1,878 research outputs found
Host genetic basis of COVID-19: from methodologies to genes
No full textThe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is having a massive impact on public health, societies, and economies worldwide. Despite the ongoing vaccination program, treating COVID-19 remains a high priority; thus, a better understanding of the disease is urgently needed. Initially, susceptibility was associated with age, sex, and other prior existing comorbidities. However, as these conditions alone could not explain the highly variable clinical manifestations of SARS-CoV-2 infection, the attention was shifted toward the identification of the genetic basis of COVID-19. Thanks to international collaborations like The COVID-19 Host Genetics Initiative, it became possible the elucidation of numerous genetic markers that are not only likely to help in explaining the varied clinical outcomes of COVID-19 patients but can also guide the development of novel diagnostics and therapeutics. Within this framework, this review delineates GWAS and Burden test as traditional methodologies employed so far for the discovery of the human genetic basis of COVID-19, with particular attention to recently emerged predictive models such as the post-Mendelian model. A summary table with the main genome-wide significant genomic loci is provided. Besides, various common and rare variants identified in genes like TLR7, CFTR, ACE2, TMPRSS2, TLR3, and SELP are further described in detail to illustrate their association with disease severity
Chiara Lubich, Meditazioni: letteratura come relazione
No full textChiara Lubich (1920–2008), although the author of 32 books published in 26 countries (178 editions, 3.2 million copies), is better known for her social engagement, as reflected in numerous awards. She began to be regarded as a literary author only in the early 2000s, and primarily from a linguistic rather than literary perspective. This article focuses on her book Meditazioni (Meditations), reconstructs its genesis by tracing the writing process from the late 1950s to her death and the 2021 critical edition, and offers a literary analysis. This reveals Lubich as a forerunner of a new conception of literature: literature as relationship – not only between author and reader, but also among subject, inspiration, and the editorial process
Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features
No full textThe impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147-173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%-60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into "Boolean quantum features," inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores ( IPGS p h 1 and IPGS p h 2 ). By applying a logistic regression with both IPGS, ( IPGS p h 2 (or indifferently IPGS p h 1 ) and age as inputs, we reached an accuracy of 84%-86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147-173) by a factor of 10%
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
No full textThe combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.</p
Chiara Lubich: A Saint for a New Global Unity
No full textIn this article the author offers an introduction to the life, thought, and impact of Chiara Lubich. He begins with a brief biographical overview and draws attention to some important features of her spiritual teaching: Jesus in the midst, Jesus Forsaken, Mary Desolate, the four nights. He draws attention to the Economy of Communion and as an expression of this spirituality in the world of business and economics, and to the figure of Chiara Luce Badano, a young adherent to the Spirituality of Unity who has been recognized as an example of how this spirituality can lead to holiness of life. The author’s judgment is that Chiara Lubich is “a saint of dialogue.
Manifesto per il museo post-etnografico
No full textThe author signes a poetic manifesto for the future of ethnographic museums, beyond colonial representational stereotypes and methodologies
Il museo come metodo. E tu, che cosa vedi?
No full textThe chapter reflects upon the current achievements, at international scale, in reference to the education of the adolescents in the museum context. Drawing upon the experience of the "Che cosa vedi?" project, developed by the author herself at the Museo del Novecento, Milan, the chapter explores the scientific horizons, the best practices and the educational methodologies more suit for working with teenagers, such as peer education and debating. "Che cosa vedi?" was focused of the work of 4 prominent Italian artists of the XX century (Lucio Fontana, Toti Scialoja, Luciano Fabro and Mario Merz)
Potentially treatable disorder diagnosed post Mortem by exome analysis in a boy with respiratory distress
No full textWe highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed a7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test for CDKL5 in the boy, which came back negative. Driven by the mother’s compelling need for a diagnosis, we moved forward performing whole exome sequencing analysis. Surprisingly, two missense mutations in compound heterozygosity were identified in the RAPSN gene encoding a receptor-associated protein with a key role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites. This gene is responsible for a congenital form of myasthenic syndrome, a disease potentially treatable with cholinesterase inhibitors. Therefore, an earlier diagnosis in this boy would have led to a better clinical management and prognosis. Our study supports the key role of exome sequencing in achieving a definite diagnosis in severe perinatal diseases, an essential step especially when a specific therapy is available
Nosological and Theranostic Approach to Vascular Malformation through cfDNA NGS Liquid Biopsy
No full textSeveral different nosological classifications have been used over time for vascular malformations (VMs) since clinical and pathological signs are largely overlapping. In a large proportion of cases, VMs are generated by somatic mosaicism in key genes, belonging to a few different molecular pathways. Therefore, molecular characterization may help in the understanding of the biological mechanisms related to the development of pathology. Tissue biopsy is not routinely included in the diagnostic path because of the need for fresh tissue specimens and the risk of bleeding. Bypassing the need for bioptic samples, we took advantage of the possibility of isolating cell-free DNA likely released by the affected tissues, to molecularly characterize 53 patients by cfDNA-NGS liquid biopsy. We found a good match between the identified variant and the clinical presentation. PIK3CA variants were found in 67% of Klippel Trenaunay Syndrome individuals; KRAS variants in 60% of arteriovenous malformations; MET was mutated in 75% of lymphovenous malformations. Our results demonstrate the power of cfDNA-NGS liquid biopsy in VMs clinical classification, diagnosis, and treatment. Indeed, tailored repurposing of pre-existing cancer drugs, such as PIK3CA, KRAS, and MET inhibitors, can be envisaged as adjuvant treatment, in addition to surgery and/or endovascular treatment, in the above-defined VMs categories, respectively
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