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BackgroundThe coverage of influenza vaccination among older adults in Norway is insufficient, especially in some immigrant groups. To improve public health, there is a need for an intervention that can increase influenza vaccination coverage. Further, interventions tailored to reduce potential barriers among immigrants can reduce health inequities. ObjectiveInfluSMS aims to determine if SMS nudging increases vaccination coverage among those aged 65 years or older (1) in Norway’s general population; (2) among immigrants born in Poland; and (3) among immigrants born in Ukraine; and evaluate the impact of SMS nudging in Norwegian versus in the official language of the native country of immigrants born in Poland or Ukraine. MethodsInfluSMS is a pragmatic randomized controlled trial conducted among people aged 65 years or older residing in Norway. Influenza vaccination coverage is the main outcome, measured in control and intervention arms for each of the 3 populations listed earlier. In all 3 populations, the control arm is standard care, that is, no individual reminder for influenza vaccination. All populations have an intervention arm that will receive an SMS nudge in the Norwegian language. In addition, the Polish and Ukrainian immigrant populations include a second intervention arm that will receive an SMS nudge in Polish or Ukrainian, respectively. In the general population, at least 23,485 individuals will be randomized to the SMS intervention arm while the rest of the population constitutes the control arm. In each of the 2 immigrant populations, we will randomize all eligible individuals 1:1:1 into the 3 arms. The intervention will take place at the start of the 2025-2026 influenza season. All eligible individuals will be passively followed up through the National Immunisation Registry, SYSVAK, from which individual influenza vaccination status 3 months after the SMS nudge will be collected. Coverage rates between arms within each population and effect sizes between the populations will be compared. The cost-effectiveness of SMS nudging will also be assessed. ResultsThe inclusion of participants will start in the third quarter of 2025, and the registry data will be available in the first quarter of 2026. Coverage rates of each strategy and coverage differences between strategies will be presented. ConclusionsSMS nudging is a scalable, inexpensive, and nonintrusive intervention that could be integrated into the national influenza vaccination program if the trial shows it effectively increases influenza vaccination coverage among older adults. Further, the trial will establish whether language is a barrier to influenza vaccination uptake among recent immigrant groups that have low influenza vaccination coverage, and to what extent this potential barrier can be diminished by SMS nudging in the official language of their native country. Trial RegistrationClinicalTrials.gov NCT06486766; https://clinicaltrials.gov/study/NCT06486766 International Registered Report Identifier (IRRID)PRR1-10.2196/63938

Maternal vaccination against pertussis is safe and provides effective protection against pertussis for the newborn, but the vaccine coverage rate remains generally low. Norway is currently planning for introduction of routine maternal pertussis vaccination. To assess maternal pertussis vaccination acceptance among pregnant Norwegian women, we surveyed women at 20–40 weeks gestation in 2019. Among the 1,148 pregnant women participating in this cross-sectional study, 73.8% reported they would accept pertussis vaccination during pregnancy if it was recommended, 6.9% would not accept and 19.2% were undecided. Predictors for low likelihood of accepting pertussis vaccination during pregnancy included low confidence in health authorities and in maternal pertussis vaccination safety and effectiveness, low awareness and adherence to influenza vaccination during pregnancy, and low awareness of pertussis vaccination. The major reasons reported for not accepting or being undecided about maternal pertussis vaccination were lack of information on vaccine safety for both mother and child. Most women reported that they would consult their general practitioner or a midwife for information if they were offered maternal pertussis vaccination. General practitioners and midwives were also regarded as the most trustworthy sources of information if the women were in doubt about accepting vaccination. We conclude that information addressing safety concerns and raising awareness about maternal pertussis vaccination could increase acceptance of maternal pertussis vaccination. Our findings highlight the pivotal role of the antenatal and primary health care services in providing such information to pregnant women.

