Diffuse pediatric high-grade glioma of methylation-based RTK2A and RTK2B subclasses present distinct radiological and histomolecular features including Gliomatosis cerebri phenotype.

Diffuse pediatric-type high-grade gliomas (pedHGG), H3- and IDH-wildtype, encompass three main DNA-methylation-based subtypes: pedHGG-MYCN, pedHGG-RTK1A/B/C, and pedHGG-RTK2A/B. Since their first description in 2017 tumors of pedHGG-RTK2A/B have not been comprehensively characterized and clinical correlates remain elusive. In a recent series of pedHGG with a Gliomatosis cerebri (GC) growth pattern, an increased incidence of pedHGG-RTK2A/B (n = 18) was observed.

Neurotrophic extracellular matrix proteins promote neuronal and iPSC astrocyte progenitor cell- and nano-scale process extension for neural repair applications.

The extracellular matrix plays a critical role in modulating cell behaviour in the developing and adult central nervous system influencing neural cell morphology, function and growth. Neurons and astrocytes, play vital roles in neural signalling and support respectively and respond to cues from the surrounding matrix environment. However, a better understanding of the impact of specific individual extracellular matrix proteins on both neurons and astrocytes is critical for advancing the development of matrix-based scaffolds for neural repair applications.

A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements.

Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes DNA to the cytoplasm. We found that the autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements.

Observing bioorthogonal macrocyclizations in the nuclear envelope of live cells using on/on fluorescence lifetime microscopy.

The reactive partnership between azides and strained alkynes is at the forefront of bioorthogonal reactions, with their cellular studies often achieved through the use of off to on fluorophores with fluorescence microscopy. In this work, the first demonstration of a bioorthogonal, macrocycle-forming reaction occurring within the nuclear envelope of live cells has been accomplished, utilising on/on fluorescence lifetime imaging microscopy for real-time continuous observation of the transformation. The fluorescent, macrocyclic BF azadipyrromethene was accessible through a double 1,3-dipolar cycloaddition within minutes, between a precursor bis-azido substituted fluorophore and Sondheimer diyne in water or organic solvents.

A NIR-Fluorochrome for Live Cell Dual Emission and Lifetime Tracking from the First Plasma Membrane Interaction to Subcellular and Extracellular Locales.

Molecular probes with the ability to differentiate between subcellular variations in acidity levels remain important for the investigation of dynamic cellular processes and functions. In this context, a series of cyclic peptide and PEG bio-conjugated dual near-infrared emissive BF-azadipyrromethene fluorophores with maxima emissions at 720 nm (at pH > 6) and 790 nm (at pH < 5) have been developed and their aqueous solution photophysical properties determined. Their inter-converting emissions and fluorescence lifetime characteristics were exploited to track their spatial and temporal progression from first contact with the plasma membrane to subcellular locales to their release within extracellular vesicles.

Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established.

Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization.

Results: Median overall survival (OS) was 15.

O-glycan determinants regulate VWF trafficking to Weibel-Palade bodies.

von Willebrand factor (VWF) undergoes complex posttranslational modification within endothelial cells (ECs) before secretion. This includes significant N- and O-linked glycosylation. Previous studies have demonstrated that changes in N-linked glycan structures significantly influence VWF biosynthesis.

DNA barcoding of the genus Apaidia Hampson, 1900 for species delimitation from Western Mediterranean fauna (Lepidoptera, Erebidae).

The genus Apaidia Hampson, 1900 is a relict Western Mediterranean genus in the South-western part of Europe and the North-western areas of the Mediterranean Africa comprising so far three species, Apaidia rufeola (Rambur, 1832), Apaidia mesogona (Godart, [1824]) and Apaidia barbarica Legrand, 1939. According to the examined material, COI mitochondrial DNA sequences and adult morphology integration supports the existence of three main lineages of Apaidia with sequence divergence rates of approximately 4.5%, which are within the range reported for other well-defined insect species.

Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs.

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10-15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells.

Dabrafenib plus Trametinib in Pediatric Glioma with V600 Mutations.

Background: Detection of the V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with V600 mutations, findings that warrant further evaluation of this combination as first-line therapy.

Methods: In this phase 2 trial, patients with pediatric low-grade glioma with V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine).

The impact of the temporal sequence of cranial radiotherapy and platin-based chemotherapy on hearing impairment in pediatric and adolescent CNS and head-and-neck cancer patients: A report from the PanCareLIFE consortium.

The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium.

An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation.

Insulin undergoes agglomeration with (subtle) changes in its biochemical environment, including acidity, application of heat, ionic imbalance, and exposure to hydrophobic surfaces. The therapeutic impact of such unwarranted insulin agglomeration is unclear and needs further evaluation. A systematic investigation was conducted on recombinant human insulin-with or without labeling with fluorescein isothiocyanate-while preparing insulin suspensions (0.

DNA barcoding and morphology reveal European and western Asian (Linnaeus, 1758) as a complex of species (Lepidoptera, Erebidae, Arctiinae).

