DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC50 = 1.5-3.3 µM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes.

Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations.

BACKGROUND: We aimed to evaluate the performance of a novel multiplex serological assay, able to simultaneously detect IgG of six infections, as a screening tool for imported diseases in migrants. METHODS: Six panels of 40 (n = 240) anonymized serum samples with confirmed infections were used as positive controls to assess the multiplex assay's sensitivity. One panel of 40 sera from non-infected subjects was used to estimate the seropositivity cutoffs, and 32 non-infected sera were used as negative controls to estimate each serology's sensitivity and specificity. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas. The sensitivity of the Luminex assay was calculated as the proportion of positive results over all positive samples identified by reference tests. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95 % confidence intervals using receiver operating characteristic analyses. RESULTS: The sensitivity/specificity were 100 %/100 % for HIV (gp41 antigen), 97.5 %/100 % for Hepatitis B virus (HBV-core antigen), 100 %/100 % for Hepatitis C virus (HCV-core antigen), 92.5 %/90.6 % for strongyloidiasis [31-kDa recombinant antigen (NIE)], 97.5 %/100 % for schistosomiasis (combined serpin Schistosoma mansoni and S.haematobium antigens) and 95 %/90.6 % for Chagas disease [combined Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP11) and paraflagellar rod proteins 2 (PFR2) antigens]. In the migrant cohort, antibody response to the combination of the T.cruzi antigens correctly identified 100 % individuals, whereas HBV-core antigen correctly identified 91.7 % and Strongyloides-NIE antigen 86.4 %. CONCLUSIONS: We developed a new, robust and accurate 8-plex Luminex assay that could facilitate the implementation of screening programmes targeting migrant populations.

Differential expression profile of genes involved in the immune response associated to progression of chronic Chagas disease.

BACKGROUND: Patients with chronic Chagas disease present marked clinical and immunological heterogeneity. During the disease, multiple immune mechanisms are activated to fight the parasite. The purpose of this study was to investigate the expression patterns of genes involved in relevant immunological processes throughout the disease in patients with chronic Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: High-throughput RT-qPCR with QuantStudio 12K Flex real-time PCR system was used to evaluate the expression of 106 immune-related genes in PBMC from a cohort of cardiac Chagas disease patients (CCC I), asymptomatic patients (IND) and healthy donors (HD) after being stimulated with T. cruzi soluble antigens. Principal component analysis (PCA), cluster analysis and volcano plots were used to identify differentially expressed genes. In addition, gene set enrichment analysis (GSEA) was employed to identify the enriched immunological pathways in which these genes are involved. PCA revealed the existence of a statistically divergent expression profile of the 36 genes correlated with PC1 between CCC I patients and HD (p < 0.0001). Differential gene expression analysis revealed upregulation of 41 genes (expression fold-change > 1.5) and downregulation of 14 genes (expression fold-change < 0.66) (p = 8.4x10-13 to p = 0.007) in CCC I patients versus HD. Furthermore, significant differences in the expression level of specific genes have been identified between CCC I and IND patients (8 up and 1 downregulated). GSEA showed that several upregulated genes in CCC I patients participate in immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, cytokines-inflammatory response and IL-10 anti-inflammatory signaling. CONCLUSIONS: Cardiac Chagas disease patients show an antigen-specific differential gene expression profile in which several relevant immunological pathways seem to be activated. Assessment of gene expression profiles reveal unique insights into the immune response that occurs along chronic Chagas disease.

[Comparison of protective colostomy vs. ileostomy in rectal cancer surgery]. / Comparación de colostomía frente a ileostomía de protección en cirugía de cáncer rectal.

