Universidad Argentina de la Empresa

Social skills and behavioural problems can vary during childhood development based on sex and the socio-environmental conditions of the home. The objective of this study was to analyse variations in social skills and behavioural problems according to individual factors (age and sex) and their associations with socio-environmental factors (parents’ education and employment and home stimulation). To do so, reports from close family members were obtained through the Preschool and Kindergarten Behaviour Scale (PKBS-2), and behaviours associated with the socio-emotional development of children aged four to eight years from households with different socio-environmental conditions in Argentina were analysed. No age-based variations were found, but there were differences according to sex. Social skills were positively correlated with parental education and home stimulation. Maternal employment was inversely correlated with social interaction. This study helps to identify which individual and socio-environmental factors modulate the expression of social skills and behavioural problems in children.

We present an experimental study of the magnetoelectric coupling in the Fe-Ga/Pb[(Mg 1 / 3Nb 2 / 3)O 3] 0.68-[PbTiO 3] 0.31 thin-film multiferroic composite using x-ray magnetic circular dichroism and ferromagnetic resonance (FMR). Our measurements show evidence for a charge-mediated coupling mechanism, suggested by the asymmetric magnetic remanence (M r e m) behavior under opposite electric fields ( ±E) and the asymmetric resonance field (H r) in the FMR measurements. Also, the FMR measurements reveal a perpendicular magnetic anisotropy that can be related to an interface charge effect and it is tunable by the E field. Ab initio calculations support the existence of a charge-mediated coupling at the Fe–Ga/PMN-PT interface.

Overcoming luminal breast cancer (BrCa) progression remains a critical challenge for improved overall patient survival. RUNX2 has emerged as a protein related to aggressiveness in triple‐negative BrCa, however its role in luminal tumors remains elusive. We have previously shown that active FGFR2 (FGFR2‐CA) contributes to increased tumor growth and that RUNX2 expression was high in hormone‐independent mouse mammary carcinomas. To elucidate the interaction between FGFR2 and RUNX2 in human BrCa, we investigated their roles in tumor progression and treatment responsiveness. Increased FGFR2 activity resulted in higher RUNX2 expression, cell proliferation, and metastasis. In contrast, silencing FGFR2 reduced these parameters. Overexpression of RUNX2 in FGFR2‐silenced cells rescued the inhibitory effects, promoting a more aggressive phenotype, even if compared with the wt RUNX2‐transfected cells, which also had increased aggressiveness compared with naïve‐transfected cells. RUNX2‐overexpressing tumors were insensitive to endocrine‐ or FGFR inhibitor treatments. Notably, the CBFβ‐RUNX complex inhibitor, AI‐14‐91, demonstrated great effectiveness in vitro. In a small cohort of luminal BrCa patients, nuclear RUNX2 expression was associated with tumor recurrence. Transcriptomic analysis strongly supported these data showing that patients with luminal carcinomas with high RUNX2 activity score have a worse progression‐free interval than those with low RUNX2 activity. Our findings suggest a complex interplay between FGFR2 and RUNX2 in regulating tumor aggressiveness. This study underscores the significance of RUNX2 in luminal BrCa progression and posits RUNX2 as a promising therapeutic target and as a potential prognostic biomarker in luminal BrCa patients.

Cells exert forces on each other and their environment, shaping the tissue. The resulting mechanical stresses can be determined experimentally or estimated computationally using stress inference methods. Over the years, mechanical stress inference has become a non-invasive, low-cost computational method for estimating the relative intercellular stresses and intracellular pressures of tissues. This mini-review introduces and compares the static and dynamic modalities of stress inference, considering their advantages and limitations. To date, most software has focused on static inference, which requires only a single microscopy image as input. Although applicable in quasi-equilibrium states, this approach neglects the influence that cell rearrangements might have on the inference. In contrast, dynamic stress inference relies on a time series of microscopy images to estimate stresses and pressures. Here, we discuss both static and dynamic mechanical stress inference in terms of their physical, mathematical, and computational foundations and then outline what we believe are promising avenues for in silico inference of the mechanical states of tissues.

Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.

