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The purpose of this work is to analyze the fourth industrial revolution and its impact on current Latin American society based on a text published by the economist Klaus Schwab in 2016. The study was carried out through a lexicometric analysis, using the IRaMuTeQ textual analysis software, from the work of Schwab, and from various technical documents published by international organizations that seek to analyze the technological reality on the continent. The technology that was previously seen as a luxury for few, has become a reference in all areas of society, markets and industry depend on it. Likewise, we review some aspects in a small theoretical framework on the state of the art, the importance of training, its evolution over time and its role as a tool for present change. With this we were able to determine the importance of the work of Klaus Schwab in the current technological field., El propósito, es indagar acerca de la cuarta revolución industrial y su impacto en la sociedad actual latinoamericana a partir de un texto escrito por el economista Klaus Schwab en 2016. El estudio se realizó mediante una investigación lexicométrica, por medio del software de análisis textual IRaMuTeQ, de la obra de Schwab, y de diversos documentos técnicos publicados por organismos internacionales que buscan determinar la realidad tecnológica en el continente. Dichas técnicas que antes eran vistas como lujo para pocos, se ha convertido en una referencia en todos los ámbitos de la sociedad, los mercados y la industria dependen de ello. Asimismo, revisamos algunos aspectos en un pequeño marco teórico sobre el estado del arte, la importancia de la formación, su evolución en el tiempo y su papel como herramienta de cambio presente. Con todo ello se determinó la importancia de la obra de Klaus Schwab en el ámbito laboral actual.

The purpose of this work is to analyze the fourth industrial revolution and its impact on current Latin American society based on a text published by the economist Klaus Schwab in 2016. The study was carried out through a lexicometric analysis, using the IRaMuTeQ textual analysis software, from the work of Schwab, and from various technical documents published by international organizations that seek to analyze the technological reality on the continent. The technology that was previously seen as a luxury for few, has become a reference in all areas of society, markets and industry depend on it. Likewise, we review some aspects in a small theoretical framework on the state of the art, the importance of training, its evolution over time and its role as a tool for present change. With this we were able to determine the importance of the work of Klaus Schwab in the current technological field., El propósito, es indagar acerca de la cuarta revolución industrial y su impacto en la sociedad actual latinoamericana a partir de un texto escrito por el economista Klaus Schwab en 2016. El estudio se realizó mediante una investigación lexicométrica, por medio del software de análisis textual IRaMuTeQ, de la obra de Schwab, y de diversos documentos técnicos publicados por organismos internacionales que buscan determinar la realidad tecnológica en el continente. Dichas técnicas que antes eran vistas como lujo para pocos, se ha convertido en una referencia en todos los ámbitos de la sociedad, los mercados y la industria dependen de ello. Asimismo, revisamos algunos aspectos en un pequeño marco teórico sobre el estado del arte, la importancia de la formación, su evolución en el tiempo y su papel como herramienta de cambio presente. Con todo ello se determinó la importancia de la obra de Klaus Schwab en el ámbito laboral actual.

The purpose of this work is to analyze the fourth industrial revolution and its impact on current Latin American society based on a text published by the economist Klaus Schwab in 2016. The study was carried out through a lexicometric analysis, using the IRaMuTeQ textual analysis software, from the work of Schwab, and from various technical documents published by international organizations that seek to analyze the technological reality on the continent. The technology that was previously seen as a luxury for few, has become a reference in all areas of society, markets and industry depend on it. Likewise, we review some aspects in a small theoretical framework on the state of the art, the importance of training, its evolution over time and its role as a tool for present change. With this we were able to determine the importance of the work of Klaus Schwab in the current technological field., El propósito, es indagar acerca de la cuarta revolución industrial y su impacto en la sociedad actual latinoamericana a partir de un texto escrito por el economista Klaus Schwab en 2016. El estudio se realizó mediante una investigación lexicométrica, por medio del software de análisis textual IRaMuTeQ, de la obra de Schwab, y de diversos documentos técnicos publicados por organismos internacionales que buscan determinar la realidad tecnológica en el continente. Dichas técnicas que antes eran vistas como lujo para pocos, se ha convertido en una referencia en todos los ámbitos de la sociedad, los mercados y la industria dependen de ello. Asimismo, revisamos algunos aspectos en un pequeño marco teórico sobre el estado del arte, la importancia de la formación, su evolución en el tiempo y su papel como herramienta de cambio presente. Con todo ello se determinó la importancia de la obra de Klaus Schwab en el ámbito laboral actual.

