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I-motifs are non-canonical, four-stranded DNA structures in cytosine-rich genomic regions, yet their protein-mediated regulation remains underexplored. Here, we identify PCBP1 (Poly(rC)-binding protein 1) as a selective i-motif-binding protein that unfolds specific i-motifs depending on their protonation and hairpin-forming propensities. Systematic truncation reveals that individual K-homology (KH) domains of PCBP1 cannot selectively bind or unfold i-motifs, but their coordinated actions restore wild-type PCBP1 functions. Using biochemical, biophysical, and molecular dynamics studies, we demonstrate that KH1+2 domains remodel i-motifs, recruiting KH3 to facilitate unfolding and efficient DNA replication. Chromatin and cell-based investigations reveal that PCBP1-knockdown increases i-motif formation at specific genomic loci, coinciding with G₁/S arrest and elevated ϒH2AX, indicative of genomic instability. During G₁/S transition, PCBP1 occupancy peaks at these i-motif loci, ensuring i-motif resolution in early S phase. These findings establish PCBP1 as a critical regulator of i-motif dynamics, directly linking its unfolding activity to G₁/S transition and genome stability.

The increasing prevalence of inflammatory bowel disease (IBD) and rising pollution from micro- and nanoplastic (MNP) particles has prompted investigations on their potential interconnection. To elucidate the complex relationship between IBD and exposure to MNPs, we induced colitis in mice using dextran sodium sulfate (DSS) and orally administered a mixture of polystyrene (PS) MNPs (diameter 10, 1, and 0.29 µm). These particles enabled a detailed examination of MNP biodistribution, innate immune cell response and gut microbiome alterations under inflammatory conditions. Specifically, the nanosized PS particles predominantly accumulated in the bloodstream and excretory organs, with enhanced accumulation in the inflamed gut/colon. Proteomic analysis of the colon revealed alterations in molecular pathways related to protein transport, metabolism, and immune responses. Specifically, we found macrophage proteome signatures with pro-inflammatory polarization, highlighting the intricate effects of MNPs on inflammation and immune cell behavior. Moreover, MNPs significantly disrupted the gut microbiome, reducing microbial diversity and shifting bacterial populations towards pro-inflammatory and potentially pathogenic species. These changes suggest that MNP exposure could exacerbate colitis through complex interactions involving MNPs, immune responses, and microbial dynamics. The widespread presence of MNPs underscores the urgent need for comprehensive strategies to address MNP pollution, its implications for disease, and potential impacts on public health.

Abstrakt

Bakgrund: Preoperativ oro och ångest är vanligt hos vuxna patienter som ska

genomgå kirurgiska ingrepp och handlar ofta om osäkerhet inför det som ska hända.

Trots att kirurgiska ingrepp och anestesi idag genomförs med hög säkerhet kvarstår

oro och ångest som ett vanligt och betydelsefullt fenomen i samband med operation.

Motiv: Tidigare forskning inom området har i stor utsträckning bestått av kvantitativ

forskning med fokus på att mäta ångestnivåer, kartlägga riskfaktorer och analyser

samband mellan ångest och kliniska utfall. Kvalitativ forskning bidrar med en

fördjupad förståelse av patientens upplevelse och kan ge viktig kunskap för omvårdnad

i den preoperativa fasen.

Syfte: Syftet var att i en litteraturstudie belysa vuxna patienters upplevelser av

preoperativ oro och ångest inför kirurgiska ingrepp.

Metod: Studien har en kvalitativ design med metasyntes som metodologisk ansats.

Datainsamlingen genomfördes i sex databaser: APA PsychInfo, Cinahl, MEDLINE,

PubMed, Scopus och Web of Science, vilket resulterade i 14 inkluderade studier.

Analysen genomfördes i en fyra stegs metod enligt SBU:s rekommendationer för

syntes av studier med kvalitativ analysmetodik.

Resultat: Analysen resulterade i tre huvudteman samt sex underteman.

Huvudtemana var Existentiell utsatthet och oro för det okända, Omgivningens och

vårdorganisationens påverkan på oro och ångest samt trygghetsskapande resurser.

Konklusion: Preoperativ oro och ångest visar sig grunda sig i flera olika faktorer och

det finns inte ett självklart sätt att möta och hantera känslorna för patienterna. Ett

stort stöd ligger hos vårdaren, där personcentrerad vård, god kommunikation, ett

tryggt vårdklimat och ett gott bemötande tillsammans kan bidra till ökad trygghet

inför kirurgiska ingrepp.

Bakgrund: I Sverige arbetar anestesisjuksköterskan med ett omfattande kliniskt ansvar och självständighet i den perioperativa vården. Luftvägshantering innefattar en central arbetsuppgift där extubering utgör ett kritiskt moment där upp till en tredjedel av luftvägskomplikationer uppstår.  Anestesisjuksköterskan bedömer, utvärderar och utför extubering av patienter dagligen. Klinisk intuition har beskrivits som en omedveten tankeprocess som stärks av erfarenhet och kan fungera som stöd i det kliniska beslutsfattandet. 

Motiv:  Det finns etablerade objektivt bedömningsbara kriterier för att en extubering ska utföras så säkert som möjligt. Emellertid är det i forskning etablerat att sjuksköterskan i det kliniska arbetet använder sin intuitiva förmåga. Kombinationen mellan objektiva parametrar och klinisk intuition är inte alltid så tydligt definierat och därför kan det finnas ett behov att fördjupa kunskapen inom ämnet. 

Syfte: Att undersöka hur anestesisjuksköterskor använder och kombinerar objektiva kriterier och klinisk intuition i beslutsfattandet inför extubering av patienter efter anestesi.

Metod: Individuella semistrukturerade intervjuer med specialistsjuksköterskor inom anestesi (n=8) genomfördes. Intervjuer analyserades med kvalitativ innehållsanalys. 

Resultat: Resultatet visade att anestesisjuksköterskorna kombinerade objektiva mätbara parametrar och den kliniska intuitionen i beslutsfattandet inför extubering. Klinisk erfarenhet spelade en stor roll för hur intuitionen upplevdes och användes i beslutsfattandet. Mindre erfarna anestesisjuksköterskor upplevde den kliniska intuitionen som subjektiv och tenderade att förlita sig mer på de objektivt mätbara kriterierna i sin beslutsprocess. I resultatet lyftes teamarbete och patientsäker vård fram som viktiga i beslutsprocessen och organisatoriska faktorer hade viss inverkan på medveten och omedveten stress. I slutändan var extuberingsbeslutet grundat i patientsäker vård.

Konklusion: Den kliniska intuitionen utvecklas över tid och blir mer framträdande genom ökad yrkeserfarenhet. Anestesisjuksköterskorna tar beslut efter patienten bästa för att skapa en patientsäker vård, vilket möjliggörs av öppet arbetsklimat, trygghet till sin kunskap och kollegialt stöd. 

Background: Type 2 diabetes mellitus (T2DM) is a chronic disease and a global health problem that is becoming increasingly common. Self-care is a central and lifelong strategy for maintaining good health outcomes in T2DM and, among other things, reduces the risk of complications. Self-care requires effort from individuals, so it is important that they take responsibility with the right support from healthcare professionals. Being newly diagnosed can involve difficulties in adapting to the disease and the lifestyle changes that come with it.

Aim: The aim of the study is to describe experiences of self-care among people with newly diagnosed T2DM.

Methods: This literature study aims to compile existing research with a qualitative design. Eight qualitative articles were identified and researched in the databases Cinahl and PubMed.

Results: The results from the articles revealed different experiences in self-care and two main categories with five subcategories were identified. The defined categories are: 1) The importance of support and promoting factors for self-care, 2) Challenges in adapting to lifestyle changes.

Conclusion: People with newly diagnosed type 2 diabetes find self-care challenging. The literature review highlights the need for person-centered support, taking well-being into account, individualized education, and guidance from healthcare services to reduce the risk of limitations in self-care and future complications.

