. The overall TLS quantity was associated with improved patient survival, irrespective of TLS maturation status. This prognostic association held true for periphery TLS but not for tumor TLS.In conclusion, TLS occurrence in NSCLC is common and its correlation with a specific immune phenotype suggests biological relevance in the local immune reaction. The prognostic significance of this scoring system on routine hematoxylin-eosin sections has the potential to augment diagnostic algorithms for NSCLC patients.
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| 12. |
- Goldmann, Torsten, et al.
(author)
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PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
- 2021
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In: Cancer Immunology and Immunotherapy. - : Springer Nature. - 0340-7004 .- 1432-0851. ; 70:9, s. 2577-2587
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Journal article (peer-reviewed)abstract
- Gene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenvironment of amplified cases. The study was based on two independent NSCLC cohorts, including 354 and 349 cases, respectively. Tissue microarrays were used to evaluate PD-L1 amplification by FISH and PD-L1 protein by immunohistochemistry. Immune infiltrates were characterized immunohistochemically by a panel of immune markers (CD3, CD4, CD8, PD-1, Foxp3, CD20, CD138, CD168, CD45RO, NKp46). Mutational status was determined by targeted sequencing. RNAseq data was available for 197 patients. PD-L1 amplification was detected in 4.5% of all evaluable cases. PD-L1 amplification correlated only weakly with mRNA and protein expression. About 37% of amplified cases were negative for PD-L1 protein. PD-L1 amplification did not show any association with the mutational status. In squamous cell cancer, PD-L1 amplified cases were enriched among patients with high tumoral immune cell infiltration and showed gene expression profiles related to immune exhaustion. In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC and suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy.
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| 13. |
- Johansson, Josefin, et al.
(author)
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Loss of Nexilin function leads to a recessive lethal fetal cardiomyopathy characterized by cardiomegaly and endocardial fibroelastosis
- 2022
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In: American Journal of Medical Genetics. Part A. - : John Wiley & Sons. - 1552-4825 .- 1552-4833. ; 188:6, s. 1676-1687
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Journal article (peer-reviewed)abstract
- The Nexilin F-Actin Binding Protein (Nexilin) encoded by NEXN is a cardiac Z-disc protein important for cardiac function and development in humans, zebrafish, and mice. Heterozygote variants in the human NEXN gene have been reported to cause dilated and hypertrophic cardiomyopathy. Homozygous variants in NEXN cause a lethal form of human fetal cardiomyopathy, only described in two patients before. In a Swedish, four-generation, non-consanguineous family comprising 42 individuals, one female had three consecutive pregnancies with intrauterine fetal deaths caused by a lethal form of dilated cardiomyopathy. Whole-exome sequencing and variant analysis revealed that the affected fetuses were homozygous for a NEXN variant (NM_144573:c.1302del;p.(Ile435Serfs*3)). Moreover, autopsy and histology staining declared that they presented with cardiomegaly and endocardial fibroelastosis. Immunohistochemistry staining for Nexilin in the affected fetuses revealed reduced antibody staining and loss of striation in the heart, supporting loss of Nexilin function. Clinical examination of seven heterozygote carriers confirmed dilated cardiomyopathy (two individuals), other cardiac findings (three individuals), or no cardiac deviations (two individuals), indicating incomplete penetrance or age-dependent expression of dilated cardiomyopathy. RNA sequencing spanning the variant in cDNA blood of heterozygote individuals revealed nonsense-mediated mRNA decay of the mutated transcripts. In the current study, we present the first natural course of the recessively inherited lethal form of human fetal cardiomyopathy caused by loss of Nexilin function. The affected family had uneventful pregnancies until week 23-24, followed by fetal death at week 24-30, characterized by cardiomegaly and endocardial fibroelastosis.
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| 14. |
- Karlsson, Elin, et al.
