Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and ‘adult-type’ diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n=22), diffuse oligodendroglial tumors (d-OTs; n=20), diffuse astrocytomas (DAs; n=17), angiocentric gliomas (n=15), and gangliogliomas (n=17). Most LGNTs (84%) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82% of DNETs and 40% of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87%), and MYB fusion genes were the most common genetic alteration in DAs (41%). A BRAF:p.V600E mutation was present in 35% of gangliogliomas and 18% of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78% of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials.

Background Due to the 2019 novel coronavirus (COVID-19) disease outbreak, social distancing measures were imposed to control the spread of the pandemic. However, isolation may affect negatively the psychological well-being and impair sleep quality. Our aim was to evaluate the sleep quality of respiratory patients during the COVID-19 pandemic lockdown. Methods All patients who underwent a telemedicine appointment from March 30 to April 30 of 2020 were asked to participate in the survey. Sleep difficulties were measured using Jenkins Sleep Scale. Results The study population consisted of 365 patients (mean age 63.9 years, 55.6% male, 50.1% with sleep-disordered breathing [SDB]). During the lockdown, 78.9% of participants were confined at home without working. Most patients (69.6%) reported at least one sleep difficulty and frequent awakenings was the most prevalent problem. Reporting at least one sleep difficulty was associated with home confinement without working, female gender and diagnosed or suspected SDB, after adjustment for cohabitation status and use of anxiolytics. Home confinement without working was associated with difficulties falling asleep and waking up too early in the morning. Older age was a protective factor for difficulties falling asleep, waking up too early and non-restorative sleep. Notably, SDB patients with good compliance to positive airway pressure therapy were less likely to report sleep difficulties. Conclusions Home confinement without working, female gender and SDB may predict a higher risk of reporting sleep difficulties. Medical support during major disasters should be strengthened and potentially delivered through telemedicine, as this comprehensive approach could reduce psychological distress and improve sleep quality.

In Saccharomyces cerevisiae, genes encoding phospholipid-synthesizing enzymes are regulated by inositol and choline (IC). The current model suggests that when these precursors become limiting, the transcriptional complex Ino2p-Ino4p activates the expression of these genes, whereas repression requires Opi1p and occurs when IC are available. In this study, microarray-based expression analysis was performed to assess the global transcriptional response to IC in a wild-type strain and in the opi1⌬, ino2⌬, and ino4⌬ null mutant strains. Fifty genes were either activated or repressed by IC in the wild-type strain, including three already known IC-repressed genes. We demonstrated that the IC response was not limited to genes involved in membrane biogenesis, but encompassed various metabolic pathways such as biotin synthesis, one-carbon compound metabolism, nitrogen-containing compound transport and degradation, cell wall organization and biogenesis, and acetylCoA metabolism. The expression of a large number of IC-regulated genes did not change in the opi1⌬, ino2⌬, and ino4⌬ strains, thus implicating new regulatory elements in the IC response. Our studies revealed that Opi1p, Ino2p, and Ino4p have dual regulatory activities, acting in both positive and negative transcriptional regulation of a large number of genes, most of which are not regulated by IC and only a subset of which is involved in membrane biogenesis. These data provide the first global response profile of yeast to IC and reveal novel regulatory mechanisms by these precursors.

Both endocardial and epicardial RF applications are simple and quick to perform and do not pose an additional risk for most patients. Furthermore we believe that it is possible to perform bilateral epicardial radiofrequency ablation of the pulmonary veins without cardiopulmonary bypass. Further refinements of the technique are needed to assure transmurality of all lesions and better results.

Primitive myxoid mesenchymal tumor of infancy is a rare sarcoma that preferentially affects infants. It can be locally aggressive and rarely metastasizes, but the long-term outcome of children with this tumor is mostly unknown. Histologically, it is characterized by primitive cells with abundant myxoid stroma. Internal tandem duplication of B-cell CLL/lymphoma 6 (BCL6)-interacting co-repressor (BCOR) exon 15 has recently been described in clear cell sarcoma of kidney, central nervous system high-grade neuroepithelial tumor with BCOR alteration, and primitive myxoid mesenchymal tumor of infancy. Herein, we report 5 cases of primitive myxoid mesenchymal tumor of infancy: 3 girls and 2 boys with mean age of 6.5 months. Tumors were located in the paraspinal region (n=3), back (n=1), or foot (n=1) and ranged in size from 2.5 to 10.2 cm. BCOR-internal tandem duplication was confirmed by PCR and sequencing in all 5 cases. The minimally duplicated region consisted of 9 residues, which is shorter than was previously reported in others BCOR-associated tumors. To assess the clinical value and specificity of the BCOR-internal tandem duplication, a group of 11 ETV6-rearranged congenital infantile fibrosarcomas were evaluated and no BCOR-internal tandem duplication was identified in any case. Though not detected in congenital infantile fibrosarcomas, BCOR and BCL6 immunoreactivity was present in >90% of the nuclei of tumor cells in each of the 5 primitive myxoid mesenchymal tumor of infancy. The presence of BCOR-internal tandem duplication in all 5 primitive myxoid mesenchymal tumors of infancy provides evidence it is a recurrent somatic abnormality and substantiates the concept that indeed this tumor is a unique sarcoma of infancy. Our findings indicate that identification of BCOR-internal tandem duplication and/or nuclear immunoreactivity for BCOR or BCL6 can aid in the diagnosis of primitive myxoid mesenchymal tumor of infancy and help to differentiate it from congenital infantile fibrosarcoma.