Bakgrund: Den mobila intensivvårdsgruppen (MIG) har som syfte att identifiera, granska och behandla patienter med ökad risk att utveckla kritisk sjukdom. Kärnan i MIG- funktionen är tidig identifiering och behandling vid klinisk försämring med målet att förbättra patientutfall. Det standardiserade bedömningsinstrumentet National Early Warning Score (NEWS) utgör grunden till MIG- aktivering och baseras på fysiologiska vitalparametrar. När dessa avviker från fastställda tröskelvärden finns skäl för aktivering av MIG- funktionen. Aktivering kan även ske utifrån ett bekymmerskriterium som baseras på allvarlig oro hos vårdande personal på avdelning trots adekvata fysiologiska tröskelvärden. Motiv: För specialistsjuksköterskan inom intensivvård är det centralt att kunna ge stöd till kollegor i tidig handläggning. Genom att studera orsaker till MIG-aktivering samt analysera skillnader mellan patienter som kvarstannar på avdelning och de som överförs till intensivvård kan ökad förståelse erhållas för hur MIG- funktionen kan utvecklas och optimeras. Syfte: Att undersöka orsaker till aktivering av den mobila intensivvårdsgruppen på vårdavdelning, kartlägga ordinerade åtgärder samt jämföra personalens skattning av NEWS- poäng och symtom mellan patienter som kvarstannade på avdelning respektive förflyttades till intensivvårdsavdelning. Metod: Studien genomfördes på Sunderby sjukhus och hade en retrospektiv kvantitativ tvärsnittsdesign baserad på 212 insamlade MIG- protokoll. Data överfördes och kodades i Excel och analyserades i statistikprogrammet Jamovi. Resultaten presenterades med deskriptiv statistik i form av medianer och procentsatser samt med jämförande analyser genom Mann Whitney U- test och Chi- två test för oberoende grupper. Resultat: Den vanligaste fysiologiska orsaken till aktivering av MIG var andningspåverkan (37,6%) följt av cirkulationspåverkan (24,8%) och medvetandegrad (9,6%). Dessutom utgjorde allmän oro 23,0% av MIG-aktivering. Av ordinerade åtgärder som riktades till patienter som kvarstannande på avdelning var 24,9% relaterade till andning och 26,2% till cirkulation. Det fanns en signifikant skillnad i NEWS- poäng mellan patienter som kvarstannade på avdelning och patienter som förflyttades till intensivvård (p= 0,003). Vid jämförelse av symtom mellan patienter som kvarstannade på avdelning och de som förflyttades till IVA sågs inga statistiskt signifikanta skillnader. Konklusion: Majoriteten av patienterna kvarstannade på avdelning efter MIG- bedömning. Skillnader i NEWS- poäng mellan grupperna indikerar att ingen enskild symtomkategori var signifikant associerad med förflyttning. Den höga andelen ordinerade åtgärder riktade till patienter som kvarstannade, samt en hög grad av klinisk stabilisering visar att MIG- funktionen bidrar till att förebygga utveckling av kritisk sjukdom.  

Bakgrund: Vattenfödslar sägs ha utövats i över tusentals år, är något som erbjuds världen över och innebär att barnet föds fram helt under vattnet. Vattnet agerar smärtlindrande vilket minskar behovet av annan smärtlindring och krystningen blir mer spontan vid en vattenfödsel, dessutom ses inga risker för barnet vid en vattenfödsel. De kvinnor som fött i vatten upplever att de hade en mer aktiv roll i sin förlossning. Barnmorskorna upplever vattenfödslar som fridfulla där hon är med kvinnan och att en vattenfödsel gav en mer kvinnocentrerad vård. 

Motiv: Vattenfödsel har under de senaste åren blivit något som allt fler kvinnor önskar. Handläggningen vid en vattenfödsel ser annorlunda ut och är ett nytt arbetssätt för barnmorskan. Därför är det av vikt att belysa barnmorskans syn och erfarenhet av vattenfödsel för att få ny kunskap och kunna erbjuda vattenfödslar i större utsträckning inom regionerna. 

Syfte: Syftet med denna studie är att belysa barnmorskors syn på och erfarenheter av vattenfödslar i de norra regionerna i Sverige.

Metod: Kvalitativ design med induktiv ansats användes. Semistrukturerade intervjuer med sju barnmorskor på fyra förlossningsavdelningar genomfördes. Materialet analyserades med kvalitativ innehållsanalys. 

Resultat: Resultatet i studien omfattar tre huvudkategorier: “Ett fysiologisk födande till gagn för både kvinnan och barnmorskan”, “Barnmorskans förhållningssätt vid vattenfödsel” och “Utmaningar med att erbjuda vattenfödsel”. 


Konklusion: Vattenfödslar bidrar till ett fysiologiskt födande med mindre interventioner och en kvinnocentrerad vård. Vattenfödsel är ett nytt arbetssätt för barnmorskan som sätter högre krav på kompetensen.

Sedation with benzodiazepines (BZs) has eventual side-effects increasing the risk for ventilator-associated pneumonia (VAP) (e.g. immunity alterations and nervous/mechanical responses), but there are some knowledge gaps on the topic. For instance, whether BZs could cause a modulation of bacterial virulence, and/or influence the host-pathogen interaction in neglected contexts to facilitate VAP. Consequently, we analyzed relevant in vitro and in vivo infection-related parameters to decipher whether they could be affected by BZs to increase the success for infection of the top VAP-causing pathogen Pseudomonas aeruginosa. While most variables were unaltered, an attenuated pathogenic impact on lung A549 cells (invasion, cytotoxicity and inflammation reduced up to ≈ 50%) appeared upon BZs exposure at high therapeutic concentrations, potentially because of effects mostly on the cultured cells. These facts could entail a BZs-associated stealth pathogen-like behavior of P. aeruginosa consisting of a weak immune activation proportional to the mild damage caused, perhaps favoring VAP onset. BZs also triggered a significantly increased biofilm formation (up to ≈ 2-fold > controls) on plastic plates and endotracheal tubes (supported by the upregulation of biofilm-related genes/KEGG pathways and increased c-di-GMP accumulation), suggesting the BZ-dependent boosted formation of these sessile reservoirs which could potentially increase bacterial release to low airways and thus VAP progression.

Background: Identifying significantly mutated genes in tumors aids in understanding disease etiology and survival and may aid in the discovery of new drug targets. We aimed to detect and characterize mutated genes from a large, well-characterized group of colorectal cancers.

Methods: In tumor and paired normal samples from 6,111 colorectal patients, we sequenced 199 genes identified from whole exome sequencing of over 1,100 tumors. Analyses focused on non-silent mutations. We classified significantly mutated genes after stratification by hypermutation status, and estimated associations of mutated genes/pathways with disease-specific (DS)-survival using Cox regression, adjusting for age, sex, mutation burden, hypermutation status, and study while accounting for multiple comparisons (n = 4,874).

Results: We identified 57 genes that were significantly mutated in colorectal cancer, including 9 that were not previously reported. Among individual genes, only BRAF p.V600E mutations were significantly associated with poorer survival after correction for multiple testing (HR 1.96, P = 2.07 × 10− 10), with a more pronounced association among those with non-hypermutated tumors (HR 2.24, P = 1.79 × 10− 12). We also observed statistically significant associations with survival for four mutated pathways: TP53/ATM (HR 1.24, P = 7.96 × 10− 4), RTK/RAS (HR 1.33, P = 3.81 × 10− 6), TGF-beta (HR 1.25, P = 1.85 × 10− 3), and WNT (HR 0.81, P = 2.52 × 10− 03).

Conclusions: We identified 9 significantly mutated genes, some of which are known drug targets. Among individual genes, only the BRAF p.V600E mutation was significantly associated with DS-survival, suggesting a limited survival impact from mutations driving colorectal cancer development.

Background: Interprofessional simulation-based education (IPSE) holds the potential to prepare healthcare students to handle the complexity of healthcare. However, complexity and resilience are traditionally not addressed deliberately in IPSE. The aim of this study was to explore the effect of resilience-focused debriefing (RFD) that addresses complexity and resilience, on reflection and teamwork in IPSE for pre-graduate healthcare students.

Methods: In a convergent mixed methods intervention study, 149 nursing and medical students in their last semester participated in a full-day IPSE course with five progressively challenging scenarios. Fifteen facilitators were instructed to use RFD. Qualitative date, comprised of transcripts from nine debriefings, were analysed using topic analysis. An intervention check was performed to assess the use of RFD. Quantitative data comprised pre-post ratings of team performance in videorecorded scenarios (1 and 5) from 18 groups using the Team Emergency Assessment Measure (TEAM). Additionally, a study-specific rating scale was employed to assess the extent of participants’ perceived challenges during scenarios.

Results: RFD helped facilitators to guide the students’ attention to the complexity of teamwork and how to manage such complex situations successfully by adapting crisis resource management principles and performing resilient actions (e.g., attunement, adaptive leadership), both as individuals and as teams. Applying RFD brought the students’ attention to how they were able to succeed despite the difficulties they encountered. Although the assessed team performance was on an acceptable level, students initially had difficulties in recognizing and learning from actions that led to successful outcomes. The significant decrease in the degree of challenges experienced suggests that students developed a greater tolerance for complexity. Nevertheless, the quantitative data showed that there was no pre-post difference in team performance as assessed by TEAM.

Conclusions: RFD can be used to increase healthcare students’ attention to the complexity of interprofessional teamwork in acute dynamic situations and help them recognize and learn from both successful actions and overcoming challenging situations. Although we did not find a significant gain in team performance, the integrated results suggest that RFD may potentially improve interprofessional teamwork. Further research is warranted to develop instruments measuring team performance that are sensitive to various aspects of resilience, as well as to deepen the understanding of RFD in the simulation-based education.

