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Article ; Online: Assessing the contribution of the chemical exposome to neurodegenerative disease.

Lefèvre-Arbogast, S / Chaker, J / Mercier, F / Barouki, R / Coumoul, X / Miller, G W / David, A / Samieri, C

2024 Volume 27, Issue 5, Page(s) 812–821

Abstract: Over the past few decades, numerous environmental chemicals from solvents to pesticides have been suggested to be involved in the development and progression of neurodegenerative diseases. Most of the evidence has accumulated from occupational or cohort ... ...

Abstract	Over the past few decades, numerous environmental chemicals from solvents to pesticides have been suggested to be involved in the development and progression of neurodegenerative diseases. Most of the evidence has accumulated from occupational or cohort studies in humans or laboratory research in animal models, with a range of chemicals being implicated. What has been missing is a systematic approach analogous to genome-wide association studies, which have identified dozens of genes involved in Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. Fortunately, it is now possible to study hundreds to thousands of chemical features under the exposome framework. This Perspective explores how advances in mass spectrometry make it possible to generate exposomic data to complement genomic data and thereby better understand neurodegenerative diseases.
MeSH term(s)	Humans ; Neurodegenerative Diseases/chemically induced ; Neurodegenerative Diseases/genetics ; Exposome ; Animals ; Environmental Exposure/adverse effects ; Genome-Wide Association Study ; Mass Spectrometry
Language	English
Publishing date	2024-04-29
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-024-01627-1
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Article: Inguinal synovial sarcoma revealed by a limb swelling: A case report.

Chaker, Jaber / Khlas, Ilyes / Bouassida, Imen / Ayed, Aymen Ben / Bousnina, Mouna / Jmal, Amine

International journal of surgery case reports

2024 Volume 115, Page(s) 109252

Abstract: Introduction and importance: Synovial sarcoma is a malignant soft tissue tumor typically found near joints; its occurrence in the inguinal region is very rare.: Case presentation: We report a 23-years-old who presented with lower limb swelling. ... ...

Abstract	Introduction and importance: Synovial sarcoma is a malignant soft tissue tumor typically found near joints; its occurrence in the inguinal region is very rare. Case presentation: We report a 23-years-old who presented with lower limb swelling. Imaging studies revealed a tumor in the groin area, compressing the femoral vein. A trucut biopsy concluded a synovial sarcoma. A complete resection was performed and the patient had adjuvant radiotherapy and chemotherapy with no evidence of reccurrence at 2-years follow-up. Clinical discussion: Synovial sarcoma accounts for approximately 8 to 10 % of all soft tissue sarcomas. It is predominantly localized near the large joints in the limbs, with the inguinal location being extremely rare. Clinical diagnosis of the mass can sometimes be challenging. A needle biopsy, followed by histological analysis, is necessary to establish the diagnosis. MRI is considered the gold standard radiological examination for local staging of the tumor. The main treatment approach for synovial sarcoma is wide-margin resection, involving en-bloc resection of the tumor with clear margins. Vascular resection and reconstruction should be considered for involved vessels. Some authors argue that resection alone is sufficient for treating primary synovial sarcoma. However, adjuvant chemotherapy may be effective in cases where surgery quality is poor, making it a non-standard treatment. Others have highlighted the potential benefits of adjuvant radiotherapy, particularly in high-grade tumors. Conclusion: Surgical excision remains the mainstay of treatment. Therefore, it is necessary to be aware of the different clinical presentations, which can sometimes be unusual.
Language	English
Publishing date	2024-01-12
Publishing country	Netherlands
Document type	Case Reports
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2024.109252
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Article ; Online: Scannotation: A Suspect Screening Tool for the Rapid Pre-Annotation of the Human LC-HRMS-Based Chemical Exposome.

Chaker, Jade / Gilles, Erwann / Monfort, Christine / Chevrier, Cécile / Lennon, Sarah / David, Arthur

Environmental science & technology

2023 Volume 57, Issue 48, Page(s) 19253–19262

Abstract: In an increasingly chemically polluted environment, rapidly characterizing the human chemical exposome (i.e., chemical mixtures accumulating in humans) at the population scale is critical to understand its impact on health. High-resolution mass ... ...

Abstract	In an increasingly chemically polluted environment, rapidly characterizing the human chemical exposome (i.e., chemical mixtures accumulating in humans) at the population scale is critical to understand its impact on health. High-resolution mass spectrometry (HRMS) profiling of complex biological matrices can theoretically provide a comprehensive picture of chemical exposures. However, annotating the detected chemical features, particularly low-abundant ones, remains a significant obstacle to implementing such approaches at a large scale. We present Scannotation (https://github.com/scannotation/Scannotation_software), an automated and user-friendly suspect screening tool for the rapid pre-annotation of HRMS preprocessed data sets. This software tool combines several MS1 chemical predictors, i.e.,
MeSH term(s)	Humans ; Adolescent ; Exposome ; Mass Spectrometry/methods
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.3c04764
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Article ; Online: Exposome chimique et approches « non ciblées » - Un changement de paradigme pour évaluer l’exposition des populations aux contaminants chimiques.