Abstract The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPA DM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPA NT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. The most frequently co-mutated genes in CEBPA DM AML are GATA2 and TET2, however the molecular mechanisms underlying this co-mutational spectrum are incomplete. By combining transcriptomic and epigenomic analyses of CEBPA-TET2 co-mutated patients with models thereof, we identify GATA2 as a conserved target of the CEBPA-TET2 mutational axis, providing a rationale for the mutational spectra in CEBPA DM AML. Elevated CEBPA levels, driven by CEBPA NT, mediate recruitment of TET2 to the Gata2 distal hematopoietic enhancer thereby increasing Gata2 expression. Concurrent loss of TET2 in CEBPA DM AML induces a competitive advantage by increasing Gata2 promoter methylation, thereby rebalancing GATA2 levels. Of clinical relevance, demethylating treatment of Cebpa-Tet2 co-mutated AML restores Gata2 levels and prolongs disease latency.

Abstract Single-cell resolution analysis of complex biological tissues is fundamental to capture cell-state heterogeneity and distinct cellular signaling patterns that remain obscured with population-based techniques. The limited amount of material encapsulated in a single cell however, raises significant technical challenges to molecular profiling. Due to extensive optimization efforts, single-cell proteomics by Mass Spectrometry (scp-MS) has emerged as a powerful tool to facilitate proteome profiling from ultra-low amounts of input, although further development is needed to realize its full potential. To this end, we carry out comprehensive analysis of orbitrap-based data-independent acquisition (DIA) for limited material proteomics. Notably, we find a fundamental difference between optimal DIA methods for high- and low-load samples. We further improve our low-input DIA method by relying on high-resolution MS1 quantification, thus enhancing sensitivity by more efficiently utilizing available mass analyzer time. With our ultra-low input tailored DIA method, we are able to accommodate long injection times and high resolution, while keeping the scan cycle time low enough to ensure robust quantification. Finally, we demonstrate the capability of our approach by profiling mouse embryonic stem cell culture conditions, showcasing heterogeneity in global proteomes and highlighting distinct differences in key metabolic enzyme expression in distinct cell subclusters.

IntroductionProinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells.MethodsA luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques.ResultsCyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression.ConclusionOur findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress.

Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.

High and equitable COVID-19 vaccination coverage is important for pandemic control and prevention of health inequity. However, little is known about socioeconomic correlates of booster vaccination coverage. In this cross-sectional study of all Norwegian adults in the national vaccination program (N = 4,190,655), we use individual-level registry data to examine coverage by levels of household income and education of primary (≥2 doses) and booster (≥3 doses) vaccination against COVID-19. We stratify the analyses by age groups with different booster recommendations and report relative risk ratios (RR) for vaccination by 25 August 2022. In the 18–44 y group, individuals with highest vs. lowest education had 94% vs. 79% primary coverage (adjusted RR (adjRR) 1.15, 95%CI 1.14–1.15) and 67% vs. 38% booster coverage (adjRR 1.55, 95% CI 1.55–1.56), while individuals with highest vs. lowest income had 94% vs. 81% primary coverage (adjRR 1.10, 95%CI 1.10–1.10) and 60% vs. 43% booster coverage (adjRR 1.23, 95%CI 1.22–1.24). In the ≥45 y group, individuals with highest vs. lowest education had 96% vs. 92% primary coverage (adjRR 1.02, 95%CI 1.02–1.02) and 88% vs. 80% booster coverage (adjRR 1.09, 95%CI 1.09–1.09), while individuals with highest vs. lowest income had 98% vs. 82% primary coverage (adjRR 1.16, 95%CI 1.16–1.16) and 92% vs. 64% booster coverage (adjRR 1.33, 95%CI 1.33–1.34). In conclusion, we document large socioeconomic inequalities in COVID-19 vaccination coverage, especially for booster vaccination, even though all vaccination was free-of-charge. The results highlight the need to tailor information and to target underserved groups for booster vaccination.

Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

Searching for sources of inspiration is central to creative design; however, we have limited knowledge of individual inspiration search strategies in response to varying levels of task constraints. We studied 39 high-school students' inspiration search strategies using Google Images. Low task constrainedness led to "divergent search" marked by quick iterations, limited design task usage, and a heterogeneous image set. Intermediate constrainedness prompted "in-depth," "on-task exploration" characterized by slow and careful iterations with more search result examination, extensive design task usage, and homogenous images. High constrainedness led to "flexible bracketing" with quick, flexible design task use, ending with heterogeneous images. Images from the intermediately and highly constrained conditions generated more ideas and were perceived as more inspiring (relative to low) in a new group of students. We discuss the idea of a 'sweet spot' of constrainedness in an inspiration search process in design and consider implications for design research and future work.

