Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.

Background: Radiologically isolated syndrome (RIS) is characterized by incidental MRI findings suggestive of multiple sclerosis in asymptomatic individuals. Emerging blood biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 protein (CHI3L1) are promising tools for evaluating neuroinflammation and neurodegeneration. Methods: This cross-sectional analysis included 47 individuals with RIS who underwent MRI and plasma biomarker assessments. Plasma levels of CHI3L1, NfL, and GFAP were measured using highly sensitive assays. Correlations between biomarkers and MRI markers, including T1-black holes (BHs), central vein sign (CVS) positive lesions, paramagnetic rim lesions (PRLs), choroid plexus volume (CPV), and thalamic and hippocampal volumes, were analyzed using linear regression. Results: Plasma CHI3L1 levels correlated with increased CPV (β = 0.347, p = 0.017) and reduced thalamic (β = -0.309, p = 0.035) and hippocampal (β = -0.535, p < 0.001) volumes. Plasma GFAP levels were associated with BHs, CVS, and PRLs, whereas plasma NfL showed no correlations with MRI measures. Conclusions: Plasma CHI3L1 correlates with subcortical grey matter atrophy and CPV increase in RIS, distinct from correlations observed with GFAP or NfL. This suggests that plasma CHI3L1 may reflect neurodegeneration and inflammation in RIS and provide insights into disease activity not captured by other biomarkers.

Background: In multiple sclerosis (MS), soluble mediators of neuroinflammation are released by activated lymphocytes and resident immune cells, leading to demyelination and neurodegeneration. Radiologically isolated syndrome (RIS) is an entity in which white matter lesions fulfilling criteria for MS occur in individuals without any suggestive symptoms. The exact nature of pro- and anti-inflammatory cytokines in blood, and their association with disease activity in RIS/MS requires further clarification. Methods: Plasma was collected and cryopreserved from healthy controls (HCs), people with RIS and relapsing-remitting MS (RRMS) at the Barlo MS Centre. All samples were analyzed with OLink Target 96 Inflammation Multiplex Immunoassay Panel. Results: Individuals with RIS (p=0.0001; p= 0.0007; p= 0.0012) and RRMS (p<0.0001; p= 0.0003; p= 0.00112) had significantly higher concentrations of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and chemokine ligand 23 (CCL23) in plasma compared to HCs, and patients with RRMS (p=0.0087) had significantly higher concentrations of HGF compared to individuals with RIS. Conclusions: Our study demonstrates that HGF, IL-6 and CCL23 are significantly increased in the plasma of patients with RIS and RRMS compared to HCs. Our observations suggest that the biology of MS is present in those with RIS, and these neuroinflammatory mediators may serve as a biomarker of disease activity.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

Objectives/Goals: Team science (TS) competency is important for translational science team collaboration. However, there are few educators available to assist teams. Asynchronous learning is an effective strategy for delivering TS content. The goal of this project is to expand TS education by providing online access to our learners using online modules. Methods/Study Population: The Collaboration and Team Science (CaTS) team at the University of Cincinnati provides a robust TS education and training program. As the need for team science gains recognition, CaTS has received increased requests for services, leading to a need to broaden TS offerings. To address this demand, the CaTS team created “Team Science 101,” an online, asynchronous, series of 15 modules covering basic team science concepts. Each module consists of an educational recording lasting an average of 20 minutes, optional topic resources, pre- and post-module surveys assessing learners’ confidence and satisfaction, post-module knowledge checks, and evaluation questions. Upon completing all modules, participants receive a completion certificate. Results/Anticipated Results: TS 101 will be piloted with a group of participants who expressed interest in asynchronous TS content and will be adjusted based on the feedback received. The associated pre- and post-module survey, post-module knowledge check, and evaluation questions will be monitored to determine learning levels and improve TS 101 overall. Canvas is the educational platform that houses these modules, allowing for participant follow-up and scalable dissemination. The CaTS team plans to disseminate TS 101 nationally and internationally for anyone interested in this resource. Discussion/Significance of Impact: There is a national effort to collect and curate TS education, training, and toolkits. TS 101 will be a useful educational tool that will expand the reach of team science educators, provide the foundation for educators to explore topics more deeply by building on the module topics, and provide education to broader audiences who lack access to TS experts.

