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- Dao Nyesiga, Gillian, et al.
(författare)
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Tolerogenic dendritic cells generated in vitro using a novel protocol mimicking mucosal tolerance mechanisms represent a potential therapeutic cell platform for induction of immune tolerance.
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are mediators between innate and adaptive immunity and vital in initiating and modulating antigen-specific immune responses. The most important site for induction of tolerance is the gut mucosa, where TGF-β, retinoic acid, and aryl hydrocarbon receptors collaborate in DCs to induce a tolerogenic phenotype. To mimic this, a novel combination of compounds – the synthetic aryl hydrocarbon receptor (AhR) agonist IGN-512 together with TGF-β and retinoic acid – was developed to create a platform technology for induction of tolerogenic DCs intended for treatment of several conditions caused by unwanted immune activation. These in vitro-generated cells, designated ItolDCs, are phenotypically characterized by their low expression of co-stimulatory and activating molecules along with high expression of tolerance-associated markers such as ILT3, CD103, and LAP, and a weak pro-inflammatory cytokine profile. When co-cultured with T cells and/or B cells, ItolDC-cultures contain higher frequencies of CD25+Foxp3+ regulatory T cells (Tregs), CD49b+LAG3+ ‘type 1 regulatory (Tr1) T cells, and IL-10-producing B cells and are less T cell stimulatory compared to cultures with matured DCs. Factor VIII (FVIII) and tetanus toxoid (TT) were used as model antigens to study ItolDC antigen-loading. ItolDCs can take up FVIII, process, and present FVIII peptides on HLA-DR. By loading both ItolDCs and mDCs with TT, antigen-specific T cell proliferation was observed. Cryo-preserved ItolDCs showed a stable tolerogenic phenotype that was maintained after stimulation with LPS, CD40L, or a pro-inflammatory cocktail. Moreover, exposure to other immune cells did not negatively impact ItolDCs’ expression of tolerogenic markers. In summary, a novel protocol was developed supporting the generation of a stable population of human DCs in vitro that exhibited a tolerogenic phenotype with an ability to increase proportions of induced regulatory T and B cells in mixed cultures. This protocol has the potential to constitute the base of a tolDC platform for inducing antigen-specific tolerance in disorders caused by undesired antigen-specific immune cell activation.
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- Holm, Karin, et al.
(författare)
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Convalescence plasma treatment of COVID-19 : results from a prematurely terminated randomized controlled open-label study in Southern Sweden
- 2021
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Ingår i: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19.Results: Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups.
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- Ljungquist, Oskar, et al.
(författare)
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Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19 : an observational study of 28 cases
- 2022
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Ingår i: Infectious Diseases. - : Taylor & Francis Group. - 2374-4235 .- 2374-4243 .- 1651-1980. ; 54:4, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment.Methods: We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28).Results: In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged.Conclusion: As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.
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| 5. |
- Wigren-Kristoferson, Caroline, et al.
(författare)
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Entrepreneurship education and gender : The man-made entrepreneur
- 2021
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Ingår i: International Journal of Globalisation and Small Business. - : InderScience Publishers. - 1479-3059 .- 1479-3067. ; 12:1, s. 5-25
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Tidskriftsartikel (refereegranskat)abstract
- As the literature on entrepreneurship education grows, the issue of equality in entrepreneurship education has been raised; i.e., whether students are educated to become entrepreneurs equally. This article provides a critical and thought-provoking analysis of a portfolio of practices that, on the surface, appear to be successful in training entrepreneurs. To this purpose, we initiate a debate on what entrepreneurship education programmes tend to omit. We provide an argument within entrepreneurship scholarship that takes into consideration the diversity and complexity of gender in entrepreneurship. We present an insightful example of what we do in our university classrooms whilst calling for a more encompassing perspective of gender within present-day teaching practice. We acknowledge that academic entrepreneurship education is gendered (Ahl, 2006) and we show how hegemonic masculine-framed foundations of entrepreneurship influence the vocabulary of teaching and learning in Sweden. The paper provides insights into how both teachers and students unluckily, fail to identify the masculinisation of entrepreneurship education.
