Avances de la bioinformática en Costa Rica: vista retrospectiva y perspectivas / Bioinformatics advances in Costa Rica: retrospective view and perspectives

Resumen Introducción: La disciplina científica de la bioinformática tiene el potencial de generar aplicaciones innovadoras para las sociedades humanas. Costa Rica, pequeña en tamaño y población en comparación con otros países de América Latina, ha ido adoptando la disciplina de manera progresiva. El reconocer los avances permite determinar hacia dónde puede dirigirse el país en este campo, así como su contribución a la región latinoamericana. Objetivo: En este manuscrito se reporta evidencia de la evolución de la bioinformática en Costa Rica, para identificar debilidades y fortalezas que permitan definir acciones a futuro. Métodos: Se realizaron búsquedas en bases de datos de publicaciones científicas y repositorios de secuencias, así como información de actividades de capacitación, redes, infraestructura, páginas web y fuentes de financiamiento. Resultados: Se observan avances importantes desde el 2010, incluyendo un aumento en oportunidades de entrenamiento y número de publicaciones, aportes significativos a las bases de datos de secuencias y conexiones por medio de redes. Sin embargo, ciertas áreas, como la masa crítica y la financiación requieren más desarrollo. La comunidad científica y sus patrocinadores deben promover la investigación basada en bioinformática, invertir en la formación de estudiantes de posgrado, aumentar la formación de profesionales, crear oportunidades laborales para carreras en bioinformática y promover colaboraciones internacionales a través de redes. Conclusiones: Se sugiere que para experimentar los beneficios de las aplicaciones de la bioinformática se deben fortalecer tres aspectos clave: la comunidad científica, la infraestructura de investigación y las oportunidades de financiamiento. El impacto de tal inversión sería el desarrollo de proyectos ambiciosos pero factibles y colaboraciones extendidas dentro de la región latinoamericana. Esto permitiría realizar contribuciones significativas para abordar los desafíos globales y la aplicación de nuevos enfoques de investigación, innovación y transferencia de conocimiento para el desarrollo de la economía, dentro de un marco de ética de la investigación.

Abstract Introduction: The scientific discipline of bioinformatics has the potential to generate innovative applications for human societies. Costa Rica, small in size and population compared to other Latin American countries, has been progressively adopting the discipline. Recognizing progress makes it possible to determine where the country can go in this field, as well as its contribution to the Latin American region. Objective: This manuscript reports evidence of the evolution of bioinformatics in Costa Rica, to identify weaknesses and strengths allowing future actions plans. Methods: We searched databases of scientific publications and sequence repositories, as well as information on training activities, networks, infrastructure, web pages and funding sources. Results: Important advances have been observed since 2010, such as increases in training opportunities and the number of publications, significant contributions to the sequence databases and connections through networks. However, areas such as critical mass and financing require further development. The scientific community and its sponsors should promote bioinformatics-based research, invest in graduate student training, increase professional training, create career opportunities in bioinformatics, and promote international collaborations through networks. Conclusions: It is suggested that in order to experience the benefits of bioinformatics applications, three key aspects must be strengthened: the scientific community, the research infrastructure, and funding opportunities. The impact of such investment would be the development of ambitious but feasible projects and extended collaborations within the Latin American region and abroad. This would allow significant contributions to address global challenges and the implementation of new approaches to research, innovation and knowledge transfer for the development of the economy, within an ethics of research framework.

Establishment of international autoantibody reference standards for the detection of autoantibodies directed against PML bodies, GW bodies, and NuMA protein.

Objectives: Reference materials are important in the standardization of autoantibody testing and only a few are freely available for many known autoantibodies. Our goal was to develop three reference materials for antibodies to PML bodies/multiple nuclear dots (MND), antibodies to GW bodies (GWB), and antibodies to the nuclear mitotic apparatus (NuMA). Methods: Reference materials for identifying autoantibodies to MND (MND-REF), GWB (GWB-REF), and NuMA (NuMA-REF) were obtained from three donors and validated independently by seven laboratories. The sera were characterized using indirect immunofluorescence assay (IFA) on HEp-2 cell substrates including two-color immunofluorescence using antigen-specific markers, western blot (WB), immunoprecipitation (IP), line immunoassay (LIA), addressable laser bead immunoassay (ALBIA), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation-mass spectrometry (IP-MS). Results: MND-REF stained 6-20 discrete nuclear dots that colocalized with PML bodies. Antibodies to Sp100 and PML were detected by LIA and antibodies to Sp100 were also detected by ELISA. GWB-REF stained discrete cytoplasmic dots in interphase cells, which were confirmed to be GWB using two-color immunofluorescence. Anti-Ge-1 antibodies were identified in GWB-REF by ALBIA, IP, and IP-MS. All reference materials produced patterns at dilutions of 1:160 or greater. NuMA-REF produced fine speckled nuclear staining in interphase cells and staining of spindle fibers and spindle poles. The presence of antibodies to NuMA was verified by IP, WB, ALBIA, and IP-MS. Conclusions: MND-REF, GWB-REF, and NuMA-REF are suitable reference materials for the corresponding antinuclear antibodies staining patterns and will be accessible to qualified laboratories.

