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Article: Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: an in-depth genetic exploration of population samples.

Treur, Jorien L / Thijssen, Anaiïs B / Smit, Dirk Ja / Tadros, Rafik / Veeneman, Rada R / Denys, Damiaan / Vermeulen, Jentien M / Barc, Julien / Bergstedt, Jacob / Pasman, Joëlle A / Bezzina, Connie R / Verweij, Karin J H

medRxiv : the preprint server for health sciences

2023

Abstract: Background: An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. While arrhythmic disorders play an important role in this, the nature of the relation between schizophrenia and arrhythmia ... ...

Abstract	Background: An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. While arrhythmic disorders play an important role in this, the nature of the relation between schizophrenia and arrhythmia is not fully understood. Methods: We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53,386 cases 77,258 controls), arrhythmic disorders (atrial fibrillation, 55,114 cases 482,295 controls; Brugada syndrome, 2,820 cases 10,001 controls) and electrocardiogram traits (heart rate (variability), PR interval, QT interval, JT interval, and QRS duration, n=46,952-293,051). First, we examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Next, we explored bidirectional causal relations between schizophrenia and arrhythmic disorders and electrocardiogram traits using Mendelian randomization. Outcomes: There was no evidence for global genetic correlations, except between schizophrenia and Brugada (r Interpretation: While there was little evidence for global genetic correlations, specific genomic regions and biological pathways important for both schizophrenia and arrhythmic disorders and electrocardiogram traits emerged. The putative causal effect of liability to schizophrenia on Brugada warrants increased cardiac monitoring and potentially early medical intervention in patients with schizophrenia. Funding: European Research Council Starting Grant.
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.21.23290286
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Article ; Online: Impairing temozolomide resistance driven by glioma stem-like cells with adjuvant immunotherapy targeting O-acetyl GD2 ganglioside.

Fleurence, Julien / Bahri, Meriem / Fougeray, Sophie / Faraj, Sébastien / Vermeulen, Sarah / Pinault, Emilie / Geraldo, Fanny / Oliver, Lisa / Véziers, Joëlle / Marquet, Pierre / Rabé, Marion / Gratas, Catherine / Vallette, François / Pecqueur, Claire / Paris, François / Birklé, Stéphane

International journal of cancer

2019 Volume 146, Issue 2, Page(s) 424–438

Abstract: Stem cell chemoresistance remains challenging the efficacy of the front-line temozolomide against glioblastoma. Novel therapies are urgently needed to fight those cells in order to control tumor relapse. Here, we report that anti-O-acetyl-GD2 adjuvant ... ...

Abstract	Stem cell chemoresistance remains challenging the efficacy of the front-line temozolomide against glioblastoma. Novel therapies are urgently needed to fight those cells in order to control tumor relapse. Here, we report that anti-O-acetyl-GD2 adjuvant immunotherapy controls glioma stem-like cell-driven chemoresistance. Using patient-derived glioblastoma cells, we found that glioma stem-like cells overexpressed O-acetyl-GD2. As a result, monoclonal antibody 8B6 immunotherapy significantly increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. Furthermore, the combination therapy decreased the expression of the glioma stem-like cell markers CD133 and Nestin and compromised glioma stem-like cell self-renewal capabilities. When tested in vivo, adjuvant 8B6 immunotherapy prevented the extension of the temozolomide-resistant glioma stem-like cell pool within the tumor bulk in vivo and was more effective than the single agent therapies. This is the first report demonstrating that anti-O-acetyl-GD2 monoclonal antibody 8B6 targets glioblastoma in a manner that control temozolomide-resistance driven by glioma stem-like cells. Together our results offer a proof of concept for using anti-O-acetyl GD2 reagents in glioblastoma to develop more efficient combination therapies for malignant gliomas.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Adjuvants, Immunologic/therapeutic use ; Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cell Line, Tumor ; Cell Self Renewal/drug effects ; Cell Self Renewal/immunology ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/immunology ; Drug Synergism ; Gangliosides/antagonists & inhibitors ; Gangliosides/immunology ; Glioblastoma/drug therapy ; Glioblastoma/immunology ; Glioblastoma/pathology ; Humans ; Mice ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/immunology ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Xenograft Model Antitumor Assays
Chemical Substances	Adjuvants, Immunologic ; Antibodies, Monoclonal ; Gangliosides ; O-acetyl-GD2 ganglioside ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2019-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.32533
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Article: Children's virilization and the use of a testosterone gel by their fathers.

Brachet, Cécile / Vermeulen, Joëlle / Heinrichs, Claudine

European journal of pediatrics

2005 Volume 164, Issue 10, Page(s) 646–647

Abstract: We report severe virilization in three unrelated children by contact with their fathers, who had been using a testosterone lipogel. ...