Ekonomiskt bistånd utgör det yttersta och sista skyddsnätet i det norska välfärdssystemet, och ärenden om ekonomiskt bistånd beslutas av Nav (Nye arbeids- og velferdsforvaltninga). Besluten om ekonomiskt bistånd fattas utifrån individuella bedömningar som grundas i både aktuell lagstiftning och individens livssituation. Syftet med denna studien är att studera hur handläggare inom Nav upplever att socialfaglig kompetens och den individuella bedömningen påverkar beslutsfattandet inom ekonomiskt bistånd. Studien ämnar även att belysa hur professionellt omdöme används i det praktiska arbetet, samt vilka faktorer som upplevs vara de mest avgörande för kvaliteten i besluten. Studien genomfördes med en kvalitativ metodansats och baseras på tre semistrukturerade intervjuer med handläggare som arbetar med ekonomiskt bistånd vid ett Nav-kontor i Norge. Intervjuerna analyserades med hjälp av riktad innehållsanalys, och tolkades i relation till domänteori samt Lipskys teori om gräsrotbyråkrater. Studiens resultat visar att den socialfagliga kompetensen upplevs som central för att kunna fatta välmotiverade och rättssäkra beslut. Handläggare med socionomutbildning beskrivs ha en större förmåga att använda ett helhetsperspektiv där klientens livssituation, aktuell lagstiftning och etiska överväganden vägs samman. Studien visar även att den individuella bedömningen är både nödvändig och komplex, samt att användandet av skön är en förutsättning för att kunna fatta beslut baserade på individens behov. Det framkommer samtidigt att variationer i hur skön används kan bidra till skillnader i beslutsfattandet. Socialfaglig kompetens, individuellbedömning och professionellt omdöme framträder som tätt sammankopplade och avgörande för kvaliteten i beslutsfattandet inom ekonomiskt bistånd. Studien belyser även risker med bristande socialfaglig kompetens, och pekar på vikten av att stärka den professionella kompetensen inom Nav för att säkerställa likvärdiga och professionella bedömningar.

Flaviviruses replicate their genomes in replication organelles (ROs) formed as bud-like invaginations on the endoplasmic reticulum membrane, which also functions as the site for virion assembly. While this localization is well established, it is not known to what extent viral membrane remodeling, genome replication, virion assembly, and maturation are coordinated. Here, we image tick-borne flavivirus replication in human cells using cryo-electron tomography. We find that the RO membrane bud is shaped by a combination of a curvature-establishing membrane modification and the pressure from intraluminal template RNA. A protein complex at the RO base extends to an adjacent membrane, where immature virus particles bud. Naturally occurring furin site variants determine whether virus particles mature in the immediate vicinity of ROs. We further visualize replication in mouse brain tissue by cryo-electron tomography. Taken together, these findings reveal a close spatial coupling of flavivirus genome replication, budding, and maturation.

This thesis examines how the door functions as a chronotope in Magda Szabó’s novel The Door (Az ajtó, 1987). The study aims to deepen the understanding of the door’s role beyond its conventional interpretation as a literary symbol. This question is analyzed using a combined theoretical framework: Mikhail Bakhtin’s concept of the threshold chronotope and Joy Ladin’s subcategories, local chronotope and overlapping chronotope.

The door as a chronotope and structural boundary leads to a diegetic gap between the narrator’s world of modern society and Emerence’s world of trauma. Furthermore, the door’s chronotopic function is the cause of the narrator’s betrayal, or, in Bakhtin’s term, a fall. This results in the collapse of Emerence’s self-created identity. 

The results contribute to scholarship by shifting the focus from the door as a symbol to a chronotope that governs the novel’s narrative development and themes. 

The following paper investigates the humor in Mikael Niemi’s novel Popular Music from Vittula (2003) [Populärmusik från Vittula (2000)]. Selected excerpts representing different forms of humor are analyzed from the perspective of previous humor research and theoretical views to demonstrate its function, construction and foundation. The analysis explores cringe humor, toilet humor, play on words, irony and wit in relation to the incongruity theory and Murray Roston’s theory of deflation, and furthermore their rhetorical function and literary, expressive aspects. The purpose of this paper is to elucidate an important part of Niemis’s authorship which should be explored further. 

The outbreak of Highly Pathogenic Avian Influenza H5N1 in U.S. dairy cattle poses substantial risks to public health, economic sustainability of farming, and global food systems. Using a Computable General Equilibrium model, we simulate its short- to medium-term impacts on Gross Domestic Product and other macro-economic outcomes for the US and its main trading partners. We simulate impacts under the current situation and realistic and reasonable worst-case scenarios. We estimate domestic economic losses ranging between 0.06% and 0.9% of US GDP, with losses to the dairy sector ranging between 3.4% and 20.6%. Trading partners increase dairy production to compensate for the loss. Current government subsidies are about 1.2% (95% HDI: 1% to 1.4%) of output losses, and likely insufficient to incentivise farmers to step up surveillance and biosecurity for mitigating the possible emergence of H5N1 strains with pandemic potential into human populations.

Background: Normal pressure hydrocephalus (NPH) is one of the few remediable causes of decline in gait and cognitive function in the ageing population. The roles of the cerebral circulation including haemodynamic reserve and cardiovascular co-morbidity in the pathogenesis, management and prognostication of NPH remain ill-defined. In this systematic review, we have updated Owler & Pickard’s review of 2001 to examine whether:

global/regional Cerebral Blood Flow (CBF) changes are specific to NPH, appropriately coupled to cerebral metabolism and/or reflect cerebral ischaemia; changes in global/regional CBF are predictive of outcome after CSF drainage; global and regional cerebrovascular autoregulation and reactivity are more sensitive predictors of outcome after CSF drainage than baseline regional CBF (rCBF); changes in global or regional CBF a cause or effect (‘chicken and the egg’) of NPH; a trial is warranted that combines assessments of haemodynamic reserve, CSF outflow resistance and response to temporary CSF drainage.

Main body: We have systematically reviewed studies from 2000–2024 assessing CBF, autoregulation, and cerebrovascular reactivity (CVR) in adult NPH. Global and regional CBF were consistently reduced in NPH, particularly in periventricular white matter and deep grey matter, but these reductions were not predictive of shunt response. CVR varied from impaired to preserved and showed greater promise as a predictor of clinical improvement after CSF drainage or shunting. Methodological heterogeneity and small sample sizes limited meta-analysis. The interplay between CBF, CSF dynamics, and brain biomechanics remains complex, with evidence suggesting that impaired haemodynamic reserve may precede irreversible tissue damage.

Conclusions: Baseline rCBF and borderline ischaemia reflect NPH networks but do not predict shunt response. CVR impairment does. It is suggested that randomised controlled trials be used to assess the predictive accuracy of combining the response of temporary CSF drainage with changes in CVR.

Previous studies have found a markedly reduced risk of cancer among Huntington’s disease (HD) patients with CAG ≥ 40, but data on cancer risk at shorter repeat numbers are lacking. The study includes 8149 subjects from Northern Sweden Health and Disease Study. Genotyping yielded a large number of intermediate allele carriers (IA, CAGn 27–35, (n = 497), normal alleles (CAGn 17–26,n = 6584), short alleles (CAG ≤ 16, n = 169) and 31 subjects with > 35 repeats, including reduced penetrance alleles (36–39; not guaranteed to suffer HD symptoms during a normal lifespan) and HD alleles > 39. Cancer diagnoses were retrieved from the Swedish Cancer Registry and the Hospital Discharge Registry and death certificates. We used Kaplan-Meier curves and Cox proportional hazard models to estimate the time to cancer, on strata of the population created by CAG repeat number intervals. Smoking status, BMI, as well as alcohol consumption were included in the models. 2735 participants (33.6%) had ≥ 1 cancer type. The Hazard-Ratio (HR) for IA carriers compared with normal alleles was similar, 0.97 CI 0.82–1.15). The reduced penetrance allele group (CAGn 36–39, n = 29) had HR of 0.54 CI 0.22–1.30 similar to what has been reported with a full penetrance allele. Intermediate allele carriers as a group did not have a reduced risk of cancer. It remains possible that reduced penetrance alleles confer lower risk of cancer, with signs of a dose-dependent protective effect of CAG repeat length. The latter finding needs to be confirmed in even larger cohorts as these repeat numbers are relatively rare.

Background: Biological age, estimated by DNA methylation-based (DNAm) clocks, has been reported to be associated with lung cancer risk. However, the extent to which tobacco smoking behaviours can explain this association and the extent to which DNAm clocks and their components can inform risk assessment for lung cancer remains to be elucidated. This study aimed to evaluate the relationship between DNAm clocks, smoking, and lung cancer risk.

Methods: We analyzed four prospective cohorts (MCCS, Australia, 324 cases/324 controls; NSHDS, Sweden, 190 cases/190 controls; EPIC, Italy, 160 cases/107 controls; and NOWAC, Norway, 115 case/70 controls) with blood samples collected before lung cancer diagnosis. Study participants were restricted to those with a history of smoking. Incidence sampling was used to match one control to each of the lung cancer cases by cohort, sex, date of blood collection, age, and smoking status in MCCS and NSHDS. The risk discriminative performance of age-adjusted DNAm clocks and their components was compared with that of the Prostate, Lung, Colorectal, and Ovarian model 2012 (PLCOm2012) lung cancer risk model.

