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: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.

Background: Meningiomas are the most common intracranial tumor with surgery, dural margin treatment, and radiotherapy as cornerstones of therapy. Response to treatment continues to be highly heterogeneous even across tumors of the same grade. Methods: Using a cohort of 2490 meningiomas in addition to 100 cases from the prospective RTOG-0539 phase II clinical trial, we define molecular biomarkers of response across multiple different, recently defined molecular classifications and use propensity score matching to mimic a randomized controlled trial to evaluate the role of extent of resection, dural marginal resection, and adjuvant radiotherapy on clinical outcome. Results: Gross tumor resection led to improved progression-free-survival (PFS) across all molecular groups (MG) and improved overall survival in proliferative meningiomas (HR 0.52, 95%CI 0.30-0.93). Dural margin treatment (Simpson grade 1/2) improved PFS versus complete tumor removal alone (Simpson 3). MG reliably predicted response to radiotherapy, including in the RTOG-0539 cohort. A molecular model developed using clinical trial cases discriminated response to radiotherapy better than standard of care grading in multiple cohorts (ΔAUC 0.12, 95%CI 0.10-0.14). Conclusions: We elucidate biological and molecular classifications of meningioma that influence response to surgery and radiotherapy in addition to introducing a novel molecular-based prediction model of response to radiation to guide treatment decisions.

While there is a recognised role of optimising lifestyle behaviours such as diet and physical activity in the management of infertility, the best practice for lifestyle management of infertility remains unknown, and factors influencing the lifestyle behaviours of people with infertility are not well understood. The aim of this systematic review is to evaluate the barriers and enablers to a healthy lifestyle in people with infertility, from the perspectives of people with infertility and health professionals, in order to inform optimal behavioural change strategies for lifestyle management of infertility. Ovid MEDLINE(R), PsycINFO, EMBASE, EBM Reviews, and CINAHL Plus were searched from inception to 12th September 2022. Eligible studies were qualitative, quantitative or mixed-methods primary studies which explored barriers and/or enablers to lifestyle for infertility management, from the perspectives of people with infertility and/or health professionals. Two independent reviewers performed quality assessment, using the Centre for Evidence-Based Management Critical Appraisal of a Survey Tool (quantitative and mixed-methods studies) and the Critical Appraisal Skills Programme Qualitative Checklist (qualitative and mixed-methods studies). Data were analysed by inductive thematic analysis with themes mapped to the Capability, Opportunity, Motivation and Behaviour (COM-B) model(1) and Theoretical Domains Framework (TDF)(2). Relevant behaviour change techniques (BCTs)(3) to target the identified enablers and barriers were suggested. After screening 10703 citations and 82 full-texts, 22 studies were included (12 quantitative, 7 mixed-methods and 3 qualitative) with 18 studies including women with infertility (n = 2442), 10 including men with infertility (n = 1372) and 6 including health professionals (n = 261). From the perspectives of people with infertility, themes related to capability (e.g. strategies for behaviour change), opportunity (e.g. limited time, resources and money) and motivation (e.g. interplay between lifestyle and emotional state); themes mapped to 8 TDF domains. From the perspectives of health professionals, themes related to capability (e.g. identification of patients appropriate for lifestyle intervention), opportunity (e.g. mode of delivery) and motivation (e.g. professional responsibility); themes mapped to 6 TDF domains. 34 BCTs were identified across the suggested interventions. This systematic review found that several interacting factors influence lifestyle in people with infertility as well as health professional behaviour with regards to provision of lifestyle interventions for infertility. These factors can be targeted for optimisation of interventions. In light of the limited number of qualitative studies, there is a need for more qualitative research to gain deeper insights into the perspectives of people with infertility and health professionals for further exploration of the complex and interacting factors which shape lifestyle during the fertility journey.

Despite understanding its impact on organizational effectiveness, practical guidance on how to train translational team (TT) leaders is lacking. Previously, we developed an evolutionary learning model of TT maturation consisting of three goal-directed phases: (1). team assembly (Formation); (2). conducting research (Knowledge Generation); and (3). dissemination and implementation (Translation). At each phase, the team acquires group-level knowledge, skills, and attitudes (KSAs) that enhance its performance. Noting that the majority of team-emergent KSAs are promoted by leadership behaviors, we examine the SciTS literature to identify the relevant behaviors for each phase. We propose that effective team leadership evolves from a hierarchical, transformational model early in team Formation to a shared, functional leadership model during Translation. We synthesized an integrated model of TT leadership, mapping a generic “functional leadership” taxonomy to relevant leadership behaviors linked to TT performance, creating an evidence-informed Leadership and Skills Enhancement for Research (LASER) training program. Empirical studies indicate that leadership behaviors are stable across time; to enhance leadership skills, ongoing reflection, evaluation, and practice are needed. We provide a comprehensive multi-level evaluation framework for tracking the growth of TT leadership skills. This work provides a framework for assessing and training relevant leadership behaviors for high-performance TTs.

