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Article: Les Journées francophones de virologie s’exportent à l’international et visitent Bruxelles.

Op de Beeck, Anne / Decroly, Etienne

2024 Volume 28, Issue 2, Page(s) 59–60

Title translation	The Journées francophones de virologie go international with a visit to Brussels.
Language	French
Publishing date	2024-04-01
Publishing country	France
Document type	Journal Article
ZDB-ID	2118387-9
ISSN	1950-6961 ; 1267-8694
ISSN (online)	1950-6961
ISSN	1267-8694
DOI	10.1684/vir.2024.1042
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Article ; Online: CRISPR/Cas9-edited ROS1 + non-small cell lung cancer cell lines highlight differential drug sensitivity in 2D vs 3D cultures while reflecting established resistance profiles.

Terrones, Marc / Deben, Christophe / Rodrigues-Fortes, Felicia / Schepers, Anne / de Beeck, Ken Op / Van Camp, Guy / Vandeweyer, Geert

Journal of translational medicine

2024 Volume 22, Issue 1, Page(s) 234

Abstract: Introduction: The study of resistance-causing mutations in oncogene-driven tumors is fundamental to guide clinical decisions. Several point mutations affecting the ROS1 kinase domain have been identified in the clinical setting, but their impact ... ...

Abstract	Introduction: The study of resistance-causing mutations in oncogene-driven tumors is fundamental to guide clinical decisions. Several point mutations affecting the ROS1 kinase domain have been identified in the clinical setting, but their impact requires further exploration, particularly in improved pre-clinical models. Given the scarcity of solid pre-clinical models to approach rare cancer subtypes like ROS1 + NSCLC, CRISPR/Cas9 technology allows the introduction of mutations in patient-derived cell lines for which resistant variants are difficult to obtain due to the low prevalence of cases within the clinical setting. Methods: In the SLC34A2-ROS1 rearranged NSCLC cell line HCC78, we knocked-in through CRISPR/Cas9 technology three ROS1 drug resistance-causing mutations: G2032R, L2026M and S1986Y. Such variants are located in different functional regions of the ROS1 kinase domain, thus conferring TKI resistance through distinct mechanisms. We then performed pharmacological assays in 2D and 3D to assess the cellular response of the mutant lines to crizotinib, entrectinib, lorlatinib, repotrectinib and ceritinib. In addition, immunoblotting assays were performed in 2D-treated cell lines to determine ROS1 phosphorylation and MAP kinase pathway activity. The area over the curve (AOC) defined by the normalized growth rate (NGR_fit) dose-response curves was the variable used to quantify the cellular response towards TKIs. Results: Spheroids derived from ROS1 Conclusion: In this study we knock-in for the first time in a ROS1 + patient-derived cell line, three different known resistance-causing mutations using CRISPR/Cas9 in the endogenous translocated ROS1 alleles. Pharmacological assays performed in 2D and 3D cell culture revealed that spheroids are more sensitive to TKIs than cells cultured as a monolayer. This direct comparison between two culture systems could be done thanks to the implementation of normalized growth rates (NGR) to uniformly quantify drug response between 2D and 3D cell culture. Overall, this study presents the added value of using spheroids and positions lorlatinib and repotrectinib as the most effective TKIs against the studied ROS1 resistance point mutations.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung ; Protein-Tyrosine Kinases/genetics ; Crizotinib ; CRISPR-Cas Systems/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Proto-Oncogene Proteins ; Drug Resistance ; Pyrazoles ; Sulfones ; Benzamides ; Aminopyridines ; Indazoles ; Lactams ; Pyrimidines
Chemical Substances	entrectinib (L5ORF0AN1I) ; lorlatinib (OSP71S83EU) ; ceritinib (K418KG2GET) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Crizotinib (53AH36668S) ; Proto-Oncogene Proteins ; ROS1 protein, human (EC 2.7.10.1) ; Pyrazoles ; Sulfones ; Benzamides ; Aminopyridines ; Indazoles ; Lactams ; Pyrimidines
Language	English
Publishing date	2024-03-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-024-04988-0
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Article ; Online: Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs.

