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 complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.

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.

Hand, foot, and mouth disease (HFMD) shows spatiotemporal heterogeneity in China. A spatiotemporal filtering model was constructed and applied to HFMD data to explore the underlying spatiotemporal structure of the disease and determine the impact of different spatiotemporal weight matrices on the results. HFMD cases and covariate data in East China were collected between 2009 and 2015. The different spatiotemporal weight matrices formed by Rook, K-nearest neighbour (KNN; K = 1), distance, and second-order spatial weight matrices (SO-SWM) with first-order temporal weight matrices in contemporaneous and lagged forms were decomposed, and spatiotemporal filtering model was constructed by selecting eigenvectors according to MC and the AIC. We used MI, standard deviation of the regression coefficients, and five indices (AIC, BIC, DIC, R2, and MSE) to compare the spatiotemporal filtering model with a Bayesian spatiotemporal model. The eigenvectors effectively removed spatial correlation in the model residuals (Moran’s I < 0.2, p > 0.05). The Bayesian spatiotemporal model’s Rook weight matrix outperformed others. The spatiotemporal filtering model with SO-SWM was superior, as shown by lower AIC (92,029.60), BIC (92,681.20), and MSE (418,022.7) values, and higher R2 (0.56) value. All spatiotemporal contemporaneous structures outperformed the lagged structures. Additionally, eigenvector maps from the Rook and SO-SWM closely resembled incidence patterns of HFMD.

Objectives/Goals: Gait performance (GP) and global cognitive functions (GCF) are both critical for maintaining independence and quality of life in senior adults. Recent studies have explored the potential link between GP and GCF, encompassing executive functions. Methods/Study Population: PRISMA guidelines will govern this systematic review. This systematic review synthesizes published research from 2000 to 2024, including peer-reviewed articles, pilot studies, and randomized controlled trials, to examine the relationship between GP (how a person walks and stands) and GCP in older adults. The exclusion criteria will be based on studies focused on physical activities unrelated to balance, meta-analysis, and systematic reviews and those published in languages other than English or Spanish. Results/Anticipated Results: Our preliminary data indicate that gait, or walking speed, is significantly correlated with GCP in older adults, with slower walking associated with poorer global cognition. Specifically, gait speed during dual-task walking shows a strong correlation with working memory (p < .001) and processing speed (p < .05) in individuals aged over 60 years. Gender differences were observed, with women over 80 walking slower than men over 85 years, who walked faster, and women exhibited poorer global cognition than men. Discussion/Significance of Impact: Overall, a gait slowing between 0.68 and 1.1 m per second could predict a marker for the risk of developing dementia, indicating that monitoring gait speed in older adults may provide early warning signs, allowing for timely interventions. Enhancing GP and GCF can improve the quality of life and independence in older adults. Acknowledgments: Research supported by NIH: Award Number HCTRECD R25MD007607 from the NIMHD.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

This article investigates the career trajectories of Hong Kong solicitors during two historical turning points, specifically 1994–1997 and 2018–2021, when hundreds of lawyers left private practice to pursue alternative career options such as business and finance, government and politics, or relocation to other countries. Data are sourced from the career mobility records of law firm partners reported in 336 monthly issues of the Hong Kong Lawyer journal between 1994 and 2021, as well as other relevant archival sources. The research examines the underlying forces that led these law firm partners to abandon their high-status positions and pursue alternative career paths during these pivotal moments in Hong Kong’s history. The findings suggest that the career trajectories of these elite professionals are not solely based on individual choices but are also shaped by their social origins and the physical and social spaces that influence their careers over time. This study contributes original insights into the complex interplay between individual, spatial and temporal factors that drive career mobility among legal professionals.

Background: Elevated BMI has been proposed as a risk factor for the development of meningioma. The relationship between body mass index (BMI) and disease control in high-grade meningioma has not yet been examined. A retrospective cohort study was performed to assess the relationship between high-grade meningioma recurrence and BMI. Methods: This is a retrospective cohort study of patients with Grade 2 or Grade 3 meningioma at a single tertiary care center between 2008 and 2017. We collected clinical data including age, sex, BMI, location, Simpson grade, brain invasion, and radiation treatments. Disease control was monitored on followup MRI scans. We stratified patients by BMI greater than or less than 25. Results: A total of 45 patients were included. Recurrence was observed in 15 patients (33.3%). There were 32 (71.1%) patients with BMI > 25, and 13 (28.9%) patients with normal BMI. Patients with elevated BMI had higher risk of recurrence (p=0.04). Multivariate analysis identified BMI as an independent predictor of recurrence. Conclusions: Our results suggest that overweight patients with a Grade 2 or Grade 3 meningioma are at higher risk of recurrence than patients with normal BMI. The explanation for this association unknown. Further research is suggested to confirm and better characterize this association.

