742875 research outputs found
Sort by
Insights into the diversity of the endophytic community in potatoes and factors affecting this diversity
No full textPlant-microbiome interactions have become a critical focus in sustainable agricultural management due to their significant impact on plant health and growth. The role of the plant microbiome in promoting plant vitality is well established. Using results from controlled greenhouse experiments, this thesis investigates the influence of environmental and host-related factors on the diversity of endophytes. Our study provides new insights for breeders seeking to incorporate microbiome-related traits into breeding programmes. This thesis starts by highlighting the concept of holobiont and emphasises the importance of plant-microbe interactions in Chapter 1. Chapter 2 provides a concise review of the strategies that have recently been employed to fully leverage the plant-microbiome interaction in agricultural practices. To delve deeper into the effect of biotic and abiotic conditions on the plant endophytic diversity, Chapter 3 highlights the significant role of soil in determining the composition of bacterial and fungal endophytes. This chapter further emphasises the stronger role of cultivars in shaping the fungal endophytes in potatoes.Chapter 4 of this thesis offers a deeper insight into plant microbiome interaction by studying the recruitment of endophytes from the rhizosphere. Source tracking analysis using FEAST package explains the discrepancies in the recruitment pattern of bacterial and fungal communities. Chapter 5 reveals that the soil microbiome inoculation effect is not limited to the rhizosphere but extends up to the endophytic compartment of the plant. Chapter 6 emphasises the importance of considering the local soil microbiome before applying microbiome-based strategies
Genomic Instability and the Tumor Microenvironment in Breast Cancer
No full textThe efficacy of immunotherapy in breast cancer is largely dictated by the state of the tumor immune microenvironment (TIME). This thesis explores three key determinants: the cGAS-STING pathway activated by genomic instability, a histopathology feature, known as mature tertiary lymphoid structures (TLS), and the TME difference in metastatic breast cancer patients. Our findings reveal that the cGAS-STING pathway is highly active in triple-negative breast cancer, where its activation is positively associated with Cyclin E1-driven genomic instability. This pathway also correlates with increased immune infiltration and improved response to immune checkpoint inhibitors. Mechanistically, Cyclin E1 overexpression was demonstrated to induce micronuclei formation and activation of innate immune signaling. Furthermore, the presence of mature TLS was identified as an independent prognostic factor for improved survival and a robust predictor of favorable immunotherapy response. Ultimately, spatial transcriptomic analysis revealed differences in the TIME between paired primary tumor and distant metastases in breast cancer patients, while the epithelial tumor cell compartment remained consistent. In conclusion, this work investigates the clinical relevance of the cGAS-STING pathway and its association with Cyclin E1, while also elucidating the clinical significance of mature TLS and TME difference in metastatic breast cancer patients. These findings provide a strong background to guide future breast cancer treatment strategies
Spectroscopic identification of bacterial source molecules yielding ROS-generating nitrogen-species in bacteria-derived carbon quantum dots with anti-biofilm properties
No full textBacteria-derived carbon-quantum-dots (CQDs) have been proposed for different applications, amongst which biofilm control. Anti-biofilm activities of bacteria-derived CQDs result from generation of reactive-oxygen-species (ROS), but the key-chemical pathways of carbonization of bacterial components and ROS-generation by bacteria-derived CQDs are unknown. Formation of low-yield, bacteria-derived CQDs (diameter 2–3 nm) upon hydrothermal-carbonization was confirmed using UV–vis absorption and fluorescence-emission spectroscopy. Amide-bands characteristic in FTIR spectra of source-bacteria remained visible in bacteria-derived CQDs. XPS indicated an N1s photo-electron binding energy peak at 399.5 eV in source-bacteria due to amines that were converted upon carbonization into pyrrolic (400.5 eV) and graphitic (401.8 eV) nitrogen in bacteria-derived CQDs. A C1s peak at 288.4 eV in source-bacteria due to carboxyl-groups related with the occurrence of amines in bacteria, but disappeared upon carbonization. Relations between the occurrence of amine nitrogen in source-bacteria with pyrrolic and graphitic nitrogen in bacteria-derived CQDs confirm that bacterial proteins are converted into pyrrolic and graphitic nitrogen-species upon hydrothermal carbonization. Relations between ROS-generation with the occurrence of pyrrolic and graphitic nitrogen-species identified these nitrogen-species in bacteria-derived CQDs as being responsible for enhanced ROS-generation and accompanying anti-biofilm activity. These findings enable selection of source-bacteria for preparing bacteria-derived CQDs with optimized ROS-generation and anti-biofilm activity.</p
Wealth inequality and economic growth:Evidence from the World Inequality Database
No full textAlthough it is often argued that wealth inequality matters more for economic growth than income inequality, this relationship has rarely been studied empirically, with a few exceptions covering a very restricted country sample or short timeframe. Leveraging hitherto unexploited wealth inequality data from the World Inequality Database, covering a panel of 165 countries between 1995 and 2019, we document a negative and statistically significant relationship between wealth inequality and economic growth. A one standard deviation increase in the wealth Gini coefficient within countries is associated with a 0.34 percentage points decline in growth rates. Instrumental variables support a causal interpretation of the results. The results survive a large battery of robustness checks, and we find no evidence to suggest a heterogeneous relationship.</p
Entrepreneurial, precarious or leaving altogether? Work trajectories in the creative industries in the Netherlands