Janssens, Katleen / Neefs, Isabelle / Ibrahim, Joe / Schepers, Anne / Pauwels, Patrick / Peeters, Marc / Van Camp, Guy / Op de Beeck, Ken

Clinical epigenetics

2023 Volume 15, Issue 1, Page(s) 111

Abstract: ... performed for both array types to "double evidence" differentially methylated probes (DE DMPs). Subsequently ... prediction model. Focusing on the clinically most interesting group (adenoma vs carcinoma), we identified 13 DE ... that the 13 DE DMPs identified in this study can be used as molecular biomarkers in the clinic.: Conclusions ...

Abstract	Background: Biomarker discovery in colorectal cancer has mostly focused on methylation patterns in normal and colorectal tumor tissue, but adenomas remain understudied. Therefore, we performed the first epigenome-wide study to profile methylation of all three tissue types combined and to identify discriminatory biomarkers. Results: Public methylation array data (Illumina EPIC and 450K) were collected from a total of 1 892 colorectal samples. Pairwise differential methylation analyses between tissue types were performed for both array types to "double evidence" differentially methylated probes (DE DMPs). Subsequently, the identified DMPs were filtered on methylation level and used to build a binary logistic regression prediction model. Focusing on the clinically most interesting group (adenoma vs carcinoma), we identified 13 DE DMPs that could effectively discriminate between them (AUC = 0.996). We validated this model in an in-house experimental methylation dataset of 13 adenomas and 9 carcinomas. It reached a sensitivity and specificity of 96% and 95%, respectively, with an overall accuracy of 96%. Our findings raise the possibility that the 13 DE DMPs identified in this study can be used as molecular biomarkers in the clinic. Conclusions: Our analyses show that methylation biomarkers have the potential to discriminate between normal, precursor and carcinoma tissues of the colorectum. More importantly, we highlight the power of the methylome as a source of markers for discriminating between colorectal adenomas and carcinomas, which currently remains an unmet clinical need.
MeSH term(s)	Epigenome ; DNA Methylation ; Humans ; Colorectal Neoplasms/genetics ; Adenoma/genetics ; Biomarkers, Tumor/genetics ; Genome-Wide Association Study
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-07-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-023-01516-7
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Article ; Online: Coxsackievirus and Type 1 Diabetes Mellitus: The Wolf's Footprints.

Eizirik, Decio L / Op de Beeck, Anne

Trends in endocrinology and metabolism: TEM

2018 Volume 29, Issue 3, Page(s) 137–139

Abstract: Enteroviruses are important environmental contributors to islet inflammation (insulitis) in type 1 diabetes mellitus (T1DM). A recent study characterized the proteomic alterations induced by Coxsackievirus type B (CVB) infection of human islets. This ... ...

Abstract	Enteroviruses are important environmental contributors to islet inflammation (insulitis) in type 1 diabetes mellitus (T1DM). A recent study characterized the proteomic alterations induced by Coxsackievirus type B (CVB) infection of human islets. This provides relevant information to decipher the words of the virus-induced 'dialog' between β cells and the immune system that leads to autoimmunity.
MeSH term(s)	Coxsackievirus Infections/immunology ; Diabetes Mellitus, Type 1/immunology ; Humans ; Islets of Langerhans/immunology ; Proteomics
Language	English
Publishing date	2018-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2017.12.002
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Article ; Online: Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs

Katleen Janssens / Isabelle Neefs / Joe Ibrahim / Anne Schepers / Patrick Pauwels / Marc Peeters / Guy Van Camp / Ken Op de Beeck

Clinical Epigenetics, Vol 15, Iss 1, Pp 1-

2023 Volume 14

Abstract: ... performed for both array types to “double evidence” differentially methylated probes (DE DMPs). Subsequently ... prediction model. Focusing on the clinically most interesting group (adenoma vs carcinoma), we identified 13 DE ... that the 13 DE DMPs identified in this study can be used as molecular biomarkers in the clinic. Conclusions ...