Background: Rectal cancer (RC) is the 3rd most frequent one in Mexico. Protective stoma in resection and anastomosis is controversial. Objective: To compare quality of life (QoL), functional capacity (FC) and complications in rectal cancer (RC) patients with low and ultralow anterior resection (LAR and ULAR) with loop transverse colostomy (LTC) versus protective ileostomy (IP). Material and methods: Comparative, observational study in patients with RC and LTC (Group 1) or IP (Group 2) from 2018-2021. FC pre and postoperative, complications, hospital readmission (HR) and assessment by other specialty (AS) were assessed; QoL was assessed with EQ-5D by telephone. Student-t test, Chi-squared test, Mann-Whitney-U test were used. Results: Group 1: 12 patients: mean preoperative FC: ECOG 0.83, Karnofsky 91.66%; postoperative: ECOG 1, Karnofsky 89.17%. Mean postoperative QoL: index value 0.76 and health status 82.5%; HR: 25%; AS: 42%. Group 2: 10 patients: mean preoperative FC: ECOG 0.80, Karnofsky 90%; postoperative: ECOG 1.5, Karnofsky 84%. Mean postoperative QoL: index value 0.68 and health status 74%; HR: 50%; AS: 80%. Complications: 100% of sample. Conclusion: The differences in QoL, FC and complications between LTC and IP in RC patients operated with LAR/ULAR were not significant.

Introducción: el cáncer rectal (CR) es el tercero más frecuente en México. El estoma de protección en la resección y anastomosis es controversial. Objetivo: comparar calidad de vida (CV), capacidad funcional (CF) y complicaciones (COMP) en pacientes con CR con resección anterior baja (RAB) y ultrabaja (RAUB) con colostomía de transverso en asa (CTA) frente a ileostomía de protección (IP). Material y métodos: estudio comparativo, observacional, en pacientes con CR con CTA (Grupo 1) o IP (Grupo 2) atendidos en 2018-2021. Se evaluó CF (escalas ECOG y Karnofsky) pre y posquirúrgicas, COMP, reingreso hospitalario (RH) y valoración por otra especialidad (VE). Se evaluó CV con la encuesta EQ-5D vía telefónica. Se utilizó t de Student, Chi cuadrada y U de Mann-Whitney. Resultados: grupo1: 12 pacientes; CF media prequirúrgica ECOG: 0.83, Karnofsky: 91.66%; posquirúrgica ECOG: 1, Karnofsky: 89.17%. CV posquirúrgica medias valor índice: 0.76 y estado funcional: 82.5%; RH: 25%, VE: 42%. Grupo 2: 10 pacientes; CF media prequirúrgica ECOG: 0.80, Karnofsky: 90%; CF media postquirúrgica ECOG: 1.5, Karnofsky: 84%; CV medias valor índice: 0.68, estado funcional: 74%; RH: 50%, VE: 80%. COMP: 100% de la muestra. Conclusiones: las diferencias en CV, CF y COMP entre CTA e IP en pacientes con CR con RAB/RAUB no fueron significativas.

Calidad de vida con y sin cirugía conservadora de esfínteres por cáncer de recto

Introducción: El cáncer colorrectal (CCR) es el tercer cáncer más frecuente y la segunda causa principal de muerte a nivel mundial con una incidencia 10,2%. El tratamiento del CCR ha cambiado durante los últimos 25 años. Se utilizan dos manejos quirúrgicos: la resección abdominoperineal (RAP) y la resección anterior baja (RAB) y la ultra baja (RAUB). La tasa de recidiva y la calidad de vida son similares. Objetivo: Comparar la calidad de vida de los pacientes con cáncer de recto tratados con resección abdominoperineal vs resecciones conservadoras de esfínteres: anterior baja y ultra baja en la UMAE Puebla. Métodos: Se realizó un estudio comparativo, observacional, transversal en pacientes con CCR atendidos durante 2015-2019 en un hospital de 3er nivel en Puebla. Se formaron dos grupos: los manejados con RAP y los manejados con RAB/RAUB. Se aplicó la escala EORT QLQ CR-29 y EuroQol. Se aplicó estadística descriptiva y U de Man-Whitney para comparaciones. Resultados: Se reclutaron 26 pacientes, 18 manejados con RAP y 8 con RAB/RAUB. Se registró una CV media en el grupo RAP de 73,72 (DE 16,92, mínimo 31,46, máximo 95,09) y en el grupo RAB/RAUB de 56,22 (DE 6,29, mínimo 47,51, máximo 68,96), con un valor de p=0,005. Conclusiones: No hay diferencia significativa en la calidad de vida de los pacientes con CCR operados por RAP, RAB y RAUB (abordaje no conservador y conservador).

