Academic Bibliography
https://biblio.ugent.be/
Ghent University Academic Bibliography2000-01-01T00:00+00:001dailyDual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids
https://biblio.ugent.be/publication/01HRVW2DB5YSZ07TWCHFHEY21E
Lasolle, Helene Schiavo, Andrea Tourneur, Adrien Gillotay, Pierre de Faria da Fonseca, Barbara Ceolin, Lucieli Monestier, Olivier Aganahi, Benilda Chomette, Laura Kizys, Marina Malta LetroHaenebalcke, LievenPieters, TimGoossens, Steven Haigh, Jody Detours, Vincent Maia, Ana Luiza Silva Costagliola, Sabine Romitti, Mirian2024Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a Braf(V637E)-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine Braf(V637E) mutation, equivalent to Braf(V600E) in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. Braf(V637E)-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed Braf(V637E) oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.application/pdfhttps://biblio.ugent.be/publication/01HRVW2DB5YSZ07TWCHFHEY21Ehttp://hdl.handle.net/1854/LU-01HRVW2DB5YSZ07TWCHFHEY21Ehttp://doi.org/10.1038/s41388-023-02889-yhttps://biblio.ugent.be/publication/01HRVW2DB5YSZ07TWCHFHEY21E/file/01HT2V44Q5GT3YYCVNH6ECA8AGengCreative Commons Attribution 4.0 International Public License (CC-BY 4.0)info:eu-repo/semantics/openAccessONCOGENEISSN: 0950-9232ISSN: 1476-5594Medicine and Health SciencesBiology and Life SciencesDual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoidsjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionThe impact of polypharmacy on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
https://biblio.ugent.be/publication/01H46005NZ01ADG706MVYCWBMR
Grymonprez, MaximPetrovic, MirkoDe Backer, TineSteurbaut, StephaneLahousse, Lies2024Background: Polypharmacy may affect outcomes in patients with atrial fibrillation (AF) using non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) due to interactions or reduced adherence, but comparative data are lacking. Therefore, the impact of polypharmacy on AF-related outcomes and benefit-risk profiles of NOACs in patients with polypharmacy were investigated.
Methods: AF patients initiating anticoagulation between 2013-2019 were included using Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate outcomes.
Results: Among 254,478 AF patients, 167,847 (66.0%) used ≥5 drugs. Polypharmacy was associated with higher stroke or systemic embolism (stroke/SE) (adjusted hazard ratio (aHR) 1.08, 95% confidence interval (CI) (1.02-1.15)), all-cause mortality (aHR 1.45, 95%CI (1.40-1.50)) and major bleeding risks (aHR 1.29, 95%CI (1.23-1.35)). Among patients with polypharmacy, NOACs were associated with lower stroke/SE (aHR 0.68, 95%CI (0.63-0.73)), all-cause mortality (aHR 0.80, 95%CI (0.77-0.84)), major bleeding (aHR 0.92, 95%CI (0.87-0.97)) and intracranial bleeding risks (aHR 0.77, 95%CI (0.69-0.85)), but higher gastrointestinal bleeding risks (aHR 1.10, 95%CI (1.01-1.19)) compared to VKAs. Major bleeding risks were lower with apixaban (aHR 0.79, 95%CI (0.74-0.85)), but non-significantly different with other NOACs compared to VKAs. Lower major bleedings risks were observed with dabigatran (aHR 0.91, 95%CI (0.85-0.97)) and apixaban (aHR 0.77, 95%CI (0.73-0.81)) compared to rivaroxaban, and with apixaban compared to dabigatran (HR 0.83, 95%CI (0.77-0.90)) and edoxaban (HR 0.77, 95%CI (0.70-0.85)).
