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Severino, M.

Publications and source records attributed to Severino, M..

2 recordsLinked to original sources

Data-driven characterization of Preterm Birth through intramodal Diffusion MRI

Preterm birth still represents a concrete emergency to be managed and addressed globally. Since cerebral white matter injury is the major form of brain impairment in survivors of premature birth, the identification of reliable, non-invasive markers of altered white matter development is of utmost importance in diagnostics. Diffusion MRI has recently emerged as a valuable tool to investigate these kinds of alterations. In this work, rather than focusing on a single MRI modality, we worked on a compound of beyond-DTI High Angular Resolution Diffusion Imaging (HARDI) techniques in a group of 46 preterm babies studied on a 3T scanner at term equivalent age and in 23 control neonates born at term. After extracting relevant derived parameters, we examined discriminative patterns of preterm birth through (i) a traditional voxel-wise statistical method such as the Tract-Based Spatial Statistics approach (TBSS); (ii) an advanced Machine Learning approach such as the Support Vector Machine (SVM) classification; (iii) establishing the degree of association between the two methods in voting white matter most discriminating areas. Finally, we applied a multi-set Canonical Correlation Analysis (CCA) in search for sources of linked alterations across modalities. TBSS analysis showed significant differences between preterm and term cohorts in several white matter areas for multiple HARDI features. SVM classification performed on skeletonized HARDI measures produced satisfactory accuracy rates, especially as for highly informative parameters about fibers directionality. Assessment of the degree of overlap between the relevant measures identified by the two methods exhibited a good, though parameter-dependent rate of agreement. Finally, CCA analysis identified joint changes precisely for those features exhibiting less correspondence between TBSS and SVM. Our results suggest that a data-driven intramodal imaging approach is crucial to extract deep and complementary information that cannot be extracted from a single modality.

bioengineering↗

Cerebral organoids expressing mutant actin genes reveal cellular mechanism underlying microcephalic cortical malformation

Actins are structural cytoskeletal proteins playing crucial roles in multiple cellular processes. Mutations in the ACTB and ACTG1 genes, encoding the ubiquitous beta- and gamma- cytoskeletal actin isoforms, respectively, cause a broad spectrum of neurodevelopmental disorders, with microcephaly as the most frequent one. Here we used patient-derived cerebral organoids to gain insight into the pathogenesis underlying this cortical malformation. Cerebral organoids from induced pluripotent stem cells (iPSCs) of patients with the Baraitser-Winter- CerebroFrontoFacial syndrome (BWCFF-S), expressing either an ACTB or an ACTG1 missense mutation, are reduced in size, showing a thinner ventricular zone (VZ). This decrease in VZ progenitors is in turn associated with a striking change in the orientation of their cleavage plane from predominantly vertical (control) to predominantly horizontal (BWCFF-S), which is incompatible with increasing VZ progenitor abundance. Various cytoskeletal and morphological irregularities of BWCFF-S VZ progenitors, notably in the apical region of these cells, seemingly contribute to their predominantly horizontal cleavage plane orientation. Our results provide insight into the cell biological basis of the microcephaly associated with BWCFF-S caused by actin mutations.

neuroscience↗