Identification of Relevant Protein Interactions with Partial Knowledge: A Complex Network and Deep Learning Approach.

Protein-protein interactions (PPIs) are the basis for understanding most cellular events in biological systems. Several experimental methods, e.g., biochemical, molecular, and genetic methods, have been used to identify protein-protein associations. However, some of them, such as mass spectrometry, are time-consuming and expensive. Machine learning (ML) techniques have been widely used to characterize PPIs, increasing the number of proteins analyzed simultaneously and optimizing time and resources for identifying and predicting protein-protein functional linkages. Previous ML approaches have focused on well-known networks or specific targets but not on identifying relevant proteins with partial or null knowledge of the interaction networks. The proposed approach aims to generate a relevant protein sequence based on bidirectional Long-Short Term Memory (LSTM) with partial knowledge of interactions. The general framework comprises conducting a scale-free and fractal complex network analysis. The outcome of these analyses is then used to fine-tune the fractal method for the vital protein extraction of PPI networks. The results show that several PPI networks are self-similar or fractal, but that both features cannot coexist. The generated protein sequences (by the bidirectional LSTM) also contain an average of 39.5% of proteins in the original sequence. The average length of the generated sequences was 17% of the original one. Finally, 95% of the generated sequences were true.

A Two-Parameter Fractional Tsallis Decision Tree.

Decision trees are decision support data mining tools that create, as the name suggests, a tree-like model. The classical C4.5 decision tree, based on the Shannon entropy, is a simple algorithm to calculate the gain ratio and then split the attributes based on this entropy measure. Tsallis and Renyi entropies (instead of Shannon) can be employed to generate a decision tree with better results. In practice, the entropic index parameter of these entropies is tuned to outperform the classical decision trees. However, this process is carried out by testing a range of values for a given database, which is time-consuming and unfeasible for massive data. This paper introduces a decision tree based on a two-parameter fractional Tsallis entropy. We propose a constructionist approach to the representation of databases as complex networks that enable us an efficient computation of the parameters of this entropy using the box-covering algorithm and renormalization of the complex network. The experimental results support the conclusion that the two-parameter fractional Tsallis entropy is a more sensitive measure than parametric Renyi, Tsallis, and Gini index precedents for a decision tree classifier.

NH2-terminal deletion of specific phosphorylation sites on PHOX2B disrupts the formation of enteric neurons in vivo.

Mutations in the paired-like homeobox 2 b (PHOX2B) gene are associated with congenital central hypoventilation syndrome (CCHS), which is a rare condition in which both autonomic dysregulation with hypoventilation and an enteric neuropathy may occur. The majority of patients with CCHS have a polyalanine repeat mutation (PARM) in PHOX2B, but a minority of patients have nonpolyalanine repeat mutations (NPARMs), some of which have been localized to exon 1. A PHOX2B-Y14X nonsense mutation previously generated in a human pluripotent stem cell (hPSC) line results in an NH2-terminus truncated product missing the first 17 or 20 amino acids, possibly due to translational reinitiation at an alternate ATG start site. This NH2-terminal truncation in the PHOX2B protein results in the loss of two key phosphorylation residues. Though the deletion does not affect the potential for PHOX2BY14X/Y14X mutant hPSC to differentiate into enteric neural crest cells (ENCCs) in culture, it impedes in vivo development of neurons in an in vivo model of human aganglionic small intestine.NEW & NOTEWORTHY A mutation that affects only 17-20 NH2-terminal amino acids in the paired-like homeobox 2 b (PHOX2B) gene hinders the subsequent in vivo establishment of intestinal neuronal cells, but not the in vitro differentiation of these cells.

Lobomycosis-like disease in common bottlenose dolphins Tursiops truncatus from Belize and Mexico: bridging the gap between the Americas.

Lobomycosis and lobomycosis-like diseases (LLD) (also: paracoccidioidomycosis) are chronic cutaneous infections that affect Delphinidae in tropical and subtropical regions worldwide. In the Americas, these diseases have been relatively well-described, but gaps still exist in our understanding of their distribution across the continent. Here we report on LLD affecting inshore bottlenose dolphins Tursiops truncatus from the Caribbean waters of Belize and from the eastern tropical Pacific Ocean off the southwestern coast of Mexico. Photo-identification and catalog data gathered between 1992 and 2017 for 371 and 41 individuals, respectively from Belize and Mexico, were examined for the presence of LLD. In Belize, 5 free-ranging and 1 stranded dolphin were found positive in at least 3 communities with the highest prevalence in the south. In Guerrero, Mexico, 4 inshore bottlenose dolphins sighted in 2014-2017 were affected by LLD. These data highlight the need for histological and molecular studies to confirm the etiological agent. Additionally, we document a single case of LLD in an adult Atlantic spotted dolphin Stenella frontalis in southern Belize, the first report in this species. The role of environmental and anthropogenic factors in the occurrence, severity, and epidemiology of LLD in South and Central America requires further investigation.