Conclusion: Polypharmacy was associated with increased thromboembolic, bleeding and mortality risks in AF patients. NOACs had better benefit-risk profiles than VKAs in patients with polypharmacy.application/pdfhttps://biblio.ugent.be/publication/01H46005NZ01ADG706MVYCWBMRhttp://hdl.handle.net/1854/LU-01H46005NZ01ADG706MVYCWBMRhttp://doi.org/10.1055/s-0043-1769735https://biblio.ugent.be/publication/01H46005NZ01ADG706MVYCWBMR/file/01H46056R18Y84TZ0A6HPF9FF5engGeorg Thieme Verlag KGCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND 4.0)info:eu-repo/semantics/openAccessTHROMBOSIS AND HAEMOSTASISISSN: 0340-6245ISSN: 2567-689XMedicine and Health SciencesBiology and Life Sciencesatrial fibrillationpolyphramacyNOACthromboembolismhaemorrhageThe impact of polypharmacy on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillationjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity
https://biblio.ugent.be/publication/8728696
Hoste, EstherLecomte, KimAnnusver, KarlVandamme, NielsRoels, JanaMaschalidi, SophiaVerboom, LienVikkula, Hanna-KaisaSze, MozesVan Hove, LisetteVerstaen, KevinMartens, ArneHochepied, TinoSaeys, YvanRavichandran, KodiKasper, Mariavan Loo, Geert2021OTULIN is a deubiquitinase for linear ubiquitin chains. Here the authors show, using genetic mouse models and single-cell RNA-sequencing, that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma via the induction of keratinocyte death, thereby implicating a function of OTULIN in keratinocyte homeostasis. OTULIN is a deubiquitinase that specifically cleaves linear ubiquitin chains. Here we demonstrate that the ablation of Otulin selectively in keratinocytes causes inflammatory skin lesions that develop into verrucous carcinomas. Genetic deletion of Tnfr1, knockin expression of kinase-inactive Ripk1 or keratinocyte-specific deletion of Fadd and Mlkl completely rescues mice with OTULIN deficiency from dermatitis and tumorigenesis, thereby identifying keratinocyte cell death as the driving force for inflammation. Single-cell RNA-sequencing comparing non-lesional and lesional skin reveals changes in epidermal stem cell identity in OTULIN-deficient keratinocytes prior to substantial immune cell infiltration. Keratinocytes lacking OTULIN display a type-1 interferon and IL-1 beta response signature, and genetic or pharmacologic inhibition of these cytokines partially inhibits skin inflammation. Finally, expression of a hypomorphic mutant Otulin allele, previously shown to cause OTULIN-related autoinflammatory syndrome in humans, induces a similar inflammatory phenotype, thus supporting the importance of OTULIN for restraining skin inflammation and maintaining immune homeostasis.application/pdfhttps://biblio.ugent.be/publication/8728696http://hdl.handle.net/1854/LU-8728696http://doi.org/10.1038/s41467-021-25944-2https://biblio.ugent.be/publication/8728696/file/8728697engCreative Commons Attribution 4.0 International Public License (CC-BY 4.0)info:eu-repo/semantics/openAccessNATURE COMMUNICATIONSISSN: 2041-1723Biology and Life SciencesMedicine and Health SciencesNF-KAPPA-BLINEAR UBIQUITININFLAMMATIONRECEPTORSHARPINMICENECROPTOSISIL-1DEFICIENTMUTATIONSOTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identityjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion3D visualization of cyanobacterial biofilms using micro-computed tomography with contrast-enhancing staining agents
https://biblio.ugent.be/publication/01HMZW7JE8BHC58AS41JNZK3PY
Schröer, LaurenzBalcaen, TimFolens, KarelBoon, NicoDe Kock, TimKerckhofs, GreetCnudde, Veerle2024Currently, biofilms colonizing surfaces are mainly imaged in 2D by conventional techniques, such as optical or scanning electron microscopy. Confocal laser scanning microscopy or optical coherence tomography can visualize biofilms in 3D, but they suffer from a limited penetration depth and cannot visualize biofilms in opaque materials. Micro-computed tomography (µCT) can overcome these issues, but µCT cannot easily distinguish biofilm structures from water due to a lack of contrast difference. Within this research, five contrast-enhancing staining agents (CESAs) were evaluated for their staining potential of cyanobacterial biofilms, aiming to visualize these biofilms in 3D. Isotonic Lugol and 1:2 hafnium(IV)-substituted Wells-Dawson polyoxometalate (Hf-WD 1:2 POM) were the most promising, as they allowed visualization of the biofilms and revealed structures in the stained biofilms. Staining