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: Status dystonicus is characterized by frequent or prolonged severe episodes of generalized dystonia. The phenomenology, etiology, and outcome is heterogenous and poorly characterized, making a standardized management approach challenging. We characterized demographics of children with status dystonicus in British Columbia admitted to the pediatric intensive care unit (PICU), management patterns, and outcomes. Methods: Clinical records at our PICU were searched via ICD-10 codes. We included cases admitted 2014-2024 who had dystonia severity grade 3-5, dystonia worse than baseline, and age >30 days old. Results: Seventy-nine records were screened; 41 admissions from 19 unique patients were included. Mean age was 7.6±4.2 years; 53% were female. Most unique patients had a genetic etiology (n=8, 42%). The presenting complaint per admission was often not dystonia (n=24, 59%); infection was the most common trigger (n=23, 56%) followed by pain (n=6, 15%). Patients received several anti-dystonia medications (mean 6.9±2.5), including clonidine, benzodiazepines, ketamine, and others. Mean PICU stay was 11.0±10.8 days; 37% had multiple PICU admissions. Two patients (4.9%) died from status dystonicus complications. Conclusions: Status dystonicus is a life-threatening emergency commonly triggered by pain and infection in patients with dystonia. Given the considerable morbidity and mortality, multi-disciplinary teams should consider standardized treatment guidelines for these complex patients.

Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.

Galaxy Zoo is an online project to classify morphological features in extra-galactic imaging surveys with public voting. In this paper, we compare the classifications made for two different surveys, the Dark Energy Spectroscopic Instrument (DESI) imaging survey and a part of the Kilo-Degree Survey (KiDS), in the equatorial fields of the Galaxy And Mass Assembly (GAMA) survey. Our aim is to cross-validate and compare the classifications based on different imaging quality and depth. We find that generally the voting agrees globally but with substantial scatter, that is, substantial differences for individual galaxies. There is a notable higher voting fraction in favour of ‘smooth’ galaxies in the DESI+zoobot classifications, most likely due to the difference between imaging depth. DESI imaging is shallower and slightly lower resolution than KiDS and the Galaxy Zoo images do not reveal details such as disc features and thus are missed in the zoobot training sample. We check against expert visual classifications and find good agreement with KiDS-based Galaxy Zoo voting. We reproduce the results from Porter-Temple+ (2022), on the dependence of stellar mass, star formation, and specific star formation on the number of spiral arms. This shows that once corrected for redshift, the DESI Galaxy Zoo and KiDS Galaxy Zoo classifications agree well on population properties. The zoobot cross-validation increases confidence in its ability to compliment Galaxy Zoo classifications and its ability for transfer learning across surveys.

Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

The snake robot can be used to monitor and maintain underwater structures and environments. The motion of a snake robot is achieved by lateral undulation which is called the gait pattern of the snake robot. The parameters of a gait pattern need to be adjusted for compensating environmental uncertainties. In this work, 3D motion dynamics of a snake robot for the underwater environment is proposed with vertical motion using the buoyancy variation technique and horizontal motion using lateral undulation. “The neutral buoyant snake robot motion in hypothetical plane and added mass effect is negligible”, these previous assumptions are removed in this work. Two different control algorithms are designed for horizontal and vertical motions. The existing super twisting sliding mode control (STSMC) is used for the horizontal serpentine motion of the snake robot. The control law is designed on a reduced-ordered dynamic system based on virtual holonomic constraints. The vertical motion is achieved by controlling the mass variation using a pump. The water pumps are controlled using the event-based controller or Proportional Derivative (PD) controller. The results of the proposed control technique are verified with various external environmental disturbances and uncertainties to check the robustness of the control approach for various path following cases. Moreover, the results of STSMC scheme are compared with SMC scheme to check the effectiveness of STSMC. The practical implementation of the work is also performed using Simscape Multibody environment where the designed control algorithm is deployed on the virtual snake robot.

For the first time in the Indian subcontinent, a series of royal burials with chariots have been recovered from the Chalcolithic period at the archaeological site Sinauli (29°8′28″N; 77°13′1″E), Baghpat district, western Uttar Pradesh, India. Eight burials were excavated from the site; among them a royal burial with copper decorated legged coffin (lid with a series of anthropomorphic figures) and headgear has also been recovered. Among these remarkable discoveries, three full-sized chariots made of wood and copper, and a sword with a wooden hilt, made this site unique at historical ground. These cultural findings signify that the ancients from this place were involved in warfare. All these recovered exclusive antiquities also proved the sophistication and the high degree of craftsmanship of the artisans. According to the 14C radiocarbon dating and recovered material culture, the site date back to 4000 yr BP (∼2000 BCE) and is thought to belong to Ochre-Coloured Pottery (OCP)/Copper Hoard culture. This culture was believed to develop in the Ganga-Yamuna Doab and was contemporary to the late phase of the Indus civilization. Altogether, the findings indicate that the time period of this culture is plausibly contemporary to Late Indus, Mesopotamian and Greece civilizations.

