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Corrigendum to "Integrating a randomized controlled trial with a parallel observational cohort study in cervical spine surgery insights from the foraminotomy ACDF cost-effectiveness trial (FACET)" [Spine J 25 (2025) 2014-2025]
No full textThe authors regret that the details of the FACET Investigator group were missing from the author listing and the collaborator group should have been listed in the acknowledgement section of the article.</p
Theoretical and phenomenological aspects of inflationary cosmology
No full textIn this thesis, we explore several alternative descriptions of the earliest stages in the history of our universe. The goal is to investigate different methodologies and theoretical frameworks that can account for this epoch, as the simplest models proposed in the late twentieth century are now in tension with recent observations. Our results indicate that this period is remarkably flexible: it can be accurately described using diverse mechanisms and ingredients, highlighting the need for new observational data to further constrain its nature
Reconciling epistemic and identity diversity:Identifying pathways to better decision-making in social groups
No full textDiverse groups encompass a wide range of insights and perspectives, which can enhance the quality of the decisions they make together. Yet, differencesin social, cultural, or professional backgrounds can also give rise to friction and misunderstanding, making it difficult for groups to realize their potential. This dissertation examines how groups can mitigate the challenges associated with diversity while harnessing the benefits it affords
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
Yoga van Spinoza:Kracht uitoefenen en het Oneindige ervaren
No full textVandaag de dag heeft de mens ongekende macht (wetenschappelijk, technologisch, militair en politiek) tot zijn beschikking, waar de hele planeet grondig voor getransformeerd moest worden. Toch wordt de mensheid op het hoogtepunt van deze macht geconfronteerd met uitdagingen waar ze volkomen machteloos tegenover lijkt te staan, van scheve sociaaleconomische verhoudingen tot klimaatrampen. De filosofie van Baruch Spinoza (1631-1677) kan een nieuw perspectief bieden om de kern van deze paradox te begrijpen en tot een mogelijke oplossing te komen. Spinoza geeft aan hoe effectieve versterking moet resulteren in een verbetering van het soort kennis waartoe we toegang hebben; en hoe, in het proces van versterking, op natuurlijke wijze een onbeperkte en onuitputtelijke bron van vitale energie ontdekt wordt, met name in de kennis van hoe elk individueel wezen deel en uitdrukking van het geheel is.Om deze beweringen echter op waarde te kunnen schatten en ernaar te kunnen handelen is het nodig Spinoza niet alleen te lezen als een theoreticus of metafysicus uit een ver verleden, maar als een beoefenaar van die contemplatieve disciplines die in India al duizenden jaren ‘yoga’ worden genoemd. Net zoals de meeste Indiase scholen benadert Spinoza’s yoga het gewone leven kritisch, maar in tegenstelling tot deze scholen wordt de oplossing niet gezocht in het uitbannen van het menselijk verlangen, maar in de diepere en intensere bekrachtiging ervan.Op deze wijze is Spinoza’s yoga geen onleesbare formule, maar een duidelijk recept dat de manier waarop we de wereld bewonen kan transformeren. Tegelijkertijd stelt Spinoza’s yoga ons in staat thema’s en praktijken uit Indiase yogatradities te heroverwegen en te problematiseren, waardoor we met een frisse blik naar hun waarde en toepasbaarheid kunnen kijken
Inter-species variability in 4,4'-methylenedianiline metabolism:Insights from human and rat precision-cut liverslices
No full textOccupational exposure to 4,4'-methylenedianiline (MDA), a precursor in polyurethane foam production, has been linked to liver disease and cancer. Most evidence, however, comes from underpowered epidemiological studies, while empirical data are mainly from animal models, which point toward liver metabolism generating reactive metabolites. We thus used precision-cut liver slices (PCLS) from human and rat donors which we exposed to MDA at 10 and 100 μM for 24 h, and supernatants were analyzed by liquid chromatography-'SWATH' mass spectrometry. The major metabolite detected in hPCLS and rPCLS was MDA's known N-acetyl derivative, comprising approximately 80-90 % of metabolites at 10 μM and 50-60 % at 100 μM. Other metabolites were phase II conjugates, including putative N-formylation and urea-glutamine and urea-ethanolamine adducts. The latter accounted for ∼10 % of metabolites at 10 μM, increasing to 50 % at 100 μM in rPCLS but only reaching ∼25 % in hPCLS. Cell viability remained at 100 % across all human conditions and in rPCLS at 10 μM, but it dropped below 5 % at 100 μM. In conclusion, this study confirmed MDA's well-known N-acetyl metabolite across both species, while also unveiling rather unusual, previously unreported conjugates. Additionally, distinct interspecies differences were observed, underscoring the need for human-based studies.</p
Metabolic brain connectivity analysis of a depressive-like phenotype in rats:a graph theory PET study
No full textThis study aimed to investigate whether there are metabolic connectivity alterations in the brain of rats with a depressive-like phenotype, using positron emission tomography (PET) and graph theory methods. Male Wistar rats were exposed to 5 days of repeated social defeat (RSD) to induce a depressive-like phenotype, and brain connectivity was assessed with [ 18F]FDG-PET. Sucrose preference tests were conducted to assess anhedonia-like behaviour, a symptom of depression. The results showed that anhedonia-like behaviour was present one day after RSD and recovered after seven days. The analysis of large-scale brain networks revealed a reduction in connectivity in the default mode network of RSD-exposed animals one day after RSD, suggesting a link between reduced connectivity and the presence of anhedonia-like behaviour. Seven days after RSD, an increase in connectivity was observed in the salience network, which coincided with the recovery of sucrose preference. Modular analysis revealed different configurations of brain regions at one and seven days after RSD, with asymmetrical segregation of left and right hemisphere structures. These findings suggest that changes in brain connectivity may play a role in the development and recovery of anhedonia-like behaviour in rats exposed to RSD and may have implications for understanding depressive phenotypes. </p