Introduction: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide, with an incidence of 10.2%. The treatment of CRC has evolved over the past 25 years. Two surgical procedures are used: abdominoperineal resection (APR) and low anterior resection (LAR) and ultra-low anterior resection (ULAR). The recurrence rate and quality of life are similar between these approaches. Objective: To compare the quality of life of rectal cancer patients treated with abdominoperineal resection versus conservative sphincter-preserving surgeries: low anterior resection (LAR) and ultra-low anterior resection (ULAR) at UMAE of Puebla. Methods: A comparative, observational, cross-sectional study was conducted on CRC patients treated between 2015 and 2019 at a tertiary-level hospital in Puebla. Two groups were formed: those managed with APR and those managed with LAR/ULAR. The EORTC QLQ-CR29 scale and EuroQol were applied. Descriptive statistics and the Mann-Whitney U test were used for comparisons. Results: A total of 26 patients were recruited, 18 with APR and 8 with LAR/ULAR. The mean quality of life score in the APR group was 73.72 (SD 16.92, minimum 31.46, maximum 95.09), and in the LAR/ULAR group was 56.22 (SD 6.29, minimum 47.51, maximum 68.96), with a p-value of 0.005. Conclusions: There is no significant difference in the quality of life of CRC patients operated with APR, LAR, and ULAR (non-conservative and conservative approaches).

Internacionalização para o incremento da produção de conhecimentos em enfermagem: estudo de reflexão / Internationalization to increase the production of knowledge in nursing: a reflection study

Objetivo: refletir sobre oportunidades para a internacionalização da Enfermagem em países lusófonos proporcionadas por uma rede internacional de conhecimentos em Enfermagem. Método: método reflexivo que conduz à percepção modificada de uma dada situação levando a novas ideias, revelando temas de análise e propostas de possíveis soluções através de um plano de ação. A reflexão concentrou-se em diálogos interdisciplinares, inovação conceitual-metodológica e fortalecimento da liderança em Enfermagem. Resultados: a reflexão focalizou: (a) o diálogo além do contexto cultural e científico lusófono para a Rede ser reconhecida como parceiro intelectual substancial; (b) a incorporação de abordagens, referenciais e desenhos de pesquisa multidisciplinares; e (c) a mobilização de conhecimento sobre causas sociais para o fortalecimento da liderança da Enfermagem global nas questões de justiça social e equidade em saúde. Considerações finais: a Enfermagem lusófona possui expertise para inovar com estratégias para reforçar a internacionalização.

Objective: reflect on opportunities for the internationalization of nursing in Lusophone countries provided by an international network of nursing knowledge. Method: a reflexive method leading to the modified perception of a given situation leading to new ideas, revealing themes of analysis and proposals for possible solutions through an action plan. This reflection focused on interdisciplinary dialogues, methodological-conceptual innovation, and strengthening of leadership in nursing. Results: the reflection focused on: 1) the dialogue beyond the Lusophone cultural and scientific context for the network to be recognized as a substantial intellectual partner; 2) the incorporation of multidisciplinary approaches, references, and research designs; and 3) the mobilization of knowledge about social causes to strengthen global nursing leadership in issues of social justice and health equity. Final considerations: Lusophone nursing has expertise to innovate with strategies to strengthen internationalization.

