The Ethics of Human Enhancement and Ferrando’s Philosophical Posthumanism

Francesca Ferrando's book Philosophical Posthumanism concentrates on some of the ethical issues connected with genetic alteration of the human species. In sympathy with her analysis, this brief article (commentary) elaborates on a parallel topic: the ethical implications of current projects to modify humans and their society with digital emerging technology.

Comprehensive Analyses of the Expression, Genetic Alteration, Prognosis Significance, and Interaction Networks of m6A Regulators Across Human Cancers

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein–protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators–potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators’ roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.

Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas

Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing’s sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.

Radiomics-based prediction of multiple gene alteration incorporating mutual genetic information in glioblastoma and grade 4 astrocytoma, IDH-mutant

Purpose In glioma, molecular alterations are closely associated with disease prognosis. This study aimed to develop a radiomics-based multiple gene prediction model incorporating mutual information of each genetic alteration in glioblastoma and grade 4 astrocytoma, IDH-mutant. Methods From December 2014 through January 2020, we enrolled 418 patients with pathologically confirmed glioblastoma (based on the 2016 WHO classification). All selected patients had preoperative MRI and isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor amplification, and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss status. Patients were randomly split into training and test sets (7:3 ratio). Enhancing tumor and peritumoral T2-hyperintensity were auto-segmented, and 660 radiomics features were extracted. We built binary relevance (BR) and ensemble classifier chain (ECC) models for multi-label classification and compared their performance. In the classifier chain, we calculated the mean absolute Shapley value of input features. Results The micro-averaged area under the curves (AUCs) for the test set were 0.804 and 0.842 in BR and ECC models, respectively. IDH mutation status was predicted with the highest AUCs of 0.964 (BR) and 0.967 (ECC). The ECC model showed higher AUCs than the BR model for ATRX (0.822 vs. 0.775) and MGMT promoter methylation (0.761 vs. 0.653) predictions. The mean absolute Shapley values suggested that predicted outcomes from the prior classifiers were important for better subsequent predictions along the classifier chains. Conclusion We built a radiomics-based multiple gene prediction chained model that incorporates mutual information of each genetic alteration in glioblastoma and grade 4 astrocytoma, IDH-mutant and performs better than a simple bundle of binary classifiers using prior classifiers’ prediction probability.

Offspring production from cryopreserved primordial germ cells in Drosophila

There is an urgent need to cryopreserve Drosophila stocks that have been maintained as living cultures for a long time. Long-term culture increases the risk of accidental loss and of unwanted genetic alteration. Here, we report that cryopreserved primordial germ cells (PGCs) can produce F1 progeny when transplanted into hosts. The cryopreserved donor PGCs could form germline stem cells in host gonads and contributed to continuous offspring production. Furthermore, the ability to produce offspring did not appear to vary with either differences between donor strains or cryopreservation duration. Therefore, we propose that our cryopreservation method is feasible for long-term storage of various Drosophila strains. These results underscore the potential usefulness of our cryopreservation method for backing up living stocks to avoid either accidental loss or genetic alteration.