Abstract Background Cervical cancer incidence is influenced by screening and risk factors in the population. The main risk factor for cervical cancer is sexually transmitted human papillomavirus (HPV), which is sexually transmitted and thus associated with sexual behavior. Smoking, parity and hormonal contraceptive use may also be associated with cervical cancer risk. We compared incidence, screening coverage and risk behaviors for cervical cancer between health regions in Norway. Methods We obtained data on incidence of cervical cancer among Norwegian women during 1992–2016 and data on screening coverage from the Cancer Registry of Norway. We obtained data on sexual behavior and smoking from a population-based survey of 16,575 Norwegian women who were 18–45 years old in 2005. Results Cervical cancer incidence was higher in the northern and southeastern region than in the middle and western region (range in incidence per 100,000 person-years during 1992–2016; north: 10.5 to 14.6; southeast: 9.3 to 12.9; mid: 6.8 to 9.5; west: 8.4 to 10.0). The incidence decreased modestly in the north (average annual percentage change (95% confidence interval) − 1.0 (− 1.2 to − 0.7)) and southeast (− 0.7 (− 1.0 to − 0.3)), but did not change significantly in the mid (− 0.3 (− 1.0 to 0.4)) and west (− 0.3 (− 0.6 to 0.0)). Compared to the national average, women in the north had earlier sexual debut, more partners and higher prevalence of ever having had a sexually transmitted infection (STI), while the opposite was observed among women in the west. Women in the middle and southeastern regions tended to be similar to the national average for sexual behaviors. Although less pronounced, the prevalence of smoking showed regional patterns similar to that observed for sexual behaviors, while ever-use of hormonal contraceptives and cervical screening coverage was similar between regions. Conclusions There were regional differences in cervical cancer incidence during the era of nationally organized cervical screening in Norway. To some extent, these differences corresponded to regional differences in risk behavior for cervical cancer in the Norwegian female population.

Climate change, with the disruption of hydrological and thermal regimes, is threatening freshwater entomological biodiversity in different ways. While extinction or distribution range change of some species can be noted relatively easily, the effects on life cycle usually require considerable data. In this short communication, we show that Ephoron virgo (Olivier, 1791), a univoltine mayfly, anticipated the date of emergence in the Tanaro River (Northwest Italy) over the last 17 years and how this is closely related to the increase in local temperatures. Since this species is known for its impressive and synchronised hatchings, we relied on official reports from the municipality of Alba, which allowed us to analyse a greater dataset, demonstrating how unconventional documents combined with direct observation or press articles can also be useful in scientific studies. [ABSTRACT FROM AUTHOR]

Single-cell proteomics can provide insights into the molecular basis for cellular heterogeneity. Here, the authors develop a multiplexed single-cell proteomics and computational workflow, and show that their strategy captures the cellular hierarchies in an Acute Myeloid Leukemia culture model.

Prevalence of different HPV genotypes is changing after HPV vaccination. The associated risks are needed for optimizing cervical cancer screening. To estimate HPV type-specific prevalence, odds ratio (OR), and positive predictive value (PPV) for cervical cytological abnormalities, we determined 41 different HPV genotypes in cervical samples from a population-based sample of 8351 women aged 18–51 years before HPV vaccination era (V501-033; NCT01077856). Prevalence of HPV16 was 4.9% (95% CI: 4.4–5.5) with the PPV for high-grade cytology 11.2%, and OR 11.9 (95% CI: 8.5–16.5). Carcinogenic HPVs included in the nonavalent vaccine (HPV16,18,31,33,45,52,58) had a population prevalence of 14.4% (95% CI: 13.5–15.4), with PPV of 8.0% (95% CI: 6.8–9.3) and OR 23.7 (95% CI: 16.0–63.5) for high-grade cytology. HPV types currently included in most screening tests, but not vaccinated against (HPV35,39,51,56,59,66,68) had a joint prevalence of 8.5% (95% CI: 7.8–9.2) with PPV of 4.4% (95% CI: 3.3–5.7) and OR of 2.9 (95% CI: 2.0–4.0) for high-grade cytology. The other 27 non-carcinogenic genotypes had a prevalence of 11.8%, PPV of 2.9% (95% CI:2.1–3.9), and OR 1.5 (95% CI: 1.1–2.2.) for high-grade cytology. These results suggest that HPV screening tests in the post-vaccination era might perform better if restricted to the HPV types in the nonavalent vaccine and screening for all 14 HPV types might result in suboptimal balance of harms and benefits.