This paper reports an expansion of the English as a second language (L2) component of the Multilingual Eye Movement Corpus (MECO L2), an international database of eye movements during text reading. While the previous Wave 1 of the MECO project (Kuperman et al., 2023) contained English as a L2 reading data from readers with 12 different first language (L1) backgrounds, the newly collected dataset adds eye-tracking data on English text reading from 13 distinct L1 backgrounds (N = 660) as well as participants’ scores on component skills of English proficiency and information about their demographics and language background and use. The paper reports reliability estimates, descriptive statistics, and correlational analyses as means to validate the expansion dataset. Consistent with prior literature and the MECO Wave 1, trends in the MECO Wave 2 data include a weak correlation between reading comprehension and oculomotor measures of reading fluency and a greater L1-L2 contrast in reading fluency than reading comprehension. Jointly with Wave 1, the MECO project includes English reading data from more than 1,200 readers representing a diversity of native writing systems (logographic, abjad, abugida, and alphabetic) and 19 distinct L1 backgrounds. We provide multiple pointers to new venues of how L2 reading researchers can mine this rich publicly available dataset.

We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.

Galaxy morphology in stellar light can be described by a series of ‘non-parametric’ or ‘morphometric’ parameters, such as concentration-asymmetry-smoothness, Gini, $M_{20}$, and Sérsic fit. These parameters can be applied to column density maps of atomic hydrogen (H 1). The H 1 distribution is susceptible to perturbations by environmental effects, for example, intergalactic medium pressure and tidal interactions. Therefore, H 1 morphology can potentially identify galaxies undergoing ram-pressure stripping or tidal interactions. We explore three fields in the WALLABY Pilot H 1 survey and identify perturbed galaxies based on a k-nearest neighbour (kNN) algorithm using an H 1 morphometric feature space. For training, we used labelled galaxies in the combined NGC 4808 and NGC 4636 fields with six H 1 morphometrics to train and test a kNN classifier. The kNN classification is proficient in classifying perturbed galaxies with all metrics – accuracy, precision, and recall – at 70–80%. By using the kNN method to identify perturbed galaxies in the deployment field, the NGC 5044 mosaic, we find that in most regards, the scaling relations of perturbed and unperturbed galaxies have similar distribution in the scaling relations of stellar mass versus star formation rate and the Baryonic Tully–Fisher relation, but the H 1 and stellar mass relation flatter than of the unperturbed galaxies. Our results for NGC 5044 provide a prediction for future studies on the fraction of galaxies undergoing interaction in this catalogue and to build a training sample to classify such galaxies in the full WALLABY survey.

In intertemporal and risky choice decisions, parametric utility models are widely used for predicting choice and measuring individuals’ impulsivity and risk aversion. However, parametric utility models cannot describe data deviating from their assumed functional form. We propose a novel method using cubic Bezier splines (CBS) to flexibly model smooth and monotonic utility functions that can be fit to any dataset. CBS shows higher descriptive and predictive accuracy over extant parametric models and can identify common yet novel patterns of behavior that are inconsistent with extant parametric models. Furthermore, CBS provides measures of impulsivity and risk aversion that do not depend on parametric model assumptions.

Ambulatory antimicrobial stewardship can be challenging due to disparities in resource allocation across the care continuum, competing priorities for ambulatory prescribers, ineffective communication strategies, and lack of incentive to prioritize antimicrobial stewardship program (ASP) initiatives. Efforts to monitor and compare outpatient antibiotic usage metrics have been implemented through quality measures (QM). Healthcare Effectiveness Data and Information Set (HEDIS®) represent standardized measures that examine the quality of antibiotic prescribing by region and across insurance health plans. Health systems with affiliated emergency departments and ambulatory clinics contribute patient data for HEDIS measure assessment and are directly related to value-based reimbursement, pay-for-performance, patient satisfaction measures, and payor incentives and rewards. There are four HEDIS® measures related to optimal antibiotic prescribing in upper respiratory tract diseases that ambulatory ASPs can leverage to develop and measure effective interventions while maintaining buy-in from providers: avoidance of antibiotic treatment for acute bronchitis/bronchiolitis, appropriate treatment for upper respiratory infection, appropriate testing for pharyngitis, and antibiotic utilization for respiratory conditions. Additionally, there are other QM assessed by the Centers for Medicare and Medicaid Services (CMS), including overuse of antibiotics for adult sinusitis. Ambulatory ASPs with limited resources should leverage HEDIS® to implement and measure successful interventions due to their pay-for-performance nature. The purpose of this review is to outline the HEDIS® measures related to infectious diseases in ambulatory care settings. This review also examines the barriers and enablers in ambulatory ASPs which play a crucial role in promoting responsible antibiotic use and the efforts to optimize patient outcomes.

