Machine learning prediction of side effects for drugs in clinical trials.

Early and accurate detection of side effects is critical for the clinical success of drugs under development. Here, we aim to predict unknown side effects for drugs with a small number of side effects identified in randomized controlled clinical trials. Our machine learning framework, the geometric self-expressive model (GSEM), learns globally optimal self-representations for drugs and side effects from pharmacological graph networks. We show the usefulness of the GSEM on 505 therapeutically diverse drugs and 904 side effects from multiple human physiological systems. Here, we also show a data integration strategy that could be adopted to improve the ability of side effect prediction models to identify unknown side effects that might only appear after the drug enters the market.

Machine learning and network medicine approaches for drug repositioning for COVID-19.

We present two machine learning approaches for drug repurposing. While we have developed them for COVID-19, they are disease-agnostic. The two methodologies are complementary, targeting SARS-CoV-2 and host factors, respectively. Our first approach consists of a matrix factorization algorithm to rank broad-spectrum antivirals. Our second approach, based on network medicine, uses graph kernels to rank drugs according to the perturbation they induce on a subnetwork of the human interactome that is crucial for SARS-CoV-2 infection/replication. Our experiments show that our top predicted broad-spectrum antivirals include drugs indicated for compassionate use in COVID-19 patients; and that the ranking obtained by our kernel-based approach aligns with experimental data. Finally, we present the COVID-19 repositioning explorer (CoREx), an interactive online tool to explore the interplay between drugs and SARS-CoV-2 host proteins in the context of biological networks, protein function, drug clinical use, and Connectivity Map. CoREx is freely available at: https://paccanarolab.org/corex/.

Dosimetry in Digital Breast Tomosynthesis Evaluated by Monte Carlo Technique.

ABSTRACT: The influence of the angular deviation of the tube during digital breast tomosynthesis (DBT) acquisition to the dose in the examined breast and in other organs and tissues is not well known. In this work, the Monte Carlo method was used with an adult female virtual anthropomorphic phantom to investigate the impact of this angular variation on the breast dose. The absorbed dose in the examined breast was normalized by the air kerma, which resulted in an absorbed dose coefficient (DT/Kair) for the breast. The absorbed dose in each organ was normalized by the glandular dose in the breast, resulting in the relative organ dose (ROD). An adult female virtual anthropomorphic phantom (FSTA_M50_H50) was incorporated into a scenario containing tomosynthesis equipment with Mo/Mo, Mo/Rh, and W/Rh target/filter combinations and tube voltages of 28 kV. The comparison between the results of the simulations considering digital mammography (DM) and DBT data showed that the DT/Kair values for the examined breast obtained with the DBT parameters were up to 24 times higher than with the DT/Kair obtained with DM parameters. A DT/Kair of 0.97 × 10-1 mGy mGy-1 was obtained in a DBT exam of the right breast. Considering the other organs, the highest ROD values were observed in the thyroid (6.45 × 10-4), eyes (3.87 × 10-4), liver (1.95 × 10-5), and eye lenses (3.21 × 10-3). A variation in the absorbed dose values for the breast and other organs was observed for all projections different from 0°.

Polícia, antropometria e datiloscopia: história transnacional dos sistemas de identificação, do rio da Prata ao Brasil / Police, anthropometry, and fingerprinting: the transnational history of identification systems from Rio de la Plata to Brazil

Resumo O artigo estuda a circulação transnacional de métodos de identificação de pessoas na América do Sul. Analisa a implementação do sistema antropométrico nas polícias de Argentina, Uruguai e Brasil a partir da última década do século XIX e as críticas que esse sistema recebeu no momento de consolidação da datiloscopia na região, no início do século XX. Em um contexto de intenso trânsito mundial de ideias, especialistas e tecnologias policiais, o bertillonage foi discutido e hibridado na América Latina. A história do sistema antropométrico nas repúblicas do rio da Prata e do Brasil envolveu diversas viagens de médicos, juristas e policiais a Paris, debates sobre sua adequação às realidades locais e a constituição de uma aberta polêmica sobre as técnicas de identificação.

