Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.

Common genes and pathways involved in the response to stressful stimuli by astrocytes: A meta-analysis of genome-wide expression studies.

Astrocytes play pivotal roles in the brain and they become reactive under stress conditions. Here, we carried out, for the first time, an integrative meta-analysis of genome-wide expression profiling of astrocytes from human and mouse exposed to different stressful stimuli (hypoxia, infections by virus and bacteria, cytokines, ethanol, among others). We identified common differentially expressed genes and pathways in human and murine astrocytes. Our results showed that astrocytes induce expression of genes associated with stress response and immune system regulation when they are exposed to stressful stimuli, whereas genes related to neurogenesis are found as downregulated. Several of the identified genes showed to be important hubs in the protein-protein interaction analysis (TRAF2, CDC37 and PAX6). This work demonstrates that despite astrocytes are highly heterogeneous and complex, there are common gene expression signatures that can be triggered under distinct detrimental stimuli, which opens an opportunity for exploring other possible markers of reactivity.

Functional Genomics of Epileptogenesis in Animal Models and Humans.

It has been estimated that epilepsies are among the top five neurological diseases with the highest burden of disease. In recent years, genome-wide expression studies (GWES) have been carried out in experimental models of epilepsy and in samples from human patients. In this study, I carried out meta-analyses and analyses of convergence for available GWES for epileptogenesis in humans and in mouse, rat, zebrafish and fruit fly models. Multiple lines of evidence (such as genome-wide association data and known druggable genes) were integrated to prioritize top candidate genes for epileptogenesis and a functional enrichment analysis was carried out. Several top candidate genes, which are supported by multiple lines of genomic evidence, such as GRIN1, KCNAB1 and STX1B, were identified. Druggable genes of potential interest (such as GABRA2, GRIK1, KCNAB1 and STX4) were also identified. An enrichment of genes regulated by the MEF2 and SOX5 transcription factors and the miR-106b-5p and miR-101-3p miRNAs was found. The current work is the first meta-analysis and convergent analysis of GWES for epileptogenesis in humans and in multiple animal models, integrating results from several genomic studies. Novel candidate genes and pathways for epileptogenesis were identified in this analysis.

Sarcopenia: Etiology, Nutritional Approaches, and miRNAs.

Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the quality of life. Although there is a consensus that sarcopenia is a multifactorial syndrome, the etiology and underlying mechanisms are not yet delineated. Moreover, research about nutritional interventions to prevent the development of sarcopenia is mainly focused on the amount and quality of protein intake. The impact of several nutrition strategies that consider timing of food intake, anti-inflammatory nutrients, metabolic control, and the role of mitochondrial function on the progression of sarcopenia is not fully understood. This narrative review summarizes the metabolic background of this phenomenon and proposes an integral nutritional approach (including dietary supplements such as creatine monohydrate) to target potential molecular pathways that may affect reduce or ameliorate the adverse effects of sarcopenia. Lastly, miRNAs, in particular those produced by skeletal muscle (MyomiR), might represent a valid tool to evaluate sarcopenia progression as a potential rapid and early biomarker for diagnosis and characterization.

A brief guide to the science and art of writing manuscripts in biomedicine.

Publishing articles in international scientific journals is the primary method for the communication of validated research findings and ideas. Journal articles are commonly used as a major input for evaluations of researchers and institutions. Few articles have been published previously about the different aspects needed for writing high-quality articles. In this manuscript, we provide an updated and brief guide for the multiple dimensions needed for writing manuscripts in the health and biological sciences, from current, international and interdisciplinary perspectives and from our expertise as authors, peer reviewers and editors. We provide key suggestions for writing major sections of the manuscript (e.g. title, abstract, introduction, methods, results and discussion), for submitting the manuscript and bring an overview of the peer review process and  of the post-publication impact of the articles.

Convergent functional genomics of cocaine misuse in humans and animal models.