Results: We found several DNAm clocks positively associated with lung cancer risk (Hannum: OR = 1.13, 95% CI = 1.02–1.26; PhenoAge: OR = 1.25, 95% CI = 1.12–1.40; DunedinPACE: OR = 1.44, 95% CI = 1.29–1.62; PCGrimAge (a principal component-denoised GrimAge): OR = 1.79, 95% CI = 1.56–2.06), after adjustment for age and tobacco smoking. Tobacco smoking explained a modest proportion of variance in most age-adjusted DNAm clocks (R2 < 11%), except for PCGrimAge, where it accounted for ~ 30% of variance in both lung cancer cases and controls. Detailed smoking adjustments attenuated the PCGrimAge association with lung cancer risk by 13%. In a secondary analysis adjusting for PCGrimAge components and the PLCOm2012 score, DNA methylation-predicted packyears emerged as an independent predictor of lung cancer risk (OR = 2.23, 95% CI = 1.58–3.14). The area under the receiver operating characteristic curve (AUC) for the PLCOm2012 model was 0.66 (95% CI = 0.61–0.71) compared with 0.72 (95% CI = 0.67–0.77) for the PCGrimAge model (Pdifference = 0.03). Combining PCGrimAge with PLCOm2012 provided similar risk discrimination as PCGrimAge alone (AUC = 0.72, 95% CI = 0.67–0.77).

Conclusions: Methylation-based biological clocks capture epigenetic marks left by exposure to tobacco smoke, and some clocks may inform lung cancer risk assessment by complementing or replacing traditional prediction models.

E-learning är idag en etablerad del av kompetensutveckling i arbetslivet och möjliggör utbildning oberoende av tid och rum. Samtidigt innebär införandet av e-learning både möjligheter och utmaningar,som förutsätter kontinuerlig förändring och kompetensutveckling. Bristen på forskning om medarbetares upplevelser av dessa digitala utbildningsmoduler kan skapa onödiga problem, särskilt eftersom e-learning används brett i många branscher. Kunskapen om kvinnliga medarbetares erfarenheter är dessutom begränsad, trots att kvinnor utgör en betydande del av arbetskraften. Tidigare studier har främst fokuserat på studenters upplevelser snarare än yrkesverksamma. Syftet med denna studie är att undersöka hur kvinnliga medarbetare inom finansbranschen upplever e-learning som kompetensutveckling, hur den tillämpas i arbetet och hur den relateras till livslångt lärande. Studien utgick från frågeställningarna, Hur upplever medarbetare e-learning som en del av sin kompetensutveckling? Tillämpas de nya kompetenserna till arbetet? Vilka upplevda utmaningar och möjligheter upplever medarbetarna med e-learning? Ser medarbetarna e-learning som en del i långsiktig kompetensutveckling? Studien genomfördes som en kvalitativ studie med semistrukturerade intervjuer. Studiens resultat visar att e-learning uppfattas som en etablerad form av kompetensutveckling, men att dess värde formas av organisatoriska, pedagogiska och kulturella förutsättningar.

Background: In plants, time information is recorded in strictly ordered sequences of development events, resulting in age-associated physiological and morphological differentiation, including clear spatial gradients from the base to the crown within a single tree. However, the molecular mechanisms driving such ontogeny-related differentiation remain largely unknown.

Results: Based on our newly generated Larix kaempferi (Lamb.) Carr. genome annotation, we identified 307 age-related genes, which were grouped into two expression clusters reflecting opposite temporal trends. Spatial expression analysis further revealed 13 differentially expressed genes along the vertical axis of the tree, suggesting their roles in regulating spatially distinct physiological traits. Yeast one-hybrid and dual-luciferase reporter assays demonstrated that LaAGL2-3b directly binds to the promoters of six genes, including LaAGL2-3a, LaAGL2-3b (self-regulation), and L. kaempferi cycloartenol synthase (LkCAS1). Over-expression of LaAGL2-3 in Arabidopsis thaliana (L.) Heynh. significantly accelerated life cycle progression, supporting its functional involvement in aging-related developmental processes.

Conclusions: Our results indicate that LaAGL2-3 shows coordinated temporal and spatial expression dynamics with other age-related genes in L. kaempferi. This coordinated pattern offers hypotheses about its potential role within age-associated regulatory processes. The genomic and transcriptomic resources generated here offer a foundation for future functional investigations and for improving our understanding of conifer development and ontogeny.

Heterozygosity at human leukocyte antigen ( HLA ) loci may improve lung cancer immunosurveillance by increasing recognition of the tumor by the immune system. Previous studies utilizing data from population-level biobanks, such as the United Kingdom Biobank and FinnGen, have identified an association between germline HLA class II ( HLA- II) heterozygosity and reduced lung cancer risk in smokers. In the present study, we evaluate the association between HLA heterozygosity and lung cancer in a large case-control study (15,302 cases and 14,580 controls) with imputed HLA allele-type information, comparing differences in HLA heterozygosity between smokers and non-smokers, among lung cancer subtypes, and at 2- and 4-digit HLA allele resolution. We identify a strong protective association of HLA -II heterozygosity in smokers compared to non-smokers, particularly at the HLA-DPB1 and HLA-DPA1 loci, and provide subtype-specific resolution. Finally, analysis of the additive effects of HLA allele heterozygosity in smokers identified significant associations with several 4-digit HLA alleles, including HLA-B∗08 : 01 , HLA-A∗01 : 01 , HLA-C∗07 : 01 , HLA-DQA1∗05 : 01 , HLA-DRB1∗03 : 01 , and HLA-C∗03 : 04 . Our study provides additional evidence, with added histologic subtype information, that germline HLA -II heterozygosity is inversely associated with lung cancer risk.

Introduction: Early-life determinants of middle-age cardiovascular health are poorly understood. This study examines associations of BMI and physical fitness in male adolescents with cardiovascular health measured by the Life's Essential 8 score in middle age.

Methods: A population-based cohort study linked BMI and physical fitness from the Swedish Military Conscription Register (men conscripted from 1972 to 1987) to cardiovascular health from the Swedish CArdioPulmonary bioImage Study (2013–2018). In 2025, a total of 8,930 men (mean age, 18.3 years) were analyzed after 38.2 years of follow-up.

Physical fitness included cardiorespiratory fitness (maximal cycle-ergometer test) and muscular strength (isometric dynamometry of knee extension, elbow flexion, and handgrip). Cardiovascular health was evaluated using the American Heart Association's Life's Essential 8 score (0–100 points; poor health: <60). Associations were assessed using linear and binomial logistic regressions and restricted cubic splines.

Results: BMI and cardiorespiratory fitness exhibited J-shaped and linear associations, respectively, with cardiovascular health. Compared with normal weight (BMI: 18.5–24.9 kg/m2), AORs of having poor cardiovascular health for overweight (BMI: 25.0–29.9 kg/m2) and obesity (BMI ≥30 kg/m2) were 2.42 (95% CI=2.00, 2.92) and 5.38 (95% CI=2.99, 9.70). No statistically significant associations were observed between muscular strength and cardiovascular health.

Conclusions: Obesity and low levels of cardiorespiratory fitness in male adolescents were associated with lower cardiovascular health in middle age, after nearly 4 decades of follow-up. Although further studies are needed, the promotion of a healthy body weight and cardiorespiratory fitness in youth may be of importance for later cardiovascular health.

We describe here possibly the first two cases of alleged Shaken Baby Syndome (SBS) in Poland, based solely on “triad findings” (encephalopathy symptoms, subdural hemorrhage/SDH, and retinal hemorrhages/RH), but without signs of relevant trauma. Case #1, a 7-week-old infant girl, is suggested to represent a case of rebleeding in a birth-related SDH. In case #2, a 13-week-old infant boy, we claim that the triad findings were related to benign external hydrocephalus (BEH). Unjustified belief that triad findings are always caused by violent shaking may, apart from the obvious legal and social effects, in case #2 also have contributed to delayed adequate treatment of increased intracranial pressure and subsequent signs of permanent brain damage.

We discuss also the traditional SBS hypothesis and its lack of solid scientific evidence, and the uneven geographical acceptance of and belief in this unvalidated hypothesis.

We use sub-Doppler optical-optical double-resonance (OODR) spectroscopy with a 3.3 µm single-frequency pump and a cavity-enhanced 1.65 µm comb probe to measure 33 ladder-type (3ν3 ← ν3) and 8 V-type (2ν3) transitions in the 5880–6090 cm-1 range of methane, reaching states with rovibrational E symmetry in the region of the P 6 and P 4 polyads, respectively. We assign the ladder-type transitions using new Hamiltonian predictions and the ExoMol line list, and the V-type transitions using the new Hamiltonian, ExoMol, HITRAN2020, and the WKLMC line lists. While 7 of the states in the 3ν3 range have been previously observed either in earlier OODR work (without cavity enhancement) with 1.5 MHz accuracy or in FTIR measurements of cold bands with 150 MHz resolution, the states reported here have uncertainties down to 150 kHz (5 × 10–6 cm-1). The E-symmetry states exhibit first-order Stark splitting, which will be reported in our future work.

