519 research outputs found
From multiculturalism to civic integration : citizenship education and integration policies in the Netherlands and England since 2000s
No full textThe article discusses one of the most compelling policy issues facing liberal democracies in Europe: What policy tools can be used to promote social cohesion in a pluralist multi-ethnic society with different moral and religious and ethical values, and cultural and linguistic traditions? We focus on the role that citizenship education has taken since the early 2000s in light of the integration of immigrant children in schools in the Netherlands and England. Citizenship education is designed to integrate immigrant groups socially, foster their loyalty to the state and encourage them to become engaged in democratic politics. Our empirical analysis advances our understanding of the policy ramifications of a new turn in integration policies directed towards stronger civic integration through sharing common values and moral standards
The Malate Aspartate Shuttle is important for de novo serine biosynthesis. Broeks et al.
No full textWe hypothesized that all MAS defects lead to a secondary serine biosynthesis defect. To study whether MAS defects lead to diminished serine and glycine biosynthesis, we performed isotopic tracing experiments in 33 HEK293 cell lines with a genetic disruption of the MAS enzymes and transporters (GOT1, MDH1, SLC25A11, MDH2, GOT2, SLC25A12/13) and corresponding WT lines, including a double knockout of the AGC transporter. Cells were incubated with [U-13C]-glucose, as serine and glycine are synthesized de novo from the glycolytic intermediate 3-phosphoglycerate (3-PG). After 8 hours of incubation with [U-13C]-glucose, 13C3-serine and 13C2-glycine concentrations were most strongly decreased in MDH1 KO cells, followed by AGC, GOT1, GOT2, OGC and MDH2 KO cells when compared to control cells. The fraction of 13C3-serine and 13C2-glycine over time confirmed diminished de novo serine and glycine biosynthesis in all MAS KO cells, serine and glycine biosynthesis being only partially hampered in OGC and MDH2 KO cells. Overall, these findings demonstrate that all MAS defects lead to decreased de novo serine and glycine biosynthesis on a cellular level. [Figures 1 & S2-3] To further investigate the underlying causes of diminished de novo serine biosynthesis in MAS KO cells, we analyzed the intracellular metabolomes of the cells incubated with [U-13C]-glucose for 8 hours using direct infusion high resolution mass spectrometry (DI-HRMS). Our data demonstrates that the abundant availability of intermediates in the first steps of glycolysis leads to an increased flux to glycerol biosynthesis in MAS KO cells, while flux from glucose to pyruvate was decreased in all KO cells. The lactate (m+3)/pyruvate (m+3) ratio was increased in all KO cells and strongly correlated with serine and glycerol 3-P synthesis from glucose. Analysis of isotope enrichment in the TCA cycle and MAS demonstrated impaired flux through TCA cycle in most MAS defects. In addition, our findings indicated that a defect in the MAS cycle from GOT2 (-AGC-GOT1-) to MDH1 results in diminished metabolite flux through the NAD+ regenerating enzyme MDH1. [Figure 2, 3, S4 & S5]THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium
No full textHowat, W.J., Blows, F.M., Provenzano, E., Brook, M.N., Morris, L., Gazinska, P., Johnson, N., McDuffus, L.-A., Miller, J., Sawyer, E.J., Pinder, S., van Deurzen, C.H.M., Jones, L., Sironen, R., Visscher, D., Caldas, C., Daley, F., Coulson, P., Broeks, A., Sanders, J., Wesseling, J., Nevanlinna, H., Fagerholm, R., Blomqvist, C., Heikkilä, P., Ali, H.R., Dawson, S.-J., Figueroa, J., Lissowska, J., Brinton, L., Mannermaa, A., Kataja, V., Kosma, V.-M., Cox, A., Brock, I.W., Cross, S.S., Reed, M.W., Couch, F.J., Olson, J.E., Devillee, P., Mesker, W.E., Seyaneve, C.M., Hollestelle, A., Benitez, J., Perez, J.I.A., Menéndez, P., Bolla, M.K., Easton, D.F., Schmidt, M.K., Pharoah, P.D., Sherman, M.E., García-Closas, M
Corrigendum to “Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer” [Eur Urol 2023;83:313–17] (European Urology (2023) 83(4) (313–317), (S0302283822025386), (10.1016/j.eururo.2022.07.023))
No full textThe authors regret that the following statement regarding author contributions was missed: Kristan van der Vos is currently a Scientific Editor for Cell Reports Medicine, which is published by Elsevier. Dr van der Vos was not involved in the peer-review process or editorial discussions about this manuscript. The authors would like to apologise for any inconvenience caused.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Pattern Recognition and Bioinformatic
Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer
No full textCisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. Patient summary: It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public. Corrigendum to “Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer” [Eur Urol 2023;83:313–17] (European Urology (2023) 83(4) (313–317), (S0302283822025386), (10.1016/j.eururo.2022.07.023)) The authors regret that the following statement regarding author contributions was missed: Kristan van der Vos is currently a Scientific Editor for Cell Reports Medicine, which is published by Elsevier. Dr van der Vos was not involved in the peer-review process or editorial discussions about this manuscript. The authors would like to apologise for any inconvenience caused.Pattern Recognition and Bioinformatic
Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features
No full textPURPOSE: Patients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, regardless of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth in the mammary gland. However, in women, the molecular mechanisms that underlie this poor prognosis of patients with PP-BCPW remain vastly underexplored, due to of lack of adequate patient numbers and outcome data. EXPERIMENTAL DESIGN: We explored whether distinct prognostic features, common to all breast cancer molecular subtypes, exist in postpartum tumor tissue. Using detailed breastfeeding data, we delineated the postweaning period in PP-BC as a surrogate for mammary gland involution and performed whole transcriptome sequencing, immunohistochemical, and (multiplex) immunofluorescent analyses on tumor tissue of patients with PP-BCPW, PP-BCDL, Pr-BC, and NP-BC. RESULTS: We found that patients with PP-BCPW having a low expression level of an immunoglobulin gene signature, but high infiltration of plasma B cells, have an increased risk for metastasis and death. Although PP-BCPW tumor tissue was also characterized by an increase in CD8+ cytotoxic T cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups. CONCLUSIONS: These data point to the importance of plasma B cells in the postweaning mammary tumor microenvironment regarding the poor prognosis of PP-BCPW patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young patients with breast cancer.Pattern Recognition and Bioinformatic
From multiculturalism to civic integration: citizenship education and integration policies in the Netherlands and England since the 2000s
No full textThe paper discusses one of the most compelling policy issues facing liberal democracies in Europe: what policy tools can be used to promote social cohesion in a pluralist multi-ethnic society with different moral and religious and ethical values, and cultural and linguistic traditions? We focus on the role that citizenship education has taken since the early 2000s in light of the integration of immigrant children in schools in the Netherlands and England. Citizenship education is designed to integrate immigrant groups socially, foster their loyalty to the state, and encourage them to become engaged in democratic politics. Our empirical analysis advances our understanding of the policy ramifications of a new turn in integration policies directed towards stronger civic integration through sharing common values and moral standards
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
No full textauthor correctio
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