No full textThis article seeks to identify variety in work trajectories in the cultural and creative industries (CCI) and the extent to which structural inequalities can be observed in who ends up in which trajectory. The omnipresent inequalities in the sector suggest that some might be in a better position to escape precarious trajectories than others. Multichannel sequence analysis is used to map the work trajectories of employees, employers and self-employed workers in the CCI in the Netherlands over 10 years. The results show that more than half of them leave the sector during the observation window. Contrary to what is often assumed, characteristics of traditional careers can be observed alongside flexible ones. Work trajectories characterised by flexible labour market positions are also the most precarious in terms of income, but make it more likely that workers stay. However, staying in the sector is less achievable for marginalised groups.</p
Experiencing difficulty in internships as a catalyst for improvement in pre-service teachers’ reflective writing skills
No full textInternships are perceived by pre-service teachers as significant activities in their training and, for some, as a test of endurance, given the difficult realities of the field. To support trainees in improving practical performance, internships often involve writing reflective texts, such as a self-evaluation report. In this study, the authors investigated the links between trainees’ performance and their writing of a report concerning that performance. They analysed 100 reports written by 20 pre-service primary school teachers. They used a mixed-methods approach to examine changes in the text itself and in the quality of their reflexivity over three years of training, for each practical performance-related profile. Their study suggests that practical performance influences the quality of reflective writing in the self-evaluation report. Results revealed that students improve their writing when they experience stronger internship difficulties, which require them to provide justifications, evaluate effects of their practice, and highlight strengths to build on.</p
Total joint arthroplasty versus trapeziectomy for trapeziometacarpal joint arthritis:5-year follow-up of a randomized controlled trial
No full textThis study presents 5-year results of a randomized controlled trial comparing total joint arthroplasty (TJA) with the Maïa prosthesis and trapeziectomy for trapeziometacarpal joint osteoarthritis. Sixty-two women aged 40 and older scheduled for surgery were randomized. The primary outcome was daily hand function using the Michigan Hand Outcomes Questionnaire (MHOQ). Secondary outcomes included MHOQ subscales, range of motion, strength, satisfaction, complications and survival. Follow-up data were available for 28 TJA and 26 trapeziectomy patients. At 5-years, TJA did not show superior patient reported outcomes on the MHOQ compared with trapeziectomy. Grip and tip pinch strength differences were not statistically significant or clinically relevant. However, key pinch strength, satisfaction and willingness to undergo the same treatment again favoured TJA. There was no statistically significant difference in revision rates between the groups. Five-year survival was 73% for trapeziectomy and 93% for TJA. Level of evidence: I. </p
Comparability of external and internal control patients for the prospective randomized HOVON-103 trial in older AML patients
No full textReal-world data (RWD) previously contributed to post-marketing regulatory decision-making, but are currently also considered as external controls to single-arm trials. The use of RWD control data may be compromised by methodological issues, urging validation of RWD control cohorts. Two external control cohorts of newly diagnosed acute myeloid leukaemia patients, one registered by the HARMONY Alliance (HA) and one by the Netherlands Cancer Registry (NCR), were compared to the control arm of the randomized HOVON-103 trial (H103 controls). All patients, aged >65 years with a WHO performance score of 0–2 (or missing), received standard induction chemotherapy. 1:1 propensity score calliper matching (PSM) was applied to improve comparability, and overall (OS) and relapse-free survival (RFS) were assessed. Fewer data elements were available in external cohorts compared to H103 controls, specifically in the NCR cohort. Baseline characteristics of the external cohorts differed from H103 controls; missing data were also more frequent and predominantly concerned WHO performance score. After PSM, HA patients demonstrated non-significantly different OS and RFS to H103 controls at 2 years (26 ± 4% vs. 31 ± 5%, p = 0.59; 24 ± 5% vs. 30 ± 6%, p = 0.52), while NCR patients had 12% lower OS (28 ± 4% vs. 40 ± 4%, p = 0.21). Validation of external control cohorts is needed before incorporating RWD control data into comparative analyses, as missing data, specifically comorbidities, and residual confounding may limit comparability.</p
Use of p53 immunohistochemistry can improve diagnostic agreement for differentiated vulvar intraepithelial neoplasia (dVIN):an international reproducibility study
No full textAims: Differentiated or HPV-independent vulvar intraepithelial neoplasia (dVIN) can progress rapidly to invasive cancer and accurate pathological diagnosis is essential to facilitate appropriate interventions. Histological similarities of dVIN with non-neoplastic lesions, however, often make the diagnosis less reproducible. We investigated among a diverse group of pathologists whether the diagnostic agreement improves with the use of p53 immunohistochemistry (IHC) interpreted using the pattern-based schema.Methods and results: Fifty haematoxylin–eosin (HE) stained archival slides (30 dVIN and 20 non-dysplastic vulvar lesions) were selected and p53-IHC was performed. Twenty-four board-certified pathologists from eight countries first assessed the HE slides alone, and after a washout period, re-evaluated them alongside the p53-IHC slides. During both rounds, slides were diagnosed as dVIN, favour dVIN, favour no-VIN or no-VIN. p53-IHC was scored as wild-type or mutant (diffuse, basal, cytoplasmic or null). Kappa (κ) statistics and McNemar's test were used for statistical analyses. Overall diagnostic agreement for dVIN saw a significant increase in the Kappa value (κ = 0.6 vs. κ = 0.4, P = 0.002) when HE and p53-IHC slides were assessed together compared with histology assessment alone, although the level of agreement remained moderate. For p53-IHC assessment, overall agreement was substantial (κ = 0.7). Diagnoses changing from no-VIN/favour no-VIN to dVIN correlated significantly with the identification of a p53-mutant pattern (P < 0.001).Conclusions: Our findings indicate that p53-IHC is a robust ancillary tool that can be reproducibly interpreted by pathologists with varying experience levels and supports the routine use of p53-IHC in cases where dVIN is considered in the differential diagnosis.</p
