Publikationer från Uppsala Universitet
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    Klimatfrågans Inramning i ett Högerpopulistiskt Parti : En studie av Sverigedemokraternas klimatpolitiska utveckling under åren 2010–2022

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    Let it shine : Autofluorescence of Papanicolaou-stain improves AI-based cytological oral cancer detection

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    Background and objectives: Oral cancer is a global health challenge. The disease can be successfully treated if detected early, but the survival rate drops significantly for late stage cases. There is a growing interest in a shift from the current standard of invasive and time-consuming tissue sampling and histological examination, towards non-invasive brush biopsies and cytological examination, facilitating continued risk group monitoring. For cost effective and accurate cytological analysis there is a great need for reliable computer-assisted data-driven approaches. However, infeasibility of accurate cell-level annotation hinders model performance, and limits evaluation and interpretation of the results. This study aims to improve AI-based oral cancer detection by introducing additional information through multimodal imaging and deep multimodal information fusion. Methods: We combine brightfield and fluorescence whole slide microscopy imaging to analyze Papanicolaou-stained liquid-based cytology slides of brush biopsies collected from both healthy and cancer patients. Given the challenge of detailed cytological annotations, we utilize a weakly supervised deep learning approach only relying on patient-level labels. We evaluate various multimodal information fusion strategies, including early, late, and three recent intermediate fusion methods. Results: Our experiments demonstrate that: (i) there is substantial diagnostic information to gain from fluorescence imaging of Papanicolaou-stained cytological samples, (ii) multimodal information fusion improves classification performance and cancer detection accuracy, compared to single-modality approaches. Intermediate fusion emerges as the leading method among the studied approaches. Specifically, the Co-Attention Fusion Network (CAFNet) model achieves impressive results, with an F1 score of 83.34% and an accuracy of 91.79% at cell level, surpassing human performance on the task. Additional tests highlight the importance of accurate image registration to maximize the benefits of the multimodal analysis. Conclusion: This study advances the field of cytopathology by integrating deep learning methods, multimodal imaging and information fusion to enhance non-invasive early detection of oral cancer. Our approach not only improves diagnostic accuracy, but also allows an efficient, yet uncomplicated, clinical workflow. The developed pipeline has potential applications in other cytological analysis settings. We provide a validated open-source analysis framework and share a unique multimodal oral cancer dataset to support further research and innovation

    Treatment and treatment outcomes of snakebite envenoming in Uganda : a retrospective analysis

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    Background: Snakebite envenoming is a neglected tropical disease that causes significant morbidity and mortality in rural sub-Saharan Africa. However, there is a notable lack of data concerning the management and treatment outcomes for those affected. This study addresses this gap by examining the management and treatment outcomes of snakebite victims in Uganda. Methods: We reviewed retrospective data of 532 snakebite cases attending 16 Ugandan health facilities from January 2017 to December 2021. Demographic characteristics and clinical data were extracted from patient records and summarized using descriptive statistics. Results: The snakebite victims had a median age of 26 y, most were male (55.3%) and had bites of unidentified snake species (92.3%). Among the 465 treated patients, 71.6% received antibiotics, 66.0% hydrocortisone, 36.3% analgesics and only 6.9% antivenom. No adverse antivenom reactions were documented. The majority (89.5%) were discharged; 1.3% died and 5.5% had unknown outcomes. Conclusions: These results suggest that snakebite envenoming affects vulnerable Ugandans, particularly young males and children. Treatment is primarily supportive, with antibiotic overuse and infrequent antivenom administration. Health provider training on appropriate snakebite management is needed to optimize outcomes

    Immunohistochemistry guided segmentation of benign epithelial cells, in situ lesions, and invasive epithelial cells in breast cancer slides

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    Digital pathology enables automatic analysis of histopathological sections using artificial intelligence. Automatic evaluation could improve diagnostic efficiency and find associations between morphological features and clinical outcome. For development of such prediction models in breast cancer, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be important. In this study, we trained an attention gated U-Net for segmentation of epithelial cells in hematoxylin and eosin stained breast cancer sections. We generated epithelial ground truths by immunohistochemistry, restaining hematoxylin and eosin sections with cytokeratin AE1/AE3, combined with pathologists’ annotations. Tissue microarrays from 839 patients, and whole slide images from two patients, were used for training and evaluation of the models. The sections were derived from four breast cancer cohorts. Tissue microarray cores from a fifth cohort of 21 patients was used as a second test set. In quantitative evaluation, mean Dice scores of 0.70, 0.79, and 0.75 were achieved for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively. In qualitative scoring (0-5) by pathologists, the best results were reached for all epithelium and invasive epithelium, with scores of 4.7 and 4.4, respectively. Scores for benign epithelium and in situ lesions were 3.7 and 2.0, respectively. The proposed model segmented epithelial cells well, but further work is needed for accurate subclassification into benign, in situ, and invasive cells