[Quality of life in patients with prostate cancer: validation of an instrument for clinical practice]. / Calidad de vida en pacientes con cáncer de próstata: la validación de un instrumento para la práctica clínica.

OBJECTIVES: Currently there are instruments to evaluate the different features of the impact on quality of life in those patients with prostate cancer undergoing any type of treatment, but most of them have 50 or more questions and they are difficult to apply in clinical practice. An English validation of a shortened version of the EPIC (Expanded Prostate Cancer Composite), the most used instrument to measure the quality of life in patients with prostate cancer, has been published recently. This version called EPIC-CP (Expanded Prostate Cancer Composite-Clinical Practice) consists of 16 questions arranged in a page, for easy and rapid clinical application. The objective of this work is to validate a Spanish version of the EPIC-CP. METHOD: An inversa-directa Spanish translation of the original version was performed. The EPIC-CP and EQ5D questionnaires were applied to 46 patients eligible to be subjected to different treatments - open prostatectomy (OP), Robotic Prostatectomy (RP), brachytherapy (Br) or conformational radiotherapy (CR) - and 82 patients already treated (9 OP, 13 RP, 7 Br, 4 CR). For reliability evaluation, the Cronbach's alpha was used to test the internal consistency for each domain of the EPIC-CP. Treated and untreated patients' scores were compared with the Wilcoxon range sum test to assess the sensitivity to change. RESULTS: Cronbach's alpha was elevated in all the EPIC-CP domains (near or greater than 0.7), indicating a high internal consistency. There was no significant difference in age and educational level between treated and untreated patients. We found significant differences between treated and untreated patients in the total EPIC CP score, in the domains of urinary incontinence, bowel function, sexual function and hormonal function. CONCLUSION: The Spanish version of the EPIC-CP is reliable and valid, so it is a useful tool to measure the quality of life in patients with prostate cancer, as well as the impact of different treatments.

Calidad de vida en pacientes con cáncer de próstata: Validación de un instrumento para la práctica clínica / Quality of life in patients with prostate cancer: validation of an instrument for clinical practice

OBJETIVO: Actualmente existen instrumentos para evaluar los distintos aspectos en el impacto sobre la calidad de vida en aquellos pacientes portadores de cáncer de próstata que son sometidos a algún tipo de tratamiento, pero la mayoría son de 50 o más preguntas y de difícil aplicación en la práctica clínica. Recientemente se ha publicado la validación en inglés de una versión acortada del instrumento más utilizado para medir la calidad de vida en pacientes con cáncer de próstata: EPIC (Expanded Prostate Cancer Composite). Esta versión denominada EPIC-CP (Expanded Prostata Cancer Composite-Clinical Practice) consiste en 16 preguntas dispuestas en una página, de fácil y rápida aplicación clínica. El objetivo primario de este trabajo fue desarrollar y validar el cuestionario EPIC-CP en español como instrumento de evaluación de calidad de vida en pacientes con cáncer de próstata (CaP). Un objetivo secundario fue la observación de las diferencias de los aspectos que impactan en la calidad de vida entre los pacientes tratados y los candidatos a tratamiento. MÉTODOS: Se realizó una traducción inversa-directa al español de la versión original de la encuesta. Se aplicaron 128 cuestionarios de calidad de vida EPIC-CP y EQ5D (cuestionario de salud del EuroQuol Group Association) a 46 (40%) pacientes candidatos a ser sometidos a diferentes tratamientos - Prostatectomía abierta (PA), Prostatectomía robótica (PR), Braquiterapia (Br) o Radioterapia Conformacional (RC)- y a 82 (64%) pacientes ya tratados (9 PA, 13 PR, 7 Br y 4 RC). Para evaluar la confiabilidad se evaluó la consistencia interna a través del Coeficiente Alfa de Cronbach para cada categoría de la EPIC-CP. Para valorar la sensibilidad al cambio se compararon las puntuaciones en pacientes tratados y no tratados con el test de Suma de Rangos de Wilcoxon. RESULTADOS: En todos los dominios de la EPIC-CP, se obtuvo un consistencia interna elevada (alfa de Cronbach 0,66-0,9). No se encontraron diferencias significativas en la edad ni en el nivel educacional entre pacientes tratados y no tratados. Se encontraron diferencias significativas en la puntuación total de la EPIC CP entre pacientes tratados y no tratados en los dominios incontinencia urinaria (p = 0,0002), función intestinal (p = 0,04), sexual (p < 0,0001) y función hormonal (p = 0,002). CONCLUSIÓN: La versión en del EPIC-CP es confiable y válida, por lo que resulta una herramienta útil para medir la calidad de vida en pacientes con CaP, así como el impacto de distintos tratamientos en ella