We study the spreading of Newtonian viscous (aqueous glycerin solution) and viscoelastic (aqueous polymer solution) drops on solid substrates with different wettabilities. For drops of the same zero-shear viscosity, we find in the early stages of spreading that viscoelastic drops (i) spread faster and (ii) their contact radius shows a different power law vs time than Newtonian drops. We argue that the effect of viscoelasticity is only observable for experimental time scales of the order of or larger than the internal relaxation time of the viscoelastic polymer solution. We attribute this behaviour to the shear thinning of the viscoelastic polymer solution. When approaching the contact line, the shear rate increases and the steady-state viscosity of the viscoelastic drop is lower than that of the Newtonian drop. We support our experimental findings with a simple (first-order) perturbation model that qualitatively agrees with our findings.

Background: Shared decision-making (SDM) is a dynamic, patient-engaged approach to collaborative medical care. Limited SDM tools exist in pregnancy. We aimed to examine the need and usability of a novel SDM tool for pharmaco-therapeutic treatment of neurological conditions in pregnancy. Methods: This is an exploratory mixed-methods study. Non-pregnant women of any age were recruited using convenience, purposive sampling from an academic neurology clinic in Toronto. Participants reported the user friendliness of the SDM by completing the systems usability (SUS) questionnaire and participated in a focus group to further elaborate on their experience. Results: Eleven participants completed the survey 45% each between age 31-40, and 51-60. Median time spent on the tool was 17.2 minutes, and median SUS score 70 (<68 being not usable). Thematic data analysis from 2 focus groups, identified technical and content improvements: use of inclusive language, simplified design, and importance of patient engagement in SDM. Conclusions: Based on our preliminary results, a SDM web-tool for medication-related concerns of pregnant patients with neurological conditions is needed and usable. With integration of patients’ lived experiences, this novel tool may serve as an anchor point for future work in this field.

OBJECTIVES/GOALS: To introduce the new Team Science Community Toolkit, co-created by community and academic partners, and showcase its potential to empower Community Organizations (COs) in achieving equity in community-engaged research (CER). METHODS/STUDY POPULATION: In response to the challenges faced by COs in CER collaborations, qualitative interviews were conducted with CO staff from historically marginalized communities. These interviews informed the development of the Team Science Community Toolkit, a collaborative effort involving a Community Advisory Board (CAB) and Team Science experts from Northwestern University. The toolkit, designed using a community-based participatory research approach, incorporates the Science of Team Science and User-Centered Design principles. Integrated into the NIH-sponsored COALESCE website, it includes templates, checklists, and interactive tools, along with a real-world simulation, to support COs in all stages of the research process. RESULTS/ANTICIPATED RESULTS: Focus groups and usability testing involving external community experts validated the toolkit’s content and usability. Participants expressed enthusiasm and a sense of empowerment, indicating that the toolkit allows them to actively shape research processes and infuse their specific voices and needs into their partnerships. The toolkit is designed to support breaking down barriers like jargon and cultural adaptability to improve accessibility and open conversation. The impact of this Team Science focused toolkit is under evaluation. This presentation will showcase the toolkit, detail its collaborative development, and explore potential applications, ultimately offering a path to more equitable and valuable community-based research. DISCUSSION/SIGNIFICANCE: By providing COs with the resources and knowledge to participate as equal partners in research collaborations, it enhances self-advocacy, transparency, and equity. The toolkit has the potential to utilize Team Science to foster productive communication in community-academic research partnerships.

In recent years, it has become increasingly evident that surveillance metrics for invasive device-associated infections (ie, central-line–associated bloodstream infections, ventilator-associated pneumonias, and catheter-associated urinary tract infections) do not capture all harms; they capture only a subset of healthcare-associated infections (HAIs). Although prevention of device-associated infections remains critical, we need to address the full spectrum of potential harms from device use and non–device-associated infections. These include complications associated with additional devices, such as peripheral venous and arterial catheters, non–device-associated infections such as nonventilator hospital-acquired pneumonia, and noninfectious device complications such as trauma, thrombosis, and acute lung injury. As authors of the device-associated infection sections in the SHEA/IDSA/APIC Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals, we highlight catheter-associated urinary tract infection as an example of the strengths and limitations of the current emphasis on device-associated infection surveillance, suggest performance metrics that present a more comprehensive picture of patient harm, and provide a high-level overview of similar issues with other infection surveillance measures.