Pictorial guide for variants of Covid-19: CT imaging and interpretation.

Typical radiologic images of Covid-19 pneumonia consists in a wide spectrum of chest manifestations, which range from peripheral predominant ground-glass opacities to an organizing pneumonia pattern, with additional features including crazy-paving, consolidations, fibrotic streaks and linear opacities. With variants imaging profile of Covid-19 evolves, producing relatively atypical/indeterminate CT pattern of pulmonary involvement, which overlap with imaging features of a variety of other respiratory diseases, including infections, drug reaction and hypersensitivity pneumonia. Our knowledge of these radiological findings is incomplete and there is a need to strengthen the recognition of the many faces of Covid-19 pneumonia.

Chest CT features of COVID-19 in vaccinated versus unvaccinated patients: use of CT severity score and outcome analysis.

Objectives: To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS).

Methods: Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained.

Genetics and Molecular Basis of Congenital Heart Defects in Down Syndrome: Role of Extracellular Matrix Regulation.

Down syndrome (DS), a complex disorder that is caused by the trisomy of chromosome 21 (Hsa21), is a major cause of congenital heart defects (CHD). Interestingly, only about 50% of individuals with Hsa21 trisomy manifest CHD. Here we review the genetic basis of CHD in DS, focusing on genes that regulate extracellular matrix (ECM) organization.

Down Syndrome Fetal Fibroblasts Display Alterations of Endosomal Trafficking Possibly due to SYNJ1 Overexpression.

Endosomal trafficking is essential for cellular homeostasis. At the crossroads of distinct intracellular pathways, the endolysosomal system is crucial to maintain critical functions and adapt to the environment. Alterations of endosomal compartments were observed in cells from adult individuals with Down syndrome (DS), suggesting that the dysfunction of the endosomal pathway may contribute to the pathogenesis of DS.

Overexpression of the Hsa21 Transcription Factor RUNX1 Modulates the Extracellular Matrix in Trisomy 21 Cells.

Down syndrome is a neurodevelopmental disorder frequently characterized by other developmental defects, such as congenital heart disease. Analysis of gene expression profiles of hearts from trisomic fetuses have shown upregulation of extracellular matrix (ECM) genes. The aim of this work was to identify genes on chromosome 21 potentially responsible for the upregulation of ECM genes and to pinpoint any functional consequences of this upregulation.

Activation of Non-Canonical Autophagic Pathway through Inhibition of Non-Integrin Laminin Receptor in Neuronal Cells.

To fight neurodegenerative diseases, several therapeutic strategies have been proposed that, to date, are either ineffective or at the early preclinical stages. Intracellular protein aggregates represent the cause of about 70% of neurodegenerative disorders, such as Alzheimer's disease. Thus, autophagy, i.

Quantitative CT texture analysis in predicting PD-L1 expression in locally advanced or metastatic NSCLC patients.

Purpose: The assessment of Programmed death-ligand 1 (PD-L1) expression has become a game changer in the treatment of patients with advanced non-small cell lung cancer (NSCLC). We aimed to investigate the ability of Radiomics applied to computed tomography (CT) in predicting PD-L1 expression in patients with advanced NSCLC.

Methods: By applying texture analysis, we retrospectively analyzed 72 patients with advanced NSCLC.

Human Trisomic iPSCs from Down Syndrome Fibroblasts Manifest Mitochondrial Alterations Early during Neuronal Differentiation.

Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction.

Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol.

Generation of an iPSC line (UNINAi001-A) from a girl with neonatal-onset epilepsy and non-syndromic intellectual disability carrying the homozygous KCNQ3 p.PHE534ILEfs*15 variant and of an iPSC line (UNINAi002-A) from a non-carrier, unaffected brother.

Heterozygous variants in the KCNQ3 gene cause epileptic and/or developmental disorders of varying severity. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a 9-year-old girl with pharmacodependent neonatal-onset epilepsy and intellectual disability who carry a homozygous single-base duplication in exon 12 of KCNQ3 (NM_004519.3: KCNQ3 c.

Inhibition of 37/67kDa Laminin-1 Receptor Restores APP Maturation and Reduces Amyloid-β in Human Skin Fibroblasts from Familial Alzheimer's Disease.

Alzheimer's disease (AD) is a fatal neurodegenerative disorder caused by protein misfolding and aggregation, affecting brain function and causing dementia. Amyloid beta (Aβ), a peptide deriving from amyloid precursor protein (APP) cleavage by-and γ-secretases, is considered a pathological hallmark of AD. Our previous study, together with several lines of evidence, identified a strict link between APP, Aβ and 37/67kDa laminin receptor (LR), finding the possibility to regulate intracellular APP localization and maturation through modulation of the receptor.

Corrigendum: Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells.

[This corrects the article DOI: 10.3389/fgene.2019.

Targeting Mitochondrial Network Architecture in Down Syndrome and Aging.

Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments.

PAX8 expression in high-grade serous ovarian cancer positively regulates attachment to ECM via Integrin β3.

Background: Ovarian cancer is the third most common cause of death among gynecologic malignancies worldwide. Understanding the biology and molecular pathogenesis of ovarian epithelial tumors is key to developing improved prognostic indicators and effective therapies. We aimed to determine the effects of PAX8 expression on the migrative, adhesive and survival capabilities of high-grade serous carcinoma cells.