Abstract The article explores the transnational circulation of methods for identifying people in South America. It analyzes both the implementation of the anthropometric system at police departments in Argentina, Uruguay, and Brazil starting in the 1890s, as well as the criticisms that were aimed at this method when fingerprinting took hold in the region in the early twentieth century. In a context of a heavy worldwide flow of ideas, experts, and technologies in policing, “bertillonage” was discussed and underwent hybridization in Latin America. The history of the anthropometric system in these three countries involved many travels by physicians, jurists, and police agents to Paris, debates over its suitability to local contexts, and an open controversy about identification techniques.

Police, anthropometry, and fingerprinting: the transnational history of identification systems from Rio de la Plata to Brazil. / Polícia, antropometria e datiloscopia: história transnacional dos sistemas de identificação, do rio da Prata ao Brasil.

The article explores the transnational circulation of methods for identifying people in South America. It analyzes both the implementation of the anthropometric system at police departments in Argentina, Uruguay, and Brazil starting in the 1890s, as well as the criticisms that were aimed at this method when fingerprinting took hold in the region in the early twentieth century. In a context of a heavy worldwide flow of ideas, experts, and technologies in policing, "bertillonage" was discussed and underwent hybridization in Latin America. The history of the anthropometric system in these three countries involved many travels by physicians, jurists, and police agents to Paris, debates over its suitability to local contexts, and an open controversy about identification techniques.

Structural divergence of plant TCTPs.

The Translationally Controlled Tumor Protein (TCTP) is a highly conserved protein at the level of sequence, considered to play an essential role in the regulation of growth and development in eukaryotes. However, this function has been inferred from studies in a few model systems, such as mice and mammalian cell lines, Drosophila and Arabidopsis. Thus, the knowledge regarding this protein is far from complete. In the present study bioinformatic analysis showed the presence of one or more TCTP genes per genome in plants with highly conserved signatures and subtle variations at the level of primary structure but with more noticeable differences at the level of predicted three-dimensional structures. These structures show differences in the "pocket" region close to the center of the protein and in its flexible loop domain. In fact, all predictive TCTP structures can be divided into two groups: (1) AtTCTP1-like and (2) CmTCTP-like, based on the predicted structures of an Arabidopsis TCTP and a Cucurbita maxima TCTP; according to this classification we propose that their probable function in plants may be inferred in principle. Thus, different TCTP genes in a single organism may have different functions; additionally, in those species harboring a single TCTP gene this could carry multiple functions. On the other hand, in silico analysis of AtTCTP1-like and CmTCTP-like promoters suggest that these share common motifs but with different abundance, which may underscore differences in their gene expression patterns. Finally, the absence of TCTP genes in most chlorophytes with the exception of Coccomyxa subellipsoidea, indicates that other proteins perform the roles played by TCTP or the pathways regulated by TCTP occur through alternative routes. These findings provide insight into the evolution of this gene family in plants.

Muertes por violencias en Argentina: dos estudios de caso en los Municipios de Venado Tuerto y San Rafael / Violence-related deaths in Argentina: two case studies in the cities of Venado Tuerto and San Rafael

