MYCN amplification drives replication stress in high-risk neuroblastoma, yet how MYCN-amplified tumour cells tolerate this stress to sustain proliferation remains poorly understood. Here we show that FBXL12, an SCF ubiquitin ligase substrate receptor that targets the Fanconi anaemia protein FANCD2 for degradation at replication forks, as well as the broader Fanconi anaemia and replication stress transcriptional program are elevated in high-risk and MYCN-amplified neuroblastoma. High FBXL12 expression independently predicts poor survival across neuroblastoma patient cohorts. FBXL12 loss stabilizes FANCD2 on chromatin, elevates ATR-dependent replication stress signalling and DNA damage during S phase, and impairs proliferation of MYCN-amplified neuroblastoma cells in vitro and in vivo. Mechanistically, MYCN directly engages the FBXL12-FANCD2 complex and antagonises FBXL12-mediated degradation of FANCD2 at replication forks, revealing that the oncogenic driver of replication stress also actively preserves the chromatin-bound FANCD2 pool required to tolerate it. Beyond S phase, FBXL12 loss disrupts FANCD2-dependent mitotic DNA synthesis and transmits unresolved replication intermediates into daughter cells. FBXL12-deficient cells consequently show transcriptional activation of MYC target gene, ATR, and mTOR signalling programs, and this pathway-concordant state confers differential sensitivity to ATR, and mTOR-targeting compounds, nominating candidate therapeutic strategies for this disease subset. Together, these findings define a MYCN-FBXL12-FANCD2 axis as a clinically relevant vulnerability in high-risk neuroblastoma. HIGHLIGHTS ### Competing Interest Statement The authors have declared no competing interest. Swedish Cancer Society Barncancerfonden, https://ror.org/05072yv34 Swedish Research Council, https://ror.org/03zttf063 Karolinska Institutet, https://ror.org/056d84691 Worldwide Cancer Research, 26-0033 Radium Hemmets Research Funds, https://ror.org/006hbj696
Highly filled magnetic filaments require binder systems that balance powder loading, melt flow, filament strength, and strand stability during material extrusion (MEX). Here, a polyolefin-based binder composed of a thermoplastic elastomer and grafted polyolefin (TPE + gPO) was used to prepare Sm2Fe17N3- and SrFe12O19-based magnetic filaments. The feedstocks were compounded, extruded into 2.85 mm filaments using a single-screw extrusion line with automatic spooling, and printed by MEX into ring-shaped specimens. Thermogravimetric analysis confirmed high powder contents, with residual masses of approximately 89 wt.% for Sm2Fe17N3 and 85 wt.% for SrFe12O19. The filaments showed good dimensional control, with a diameter of 2.85 ± 0.07 mm and ovality ≤ 0.017 mm. Small-amplitude oscillatory rheology at 200-240 °C showed pronounced shear-thinning behavior and an elastic-dominant response (G' > G″) over 0.01-100 Hz, supporting flow through the nozzle and shape retention after deposition. Mechanical testing confirmed sufficient handling performance, with a maximum flexural stress of 36.1 ± 0.1 MPa for SrFe12O19 and a flexural modulus up to 5.5 ± 0.2 GPa for Sm2Fe17N3. The results demonstrate that the TPE + gPO binder provides a suitable processing window for highly filled magnetic filaments for MEX-printed bonded magnets.
In this technical talk we discuss Kiavi's flavor of microfrontends and reflect on our experiences with the Microfrontends architectural style over the past five at Kiavi.
Background:Asylum seekers and refugees are at increased risk of mental illness. Previous research suggests underutilization and delayed access to care in this the population. This study aims to explore if screening during a health examination is associated with mental health care utilization among refugees and asylum seekers. Methods:A retrospective cohort study examined mental healthcare utilization patterns during the five months following voluntary health examinations among asylum seekers and refugees screened with the Refugee Health Screener (RHS-13). We analyzed data from 7726 individuals across five primary healthcare clinics in the Stockholm Region, Sweden, between 2019 and 2022. Outcomes included utilization of mental healthcare within primary care, with and without a recorded diagnosis, and referrals to other mental health units. Results:Individuals who were screened had a fivefold increase in mental healthcare utilization compared to those who were not screened (odds ratio (OR) 5.09, 95% confidence interval (CI): 3.69-7.04). Both individuals aged 26-39 OR 2.13, (95% CI 1.37-3.31) and 40 year and older OR 2.11, (95% CI 1.34-3.31) were significantly more likely to utilize healthcare compared to the youngest group. Refugees and asylum seekers from the Middle East and North Africa (OR 0.59, 95% CI 0.38-0.90) had a lower likelihood of utilizing mental health care compared to those from Asia. Conclusion:Screening was associated with a significant increase in mental healthcare utilization. This underscores that integrating mental health screening into routine health examinations can identify mental illness earlier and create more accessible pathways to mental health services.
Abstract The increasing demand for electricity and the need for decarbonization has intensified interest in natural gas–hydrogen fuel blends as an alternative for gas turbine systems. However, limited studies have evaluated their performance under tropical climate conditions. This study presents the energy, exergy, and exergoeconomic analysis of a combined cycle power plant operating with natural gas–hydrogen mixtures, with hydrogen fractions ranging from 0% to 100% in increments of 10%. The effect of compressor inlet air cooling is also assessed for temperatures between 8.8 °C and 15 °C. Results indicate that reducing the compressor inlet temperature to 8.8 °C maximizes gas turbine power output and reduces nitrogen oxide emissions. Increasing the hydrogen fraction enhances power output, particularly above 60% hydrogen, with gains between 0.06% and 0.54% per 10% increment. Exergy destruction decreases by up to 1.52%, while exergy efficiency shows a slight decline. From an economic perspective, electricity generation cost increases significantly for hydrogen fractions above 60%. These findings suggest that moderate hydrogen blending improves system performance and emissions, whereas high hydrogen concentrations require careful economic evaluation.
