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.

Evidence indicates hypervitaminosis A may be attributed to overconsumption of natural preformed vitamin A (VA) and overlapping VA intervention strategies. Hypervitaminosis A can disrupt metabolic processes; however, the extent and mechanisms of these impacts are not well understood. This study aims to assess metabolic differences related to hypervitaminosis A and VA supplementation by performing metabolomics analysis. A subsample of South African preschoolers participating in the country’s VA supplementation programme was selected. Participants were divided into two groups: adequate VA (n 15; 0·59–0·99 µmol/g total liver reserve and high VA (n 15; ≥ 1·0 µmol/g total liver reserve). Serum samples were collected at baseline and 28 d after consuming a 200 000 IU VA supplement. Lipidomics and oxylipins assays were conducted using ultraperformance LC-MS. At baseline, unsaturated lysophosphatidylcholines and unsaturated phosphatidylcholines were significantly lower in the high VA group (P < 0·05). A group-by-time interaction with VA supplementation was observed for polyunsaturated lysophosphatidylcholines and polyunsaturated phosphatidylcholines (P < 0·05). Additionally, a group effect was noted for oxylipins, and a time effect in response to VA supplementation was seen with decreased arachidonic acid and lipoxygenase- and non-enzymatically derived oxylipins (P < 0·05). Hypervitaminosis A is associated with modifications in lipids involved in cell structure and signalling, particularly unsaturated lysophosphatidylcholines and phosphatidylcholines. Further research is needed to identify the mechanisms behind these modifications, their physiological effects and their potential as biomarkers of elevated vitamin A status.

University students often make less healthful dietary choices whilst at university however, do not typically receive advice and support to help them eat more healthily(1,2). A tool which could be provided to students to promote more favourable dietary behaviours is the eNutri web-based app which includes a food frequency questionnaire (FFQ) and delivers automated personalised nutrition advice (PNA) and a diet quality score (DQS) consisting of 11 food/nutrient components(3). The PNA includes scores and general advice for each component and, for the user’s three lowest scoring components, recommends which foods to eat more/less frequently to improve their DQS. As part of a 4-week intervention study, we aimed to explore the perceptions of the eNutri PNA in UK university students.

As part of this intervention, 14 students from the Universities of Reading and Hertfordshire completed the eNutri FFQ and received their PNA. At the end of the study, they rated how much they agreed with statements about the perceived value and benefit (if any) of the eNutri PNA tool, on a 6-point scale ranging from strongly disagree to strongly agree. The percentage of respondents reported is the total number who responded “somewhat agree”, “agree”, or “strongly agree” to each statement.

Of the 14 students, 79% were female with a mean age of 25y (range = 18-37y) and mean BMI of 24.7kg/m2 (range = 19.4-31.9kg/m2). At baseline, the average importance of a healthy diet to the participants (n = 13) was rated at 7.2 out of 10 (with 0 being ‘not important at all’ and 10 being ‘very important’). In total, 57% of respondents indicated that they felt they ‘were eating a healthier diet because of the eNutri advice received’ and only 14% reported that ‘the advice did not motivate them to make changes to their diet’. Furthermore, 64% of respondents indicated that the ‘eNutri PNA gave them confidence in their ability to make changes to their diet’ and that it ‘supported them to do so’. Half of the students agreed that ‘they would want to use eNutri long term to track their progress and receive regular PNA’. In addition, 79% agreed that ‘eNutri should be offered to all university students to help them make healthier food choices’, and that if eNutri was offered to them for free by their university, ‘it would be a valuable student benefit’ and they ‘would want to use it again’.

In general, university students indicated the eNutri PNA tool supported them to eat healthier and providing access to the wider student population would be beneficial to encourage healthy eating at university. These findings along with the quantitative data from the PNA intervention which is currently being analysed will support the development of larger, suitably-powered studies to confirm these findings.

OBJECTIVES/GOALS: Mayo Clinic (MC) launched the Rapid Activation Trial (RAT) pilot program in 2022 to expedite the activation of high priority and high impact clinical trials. The objective was to develop a process for rapid activation through robust screening, prioritization, and project management (PM) support. METHODS/STUDY POPULATION: The project team developed a robust screening and approval process for the RAT program using a combination of an objective scoring tool (based on strategic priorities) and a diverse selection committee to screen and approve eligible trials. Sponsors had to commit to RAT program timelines. Upon approval, trials were prioritized at the highest level within each business unit involved in the activation process. The number of trials approved annually were limited to 8 to manage volume and facilitate seamless prioritization with an activation timeline goal of 6 weeks. Project management support for RAT program focused on financial, regulatory, logistical, and operational elements to open trials expeditiously. RESULTS/ANTICIPATED RESULTS: In 2022, thirteen (13) applications were received and eight (8) were approved by the RAT selection committee. The approved trials activated with a median open to enrollment time of 6.4 weeks from engaging with business units. They also aligned closely with organization’s strategic priorities, including but not limited to Investigator Initiated Trials, Multi-Site protocols, IND/IDE protocols, Rare Diseases, First in Human and Commercialization potential trials. PI and study team feedback was positive. In 2023, the RAT program was renewed due to the pilot’s significant success in 2022. The goal is to open 10 trials and 5 have been activated by the end of Q3, 2023 with a median timeline of 6 weeks. DISCUSSION/SIGNIFICANCE: Rapid activation of high priority and high impact clinical trials enables an organization to strategically prioritize and open complex clinical trials. This allows the delivery of innovative, timely cures to patients in an expeditious timeline.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

The current study investigated the effects of pre-grazing herbage mass (PGHM, 1500 or 2500 kg dry matter (DM)/ha) and post-grazing sward height (PGSH, 4 or 6 cm) on herbage production and its nutritive value and DM intake, grazing behaviour and growth of Charolais steers (n = 96; 12 months of age; 396 ± 19.0 kg) during a 222-day grazing season, and the subsequent effect of an indoor finishing diet (grass silage alone or supplemented with concentrates) for 146 days, on performance and carcass traits. Steers were assigned to one of 12 grazing groups and group was assigned to a 2 (PGHM) × 2 (PGSH) factorial arrangement of treatments. At the end of the grazing season, live-weight was 16 kg heavier for PGHM-1500 than PGHM-2500 and 34 kg heavier for PGSH-6 than PGSH-4. After indoor finishing, there was no difference in carcass weight between PGHM treatments, but PGSH-6 had a 19 kg heavier carcass than PGSH-4. Herbage production was 881 and 517 kg DM/ha greater for PGHM-2500 than PGHM-1500 and for PGSH-4 than PGSH-6, respectively. Grazing stocking rate did not differ between PGHM treatments but PGSH-4 carried 1.35 more steers/ha than PGSH-6. Supplementing concentrates during the indoor period increased carcass weight (42 kg) and fat score (2.10 units). In conclusion, grazing to 6 rather than 4 cm, increased individual carcass weight but not carcass weight gain/ha. Compared to PGHM-2500, grazing PGHM-1500 increased steer live-weight gain at pasture, but did not affect carcass weight following indoor finishing.

Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.