The HITRAN database is a curated compilation of validated molecular spectroscopic parameters, established in the early 1970s. It is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of six major components. These components include the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimentally derived absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. Responding to community requests, HITRAN2024 also incorporates — for the first time — a water-vapor continuum model.

This paper describes the details of the choices of data and their compilation for the 2024 quadrennial edition of HITRAN. The HITRAN2024 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2020 (including various updates during the intervening years).

The extent of the updates of the line-by-line section in the HITRAN2024 edition ranges from updating a few lines of specific molecules/isotopologues to complete replacements of the lists, and also the introduction of additional isotopologues and six new (to HITRAN) molecules: H3+, CH3, S2, COFCl, HONO, ClNO2. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. In addition, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often bringing the uncertainties down to unprecedented levels below 0.1%.

The HITRAN2024 edition is available through www.hitran.org as well as the HITRAN Application Programming Interface (HAPI). The functionality of the tools to work with the HITRAN data has been extended for the new edition.

Intro: Population-based studies predominantly focused on carcinoma of the parotid gland (CPG) are rare. The study aims were to analyze the incidence of CPG and to assess treatment outcomes in relation to histopathology, preoperative diagnosis and adjuvant radiotherapy.

Methods: A retrospective analysis was conducted on data from the Swedish Head and Neck Cancer Register (SweHNCR), including 1,018 patients diagnosed with CPG between 2008 and 2019.

Results: The age-adjusted incidence remained stable with a mean of 0.9 (range 0.65–1.08) cases per 100,000 person-years (ASR-Europe). Curative treatment was administered to 90 % of the patients, with a recurrence rate of 9 % within 3 years. The highest recurrence rates were observed in patients with salivary duct carcinoma and adenocarcinoma, while patients with acinic cell and mucoepidermoid carcinomas had lower recurrence rates. For stage I–II tumors, the 5-year relative survival was unaffected by whether the malignant diagnosis was known preoperatively. Male sex, increasing age, stage III–IV disease, and a World Health Organization/ Eastern Cooperative Oncology Group (WHO/ECOG) performance status 2–4 was independently associated with increased overall mortality risk, whereas the timing of adjuvant radiotherapy was not.

Conclusion: This study contributes to establishing the incidence and treatment outcomes of CPG in Sweden and highlights the diverse histopathological diagnoses of these tumors. Notably, unknown malignancy at the time of surgery did not impact survival in early-stage disease, and the timing of postoperative radiotherapy was not associated with overall survival.

Context: Substantial diagnostic delay in acromegaly contributes to increased morbidity and mortality. Screening attempts in high-risk groups have yielded few positive cases, underscoring the need for simple and precise prescreening methods.

Objective: Machine-learning analysis of facial images shows promise for acromegaly detection but requires validation in larger, well-characterized cohorts using robust machine-learning frameworks as performed in this study.

Methods: Facial images from different angles were collected via smartphone from 155 acromegaly patients (79% biochemically controlled) and 153 matched controls at all Swedish university hospitals. Six machine-learning models were trained to distinguish acromegaly from control images, including 3 deep neural networks pretrained on diverse image datasets (ImageNet models: ResNet50, InceptionV2, and DenseNet121) and 1 network pretrained specifically on facial images (FaRL). Model performance was compared to assessment by 12 experienced endocrinologists.

Results: The diagnostic accuracy of the FaRL-based model was superior to all ImageNet models and matched the accuracy of human experts (area under the receiver operating characteristic curve 0.89 for both) with similar specificity (0.87 vs 0.93) but higher sensitivity (0.82 vs 0.66). Classification agreement between the best machine-learning model (FaRL) and human experts was 86% for true negatives and 60% for true positives. Machine-learning models and human experts both showed greater sensitivity in identifying acromegaly in male patients.

Conclusion: A deep learning model pretrained on facial features (FaRL) can detect acromegaly from standard photographs with accuracy comparable to that of expert endocrinologists. This supports the feasibility of face analysis as a screening tool for acromegaly.

The nuclear pore complex (NPC) is composed of multiple nucleoporins (NUPs) and enables the exchange of RNA and proteins between the nucleus and cytoplasm. NUP98 is one of the major components of the NPC, being involved in the RNA export pathway by interacting with several transport factors. Previous studies have suggested both proviral and antiviral functions of NUP98 in viral infection, yet little is known about its function in orthoflavivirus infection. In this study we show that NUP98 is a proviral cellular protein that is recruited to the cytoplasm during orthoflavivirus infection. We observe that NUP98 is found specifically in the vicinity of the replication vesicles during infections with tick-borne encephalitis virus, Japanese encephalitis virus, and yellow fever virus. Furthermore, using surface plasmon resonance, cross-link immunoprecipitation, and cross-link immunoprecipitation-sequencing we observe that the C-Terminal domain of NUP98 directly interacts with a conserved site of the viral RNA (vRNA) in the E coding region promoting viral replication. We identified a peptide that binds to NUP98 that is antivirally active against several orthoflaviviruses by outcompeting the binding between NUP98 and vRNA, making NUP98 an attractive target for antiviral development.

Satiation is essential for energy homeostasis and is dysregulated in metabolic disorders like obesity and eating disorders such as anorexia nervosa. While satiation engages a large neural network across brain regions, how the communication within this network depends on metabolic fluctuations is unclear. This study shows that nutrient access can affect neuron-to-neuron communication in this network by regulating excitatory synaptic plasticity through O-GlcNAc transferase (OGT) in αCaMKII satiation neurons in the paraventricular nucleus (PVN). Using cell-specific knockout mice and electrophysiological recordings, we demonstrate that OGT deletion in PVNαCaMKII neurons increases input resistance and neuronal excitability while preserving basic membrane electrical properties. Strikingly, feeding triggered a robust 3.8-fold increase in excitatory synaptic input in wild-type neurons, whereas OGT-knockout neurons failed to exhibit this feeding-induced synaptic activation and instead displayed a paradoxical trend towards decreased synaptic activity upon food intake. Furthermore, OGT deletion destabilized glucose-dependent synaptic responses, with knockout neurons displaying maladaptive depression of excitatory transmission in conditions where stability is normally preserved. These findings establish OGT as a nutrient-sensitive modulator of synaptic plasticity that ensures appropriate satiation signaling by coupling metabolic state to synaptic plasticity.

The Eurasian eagle owl has declined in population, particularly in northern Sweden, making it crucial to understand the habitat characteristics that contribute to successful breeding sites to support recovery and implement more effective conservation measures. Habitat preferences in northern Sweden were examined through GIS-analysis of 30 occupied nests and 30 abandoned nests dispersed across Västerbotten and Västernorrland county, assuming that nests were abandoned due to suboptimal surroundings. A generalized linear model (GLM) was applied to land-cover data to model the probability of eagle owls breeding in different surrounding habitats at two spatial scales: within a 1-km and a 3-km radius area around each site. On the larger scale the probability of breeding increased with increasing forest cover, but only up to a moderate amount (58%) of forest, and sea area showed a near significant positive correlation with increased probability of breeding. On the smaller scale, several variables influenced the probability of breeding, with open vegetation and freshwater (positive), as well as small powerlines, roads and open land without vegetation (negative), being the most important. The effect of sea was more complex, initially decreasing the probability of breeding but showing a positive influence in interaction with other open land. Similarly, small powerlines had a negative effect and an interaction with road density revealed that the combined presence of both infrastructures further reduced breeding probability. Freshwater area increased breeding probability and buffered the negative effect of large, forested areas at the smaller spatial scale. Conversely, open vegetation had a negative effect when combined with large, forested areas, possibly reflecting inland regions that are less suitable for breeding. The more complex selection patterns observed within the smaller area suggest that nest-site selection is scale-dependent. An overview of the breeding site locations shows that many inland sites have been abandoned, while coastal sites remain occupied. This study suggests that the observed pattern may be driven by more stable prey availability, such as birds compensating for fluctuating vole populations, and by a more heterogeneous landscape structure typically found in coastal areas. Furthermore, the results underscore the importance of both open foraging areas and protective, stable environments near the nest.