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- Wigren-Kristoferson, Caroline, et al.
(författare)
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Exploring the masculinization of innovation practice within a municipality
- 2021
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Ingår i: International Journal of Gender and Entrepreneurship. - : Emerald Group Publishing Limited. - 1756-6266 .- 1756-6274. ; 13:3, s. 243-258
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study is to generate an empirically informed theoretical framework which can be used to analyze the relationship between gender and innovation in the context of a municipality. The authors present and analyze three illustrative tales from a feminist perspective. The authors thus offer a more balanced approach to the conceptualization of gendered ascriptions with respect to the possible outcomes of innovation work in a public context. Design/methodology/approach: An ethnographic account which employed “shadowing” as a method of observation. Findings: The article presents a debate on how the social construction of gender and innovation can be placed in the context of a municipal reality. Our analysis reveals how the complexities of a gendered work life within a municipality can create paradoxes. A constructionism approach was used in the identification of hidden and unspoken paradoxes that exist in public spheres. Research limitations/implications: The authors used empirical tales from a very specific context, namely a Swedish municipality. The central implication of this study is the recognition of innovation as being masculine-gendered within the feminine context. This implication thereby deepens our understanding of gender paradoxes in the public sector. Practical implications: This study provides insights to practitioners who intend to work with innovation in a public organization. Social implications: The social implications of this study is that when a male-gendered concept like innovation is implemented in a female-gendered context, like a municipality, it is of importance to contextualize the concept. Originality/value: The empirical value of examples of a gendered work landscape at a Swedish municipality.
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| 7. |
- Wigren-Kristoferson, Caroline, et al.
(författare)
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Rethinking embeddedness : a review and research agenda
- 2022
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Ingår i: Entrepreneurship and Regional Development. - : Taylor & Francis. - 0898-5626 .- 1464-5114. ; 34:1-2, s. 32-56
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Tidskriftsartikel (refereegranskat)abstract
- We conduct a comprehensive review of embeddedness in entrepreneurship research. Although the term “embeddedness” is frequently used in this field of study, less is known about the ways in which it is operationalized and applied. Using criterion sampling, we analyse 198 articles in order to investigate how embeddedness is conceptualized and what role it plays in the extant entrepreneurship literature. We categorize our findings based on different phases of the entrepreneurial process (early, mature and exit) and outline the dominant focus and the main conceptualization of embeddedness for each phase. We highlight important learnings for each of the three phases and identify potential areas for conceptual development. Across the phases, we find that embeddedness and context are often used interchangeably. We thus call for construct clarity in the field. In the existing literature, entrepreneurs are generally portrayed as reactive to embeddedness, resulting in a loss of entrepreneurial agency. To remedy this, we introduce the term agencement, which takes into account the relationship between the entrepreneurship and embeddedness. Further, entrepreneurs are found to be embedded in multiple contexts at the same time, and embeddedness can be understood at different levels and to different degrees. To address this complexity, it is relevant to focus on the embedding process itself, acknowledging that it takes place in social interactions including cultural, cognitive, and emotional aspects between contexts and across levels. While the extant literature supports the notion that embeddedness is important for understanding entrepreneurship and entrepreneurs, it does not necessarily support our understanding of how embeddedness takes form or why it takes certain forms. We therefore include a call for future research to turn to process and practice theories.
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| 8. |
- Yao Mattisson, Ingrid, et al.
(författare)
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Immune responses against oxidized LDL as possible targets for prevention of atherosclerosis in systemic lupus erythematosus
- 2021
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE−/− mice). Promoting LDL tolerance through mucosal immunization with an apolipoprotein B-100 peptide p45 (amino acids 661–680) and cholera toxin B-subunit fusion protein increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Treatment with the oxidized LDL-specific antibody Orticumab reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. The present study provides support for oxLDL as a possible target for prevention of cardiovascular complications in SLE. © 2021 The Author(s)
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