Objetivo: reflexionar sobre las oportunidades de internacionalización de la Enfermería en los países de lengua portuguesa proporcionadas por una red internacional de conocimiento en Enfermería. Método: método reflexivo que conduce a una percepción modificada de una situación que lleva a nuevas ideas, revelando temas de análisis y propuestas de posibles soluciones por medio de un plan de acción. La reflexión se centró en los diálogos interdisciplinarios, la innovación conceptual-metodológica y el fortalecimiento del liderazgo en enfermería. Resultados: la reflexión tuvo como foco: (a) el diálogo más allá del contexto cultural y científico de la lengua portuguesa para que la Red sea reconocida como un socio intelectual sustancial; (b) la incorporación de enfoques, referencias y diseños de investigación multidisciplinarios; y (c) la movilización de conocimiento sobre las causas sociales para fortalecer el liderazgo mundial de enfermería en temas de justicia social y equidad en salud. Consideraciones finales: La Enfermería em países de lengua portuguesa tiene el expertise para innovar con estrategias para reforzar la internacionalización.

Análise de particularidades da participação lusófona em uma Rede de Conhecimentos em Enfermagem / Análisis de las particularidades de la participación lusófona en una Red de Conocimientos de Enfermería / Analysis of the particularities of Lusophone participation in a Nursing Knowledge Network

Resumo Objetivo Descrever o exercício conceitual de reflexão sobre as possibilidades e particularidades da participação das Escolas de Enfermagem e Faculdades de Enfermagem lusófonas na Rede de Conhecimentos em Enfermagem. Método Análise das informações obtidas em um levantamento de recursos institucionais de acordo com o marco conceitual proposto por Prug e Prusak sobre rede de conhecimentos. A ponderação de aspectos positivos e negativos - analisando o aprendizado com as informações - levou em consideração as possíveis soluções para um plano de ação. Resultados Tanto nas ações institucionais para suportar a pesquisa em Enfermagem como nos benefícios almejados com a participação na Rede existe o interesse na internacionalização da pesquisa e no trabalho colaborativo. Com a ampliação dos horizontes da ciência da Enfermagem lusófona, este trabalho visa aumentar o impacto da pesquisa e agilizar a divulgação e a utilização dos resultados, tanto na educação como na clínica. Conclusão e Implicações para a prática A participação das referidas instituições oferece inúmeras possibilidades de demonstrar originalidade, criatividade e perícia de sua prática docente e de pesquisa, favorecendo o compartilhamento de ideias e práticas. A prática de produção científica, por docentes e discentes, pode ser aprimorada pelo refinamento de modos de pensar, criar, produzir e disseminar.

Resumen Objetivo Describir el ejercicio conceptual de reflexión de las posibilidades y particularidades de la participación de facultades de Enfermería de lengua portuguesa en la Red de Conocimientos de Enfermería. Método Análisis de datos obtenidos de un sondeo de recursos institucionales bajo el marco conceptual de Prug y Prusak sobre la red de conocimiento. El planteamiento de aspectos positivos y negativos del aprendizaje abarcó soluciones para elaborar un plan de acción. Resultados En las acciones institucionales de apoyo a la investigación en Enfermería y los beneficios aspirados con la participación en la Red, existe un interés por la internacionalización de la investigación y el trabajo colaborativo -que tiene como objetivo aumentar el impacto de la investigación, estimular la divulgación y el aprovechamiento de los resultados en la enseñanza y la clínica, con la ampliación de los horizontes de la Enfermería de instituciones de habla portuguesa. Conclusión e Implicaciones en la práctica La Red ofrece numerosas posibilidades para las instituciones participantes respecto a la demostración de originalidad, creatividad y experiencia en la práctica docente y de investigación, fomentando el intercambio de ideas y prácticas. La práctica de la producción científica por profesores y estudiantes puede verse mejorada por la reflexión, creación, producción y difusión de conocimientos.

Abstract Objective To describe the conceptual exercise of reflecting on the possibilities and particularities of the participation of Lusophone schools of nursing in the Nursing Knowledge Network. Method An analysis was conducted using information obtained from an environmental scan of institutional resources following the conceptual framework by Prug and Prusak on the knowledge networks. The learnings reported in the analysis are based on the collected information and reflections on the positive and negative aspects of participation, while proposing possible solutions for an action plan. Results There is interest in the internationalization of research and collaborative work both as institutional actions to support nursing research and potential benefits due to participation in the Network. The collaborative work has potential to increase the impact of research, expedite dissemination and use of results both in education and in clinical practice, broadening the horizons of Lusophone nursing science. Conclusion and Implications for practice Participation of these institutions in the Network offers numerous possibilities to demonstrate the originality, creativity and expertise of their teaching and research practice, encouraging the sharing of ideas and practices. The practice of scientific production in all its scenarios by educators and students can be improved through refined ways of thinking, creating, producing, and disseminating knowledge.