The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.

Background: Neurosurgery is a high-risk specialty with a low margin of error. We aim to assess the risk of neurosurgeons being involved in medicolegal cases in Canada. Methods: This retrospective descriptive study evaluated ten years (2012-2021) of closed legal cases, college cases, and hospital complaints against neurosurgeons with data from the CMPA. Included cases were cranial cases, VP shunts, or cases where a catheter or wire was inserted into the brain. Cases excluded angiography, radiation, ultrasound, or percutaneous procedures. Results: We identified 77 cases (66 urgent or emergent). Neurosurgeons had a significantly higher medicolegal risk than the CMPA surgeon membership, however lower risk compared to all physician specialties. Legal cases accounted for 69% with favourable outcomes in 52%. Forty-one cases involved post-operative complications and 16 cases involved VP shunts. Multiple surgeons or residents could be involved spanning age groups and years in practice. Thirty-four cases had a harmful incident, 41% of these severe. The majority of cases occurred at urban centers. The average case duration was 41 months. Conclusions: This study provides a recent medicolegal analysis of cranial neurosurgery in Canada. We identified areas of common complaints and hope the data can be used to mitigate risk surgical risk in the future.

Background: In meningiomas, CDKN2A/B deletions are associated with poor outcomes but are rare in most cohorts (1-5%). Large molecular datasets are therefore required to explore these deletions and their relationship to other prognostic CDKN2A alterations. Methods: We utilized multidimensional molecular data of 560 meningiomas from 5 independent cohorts to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Results: Meningiomas with either CDKN2A/B deletions (partial or homozygous loss) or an intact CDKN2A gene locus but elevated mRNA expression (CDKN2Ahigh) both had poor clinical outcomes. Increased CDKN2A mRNA expression was a poor prognostic factor independent of CDKN2A deletion. CDKN2A expression and p16 protein increased with tumor grade and more aggressive molecular and methylation groups. CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycling pathways dysregulated at different checkpoints. p16 immunohistochemistry was unreliable in differentiating between meningiomas with and without CDKN2A deletions, but increased positivity was associated with increased mRNA expression. CDKN2Ahigh meningiomas were associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. Conclusions: These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.

We investigated whether the one-time application of polymer-coated urea (PCU) before transplanting could simultaneously improve the grain yield and nitrogen use efficiency (NUE) of japonica-indica hybrid rice (JIHR) through a field experiment. The local high-yield JIHR cultivar Chunyou-927 was field grown during the rice-growing seasons in 2019 and 2020. The experiment consisted of three treatments: no nitrogen application (0N), application of conventional urea (CU), and the one-time application of PCU. Grain yield was 1.0–1.3 t/ha higher, and agronomic NUE (kg grain yield increase per kg N applied) was 5.2–5.9 kg/kg higher, respectively, under the PCU treatment compared with the CU treatment across the two study years. When compared with the CU treatment, the PCU treatment could (1) improve root morphological trait, (2) reduce redundant vegetative growth during the early growth period, (3) increase matter production during the mid and late growth period, and (4) increase plant activity during the grain-filling period. Overall, our findings indicate that one-time PCU application before transplanting of the JIHR cultivar holds great promise for increasing grain yield and NUE.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

The spatio-temporal variation of leaf chlorophyll content is an important crop phenotypic trait that is of great significance for evaluating crop productivity. This study used a soil-plant analysis development (SPAD) chlorophyll meter for non-destructive monitoring of leaf chlorophyll dynamics to characterize the patterns of spatio-temporal variation in the nutritional status of maize (Zea mays L.) leaves under three nitrogen treatments in two cultivars. The results showed that nitrogen levels could affect the maximum leaf SPAD reading (SPADmax) and the duration of high SPAD reading. A rational model was used to measure the changes in SPAD readings over time in single leaves. This model was suitable for predicting the dynamics of the nutrient status for each leaf position under different nitrogen treatments, and model parameter values were position dependent. SPADmax at each leaf decreased with the reduction of nitrogen supply. Leaves at different positions in both cultivars responded differently to higher nitrogen rates. Lower leaves (8th–10th positions) were more sensitive than the other leaves in response to nitrogen. Monitoring the SPAD reading dynamic of lower leaves could accurately characterize and assess the nitrogen supply in plants. The lower leaves in nitrogen-deficient plants had a shorter duration of high SPAD readings compared to nitrogen-sufficient plants; this physiological mechanism should be studied further. In summary, the spatio-temporal variation of plant nitrogen status in maize was analysed to determine critical leaf positions for potentially assisting in the identification of appropriate agronomic management practices, such as the adjustment of nitrogen rates in late fertilization.

