Elena García González

@article{D2JA00267A,

title = {Cu fractionation, isotopic analysis, and data processing via machine learning: new approaches for the diagnosis and follow up of Wilson's disease via ICP-MS},

author = {M. Carmen García-Poyo and Sylvain Bérail and Anne Laure Ronzani and Luis Rello and Elena García-González and Flávio V. Nakadi and Maite Aramendía and Javier Resano and Martín Resano and Christophe Pécheyran},

url = {http://dx.doi.org/10.1039/D2JA00267A},

doi = {10.1039/D2JA00267A},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {J. Anal. At. Spectrom.},

volume = {38},

issue = {1},

pages = {229-242},

publisher = {The Royal Society of Chemistry},

abstract = {Information about Cu fractionation and Cu isotopic composition can be paramount when investigating Wilson's disease (WD). This information can provide a better understanding of the metabolism of Cu. Most importantly, it may provide an easy way to diagnose and to follow the evolution of WD patients. For such purposes, protocols for Cu determination and Cu isotopic analysis via inductively coupled plasma mass spectrometry were investigated in this work, both in bulk serum and in the exchangeable copper (CuEXC) fractions. The CuEXC protocol provided satisfactory recovery values. Also, no significant mass fractionation during the whole analytical procedure (CuEXC production and/or Cu isolation) was detected. Analyses were carried out in controls (healthy persons), newborns, patients with hepatic disorders, and WD patients. While the results for Cu isotopic analysis are relevant (e.g., δ65Cu values were lower for both WD patients under chelating treatment and patients with hepatic problems in comparison with those values obtained for WD patients under Zn treatments, controls, and newborns) to comprehend Cu metabolism and to follow up the disease, the parameter that can help to better discern between WD patients and the rest of the patients tested (non-WD) was found to be the REC (relative exchangeable Cu). In this study, all the WD patients showed a REC higher than 17%, while the rest showed lower values. However, since establishing a universal threshold is complicated, machine learning was investigated to produce a model that can differentiate between WD and non-WD samples with excellent results (100% accuracy, albeit for a limited sample set). Most importantly, unlike other ML approaches, our model can also provide an uncertainty metric to indicate the reliability of the prediction, overall opening new ways to diagnose WD.},

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tppubtype = {article}

}

@article{GARCIAPOYO2021106306,

title = {Evaluation of electrothermal vaporization for sample introduction aiming at Cu isotopic analysis via multicollector-inductively coupled plasma mass spectrometry},

author = {M. Carmen García-Poyo and Anne Laure Ronzani and Jérôme Frayret and Sylvain Bérail and Luis Rello and Elena García-González and Bénédicte Lelièvre and Flávio V. Nakadi and Maite Aramendía and Martín Resano and Christophe Pécheyran},

url = {https://www.sciencedirect.com/science/article/pii/S0584854721002639},

doi = {https://doi.org/10.1016/j.sab.2021.106306},

issn = {0584-8547},

year  = {2021},

date = {2021-01-01},

journal = {Spectrochimica Acta Part B: Atomic Spectroscopy},

volume = {185},

pages = {106306},

abstract = {A new method for Cu isotopic analysis was developed using a commercially available electrothermal vaporization (ETV) device coupled to multicollector-inductively coupled plasma mass spectrometry (MC-ICP-MS). The method demonstrated potential for the isotopic analysis of microsamples (e.g., 5 μL) in a biological context. For example, Cu isotopic analysis of NIST 3114 (diluted to 1 mg L−1 Cu) using self-bracketing provided average δ65Cu values of 0.00 ± 0.17‰ (2SD},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{D1JA00155H,

title = {Determination of Cu in blood via direct analysis of dried blood spots using high-resolution continuum source graphite furnace atomic absorption spectrometry},

author = {M. Carmen García-Poyo and Christophe Pécheyran and Luis Rello and Elena García-González and Sharay Alonso Rodríguez and Flávio V. Nakadi and Maite Aramendía and Martín Resano},

url = {http://dx.doi.org/10.1039/D1JA00155H},

doi = {10.1039/D1JA00155H},

year  = {2021},

date = {2021-01-01},

journal = {J. Anal. At. Spectrom.},

volume = {36},

issue = {8},

pages = {1666-1677},

publisher = {The Royal Society of Chemistry},

abstract = {The performance of state-of-the-art high-resolution continuum source graphite furnace atomic absorption spectrometry (HR CS GFAAS) instrumentation and four novel devices to produce dried blood spots of perfectly defined volumes is evaluated with the aim of developing a simple, direct method for the determination of Cu in blood samples. In all cases, it is feasible to obtain accurate quantitative information using any of the four devices tested (Mitra, HemaXis DB10, Capitainer qDBS and HemaPEN) via simple external calibration with aqueous standards. One of the main differences in the performance of such devices is related to the blanks obtained, such that HemaXis DB10 and HemaPEN are preferred when abnormally low Cu levels (500 μg L−1 or lower), associated with some diseases, need to be determined. The results prove that accurate values with RSD values below 10% can be achieved for these devices even for such Cu levels, while for Capitainer qDBS and, to a higher extent, for Mitra, blank variations will ultimately increase the uncertainty. It is important to stress that analysis of four real samples using both venipuncture and all the DBS specimens showed a very good agreement. Thus, the approach proposed could be readily applied, such that patients with disorders requiring Cu control can prepare their own samples and submit them via postal mail to labs for HR CS GFAAS direct and fast analysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{D0JA00494D,

title = {Laser ablation of microdroplets for copper isotopic analysis via MC-ICP-MS. Analysis of serum microsamples for the diagnosis and follow-up treatment of Wilson's disease},

author = {M. Carmen García-Poyo and Sylvain Bérail and Anne Laure Ronzani and Luis Rello and Elena García-González and Bénédicte Lelièvre and Paul Cales and Flavio V. Nakadi and Maite Aramendía and Martín Resano and Christophe Pécheyran},

url = {http://dx.doi.org/10.1039/D0JA00494D},

doi = {10.1039/D0JA00494D},

year  = {2021},

date = {2021-01-01},

journal = {J. Anal. At. Spectrom.},

volume = {36},

issue = {5},

pages = {968-980},

publisher = {The Royal Society of Chemistry},

abstract = {Cu isotopic analysis can provide valuable insight when investigating Wilson's disease (WD), but one of the problems related to this type of study is that usually low sample volumes are available and/or low Cu concentrations are found in these samples. This paper presents a new approach for Cu isotope ratio determination that requires only 1 μL of pre-treated serum sample per replicate (after Cu separation and preconcentration to a Cu concentration range between 0.3 and 4 mg L−1). Cu determination was carried out by direct μ-injection of 1 μL of pretreated serum samples into an ICP-MS, offering a LOD of 3 μg L−1. For Cu isotopic analysis, the method presented is based on micro-volume deposition on a pure silicon wafer and subsequent ablation analysis by fsLA-MC-ICP-MS. Cu isotopic analysis of NIST 3114 at 1 mg L−1 Cu concentration with the self-bracketing method provided average δ65Cu values of −0.01 ± 0.19‰ (2SD) and an internal precision value of 517 ppm. This method was deployed for the analysis of serum samples from WD patients under different treatments, as well as healthy newborns and patients with other liver disorders. The results seem to link decreased δ65Cu values to Cu release from the liver, further demonstrating the potential of this type of analysis in the biomedical context.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32745579,

title = {Serum protein profile analysis in lysosomal storage disorders patients},

author = {Laura López de Frutos and Elena García-González and Beatriz García-Rodríguez and Yolanda González-Irazabal and Carlos Lahoz and Pilar Irún and Jorge J Cebolla and Pilar Giraldo},

doi = {10.1016/j.cca.2020.07.056},

issn = {1873-3492},

year  = {2020},

date = {2020-11-01},

journal = {Clin Chim Acta},

volume = {510},

pages = {430--436},

abstract = {INTRODUCTION: Serum protein electrophoresis (SPE) is a well-established technique to identify alterations in plasma protein profiles, caused by diseases as multiple myeloma (MM). In addition, it could be a cost-effective technique to discover new plasma biomarkers. Relation between MM and lysosomal storage diseases (LSDs) as Gaucher disease has been set out but, it has not been evaluated on other LSDs nor the utility of the SPE as first step on LSDs biomarkers discovery projects.



MATERIALS AND METHODS: Stored plasma samples at diagnosis from several LSDs patients underwent analysis. Quality control was checked prior to the SPE was analyzed by capillary electrophoresis. The analysis for monoclonal spikes and the differences between each fraction on patients' samples vs the control data previously published, were evaluated. Furthermore, immunoprotein quantification and free light chains ratio were done by nephelometry and turbidimetry.



RESULTS: Seventy-five samples of LSD patients at diagnosis, were assessed. The frequency of the MGUS on LSDs patients was not higher than in general population whereas one lysosomal acid lipase deficiency infant showed increased IgA and kappa deviation. Regarding to the usefulness of SPE in biomarkers discovery, statistically significant differences were observed on SPE fractions between LSDs and healthy population.



DISCUSSION: The evaluation of SPE fractions can be a useful tool to understand pathophysiologic aspects in LDSs and, to simplify new marker discovery projects. In some of them, the MGUS appearance is a risk factor for the MM development despite its frequency is not increased on the studied LSDs at diagnosis.},

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pubstate = {published},

tppubtype = {article}

}