Humoral and Cellular Immune Response in Asymptomatic Dogs with Visceral Leishmaniasis: A Review.

Visceral leishmaniasis is one of the deadliest parasitic diseases in the world and affects both humans and dogs. The host immune response to Leishmania infection plays a critical role in the evolution of canine visceral leishmaniasis (CVL) and consequently in the manifestation of clinical signs. The asymptomatic form of the disease is a major concern in the diagnosis of CVL and in the transmission control of Leishmania infection. Asymptomatic dogs are found in large proportions in endemic areas and are an unquantifiable source of infection. The present review analyzes the possible relationship between the activation of the antigen-specific immune response of the host and resistance or susceptibility to CVL. The review focuses on works that address the characterization of the humoral and cellular immune response profile, at both the functional and phenotypic levels, in infected dogs. Most studies relate the absence of clinical symptomatology to an increased proliferative response and a Th1 cytokine profile. Despite the numerous findings pointing to a differential immune response in asymptomatic dogs, the contradictory results reported in this review highlight the importance of establishing a precise clinical classification of the disease, performing more longitudinal studies, and including a higher number of animals in trials.

Corrigendum: Genetic Regulation of Alginate Production in Azotobacter vinelandii a Bacterium of Biotechnological Interest: A Mini-Review.

[This corrects the article DOI: 10.3389/fmicb.2022.845473.].

High volume online post-dilution hemodiafiltration: how relevant is it in chronic kidney disease? / Hemodiafiltração on-line pós-dilucional de alto volume: qual sua real importância na doença renal crônica?

ABSTRACT Online hemodiafiltration is potentially a superior mode of dialysis compared to conventional hemodialysis. However, prospective randomized controlled trials have failed to demonstrate such superiority. Post-hoc analyses of these trials have indicated that high volume post-dilution hemodiafiltration is associated with lower death rates than conventional dialysis. This study discusses whether the lower death rates ascribed to high volume hemodiafiltration are linked to convection volume or the time on dialysis needed to achieve high convection volumes.

RESUMO A hemodiafiltração on-line é uma modalidade de diálise com potencial de superioridade sobre a hemodiálise convencional. Entretanto, estudos prospectivos, randomizados e controlados falharam em demonstrar a superioridade da hemodiafiltração. Análises post hoc desses estudos sugerem que a hemodiafiltração pós-dilucional de alto volume apresenta taxa de mortalidade inferior à hemodiálise convencional. Neste estudo, discutimos se a menor taxa de mortalidade da hemodiafiltração de alto volume está associada ao volume de convecção ou ao tempo de diálise necessário para atingir um alto volume de convecção.

Genetic Regulation of Alginate Production in Azotobacter vinelandii a Bacterium of Biotechnological Interest: A Mini-Review.

Alginates are a family of polymers composed of guluronate and mannuronate monomers joined by ß (1-4) links. The different types of alginates have variations in their monomer content and molecular weight, which determine the rheological properties and their applications. In industry, alginates are commonly used as additives capable of viscosifying, stabilizing, emulsifying, and gelling aqueous solutions. Recently, additional specialized biomedical uses have been reported for this polymer. Currently, the production of alginates is based on the harvesting of seaweeds; however, the composition and structure of the extracts are highly variable. The production of alginates for specialized applications requires a precise composition of monomers and molecular weight, which could be achieved using bacterial production systems such as those based on Azotobacter vinelandii, a free-living, non-pathogenic bacterium. In this mini-review, we analyze the latest advances in the regulation of alginate synthesis in this model.