Abstract	We report severe virilization in three unrelated children by contact with their fathers, who had been using a testosterone lipogel.
MeSH term(s)	Administration, Cutaneous ; Aged ; Androgens/administration & dosage ; Androgens/adverse effects ; Child Behavior ; Child, Preschool ; Fathers ; Female ; Humans ; Infant ; Male ; Puberty, Precocious/chemically induced ; Testosterone/administration & dosage ; Testosterone/adverse effects ; Testosterone/blood ; Virilism/chemically induced
Chemical Substances	Androgens ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2005-10
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	194196-3
ISSN	1432-1076 ; 0340-6199 ; 0943-9676
ISSN (online)	1432-1076
ISSN	0340-6199 ; 0943-9676
DOI	10.1007/s00431-005-1714-z
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Article ; Online: Predicting outcomes for children with neuroblastoma.

Vermeulen, Joëlle / De Preter, Katleen / Mestdagh, Pieter / Laureys, Geneviève / Speleman, Frank / Vandesompele, Jo

Discovery medicine

2010 Volume 10, Issue 50, Page(s) 29–36

Abstract: One of the main challenges in clinical cancer research remains to be accurate outcome prediction at the time of diagnosis. Although not frequent in absolute terms, neuroblastoma represents an important clinical challenge, as it is fatal in almost half of ...

Abstract	One of the main challenges in clinical cancer research remains to be accurate outcome prediction at the time of diagnosis. Although not frequent in absolute terms, neuroblastoma represents an important clinical challenge, as it is fatal in almost half of the patients despite advances in multimodal anti-cancer therapies. Four major risk stratification systems for neuroblastoma patients are currently being used in various parts of the world. Systems are based on a combination of various clinical, histopathological, and biological factors. Accordingly, different therapeutic schemes exist ranging from wait-and-see approaches to intensive multimodal therapies. Clinical experience with the currently used risk stratification systems suggests that the stratification of patients for treatment is useful, but patients with the same clinico-pathological parameters, receiving the same treatment, can have markedly different clinical courses. Therefore, the challenge remains to identify additional tumor-specific and sensitive prognostic markers for improved risk estimation at the time of diagnosis and to improve the choice of risk-related therapy. Various studies have put forward new prognostic markers, including copy number aberrations, gene expression signatures, and epigenetic markers.
MeSH term(s)	Child ; Humans ; Neuroblastoma/genetics ; Neuroblastoma/pathology ; Neuroblastoma/therapy ; Prognosis ; Risk Factors ; Treatment Outcome
Language	English
Publishing date	2010-07
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1944-7930
ISSN (online)	1944-7930
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Article ; Online: Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling.

Galan, Diogo T / Bito, Virginie / Claus, Piet / Holemans, Patricia / Abi-Char, Joëlle / Nagaraju, Chandan K / Dries, Eef / Vermeulen, Kristel / Ventura-Clapier, Renée / Sipido, Karin R / Driesen, Ronald B

American journal of physiology. Heart and circulatory physiology

2016 Volume 311, Issue 5, Page(s) H1075–H1090

Abstract: Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that ... ...

Abstract	Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MI
MeSH term(s)	AMP-Activated Protein Kinases/genetics ; Animals ; Blotting, Western ; Cardiomyopathies/diagnostic imaging ; Cardiomyopathies/etiology ; Cardiomyopathies/metabolism ; Cardiomyopathies/pathology ; Cell Respiration ; Cicatrix ; Coronary Stenosis/complications ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Electron Transport Complex IV/metabolism ; Glucose Transport Proteins, Facilitative/genetics ; Glycogen/metabolism ; Magnetic Resonance Imaging ; Microscopy, Electron ; Microscopy, Fluorescence ; Mitochondria, Heart/metabolism ; Myocardial Infarction/diagnostic imaging ; Myocardial Infarction/etiology ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardial Perfusion Imaging ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/ultrastructure ; Oxygen Consumption ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Stroke Volume ; Sus scrofa ; Swine ; Ventricular Remodeling
Chemical Substances	Glucose Transport Proteins, Facilitative ; RNA, Messenger ; Glycogen (9005-79-2) ; Electron Transport Complex II (EC 1.3.5.1) ; Electron Transport Complex IV (EC 1.9.3.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Electron Transport Complex I (EC 7.1.1.2)
Language	English
Publishing date	2016-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00945.2015
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Article ; Online: 59-gene prognostic signature sub-stratifies high-risk neuroblastoma patients.

