Publikationer från Uppsala Universitet
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B Cell dysfunction in tumor-draining lymph nodes predicts relapse in oral squamous cell carcinoma
Oral squamous cell carcinoma (OSCC) presents a persistent clinical challenge, with high recurrence rates and limited improvements in survival despite therapeutic advances. Tumor-draining lymph nodes (TDLNs) are key immunological sites where anti-tumor responses are orchestrated, yet the prognostic relevance of B cell phenotypes in TDLNs remains underexplored. TDLNs from 49 OSCC patients treated at Karolinska University Hospital were prospectively analyzed. Single-cell suspensions were examined using multicolor flow cytometry to characterize B cell subsets (naïve, memory, plasma cells) and expression of immunoregulatory markers (CD11c, CD24, CXCR5, CD73, HLA-DR, PD-L1). B cell profiles were correlated with clinical outcomes, including disease-free survival (DFS) and overall survival (OS). Disease-free patients exhibited a distinct B cell profile marked by a higher proportion of naïve B cells, strong CXCR5 and CD11c expression, and increased plasma cell differentiation. Recurrence was associated with elevated CD24, CD73, and HLA-DR expression, markers linked to immunoregulatory or dysfunctional B cell states. Interestingly, high PD-L1 expression on memory B cells correlated with improved prognosis, suggesting a context-dependent immune function. In line with these observations, multivariate analysis confirmed HLA-DR expression, together with nodal status, as independent prognostic factors for survival in OSCC. B cell phenotypes in OSCC TDLNs are strongly associated with patient outcomes. A microenvironment enriched in naïve and functionally active B cells supports durable tumor control, whereas regulatory/exhausted phenotypes are linked to recurrence. These findings position B cell markers as promising prognostic indicators and therapeutic targets in OSCC, warranting validation in larger cohorts and functional studies
The high-redshift signatures of Population III stars
The first stars, refereed to as Population III (Pop III), played a very important role in the evolution of the early universe. However, we have yet to observe them. Simulations of Pop III stars show that they likely behave rather differently from the stars we are familiar with today. In this project, we explore how different evolutionary models, specifically including rotation, impact the UV-properties of Pop III stars and the observational consequences of these differences. We find that fast rotation may give rise to a very strong HeIIλ1640 nebular emission line (EW ∼ 100 Å) even for stars with as low masses as 20M⊙. This is in contrast to previous studies that require very top-heavy IMFs (containing stars≥100M⊙) in order to reach such equivalent widths. Consequently, a JWST observation of a Pop III candidate galaxy with such a strong line may not alone be able to constrain the properties of the Pop III IMF and the behaviour of these stars. However, we find that for some parts of the parameter space for Pop III formation, SKA may be sensitive to differences in the 21-cm global signal and power spectrum between a population of rotating and non-rotating Pop III stars
Våldsutsatta kvinnors erfarenheter av bemötande i vården : En litteraturstudie om kvinnor som upplever våld i nära relation
Introduktion: Våld i nära relationer är ett omfattande folkhälsoproblem som drabbar kvinnor världen över. Våldet kan vara fysiskt, psykiskt, sexuellt, ekonomiskt, materiellt eller latent och leder ofta till allvarliga fysiska, psykiska och sociala konsekvenser. Hälso- och sjukvården har en central roll i att identifiera och stödja våldsutsatta kvinnor. Syfte: Syftet var att beskriva kvinnor utsatta för våld i nära relationers erfarenheter av bemötande i vården. Metod: Litteraturstudien baserades på tio kvalitativa originalartiklar från PubMed och CINAHL. Dessa kvalitetsgranskades med hjälp av SBU:s granskningsmall. Resultatet analyserades genom en systematiskt process där olika kategorier identifierades. Resultat: Tre huvudkategorier identifierades: att våga berätta om våld i nära relation, tillgängligheten och resursernas påverkan på vårdens bemötande samt bemötandet efter att ha berättat om våld i nära relation. Studiens resultat betonade vikten av att hälso- och sjukvårdspersonal ställer frågan om våldsutsatthet. Trygghet, empati och respekt från hälso-och sjukvårdspersonal var avgörande för att våga berätta, medan rädsla för att bli dömd eller misstrodd samt bristande lyhördhet utgjorde hinder. Brist på tid och resurser ledde ofta till uteblivet eller fördröjt stöd, och många kvinnor upplevde att de inte fick det stöd de förväntade sig trots att våldsproblematiken framkom. Slutsats: Denna litteraturstudie visade att kvinnors erfarenheter av hälso-och sjukvården efter våld i nära relation präglas av både positiva och negativa aspekter. Det belyser behovet av utbildning, organisatoriskt stöd och evidensbaserade arbetssätt för att säkerställa adekvat stöd.Background: Intimate partner violence is a major public health issue affecting women worldwide. The violence can be physical, psychological, sexual, economic, material, or latent, and often leads to serious physical, psychological, and social consequences. The health care sector plays a central role in identifying and supporting women exposed to violence. Aim: The aim of this study was to describe the experiences of women exposed to intimate partner violence regarding their encounters with healthcare services. Method: The literature study was based on ten qualitative original articles from PubMed and CINAHL. These were quality-assessed using SBU’s appraisal template. The data were analyzed using a systematic process aimed at identifying and organizing emerging categories. Results: Three main categories were identified: the courage to disclose experiences of intimate partner violence, the impact of accessibility and resources on healthcare interactions, and the healthcare encounter following disclosure. The findings highlight the importance of healthcare professionals actively asking about violence, as safety, empathy and respect were crucial for women's willingness to disclose. In contrast, fear of judgement, disbelief and a lack of sensitivity acted as barriers. Limited time and resources often led to inadequate support and unmet care expectations. Conclusion: This literature review showed that women’s experiences of healthcare following intimate partner violence encompass both positive and negative aspects. The findings highlight the need for education, organizational support and evidence-based practices to ensure adequate care and support
