Text Mining of Biomedical Articles Using the Konstanz Information Miner (KNIME) Platform: Hemolytic Uremic Syndrome as a Case Study.

OBJECTIVES: Automated systems for information extraction are becoming very useful due to the enormous scale of the existing literature and the increasing number of scientific articles published worldwide in the field of medicine. We aimed to develop an accessible method using the open-source platform KNIME to perform text mining (TM) on indexed publications. Material from scientific publications in the field of life sciences was obtained and integrated by mining information on hemolytic uremic syndrome (HUS) as a case study. METHODS: Text retrieved from Europe PubMed Central (PMC) was processed using specific KNIME nodes. The results were presented in the form of tables or graphical representations. Data could also be compared with those from other sources. RESULTS: By applying TM to the scientific literature on HUS as a case study, and by selecting various fields from scientific articles, it was possible to obtain a list of individual authors of publications, build bags of words and study their frequency and temporal use, discriminate topics (HUS vs. atypical HUS) in an unsupervised manner, and cross-reference information with a list of FDA-approved drugs. CONCLUSIONS: Following the instructions in the tutorial, researchers without programming skills can successfully perform TM on the indexed scientific literature. This methodology, using KNIME, could become a useful tool for performing statistics, analyzing behaviors, following trends, and making forecast related to medical issues. The advantages of TM using KNIME include enabling the integration of scientific information, helping to carry out reviews, and optimizing the management of resources dedicated to basic and clinical research.

[Obtaining new information on hemolytic uremic syndrome by text mining]. / Obtención de nueva información sobre el síndrome urémico hemolítico mediante minería de texto.

Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy, hemolytic anemia, thrombocytopenia and acute renal failure. It can cause from permanent sequelae to death, mainly in children. In this work, using text mining (TM), we analyzed the explicit and implicit text of 16 192 original scientific articles on HUS indexed in the Europe PMC database. The objectives were to examine behaviors, track trends, and make predictions and cross-check data with other sources of information. For the analysis we used -among other computational tools- specially developed workflows (WF) in the KNIME platform. The TM on the words of the abstracts of the publications made it possible to: detect undescribed associations between events related to HUS; extract underlying information; make thematic clustering using unsupervised algorithms; make forecasting about the course of research associated with the topic. Both the approach and the WFs developed to perform Data Science on HUS can be applied to other biomedical topics and other scientific databases, making it possible to analyze relevant aspects in the field of human health to improve research, prevention and treatment of multiples diseases.

El síndrome urémico hemolítico (SUH) está caracterizado por microangiopatía trombótica, anemia hemolítica, trombocitopenia e insuficiencia renal aguda. Puede causar desde secuelas permanentes hasta muerte, principalmente en niños. En este trabajo, utilizando minería de textos (MT), se analizó el texto explícito e implícito de 16 192 artículos científicos originales sobre SUH indexados en la base de datos de Europe PMC. Los objetivos fueron examinar comportamientos, realizar seguimiento de tendencias, hacer predicciones y cruzar datos con otras fuentes de información. Para el análisis se utilizaron ­entre otras herramientas informáticas­ flujos de trabajo (FT) especialmente desarrollados en la plataforma KNIME. La MT sobre las palabras de los resúmenes de las publicaciones permitió: detectar asociaciones no descritas entre eventos relacionados con SUH; extraer información subyacente; hacer agrupamientos temáticos mediante algoritmos no supervisados; realizar predicciones sobre el curso de las investigaciones asociadas al tema. Tanto el abordaje como los FT desarrollados para realizar Ciencia de Datos sobre SUH pueden aplicarse a otros temas biomédicos y a otras bases de datos científicos, permitiendo analizar aspectos relevantes en el campo de la salud humana para mejorar la investigación, la prevención y el tratamiento de múltiples enfermedades.

Obtención de nueva información sobre el síndrome urémico hemolítico mediante minería de texto / Obtaining new information on hemolytic uremic syndrome by text mining

Resumen El síndrome urémico hemolítico (SUH) está caracterizado por microangiopatía trombótica, anemia hemolítica, trombocitopenia e insuficiencia renal aguda. Puede causar desde secuelas permanentes hasta muerte, principalmente en niños. En este trabajo, utilizando minería de textos (MT), se analizó el texto explícito e implícito de 16 192 artículos científicos originales sobre SUH indexados en la base de datos de Europe PMC. Los objetivos fueron examinar comportamientos, realizar seguimiento de tendencias, hacer predicciones y cruzar datos con otras fuentes de información. Para el análisis se utilizaron -entre otras herramientas infor máticas- flujos de trabajo (FT) especialmente desarrollados en la plataforma KNIME. La MT sobre las palabras de los resúmenes de las publicaciones permitió: detectar asociaciones no descritas entre eventos relacionados con SUH; extraer información subyacente; hacer agrupamientos temáticos mediante algoritmos no supervisados; realizar predicciones sobre el curso de las investigaciones asociadas al tema. Tanto el abordaje como los FT desarrollados para realizar Ciencia de Datos sobre SUH pueden aplicarse a otros temas biomédicos y a otras bases de datos científicos, permitiendo analizar aspectos relevantes en el campo de la salud humana para me jorar la investigación, la prevención y el tratamiento de múltiples enfermedades.