Background: Data from the Global Burden of Disease Study 2016 recently estimated that after opioid and cannabis use disorders, cocaine use disorders were among the most common, with around 5.8 million cases around the world. Several genome-wide expression studies (GWES) for cocaine misuse have been carried out in brain tissues from patients and controls and in mouse and rat models.Objectives: In the current work, we used a convergent functional genomics approach to identify novel candidate genes and pathways for cocaine misuse.Methods: We carried out meta-analyses for available GWES for cocaine misuse in humans and mouse and rat models (three, four, and two GWES, respectively). Multiple lines of evidence (GWES, genome-wide association and epigenomic data) were integrated to prioritize top candidate genes, and a functional enrichment analysis was carried out.Results: Several top candidate genes supported by multiple lines of genomic evidence, and with known roles in brain plasticity, were identified: APP, GRIN2A, GRIN2B, KCNA2, MAP4, PCDH10, PPP3CA, SNCB, and SV2C. An enrichment of genes regulated by the AP1 transcription factor was found.Conclusion: This is the first meta-analysis of GWES for cocaine misuse in humans and mouse and rat models. The analysis of convergence of multiple lines of genome-wide evidence identified novel candidate genes and pathways for cocaine misuse, which are of basic and clinical importance.

Current trends and future perspectives for medical education in Colombia.

Colombia is the second largest country in South America. In this article, we provide an overview of medical education in Colombia, including a description of existing public and private medical schools and available undergraduate and postgraduate programs. Medical education in Colombia has evolved through time, following international trends. In addition to 61 undergraduate medical programs, there are 529 postgraduate clinical, 30 PhD, and 131 Master programs in health sciences in Colombia. We identify current challenges and highlight future perspectives for medical education in Colombia.

Scientific productivity in neurosciences in Latin America: a scientometrics perspective.

Background: Neurosciences research has increased significantly in recent years around the world. It has led to the development of interdisciplinary work, moving from activities from isolated fields (such as biology, psychology or neurology) to research that involves different scientific perspectives. In developing regions, such as Latin America, it has additional challenges, related to available funding and infrastructure.Aim: To analyze key factors in scientific productivity in neurosciences in Latin America.Methods: A bibliometric analysis of the scientific productivity in neurosciences in main five Latin American countries (Argentina, Brazil, Chile, Colombia and Mexico) was carried out.Results: Brazil was the largest producer of scientific articles, and receptor of citations, in neurosciences in 1998-2017, followed by Mexico. We identified highly cited papers, top institutions, networks of authors, main journals and key areas in neurosciences for this period in the 5 countries.Conclusions: Scientific productivity in neurosciences in Latin America would benefit from the consolidation of more regional, interdisciplinary and international research networks. In this work, we discuss key elements for the consolidation of neurosciences research in Latin America.

Available Software for Meta-analyses of Genome-wide Expression Studies.

Advances in transcriptomic methods have led to a large number of published Genome-Wide Expression Studies (GWES), in humans and model organisms. For several years, GWES involved the use of microarray platforms to compare genome-expression data for two or more groups of samples of interest. Meta-analysis of GWES is a powerful approach for the identification of differentially expressed genes in biological topics or diseases of interest, combining information from multiple primary studies. In this article, the main features of available software for carrying out meta-analysis of GWES have been reviewed and seven packages from the Bioconductor platform and five packages from the CRAN platform have been described. In addition, nine previously described programs and four online programs are reviewed. Finally, advantages and disadvantages of these available programs and proposed key points for future developments have been discussed.

Predatory journals: Do not judge journals by their Editorial Board Members.

Objective: Given that often the quality of journals is based on its editors, the objective of this study was to describe quantitatively the profiles of members of editorial boards (MEBs) of presumed predatory journals. Methods: The following information was retrieved from 1015 editors taken from journals listed in Beall's list: country, university, position, and degree. The Scopus website was used to identify the number of citations, documents, and h-index. Results: Presumed open access predatory journals are including all types of profiles as their MEBs, which include fake and unqualified editors, but mostly very high-qualified scientists who are professors, medical doctors and/or had a PhD. MEBs were located in 74 different countries, most had an affiliation in the United States of America (USA) (44.4%). The median of publications per editor was 43, number of citations 664 and h-index 14. Conclusions: The results dispute the common belief that it is possible to identify predatory journals by checking their editorial boards. Scientists should not rely on the editors to determine if a journal is predatory. If an author has doubt, the editors should be contacted.

Network analysis of multiple risk factors for mental health in young Colombian adults.