Different Patterns of Frequency, Lichen Specificity and Thallus Location Between the Yeast and Filamentous Phases of Two Lichen-Inhabiting Basidiomycetes
Many fungi have a dimorphic life cycle, alternating between unicellular yeast and multicellular filamentous phases. Although dimorphism is assumed for many lichen-associated basidiomycetes, the existence of a yeast stage has rarely been confirmed. Using taxon-specific PCR and FISH-CLSM, we studied Tremella hypogymniae and T. tubulosae Tremellomycetes), two presumably dimorphic species previously known only from their filamentous phase in galls on the lichens Hypogymnia physodes and H. tubulosa, respectively. We investigated their presence and frequency, lichen ranges and within-thallus distribution of life-cycle stages. We also explored the co-occurrence of both species with Cystobasidiomycetes—one of the most widespread lichen-associated yeast lineages—in the same lichen thalli. The filamentous phase of Tremella hypogymniae and T. tubulosae was confined to a single lichen species each, whereas the yeast phase occurred in several closely related lichens. Both phases co-occurred with various Cystobasidiomycete lineages. Filamentous structures were restricted to galls, whereas gall-free thalli contained Tremella yeasts in the cortex, soredia and medulla, and pseudohyphae in the cortex. The presence of yeasts in soredia suggests co-dispersal with other lichen symbionts. These findings reveal narrow specificity in the filamentous phase but broader associations in the yeast phase, pointing to complex interactions within the lichen symbiosis.De två första författarna delar förstaförfattarskapet</p
Evolution of Large Polymorphic Inversions in a Panmictic Songbird
Chromosomal inversions have long been appreciated as an important source of genetic diversity, local adaptation, and speciation. However, selection pressures maintaining ancestral and derived alleles at high frequency over extended periods of time remain poorly characterized. Using genome-wide single-nucleotide polymorphism markers and shared barcodes of linked-read sequences from 20 wild and 7 captive zebra finches Taeniopygia guttata, we systematically scanned a high-quality zebra finch reference genome and identified all large polymorphic inversions that segregate at high minor allele frequencies. Apart from the known polymorphic inversions on chromosomes Tgu5, Tug11, Tgu13, and TguZ, we characterized two inversions on microchromosomes Tgu26 and Tgu27 and identified another eight putative inversions, located mostly on microchromosomes and ranging in size from 0.42 to 65.22 Mb. Population genomic analyses show that most of the six bona fide inversions are complex, containing short nested inversions. The early inversions emerged an estimated 0.6 to 2.2 million years ago and segregate at relatively high frequencies in the wild (minor haplotype frequency range: 0.289 to 0.429). Based on fitness-related measures of about 5,000 captive zebra finches, we conclude that three of the inversion polymorphisms (Tgu11, Tgu27, and TguZ) may be maintained by net heterosis. In the youngest of the six inversions (Tgu13), the derived haplotype showed weak positive additive effects on various fitness components. In combination with previous discoveries, we provide a comprehensive overview of the genomic distribution and evolutionary dynamics of large polymorphic inversions in the panmictic zebra finch. Our findings highlight (i) that microchromosomes may harbor quite a few additional inversion polymorphisms, (ii) that most of the inversions contain smaller nested or overlapping inversions, and (iii) that inversions were most likely maintained by weak heterosis with small fitness effects requiring large sample sizes to be detected
After Childhood Cancer : The Feasibility and Acceptability of Guided Internet-Administered CBT for Parents
This thesis comprises five studies aiming to: (1) examine the feasibility and acceptability of an intervention tailored to parents of children treated for cancer (EJDeR) and study procedures in the ENGAGE feasibility study (ENGAGE), and (2) inform refinements and modifications of EJDeR and study procedures in preparation for a pilot RCT (CHANGE-pilot) and a subsequent fully powered superiority RCT. Study I (ENGAGE) was a feasibility study examining the feasibility and acceptability of EJDeR and related study procedures. Overall, EJDeR and ENGAGE study procedures were feasible and acceptable, with most progression criteria met. Study II was a Study Within A Trial (SWAT) investigating the effect of personalised versus non-personalised study invitation letters on recruitment rates in ENGAGE. No significant effect of personalisation on recruitment rates was found. Study III was a qualitative interview study examining concerns reported by parents to inform further adaptation of EJDeR. Parents reported concerns related to feeling lost and lonely in life, low mood, parenting difficulties, productivity difficulties, relationship challenges, stress reactions, and worry. Study IV was a qualitative interview study exploring the feasibility and acceptability of EJDeR and ENGAGE study procedures from the perspective of parents to inform refinements and modifications to EJDeR and study procedures. Overall, parents found EJDeR acceptable and relevant, however, some reported feeling too well to benefit. A need for more content on relationships with family as well as others, the cancer experience, and trauma was described. Study procedures were overall reported as acceptable, but with too many assessments. Study V was a description of and reflection on a collaborative data analysis (CDA) approach used with public contributors when analysing interviews exploring the acceptability and feasibility of EJDeR and ENGAGE study procedures (Study IV). Reflections from public contributors and research team members suggested the CDA approach had potential impacts on findings, e.g., by adding nuance. This thesis contributes to the literature on the feasibility testing of complex interventions. Furthermore, it illustrates how SWATs can address research questions about effective study procedures. Finally, it provides an example of the inclusion of public contribution in the feasibility phase to enhance the credibility of findings.