with isotonic Lugol could clearly visualize bundles of filaments within the biofilm, while Hf-WD 1:2 POM revealed a smooth biofilm. It is assumed that both CESAs have a different affinity towards the biofilms and could thus be used complementary. Monolacunary Wells-Dawson polyoxometalate (Mono-WD POM) showed moderate discrimination while staining with cationic iodinated CA4+ and Hexabrix® (Guerbet) containing anionic ioxaglate did not allow to distinctly visualize the biofilms. These results indicate that µCT, together with CESAs such as isotonic Lugol and Hf-WD 1:2 POM, can be used as a tool to image extensive biofilms or microbial mats in 3D. Further research will determine whether these CESAs are suitable for visualizing biofilms within opaque porous media.application/pdfhttps://biblio.ugent.be/publication/01HMZW7JE8BHC58AS41JNZK3PYhttp://hdl.handle.net/1854/LU-01HMZW7JE8BHC58AS41JNZK3PYhttp://doi.org/10.1016/j.tmater.2024.100024https://biblio.ugent.be/publication/01HMZW7JE8BHC58AS41JNZK3PY/file/01HMZWR16W7M74PPHVC3DC6HHWengCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND 4.0)info:eu-repo/semantics/openAccessTOMOGRAPHY OF MATERIALS AND STRUCTURESISSN: 2949-673XBiology and Life SciencesContrast agentsµCTContrast-enhanced computed tomographyMicrobial matsIsotonic LugolHf-WD 1:2 POM3D visualization of cyanobacterial biofilms using micro-computed tomography with contrast-enhancing staining agentsjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionDrivers behind co-occurrence patterns between pathogenic bacteria, protozoa, and helminths in populations of the multimammate mouse, Mastomys natalensis
https://biblio.ugent.be/publication/01HMZVCNTAB9KCHDR54TRE27NZ
Vanden Broecke, Bram Tafompa, Pamela Jones June Mwamundela, Baraka Edson Bernaerts, Lisse Ribas, Alexis Mnyone, Ladslaus L. Leirs, Herwig Marien, Joachim2023Advances in experimental and theoretical work increasingly suggest that parasite interactions within a single host can affect the spread and severity of wildlife diseases. Yet empirical data to support predicted co-infection patterns are limited due to the practical challenges of gathering convincing data from animal populations and the stochastic nature of parasite transmission. Here, we investigated co-infection patterns between micro-(bacteria and protozoa) and macroparasites (gastro-intestinal helminths) in natural populations of the multimammate mouse (Mastomys natalensis). Fieldwork was performed in Morogoro (Tanzania), where we trapped 211 M. natalensis and tested their behaviour using a modified open-field arena. All animals were checked for the presence of helminths in their gastro-intestinal tract, three bacteria (Anaplasma, Bartonella, and Borrelia) and two protozoan genera (Babesia and Hepatozoon). Besides the presence of eight different helminth genera (reported earlier), we found that 19% of M. natalensis were positive for Anaplasma, 10% for Bartonella, and 2% for Hep-atozoon species. Hierarchical modelling of species communities was used to investigate the effect of the different host-related factors on these parasites' infection probability and community structure. Our results show that the infection probability of Bartonella increased with the host's age, while the infection probability of Anaplasma peaked when individuals reached adulthood. We also observed that less explorative and stress-sensitive in-dividuals had a higher infection probability with Bartonella. Finally, we found limited support for within-host interactions between micro-and macroparasites, as most co-infection patterns could be attributed to host exposure time.application/pdfhttps://biblio.ugent.be/publication/01HMZVCNTAB9KCHDR54TRE27NZhttp://hdl.handle.net/1854/LU-01HMZVCNTAB9KCHDR54TRE27NZhttp://doi.org/10.1016/j.actatropica.2023.106939https://biblio.ugent.be/publication/01HMZVCNTAB9KCHDR54TRE27NZ/file/01HT2A1WERASNJRRRYP1T1XC90engNo license (in copyright)info:eu-repo/semantics/restrictedAccessACTA TROPICAISSN: 0001-706XISSN: 1873-6254Biology and Life SciencesLASSA FEVERBARTONELLA INFECTIONMALARIA PARASITESRODENTSPERSONALITYECOLOGYRISKCOINFECTIONCOMMUNITIESMURIDAEMastomysnatalensis1Bartonella2Anaplasma3Hepatozoon4Animalpersonality5Co-infection6TanzaniaDrivers behind co-occurrence patterns between pathogenic bacteria, protozoa, and helminths in populations of the multimammate mouse, Mastomys natalensisjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion