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Machine learning-based identification of efficient and restrictive physiological subphenotypes in acute respiratory distress syndrome
(Springer Science and Business Media LLC, 2025-03-01)
Gabriela Meza-Fuentes
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DELGADO BECERRA, OROZIMBA IRIS
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Mario Barbé
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Ignacio Sánchez
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RETAMAL LUCERO, MAURICIO ANTONIO
Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality, characterized by significant clinical heterogeneity. This heterogeneity complicates treatment selection and patient inclusion in clinical trials. Therefore, the objective of this study is to identify physiological subphenotypes of ARDS using machine learning, and to determine ventilatory variables that can effectively discriminate between these subphenotypes in a bedside setting with high performance, highlighting potential utility for future clinical stratification approaches.</jats:p> Methodology A retrospective cohort study was conducted using data from our ICU, covering admissions from 2017 to 2021. The study included 224 patients over 18 years of age diagnosed with ARDS according to the Berlin criteria and undergoing invasive mechanical ventilation (IMV). Data on physiological and ventilatory variables were collected during the first 24 h IMV. We applied machine learning techniques to categorize subphenotypes in ARDS patients. Initially, we employed the unsupervised Gaussian Mixture Classification Model approach to group patients into subphenotypes. Subsequently, we applied supervised models such as XGBoost to perform root cause analysis, evaluate the classification of patients into these subgroups, and measure their performance.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Our models identified two ARDS subphenotypes with significant clinical differences and significant outcomes. Subphenotype Efficient (<jats:italic>n</jats:italic> = 172) was characterized by lower mortality, lower clinical severity and presented a less restrictive pattern with better gas exchange compared to Subphenotype Restrictive (<jats:italic>n</jats:italic> = 52), which showed the opposite. The models demonstrated high performance with an area under the ROC curve of 0.94, sensitivity of 94.2% and specificity of 87.5%, in addition to an F1 score of 0.85. The most influential variables in the discrimination of subphenotypes were distension pressure, respiratory frequency and exhaled carbon dioxide volume.Conclusion This study presents an approach to improve subphenotype categorization in ARDS. The generation of clustering and prediction models by machine learning involving clinical, ventilatory mechanics, and gas exchange variables allowed for more accurate stratification of patients. These findings have the potential to optimize individualized treatment selection and improve clinical outcomes in patients with ARDS.</jats:p> Graphical Abstract
Scopus© Citations 2 5
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Individualized evaluation of the total dose received by radiotherapy patients: Integrating in-field, out-of-field, and imaging doses
(Elsevier BV, 2025-01)
Maite Romero-Expósito
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Beatriz Sánchez-Nieto
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Mercedes Riveira-Martin
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Mona Azizi
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Angeliki Gkavonatsiou
Scopus© Citations 10 9
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The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease
(2023)
Maria Carolina Dalmasso
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Itziar de Rojas
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Natividad Olivar
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Carolina Muchnik
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Bárbara Angel
<jats:title>Abstract</jats:title><jats:sec><jats:title>INTRODUCTION</jats:title><jats:p>Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta‐analysis and tested their genetic risk score (GRS) performance in this admixed population.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>We detected apolipoprotein E ε4 as the single genome‐wide significant signal (odds ratio = 2.93 [2.37–3.63], <jats:italic>P</jats:italic> = 2.6 × 10<jats:sup>−23</jats:sup>). The meta‐analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD‐GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose.</jats:p></jats:sec><jats:sec><jats:title>DISCUSSION</jats:title><jats:p>We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet"> <jats:list-item><jats:p>This is the first genome‐wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile.</jats:p></jats:list-item> <jats:list-item><jats:p>Trans‐ethnic meta‐analysis reveals four new loci involving lysosomal function in AD.</jats:p></jats:list-item> <jats:list-item><jats:p>This is the first independent replication for <jats:italic>TREM2L</jats:italic>, <jats:italic>IGH‐gene‐cluster</jats:italic>, and <jats:italic>ADAM17</jats:italic> loci.</jats:p></jats:list-item> <jats:list-item><jats:p>A genetic risk score (GRS) developed in Europeans performed well in this population.</jats:p></jats:list-item> <jats:list-item><jats:p>The higher the Native American ancestry the lower the GRS values.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec>
Scopus© Citations 3 1
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Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine
(2023)
Macarena Las Heras
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Benjamín Szenfeld
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Rami A. Ballout
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Emanuele Buratti
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Silvana Zanlungo
<jats:title>Abstract</jats:title><jats:p>Niemann-Pick type C (NPC) disease is a lysosomal storage disease (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss of function mutations in the <jats:italic>NPC1</jats:italic> and <jats:italic>NPC2</jats:italic> genes. NPC patients can present with a broad phenotypic spectrum, with differences at the age of onset, rate of progression, severity, organs involved, effects on the central nervous system, and even response to pharmacological treatments. This article reviews the phenotypic variation of NPC and discusses its possible causes, such as the remaining function of the defective protein, modifier genes, sex, environmental cues, and splicing factors, among others. We propose that these factors should be considered when designing or repurposing treatments for this disease. Despite its seeming complexity, this proposition is not far-fetched, considering the expanding interest in precision medicine and easier access to multi-omics technologies.</jats:p>
Scopus© Citations 7 2
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Management of radioiodine refractory differentiated thyroid cancer: the Latin American perspective
(2023)
Fabian Pitoia
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Rafael Selbach Scheffel
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Ines Califano
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Alicia Gauna
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TALA JURY, HERNAN PABLO
Scopus© Citations 5 1
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Editorial: SLC6A1: the past, present and future
(2023)
Katrine M. Johannesen
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Eduardo Pérez-Palma
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Guido Rubboli
Scopus© Citations 2
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Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America
(2021)
Mauricio Salvo
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Evelin González-Feliú
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Jessica Toro
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Iván Gallegos
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Ignacio Maureira
<jats:p>Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.</jats:p>
2Scopus© Citations 13
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Individualized luteal phase support using additional oral dydrogesterone in artificially prepared frozen embryo transfer cycles: is it beneficial?
(2023)
Shari Mackens
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Pais Leal, María Francisca
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Panagiotis Drakopoulos
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Samah Amghizar
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Caroline Roelens
9Scopus© Citations 15
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MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies
(2022)
RIVAS VERA, SOLANGE VERÓNICA
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Arnaldo Marín
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Suraj Samtani
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Evelin González-Feliú
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ARMISEN YAÑEZ, RICARDO AMADO
<jats:p>The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.</jats:p>
Scopus© Citations 15 16
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Genetic Background Matters: Population-Based Studies in Model Organisms for Translational Research
(2022)
Valeria Olguín
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Anyelo Durán
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Macarena Las Heras
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Juan Carlos Rubilar
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Francisco A. Cubillos
<jats:p>We are all similar but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly, and yeast panels with insightful applications for translational research.</jats:p>
46Scopus© Citations 8

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