High volume online post-dilution hemodiafiltration: how relevant is it in chronic kidney disease?

Online hemodiafiltration is potentially a superior mode of dialysis compared to conventional hemodialysis. However, prospective randomized controlled trials have failed to demonstrate such superiority. Post-hoc analyses of these trials have indicated that high volume post-dilution hemodiafiltration is associated with lower death rates than conventional dialysis. This study discusses whether the lower death rates ascribed to high volume hemodiafiltration are linked to convection volume or the time on dialysis needed to achieve high convection volumes.

Training-professional profile of nurses teaching at the Technical Schools of the Unified Health System / Perfil formación-profesional del enfermero docente en las Escuelas Técnicas del Sistema Único de Salud / Perfil formativo-profissional dos enfermeiros docentes das Escolas Técnicas do Sistema Único de Saúde

ABSTRACT Objective: to describe the training-professional profile of nursing professors in the vocational course in nursing at the Technical Schools of the Unified Health System. Methods: a quantitative descriptive research, carried out with 61 nurses who are professors of technical courses in nursing at five technical schools in three Brazilian regions. Data were collected through an online questionnaire and submitted to descriptive analysis. Results: only 36% of teaching nurses were licensed and 80% had a specialization in nursing or health. Although 95.1% of participants considered training for teaching necessary, 44.2% did not have qualifications for this job. The average length of work in care was 8 years, focusing on the hospital network. Conclusion: the need for professor training and investment in it is evidenced, as the training of essential workers for nursing care and consolidation of the Unified Health System is on the agenda.

RESUMEN Objetivo: describir el perfil formativo-profesional de los profesores de enfermería en el curso técnico en enfermería de las Escuelas Técnicas del Sistema Único de Salud. Métodos: investigación cuantitativa, descriptiva, realizada con 61 enfermeras que son profesoras de cursos técnicos en enfermería en cinco escuelas técnicas en tres regiones brasileñas. Los datos se recopilaron a través de un cuestionario en línea y se sometieron a análisis descriptivo. Resultados: se destaca que solo el 36% de los profesores de enfermería tenía licencia y el 80% tenía especialización en el campo de la enfermería o la salud. Si bien el 95,1% de los participantes consideró necesaria la formación para la docencia, el 44,2% no tenía la calificación para este puesto. El tiempo promedio de experiencia en la atención fue de 8 años, con foco en la red hospitalaria. Conclusión: se evidencia la necesidad de formación e inversión docente en la misma, ya que la formación de los trabajadores esenciales para la atención de enfermería y la consolidación del Sistema Único de Salud está en la agenda.

RESUMO Objetivo: descrever o perfil formativo-profissional dos enfermeiros docentes do curso técnico em enfermagem das Escolas Técnicas do Sistema Único de Saúde. Métodos: pesquisa quantitativa, do tipo descritiva, realizada com 61 enfermeiros professores de cursos técnicos em enfermagem de cinco escolas técnicas de três regiões brasileiras. Os dados foram coletados por questionário online e submetidos à análise descritiva. Resultados: destaca-se que apenas 36% dos enfermeiros docentes eram licenciados e 80% tinham especialização na área de enfermagem ou saúde. Apesar de 95,1% dos participantes considerar necessária a formação para o ensino, 44,2% não tinha qualificação para este trabalho. O tempo médio de atuação na assistência foi de 8 anos, concentrando-se na rede hospitalar. Conclusão: evidencia-se a necessidade de formação docente e o investimento nesta, pois está em pauta a formação de trabalhadores essenciais para o cuidado em enfermagem e consolidação do Sistema Único de Saúde.

Combining word embeddings to extract chemical and drug entities in biomedical literature.