(author)
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High affinity between CREBBP/p300 and NCOA evolved in vertebrates
- 2020
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In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 29:7, s. 1687-1691
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Journal article (peer-reviewed)abstract
- The interaction between the transcriptional coactivators CREBBP/p300 and NCOA is governed by two intrinsically disordered domains called NCBD and CID, respectively. The CID domain emerged within the NCOA protein in deuterostome animals (including vertebrates) after their split from the protostomes (molluscs, worms, and arthropods). However, it has not been clear at which point a high affinity interaction evolved within the deuterostome clade and whether all present-day deuterostome animals have a high affinity NCBD:CID interaction. We have here expressed and measured affinity for NCBD and CID domains from animal species representing different evolutionary branches of the deuterostome tree. While all vertebrate species have high-affinity NCBD:CID interactions we found that the interaction in the echinoderm purple sea urchin is of similar affinity as that of the proposed ancestral domains. Our findings demonstrate that the high-affinity NCBD:CID interaction likely evolved in the vertebrate branch and question whether the interaction between CREBBP/p300 and NCOA is essential in nonvertebrate deuterostomes. The data provide an example of evolution of transcriptional regulation through protein-domain based inventions.
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| 15. |
- Knutsen, Carl Henrik, et al.
(author)
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Conceptual and Measurement Issues in Assessing Democratic Backsliding
- 2023
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Other publication (other academic/artistic)abstract
- This paper addresses three interrelated questions. First, how strong is the evidence that democracy has declined globally over the last decade? Second, how should we best measure (change in) democracy? Third, given that much of the recent evidencefor global backsliding comes from measurement projects that rely on expert ratings, is there evidence that experts have become harsher judges of democratic quality in recent years? We begin our analysis with a discussion of how to conceptualize democracy and democratic backsliding, stressing that for contested concepts such as democracy, no one operationalization is likely to reign supreme. We then dissect the distinction between “subjective” and “objective” measures, examining how measurement error can affect even seemingly objective indicators, and highlight how subjectivity pervades all measurement enterprises. Next, focusing on V–Dem’s methodology, we show—through both theoretical considerations and empirical tests—that it is highly unlikely that time-varying expert biases drive recent declines in estimates of the state of global democracy. Finally we evaluate Little and Meng’s (2023) recent attempt to assess the prevailing case for global backsliding using “objective” measures. We demonstrate multiple issues that make their measurement strategy ill-suited to studying trends in global democracy.
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| 16. |
- Knutsen, Carl Henrik, et al.
(author)
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Conceptual and Measurement Issues in Assessing Democratic Backsliding
- 2024
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In: PS-POLITICAL SCIENCE & POLITICS. - 1049-0965 .- 1537-5935. ; 57:2
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Journal article (peer-reviewed)abstract
- During the past decade, analyses drawing on several democracy measures have shown a global trend of democratic retrenchment. While these democracy measures use radically different methodologies, most partially or fully rely on subjective judgments to produce estimates of the level of democracy within states. Such projects continuously grapple with balancing conceptual coverage with the potential for bias (Munck and Verkuilen 2002; Przeworski et al. 2000). Little and Meng (L&M) (2023) reintroduce this debate, arguing that "objective" measures of democracy show little evidence of recent global democratic backsliding.1 By extension, they posit that time-varying expert bias drives the appearance of democratic retrenchment in measures that incorporate expert judgments. In this article, we engage with (1) broader debates on democracy measurement and democratic backsliding, and (2) L&M's specific data and conclusions.
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| 17. |
- Knutsson, Pavleta, 1980, et al.
(author)
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Phycoremediation of heavy metals in ashes
- 2014
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In: Chalmers Life Science Area of Advance Meeting, May 5, Göteborg.
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Conference paper (other academic/artistic)abstract
- A growing problem in today’s society is the increasing amount of ash from the production of electricity and heat. Ash contains heavy metals that may be harmful to the environment. By using algae as ion exchangers, the ashes can be purified from certain heavy metals before deposit and its environmental impact is decreased [1]. Algal cell wall contains functional groups, such as amino-, carboxyl-, hydroxyl- and suphate groups, to which the various metal ions can bind bind [3]. An ion exchange of bound metal ions toward heavy metal ions can occur when the cell wall comes in contact with, for example, leachate from the ashes [1]. The process of using algae for environmental remediation is called phycoremediation.Within this project, we study the potential of microalgae for remediating ash from heavy metals, by measuring the metal binding capacity by three phytoplankton species: Chlorella salina, Dunaliella salina and Scendesmus obliquus. The heavy metals assayed are divalent ions of mercury (Hg), cadmium (Cd), copper (Cu), lead (Pb), zinc (Zn). The effect of pH has been investigated as well as total binding over time. To apply the method on a more authentic situation, the binding of metals from combustion ash was investigated.