El tratamiento de los datos abiertos públicos es un tema que cada vez se encuentra más auge, ya que permite incentivar las iniciativas de transparencia en entidades gubernamentales, como así también en diversas empresas privadas. Este nuevo paradigma tiene como uno de sus ejes centrales, el tratamiento de los datos abiertos para que puedan ser manipulados mediante técnicas específicas con software y servicios que permiten el almacenamiento de estos en otras bases de datos para su utilización. Esto representa una gran ventaja en aspectos de transparencia en el contexto de Gobierno Abierto, sin embargo, esta apertura de datos expone diversos desafíos en cuanto a la privacidad y seguridad, debido a que puede poner en riesgo la privacidad de los ciudadanos en caso de que no se implementen medidas adecuadas. El objetivo de este trabajo es presentar un relevamiento sobre el estado de situación en este contexto, por lo que, para ello, se analizaron algunos casos de estudios y ejemplos prácticos de organizaciones, con el fin de trabajar en las falencias y problemáticas en lo que respecta a la privacidad y seguridad en el tratamiento de los datos abiertos públicos. Como siguiente punto, se trabajó en una propuesta de una serie de buenas prácticas y políticas para brindar una adecuada protección de la confidencialidad de datos. Finalmente, se analiza que utilizar estas prácticas, no solo podrá mejorar la protección de datos disponibles, sino que también, permitirá fortalecer la confianza pública en este tipo de iniciativas. Palabras clave: datos abiertos; seguridad; protección de datos; derecho a la privacidad.

Background/Objectives: Prostate cancer (PCa) is the leading malignancy and the third most common cause of cancer-related death in Argentinian men. Predicting outcomes in localized PCa remains difficult due to tumor heterogeneity. In this study, we assessed the impact of AR (CAG)n and APEX1 c.444T>G polymorphisms on biochemical relapse in Argentine patients with localized PCa. Methods: We genotyped blood samples from 123 PCa patients for AR (CAG)n and APEX1 p.Asp148Glu (c.444T>G) polymorphisms. Associations with clinicopathological parameters and biochemical relapse-free survival (BRFS) were assessed. Results: AR (CAG)20–23 was associated with a family history of breast/ovarian cancer (p = 0.0469). The combination of AR (CAG)20–23 and APEX1 c.444TT/GG correlated with a 2.89 times higher risk of biochemical relapse (log-rank p = 0.006). Multivariable analysis confirmed AR and APEX1 polymorphisms as independent predictors of biochemical relapse (HR = 3.95, p = 0.002). In patients with PSA levels <10 ng/mL, combined AR (CAG)20–23 and APEX1 c.444TT/GG genotypes were significantly associated with an increased risk of biochemical relapse (HR = 2.61, p = 0.044). Multivariable analysis confirmed the prognostic significance of these genotypes (HR = 3.44, p = 0.02). Conclusions: This study has identified AR (CAG)n and APEX1 c.444T>G polymorphisms as independent predictors of PCa relapse in Argentinian patients, suggesting their potential use in improving prognostic models.

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-scale transcriptomic datasets. The resulting seven-gene signature (KMT5C, DPP4, TYMS, CDC25B, IRF5, MEN1, and DNMT3B) was validated across independent cohorts and patient-derived xenograft (PDX) models. This signature demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, and overall survival. Importantly, the signature not only identified specific NEPC subtypes, such as large-cell neuroendocrine carcinoma, which is associated with very poor outcomes, but also predicted a poor prognosis for PCa cases that exhibit this molecular signature, even when they were not histopathologically classified as NEPC. This dual prognostic and classifier capability makes the seven-gene signature a robust tool for personalized medicine, providing a valuable resource for predicting disease progression and guiding treatment strategies in PCa management.

Este artículo se deriva de la investigación la educación lectora y su vinculación con las economías campesinas, familiares y comunitarias (ECFC): una mirada a través de contextos culturales (bibliotecas) y escolares (escuelas rurales), el caso de Argentina. Presenta un ejercicio crítico de revisión documental, bajo un enfoque de justicia social que retoma ideas de la Doctrina Peronista, para exponer un contexto sobre la configuración de lo rural en el país, mediante una exploración de la normativa, las instituciones líderes en los procesos rurales, algunos hitos y las políticas públicas actuales. Cierra con las posibilidades de articulación de las economías campesinas con la educación y la cultura.

Presentación de dosier. Bibliotecología social: aportes, reflexiones y perspectivas desde América Latina y el Caribe - parte 1

We present a study of the properties related to the magnetization reversal process in two thin-film samples with magnetic stripe domains: Fe0.82Ga0.18 (Fe–Ga) and Ni0.81Fe0.19 (permalloy). In Fe–Ga thin films, we focus on magnetization reversal driven by thermal activation by considering the magnetic viscosity behavior. The results suggest that the reversal process occurs gradually, where the magnetization switches direction via ∼10 nm-long jumps of the magnetic domain walls. On the other hand, vectorial hysteresis loops were performed in permalloy thin films with the aim to study the behavior of the transverse magnetization component (perpendicular to the applied field) during the magnetization reversal process. We show that the measurement of the transversal magnetization component shows a much higher sensitivity for the determination of the in-plane magnetic anisotropy than the usual hysteresis loops where the magnetization is parallel to the applied field. Moreover, this allows to highlight the competition between the intrinsic and rotatable anisotropies in thin films that present stripe domains.