Abstract Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy, hemolytic anemia, thrombocytopenia and acute renal failure. It can cause from permanent sequelae to death, mainly in children. In this work, using text mining (TM), we analyzed the explicit and implicit text of 16 192 original scientific articles on HUS indexed in the Europe PMC database. The objectives were to examine behaviors, track trends, and make predictions and cross-check data with other sources of information. For the analysis we used -among other computational tools- specially developed workflows (WF) in the KNIME platform. The TM on the words of the abstracts of the publications made it possible to: detect undescribed associations between events related to HUS; extract underly ing information; make thematic clustering using unsupervised algorithms; make forecasting about the course of research associated with the topic. Both the approach and the WFs developed to perform Data Science on HUS can be applied to other biomedical topics and other scientific databases, making it possible to analyze relevant aspects in the field of human health to improve research, prevention and treatment of multiples diseases.

Minería de texto en publicaciones científicas con autores Argentinos / Text mining in scientific publications with Argentine authors

Resumen En el presente trabajo utilizamos la minería de texto como herramienta de tratamiento de una gran base de datos científica, con el objetivo de obtener nueva información de todas las publicaciones firmadas por autores argentinos e indexadas hasta 2019 en el área de las ciencias de la vida. Se analizaron más de 75 000 artículos, publicados en alrededor de 5000 medios, firmados por cerca de 186 000 autores con lugar de trabajo en la Argentina o en colaboraciones con laboratorios argentinos. Mediante herramientas automatizadas, que fueron desarrolladas ad hoc, se analizó el texto de alrededor de 70 800 resúmenes y se buscaron, mediante detección digital no supervisada, los principales temas abordados, su relación con problemáticas de salud en la Argentina y su tratamiento. Se presentan, además, resultados del número de publicaciones por año, las revistas que las publicaron, y sobre sus autores y colaboraciones. Estos resultados, junto con las predicciones que se obtuvieron, podrían constituirse en una herramienta útil para optimizar el manejo de recursos dedicados a la investigación básica y clínica.

Abstract In the present work we use text mining as a treatment tool for a large scientific database, with the aim of obtaining new information about all the publications signed by Argentine authors and indexed until 2019, in the area of life sciences. More than 75 000 articles were analysed, published in around 5000 media, signed by about 186 000 authors with a workplace in Argentina or in collaborations with Argentine laboratories. Using automated tools that were developed ad hoc, the text of around 70 800 abstracts was analysed, seeking, through non-supervised digital detection, the main topics addressed by the authors, and the relationship with health problems in Argentina and their treat ment. Results are also presented regarding the number of publications per year, the journals that have published them, and their authors and collaborations. These results, together with the predictions that were obtained, could become a useful tool to optimize the management of resources dedicated to basic and clinical research.

[Text mining in scientific publications with Argentine authors]. / Minería de texto en publicaciones científicas con autores argentinos.

In the present work we use text mining as a treatment tool for a large scientific database, with the aim of obtaining new information about all the publications signed by Argentine authors and indexed until 2019, in the area of life sciences. More than 75 000 articles were analysed, published in around 5000 media, signed by about 186 000 authors with a workplace in Argentina or in collaborations with Argentine laboratories. Using automated tools that were developed ad hoc, the text of around 70 800 abstracts was analysed, seeking, through non-supervised digital detection, the main topics addressed by the authors, and the relationship with health problems in Argentina and their treatment. Results are also presented regarding the number of publications per year, the journals that have published them, and their authors and collaborations. These results, together with the predictions that were obtained, could become a useful tool to optimize the management of resources dedicated to basic and clinical research.

En el presente trabajo utilizamos la minería de texto como herramienta de tratamiento de una gran base de datos científica, con el objetivo de obtener nueva información de todas las publicaciones firmadas por autores argentinos e indexadas hasta 2019 en el área de las ciencias de la vida. Se analizaron más de 75 000 artículos, publicados en alrededor de 5000 medios, firmados por cerca de 186 000 autores con lugar de trabajo en la Argentina o en colaboraciones con laboratorios argentinos. Mediante herramientas automatizadas, que fueron desarrolladas ad hoc, se analizó el texto de alrededor de 70 800 resúmenes y se buscaron, mediante detección digital no supervisada, los principales temas abordados, su relación con problemáticas de salud en la Argentina y su tratamiento. Se presentan, además, resultados del número de publicaciones por año, las revistas que las publicaron, y sobre sus autores y colaboraciones. Estos resultados, junto con las predicciones que se obtuvieron, podrían constituirse en una herramienta útil para optimizar el manejo de recursos dedicados a la investigación básica y clínica.

Human AQP1 is a constitutively open channel that closes by a membrane-tension-mediated mechanism.