With the objective to investigate associations between sociodemographic characteristics and participation in interventions designed to increase participation in cervical cancer screening among under‐screened women, we randomized a random sample of 6000 women in Norway aged 35–69 years who had not attended cervical screening for ≥10 years to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self‐sampling kit (opt‐in), or (iii) a self‐sampling kit unsolicited (send‐to‐all). We analyzed how sociodemographic characteristics were associated with screening participation within and between screening arms. In the send‐to‐all arm, increased screening participation ranged from 17.1% (95% confidence interval [95% CI] = 10.3% to 23.8%) to 30.0% (95% CI = 21.5% to 38.6%) between sociodemographic groups. In the opt‐in arm, we observed smaller, and at times, non‐significant increases within the range 0.7% (95% CI = −5.8% to 7.3%) to 19.1% (95% CI = 11.6% to 26.7%). In send‐to‐all versus control comparisons, there was greater increase in participation for women in the workforce versus not (6.1%, 95% CI = 1.6% to 10.6%), with higher versus lower income (7.6%, 95% CI = 2.2% to 13.1%), and with university versus primary education (8.5%, 95% CI = 2.4% to 14.6%). In opt‐in versus control comparisons, there was greater increase in participation for women in the workforce versus not (4.6%, 95% CI = 0.7% to 8.5%), with higher versus lower income (6.3%, 95% CI = 1.5% to 11.1%), but lower increase for Eastern European versus Norwegian background (−12.7%, 95% CI = −19.7% to −5.7%). Self‐sampling increased cervical screening participation across all sociodemographic levels, but inequalities in participation should be considered when introducing self‐sampling, especially with the goal to reach long‐term non‐attending women. [ABSTRACT FROM AUTHOR]

Aims: Teenage pregnancy may have negative consequences for the mother and the infant. The aim of the study was to examine whether selected individual factors occurring early in life were associated with teenage pregnancy. Methods: In a population-based, cross-sectional questionnaire study among 34,455 women from Denmark, Norway, and Sweden aged 20–45 years, who had first sexual intercourse (FSI) at age 13–19 years, we assessed the association between early smoking and drinking initiation (i.e., before the age of 13), contraceptive use at FSI, and teenage pregnancy. Log-linear binary regression models were fitted to estimate the relative risk (RR) with 95% confidence intervals (CIs) of teenage pregnancy according to the three exposure variables, overall and by age at FSI. Furthermore, the outcomes of the teenage pregnancies were examined according to age at FSI. Results: Teenage pregnancy occurred in 11% of the population. Both early smoking initiation (RR: 1.6; 95% CI: 1.4–1.8), early drinking initiation (RR: 1.2; 95% CI: 1.0–1.4), and non-use of contraceptives at FSI (RR: 1.9; 95% CI: 1.8–2.0) were associated with teenage pregnancy. The associations for early smoking initiation and non-use of contraceptives remained when analyses were stratified by age at FSI. Almost 60% of all teenage pregnant women had an induced abortion and less than 30% gave birth. Conclusions: Individual factors, including early smoking and drinking initiation, and non-use of contraceptives at FSI, were associated with teenage pregnancy regardless of age at FSI. This emphasizes the necessity of focusing on early risk-taking behavior as a potential modifier to prevent teenage pregnancy. [ABSTRACT FROM AUTHOR]