El Código Civil y Comercial de la Nación argentino establecía hasta diciembre 2023 que, en casos de obligaciones de dar dinero en moneda distinta al peso argentino, el deudor podía liberarse dando el equivalente en moneda de curso legal. Sin embargo, las restricciones gubernamentales en el acceso a la moneda extranjera han generado brechas cambiarias. La cuestión radica en determinar dicha equivalencia, ya que existen múltiples cotizaciones con diferencias significativas desde la promulgación de la Ley Nº 27.541. Así, en mercados cambiarios regulados los deudores plantean cancelar sus obligaciones al menor tipo de cambio posible, y los acreedores al mayor. Aquí se analiza jurisprudencia de tribunales de segunda instancia en la materia, identificando decisiones y sus fundamentos y reflexionando sobre los problemas que se pueden generar en economías de tipo de cambio múltiple.

Prostate cancer is a highly heterogeneous disease; therefore, estimating patient prognosis accurately is challenging due to the lack of biomarkers with sufficient specificity and sensitivity. One of the current challenges lies in integrating genomic and transcriptomic data with clinico-pathological features and in incorporating their application in everyday clinical practice. Therefore, we aimed to model a risk score and nomogram containing long non-coding RNA (lncRNA) expression and clinico-pathological data to better predict the probability of prostate cancer progression. We performed bioinformatics analyses to identify lncRNAs differentially expressed across various prostate cancer stages and associated with progression-free survival. This information was further integrated into a prognostic risk score and nomogram containing transcriptomic and clinico-pathological features to estimate the risk of disease progression. We used RNA-seq data from 5 datasets from public repositories (total n = 178) comprising different stages of prostate cancer: pre-treatment primary prostate adenocarcinomas, post-treatment tumors and metastatic castration resistant prostate cancer. We found 30 lncRNAs with consistent differential expression in all comparisons made using two R-based packages. Multivariate progression-free survival analysis including the ISUP group as covariate, revealed that 7/30 lncRNAs were significantly associated with time-to-progression. Next, we combined the expression of these 7 lncRNAs into a multi-lncRNA score and dichotomized the patients into low- or high-score. Patients with a high-score showed a 4-fold risk of disease progression (HR = 4.30, 95 %CI = 2.66–6.97, p = 3.1e-9). Furthermore, we modelled a combined risk-score containing information on the multi-lncRNA score and ISUP group. We found that patients with a high-risk score had nearly 8-fold risk of progression (HR = 7.65, 95 %CI = 4.05–14.44, p = 3.4e-10). Finally, we created and validated a nomogram to help uro-oncologists to better predict patient's risk of progression at 3- and 5-years post-diagnosis. In conclusion, the integration of lncRNA expression data and clinico-pathological features of prostate tumors into predictive models might aid in tailored disease risk assessment and treatment for patients with prostate cancer.

e15154 Background: The analysis of somatic genomic alterations, evaluation of DNA mismatch repair (MMR) proteins, and examination of PD-L1 expression in tumor biopsies are crucial for prognosis and informed therapeutic decisions. However, their clinical implementation in Argentina faces challenges due to economic costs and lack of evidence. To address this, we conducted a retrospective study to assess the impact of this molecular panel testing on treatment decisions and clinical management of cancer patients in Argentina. Additionally, we evaluated its ability to detect clinically relevant alterations and analyzed the frequency and co-occurrence of mutations in our cohort. Methods: Tumor tissue samples from 266 patients with primary tumors, representing 26 different anatomical sites (53% lung cancer), underwent molecular testing using the Optimus panel developed by Biomakers. The assay integrates somatic sequencing of 52 genes through NGS with IHC assessment of MMR and PD-L1 proteins. A retrospective evaluation of the clinical effectiveness of the test was conducted on 133 patients. Genomic and clinical data were analyzed using R with the pairwise Fisher’s exact test applied for statistical analysis. Results: This panel facilitates molecular characterization, identifying clinically relevant genetic alterations in 65% of patients and detecting deficiency in MMR proteins in 3%. Findings align with global clinical trial availability for identified alterations in 97% of cases. KRAS is the most frequently mutated gene (38%), followed by EGFR (19%), PIK3CA (12%), BRAF (9%), CDK4, and CTNNB1 (5% each), correlating with lung cancer overrepresentation. Simultaneous alterations in EGFR, PIK3CA, CTNNB1, and KIT genes were observed. Pan-tumoral interaction analysis revealed mutual exclusivity between KRAS mutations and those in EGFR, BRAF, CDK4, and CTNNB1. CTNNB1 mutations co-occurred with EGFR mutations, akin to KIT and PDGFRA (p<0.05). The retrospective analysis indicated that the Optimus panel contributed to clinical management of patients in 56% of cases, with 85% detecting clinically relevant variants, aiding treatment definition in 74% of these cases. Conclusions: The Biomakers-developed Optimus panel empowers the molecular characterization of genomic and proteomic biomarkers across tumor types. Its significance in clinical practice lies in contribution to vital decision-making processes, particularly in treatment selection.

