Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

Ice shelves affect the stability of ice sheets by supporting the mass balance of ice upstream of the grounding line. Marine ice, formed from supercooled water freezing at the base of ice shelves, contributes to mass gain and affects ice dynamics. Direct measurements of marine ice thickness are rare due to the challenges of borehole drilling. Here we assume hydrostatic equilibrium to estimate marine ice distribution beneath the Amery Ice Shelf (AIS) using meteoric ice-thickness data obtained from radio-echo sounding collected during the Chinese National Antarctic Research Expedition between 2015 and 2019. This is the first mapping of marine ice beneath the AIS in nearly 20 years. Our new estimates of marine ice along two longitudinal bands beneath the northwest AIS are spatially consistent with earlier work but thicker. We also find a marine ice layer exceeding 30 m of thickness in the central ice shelf and patchy refreezing downstream of the grounding line. Thickness differences from prior results may indicate time-variation in basal melting and freezing patterns driven by polynya activity and coastal water intrusions masses under the ice shelf, highlighting that those changes in ice–ocean interaction are impacting ice-shelf stability.

The formation of Kelvin–Helmholtz-like rollers (referred to as K–H rollers) over riblet surfaces has been linked to the drag-increasing behaviour seen in certain riblet geometries, such as sawtooth and blade riblets, when the riblet size reaches sufficiently large viscous scales (Endrikat et al. (2021a), J. Fluid Mech. 913, A37). In this study, we focus on the sawtooth geometry of fixed physical size, and experimentally examine the response of these K–H rollers to further increases in viscous scaled riblet sizes, by adopting the conventional approach of increasing freestream speeds (and consequently, the friction Reynolds number). Rather than continual strengthening, the present study shows a gradual weakening of these K–H rollers with increasing sawtooth riblet size. This is achieved by an analysis of the roller geometric characteristics using both direct numerical simulations and hot-wire anemometry databases at matched viscous scaled riblet spacings, with the former used to develop a novel methodology for detecting these rollers via streamwise velocity signatures (e.g. as acquired by hot wires). Spectral analysis of the streamwise velocity time series, acquired within riblet grooves, reveals that the frequencies (and the streamwise wavelengths) of the K–H rollers increase with increasing riblet size. Cross-correlation spectra, estimated from unique two-point hot-wire measurements in the cross-plane, show a weakening of the K–H rollers and a reduction in their wall-normal coherence with increasing riblet size. Besides contributing to our understanding of the riblet drag-increasing mechanisms, the present findings also have implications for the heat transfer enhancing capabilities of sawtooth riblets, which have been associated previously with the formation of K–H rollers. The present study also suggests conducting future investigations by decoupling the effects of viscous scaled riblet spacing and friction Reynolds numbers, to characterise their influence on the K–H rollers independently.