BACKGROUND: Natural language processing (NLP) and text mining technologies for the extraction and indexing of chemical and drug entities are key to improving the access and integration of information from unstructured data such as biomedical literature. METHODS: In this paper we evaluate two important tasks in NLP: the named entity recognition (NER) and Entity indexing using the SNOMED-CT terminology. For this purpose, we propose a combination of word embeddings in order to improve the results obtained in the PharmaCoNER challenge. RESULTS: For the NER task we present a neural network composed of BiLSTM with a CRF sequential layer where different word embeddings are combined as an input to the architecture. A hybrid method combining supervised and unsupervised models is used for the concept indexing task. In the supervised model, we use the training set to find previously trained concepts, and the unsupervised model is based on a 6-step architecture. This architecture uses a dictionary of synonyms and the Levenshtein distance to assign the correct SNOMED-CT code. CONCLUSION: On the one hand, the combination of word embeddings helps to improve the recognition of chemicals and drugs in the biomedical literature. We achieved results of 91.41% for precision, 90.14% for recall, and 90.77% for F1-score using micro-averaging. On the other hand, our indexing system achieves a 92.67% F1-score, 92.44% for recall, and 92.91% for precision. With these results in a final ranking, we would be in the first position.

CD8+ T Cell Response Quality Is Related to Parasite Control in an Animal Model of Single and Mixed Chronic Trypanosoma cruzi Infections.

Chagas disease (ChD) is a chronic infection caused by Trypanosoma cruzi. This highly diverse intracellular parasite is classified into seven genotypes or discrete typing units (DTUs) and they overlap in geographic ranges, vectors, and clinical characteristics. Although studies have suggested that ChD progression is due to a decline in the immune response quality, a direct relationship between T cell responses and disease outcome is still unclear. To investigate the relationship between parasite control and immune T cell responses, we used two distinct infection approaches in an animal model to explore the histological and parasitological outcomes and dissect the T cell responses in T. cruzi-infected mice. First, we performed single infection experiments with DA (TcI) or Y (TcII) T. cruzi strains to compare the infection outcomes and evaluate its relationship with the T cell response. Second, because infections with diverse T. cruzi genotypes can occur in naturally infected individuals, mice were infected with the Y or DA strain and subsequently reinfected with the Y strain. We found different infection outcomes in the two infection approaches used. The single chronic infection showed differences in the inflammatory infiltrate level, while mixed chronic infection by different T. cruzi DTUs showed dissimilarities in the parasite loads. Chronically infected mice with a low inflammatory infiltrate (DA-infected mice) or low parasitemia and parasitism (Y/Y-infected mice) showed increases in early-differentiated CD8+ T cells, a multifunctional T cell response and lower expression of inhibitory receptors on CD8+ T cells. In contrast, infected mice with a high inflammatory infiltrate (Y-infected mice) or high parasitemia and parasitism (DA/Y-infected mice) showed a CD8+ T cell response distinguished by an increase in late-differentiated cells, a monofunctional response, and enhanced expression of inhibitory receptors. Overall, our results demonstrated that the infection outcomes caused by single or mixed T. cruzi infection with different genotypes induce a differential immune CD8+ T cell response quality. These findings suggest that the CD8+ T cell response might dictate differences in the infection outcomes at the chronic T. cruzi stage. This study shows that the T cell response quality is related to parasite control during chronic T. cruzi infection.

Training-professional profile of nurses teaching at the Technical Schools of the Unified Health System.

OBJECTIVE: to describe the training-professional profile of nursing professors in the vocational course in nursing at the Technical Schools of the Unified Health System. METHODS: a quantitative descriptive research, carried out with 61 nurses who are professors of technical courses in nursing at five technical schools in three Brazilian regions. Data were collected through an online questionnaire and submitted to descriptive analysis. RESULTS: only 36% of teaching nurses were licensed and 80% had a specialization in nursing or health. Although 95.1% of participants considered training for teaching necessary, 44.2% did not have qualifications for this job. The average length of work in care was 8 years, focusing on the hospital network. CONCLUSION: the need for professor training and investment in it is evidenced, as the training of essential workers for nursing care and consolidation of the Unified Health System is on the agenda.

Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects.

Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control.

Variability of the Pr77 sequence of L1Tc retrotransposon among six T. cruzi strains belonging to different discrete typing units (DTUs).