In this study, we present a systematic analysis of the relation between the structural properties and magnetic anisotropies of as-grown and heat-treated polycrystalline Fe 1−x Ga x (0.11 <x< 0.19) thin films deposited on glass and Si(100) substrates. The results show that the crystallographic texture of the films has a significant impact on the evolution of the magnetic anisotropies. The samples grown on glass do not exhibit a preferred texture while, for samples grown on Si(100), the appearance of a weak in-plane fourfold magnetic anisotropy is reported. Such anisotropy is enhanced and better defined in the heat treated samples. Via a phenomenological model we show that this anisotropy has a microstructural origin. These findings demonstrate the possibility of tuning magnetic anisotropies by growing on different substrates and/or performing thermal treatments, which in turn reinforces the possibility of developing smart magnetic switching materials for electronic applications.

The current Argentinean legal system grants the right to education the status of a fundamental right. As it has been recognized in the Constitution, as well as, international statues, including human rights treaties; right to education has been considered a pillar of democratic society since the return of democracy in 1983. The relation between education and democratic society has been stressed many times by the Argentinean Courts.

Abstract

Prostate cancer (PCa) is the second most diagnosed cancer in men globally, and it is positioned as the fifth leading cause of cancer-related death in males. PCa aggressiveness and mortality is intricately linked to the metastatic disease, which is propelled by PCa stem cells (PCSCs). We have previously showcased the strong antitumoral role heme oxygenase-1 (HO-1) exerts in PCa. However, little is known about the association of HO-1 with the stemness capacity of PCa cells. In this work, we first performed clonogenic assays in PCa cells (PC3 and C4-2B) to assess colony formation, which evidenced a reduction on the stem-like properties of tumor cells treated with hemin (FDA approved drug and specific HO-1 inducer and activator). Next, we employed an indirect co-culture system of PCa cells (PC3) grown with bone progenitors (MC3T3) to emulate the dynamic PCa-bone crosstalk. PC3 cells were pre-treated or not with hemin. We performed comprehensive RNA-seq analyses and assessed the transcriptome of PC3 cells focusing on genes associated with stemness (CD44, CD133 and other pluripotency markers), metastasis and a stem-like signature previously identified by our group (ADAM15, BCL2L1, LTBR, MBNL2, SPINT1). PC3 cells that were co-cultured with MC3T3 displayed upregulated PCSC and pluripotency markers, as well as BCL2L1 and LTBR, when compared with PC3 cells cultured alone. Intriguingly, pre-treatment of PC3 cells with hemin prior to the co-culture impaired the upregulation of these genes, including the PCSC marker CD44, underscoring the protective effect of HO-1 induction against the pro-stemness effect triggered by bone progenitors secreted factors. Furthermore, we extended our analysis using PCa patients’ survival and transcriptomic publicly available data (TCGA-PRAD (n=565), SU2C-PRAD (n=444), FHCRC-PRAD (n=176)), which revealed that ADAM15, BCL2L1, LTBR and SPINT1 expression was higher in bone metastases vs. primary PCa (p<0.001). Moreover, POU5F1, ALDH1L2, ADAM15, BCL2L1, LTBR and SPINT1 presented higher expression in bone metastases vs. other sites of metastasis (p<0.01). We also performed multiple survival analyses including progression-free, metastasis-free, biochemical relapse-free and overall survival (TCGA-PRAD, GSE116918, GSE70770) which revealed that CD44 expression is associated with increased risk of metastasis (p<0.05), while patients with high expression of SOX2, ALDH1B1 and ALDH1L2 showed shorter times to biochemical relapse (p<0.05) Altogether, HO-1 expression modulates stemness and metastasis-related genes in PCa cells, steering tumor cells towards a more differentiated state and counteracting the pro-stemness effect inherent to the communication with bone progenitors. These findings support the antitumoral role of HO-1 in PCa and underscores CD44 as an HO-1-modulated compelling candidate for further investigations. Citation Format: Agustina Ayelen Sabater, Ines Achinelli, Pablo Sanchis, Nicolas Anselmino, Juan Bizzotto, Gaston Pascual, Rocio Seniuk, Javier Cotignola, Elba Vazquez, Geraldine Gueron, Ayelen Toro. Heme oxygenase 1 pulls the brake on stemness-induced properties by prostate cancer-bone crosstalk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2787.