Organotypic 3D Cell-Architecture Impacts the Expression Pattern of miRNAs–mRNAs Network in Breast Cancer SKBR3 Cells

Background. Currently, most of the research on breast cancer has been carried out in conventional two-dimensional (2D) cell cultures due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell–cell and cell–extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. In this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differentially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2 × 105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both miRNAs, and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene ontology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cytoskeleton organization, as well as in the MAPK and AGE–RAGE signaling KEGG-pathways. Interestingly, hsa-mir-122-5p (Fold Change (FC) = 15.4), hsa-mir-369-3p (FC = 11.4), and hsa-mir-10b-5p (FC = 20.1) regulated up to 81% of the 70 downregulated DE-mRNAs. Conclusion. The organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of the miRNAs–mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell–cell and cell–ECM as well as the change in the culture architecture impacts gene expression, and, therefore, support the pertinence of migrating breast cancer research from conventional cultures to 3D models

Hilando generaciones y moda

En el proyecto PAP llamado Hilando Generaciones y Moda del cual se presenta este reporte del periodo otoño 2022, el propósito general fue el de crear espacios en los cuales se diera paso a la colaboración intergeneracional e intercultural a través de la capacitación en costura y diseño de modas. Un espacio en donde los participantes pudieran intercambiar conocimientos, diálogos y trabajar en equipo, pero, sobre todo, mostrando empatía, confianza e interactuando mientas se conocen los estudiantes y las personas mayores. En este periodo escolar se elaboraron prendas de vestir para el uso personal y familiar de las personas mayores, se llevó a cabo una sesión fotográfica con las personas mayores, una pasarela para la exposición de las prendas, un documental y una revistacatálogo con las prendas. Las primeras sesiones se dedicaron a la sensibilización de los alumnos para con la población de personas mayores y con esto se dio pie para la interacción y convivencia entre los estudiantes y personas mayores, principalmente en las instalaciones del Centro Tapatío de atención al Adulto Mayor (CETAM) y en uno de los centros de día del DIF. Los estudiantes estuvieron interactuando con las personas mayores, en los que se generó una relación profunda de comprensión y empatía, y se crearon importantes resultados como las prendas, una capa tejida por alumnos y personas mayores, revistacatálogo, pasarela y un visible entramado entre las dos generaciones: jóvenes y personas mayores.ITESO, A.C

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients

Objectives: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. Methods: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. Results: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Conclusion: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/

Aquello que me habita : el bosque nativo

El trabajo colectivo enriquece las miradas, la interdisciplinariedad las multiplica. En este proyecto, buscamos abrir el juego para pensar- reflexionar e imaginar aquello que nos habita referido a la temática del bosque nativo. Lo hacemos desde distintas disciplinas, en un mismo formato: el libro de artista. Aquí, percibimos con todos los sentidos que se abre un espacio, un lugar para habitar y ser, para dejar nuestras vivencias, experiencias, sensaciones y sentimientos; para dejar nuestra huella, esa marca que entre la estructura y la cognición, entre el juego y la experimentación, permiten que algo surja. Es un libro de artista donde, retomando las palabras de Oller Navarro, en El libro como obra plástica (2011), “su sentido se encuentra primero en el aspecto lúdico que representa la definición del libro”. Gran parte de los autores que participamos en esta propuesta formamos parte del equipo de investigación: “Interrelación de poéticas fronterizas. Producción, recepción y enseñanza del arte en espacios diversos con tecnologías del presente”. SECyT- UNC-2018-2021; otros son invitados especialistas de interés. Este libro, refleja la variedad y la inclusión. Variedad en cuanto naturaleza; el bosque, como espacio que nos habita y que habitamos. Finalmente, este espacio de encuentro en formato libro, nos permite una comunicación horizontal y respetuosa entre personas que trabajan en la Instalación inmersiva “Paisajes y sentidos. Americanismos en la lengua”

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community