Background Vafidemstat (ORY-2001) is a clinical stage inhibitor of the Lysine Specific Demethylase KDM1A in development for treatment of neurodegenerative and psychiatric diseases. KDM1A demethylates H3K4me1/2 and together with the histone deacetylases HDAC1/2, it forms part of co-repressor complexes recruited by zinc finger factors to control transcription. The exact role of KDM1A in neuroinflammation remained to be explored. Methods Compounds were administered p.o. gavage to mice with MOG35-55 induced experimental autoimmune encephalomyelitis or mice infected with Theiler’s murine encephalomyelitis virus. Immune cell infiltration was analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by ELISA. Genome wide gene expression in spinal cord and brain were analyzed by two-color microarray analysis and qRT-PCR. Results ORY-2001 improved the clinical score in mouse experimental autoimmune encephalomyelitis and in mice infected with the Theiler’s murine encephalomyelitis virus. The compound reduced lymphocyte egress and infiltration of immune cells in the spinal cord and prevented demyelination. ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the induction of the inflammatory gene expression signature in the central nervous system more potently. Gene expression changes and axonal protection in animals, and protection against glutamate excitoxicity in spinal cord explants support that ORY-2001 has neuroprotective qualities. Conclusions ORY-2001 exerts therapeutic activity in two mouse models of multiple sclerosis. The anti-inflammatory properties of ORY-2001 are being tested in a Phase IIa clinical trial in patients with relapse remitting and secondary progressive multiple sclerosis, and in severely ill COVID-19 patients at risk for acute respiratory distress syndrome.

Lysine specific demethylase 1 (LSD1; also known as KDM1A), is an epigenetic modulator that modifies the histone methylation status. KDM1A forms a part of protein complexes that regulate the expression of genes involved in the onset and progression of diseases such as cancer, central nervous system (CNS) disorders, viral infections, and others. Vafidemstat (ORY-2001) is a clinical stage inhibitor of KDM1A in development for the treatment of neurodegenerative and psychiatric diseases. However, the role of ORY-2001 targeting KDM1A in neuroinflammation remains to be explored. Here, we investigated the effect of ORY-2001 on immune-mediated and virus-induced encephalomyelitis, two experimental models of multiple sclerosis and neuronal damage. Oral ad-ministration of ORY-2001 ameliorated clinical signs, reduced lymphocyte egress and infiltration of immune cells into the spinal cord, and prevented demyelination. Interestingly, ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the inflammatory gene expression signature characteristic ofEAE in the CNS of mice more potently. In addition, ORY-2001 induced gene expression changes con-cordant with a potential neuroprotective function in the brain and spinal cord and reduced neuronal glutamate excitotoxicity-derived damage in explants. These results pointed to ORY-2001 as a promising CNS epigenetic drug able to target neuroinflammatory and neurodegenerative diseases and provided preclinical support for the subsequent design of early-stage clinical trials.

This work investigates some of the possibilities of opinion mining studies, or sentiment analysis, in audiovisual materials present on the Internet. From the comments made on YouTube to an interview with Paulo Freire, we have been able to extract trends and guidelines from a historical series of comments between the period 2007-2019. Thanks to the use of some R packages and the analysis of the metrics provided by YouTube, it has been possible to verify that the comments were following a trend that clearly coincided with key political moments in Brazil. The comments were influenced by opinion groups that sought to destabilize and despise any element contrary to their ideas., Este trabajo indaga algunas de las posibilidades de los estudios de minería de opinión, o análisis de sentimientos, en materiales audiovisuales presentes en Internet. A partir de los comentarios realizados en YouTube a una entrevista a Paulo Freire, hemos podido extraer tendencias y pautas de una serie histórica de comentarios entre el periodo 2007-2019. Gracias al uso de algunos paquetes de R y al análisis de las métricas proporcionadas por YouTube, ha sido posible comprobar que los comentarios seguían una tendencia que coincidía claramente con momentos políticos clave en Brasil. Los comentarios estaban influidos por grupos de opinión que buscaban desestabilizar y despreciar cualquier elemento contrario a sus ideas.

[Purpose] Iadademstat is a novel, highly potent, and selective inhibitor of LSD1 (KDM1A), with preclinical in vitro and in vivo antileukemic activity. This study aimed to determine safety and tolerability of iadademstat as monotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML)., [Methods] This phase I, nonrandomized, open-label, dose-escalation (DE), and extension-cohort (EC) trial included patients with R/R AML and evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antileukemic activity of this orally bioavailable first-in-class lysine-specific demethylase 1 inhibitor., [Results] Twenty-seven patients were treated with iadademstat on days 1 to 5 (5-220 µg/m2/d) of each week in 28-day cycles in a DE phase that resulted in a recommended dose of 140 µg/m2/d of iadademstat as a single agent. This dose was chosen to treat all patients (n = 14) in an EC enriched with patients with MLL/KMT2A-rearranged AML. Most adverse events (AEs) were as expected in R/R AML and included myelosuppression and nonhematologic AEs, such as infections, asthenia, mucositis, and diarrhea. PK data demonstrated a dose-dependent increase in plasma exposure, and PD data confirmed a potent time- and exposure-dependent induction of differentiation biomarkers. Reductions in blood and bone marrow blast percentages were observed, together with induction of blast cell differentiation, in particular, in patients with MLL translocations. One complete remission with incomplete count recovery was observed in the DE arm., [Conclusion] Iadademstat exhibits a good safety profile together with signs of clinical and biologic activity as a single agent in patients with R/R AML. A phase II trial of iadademstat in combination with azacitidine is ongoing (EudraCT No.: 2018-000482-36).