Investigation into the clinical features, treatment patterns, and survival of older men with prostate cancer in Sweden and Belgium
Background: A Dutch population-based study showed that older men with intermediate- or high-risk prostate cancer (PCa) were treated with curative intent less often than younger patients. To assess generalisability, we investigated treatment patterns in men with all PCa stages aged <70 years versus >70 years in Sweden and Belgium. Patients and methods: Men diagnosed with PCa between 2005 and 2015 were identified from the Prostate Cancer data Base Sweden and from two centres in Ghent and Leuven, Belgium. Multivariable logistic regression, adjusting for PCa stage, prostate-specific antigen, Gleason score, and Charlson comorbidity index, assessed the impact of age (70 years) on curative treatment in intermediate- and high-risk PCa. Ten-year relative survival was calculated for four age groups per country to assess excess mortality versus the general population. Results: In total, 58 092 men <70 years and 50 886 men >70 years were diagnosed in Sweden, Leuven, and Ghent. In both countries, patients aged >70 years were less likely to receive curative treatments for intermediate- and high-risk PCa versus those <70 years. In Sweden, 10-year relative survival was roughly 90-95% across all four age groups. In Leuven, survival was 100% for all except those >80 years, where it was 90%. Conclusion: Men aged >70 years were treated with curative intent less frequently for intermediate- and high-risk PCa compared with younger men. The differing relative survival rates reflect heterogeneity in PCa stage distribution between countries. Age should be considered when planning curative treatments, but it should not be the sole determinant of therapeutic decisions
Upplevelser av samverkan : Förskollärares och vårdnadshavares erfarenheter av samverkansarbetet kring barn i behov av särskilt stöd
Midsummer in the Pontiac Silverdome : Migration, Modernity, and Memory
One of the most iconic sports moments in Swedish history took place in the United States. It was Midsummer’s Eve on 24 June 1994, and the place was the Pontiac Silverdome outside Detroit, Michigan. The occasion: the FIFA World Cup in men’s soccer. Beyond the realm of sports, the 1994 World Cup was also a significant event in the modern history of Swedish-American relations. As Dag Blanck has shown, the ways in which the United States and Sweden have related to each other have been defined by “the two M’s”—migration and modernity. The nineteenth- and early twentieth-century mass migration from Sweden to the United States created a network of contacts between the countries, while modernity has been a significant lens through which Swedes have viewed the United States and Americans have viewed Sweden. Perhaps, however, the World Cup, and the midsummer night’s game in the Silverdome, shows the need to add a third M to the mix, namely, memory
SecureRide : Detecting Safety-Threatening Behavior of E-Scooters Using Battery Information
Reckless usage of electric (e-) scooters causes many injury accidents, raising critical safety concerns. Despite newly introduced regulations, specifically, speed limits and sidewalk driving prohibitions, the number of accidents increases due to the challenges in enforcement. Therefore, a reliable method to detect safety-threatening illegal behaviors of e-scooters is essential to mitigate this growing problem. In this article, we propose SecureRide, a system that accurately detects illegal e-scooter behaviors, i.e., speeding violation and sidewalk riding, at runtime using only battery information, without the need for additional sensors. To this end, we first design a neural network-based illegal behavior predictor that takes sequences of three battery factors, i.e., voltage, current, and capacity, as inputs. The model architecture is optimized based on time constraints, target accuracy, and resource constraints of the target devices. Next, we devise a runtime detection strategy to achieve both high accuracy and low detection time. SecureRide operates in two modes with different predictors-lightweight-quick and complex-accurate models-depending on the driving situation, ensuring both high accuracy and low detection time. We extensively validate SecureRide based on actual driving experiments. Our results show that SecureRide detects illegal behaviors with an accuracy of up to 99.77% within 1.01 seconds