Using adaptive genetic algorithms combined with high sensitivity single cell-based technology to detect bladder cancer in urine and provide a potential noninvasive marker for response to anti-PD1 immunotherapy.

OBJECTIVE: To use adaptive genetic algorithms (AGA) in combination with single-cell flow cytometry technology to develop a noninvasive test to detect bladder cancer. MATERIALS AND METHODS: Fifty high grade, cystoscopy confirmed, superficial bladder cancer patients, and 15 healthy donor early morning urine samples were collected in an optimized urine collection media. These samples were then used to develop an assay to distinguish healthy from cancer patients' urine using AGA in combination with single-cell flow cytometry technology. Cell recovery and test performance were verified based on cystoscopy and histology for both bladder cancer determination and PD-L1 status. RESULTS: Bladder cancer patients had a significantly higher percentage of white blood cells with substantial PD-L1 expression (P< 0.0001), significantly increased post-G1 epithelial cells (P < 0.005) and a significantly higher DNA index above 1.05 (P < 0.05). AGA allowed parameter optimization to differentiate normal from malignant cells with high accuracy. The resulting prediction model showed 98% sensitivity and 87% specificity with a high area under the ROC value (90%). CONCLUSIONS: Using single-cell technology and machine learning; we developed a new assay to distinguish bladder cancer from healthy patients. Future studies are planned to validate this assay.

Pandemia y ansiedad social / Pandemic and social anxiety

La pandemia del COVID-19 ha generado una crisis en el ser humano y en su contexto de cómo vivir ante lo desconocido, estableciendo parámetros de un desequilibrio de la salud mental y una reinvención de sostenimiento imaginario de lo incomprensible, desarticulando los esquemas socialmente aceptados y articulando modelos nuevos que le permitan al hombre continuar con la vida, encontrando formas de fortalecer al Eros y disminuir la proliferación de Thanatos. (AU)

The COVID-19 pandemic has generated a crisis in the human being and in its context of how to live in the face of the unknown, establishing parameters of an imbalance of mental health and a reinvention of imaginary maintenance of the incomprehensible, disarticulating socially accepted schemes and articulating new models that allow man to continue with life, finding ways to strengthen Eros and decrease the proliferation of Thanatos (AU)

¿El siglo de las luces? / The lights century?

El siglo de las luces es una reflexión sobre el excesivo racionalismo de la medicina actual frente a los problemas del inconsciente dejando de lado el análisis del inconsciente del sujeto y la posibilidad del sujeto de mirarse así mismo.

This paper is a reflection about the excessive rationalism of current medici-ne against the unconscious problems leaving aside the analysis of the un-conscious of the person and the possibility of the person to look at himself.

Emerging microRNAs in cancer diagnosis, progression, and immune surveillance.

MicroRNAs (miRNAs) are small noncoding RNAs that function in post-transcriptional regulation of gene expression. Dysregulation of miRNAs has been reported in different stages of cancer development and progression. This dysregulation results in different miRNA profiles between cancer and normal tissues. Many studies have shown a significant correlation between miRNA profile and cancer diagnosis and prognosis. Additionally, since a single miRNA regulates multiple mRNA targets, miRNAs dysregulation can affect several pathways involved in cancer development. Finally, due to their regulatory role in immune cell development, many recent studies have reported that certain miRNAs play key roles in cancer immunology. In this brief review, we discuss the role of miR-21 and miR-375 in the RAS pathway as well as their role in cancer diagnosis and progression, along with the role of other select miRNAs in cancer immune surveillance.