    Thermal Runaway in Large-Format Lithium-Ion Batteries : Experimental, Diagnostic, and Modeling Approaches for Safer Battery Design

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    Ensuring the safety of lithium-ion batteries requires robust methods to study thermal runaway (TR) and its propagation (TRP). While accelerating rate calorimetry (ARC) has been the standard method, it is costly and limited in applicable cell sizes. This thesis develops empirical and novel approaches that provide cost-effective and scalable alternatives. First, TRP tests on 157 Ah LiNi0.8Mn0.1Co0.1O2 cells using widely available thermocouples were analyzed, enabling the estimation of onset and maximum temperatures, heat release, and temperature increase rates. Results showed close agreement with ARC, while offering broader applicability and lower complexity. Next, pouch and prismatic LiNi0.5Mn0.3Co0.2O2 cells were investigated with multidimensional sensors (i.e., force, gas, voltage, temperature), which allowed for a comprehensive safety characterization and revealed a consistent failure sequence of swelling, venting, gas emission, internal short circuit, and TR. While no significant format differences were found under overcharging, prismatic cells exhibited superior safety under overheating due to their higher mechanical strength and thermal dissipation. Scaling effects were then explored by comparing lab-scale coin cells (8.6 mAh) with industrial-scale cells up to 157 Ah, showing that small-scale tests are highly sensitive to the trigger methods, whereas industrial-scale cells yielded comparatively consistent normalized heat release, highlighting the limitations of downscaling. The TRP methodology was extended to map heat transfer in modules, where busbars and thermal pads were identified as critical heat conduction pathways, and in-situ measurements showed that thermal conductivity of pads under TR conditions deviated substantially from nominal values, strongly influencing TRP time. Finally, computational modeling was employed to simulate aging effects on TR, demonstrating that early aging accelerates TRP due to SEI growth, while late aging reduces total heat release due to further degradations but still sustains faster propagation than fresh batteries. Collectively, these studies integrate empirical diagnostics, module-level analysis, and computational modeling to provide a comprehensive picture of TR across scales, formats, and aging states. The methods and insights developed here support both academic research and industrial applications, offering practical guidelines for safer design and operation of large-format lithium-ion batteries in heavy-duty electric vehicles

    Antimicrobial properties and bioactivity of zirconia-based biocomposites

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    Zirconia-based composites are promising materials for medical and dental applications. They are widely used due to their osteoconductivity and chemical stability. Moreover, when modified with beneficial fillers, they combine mechanical strength with bioactivity. This study addresses the interplay between bioactive fillers, cytotoxicity, antibacterial activity, and reactive oxygen species (ROS) levels in ZrO2 composites. The composites were tested for their biological properties. Thanks to hydrothermally obtained zirconia used in ZrO2/HAp composites the sintering temperature was reduced, which limited hydroxyapatite decomposition. However, ZrO2/HAp composites revealed higher cytotoxicity and ROS levels, linked to calcium ion release resulting from the partial HAp decomposition. Composites with BGCu exhibited strong antibacterial activity and acceptable cytotoxicity due to copper ions disrupting microbial structures and inducing oxidative stress. hBN-containing composites displayed moderate bacteriostatic activity but higher cytotoxicity than BGCu composites. These findings highlight the potential of ZrO2/BGCu composites as bioactive materials for bone regeneration and antimicrobial applications. While composites with hydroxyapatite demonstrate a balance between bioactivity and cytotoxicity, BGCu emerge as a promising modification to enhance antibacterial properties with controlled cytotoxicity. Further research is needed to optimise filler compositions to balance ion release, biological stability, and functionality

    Opportunities and challenges with automated quality assurance work in swedish civil engineering and infrastructure projects