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| 18. |
- Lindberg, Klara, et al.
(author)
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Herbal medicine promotion for a restorative bioeconomy in tropical forests: A reality check on the Brazilian Amazon
- 2023
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In: Forest Policy and Economics. - 1389-9341. ; 155
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Journal article (peer-reviewed)abstract
- Herbal medicine has experienced a renaissance both for health reasons and as part of a bioeconomy for regions rich in biodiversity and traditional knowledge. Medicinal plant value chains can promote local development and sustainable livelihoods that are critical for forest frontiers in need of inclusive economic alternatives. This sector can become an example of restorative bioeconomy, which not only maintains but enhances nature's contributions to people – notably to historically marginalized actors such as Indigenous peoples. However, a reality check is due. Using the Amazon as an emblematic case study, this article examines Brazil's context and policy framework on herbal medicine promotion. It draws from a literature review as well as 23 key-informant interviews and field visits to 10 local herbal medicine value chain initiatives. Our findings expose a closing window of opportunity, as while deforestation and forest degradation advances, Brazil's herbal medicine promotion has fallen short of its potentials for development and inclusiveness. Insufficient attention to traditional knowledge or to research on Brazil's native biodiversity, regulatory stringency without converse support to integrate marginalized actors, and ambivalent social acceptability of herbal medicine have been key barriers to advancing the sector. We conclude that herbal medicine offers a clear case of restorative bioeconomy with double potential to address historical inequalities both on healthcare access and socioeconomic inclusiveness, but delivering on that requires much more participatory research, attention to local capacity enhancement, and a better understanding of herbal medicine promotion in multicultural social settings.
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| 19. |
- Mattisson, Jonas, 1994-, et al.
(author)
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Loss of chromosome Y in regulatory T cells
- 2024
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In: BMC Genomics. - : BioMed Central (BMC). - 1471-2164. ; 25:1
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Journal article (peer-reviewed)abstract
- BackgroundMosaic loss of chromosome Y (LOY) in leukocytes is the most prevalent somatic aneuploidy in aging humans. Men with LOY have increased risks of all-cause mortality and the major causes of death, including many forms of cancer. It has been suggested that the association between LOY and disease risk depends on what type of leukocyte is affected with Y loss, with prostate cancer patients showing higher levels of LOY in CD4 + T lymphocytes. In previous studies, Y loss has however been observed at relatively low levels in this cell type. This motivated us to investigate whether specific subsets of CD4 + T lymphocytes are particularly affected by LOY. Publicly available, T lymphocyte enriched, single-cell RNA sequencing datasets from patients with liver, lung or colorectal cancer were used to study how LOY affects different subtypes of T lymphocyte. To validate the observations from the public data, we also generated a single-cell RNA sequencing dataset comprised of 23 PBMC samples and 32 CD4 + T lymphocytes enriched samples.ResultsRegulatory T cells had significantly more LOY than any other studied T lymphocytes subtype. Furthermore, LOY in regulatory T cells increased the ratio of regulatory T cells compared with other T lymphocyte subtypes, indicating an effect of Y loss on lymphocyte differentiation. This was supported by developmental trajectory analysis of CD4 + T lymphocytes culminating in the regulatory T cells cluster most heavily affected by LOY. Finally, we identify dysregulation of 465 genes in regulatory T cells with Y loss, many involved in the immunosuppressive functions and development of regulatory T cells.ConclusionsHere, we show that regulatory T cells are particularly affected by Y loss, resulting in an increased fraction of regulatory T cells and dysregulated immune functions. Considering that regulatory T cells plays a critical role in the process of immunosuppression; this enrichment for regulatory T cells with LOY might contribute to the increased risk for cancer observed among men with Y loss in leukocytes.
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| 20. |
- Mezheyeuski, Artur, et al.
(author)
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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
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Journal article (peer-reviewed)abstract
- Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.
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| 21. |
- Moro, Carlos Fernandez, et al.