David, Arthur / Chaker, Jade / Multigner, Luc / Bessonneau, Vincent

Medecine sciences : M/S

2021 Volume 37, Issue 10, Page(s) 895–901

Abstract: The technological advances in high-resolution mass spectrometry (HRMS), associated with the development of bioinformatics tools, allows the simultaneous detection of tens of thousands of chemical signals in biological matrices, including exogenous (i.e. ... ...

Title translation	Chemical exposome and non-targeted approaches.
Abstract	The technological advances in high-resolution mass spectrometry (HRMS), associated with the development of bioinformatics tools, allows the simultaneous detection of tens of thousands of chemical signals in biological matrices, including exogenous (i.e. xenobiotics) and endogenous molecules. These novel approaches based on HRMS, called "non-targeted" approaches, provide a unique opportunity to capture exposures to a wide range of chemicals (i.e. the internal chemical exposome) in populations, and to better understand the links between chemical exposures and the occurrence of chronic diseases.
MeSH term(s)	Environmental Exposure/analysis ; Exposome ; Humans ; Mass Spectrometry
Language	French
Publishing date	2021-10-14
Publishing country	France
Document type	Journal Article
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2021088
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Article ; Online: Axillary Cutaneous Hemosiderosis in a Patient With Hyperhidrosis, After Intravenous Iron Infusion.

Fernandez-Flores, Angel / Fernandez-Parrado, Miriam / Alzoghby-Abi Chaker, Jacques / Angulo, Ana Graciela

The American Journal of dermatopathology

2023 Volume 45, Issue 7, Page(s) 463–465

Abstract: Abstract: Hemosiderosis consists of an iron deposit in tissues, which does not cause organic damage to them. However, in the case of the skin, being an organ exposed to sight, siderosis can produce a brownish coloration that is aesthetically ... ...

Abstract	Abstract: Hemosiderosis consists of an iron deposit in tissues, which does not cause organic damage to them. However, in the case of the skin, being an organ exposed to sight, siderosis can produce a brownish coloration that is aesthetically discomforting for the individual. Most cutaneous sideroses are because of venous insufficiency with hemorrhagic extravasation. There is also a group secondary to iron extravasation in the injection site of the transfusion. However, there are very few cases in which an intravenous injection of an iron preparation has produced diffuse siderosis in extensive areas of the skin. We present the case of a 31-year-old woman with hyperhidrosis, who was transfused as a result of postpartum hemorrhage and, shortly after receiving an intravenous iron infusion, developed extensive hyperpigmentation in both axillae.
MeSH term(s)	Female ; Pregnancy ; Humans ; Adult ; Iron ; Hemosiderosis/chemically induced ; Siderosis/complications ; Hyperpigmentation/complications ; Hyperhidrosis/complications
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	448469-1
ISSN	1533-0311 ; 0193-1091
ISSN (online)	1533-0311
ISSN	0193-1091
DOI	10.1097/DAD.0000000000002461
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Article ; Online: Modeling the fate of organic nitrogen during anaerobic digestion: Development of a bioaccessibility based ADM1.

Bareha, Y / Girault, R / Guezel, S / Chaker, J / Trémier, A

Water research

2019 Volume 154, Page(s) 298–315

Abstract: Simulating the fate of nitrogen during anaerobic digestion is required to predict the characteristics of digestates and to improve their exploitation for agricultural uses. The aim of this study was to develop a modified ADM1 model that includes ... ...

Abstract	Simulating the fate of nitrogen during anaerobic digestion is required to predict the characteristics of digestates and to improve their exploitation for agricultural uses. The aim of this study was to develop a modified ADM1 model that includes bioaccessibility-based fractionation to accurately simulate the fate of nitrogen during anaerobic digestion. To this end, two complementary approaches were used: (i) changes in the bioaccessibility of protein and non-protein compounds were assessed on eight substrates during anaerobic digestion in batch experiments using the "EPS" fractionation method; (ii) experimental results were used to develop a bio-kinetic model based on anaerobic digestion model n°1. This new model incorporates bioaccessibility-based fractionation in its input state variables. The model was successfully calibrated and model evaluation showed that predicted methane production, ammonium production and changes in protein and non-protein bioaccessibility during anaerobic digestion were accurate.
MeSH term(s)	Anaerobiosis ; Bioreactors ; Kinetics ; Nitrogen
Chemical Substances	Nitrogen (N762921K75)
Language	English
Publishing date	2019-02-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	202613-2
ISSN	1879-2448 ; 0043-1354
ISSN (online)	1879-2448
ISSN	0043-1354
DOI	10.1016/j.watres.2019.02.011
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Article ; Online: Corrigendum to "Modeling the fate of organic nitrogen during anaerobic digestion: Development of a bioaccessibility based ADM1".

