ARAX: a graph-based modular reasoning tool for translational biomedicine.

MOTIVATION: With the rapidly growing volume of knowledge and data in biomedical databases, improved methods for knowledge-graph-based computational reasoning are needed in order to answer translational questions. Previous efforts to solve such challenging computational reasoning problems have contributed tools and approaches, but progress has been hindered by the lack of an expressive analysis workflow language for translational reasoning and by the lack of a reasoning engine-supporting that language-that federates semantically integrated knowledge-bases. RESULTS: We introduce ARAX, a new reasoning system for translational biomedicine that provides a web browser user interface and an application programming interface (API). ARAX enables users to encode translational biomedical questions and to integrate knowledge across sources to answer the user's query and facilitate exploration of results. For ARAX, we developed new approaches to query planning, knowledge-gathering, reasoning and result ranking and dynamically integrate knowledge providers for answering biomedical questions. To illustrate ARAX's application and utility in specific disease contexts, we present several use-case examples. AVAILABILITY AND IMPLEMENTATION: The source code and technical documentation for building the ARAX server-side software and its built-in knowledge database are freely available online (https://github.com/RTXteam/RTX). We provide a hosted ARAX service with a web browser interface at arax.rtx.ai and a web API endpoint at arax.rtx.ai/api/arax/v1.3/ui/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RTX-KG2: a system for building a semantically standardized knowledge graph for translational biomedicine.

BACKGROUND: Biomedical translational science is increasingly using computational reasoning on repositories of structured knowledge (such as UMLS, SemMedDB, ChEMBL, Reactome, DrugBank, and SMPDB in order to facilitate discovery of new therapeutic targets and modalities. The NCATS Biomedical Data Translator project is working to federate autonomous reasoning agents and knowledge providers within a distributed system for answering translational questions. Within that project and the broader field, there is a need for a framework that can efficiently and reproducibly build an integrated, standards-compliant, and comprehensive biomedical knowledge graph that can be downloaded in standard serialized form or queried via a public application programming interface (API). RESULTS: To create a knowledge provider system within the Translator project, we have developed RTX-KG2, an open-source software system for building-and hosting a web API for querying-a biomedical knowledge graph that uses an Extract-Transform-Load approach to integrate 70 knowledge sources (including the aforementioned core six sources) into a knowledge graph with provenance information including (where available) citations. The semantic layer and schema for RTX-KG2 follow the standard Biolink model to maximize interoperability. RTX-KG2 is currently being used by multiple Translator reasoning agents, both in its downloadable form and via its SmartAPI-registered interface. Serializations of RTX-KG2 are available for download in both the pre-canonicalized form and in canonicalized form (in which synonyms are merged). The current canonicalized version (KG2.7.3) of RTX-KG2 contains 6.4M nodes and 39.3M edges with a hierarchy of 77 relationship types from Biolink. CONCLUSION: RTX-KG2 is the first knowledge graph that integrates UMLS, SemMedDB, ChEMBL, DrugBank, Reactome, SMPDB, and 64 additional knowledge sources within a knowledge graph that conforms to the Biolink standard for its semantic layer and schema. RTX-KG2 is publicly available for querying via its API at arax.rtx.ai/api/rtxkg2/v1.2/openapi.json . The code to build RTX-KG2 is publicly available at github:RTXteam/RTX-KG2 .

[Perceived urgency of medical condition and use of health care services in Medellín, Colombia, 2005-2006]. / Morbilidad sentida de las urgencias médicas y la utilización de los servicios de salud en Medellín, Colombia, 2005-2006.

INTRODUCTION: Medellín has a population of 2.1 million and has 47 acute care hospitals that provide emergency health care services. Perceived seriousness of a medical condition in addition to accessibility and availability of care may influence the use of health care services in the region. OBJECTIVES: A broad-spectrum survey was conducted to rate the urgency of a health condition as perceived by the patient and how that patient proceeded to make use of health care services. MATERIALS AND METHODS: The cross sectional survey was conducted, using door-to-door personal interviews in 1,442 homes from 70 neighborhoods. RESULTS: Of the 612,689 individuals interviewed, 533,718 (87,11%) reported that they have had a medical emergency. Respiratory difficulties were the most frequent reason for visiting a health care facility as reported by 113,153 (21.2%) of the participants. Of the 532,718 visits reported, 501,558 (93.97%) led to a hospital admission. Of the 21,042 visits not leading to an admission, 42.0% were considered as non-urgent by the hospital staff. Visits admissions reports were missing, 11.118 (2.08%). CONCLUSIONS: In Medellín, the incidence of medical emergencies leading to a health care facility visit is high. The high prevalence of respiratory emergencies and other conditions that can be managed outside the emergency service indicates the need for a pre-hospital emergency service.