BACKGROUND: A considerable proportion of young adults are affected by psychological distress at any time and an important fraction of them may develop mental disorders. Use of novel approaches for the analysis of data from multiple psychological scales might facilitate the identification of key indicators of mental health. AIMS: The aim of current study was to examine the relationship between multiple risk factors for mental illness, using a network analysis perspective. METHODS: A sample of 334 young Colombian adults (mean age = 21.7) were evaluated with validated scales measuring several psychosocial factors previously associated with mental health (e.g. worry, sleep problems, suicidal ideation, childhood abuse, alcohol related-problems and personality traits). A total of 24 nodes were included in the network analysis and topology, centrality, and stability of the networks were studied. RESULTS: Specific nodes that occupied critical positions in the network were identified, with worry, perceived distress and low energy being the most central nodes. CONCLUSIONS: Our explorative findings suggest that a network analysis might identify risk factors that have a central role in the multiple dimensions of emotional health in young adults. These novel analyses could have important applications for the understanding of the psychological functioning affecting mental health.

Effect of master mixes on the measurement of telomere length by qPCR.

Alterations in telomere length (TL) have been associated with several diseases and a method based on qPCR, the Monochrome Multiplex Real-Time Quantitative PCR (MMQPCR) technique, has been used extensively for the analysis of TL. Some previous studies have been found that certain methodological conditions can affect the measurement of TL. The aim of the study was to evaluate the performance of eight different commercially available SYBR Green and High-Resolution Melting (HRM) mixes on the measurement of TL by the MMQPCR method. Four SYBR Green and four HRM mixes were tested and the measurement of TL was expressed by the T/S ratio. It was found that the type of master mix used in MMQPCR influences the measurement of TL, affecting aspects such as the specificity and consistency of the results. Our results are the first description of the effects of different master mixes on TL analysis by MMQPCR and highlight the importance of the future methodological improvement of this broadly used technique.

Personality traits and health-related quality of life: the mediator role of coping strategies and psychological distress.

BACKGROUND: The study of health-related quality of life (HRQOL) is an important topic in mental health around the globe. However, there is the need for more evidence about the cumulative influence of psychological variables on HRQOL. The main aim of the study was to evaluate how specific personality traits might explain scores in HRQOL and to explore how this relationship might be mediated by coping styles and psychological distress. METHODS: Young Colombian subjects (N = 274) were included (mean age: 21.3; SD = 3.8). The Short-Form Health Survey was used to measure HRQOL. For assessment of psychological variables, the Hospital Anxiety and Depression Scale, the Zung Self-Rating Anxiety Scale, The Coping Inventory for Stressful Situations and the short version of Big Five Inventory were used. RESULTS: The personality trait that was the best predictor of HRQOL was openness to experience, forming an explanatory model for HRQOL, along with emotional coping style and depressive and anxious symptoms. Emotional coping style and psychological distress were significant mediators of the relationship between openness and HRQOL. CONCLUSIONS: Our findings provide additional data about the cumulative influence of specific psychological variables on HRQOL, in a mostly young female Latin American sample.

Genome-Wide Expression Profiles for Ischemic Stroke: A Meta-Analysis.

BACKGROUND: Genome-wide expression studies (GWES), using microarray platforms, have allowed a deeper understanding of the molecular factors involved in the pathophysiology of ischemic stroke (IS), one of the main global causes of mortality and disability. METHODS: In the current work, we carried out a meta-analysis of available GWES for IS. Bioinformatics and computational biology analyses were applied to identify enriched functional categories and convergence with other genomic datasets for IS. RESULTS: Three primary datasets were included and in the meta-analyses for GWES and IS, 41 differentially expressed (DE) genes were identified using a random effects model. Thirteen of these genes were downregulated and 28 were upregulated. An analysis of functional categories found a significant enrichment for the Gene Ontology Term "Inflammatory Response" and for binding sites for the PAX2 transcription factor. CONCLUSIONS: The list of DE genes identified in this meta-analysis of GWES for IS is useful for future genetic and molecular studies, which would allow the identification of novel mechanisms involved in the pathophysiology of IS. Several of the DE genes found in this meta-analysis have known functional roles related to mechanisms involved in the pathophysiology of IS. It is recognized the role of the inflammatory response in the pathophysiology of IS.

APOE gene and neuropsychiatric disorders and endophenotypes: A comprehensive review.

The Apolipoprotein E (APOE) gene is one of the main candidates in neuropsychiatric genetics, with hundreds of studies carried out in order to explore the possible role of polymorphisms in the APOE gene in a large number of neurological diseases, psychiatric disorders, and related endophenotypes. In the current article, we provide a comprehensive review of the structural and functional aspects of the APOE gene and its relationship with brain disorders. Evidence from genome-wide association studies and meta-analyses shows that the APOE gene has been significantly associated with several neurodegenerative disorders. Cellular and animal models show growing evidence of the key role of APOE in mechanisms of brain plasticity and behavior. Future analyses of the APOE gene might find a possible role in other neurological diseases and psychiatric disorders and related endophenotypes. © 2016 Wiley Periodicals, Inc.

Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.

The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia. Here, we report that mice defective of the nicastrin subunit of γ-secretase in oligodendrocytes have hypomyelination in the central nervous system. These mice have altered dopamine signaling and display profound abnormal phenotypes reminiscent of schizophrenia. In addition, we identify an association of the nicastrin gene with a human schizophrenia cohort. These observations implicate γ-secretase and its mediated neurodevelopmental pathways in schizophrenia and provide support for the "myelination hypothesis" of the disease. Moreover, by showing that schizophrenia and obsessive-compulsive symptoms could be modeled in animals wherein a single genetic factor is altered, our work provides a biological basis that schizophrenia with obsessive-compulsive disorder is a distinct subtype of schizophrenia.

Spurious alternative impact factors: The scale of the problem from an academic perspective.

The recent explosion in the number of predatory journals has led to the appearance of questionable websites providing fake or spurious impact factors, which are analyzed and discussed here. We believe that academic associations, universities, and research funding bodies must take action to stop these questionable practices.

Substance use and suicide risk in a sample of young Colombian adults: An exploration of psychosocial factors.

BACKGROUND AND OBJECTIVES: Young adults might engage in many risk behaviors, including alcohol and drug use, which could lead to mental health problems, such as suicide. The aim of this study was to examine specific psychosocial and clinical factors that could influence the possible relationship between polysubstance use (PSU) and suicide risk in a sample of young Colombian participants. METHODS: A sample of 274 young participants (mean age = 21.3 years) was evaluated with two substance use screening tests (ASSIST and AUDIT) and five scales for clinical and psychosocial factors and suicide risk: The Center for Epidemiologic Studies Depression scale, Zung Self-Rating Anxiety scale, Family APGAR, the Childhood Trauma Questionnaire, and the Plutchik Suicide Risk scale. Correlation and multiple regression analyses were conducted. RESULTS: Use of cannabis and tobacco was significantly correlated with suicide risk in the total sample (p < .05). Depressive and anxiety symptoms, family functioning, and emotional abuse during childhood were significantly associated with suicide risk (p < .001), while alcohol use, anxiety symptoms, and family functioning were variables significantly related to PSU. DISCUSSION AND CONCLUSIONS: Our findings are consistent with previous evidence suggesting a relationship between substance use, several psychosocial factors, and suicide risk in young participants. SCIENTIFIC SIGNIFICANCE: Our study is one of the first reports the relationship between substance use and suicide risk in a Latin American population. (Am J Addict 2017;26:388-394).

Functional genomics of candidate genes derived from genome-wide association studies for five common neurological diseases.

AIM: Recent genome-wide association studies (GWAS) are identifying novel candidate genes for several neurological diseases (NDs). However, a global functional analysis of those genes derived from GWAS for NDs is missing. We explored the genomic and functional features of novel candidate genes for five common NDs: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke and migraine. MATERIALS AND METHODS: A functional enrichment analysis was performed for GWAS-derived genes, for categories such as Kyoto Encyclopedia of Genes and Genomes pathways, gene expression, InterPro domains, transcription factor binding sites, gene ontology (GO) terms and microRNA (miRNA) targets. An analysis of protein-protein interactions was carried out. RESULTS: Six hundred and forty-two unique single nucleotide polymorphisms (SNPs) were identified for the five NDs and 2.3% of them were non-synonymous SNPs. There were no common SNPs for all five NDs and eight genes were associated with more than one ND. The enrichment analysis showed significant values for several GO categories, such as cell-cell adhesion and location in neurites and for expression in prefrontal cortex. An analysis of protein-protein interactions showed the evidence of a large component. Fifty-one of these GWAS-derived genes are known to be potentially druggable and twelve are known to harbor mutations for neuropsychiatric disorders. CONCLUSIONS: Our results suggest that there is little overlap between the genes identified in GWAS for the five common NDs. Identification of functional categories in the GWAS-derived candidate genes for common NDs could lead to a better understanding of their functional consequences and could be useful for the future discovery of additional genetic risk factors for those diseases.

Success stories in genomic medicine from resource-limited countries.

In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.