(author)
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An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Journal article (peer-reviewed)abstract
- A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR(high) stroma at the liver edge to FAP(high) stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
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| 22. |
- Näsman, Amanda, et al.
(author)
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Asthma and Asthma Medication Are Common among Recreational Athletes Participating in Endurance Sport Competitions
- 2018
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In: Canadian Respiratory Journal. - : Hindawi Publishing Corporation. - 1198-2241 .- 1916-7245. ; 2018
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Journal article (peer-reviewed)abstract
- Background: Asthma prevalence is high among elite endurance athletes, but little is known about its prevalence among competitive recreational athletes. The aim of this study was to determine the prevalence of self-reported asthma and asthma medication use among competitive recreational endurance athletes and their association with training.Methods: A web survey on asthma and medication was conducted among 38,603 adult participants of three Swedish endurance competitions (cross-country running, cross-country skiing, and swimming).Results: The overall response rate was 29%. The prevalence of self-reported asthma (physician-diagnosed asthma and use of asthma medication in the last 12 months) was 12%. Among those reporting asthma, 23% used inhaled corticosteroids and long-acting beta-agonists daily. We found no association between training volume and daily use of asthma medication, except a trend in relation to short-acting beta-agonists. Independent predictors of self-reported asthma were female sex, allergic rhinitis, previous eczema, family history of asthma, cycling, and training for >5 h 50 min/week.Conclusions: The prevalence of self-reported asthma among Swedish competitive recreational endurance athletes appears to be higher than that in the general Swedish population. A large proportion of recreational athletes were reported with asthma use medications, indicating an association between high physical activity and self-reported asthma among competitive recreational athletes.
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| 23. |
- Roshanbin, Sahar, 1984-, et al.
(author)
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Histological characterization of orphan transporter MCT14 (SLC16A14) shows abundant expression in mouse CNS and kidney
- 2016
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In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 17
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Journal article (peer-reviewed)abstract
- Background: MCT14 (SLC16A14) is an orphan member of the monocarboxylate transporter (MCT) family, also known as the SLC16 family of secondary active transmembrane transporters. Available expression data for this transporter is limited, and in this paper we aim to characterize MCT14 with respect to tissue distribution and cellular localization in mouse brain. Results: Using qPCR, we found that Slc16a14 mRNA was highly abundant in mouse kidney and moderately in central nervous system, testis, uterus and liver. Using immunohistochemistry and in situ hybridization, we determined that MCT14 was highly expressed in excitatory and inhibitory neurons as well as epithelial cells in the mouse brain. The expression was exclusively localized to the soma of neurons. Furthermore, we showed with our phylogenetic analysis that MCT14 most closely relate to the aromatic amino acid- and thyroid-hormone transporters MCT8 (SLC16A2) and MCT10 (SLC16A10), in addition to the carnitine transporter MCT9 (SLC16A9). Conclusions: We provide here the first histological mapping of MCT14 in the brain and our data are consistent with the hypothesis that MCT14 is a neuronal aromatic-amino-acid transporter.
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| 24. |
- Schiza, Aglaia, et al.
(author)
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Tumour-infiltrating lymphocytes add prognostic information for patients with low-risk DCIS : findings from the SweDCIS randomised radiotherapy trial
- 2022
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 168, s. 128-137
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Journal article (peer-reviewed)abstract
- BACKGROUND: The immune microenvironment is an important modulator of tumour progression and treatment response. In invasive breast cancer, assessment of tumour-infiltrating lymphocytes (TILs) provides prognostic and predictive information. However, the clinical impact of TILs for ductal carcinoma in situ (DCIS) has not yet been demonstrated.PATIENTS AND METHODS: Post hoc analysis of the SweDCIS randomised radiotherapy trial including primary DCIS cases following breast-conserving surgery. TILs were assessed on haematoxylin-eosin sections (n = 711) according to the International Immuno-Oncology Biomarker Working Group guidelines. TILs-scores were analysed as continuous and dichotomised (≤5% versus >5%) variable regarding ipsilateral breast events (IBEs) as the predefined primary endpoint.RESULTS: Most women (61.9%) showed a TILs prevalence of ≤5%. High TILs-scores were associated with larger lesion size, human epidermal growth factor receptor 2 (HER2)-positivity, higher nuclear grade, and KI67-score. DCIS cases with high TILs prevalence had a significant increased cumulative IBE incidence at five years post-surgery (TILslow-versus TILshigh 9% versus 18%; p < 0.001). Among patients with HER2-negative DCIS, high TILs remained an independent poor prognosis marker for IBE risk in multivariable analysis with an adjusted hazard ratio of 2.41 [95%CI 1.17-4.95, p = 0.017]. Including TILs-status provided a refined stratification of patients with general low-risk DCIS (grade <3, size <25 mm, free margin). No interaction between TILs and radiotherapy benefits was detected.CONCLUSION: High TILs are associated with higher IBE risk over 5-years post-surgery, particularly for HER2-negative DCIS. Our data indicate that TILs should be integrated into the clinical workup to define patients with low-risk DCIS who can omit adjuvant therapy or patients with potential benefits from immunotherapy.