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    This study examines the opportunities and challenges of implementing automated quality assurance processes in Swedish civil engineering and infrastructure projects. With a combination of literature review, interviews, and three technical proposals, various factors influencing the feasibility of automation are examined. The study includes four qualitative interviews with data coordinators at the company Iterio. Key factors from the interviews are identified and formed to different themes. Those are analyzed using a thematic analysis. Based on the interview responses and the software FME, three technical proposals are developed. These proposals, along with the interview findings, answers the research questions: What factors affect the opportunities and challenges of automated quality assurance, and how can such automation be implemented technically? The results show that there are significant potential for automation. For example, there are several powerful software’s available that can handle files in various formats. However, many challenges remain, for example, the need for standardized input data and technical knowledge among those who are going to work with these new systems. Introducing automation as a way of working may also require a change in procurement, as it is difficult to estimate the number of hours it takes to implement automation, as well as the time it would save

    Revisiting Ego Depletion : Evidence from Multi-Lab Collaborations

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    The ego depletion effect posits that initial exertion of self-control impairs subsequent self-regulatory performance. Despite being examined in over 1000 independent studies and cited extensively, recent large-scale studies have questioned its validity. We propose that the replicability of ego depletion may hinge on the intensity of the manipulation. Our new paradigm, involving a demanding antisaccade task lasting for 30-40 min followed by a Go-Nogo task, was tested across 14 samples, totaling 2078 participants worldwide, both in laboratory settings and online. Results consistently demonstrated significant ego depletion effects (d = 0.31 to 0.35) with minimal heterogeneity (I2 = 0). Bayesian meta-analysis further supported these findings with strong evidence (BF10 > 700). This study underscores the importance of manipulation intensity in ego depletion research and provides a reliable method for future studies. These findings have significant implications for resolving empirical controversies in ego depletion and addressing the broader replication crisis in psychology

    Exercise Recommendations and Practical Considerations for Asthma Management—An EAACI Position Paper

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    Exercise is an important treatment for people with asthma and should be considered alongside pharmacological therapy when developing personalised asthma management plans. Despite this, there remains limited guidance concerning the practicalities of asthma-specific exercise prescription. This European Academy of Allergy and Clinical Immunology task force was therefore established to achieve three fundamental aims: first, to provide an up-to-date perspective concerning the role of exercise for asthma management (i.e., describe the disease modifying potential of exercise and associated impact on asthma-related extrapulmonary comorbidities); second, to develop pragmatic recommendations to facilitate safe and effective exercise prescription; and third, to identify key unmet needs and provide focused direction for future research. The position paper is structured as a practically focused document, with recommendations formulated according to best available scientific evidence and expert opinion, with an emphasis on providing healthcare providers with pragmatic advice that can be implemented during routine asthma review

    Giant transposons promote strain heterogeneity in a major fungal pathogen

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    Fungal infections are difficult to prevent and treat in large part due to strain heterogeneity, which confounds diagnostic predictability. Yet, the genetic mechanisms driving strain-to-strain variation remain poorly understood. Here, we determined the extent to which Starships—giant transposons capable of mobilizing numerous fungal genes—generate genetic and phenotypic variability in the opportunistic human pathogen Aspergillus fumigatus. We analyzed 519 diverse strains, including 11 newly sequenced with long-read technology and multiple isolates of the same reference strain, to reveal 20 distinct Starships that are generating genomic heterogeneity over timescales relevant for experimental reproducibility. Starship-mobilized genes encode diverse functions, including known biofilm-related virulence factors and biosynthetic gene clusters, and many are differentially expressed during infection and antifungal exposure in a strain-specific manner. These findings support a new model of fungal evolution wherein Starships help generate variation in genome structure, gene content, and expression among fungal strains. Together, our results demonstrate that Starships are a previously hidden mechanism generating genotypic and, in turn, phenotypic heterogeneity in a major human fungal pathogen. IMPORTANCE No “one size fits all” option exists for treating fungal infections in large part due to genetic and phenotypic variability among strains. Accounting for strain heterogeneity is thus fundamental for developing efficacious treatments and strategies for safeguarding human health. Here, we report significant progress toward achieving this goal by uncovering a previously hidden mechanism generating heterogeneity in the human fungal pathogen Aspergillus fumigatus: giant transposons, called Starships, that span dozens of kilobases and mobilize fungal genes as cargo. By conducting a systematic investigation of these unusual transposons in a single fungal species, we demonstrate their contributions to population-level variation at the genome, pangenome, and transcriptome levels. The Starship compendium we develop will not only help predict variation introduced by these elements in laboratory experiments but will serve as a foundational resource for determining how Starships impact clinically relevant phenotypes, such as antifungal resistance and pathogenicity

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    Publikationer från Uppsala Universitet
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