Currently, the genus Schrank, 1802 includes approximately 16 species in the Palaearctic region, depending on the taxonomic interpretation. Here, populations of the (Linnaeus, 1758) morphospecies complex were studied from Europe to the Middle East (Turkey, northern Iran) by molecular methods. Morphological treatment has traditionally revealed the presence of five nominal taxa: (Linnaeus, 1758), (Boisduval, 1829), (Freyer, 1831), de Freina, 1983, and Romanoff, 1884.

Substituent directed cellular imaging in the 800-850 nm range with BF-azadipyrromethene fluorophores.

Three bis(anilino)-substituted NIR-AZA fluorophores have been designed, synthesized and tested to bridge the availability gap of molecular fluorophores for live-cell microscopy imaging in the 800-850 nm spectral range. The concise synthetic route allows for the later stage introduction of three tailored peripheral substituents which guides the sub-cellular localization and imaging. Live-cell fluorescence imaging of lipid droplets, plasma membrane and cytosolic vacuoles was successfully achieved.

Gold-catalyzed -selective cyclization of alkynylcyclobutanecarboxamides: synthesis of cyclobutane-fused dihydropyridones.

Cyclobutane-fused dihydropyridones can be efficiently synthesized by a completely -selective gold-catalyzed cyclization of alkynylcyclobutanes bearing an appended amide, which proceeds under mild conditions. The observed selectivity, which is reversed from that previously observed for the cyclization of related alcohols and acids, is supported by DFT calculations.

Identifying STEDable BF-Azadipyrromethene Fluorophores.

BF-azadipyrromethenes are highly versatile fluorophores used for cellular and in vivo imaging in the near-infrared and far-red regions of the spectrum. As of yet, their use in conjunction with super-resolution imaging methodologies has not been explored. In this report, a series of structurally related BF-azadipyrromethenes has been examined for their suitability for use with stimulated emission depletion (STED) nanoscopy.

An annotated checklist of the Pyralidae of the region of Murcia (Spain) with new records, distribution and biological data (Lepidoptera, Pyraloidea, Pyralidae).

Background: The Murcia Region (south-eastern Iberian Peninsula) has a great diversity of Lepidopteran fauna, as a zoogeographical crossroads and biodiversity hotspot with more than 850 butterflies and moth species recorded.

New Information: In the present paper, based on an examination of museum specimens, published records and new samples, a comprehensive and critical species list of Pyralidae moths (Lepidoptera, Pyraloidea) is synthesised. In total, three subfamilies, 67 genera and 142 species have been recorded and these are listed, along with their collection, literature references and biological data, including chorotype, voltinism and the flight period in the study area.

Double click macrocyclization with Sondheimer diyne of aza-dipyrrins for B-F bioorthogonal imaging.

Sequential azide/diyne cycloadditions proved highly effective for the macrocyclization of a bis-azido aza-dipyrrin. Macrocyclic aza-dipyrrin could be produced in 30 min at rt in water with changes in fluorescence intensity and lifetimes measurable upon reaction. Live cell microscopy showed that aza-dipyrrins were suitable for confocal and STED super-resolution imaging and a bioorthogonal response to macrocyclization could be detected in cellular compartments.

Exploiting directed self-assembly and disassembly for off-to-on fluorescence responsive live cell imaging.

A bio-responsive nanoparticle was formed by the directed self-assembly (DSA) of a hydrophobic NIR-fluorophore with poloxamer P. Fluorophore emission was switched off when part of the nanoparticle, however upon stimulus induced nanoparticle dis-assembly the emission switched on. The emission quenching was shown to be due to fluorophore hydration and aggregation within the nanoparticle and the turn on response attributable to nanoparticle disassembly with embedding of the fluorophore within lipophilic environments.

Early molecular diagnosis of BRAF status drives the neurosurgical management in BRAF V600E-mutant pediatric low-grade gliomas: a case report.

Background: To date, this is the only report showing with close and consecutive magnetic resonance images the extremely rapid response of two types of pediatric low-grade gliomas (PLGG) to vemurafenib and its impact on the surgical approach.

Cases Presentation: We report two cases of symptomatic PLGG treated with vemurafenib, a BRAF inhibitor: in a 12-year-old girl it was used as first-line medical treatment, reducing the tumor by 45% within a month and stabilizing to 76% after a year; in a 3-year-old boy with no improvement after SIOP LGG 2004 Protocol, vemurafenib induced in only one week a 34% shrinkage and solved the hydrocephalus, avoiding surgical operation. DISCUSSION AND CONCLUSIONS: Our cases demonstrate how an early molecular diagnosis of BRAF mutations through the neurosurgical biopsy is essential to promptly start targeted therapies.

High dose craniospinal irradiation as independent risk factor of permanent alopecia in childhood medulloblastoma survivors: cohort study and literature review.

Purpose: Our aim was to determine the main risk factors related to the occurrence of permanent alopecia in childhood medulloblastoma (MB) survivors.

Methods: We retrospectively analyzed the clinical features of all consecutive MB survivors treated at our institute. We divided the patients into 3 groups depending on the craniospinal irradiation (CSI) dose received and defined permanent alopecia first in terms of the skin region affected (whole scalp and nape region), then on the basis of the toxicity degree (G).