Este artículo ofrece los resultados de un estudio comparado de dos municipios: Venado Tuerto y San Rafael de la República Argentina, que presentaron tendencias diferentes en relación a las tasas de homicidios por armas de fuego. La metodología combinó dos estrategias de análisis: por un lado, entrevistas semi-estructuradas con informantes clave (funcionarios municipales y provinciales en distintas áreas de la gestión, y referentes de organizaciones no gubernamentales) y, por el otro, grupos focales con actores vinculados a la atención médica, la educación y las instituciones religiosas. Los resultados sugieren una distancia muy corta entre las ciudades en las cuales las tasas han aumentado y aquellas en las que han disminuido. La diferencia más significativa es que en Venado Tuerto se encontró una mayor fragilidad en las instituciones públicas, por la falta de articulación entre las mismas. En tanto en San Rafael, los actores entrevistados atribuyen el bajo nivel de conflictividad a una red de prevención de violencias en la cual se coordinan agencias provinciales y municipales. Sin tratarse, ni Venado Tuerto, ni San Rafael, de ciudades violentas en los niveles latinoamericanos más truculentos, ambas muestran resultados diferentes que apuntan directamente a la posibilidad de juntar a las instituciones en un entramado de conversaciones, acuerdos y políticas en conjunto.

This article presents the results of a comparative study of two Argentinian cities, namely Venado Tuerto and San Rafael, which revealed different trends in the rates of firearm-related homicides. The methodology combined two strategies of analysis: semi-structured interviews with key informants (municipal and provincial government agents in different areas of management, as well as members of non-governmental organizations) and focus groups with actors involved in medical care, education, and religious institutions. The results suggest little difference between cities in which rates have increased and those in which rates have decreased. The most significant difference was that in Venado Tuerto a greater fragility of public institutions was observed due to the lack of articulation between such institutions. In San Rafael, the actors interviewed attribute the low level of conflict to a violence prevention network in which provincial and municipal agencies interact. Although neither city is violent at the most critical Latin American levels, the different results shown in Venado Tuerco and San Rafael indicate the possibility of bringing institutions together in a joint framework of conversations, agreements and policies.

[Violence-related deaths in Argentina: two case studies in the cities of Venado Tuerto and San Rafael]. / Muertes por violencias en Argentina: dos estudios de caso en los Municipios de Venado Tuerto y San Rafael.

This article presents the results of a comparative study of two Argentinian cities, namely Venado Tuerto and San Rafael, which revealed different trends in the rates of firearm-related homicides. The methodology combined two strategies of analysis: semi-structured interviews with key informants (municipal and provincial government agents in different areas of management, as well as members of non-governmental organizations) and focus groups with actors involved in medical care, education, and religious institutions. The results suggest little difference between cities in which rates have increased and those in which rates have decreased. The most significant difference was that in Venado Tuerto a greater fragility of public institutions was observed due to the lack of articulation between such institutions. In San Rafael, the actors interviewed attribute the low level of conflict to a violence prevention network in which provincial and municipal agencies interact. Although neither city is violent at the most critical Latin American levels, the different results shown in Venado Tuerco and San Rafael indicate the possibility of bringing institutions together in a joint framework of conversations, agreements and policies.

Juan César García y el movimiento latinoamericano de medicina social: notas sobre una trayectoria de vida / Juan César García and the Latin American social medicine movement: notes on a life trajectory

Este artículo analiza la trayectoria de Juan César García, uno de los referentes del movimiento latinoamericano de medicina social. La pregunta que desencadenó este trabajo buscó indagar el momento y las circunstancias en que García incorporó para sí la matriz del marxismo para pensar los problemas de salud. De esta manera, siguiendo los lineamientos metodológicos propuestos por Pierre Bourdieu, utilizamos la noción de "trayectoria de vida" para reconstruir un recorrido vital que se bifurca en varias rutas: de su Necochea natal a la ciudad de La Plata, desde allí hasta Santiago de Chile y, finalmente, sus innumerables viajes desde Washington hacia gran parte de América Latina. Para ello, realizamos entrevistas semiestructuradas con informantes clave: familiares, amigos y colegas de Argentina, Brasil, Ecuador y Cuba. Asimismo, analizamos los títulos de su biblioteca personal, donada a la fundación internacional que lleva su nombre, y documentos de distintos archivos particulares.