OBJECTIVES: Currently there are instruments to evaluate the different features of the impact on quality of life in those patients with prostate cancer undergoing any type of treatment, but most of them have 50 or more questions and they are difficult to apply in clinical practice. An English validation of a shortened version of the EPIC (Expanded Prostate Cancer Composite), the most used instrument to measure the quality of life in patients with prostate cancer, has been published recently. This version called EPIC-CP (Expanded Prostate Cancer Composite-Clinical Practice) consists of 16 questions arranged in a page, for easy and rapid clinical application. The objective of this work is to validate a Spanish version of the EPIC-CP. METHOD: An inversa-directa Spanish translation of the original version was performed. The EPIC-CP and EQ5D questionnaires were applied to 46 patients eligible to be subjected to different treatments - open prostatectomy (OP), Robotic Prostatectomy (RP), brachytherapy (Br) or conformational radiotherapy (CR) - and 82 patients already treated (9 OP, 13 RP, 7 Br, 4 CR). For reliability evaluation, the Cronbach's alpha was used to test the internal consistency for each domain of the EPIC-CP. Treated and untreated patients' scores were compared with the Wilcoxon range sum test to assess the sensitivity to change. RESULTS: Cronbach's alpha was elevated in all the EPIC-CP domains (near or greater than 0.7), indicating a high internal consistency. There was no significant difference in age and educational level between treated and untreated patients. We found significant differences between treated and untreated patients in the total EPIC CP score, in the domains of urinary incontinence, bowel function, sexual function and hormonal function. CONCLUSIÓN: The Spanish version of the EPIC-CP is reliable and valid, so it is a useful tool to measure the quality of life in patients with prostate cancer, as well as the impact of different treatments

Molecular modeling applied to anti-cancer drug development.

In the past, anti-cancer drugs were identified and developed without focusing on a particular macromolecular target. Currently, the fields of molecular biochemistry, molecular biology, genetics and pharmacology, among other disciplines, have grown considerably in their ability to identify biological targets. These disciplines are now searching for specific targets to treat cancer. These targets exist in different cellular compartments (membrane, cytoplasm, nucleus) as proteins, glycoproteins, nucleic acids, etc. Computational tools have recently been used to explore such targets and to corroborate previously obtained experimental data. These methods have also been used to design new drugs with the aim of decreasing illness and the economic resources needed to discover drug candidates. Some of these computational methods include quantum mechanics (ab initio and density functional theories) and molecular mechanics (docking, molecular dynamics, and protein folding). Docking and molecular dynamics are the most commonly used computational tools for elucidating cancer targets. Using these tools, one can identify the recognition processes between ligands and targets at the atomic level. In addition, one can identify the affinity and conformational changes of these molecular complexes. In conclusion, we propose that the use of such tools is necessary in order to identify new anti-cancer drugs.

Osteosarcoma paraosteal (juxtacortical): revisión de un caso clínico patológico en un perro / Paraosteal (juxtacortical) osteosarcoma: report of clinical-pathological case in a dog

El osteosarcoma paraosteal constituye una neoplasia primaria de hueso, caracterizada por desarrollarse en la superficie ósea; está compuesta por tejido fibroso, óseo y cartilaginoso bien diferenciado pero con características de malignidad. El caso se presentó en un perro Pastor Alemán, macho, de 8 años de edad, diagnosticado por punción con aguja delgada y estudio radiográfico, y confirmado por estudio histológico