Bareha, Y / Girault, R / Guezel, S / Chaker, J / Trémier, A

Water research

2019 Volume 155, Page(s) 487

Language	English
Publishing date	2019-04-04
Publishing country	England
Document type	Published Erratum
ZDB-ID	202613-2
ISSN	1879-2448 ; 0043-1354
ISSN (online)	1879-2448
ISSN	0043-1354
DOI	10.1016/j.watres.2019.03.022
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Article ; Online: Human sperm cells can form paracetamol metabolite AM404 that directly interferes with sperm calcium signalling and function through a CatSper-dependent mechanism.

Rehfeld, A / Frederiksen, H / Rasmussen, R H / David, A / Chaker, J / Nielsen, B S / Nielsen, J E / Juul, A / Skakkebæk, N E / Kristensen, D M

Human reproduction (Oxford, England)

2022 Volume 37, Issue 5, Page(s) 922–935

Abstract: Study question: Do paracetamol (N-acetyl-para-aminophenol (APAP) or acetaminophen) and/or its metabolites affect human sperm Ca2+-signalling and function?: Summary answer: While APAP itself does not interact with Ca2+-signalling in human sperm, its ... ...

Abstract	Study question: Do paracetamol (N-acetyl-para-aminophenol (APAP) or acetaminophen) and/or its metabolites affect human sperm Ca2+-signalling and function? Summary answer: While APAP itself does not interact with Ca2+-signalling in human sperm, its metabolite N-arachidonoyl phenolamine (AM404), produced via fatty acid amide hydrolase (FAAH), interferes with human sperm Ca2+-signalling and function through a suggested CatSper channel-dependent action. What is known already: Studies have shown that adult men with high urinary levels of over-the-counter mild analgesic APAP have impaired sperm motility and increased time-to-pregnancy. Study design, size, duration: This study consists of (i) an in vivo human pharmaceutical APAP exposure experiment to understand to what degree APAP reaches the sperm cells in the seminal fluid; (ii) in vitro calcium imaging and functional experiments in freshly donated human sperm cells to investigate CatSper channel-dependent activation by APAP and its metabolites; and (iii) experiments to understand the in situ capabilities of human sperm cells to form APAP metabolite AM404. Participants/materials, setting, methods: Three healthy young males participated in the in vivo human exposure experiment after prior consent. Human semen samples were provided by healthy young volunteer donors after prior consent on the day of the in vitro experiments. Main results and the role of chance: Pharmaceutical APAP exposure reaches the seminal plasma in high micromolar concentrations and accumulates in the seminal plasma between 3 and 5 days of exposure (P-value 0.023). APAP and its primary metabolite 4-aminophenol (4AP) do not interact with human sperm Ca2+-signalling. Instead, the APAP metabolite AM404 produced via FAAH interferes with human sperm Ca2+-signalling through a CatSper-dependent action. Also, AM404 significantly increases sperm cell penetration into viscous mucous (P-value of 0.003). FAAH is functionally expressed in human sperm cells in the neck/midpiece region, as evidenced by immunohistochemical staining and the ability of human sperm cells to hydrolyse the fluorogenic FAAH substrate arachidonyl 7-amino, 4-methyl coumarin amide in an FAAH-dependent manner. Importantly, human sperm cells have the capacity to form AM404 in situ after exposure to 4AP (P-value 0.0402 compared to vehicle-treated sperm cells). Limitations, reasons for caution: The experiments were conducted largely in vitro. Future studies are needed to test whether APAP can disrupt human sperm function in vivo through the action of AM404. Wider implications of the findings: We hypothesize that these observations could, at least in part, be responsible for the negative association between male urinary APAP concentrations, sperm motility and time-to-pregnancy. Study funding/competing interest(s): D.M.K. is funded by the Lundbeck Foundation, grant number R324-2019-1881, and the Svend Andersen Foundation. A.R. is funded by a BRIDGE-Translational Excellence Programme grant funded by the Novo Nordisk Foundation, grant agreement number: NNF18SA0034956. All authors declare no competing interests. Trial registration number: N/A.
MeSH term(s)	Acetaminophen/pharmacology ; Adult ; Arachidonic Acids ; Calcium/metabolism ; Calcium Channels/metabolism ; Humans ; Male ; Pharmaceutical Preparations/metabolism ; Progesterone/metabolism ; Sperm Motility ; Spermatozoa/metabolism
Chemical Substances	Arachidonic Acids ; Calcium Channels ; Pharmaceutical Preparations ; Acetaminophen (362O9ITL9D) ; Progesterone (4G7DS2Q64Y) ; Calcium (SY7Q814VUP) ; N-(4-hydroxyphenyl)arachidonylamide (XVJ94H0U21)
Language	English
Publishing date	2022-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632776-x
ISSN	1460-2350 ; 0268-1161 ; 1477-741X
ISSN (online)	1460-2350
ISSN	0268-1161 ; 1477-741X
DOI	10.1093/humrep/deac042
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Article ; Online: From Metabolomics to HRMS-Based Exposomics: Adapting Peak Picking and Developing Scoring for MS1 Suspect Screening.