Vermeulen, Joëlle / De Preter, Katleen / Laureys, Geneviève / Speleman, Frank / Vandesompele, Jo

The Lancet. Oncology

2009 Volume 10, Issue 11, Page(s) 1030

MeSH term(s)	Biomarkers, Tumor/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; N-Myc Proto-Oncogene Protein ; Neuroblastoma/genetics ; Neuroblastoma/mortality ; Neuroblastoma/pathology ; Neuroblastoma/therapy ; Nuclear Proteins/genetics ; Oncogene Proteins/genetics ; Predictive Value of Tests ; Risk Assessment ; Risk Factors ; Treatment Outcome
Chemical Substances	Biomarkers, Tumor ; MYCN protein, human ; N-Myc Proto-Oncogene Protein ; Nuclear Proteins ; Oncogene Proteins
Language	English
Publishing date	2009-11
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(09)70325-0
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Measurable impact of RNA quality on gene expression results from quantitative PCR.

Vermeulen, Joëlle / De Preter, Katleen / Lefever, Steve / Nuytens, Justine / De Vloed, Fanny / Derveaux, Stefaan / Hellemans, Jan / Speleman, Frank / Vandesompele, Jo

Nucleic acids research

2011 Volume 39, Issue 9, Page(s) e63

Abstract: Compromised RNA quality is suggested to lead to unreliable results in gene expression studies. Therefore, assessment of RNA integrity and purity is deemed essential prior to including samples in the analytical pipeline. This may be of particular ... ...

Abstract	Compromised RNA quality is suggested to lead to unreliable results in gene expression studies. Therefore, assessment of RNA integrity and purity is deemed essential prior to including samples in the analytical pipeline. This may be of particular importance when diagnostic, prognostic or therapeutic conclusions depend on such analyses. In this study, the comparative value of six RNA quality parameters was determined using a large panel of 740 primary tumour samples for which real-time quantitative PCR gene expression results were available. The tested parameters comprise of microfluidic capillary electrophoresis based 18S/28S rRNA ratio and RNA Quality Index value, HPRT1 5'-3' difference in quantification cycle (Cq) and HPRT1 3' Cq value based on a 5'/3' ratio mRNA integrity assay, the Cq value of expressed Alu repeat sequences and a normalization factor based on the mean expression level of four reference genes. Upon establishment of an innovative analytical framework to assess impact of RNA quality, we observed a measurable impact of RNA quality on the variation of the reference genes, on the significance of differential expression of prognostic marker genes between two cancer patient risk groups, and on risk classification performance using a multigene signature. This study forms the basis for further rational assessment of reverse transcription quantitative PCR based results in relation to RNA quality.
MeSH term(s)	Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Electrophoresis, Microchip ; Gene Expression Profiling/standards ; Humans ; RNA, Messenger/analysis ; RNA, Messenger/standards ; RNA, Neoplasm/analysis ; RNA, Neoplasm/standards ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Biomarkers, Tumor ; RNA, Messenger ; RNA, Neoplasm
Language	English
Publishing date	2011-02-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkr065
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Article ; Online: SYN-JEM: A Quantitative Job-Exposure Matrix for Five Lung Carcinogens.

Peters, Susan / Vermeulen, Roel / Portengen, Lützen / Olsson, Ann / Kendzia, Benjamin / Vincent, Raymond / Savary, Barbara / Lavoué, Jérôme / Cavallo, Domenico / Cattaneo, Andrea / Mirabelli, Dario / Plato, Nils / Fevotte, Joelle / Pesch, Beate / Brüning, Thomas / Straif, Kurt / Kromhout, Hans

The Annals of occupational hygiene

2016 Volume 60, Issue 7, Page(s) 795–811

Abstract: Objective: The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, ... ...

Abstract	Objective: The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons (by its proxy benzo(a)pyrene (BaP)) and respirable crystalline silica). A quantitative job-exposure matrix (JEM) was developed based on statistical modeling of large quantities of personal measurements. Methods: Empirical linear models were developed using personal occupational exposure measurements (n = 102306) from Europe and Canada, as well as auxiliary information like job (industry), year of sampling, region, an a priori exposure rating of each job (none, low, and high exposed), sampling and analytical methods, and sampling duration. The model outcomes were used to create a JEM with a quantitative estimate of the level of exposure by job, year, and region. Results: Decreasing time trends were observed for all agents between the 1970s and 2009, ranging from -1.2% per year for personal BaP and nickel exposures to -10.7% for asbestos (in the time period before an asbestos ban was implemented). Regional differences in exposure concentrations (adjusted for measured jobs, years of measurement, and sampling method and duration) varied by agent, ranging from a factor 3.3 for chromium-VI up to a factor 10.5 for asbestos. Conclusion: We estimated time-, job-, and region-specific exposure levels for four (asbestos, chromium-VI, nickel, and RCS) out of five considered lung carcinogens. Through statistical modeling of large amounts of personal occupational exposure measurement data we were able to derive a quantitative JEM to be used in community-based studies.
MeSH term(s)	Air Pollutants, Occupational/analysis ; Asbestos/analysis ; Canada ; Carcinogens/analysis ; Chromium/analysis ; Europe ; Humans ; Lung Neoplasms/etiology ; Nickel/analysis ; Occupational Exposure/analysis ; Polycyclic Aromatic Hydrocarbons/analysis ; Silicon Dioxide/analysis
Chemical Substances	Air Pollutants, Occupational ; Carcinogens ; Polycyclic Aromatic Hydrocarbons ; Chromium (0R0008Q3JB) ; Asbestos (1332-21-4) ; Silicon Dioxide (7631-86-9) ; Nickel (7OV03QG267)
Language	English
Publishing date	2016-06-09
Publishing country	England
Document type	Journal Article
ZDB-ID	390312-6
ISSN	1475-3162 ; 0003-4878
ISSN (online)	1475-3162
ISSN	0003-4878
DOI	10.1093/annhyg/mew034
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Article ; Online: Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients.