Implicancias en la actividad física y la salud del Programa CicloRecreoVía en Chile / Physical activity and health implications of the CicloRecreoVia program in Chile

Background: With approximately 66% of the population overweight and nearly 90% with sedentary lifestyles, obesity has become a major public health problem in Chile. Thus, in the last fifteen years health policies have promoted active lifestyles. An interesting initiative in this context is the CicloRecreoVia program, which closes a set of public streets on Sunday mornings, allowing people to carry out PA in streets free of vehicles. Aim: To characterize PA and mobility patterns of participants of the CicloRecreoVía program in Santiago. Material and Methods: 401 participants of five circuits of the CicloRecreoVia surveyed on the type, frequency and durantion of the PA carried out, their daily mobility habits, motivations for attending the CicloRecreoVia, self-perceived health condition, among other aspects. Results: Participants spent 113 minutes in the CicloRecreoVia, 77% declared walking or bicycling at least 10 minutes per day and 56.7% traveled actively (bicycling or walking) at least four times per week. Finally, 69.1% perceived their health condition "better" or "much better" than one year ago. In addition, it was noted that CicloRecreoVías attracted different type of participants depending on their location in the city. Conclusions: In line with previous studies, most users achieve about 75% of the weekly PA recommended by attending the CicloRecreoVía, and the main motivations to attend the program were to make PA, to be outdoor and to socialize. As a result, the CicloRecreoVía has the potential to become an effective public nationwide health policy to combat obesity.

Building a Personalized Cancer Treatment System.

This paper reports the process by which a personalized cancer treatment system was built, following a user-centered approach. We give some background on personalized cancer treatment, the particular tumor chemosensitivity assay supported by the system, as well as some quality and legal issues related to such health systems. We describe how Contextual Design was applied when building the system. Contextual design is a user-centered design technique involving seven steps. We also provide some details about the system implementation. Finally, we explain how the Think-Aloud protocol and Heuristic Evaluation methods were used to evaluate the system and report its results. A qualitative assessment from the users perspective is also provided. Results from the heuristic evaluation indicate that only one of ten heuristics was missing from the system, while five were partially covered and four were fully covered.

Outdoor gyms in Santiago: urban distribution and effects on physical activity

Abstract: Aims To put together a registry of the location of all existing outdoor gyms (OGs) in Santiago, Chile, and establish a profile of the users of these gyms. Methods: All OGs in Santiago located in public spaces were identified and geo-referenced, and an accessibility analysis of them was carried out. A total of 1,023 users of OGs were surveyed (71% men, average age 31.5 years old, SD =16.6), about the frequency of use of OGs, amount of time spent using them, transportation habits, motivation for usage, and their perceptions regarding their own health, among other questions. In addition, each person's neck circumference was measured. Results There are 1,981 OGs in the city squares, sidewalks and parks, mostly located in poorest areas of the city. Most OG users live less than one kilometer away from an OG. Discussion: In line with international studies, this research demonstrates that OGs have positive collateral effects, as they not only contribute to users to increase their physical activity, but also because they attract people with sedentary lifestyles to make physical activity. This, in turn, might contribute to make urban areas more livable and safer, for they bring new "eyes to the street" and permit to use cities' under-occupied public spaces. Conclusion: The proliferation of outdoor gyms should be regarded as an opportunity for public health policies aimed at tackling the obesity problem and increasing the physical activity of people.(AU)

Biopiracy of natural products and good bioprospecting practice.

BACKGROUND: Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge. METHODS: Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed 'PhytCancer -Phytotherapy to Fight Cancer' (www.phyt-cancer.uni-mainz.de). As a starting point, we have chosen the topic "biopiracy", since we feel this is of pragmatic significance for scientists working with medicinal plants. RESULTS: It was argued that the patenting of herbs or natural products by pharmaceutical corporations disregarded the ownership of the knowledge possessed by the indigenous communities on how these substances worked. Despite numerous court decisions in U.S.A. and Europe, several international treaties, (e.g. from United Nations, World Health Organization, World Trade Organization, the African Unity and others), sharing of a rational set of benefits amongst producers (mainly pharmaceutical companies) and indigenous communities is yet a distant reality. In this paper, we present an overview of the legal frameworks, discuss some exemplary cases of biopiracy and bioprospecting as excellent forms of utilization of natural resources. CONCLUSIONS: We suggest certain perspectives, by which we as scientists, may contribute towards prevention of biopiracy and also to foster the fair utilization of natural resources. We discuss ways, in which the interests of indigenous people especially from developing countries can be secured.