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| 25. |
- Wengström, Niklas, et al.
(author)
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Flodpärlmusslans status i Västra Götalands län : En inventering av åtta av länets vattendrag 2021
- 2021
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Reports (other academic/artistic)abstract
- Som en del i Länsstyrelsens miljöövervakningsprogram genomfördes 2021 inventeringar av flodpärlmusslor (Margaritifera margaritifera) i åtta vattendrag i Västra Götalands län. Resultaten ger nödvändigt underlag för att bedöma musslans status och är stöd till bland annat naturvårdsinsatser. Resultaten är även ett viktigt underlag för uppföljningen av miljömålen Levande sjöar och vattendrag samt Ett rikt växt- och djurliv.Under 2021 har inventering av flodpärlmussla genomförts i Lindåsabäcken, Lärjeån, Kolarebäcken, Nordån, Slereboån, Stommebäcken, Sörån och Teåkersälven. Syftet med inventeringarna har varit att undersöka statusen på de olika populationerna och att jämföra detta med tidigare inventeringar.Inventeringar och rapport har utförts av EnviroPlanning AB och Sportfiskarna på uppdrag av Länsstyrelsen i Västra Götalands län och de tackas för sina insatser. De ansvarar för rapportens innehåll och rapporten behöver därmed inte representera Länsstyrelsens ståndpunkt.
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| 26. |
- Wilson, Matthew C., et al.
(author)
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Episodes of liberalization in autocracies: a new approach to quantitatively studying democratization
- 2023
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In: Political Science Research and Methods. - : Cambridge University Press (CUP). - 2049-8470 .- 2049-8489. ; 11:3, s. 501-520
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Journal article (peer-reviewed)abstract
- This paper introduces a new approach to the quantitative study of democratization. Building on the comparative case-study and large-N literature, it outlines an episode approach that identifies the discrete beginning of a period of political liberalization, traces its progression, and classifies episodes as successful versus different types of failing outcomes, thus avoiding potentially fallacious assumptions of unit homogeneity. We provide a description and analysis of all 383 liberalization episodes from 1900 to 2019, offering new insights on democratic "waves". We also demonstrate the value of this approach by showing that while several established covariates are valuable for predicting the ultimate outcomes, none explain the onset of a period of liberalization.
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| 27. |
- Wilson, Matthew C., et al.
(author)
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Successful and Failed Episodes of Democratization: Conceptualization, Identification, and Description
- 2020
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In: SSRN Electronic Journal. - Göteborg : Göteborgs universitet. - 1556-5068.
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Other publication (other academic/artistic)abstract
- What explains successful democratization? This paper makes four contributions towards providing more sophisticated answers to this question. Building on the comparative case study and large-N literature, it first presents a new approach to conceptualizing the discrete beginning of a period of political liberalization, tracing its progression, and classifying episodes by successful vs. different types of failing outcomes, thus avoiding potentially fallacious assumptions of unit homogeneity. Second, it provides the first ever dataset (EPLIB) of the full universe of episodes from 1900 to 2018, and third, it demonstrates the value of this approach, showing that while several established covariates are useful for predicting outcomes, none of them seem to explain the onset of a period of liberalization. Fourth, it illustrates how the identification of episodes makes it possible to study processes quantitatively using sequencing methods to detail the importance of the order of change for liberalization outcomes.
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