Osteoporosis is characterized by an imbalance in bone remodeling, resulting in bone loss and increased fracture risk. Inflammatory diseases, such as rheumatoid arthritis, are strongly associated with secondary osteoporosis due to inflammation-induced bone loss. Pro-inflammatory cytokines, particularly TNF-α, disrupt bone homeostasis by promoting osteoclastogenesis and inhibiting osteoblast function. The Wnt signaling pathway is essential for bone formation and is suppressed in inflammatory conditions. WNT16, an osteoblast-derived ligand, increases bone mass mainly by inhibiting osteoclast differentiation but has also been found to stimulate osteoblast activity. Here we demonstrate that TNF-α downregulates Wnt16 mRNA expression in primary osteoblasts, suggesting that inflammation may impair WNT16 expression and thereby reduce bone mass. To evaluate whether pharmacological or genetical elevation of WNT16 levels can mitigate inflammation-induced bone loss, we examined the effect of WNT16 in three mouse models of local and systemic inflammation. In a knee arthritis model, intra-articular delivery of WNT16 liposomes failed to prevent local bone loss. Similarly, although osteoblast-specific WNT16 overexpression increased the overall bone mass, it did not protect against either local calvarial bone loss or systemic bone loss induced by Toll-like receptor 2 (TLR2) activation. Furthermore, in a model of systemic inflammation induced by Staphylococcus aureus, WNT16 overexpression did not preserve vertebral trabecular bone, despite increased baseline bone mass. These findings demonstrate that WNT16, although increasing the overall bone mass, is insufficient to counteract inflammation-driven bone loss.

Abstract 

The aim of this study is to examine how staff, unit managers and legal guardians in different parts of care services experience technological development throughout their years of practice. The focus lies on both the opportunities and challenges that digitalization brings to everyday work. The study also highlights how technology affects various work tasks within care services and how it shapes professional roles. To address the aim, two research questions were formulated: (I) In what ways do staff, unit managers and legal guardians perceive that technology has improved their work? (II) Do staff, unit managers and legal guardians experience that technology has introduced challenges or deterioration in their work and professional practice?

The study draws on theories of street-level bureaucracy, discretion and socialisation to understand how the respondents are influenced by and relate to technological systems in their work. The data consists of qualitative interviews with five staff members, two unit managers and one legal guardian whose assignment involves extensive contact with care services. They describe how technological systems have been implemented, changed work routines, and affect interactions with service users. Their accounts reveal both positive experiences and challenges linked to digitalization.

The findings show that technology is now an integral part of the participants’ everyday work. It is used in both administrative tasks and direct client work. Several participants describe how technology saves time on routine tasks and enables a greater focus on relational work. Direct contact with service users is considered by many to strengthen the quality of care. Technology also facilitates communication, coordination and an overview of work tasks, which contributes to a sense of structure and security.

At the same time, the participants highlight several challenges. When technology is implemented without staff involvement, systems are often perceived as inadequate. This leads to frustration, increased workload and reduced discretion, which in turn may negatively affect the quality of care. The analysis shows that staff influence over how technology is used is crucial for professional autonomy, while top‑down control can reduce motivation and engagement. Respondents emphasise that empathy, presence and social support cannot be replaced by digital solutions. However, the use of technology can shape workplace socialisation and internal collaboration. The effects of technological development vary depending on how systems are introduced and function in practice. When technology works well, it makes work more efficient and strengthens staff and service users' relationships. However, inadequate systems can negatively affect the work environment, care quality and trust. This study demonstrates that technology can both improve and hinder care work. Much depends on how systems function and the organisational conditions surrounding their use. An important conclusion is that a balance is needed between digitalization, staff discretion and human interaction to protect the core values of care in an increasingly digitalized sector.

Keywords: Digitalization, Technological development, Care staff, Daily work, Care quality 

Shared research facilities (SRFs) offer researchers cost-effective access to advanced analytical instrumentation that individual laboratories may find challenging to acquire or maintain. By centralizing resources, SRFs support a diverse user community including students, early-career scientists, senior principal investigators, and industrial collaborators, while providing expert technical support and ensuring efficient use of infrastructure and funding. These facilities not only drive research productivity and foster interdisciplinary collaboration, but also serve as centers for training the next generation of scientists. In this article, SRFs that offer solid-state nuclear magnetic resonance (NMR) capabilities are discussed, highlighting representative examples, their accessibility, governance models, technical operations, application areas, and data-sharing practices. Usage data reveal that solid-state NMR-based SRFs strongly align with high-priority research goals, contributing to impactful projects across chemistry, life sciences, and materials science, as reflected in publication outcomes. The article also emphasizes that the collaborative networks among SRFs enhance knowledge exchange and resource coordination. Such coordinated inter-facility partnerships are expected to address emerging challenges, ultimately supporting sustainable infrastructure that meets the evolving needs of the solid-state NMR community.

Tvångssyndrom eller det engelska ordet OCD står för obssesive compulsive disorder. Det är 2 % av världens befolkning som drabbas av tvångssyndrom, vilket motsvarar 200 000 personer i Sverige. Tvångssyndrom/OCD anses vara en av det svåraste sjukdomarna att behandla och kunskapen är begränsad. Bland dessa personer finns det anhöriga som även dem påverkas av denna sjukdom, en målgrupp som ofta glöms bort av samhället. Därför är syftet med denna studie att undersöka anhörigas erfarenheter av att leva med en närstående som har diagnosen tvångssyndrom/OCD med fokus på hur anhörigas livssituation påverkas och vilka konsekvenser och begränsningar det kan medföra. Studien använder sig av en enkät som spreds till anhöriga runt om i hela landet. Enkätsvaren analyserades genom regression och tematisk analys. Det teorier som framkommer i studien är familjesystemteorin kring familjens känslomässiga system och teorin om coping kring hur anhöriga hanterar stressfulla situationer. 

Resultatet visar att anhöriga påverkas av sin närståendes tvång dagligen och deras livssituation påverkas i stor utsträckning. Respondenterna uppskattade högt att det prioriterar tvånget för annat och undviker att utföra handlingar som kan öka den närståendes tvång. Anhöriga begränsas i sina liv genom att behöva anpassa sig utifrån den närstående och avstår från att träffa vänner. Många av det anhöriga som svarade på enkäten beskriver sin känsla av maktlöshet i att inte kunna hjälpa den närstående, tappat kontrollen över sitt liv och maktlösheten inom vården. I slutsatsen framkom det att anhörigas livssituation påverkas eftersom familjens behov blir förbisedda och de behöver prioritera tvånget före allt annat. Deras liv blir begränsade både utanför och i hemmet, vilket kan leda till isolering i hemmet. Anhöriga tappar kontrollen över sitt eget liv och får inte det stöd som behövs av vården. 

Syftet med denna studie är att utreda vad umgängessabotage innebär och vilka konsekvenser det kan få i vårdnadstvister. Studien har genomförts genom att granska domar från tings- och hovrätt gällande vårdnadstvister där umgängessabotage har förekommit. Domarna har hämtats från den juridiska databasen Juno och totalt har fem domar granskats, med domar från både tingsrätt och hovrätt hos alla fem. Domarna har analyserats med hjälp av tematisk analys. Resultatet visar att umgängessabotage ofta är en mycket liten del i en ofta större och mer komplex konflikt. Umgängessabotage kan innebära att man genomför en vårdnadsöverflytt, men när det blir utfallet är en ofta till följd av en komplex bedömning. Det finns inga tydliga riktlinjer för hur umgängessabotage ska bedömas i förhållande till andra principer och faktorer. Varje fall är individuellt och har sina egna faktorer vilket gör det svårt att dra en tydlig riktlinje.  

Mycket av fokus i vårdnadstvister ligger på föräldrarna och deras rätt till barnen i stället för barnens rätt till båda föräldrar, även om det inte är ursprungstanken. När konflikten ligger mellan föräldrarna och föräldrarnas fokus ligger på deras intressen kan det vara svårt att styra tillbaka konversationen till barnet. Barnet kan vara föräldrarnas intresse men kan också ses som en resurs att använda för att hämnas eller vinna över den andre. I vilket fall är det barnet som far mest illa i situationen och forskning visar att det finns stora risker för dessa barn.  

The human macrophage galactose-type lectin (MGL) recognizes exposed GalNAc residues abundantly found in tumor O-glycans. Herein, we have used an integrative chemical, structural, and functional approach to unravel the intricate specificity and molecular determinants that underlie the recognition of Thomsen-nouveau (Tn), the sialylated variant (STn), and Thomsen-Friedenreich (TF) O-glycans by the carbohydrate recognition domain of the MGL (MGL-CRD) at the molecular and cellular levels. The MGL-CRD prefers binding to Tn > STn ≫ TF O-glycans. In this molecular context, NMR, isothermal titration calorimetry, and molecular dynamics simulations revealed quantitative key structural and dynamic differences in binding, depending on the O-glycan. Interestingly, the density of Tn epitopes was critical for engaging multiple MGL-CRDs to MUC1 Tn-glycopeptides; however, the enthalpy–entropy balance strongly influenced the affinity, and a higher Tn density did not improve the binding. Cell-based mucin arrays recapitulated the MGL-CRD binding preference (Tn > STn ≫TF), but no preference for a specific O-glycan pattern in mucins was observed. The MGL-CRD also selectively recognizes glycoengineered gastric cancer cells expressing Tn/STn. Conversely, in the cellular context, employing CHO cells expressing the full-length MGL (CHO+MGL) allowed analysis of the MGL binding properties in its native presentation toward tagged isolated mucin reporters. Specificity for short tumor-associated O-glycans without any preference for a specific mucin was confirmed. Stunningly, the CHO+MGL cells revealed that the MGL shows similar binding to the STn and TF mucin reporters, suggesting that its natural oligomeric state displays promiscuous binding to simple O-glycans. Conceptually, the key role of glycan and lectin presentations for binding is thus highlighted. Moreover, this suggests the compelling scenario that the MGL serves as a universal receptor for truncated cancer-associated O-glycans.