Zeka, Fjoralba / Decock, Anneleen / Van Goethem, Alan / Vanderheyden, Katrien / Demuynck, Fleur / Lammens, Tim / Helsmoortel, Hetty H / Vermeulen, Joëlle / Noguera, Rosa / Berbegall, Ana P / Combaret, Valérie / Schleiermacher, Gudrun / Laureys, Geneviève / Schramm, Alexander / Schulte, Johannes H / Rahmann, Sven / Bienertová-Vašků, Julie / Mazánek, Pavel / Jeison, Marta /

Ash, Shifra / Hogarty, Michael D / Moreno-Smith, Mirthala / Barbieri, Eveline / Shohet, Jason / Berthold, Frank / Van Maerken, Tom / Speleman, Frank / Fischer, Matthias / De Preter, Katleen / Mestdagh, Pieter / Vandesompele, Jo

JCI insight

2018 Volume 3, Issue 23

Abstract: In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were ...

Abstract	In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor/blood ; Child ; Child, Preschool ; Circulating MicroRNA/blood ; Female ; Humans ; Male ; Mice ; MicroRNAs/blood ; Middle Aged ; Neoplasm Metastasis/diagnosis ; Neoplasm Staging ; Neuroblastoma/blood ; Neuroblastoma/diagnosis ; Transplantation, Heterologous ; Young Adult
Chemical Substances	Biomarkers, Tumor ; Circulating MicroRNA ; MIRN92 microRNA, human ; MicroRNAs
Language	English
Publishing date	2018-12-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.97021
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Article ; Online: The microRNA body map: dissecting microRNA function through integrative genomics.

Mestdagh, Pieter / Lefever, Steve / Pattyn, Filip / Ridzon, Dana / Fredlund, Erik / Fieuw, Annelies / Ongenaert, Maté / Vermeulen, Joëlle / De Paepe, Anne / Wong, Linda / Speleman, Frank / Chen, Caifu / Vandesompele, Jo

Nucleic acids research

2011 Volume 39, Issue 20, Page(s) e136

Abstract: While a growing body of evidence implicates regulatory miRNA modules in various aspects of human disease and development, insights into specific miRNA function remain limited. Here, we present an innovative approach to elucidate tissue-specific miRNA ... ...

Abstract	While a growing body of evidence implicates regulatory miRNA modules in various aspects of human disease and development, insights into specific miRNA function remain limited. Here, we present an innovative approach to elucidate tissue-specific miRNA functions that goes beyond miRNA target prediction and expression correlation. This approach is based on a multi-level integration of corresponding miRNA and mRNA gene expression levels, miRNA target prediction, transcription factor target prediction and mechanistic models of gene network regulation. Predicted miRNA functions were either validated experimentally or compared to published data. The predicted miRNA functions are accessible in the miRNA bodymap, an interactive online compendium and mining tool of high-dimensional newly generated and published miRNA expression profiles. The miRNA bodymap enables prioritization of candidate miRNAs based on their expression pattern or functional annotation across tissue or disease subgroup. The miRNA bodymap project provides users with a single one-stop data-mining solution and has great potential to become a community resource.
MeSH term(s)	Animals ; Cell Line, Tumor ; Data Mining ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Genomics ; Humans ; Mice ; MicroRNAs/metabolism ; Models, Genetic ; Molecular Sequence Annotation ; RNA, Messenger/metabolism ; Rats ; Software ; Transcription Factors/metabolism
Chemical Substances	MicroRNAs ; RNA, Messenger ; Transcription Factors
Language	English
Publishing date	2011-08-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkr646
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