The cooperative guidance problem of multiple inferior missiles intercepting a hypersonic target with the specific impact angle constraint in the two-dimensional plane is addressed in this paper, taking into consideration variations in a missile’s speed. The guidance law is designed with two subsystems: the direction of line-of-sight (LOS) and the direction of normal to LOS. In the direction of LOS, by applying the algebraic graph theory and the consensus theory, the guidance command is designed to make the system convergent in a finite time to satisfy the goal of cooperative interception. In the direction of normal to LOS, the impact angle is constrained to transform into the LOS angle at the time of interception. In view of the difficulty of measuring unknown target acceleration information in real scenarios, the guidance command is designed by utilising a super-twisting algorithm based on a nonsingular fast-terminal sliding mode (NFTSM) surface. Numerical simulation results manifest that the proposed guidance law performs efficiently and the guidance commands are free of chattering. In addition, the overall performance of this guidance law is assessed with Monte Carlo runs in the presence of measurement errors. The simulation results demonstrate that the robustness can be guaranteed, and that overall efficiency and accuracy in intercepting the hypersonic target are achieved.

The settling velocity of porous particles in linear stratification is affected by the diffusive exchange between interstitial and ambient water. The extent to which buoyancy and interstitial mass adaptation alters the settling velocity depends on the ratio of the diffusive and viscous time scales. We conducted schlieren experiments and lattice Boltzmann simulations for highly porous (95 %) but impermeable spheres settling in linear stratification. For a parameter range that resembles marine porous particles, ‘marine aggregates’, i.e. low Reynolds numbers ($0.05\leq \textit {Re}\leq 10$), intermediate Froude numbers ($0.1\leq \textit {Fr}\leq 100$) and Schmidt number of salt ($\textit {Sc}=700$), we observe delayed mass adaptation of the interstitial fluid due to lower-density fluid being dragged by a particle that forms a density boundary layer around the particle. The boundary layer buffers the diffusive exchange of stratifying agent with the ambient fluid, leading to an enhanced density contrast of the interstitial pore fluid. Stratification-related drag enhancement by means of additional buoyancy of dragging lighter fluid and buoyancy-induced vorticity resembles earlier findings for solid spheres. However, the exchange between density boundary layer and pore fluid substantially increases stratification drag for small $\textit {Fr}$. To estimate the effect of stratification on marine aggregates settling in the ocean, we derived scaling laws and show that small particles ($\leq$0.5 mm) experience enhanced drag which increases retention times by 10 % while larger porous particle (>0.5 mm) settling is dominated by delayed mass adaptation that diminishes settling velocity by 10 % up to almost 100 %. The derived relationships facilitate the integration of stratification-dependent settling velocities into biogeochemical models.

High-energy and high-intensity lasers are essential for pushing the boundaries of science. Their development has allowed leaps forward in basic research areas, including laser–plasma interaction, high-energy density science, metrology, biology and medical technology. The Helmholtz International Beamline for Extreme Fields user consortium contributes and operates two high-peak-power optical lasers using the high energy density instrument at the European X-ray free electron laser (EuXFEL) facility. These lasers will be used to generate transient extreme states of density and temperature to be probed by the X-ray beam. This paper introduces the ReLaX laser, a short-pulse high-intensity Ti:Sa laser system, and discusses its characteristics as available for user experiments. It will also present the first experimental commissioning results validating its successful integration into the EuXFEL infrastructure and viability as a relativistic-intensity laser driver.

Owing to their ultra-high accelerating gradients, combined with injection inside micrometer-scale accelerating wakefield buckets, plasma-based accelerators hold great potential to drive a new generation of free-electron lasers (FELs). Indeed, the first demonstration of plasma-driven FEL gain was reported recently, representing a major milestone for the field. Several groups around the world are pursuing these novel light sources, with methodology varying in the use of wakefield driver (laser-driven or beam-driven), plasma structure, phase-space manipulation, beamline design, and undulator technology, among others. This paper presents our best attempt to provide a comprehensive overview of the global community efforts towards plasma-based FEL research and development.