Abstract	Abstract Background Biomarker discovery in colorectal cancer has mostly focused on methylation patterns in normal and colorectal tumor tissue, but adenomas remain understudied. Therefore, we performed the first epigenome-wide study to profile methylation of all three tissue types combined and to identify discriminatory biomarkers. Results Public methylation array data (Illumina EPIC and 450K) were collected from a total of 1 892 colorectal samples. Pairwise differential methylation analyses between tissue types were performed for both array types to “double evidence” differentially methylated probes (DE DMPs). Subsequently, the identified DMPs were filtered on methylation level and used to build a binary logistic regression prediction model. Focusing on the clinically most interesting group (adenoma vs carcinoma), we identified 13 DE DMPs that could effectively discriminate between them (AUC = 0.996). We validated this model in an in-house experimental methylation dataset of 13 adenomas and 9 carcinomas. It reached a sensitivity and specificity of 96% and 95%, respectively, with an overall accuracy of 96%. Our findings raise the possibility that the 13 DE DMPs identified in this study can be used as molecular biomarkers in the clinic. Conclusions Our analyses show that methylation biomarkers have the potential to discriminate between normal, precursor and carcinoma tissues of the colorectum. More importantly, we highlight the power of the methylome as a source of markers for discriminating between colorectal adenomas and carcinomas, which currently remains an unmet clinical need.
Keywords	Colorectal cancer ; Methylation ; Biomarkers ; Adenoma ; Carcinoma ; Medicine ; R ; Genetics ; QH426-470
Subject code	310
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β cells.

Szymczak, Florian / Alvelos, Maria Inês / Marín-Cañas, Sandra / Castela, Ângela / Demine, Stéphane / Colli, Maikel Luis / Op de Beeck, Anne / Thomaidou, Sofia / Marselli, Lorella / Zaldumbide, Arnaud / Marchetti, Piero / Eizirik, Décio L

Science advances

2022 Volume 8, Issue 37, Page(s) eabn5732

Abstract: IFNα is a key regulator of the dialogue between pancreatic β cells and the immune system in early type 1 diabetes (T1D). IFNα up-regulates HLA class I expression in human β cells, fostering autoantigen presentation to the immune system. We observed by ... ...

Abstract	IFNα is a key regulator of the dialogue between pancreatic β cells and the immune system in early type 1 diabetes (T1D). IFNα up-regulates HLA class I expression in human β cells, fostering autoantigen presentation to the immune system. We observed by bulk and single-cell RNA sequencing that exposure of human induced pluripotent-derived islet-like cells to IFNα induces expression of HLA class I and of other genes involved in antigen presentation, including the transcriptional activator NLRC5. We next evaluated the global role of NLRC5 in human insulin-producing EndoC-βH1 and human islet cells by RNA sequencing and targeted gene/protein determination. NLRC5 regulates expression of HLA class I, antigen presentation-related genes, and chemokines. NLRC5 also mediates the effects of IFNα on alternative splicing, a generator of β cell neoantigens, suggesting that it is a central player of the effects of IFNα on β cells that contribute to trigger and amplify autoimmunity in T1D.
MeSH term(s)	Alternative Splicing ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/metabolism ; Humans ; Insulin-Secreting Cells ; Interferon-alpha/pharmacology ; Intracellular Signaling Peptides and Proteins/metabolism ; Islets of Langerhans/metabolism ; Transcription, Genetic
Chemical Substances	Interferon-alpha ; Intracellular Signaling Peptides and Proteins ; NLRC5 protein, human
Language	English
Publishing date	2022-09-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abn5732
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Article ; Online: Viral infections in type 1 diabetes mellitus--why the β cells?

Op de Beeck, Anne / Eizirik, Decio L

Nature reviews. Endocrinology

2016 Volume 12, Issue 5, Page(s) 263–273

Abstract: Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β ... ...

Abstract	Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection--particularly by enteroviruses (for example, coxsackievirus)--as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/pathology ; Diabetes Mellitus, Type 1/prevention & control ; Humans ; Insulin-Secreting Cells/pathology ; Virus Diseases/complications ; Virus Diseases/genetics ; Virus Diseases/pathology
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2489381-X
ISSN	1759-5037 ; 1759-5029
ISSN (online)	1759-5037
ISSN	1759-5029
DOI	10.1038/nrendo.2016.30
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Article ; Online: Interferons are key cytokines acting on pancreatic islets in type 1 diabetes.