Background: Cerebrospinal fluid (CSF) leak is a common complication of minimally invasive tubular microdiscectomy (MIM). However, it is not known whether patients with CSF leak can be safely discharged home the same day. Methods: This is a retrospective cohort study of patients with incidental durotomy after MIM from January, 2009 to August, 2023. Patient demographic information, surgery information, CSF leak management, and postoperative outcomes were recorded. Results: There were 16 patients (53%) who were admitted to hospital and 14 (47%) patients discharged home the same day post CSF leak. There were no differences in patient demographics between the two groups at baseline. Twenty-nine out of 30 (97%) of the patients had onlay duraplasty, and one (3%) patient was repaired using sutures. The hospitalized group was kept on bed rest overnight or 24 hours. The discharge group was kept on best rest for 2 hours or mobilized immediately after surgery. The average length of admission for the hospitalized group was 2.4 ± 4.0 days. No patients in either group required readmission or revision surgery for CSF leak. Conclusions: Patients with CSF leak post minimally invasive tubular microdiscectomy can be safely discharged home the same day provided that duraplasty or primary repair was performed intraoperatively.

Sulfosalt assemblages in a specimen from the Boliden Au–Cu–(As) deposit in northern Sweden, comprise micrometre to nanometre scale intergrowths of Se-rich izoklakeite and tintinaite with average formulae and calculated homologue number (N) given as: (Cu1.88Fe0.18)2.06(Pb22.92Ag1.47Cd0.01Zn0.01)24.41(Sb13.12Bi8.69)21.8(S50.19Se6.43Te0.12)56.73, N = 3.83, and (Cu1.31Fe0.74)2.05(Pb10.58Ag0.18Cd0.05Zn0.02)10.83(Sb10.2Bi5.23)15.43(S32.22Se2.46)34.7, N = 2.05, respectively. Tintinaite coexists with (Bi, Se)-rich jamesonite. High-angle annular dark field scanning transmission electron microscopy (HAADF STEM) imaging reveals chessboard structures comprising PbS and SnS modules with the number of atoms in the octahedral (M) sites counted as: n1 = 18 and n2 = 8 for tintinaite and n1 = 30 and n2 = 16 for izoklakeite. The homologue number can be calculated using the formula: N = (n1/6)–1 and N = n2/4 for PbS and SnS modules giving NTti = 2 and NIz = 4. A new N = 3 homologue, defined by n = 12 and n = 24 SnS and PbS modules, respectively, is identified as single or double units within areas with intergrowths between kobellite and izoklakeite. HAADF STEM imaging also reveals features attributable to lone electron pair micelles within the Sb-rich kobellite homologues. Atomic-resolution EDS STEM chemical mapping of Pb–Bi–Sb-sulfosalts shows a correlation with crystal structural modularity. The maps also highlight sites in the SnS modules of tintinaite in which Sb > Bi. Coherent nanoscale intergrowths between tintinaite and izoklakeite define jigsaw patterns evolving from chessboard structures and are considered to have formed during co-crystallisation of the two phases. Displacement textures and crosscutting veinlets (a few nm in width) are interpreted as evidence for superimposed syn-metamorphic deformation and are associated with the redistribution of Bi and Se. Imaging and mapping using HAADF STEM techniques is well suited to characterisation of Pb–Sb–Bi-sulfosalt phases, offering largely untapped potential to unravel the evolution of chessboard structures with applications across mineralogy but also extending into allied fields.

Ultrafast optical probing is a widely used method of underdense plasma diagnostic. In relativistic plasma, the motion blur limits spatial resolution in the direction of motion. For many high-power lasers the initial pulse duration of 30–50 fs results in a 10–15 μm motion blur, which can be reduced by probe pulse post-compression. Here we used the compression after compressor approach [Phys.-Usp. 62, 1096 (2019); JINST 17 P07035 (2022)], where spectral broadening is performed in thin optical plates and is followed by reflections from negative-dispersion mirrors. Our initially low-intensity probe beam was down-collimated for a more efficient spectral broadening and higher probe-to-self-emission intensity ratio. The setup is compact, fits in a vacuum chamber and can be implemented within a short experimental time slot. We proved that the compressed pulse retained the high quality necessary for plasma probing.

Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.

Helicopters are used in complex and harsh operational environments, such as search and rescue missions and firefighting, that require operating in ground proximity, tracking targets while avoiding impacting obstacles, namely a combination of point tracking (positive) and boundary avoidance (negative) objectives. A simulation task representing simplified helicopter dynamics is used to investigate point tracking and boundary avoidance tasks. The variance and regression analysis are used to study the effects of task conditions on participants’ tracking errors and input aggression. The overall tracking error shows a negative correlation with input aggression. The participants tend to have higher input aggression and lower tracking error near the boundaries, exposing the switching of manipulation input strategies under different task conditions. It also suggests a potential way of designing simulation tasks for human operators manipulating helicopters and a trigger for investigating pilots’ biodynamic feedthrough.