Continuous Integration and Continuous Deployment (CI/CD) is widely adopted in modern software development. Current auto-scaling tools incloud environments are based on hardware-level metrics, limiting their ability to anticipate workload changes in a stateful cloud. This thesis investigates the usefulness of applying machine learning to predict the workload of CI/CD pipelines. The models are trained on historical job and pipeline data. Numerous preprocessing and feature techniques are explored to transform the historical data to suitable machine learning input. Two models are tested and evaluated; Random Forest Regression and Long Short-Term Memory (LSTM), with and without continuous learning. The models are evaluated on their ability to predict the workload of all occurring job types in a near future. The results indicate that all models can achieve some form of predictability, but the LSTM continuous learning model suggests to be the most accurate. However, the predictability decreases the longer test data is from the original training interval. The models also show the weakest predictability in less frequently used jobs. The findings suggest that machine learning models can contribute to reduced developer waiting time when predictions are accurate, without increasing a current static rules based solution. Future work includes exploring additional models and features, evaluate the models in a simulated real life scenario and using more computationally capable hardware.

Iron-rich minerals, such as hematite (α-Fe2O3), are prominent constituents of the Martian surface; they are considered to be potential indicators of past aqueous activity and habitability. This study investigated the interaction between the extremophilic black fungus Rhinocladiella similis LaBioMMi 1217 and hematite under simulated laboratory conditions on Mars, focusing on redox-mediated dissolution processes, metabolic adaptations, and biosignature formation. The fungus was cultivated with powdered and polished hematite substrates, and mineral alteration was monitored through physicochemical measurements and scanning electron microscopy (SEM). Genome mining was performed to identify and map genes involved in iron metabolism. The metabolic profile of the fungus under hematite treatment was assessed via untargeted metabolomics. Over 15 days, the cultures exhibited marked acidification (pH decreased from 7.0 to 4.7) and a 10-fold increase in the dissolved Fe2+ ion concentration (26–270 mg/L), indicating metabolically driven iron reduction. SEM revealed surface etching and localized roughening consistent with microbially induced weathering, whereas these changes were absent in the abiotic controls. Genes linked to siderophore biosynthesis (sidA, sidC, sidD, sidF, sidH, sidI, and sidL) and reductive iron assimilation (FET3, FTR1, and FRE1) were identified. Untargeted metabolomics confirmed the secretion of organic acids, iron-chelating siderophores (e.g., ferrichrome C), and redox-active aromatic compounds in the presence of hematite, supporting a multifaceted strategy that combines acidification, chelation, and redox mediation. Collectively, these results show that the fungus actively promotes hematite dissolution through organic molecule-mediated mechanisms. Such interactions hold astrobiological relevance, as fungal modification of hematite might lead to the production of diagnostic chemical and mineralogical biosignatures, informing future life-detection strategies on Mars.

Enligt förskolans läroplan ska barns delaktighet och inflytande utgöra centrala värden i utbildningens demokratiska grund. Trots detta visar tidigare forskning och praktik att barns inflytande i planerade undervisningssituationer inte alltid är självklart, trots att det utgör en viktig del av förskollärares professionella uppdrag. Syftet med denna studie är att bidra med fördjupad kunskap om hur barns delaktighet och inflytande förstås och möjliggörs i förskolans planerade undervisning. Studien är har genomförts med en kvalitativ metod, där semistrukturerade intervjuer använts som metod för datainsamling. Ett bekvämlighetsurval tillämpades och totalt intervjuades åtta förskollärare. Resultatet visar att barns delaktighet och inflytande i den planerade undervisningen ofta begränsas av organisatoriska faktorer såsom tidsbrist och stora barngrupper. Vidare framkommer att barns möjligheter till inflytande i hög grad är beroende av förskollärarnas tolkningar samt de förhållningssätt som pedagoger har i undervisningssituationen. Studien visar även att de strategier och arbetssätt som används för att främja barns delaktighet är nära kopplade till professionellt ansvar, som förutsätter kontinuerliga reflektioner för att barns deltagande inte ska reduceras till ett mer styrt eller symboliskt deltagande.

Syftet med denna studie är att utveckla kunskap om förskollärares didaktiska arbetssätt föratt främja barns språkutveckling och förebygga språksvårigheter i förskolan, med särskiltfokus på barn med uppmärksammade språkliga svårigheter. Studien genomfördes med enkvalitativ metod och bygger på semistrukturerade intervjuer med åtta yrkesverksammaförskollärare från fem olika kommuner. Det empiriska materialet analyserades med stöd avett sociokulturellt perspektiv på lärande, med begreppen mediering, scaffolding ochproximal utvecklingszon som analytiska verktyg. Resultatet visar att förskollärare använderbåde generella och riktade språkstimulerande strategier i den dagliga verksamheten, därdokumentation och kartläggning fungerar som didaktiska redskap för att anpassaundervisningen även om det finns en tveksamhet kring i vilken utsträckning barnensspråkkunskaper faktiskt ska bedömas. Samtidigt framträder organisatoriska utmaningar,såsom stora barngrupper och begränsad planeringstid, som faktorer som påverkarmöjligheterna att ge individanpassat språkligt stöd. Studien belyser förskollärarens komplexaprofessionella roll i mötet mellan styrdokumentens krav och den pedagogiska praktiken.

I förskolans styrdokument framgår det att verksamheten ska vara tillgänglig och likvärdig för alla barn. Tydliggörande pedagogik lyfts fram som ett arbetssätt vilket kan bidra till att skapa struktur som bidrar till begriplighet, hanterbarhet och meningsfullhet för att skapa en känsla av sammanhang i förskolans vardag. Syftet med studien är att öka kunskapen avseende förskollärares arbete för en tillgänglig utbildning för alla barn i förskolan, med inriktning på tydliggörande pedagogik. Studien baseras på kvalitativa, semistrukturerade intervjuer med åtta förskollärare. Resultatet visar att tydliggörande pedagogik beskrivs som ett arbetssätt som omfattar både pedagogers förhållningssätt och den fysiska miljön. Tydlig kommunikation, visuella stöd och strukturerade miljöer framträder som centrala faktorer för att skapa trygghet och delaktighet för barnen. Samtidigt framkommer utmaningar i form av organisatoriska förutsättningar och behov av ökad kunskap hos förskollärarna avseende tydliggörande pedagogik. Studien visar att tydliggörande pedagogik kan bidra till att skapa en mer inkluderande förskoleverksamhet där alla barns behov ges utrymme och stärker arbetet mot en förskola för alla.

Women, migrants and those in manual occupations face barriers in the labor market and are more vulnerable to unemployment, which in turn may impact mental health and contributes to inequalities. Previous research has not considered the intertwinement of multiple inequalities. This study examined intersectional inequalities (intersecting gender, social class, and migration status) in poor mental health and the mediation role of unemployment in the Spanish adult population, using the 2012 and 2017 cross-sectional Spanish National Health Surveys (n = 22,383, 18–64 years, response rates: 89.6 % and 74.0 %). Mental health was measured using the GHQ-12 and classified into good and poor. Unemployment was classified as employed or unemployed. Gender (men or women), social class (manual or non-manual) and migration status (born in Spain or migrant) were cross-classified in eight intersectional strata. Intersectional mediation analysis showed that, compared to non-manual native men, poorer mental health was found in women, migrants and manual occupations (total effect). Unemployment completely mediates mental health inequalities in strata of men with manual occupations but partially in strata of women. Moreover, mental health inequality was explained by both higher unemployment prevalence (pure indirect effect) and by greater vulnerability to unemployment (mediated interaction effect) among native men and women in manual occupations and immigrant women in non-manual occupations compared to non-manual native men. In conclusion, complex mental health inequalities seem to be underpinned by the dual processes of higher risks and worse consequences of unemployment. Health policies should target strata of manual occupations since they were more likely to be unemployed.

Background: The rate of retained common bile duct stones (CBDS) following cholecystectomy can only be estimated if CBDS managed conservatively as well as CBDS treated with endoscopic retrograde cholangiopancreatography (ERCP) are identified. The aim was to explore the rate of retained CBDS and evaluate performance of ERCP as proxy for retained CBDS in a population-based setting.

Methods: Data were collected from The Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) on patients who underwent cholecystectomy 2015–2020 with suspected CBDS at South General Hospital, Stockholm, Sweden. Medical records were reviewed to identify rate of patients with events raising suspicion of passage of retained CBDS and compare this to the rate of ERCP for retained CBDS.

Results: A total of 182 of 386 patients (47.2%) had CBDS on intraoperative cholangiography (IOC). During follow-up, 33 of the 182 presented with retained CBDS according to medical records. Of these, 24 had an ERCP registered in GallRiks with retained CBDS reported, whereas 9 had retained CBDS according to medical records only.