All trypanosomatid genomes are colonized by non-LTR retrotransposons which exhibit a highly conserved 77-nt sequence at their 5' ends, known as the Pr77-hallmark (Pr77). The wide distribution of Pr77 is expected to be related to the gene regulation processes in these organisms as it has promoter and HDV-like ribozyme activities at the DNA and RNA levels, respectively. The identification of Pr77 hallmark-bearing retrotransposons and the study of the associations of mobile elements with relevant genes have been analyzed in the genomes of six strains of Trypanosoma cruzi belonging to different discrete typing units (DTUs) and with different geographical origins and host/vectors. The genomes have been sequenced, assembled and annotated. BUSCO analyses indicated a good quality for the assemblies that were used in comparative analyses. The results show differences among the six genomes in the copy number of genes related to virulence processes, the abundance of retrotransposons bearing the Pr77 sequence and the presence of the Pr77 hallmarks not associated with retroelements. The analyses also show frequent associations of Pr77-bearing retrotransposons and single Pr77 hallmarks with genes coding for trans-sialidases, RHS, MASP or hypothetical proteins, showing variable proportion depending on the type of retroelement, gene class and parasite strain. These differences in the genomic distribution of active retroelements and other Pr77-containing elements have shaped the genome architecture of these six strains and might be contributing to the phenotypic variability existing among them.

Serological reactivity against T. cruzi-derived antigens: Evaluation of their suitability for the assessment of response to treatment in chronic Chagas disease.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects more than 6 million people worldwide. Following a mostly asymptomatic acute phase, the disease progresses to a long-lasting chronic phase throughout which life-threatening disorders to the heart and/or gastrointestinal tract will manifest in about 30% of those chronically infected. During the chronic phase, the parasitemia is low and intermittent, while a high level of anti-T. cruzi antibodies persist for years. These two features hamper post-chemotherapeutic follow-up of patients with the tools available. The lack of biomarkers for timely assessment of therapeutic response discourages a greater use of the two available anti-parasitic drugs, and complicates the evaluation of new drugs in clinical trials. Herein, we investigated in a blinded case-control study the serological reactivity over time of a group of parasite-derived antigens to potentially address follow up of T. cruzi chronically infected subjects after treatment. We tested PFR2, KMP11, HSP70, 3973, F29 and the InfYnity multiplexed antigenic array, by means of serological assays on a multi-national retrospective collection of samples. Some of the antigens exhibited promising results, underscoring the need for further studies to determine their potential role as treatment response biomarkers.

Collecting specialty-related medical terms: Development and evaluation of a resource for Spanish.

BACKGROUND: Controlled vocabularies are fundamental resources for information extraction from clinical texts using natural language processing (NLP). Standard language resources available in the healthcare domain such as the UMLS metathesaurus or SNOMED CT are widely used for this purpose, but with limitations such as lexical ambiguity of clinical terms. However, most of them are unambiguous within text limited to a given clinical specialty. This is one rationale besides others to classify clinical text by the clinical specialty to which they belong. RESULTS: This paper addresses this limitation by proposing and applying a method that automatically extracts Spanish medical terms classified and weighted per sub-domain, using Spanish MEDLINE titles and abstracts as input. The hypothesis is biomedical NLP tasks benefit from collections of domain terms that are specific to clinical subdomains. We use PubMed queries that generate sub-domain specific corpora from Spanish titles and abstracts, from which token n-grams are collected and metrics of relevance, discriminatory power, and broadness per sub-domain are computed. The generated term set, called Spanish core vocabulary about clinical specialties (SCOVACLIS), was made available to the scientific community and used in a text classification problem obtaining improvements of 6 percentage points in the F-measure compared to the baseline using Multilayer Perceptron, thus demonstrating the hypothesis that a specialized term set improves NLP tasks. CONCLUSION: The creation and validation of SCOVACLIS support the hypothesis that specific term sets reduce the level of ambiguity when compared to a specialty-independent and broad-scope vocabulary.