In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19.

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively. Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19. Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics. Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at https://github.com/muntisa/immuno-drug-repurposing-COVID-19.

Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report.

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). CASE PRESENTATION: Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. CONCLUSIONS: This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.

Asociación entre síntomas depresivos satisfacción corporal y estado nutricional en niños y adolescentes / The relationschip between depressive symptoms, nutricional stratus and corporal dissatisfaction in adolescents

El objetivo de este trabajo es estudiar la relación entre síntomas depresivos, estado nutricional e insatisfacción corporal en adolescentes. Nuestra hipótesis es que el estado nutricional esta asociado a sintomatología depresiva y que esta asociación puede estar mediada por el grado de insatisfacción corporal. La muestra corresponde a adolescentes, de ambos sexos, de 10 a 19 años, entre 5° básico y 4° medio, de Liceos Municipalizados de Hombres y de Mujeres de la comuna de Independencia. Obtenido su asentimiento y el consentimiento de sus padres, se procedió a la medición de peso y talla de 285 sujetos, a fin de obtener su índice de masa corporal (IMC), clasificándose en bajo peso, peso normal, riesgo de obesidad y obesidad, de acuerdo a las curvas de IMC para la edad del CDCNCHS. Se aplicó el Cuestionario de Depresión Infantil (CDI) considerándose los puntos de corte 14, 15 a 18 y 19, y el Cuestionario de Insatisfacción Corporal de la Universidad de Dallas, modificado por Rubén Zukerfeld (CIC) que clasifica a la muestra según insatisfacción corporal ausente, estándar, intensa y muy intensa. Los resultados muestran una prevalencia de síntomas depresivos superior que en estudios internacionales para el tramo etario, 15,8 por ciento considerando punto de corte 19, y 31,2 por ciento si consideramos punto de corte 15 (especificidad de 90 por ciento). Se encontraron cifras de obesidad (12,3 por ciento) y riesgo de obesidad (19,6 por ciento) acordes a la realidad nacional en este periodo evolutivo. No se observó una relación, directa y significativa, entre estado nutricional y síntomas depresivos, sin embrago si se encuentra una asociación entre insatisfacción corporal y sintomatología depresiva, lo que plantea el desafío de comprender mejor el significado de la corporalidad para el sujeto en este periodo evolutivo.

This work aims to explore the relationship between depressive symptoms, nutritional status and corporal dissatisfaction in adolescents. Our hypothesis is that the nutritional state this associated with depressive symptomatology and that this association can be mediated by the degree of corporal dissatisfaction. The sample is adolescents of both sexes, 10 to 19 years, between 5 th. To 12th, grade in mixed (female and male), public school at the Independencia’s neighborhood. Obtained their consent and the consent of their parents, we proceeded to the measurement of weight and height of 285 students to obtain their Body Mass Index (BMI), BMI classifying into low weight, normal weight, risk of obesity and obesity, according to the IMC curves for the age of CDC-NCHS. Was applied the questionnaire child depression (CDI) whereas the 14, 15 and 18 and 19, breakpoints and the Dissatisfaction Body Questionnaire (DBQ) of the University of Dallas, questionnaire amended by Rubén Zukerfeld that classifies the sample according to body dissatisfaction absent, standard, intense and very intense. The results show a higher prevalence of depressive symptoms that in international studies for the installment age, 15.8 percent whereas breakpoint 19 and 31.2 percent considering breakpoint 15 (90 percent specificity). Found obesity’s figures (12.3 per cent) and obesity’s risk (19.6 percent) according to the national reality in this evolutionary period. The study show that not observed a direct and significant relationship between nutritional status and depressive symptoms, however, was founding an association between body dissatisfaction and depressive symptomatology. These conclusion, posed the challenge to obtain a better understanding the meaning of the body image for the peoples in this evolutionary period.