Conclusion: Postoperative ERCP found valid as proxy for retained stones following surgery for CBDS and can be a quality measure for management of patients undergoing gallstone surgery with suspicion of CBDS.

Sammanfattning: Juridiska institutionen motsätter sig att den föreslagna lagen om tillfällig verkställighet av svenska fängelsestraff utomlands införs och att avtalet med Estland godkänns. För det fall att en sådan lag införs anser juridiska institutionen att lagen ska vara tidsbegränsad.

Förutom en inledande övergripande kommentar följer universitetets yttrande de olika rubrikerna i utredningen.

In this paper we introduce a systemic approach for predictive and prescriptive maintenance framed within the larger system of systems, as exemplified by a use case in mining. Developments are presented as systematic, while there is a focus on improved availability modeling using the time usage model with a corresponding UML/SysML StateMachine representation. Data becomes connected with a more elaborated definition of time, with failure modes and analytics in reliability engineering being supported by improved underlying information structures.

Understanding the structure and drivers of parasite communities including species assembly patterns, diversity, abundance, and aggregation is crucial in assessing the health of wild populations and the dynamics of host-parasite interactions within ecosystems. This study analyzed tick communities parasitizing the critically endangered black rhinoceros and the near threatened white rhinoceros metapopulation in twelve sanctuaries in Kenya. A total of 14,302 ticks from 20 tick species across four genera, Dermacentor (1 species), Rhipicephalus (8 species), Amblyomma (8 species) and Hyalomma (3 species) were sampled from 372 rhinoceroses. The most dominant species included Amblyomma gemma (23.28 %), Amblyomma sparsum (22.28 %) and Rhipicephalus pulchellus (18.94 %). Six tick communities were identified based on similarity in relative tick species composition. Mean NDVI and temperature were the major drivers of tick communities. Asymptotic Hill-Shannon and Hill-Simpson tick diversity metrics were 8.12 and 6.26 respectively for the Kenyan rhinoceros metapopulation. Species diversity varied between sanctuaries with Nairobi National Park (NNP) having the highest diversity (Hill-Shannon: 6.35, Hill-Simpson: 5.8) and Sera Rhinoceros Sanctuary (SER) the lowest diversity, (1.83, 1.69). The Intensive Protection Zone (IPZ) and Nairobi National Park had the greatest species richness (14 and 13 respectively), while Sera Rhinoceros Sanctuary had the lowest (2). Spatial heterogeneity in NDVI and species abundance were major drivers of species richness and Hill-Shannon species diversity. The number of ticks per rhinoceros was highly variable with a mean (SD) of 38.53 + 40.59 ticks per host, indicating strong tick aggregation among hosts. Significant positive interspecies correlations suggest a great role of host factors in tick infestation. Environmental factors, including temperature, NDVI, and rainfall, influenced tick abundance. Host-related factors, such as age, and sex, also played critical roles. This research improves our understanding of rhinoceros tick communities, diversity, and abundance patterns, with implications for tick control, tick-borne disease surveillance and rhino conservation in Kenya.

Fungi play essential roles in key ecosystem functions and processes, yet they often occur in inconspicuous, species-rich, and complex communities that remain difficult to study. Studies of fungal communities based on DNA extracted from environmental samples commonly rely on clustering sequence reads into units of diversity, followed by taxonomic identification and, in some cases, linkage to ecological traits. In this study, we evaluated how two clustering approaches—amplicon sequence variants (ASVs) and operational taxonomic units (OTUs)—affect the characterization of fungal communities. Despite minor differences, both approaches recovered consistent taxonomic patterns and community structure. Although both methods produced a similar total number of sequence clusters, they differed in representation of fungal community composition. All ASV representative sequences matched OTU representative sequences with at least 92.2% similarity, whereas several rare OTUs showed low similarity to ASV reads, suggesting differences in the detection of low-abundance taxa. However, only a small fraction of OTU reads (< 0.1%) lacked a corresponding ASV, indicating that ASVs captured nearly all OTU-defined taxa. In contrast, 14% of ASV reads assigned to species hypotheses (SHs) did not match any OTU reads assigned to SHs, whereas only 1.3% of OTU SH-assigned reads lacked a corresponding ASV match. ASVs generally provided higher resolution than OTUs, as abundant SHs were often represented by multiple ASVs, suggesting that ASVs capture intraspecific diversity. Consequently, ASVs should not be used as direct species proxies but instead require post hoc grouping to reflect species-level diversity. OTUs-based community composition aligned more clearly with soil properties, particularly the N:C ratio. Overall, both approaches provided a similar overview of broad-scale species richness. The choice between two clustering methods depends on the research question and the desired level of taxonomic resolution, and our results provide little support for the claim that ASVs should categorically replace taxonomic units in marker-gene data analysis.

This article presents an analysis of responses to some of the mutually reinforcing challenges facing European higher education (HE) systems. In a context of ‘polycrises’, defined by European Commission President Juncker (2016) along the lines of economic, financial, social, and security challenges across different policy domains, HE responses have been varied and reflecting the peculiarities of national contexts. We focus on Swedish shifts in discourses and practices in relation to HE internationalisation, as a response to the perceived geopolitical and security threats. These crises have produced policies with distinct effects on universities, and on individual academics. The article does two things: First, it presents a critical analysis of the crisis context across European HE policy and in the national and HE context of Sweden. Second, drawing on large qualitative research, it discusses the consequences of these crises on academic identities, with a particular focus on academic mobility. The article contributes to knowledge on the experience of individual academics who develop careers in often difficult circumstances and highlights the need to integrate individual experiences and perceptions with HE-wide policies and discourses. 

Purpose: Glaucoma is characterized by progressive retinal ganglion cell degeneration. Nicotinamide supplementation has demonstrated neuroprotective potential in glaucoma by raising retinal and optic nerve nicotinamide adenine dinucleotide (NAD) via the salvage pathway, dependent on nicotinamide phosphoribosyltransferase (NAMPT). The NAMPT is essential for retinal function, and its extracellular form (eNAMPT) has been detected in blood. Reduced circulating eNAMPT could indicate impaired NAD biosynthetic capacity and glaucomatous neurodegeneration susceptibility.

Methods: We (i) developed a specific, semiquantitative assay to detect plasma eNAMPT, (ii) explored its potential as biomarker, and (iii) assessed the effect of 2-week nicotinamide supplementation on circulating levels. This was done in samples from a prospective clinical trial at the Eye Clinic, Umeå University Hospital (Sweden), including 30 controls and 90 patients with glaucoma.

Results: A Western blotting assay was designed, detecting eNAMPT (52 kilodalton [kDa]) and transferrin (77 kDa) as housekeeping protein from 0.2 µL EDTA-plasma. Intra- and inter-assay variability were 14.9% and 37.9%, respectively. eNAMPT levels showed no difference between glaucoma and controls, nor changes after supplementation.

Conclusions: eNAMPT is readily and specifically detected by Western blotting in plasma from healthy controls and patients with glaucoma. Given the role of NAD/NAMPT in neurodegeneration, this study provides a platform for specific detection of eNAMPT in liquid biopsies. Further studies specifically designed to study eNAMPT are needed to clarify its role in retinal ganglion cell degeneration and the therapeutic response to nicotinamide.

Translational Relevance: This study established a method to sensitively detect plasma eNAMPT of patients with glaucoma and controls, providing a basis for future biomarker development.

Syftet med denna studie är att undersöka hur förskollärare beskriver den ekonomiska hållbarhetens roll i förskolan. Detta var intressant att undersöka eftersom hur förskollärare kan arbeta med den ekonomiska hållbarhetsdimensionen i förskolan, i stort sett saknas i tidigare forskning. Dessutom visar sig hållbar utveckling sig i tidigare forskning, ofta medfölja en osäkerhet hos pedagoger att omsätta i förskolans vardag och undervisning på grund av kunskapsbrist i ämnet. Denna osäkerhet blir dock problematisk i förhållande till förskolans läroplan (Skolverket, 2025) som lyfter vikten av att alla som verkar inom förskolan ska verka för en hållbar utveckling, och lägga grunden för ett intresse och ansvar hos barnen för en hållbar utveckling.

Studien tar sin utgångspunkt i utbildningstraditionerna normativ, faktabaserad och pluralistiska för att på ett djupare plan förstå och kunna besvara studiens syfte och frågeställningar. Studien är genomförd ur en kvalitativ ansats där semistrukturerade intervjuer genomförts. Därefter har resultatet tagits fram genom en tematisk analys. Resultatet visar på att om än det finns undantag, uttrycker majoriteten av förskollärarna som intervjuats, att den ekonomiska dimensionen är svårast att förstå och implementera i förskoleundervisningen. Därmed hamnar ofta den ekonomiska dimensionen ofta i skymundan, i förhållande till den ekologiska och sociala. Den slutsats denna studie landar i, är att utbildning och kompetensutbyte mellan förskollärare krävs, för att bryta den ekonomiska dimensionens osynlighet i förskolan.