Percepción de la señalización y orientación espacial de los usuarios de tres complejos hospitalarios de Santiago, Chile / A survey about client orientation and wayfinding in Chilean hospitals

Background: Sense of orientation in hospitals can be tricky considering the large extension of buildings and the inadequate signage. Aim: To report some of the findings of a larger research project on wayfinding and patient navigation in Chilean hospitals. Material and Methods: Five hundred nine hospital users waiting for attention in three hospitals were contacted and asked to answer a survey that lasted 10 minutes, about wayfinding and sense of orientation within the hospital. Results: Users declared to have a good opinion of existing signage in the three hospitals analyzed as well as their architectural organization in terms of their capacity to orient people. However, the vast majority of users asked for directions to navigate within the hospital to staff and medical personnel. Conclusions: Patient navigation problems are imposing a great “hidden” cost to hospitals management due to missed appointments.

Where is my car? examining wayfinding behavior in a parking lot

This article examines wayfinding behavior in an extended parking lot belonging to one of the largest shopping malls in Santiago, Chile. About 500 people were followed while going to the mall and returning from it, and their trajectories were mapped and analyzed. The results indicate that inbound paths were, in average, 10% shorter that outbound paths, and that people stopped three times more frequently when leaving the mall than when accessing it. It is argued that these results are in line with previous research on the subject, which stress the importance of environmental information in shaping people`s behavior.

En los ojos de Guliver: información contextual y sentido de orientación / In Gulliver's eyes: contextual information and sense of orientation

Este manuscrito estudia el sentido de orientación de las personas en situaciones en que existe información de tipo contextual, que permite a las personas a ver locaciones muy distantes. Para ello se preguntó a 133 individuos indicar la ubicación de cinco hitos próximos y lejanos de la ciudad de Valparaíso, en 2 situaciones distintas: miradores urbanos y lugares en el medio de la trama urbana en el que la visión de información contextual no es posible. Los resultados mostraron que no existía una asociación entre la Precisión Promedio por Persona y el sexo, edad, o el grado familiaridad, pero que sí con el lugar donde se habían hecho estas estimaciones.

This manuscript examines how people gain a sense of orientation in scenarios where large-scale, contextual information is available. Two locations of the city of Valparaiso where one can see the entire city from the heights were selected for an experiment, as well as two areas in the middle of the urban grid where no large-scale information was available. A total of 133 people were asked to point to five non-visible landmarks in these scenarios and their estimations were compared with the real position of each target. Results showed no association between this value and people's gender, age or familiarity with the neighborhood. However, a positive relationship was found between this value and the places in which estimates were made.

Straight to the point: how people encode linear discontinuations

Spatial discontinuations, as those found in cities and buildings, are everyday events. But, how do we encode and classify such misalignments? This is the topic of this paper. Twenty participants were asked to classify a total of 51 icons showing an upward-moving line being misaligned to the right, left and straight down. The results show that subjects were very sensitive to slight discontinuations occurring to vertical lines and that there was not exact symmetry between the left and right axis, meaning that the pieces slightly misaligned to the left were encoded differently than those misaligned to the right.

miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells.

Toxicity and relapses from the immunochemotherapy used to treat chronic lymphocytic leukemia (CLL) prompt continued interest in gentle but effective targeted treatment options for the mainly elderly population suffering from this disease. Here, we report the definition of critical CLL cell survival pathways that can be targeted by ectopic reexpression of the miRNA genes miR-130a and miR-143 which are widely downregulated in CLL. Notably, miR-130a inhibited autophagy by reducing autophagosome formation, an effect mediated by downregulation of the genes ATG2B and DICER1, the latter of which is a major component of the miRNA silencing machinery. In support of the concept of a fundamental connection between miRNA disregulation and altered autophagic flux in this cancer, we showed that RNA interference-mediated knockdown of DICER1 expression was sufficient to reduce autophagy in primary or established cultures of CLL cells. Together, our findings show that miR-130a modulates cell survival programs by regulating autophagic flux, and they define roles for miR-130a and Dicer1 in a regulatory feedback loop that mediates CLL cell survival.

Microglia isolated from patients with glioma gain antitumor activities on poly (I:C) stimulation.

The role of microglia, the brain-resident macrophages, in glioma biology is still a matter of debate. Clinical observations and in vitro studies in the mouse model indicate that microglia and macrophages that infiltrate the brain tumor tissue in high numbers play a tumor-supportive role. Here, we provide evidence that human microglia isolated from brain tumors indeed support tumor cell growth, migration, and invasion. However, after stimulation with the Toll-like receptor 3 agonist poly (I:C), microglia secrete factors that exerted toxic and suppressive effects on different glioblastoma cell lines, as assessed in cytotoxicity, migration, and tumor cell spheroid invasion assays. Remarkably, these effects were tumor-specific because the microglial factors impaired neither growth nor viability of astrocytes and neurons. Culture supernatants of tumor cells inhibited the poly (I:C) induction of this microglial M1-like, oncotoxic profile. Microglia stimulation before coculture with tumor cells circumvented the tumor-mediated suppression, as demonstrated by the ability to kill and phagocytose glioma cells. Our results show, for the first time to our knowledge, that human microglia exert tumor-supporting functions that are overridden by tumor-suppressing activities gained after poly (I:C) stimulation.