This article analyzes the trajectory of Juan César García, one of the referential figures of the Latin American social medicine movement. The question that inspired this work sought to uncover in what moment and in what circumstances García incorporated a Marxist framework into his way of thinking about health problems. Following the methodological guidelines proposed by Pierre Bourdieu, we used the concept of "life trajectories" to reconstruct a life path that divides in various directions: from his birthplace in Necochea to the city of La Plata, from there to Santiago de Chile and, finally, his numerous trips from Washington DC to a large part of Latin America. In order to trace these paths, we carried out semi-structured interviews with key informants: family members, friends, and colleagues from Argentina, Brazil, Ecuador and Cuba. We also analyzed the books included in his personal library, donated after his death to the international foundation that carries his name, and documents from different personal archives.

Médicos y policías durante la epidemia de fiebre amarilla (Buenos Aires, 1871) / Police officers and medical doctors during the yellow fever epidemic (Buenos Aires, 1871)

Este trabajo analiza la actuación de médicos y policías durante la epidemia de fiebre amarilla que tuvo lugar en la ciudad de Buenos Aires en 1871. Aunque las embestidas de enfermedades infectocontagiosas fueron recurrentes durante el siglo XIX, la epidemia de fiebre amarilla constituye un quiebre, no solo por sus dimensiones cuantitativas y por los efectos materiales sobre la ciudad, sino también por las querellas que suscitó entre discursos en pugna. En particular, se intenta mostrar aquí cómo las figuras de los médicos y los policías fueron posicionadas en relación al tema del héroe y del sacrificado en cumplimiento del deber.

This paper examines the action of medical doctors and policemen during the yellow fever epidemic in Buenos Aires (1871). Even though during the XIX century epidemics were frequent, the yellow fever one constitutes a break, not only because of its scope and material effects on the city, but also because it opened a crisis of hegemonic discourses. In particular, the paper scrutinizes the effects of the yellow fever epidemics on the figures of doctors and policemen, who were redesigned in light of tropes of heroism and sacrifice.

Mens sana in corpore sano: José M. Ramos Mejía and the medicalization of the argentine society / Mens sana in corpore sano: José M. Ramos Mejía and the medicalization of the argentine society

Este artículo trata sobre un período de la historia argentina en el cual la "mirada médica", a través de un grupo de prestigiosos intelectuales, se convirtió en una clave de interpretación de la sociedad argentina. El análisis gira en torno a la obra de uno de los médicos higienistas más influyentes, José María Ramos Mejía, deteniéndose especialmente en su libro más famoso: Las multitudes argentinas (1899). La hipótesis principal que recorre el texto es la siguiente: la medicalización de la sociedad, acentuada luego de las epidemias de cólera y fiebre amarilla de mediados del siglo XIX, ofreció a las elites públicas la posibilidad de construir dominios legítimos de intervención estatal. Intromisiones del Estado en la vida privada que, además de ser algo resistidas por la población, entraban en tensión con los principios teóricos del liberalismo que los propios miembros de la elite defendían...(AU)

Mens sana in corpore sano: José M. Ramos Mejía and the medicalization of the argentine society / Mens sana in corpore sano: José M. Ramos Mejía and the medicalization of the argentine society

Este artículo trata sobre un período de la historia argentina en el cual la "mirada médica", a través de un grupo de prestigiosos intelectuales, se convirtió en una clave de interpretación de la sociedad argentina. El análisis gira en torno a la obra de uno de los médicos higienistas más influyentes, José María Ramos Mejía, deteniéndose especialmente en su libro más famoso: Las multitudes argentinas (1899). La hipótesis principal que recorre el texto es la siguiente: la medicalización de la sociedad, acentuada luego de las epidemias de cólera y fiebre amarilla de mediados del siglo XIX, ofreció a las elites públicas la posibilidad de construir dominios legítimos de intervención estatal. Intromisiones del Estado en la vida privada que, además de ser algo resistidas por la población, entraban en tensión con los principios teóricos del liberalismo que los propios miembros de la elite defendían...