Chaker, Jade / Gilles, Erwann / Léger, Thibaut / Jégou, Bernard / David, Arthur

Analytical chemistry

2020 Volume 93, Issue 3, Page(s) 1792–1800

Abstract: The technological advances of cutting-edge high-resolution mass spectrometry (HRMS) have set the stage for a new paradigm for exposure assessment. However, some adjustments of the metabolomics workflow are needed before HRMS-based methods can detect the ... ...

Abstract	The technological advances of cutting-edge high-resolution mass spectrometry (HRMS) have set the stage for a new paradigm for exposure assessment. However, some adjustments of the metabolomics workflow are needed before HRMS-based methods can detect the low-abundant exogenous chemicals in human matrixes. It is also essential to provide tools to speed up marker identifications. Here, we first show that metabolomics software packages developed for automated optimization of XCMS parameters can lead to a false negative rate of up to 80% for chemicals spiked at low levels in blood. We then demonstrate that manual selection criteria in open-source (XCMS, MZmine2) and vendor software (MarkerView, Progenesis QI) allow to decrease the rate of false negative up to 4% (MZmine2). We next report an MS1 automatized suspect screening workflow that allows for a rapid preannotation of HRMS data sets. The novelty of this suspect screening workflow is to combine several predictors based on
MeSH term(s)	Algorithms ; Mass Spectrometry ; Metabolomics ; Software
Language	English
Publishing date	2020-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.0c04660
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Article ; Online: Comprehensive Evaluation of Blood Plasma and Serum Sample Preparations for HRMS-Based Chemical Exposomics: Overlaps and Specificities.

Chaker, Jade / Kristensen, David Møbjerg / Halldorsson, Thorhallur Ingi / Olsen, Sjurdur Frodi / Monfort, Christine / Chevrier, Cécile / Jégou, Bernard / David, Arthur

Analytical chemistry

2022 Volume 94, Issue 2, Page(s) 866–874

Abstract: Sample preparation of biological samples can have a substantial impact on the coverage of small molecules detectable using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). This initial step is particularly critical for the detection of ... ...

Abstract	Sample preparation of biological samples can have a substantial impact on the coverage of small molecules detectable using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). This initial step is particularly critical for the detection of externally derived chemicals and their metabolites (internal chemical exposome) generally present at trace levels. Hence, our objective was to investigate how blood sample preparation methods affect the detection of low-abundant chemicals and to propose alternative methods to improve the coverage of the internal chemical exposome. We performed a comprehensive evaluation of 12 sample preparation methods (SPM) using phospholipid and protein removal plates (PLR), solid phase extraction plates (SPE), supported liquid extraction cartridge (SLE), and conventionally used protein precipitation (PPT). We implemented new quantitative and qualitative criteria for nontargeted analyses (detection frequency, recoveries, repeatability, matrix effect, low-level spiking significance, method detection limits, throughput, and ease of use) to amply characterize these SPM in a step-by-step-type approach. As a final step, PPT and one PLR plate were applied to cohort plasma and serum samples injected in triplicate to monitor batch repeatability, and annotation was performed on the related data sets to compare the respective impacts of these SPM. We demonstrate that sample preparation significantly affects both the range of observable compounds and the level at which they can be observed (only 43%-54% of total features are overlapping between the two SPM). We propose to use PPT and PLR on the same samples by implementing a simple analytical workflow as their complementarity would allow the broadening of the visible chemical space.
MeSH term(s)	Chromatography, High Pressure Liquid/methods ; Chromatography, Liquid ; Humans ; Plasma ; Solid Phase Extraction/methods ; Tandem Mass Spectrometry/methods
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.1c03638
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