First trimester ultrasound features of X-linked Opitz syndrome and early molecular diagnosis: case report and review of the literature.

X-linked Opitz G/BBB syndrome (XLOS) is a multiple congenital disorder inherited in an X-linked manner. XLOS may be suspected, in prenatal age, on the basis of sonographic findings in the second and/or third trimester of gestation. Pathogenetic variants in gene have been reported in individuals with XLOS.

Pioglitazone Improves Mitochondrial Organization and Bioenergetics in Down Syndrome Cells.

Mitochondrial dysfunction plays a primary role in neurodevelopmental anomalies and neurodegeneration of Down syndrome (DS) subjects. For this reason, targeting mitochondrial key genes, such as , is emerging as a good therapeutic approach to attenuate cognitive disability in DS. After demonstrating the efficacy of the biguanide metformin (a activator) in a cell model of DS, we extended the study to other molecules that regulate the pathway acting on genes.

Mitochondrial dysfunction in down syndrome: molecular mechanisms and therapeutic targets.

Trisomy of chromosome 21 (TS21) is the most common autosomal aneuploidy compatible with postnatal survival with a prevalence of 1 in 700 newborns. Its phenotype is highly complex with constant features, such as mental retardation, dysmorphic traits and hypotonia, and variable features including heart defects, susceptibility to Alzheimer's disease (AD), type 2 diabetes, obesity and immune disorders. Overexpression of genes on chromosome-21 (Hsa21) is responsible for the pathogenesis of Down syndrome (DS) phenotypic features either in a direct or in an indirect manner since many Hsa21 genes can affect the expression of other genes mapping to different chromosomes.

Prenatally diagnosed distal 16p11.2 microdeletion with a novel association with congenital diaphragmatic hernia: a case report.

A prenatal case presenting with congenital diaphragmatic hernia (CDH) and distal 16p11.2 microdeletion suggests two possible causative hypotheses: (1) a functional effect of chromatin loopings between the distal and the proximal 16p11.2 microdeletion traits, associated with CHD; (2) a possible role of , a deleted gene involved in diaphragm development.

Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the Hearts of Down Syndrome Fetuses.

Dosage-dependent upregulation of most of chromosome 21 (Hsa21) genes has been demonstrated in heart tissues of fetuses with Down syndrome (DS). Also miRNAs might play important roles in the cardiac phenotype as they are highly expressed in the heart and regulate cardiac development. Five Hsa21 miRNAs have been well studied in the past: miR-99a-5p, miR-125b-2-5p, let-7c-5p, miR-155-5p, and miR-802-5p but few information is available about their expression in trisomic tissues.

Metformin restores the mitochondrial network and reverses mitochondrial dysfunction in Down syndrome cells.

Alterations in mitochondrial activity and morphology have been demonstrated in human cells and tissues from individuals with Down syndrome (DS), as well as in DS mouse models. An impaired activity of the transcriptional coactivator PGC-1α/PPARGC1A due to the overexpression of chromosome 21 genes, such as NRIP1/RIP140, has emerged as an underlying cause of mitochondrial dysfunction in DS. We tested the hypothesis that the activation of the PGC-1α pathway might indeed reverse this mitochondrial dysfunction.

Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities.

The High Mobility Group A1 proteins (HMGA1) are nonhistone chromatinic proteins with a critical role in development and cancer. We have recently reported that HMGA1 proteins are able to increase the expression of spindle assembly checkpoint (SAC) genes, thus impairing SAC function and causing chromosomal instability in cancer cells. Moreover, we found a significant correlation between HMGA1 and SAC genes expression in human colon carcinomas.

Rab7 Regulates CDH1 Endocytosis, Circular Dorsal Ruffles Genesis, and Thyroglobulin Internalization in a Thyroid Cell Line.

Rab7 regulates the biogenesis of late endosomes, lysosomes, and autophagosomes. It has been proposed that a functional and physical interaction exists between Rab7 and Rac1 GTPases in CDH1 endocytosis and ruffled border formation. In FRT cells over-expressing Rab7, increased expression and activity of Rac1 was observed, whereas a reduction of Rab7 expression by RNAi resulted in reduced Rac1 activity, as measured by PAK1 phosphorylation.

Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation.

Background: Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea), a decrease in the initial primordial follicle number, high follicle-stimulating hormone (FSH) levels and hypoestrogenism. Although the etiology of a majority of POI cases is not yet identified, several data suggest that POI has a strong genetic component. Conventional cytogenetic and molecular analyses have identified regions of the X chromosome that are associated with ovarian function, as well as POI candidate genes, such as FMR1 and DIAPH2.

A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2.

Background: Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation.

NRIP1/RIP140 siRNA-mediated attenuation counteracts mitochondrial dysfunction in Down syndrome.

Mitochondrial dysfunction, which is consistently observed in Down syndrome (DS) cells and tissues, might contribute to the severity of the DS phenotype. Our recent studies on DS fetal hearts and fibroblasts have suggested that one of the possible causes of mitochondrial dysfunction is the downregulation of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α or PPARGC1A)--a key modulator of mitochondrial function--and of several nuclear-encoded mitochondrial genes (NEMGs). Re-analysis of publicly available expression data related to manipulation of chromosome 21 (Hsa21) genes suggested the nuclear receptor interacting protein 1 (NRIP1 or RIP140) as a good candidate Hsa21 gene for NEMG downregulation.