Acerca de la racionalidad y la irracionalidad de nuestras decisiones / About rationality and irrationality of our decisions

Tal como sugiere su nombre, este texto postula que el comportamiento humano es fundamentalmente irracional, esto es, está gobernado por aspectos emocionales difíciles de explicar de acuerdo a explicaciones lógicas. Esta "irracionalidad" esta, no obstante lejos de ser aleatoria y estrictamente personal, sino que corresponde a un patrón regular con ciertas leyes y principios. Más aún, tal irracionalidad comprende distintos ámbitos del comportamiento, desde los procesos detrás de la compra de bienes muebles o inmuebles a los que definen las acciones éticas de las personas.

As its title suggests, this book postulates that human behavior is fundamentally irrational, that is, driven by emotional factors that are difficult to understand for logical mind. This irrationality is, nonetheless, neither random or subjective, but to some extent predictable and rather universal. Furthermore, such irrational reasoning can be found at different levels , from the way in which people acquire small or large-scale goods (a TV set or a house respectively), to the way in which individuals make ethical decisions.

Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production.

The antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malaria parasites, ART cytotoxicity originates from interactions with heme-derived iron within the food vacuole. The analogous digestive compartment of mammalian cells, the lysosome, similarly contains high levels of redox-active iron and in response to specific stimuli can initiate mitochondrial apoptosis. We thus investigated the role of lysosomes in ART-induced PCD and determined that in MCF-7 breast cancer cells ART activates lysosome-dependent mitochondrial outer membrane permeabilization. ART impacted endolysosomal and autophagosomal compartments, inhibiting autophagosome turnover and causing perinuclear clustering of autophagosomes, early and late endosomes, and lysosomes. Lysosomal iron chelation blocked all measured parameters of ART-induced PCD, whereas lysosomal iron loading enhanced death, thus identifying lysosomal iron as the lethal source of reactive oxygen species upstream of mitochondrial outer membrane permeabilization. Moreover, lysosomal inhibitors chloroquine and bafilomycin A1 reduced ART-activated PCD, evidencing a requirement for lysosomal function during PCD signaling. ART killing did not involve activation of the BH3-only protein, Bid, yet ART enhanced TNF-mediated Bid cleavage. We additionally demonstrated the lysosomal PCD pathway in T47D and MDA-MB-231 breast cancer cells. Importantly, non-tumorigenic MCF-10A cells resisted ART-induced PCD. Together, our data suggest that ART triggers PCD via engagement of distinct, interconnected PCD pathways, with hierarchical signaling from lysosomes to mitochondria, suggesting a potential clinical use of ART for targeting lysosomes in cancer treatment.

Moviéndose con la mente y el cuerpo: entendiendo la diferencia entre planear y realizar rutas en el espacio construido / Moving with the mind and the body: understanding the gap between planning and executing routes in the built environment

Este escrito estudió hasta qué punto las personas, al momento de ir de un punto A a uno B, realizan las rutas planeadas previamente, y si éstas son idénticas para ir que para volver. Se pidió a 42 participantes estudiar un plano del campus principal de la UTFSM, y trazar las rutas que eligirían para ir entre dos pares de puntos. Una vez terminada esta tarea, los participantes debieron recorrer en la realidad las rutas trazadas. Los resultados mostraron que las rutas trazadas en papel no necesariamente coincidieron con las rutas realizadas en terreno, y que, en la mayoría de los casos, las rutas A-B/B-A y X-Y/Y-X no fueron simétricas. Se concluye sugiriendo que los criterios de elección de ruta cambian porque el razonamiento espacial de las personas es inherentemente situado, esto es, moldeado por el entorno en que se lleva a cabo.

This paper is concerned with route behavior in people. Specifically, it aims to better understand whether people follow routes planned in advance, and whether these routes are identical irrespective of the direction of travel. A total of 42 participants (27 belonging to UTFSM and 15 from outside) were asked to trace routed between a pair of points in a map of the campus. After that, they were brought to these places and asked to physically navigate these routes. The main results showed that planned routes were not necessarily employed in real-world scenarios, and that people often changed routes depending on the direction of travel. These results suggest that route choice criteria are somehow dependant on contextual information.