Coomans de Brachène, Alexandra / Alvelos, Maria Ines / Szymczak, Florian / Zimath, Priscila L / Castela, Angela / Marmontel de Souza, Bianca / Roca Rivada, Arturo / Marín-Cañas, Sandra / Yi, Xiaoyan / Op de Beeck, Anne / Morgan, Noel G / Sonntag, Sebastian / Jawurek, Sayro / Title, Alexandra C / Yesildag, Burcak / Pattou, François / Kerr-Conte, Julie / Montanya, Eduard / Nacher, Montserrat /

Marselli, Lorella / Marchetti, Piero / Richardson, Sarah J / Eizirik, Decio L

Diabetologia

2024 Volume 67, Issue 5, Page(s) 908–927

Abstract: Aims/hypothesis: The proinflammatory cytokines IFN-α, IFN-γ, IL-1β and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, ...

Abstract	Aims/hypothesis: The proinflammatory cytokines IFN-α, IFN-γ, IL-1β and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, the specific role of each of these cytokines individually on pancreatic beta cells remains unknown. Methods: We used deep RNA-seq analysis, followed by extensive confirmation experiments based on reverse transcription-quantitative PCR (RT-qPCR), western blot, histology and use of siRNAs, to characterise the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by type 1 diabetes. Results: IFN-α and IFN-γ had a greater impact on the beta cell transcriptome when compared with IL-1β and TNF-α. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from individuals with type 1 diabetes, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to 'danger signals' such as viral infections. Zinc finger NFX1-type containing 1 (ZNFX1), a double-stranded RNA sensor, was identified as highly induced by IFNs and shown to play a key role in the antiviral response in beta cells. Conclusions/interpretation: These data suggest that IFN-α and IFN-γ are key cytokines at the islet level in human type 1 diabetes, contributing to the triggering and amplification of autoimmunity.
MeSH term(s)	Humans ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/metabolism ; Interferons/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Interferon-gamma/metabolism ; Islets of Langerhans/metabolism
Chemical Substances	Cytokines ; Interferons (9008-11-1) ; Tumor Necrosis Factor-alpha ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2024-02-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-024-06106-7
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Article ; Online: Coxsackievirus B Tailors the Unfolded Protein Response to Favour Viral Amplification in Pancreatic β Cells.

Colli, Maikel L / Paula, Flavia M / Marselli, Lorella / Marchetti, Piero / Roivainen, Merja / Eizirik, Decio L / Op de Beeck, Anne

Journal of innate immunity

2019 Volume 11, Issue 4, Page(s) 375–390

Abstract: Type 1 diabetes (T1D) is an autoimmune disease characterized by islet inflammation and progressive pancreatic β cell destruction. The disease is triggered by a combination of genetic and environmental factors, but the mechanisms leading to the triggering ...