This work presents experimental results combined with model-dependent predictions regarding the osmotic-permeability regulation of human aquaporin 1 (hAQP1) expressed in Xenopus oocyte membranes. Membrane elastic properties were studied under fully controlled conditions to obtain a function that relates internal volume and pressure. This function was used to design a model in which osmotic permeability could be studied as a pressure-dependent variable. The model states that hAQP1 closes with membrane-tension increments. It is important to emphasize that the only parameter of the model is the initial osmotic permeability coefficient, which was obtained by model-dependent fitting. The model was contrasted with experimental records from emptied-out Xenopus laevis oocytes expressing hAQP1. Simulated results reproduce and predict volume changes in high-water-permeability membranes under hypoosmotic gradients of different magnitude, as well as under consecutive hypo- and hyperosmotic conditions. In all cases, the simulated permeability coefficients are similar to experimental values. Predicted pressure, volume, and permeability changes indicate that hAQP1 water channels can transit from a high-water-permeability state to a closed state. This behavior is reversible and occurs in a cooperative manner among monomers. We conclude that hAQP1 is a constitutively open channel that closes mediated by membrane-tension increments.

A counterpoint between computer simulations and biological experiments to train new members of a laboratory of physiological sciences.

When new members join a working group dedicated to scientific research, several changes occur in the group's dynamics. From a teaching point of view, a subsequent challenge is to develop innovative strategies to train new staff members in creative thinking, which is the most complex and abstract skill in the cognitive domain according to Bloom's revised taxonomy. In this sense, current technological and digital advances offer new possibilities in the field of education. Computer simulation and biological experiments can be used together as a combined tool for teaching and learning sometimes complex physiological and biophysical concepts. Moreover, creativity can be thought of as a social process that relies on interactions among staff members. In this regard, the acquisition of cognitive abilities coexists with the attainment of other skills from psychomotor and affective domains. Such dynamism in teaching and learning stimulates teamwork and encourages the integration of members of the working group. A practical example, based on the teaching of biophysical subjects such as osmosis, solute transport, and membrane permeability, which are crucial in understanding the physiological concept of homeostasis, is presented.

Uroguanylin regulates net fluid secretion via the NHE2 isoform of the Na/H+ exchanger in an intestinal cellular model.

Uroguanylin (UGN) has been proposed as a key regulator of salt and water intestinal transport. Uroguanylin activates cell-surface guanylate cyclase C receptor (GC-C) and modulates cellular function via cyclic GMP (cGMP), thus increasing electrolyte and net water secretion. It has been suggested that the action of UGN could involve the Na(+)/H(+) exchanger, but the actual contribution of this transporter still remains unclear. The objective of our study was to investigate the putative effects of UGN on some members of the Na(+)/H(+) exchanger family (NHEs), as well as to clarify its consequences on transepithelial fluid flow in T84 cells. In order to do so, transepithelial fluid flow (J(v)) was studied by optic techniques and intracellular pH (pH(i)) was measured with a fluorescence method. Results showed that NHE2 is found at the apical membrane and has a major role in Na(+) absorption; NHE1 and NHE4 are localized at the basolateral membrane with a house-keeping role in steady state pH(i). In the assayed conditions, cell exposure to apical UGN increases net secretory J(v), without changing short-circuit currents nor transepithelial resistance, and reduces NHE2 activity. Therefore, at physiological pH, the effect on net J(v) was produced mainly by a reduction in normal Na(+) absorption through NHE2, rather than by the stimulation of electrolyte secretion. Our study shows that the effect of UGN on pH(i) is GC-C/cGMP-mediated and enhanced by sildenafil, thus involving PDE5 enzyme. Additionally, cell exposure to apical UGN results in intracellular alkalinization, probably due to indirect effects on basolateral NHE1 and NHE4, which have a major role in pH(i) regulation.

Water flux through human aquaporin 1: inhibition by intracellular furosemide and maximal response with high osmotic gradients.

This work studies water permeability properties of human aquaporin 1 (hAQP1) expressed in Xenopus laevis oocyte membranes, applying a technique where cellular content is replaced with a known medium, with the possibility of measuring intracellular pressure. Consequences on water transport-produced by well-known anisotonic gradients and by the intracellular effect of probable aquaporin inhibitors-were tested. In this way, the specific intracellular inhibition of hAQP1 by the diuretic drug furosemide was demonstrated. In addition, experiments imposing anisotonic mannitol gradients with a constant ionic strength showed that the relationship between water flux and the applied mannitol gradient deflects from a perfect osmometer response when the gradient is higher than 150 mosmol kg (W) (-1) . These results would indicate that the passage of water molecules through hAQP1 may have a maximum rate. As a whole, this work demonstrates the technical advantage of controlling both intracellular pressure and medium composition in order to study biophysical properties of hAQP1, and contributes information on water channel behavior under osmotic challenges and the discovery of new inhibitors.

From membrane pores to aquaporins: 50 years measuring water fluxes.

This review focuses on studies of water movement across biological membranes performed over the last 50 years. Different scientific approaches had tried to elucidate such intriguing mechanism, from hypotheses emphasizing the role of the lipid bilayer to the cloning of aquaporins, the ubiquitous proteins described as specific water channels. Pioneering and clarifying biophysical work are reviewed beside results obtained with the help of recent sophisticated techniques, to conclude that great advances in the subject live together with old questions without definitive answers.