Actividad antiviral in vitro de extractos de Hura crepitans y Codiaeum variegatum en la replicación de herpes virus bovino tipo-1 y virus de estomatitis vesicular / In vitro antiviral activity of extracts from Hura crepitans y Codiaeum variegatum on bovine herpes virus type-1 and vesicular stomatitis virus replication

Hojas de las plantas Hura crepitans y Codiaeum variegatum se recolectaron en la ciudad de Medellín (Colombia), para determinar la actividad biológica (Actividad citotóxica [AC] y antiviral [AAV]) de cuatro extractos de éstas (hexánico, en acetato de etilo, metanólico y acuoso) sobre los virus de Estomatitis Vesicular (VSV) serotipos Indiana y New Jersey y Herpes Virus Bovino tipo-1 cepa Bogotá (BHV-1B). El tamizaje de actividad biológica de los extractos se realizó en monocapas de células BHK-21. Luego los extractos promisorios, pasaron a la fase cuantitativa de AAV por el ensayo de MTT [3-(4,5-dimethylthiazol–2-yl)-2,5-diphenyltetrazolium bromide] para determinar la concentración citotóxica 50 (CC50), la concentración inhibitoria 50 (IC50) y el índice de selectividad (IS). Ninguno de los extractos de las cuatro plantas presentó AAV contra VSV, mientras que los extractos hexánico, en acetato de etilo y metanólico de H. crepitans confirieron resistencia a la infección por BHV-1B con IC50 de 17.41, 7.87 y 2.75 µ g/ml, respectivamente. El extracto con mejor IS (relación entre IC50 y CC50) fue el hexánico de H. crepitans (IS > 17.4). Estos resultados sugieren que pueden existir compuestos en el extracto hexánico de H. crepitans con una actividad promisoria anti BHV-1B. Este estudio es pionero en demostrar actividad antiviral de extractos de plantas de la especie Euphorbiaceae contra BHV-1B.

Leaves from Hura crepitans and Codiaeum variegatum plants were collected in Medellín, Colombia to determine its cytotoxic [CA] and antiviral activity [AVA]. Four extracts were prepared using hexane, ethyl acetate, methanol and water; the antiviral activity was tested against Vesicular Stomatitis Virus (VSV), serotypes Indiana and New Jersey and Bovine Herpes Virus (type 1 Bogotá strain). The preliminary biological activity of each of the eight extracts was determined on BHK-21 cell monolayers using 96 well-plates. Then, promissory extracts were further tested using the MTT [3-(4,5-dimethylthiazol–2-yl)-2,5-diphenyltetrazolium bromide] assay to determine the cytotoxic concentration 50 (CC50), the inhibitory concentration 50 (IC50 ), and the selectivity index (SI). None of the evaluated plants exhibited AVA against VSV, whereas the extracts in hexane, ethyl acetate and methanol from Hura crepitans protected cell monolayer from infection against BHV-Bogotá with IC50 of 17.41, 7.87 and 2.75 µ g/ml respectively. The best IS was hexane of H. crepitans (SI > 17.4). These results suggest that this extract contains antiviral compounds. This research is pioneer demonstrating AVA against BHV-1B in extracts from plants of the Euphorbiaceae family.

Audición del paciente hipertenso crónico controlado / Hearing in controlled chronic hypertensive patient

Estudios epidemiológicos postulando una presunta relación entre hipertensión arterial e hipoacusia habrían sido ratificados por diversas investigaciones experiementales en ratas hipertensas genéticamente. Este hecho generó el interés en determinar la verdadera magnitud del compromiso auditivo en seres humanos con hipertensión arterial crónica. Se realizó estudio audiométrico completo en pacientes hipertensos crónicos controlados en centros especializados. Se descartó a todo portador de patología de oído medio o interno de etiología o causa precisable, o con antecedentes de exposición laboral a ruidos intensos, diabetes, lue, drogas ototóxicas, barnizadores o hipertensión de antiguedad inferior a 3 años. Los resultados obtenidos en 217 pacientes hipertensos crónicos controlados fueron promediados, configurando diversos perfiles audiométricos de acuerdo a grupos de edad de éstos y comparándose con una población sana suburbana y rural, calificada como grupo control. El análisis comparativo de los resultados de ambos grupos no reveló diferencias significativas, permitiendo postular que el perfil audiométrico en población hipertensa crónica controlada es similar al de la población general. Por consiguiente, estos hallazgos discrepan con recientes trabajos experimentales que pretenden vincular hipertensión arterial e hipoacusia. Factores predisponentes individuales (estructurales o metabólicos) podrían, en casos aislados, provocar pérdida auditiva, no representando la evolución habitual en pacientes hipertensos crónicos