Abstract	Type 1 diabetes (T1D) is an autoimmune disease characterized by islet inflammation and progressive pancreatic β cell destruction. The disease is triggered by a combination of genetic and environmental factors, but the mechanisms leading to the triggering of early innate and late adaptive immunity and consequent progressive pancreatic β cell death remain unclear. The insulin-producing β cells are active secretory cells and are thus particularly sensitive to endoplasmic reticulum (ER) stress. ER stress plays an important role in the pathologic pathway leading to autoimmunity, islet inflammation, and β cell death. We show here that group B coxsackievirus (CVB) infection, a putative causative factor for T1D, induces a partial ER stress in rat and human β cells. The activation of the PERK/ATF4/CHOP branch is blunted while the IRE1α branch leads to increased spliced XBP1 expression and c-Jun N-terminal kinase (JNK) activation. Interestingly, JNK1 activation is essential for CVB amplification in both human and rat β cells. Furthermore, a chemically induced ER stress preceding viral infection increases viral replication, in a process dependent on IRE1α activation. Our findings show that CVB tailors the unfolded protein response in β cells to support their replication, preferentially triggering the pro-viral IRE1α/XBP1s/JNK1 pathway while blocking the pro-apoptotic PERK/ATF4/CHOP pathway.
MeSH term(s)	Animals ; Cell Line ; Coxsackievirus Infections/immunology ; Coxsackievirus Infections/metabolism ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/metabolism ; Endoribonucleases/genetics ; Endoribonucleases/metabolism ; Enterovirus B, Human/physiology ; Humans ; Immune Evasion ; Insulin-Secreting Cells/immunology ; Insulin-Secreting Cells/virology ; MAP Kinase Kinase 4/metabolism ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Rats ; Signal Transduction ; Unfolded Protein Response/immunology ; Virus Replication ; X-Box Binding Protein 1/genetics ; X-Box Binding Protein 1/metabolism
Chemical Substances	Ern1 protein, rat ; Multienzyme Complexes ; X-Box Binding Protein 1 ; Xbp1 protein, rat ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; MAP Kinase Kinase 4 (EC 2.7.12.2) ; Endoribonucleases (EC 3.1.-)
Language	English
Publishing date	2019-02-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454158-8
ISSN	1662-8128 ; 1662-811X
ISSN (online)	1662-8128
ISSN	1662-811X
DOI	10.1159/000496034
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Article ; Online: Preclinical evaluation of tyrosine kinase 2 inhibitors for human beta-cell protection in type 1 diabetes.

Coomans de Brachène, Alexandra / Castela, Angela / Op de Beeck, Anne / Mirmira, Raghavendra G / Marselli, Lorella / Marchetti, Piero / Masse, Craig / Miao, Wenyan / Leit, Silvana / Evans-Molina, Carmella / Eizirik, Decio L

Diabetes, obesity & metabolism

2020 Volume 22, Issue 10, Page(s) 1827–1836

Abstract: Aim: Type 1 diabetes (T1D) is a chronic autoimmune disease leading to progressive loss of pancreatic beta cells. Interferon (IFN)-α plays a critical role in the crosstalk between pancreatic beta cells and the immune system in early insulitis. In human ... ...

Abstract	Aim: Type 1 diabetes (T1D) is a chronic autoimmune disease leading to progressive loss of pancreatic beta cells. Interferon (IFN)-α plays a critical role in the crosstalk between pancreatic beta cells and the immune system in early insulitis. In human beta cells IFNα signals through JAK1 and TYK2, leading to endoplasmic reticulum stress, inflammation and HLA class I overexpression. IFNα, acting synergistically with IL-1β, induces apoptosis. Polymorphisms in TYK2 that decrease its activity are associated with protection against T1D, and we hypothesized that pharmacological inhibitors that specifically target TYK2 could protect human beta cells against the deleterious effects of IFNα. Materials and methods: Two TYK2 inhibitors provided by Nimbus Lakshmi were tested in human insulin-producing EndoC-βH1 cells and human islets to evaluate their effect on IFNα signalling, beta-cell function and susceptibility to viral infection using RT-qPCR, western blot, immunofluorescence, ELISA and nuclear dyes. Results: The two TYK2 inhibitors tested prevented IFNα-induced human beta-cell gene expression in a dose-dependent manner. They also protected human islets against IFNα + IL-1β-induced apoptosis. Importantly, these inhibitors did not modify beta-cell function or their survival following infection with the potential diabetogenic coxsackieviruses CVB1 and CVB5. Conclusions: The two TYK2 inhibitors tested inhibit the IFNα signalling pathway in human beta cells, decreasing its pro-inflammatory and pro-apoptotic effects without sensitizing the cells to viral infection. The preclinical findings could pave the way for future clinical trials with TYK2 inhibitors for the prevention and treatment of type 1 diabetes.
MeSH term(s)	Apoptosis ; Cytoprotection ; Diabetes Mellitus, Type 1/drug therapy ; Endoplasmic Reticulum Stress ; Humans ; Insulin-Secreting Cells ; TYK2 Kinase/genetics
Chemical Substances	TYK2 Kinase (EC 2.7.10.2)
Language	English
Publishing date	2020-07-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.14104
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