The incidence of Kawasaki Disease has a peak in the winter months with a trough in late summer/early fall. Environmental/exposure factors have been associated with a time-varying incidence. These factors were altered during the COVID-19 pandemic. The study was performed through the International Kawasaki Disease Registry. Data from patients diagnosed with acute Kawasaki Disease and Multiple Inflammatory Syndrome-Children were obtained. Guideline case definitions were used to confirm site diagnosis. Enrollment was from 1/2020 to 7/2023. The number of patients was plotted over time. The patients/month were tabulated for the anticipated peak Kawasaki Disease season (December–April) and non-peak season (May–November). Data were available for 1975 patients from 11 large North American sites with verified complete data and uninterrupted site reporting. The diagnosis criteria were met for 531 Kawasaki Disease and 907 Multiple Inflammatory Syndrome-Children patients. For Multiple Inflammatory Syndrome-Children there were peaks in January of 2021 and 2022. For Kawasaki Disease, 2020 began (January–March) with a seasonal peak (peak 26, mean 21) with a subsequent fall in the number of cases/month (mean 11). After the onset of the pandemic (April 2020), there was no clear seasonal Kawasaki Disease variation (December–April mean 12 cases/month and May–November mean 10 cases/month). During the pandemic, the prevalence of Kawasaki Disease decreased and the usual seasonality was abolished. This may represent the impact of pandemic public health measures in altering environmental/exposure aetiologic factors contributing to the incidence of Kawasaki Disease.

We present the Pilot Survey Phase 2 data release for the Wide-field ASKAP L-band Legacy All-sky Blind surveY (WALLABY), carried-out using the Australian SKA Pathfinder (ASKAP). We present 1760 H i detections (with a default spatial resolution of 30′′) from three pilot fields including the NGC 5044 and NGC 4808 groups as well as the Vela field, covering a total of $\sim 180$ deg$^2$ of the sky and spanning a redshift up to $z \simeq 0.09$. This release also includes kinematic models for over 126 spatially resolved galaxies. The observed median rms noise in the image cubes is 1.7 mJy per 30′′ beam and 18.5 kHz channel. This corresponds to a 5$\sigma$ H i column density sensitivity of $\sim 9.1\times10^{19}(1 + z)^4$ cm$^{-2}$ per 30′′ beam and $\sim 20$ km s$^{-1}$ channel and a 5$\sigma$ H i mass sensitivity of $\sim 5.5\times10^8 (D/100$ Mpc)$^{2}$ M$_{\odot}$ for point sources. Furthermore, we also present for the first time 12′′ high-resolution images (“cut-outs”) and catalogues for a sub-sample of 80 sources from the Pilot Survey Phase 2 fields. While we are able to recover sources with lower signal-to-noise ratio compared to sources in the Public Data Release 1, we do note that some data quality issues still persist, notably, flux discrepancies that are linked to the impact of side lobes associated with the dirty beams due to inadequate deconvolution. However, in spite of these limitations, the WALLABY Pilot Survey Phase 2 has already produced roughly a third of the number of HIPASS sources, making this the largest spatially resolved H i sample from a single survey to date.

Scholarly activity is a key component of most residency programmes. To establish fundamental research skills and fill gaps within training curricula, we developed an online, asynchronous set of modules called Research 101 to introduce trainees to various topics that are germane to the conduct of research and evaluated its effectiveness in resident research education. Research 101 was utilised by residents at One Brooklyn Health in Brooklyn, NY. Resident knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a multiple-choice quiz. Pre-module survey results indicated that residents were most confident with the Aligning expectations, Introduction to research, and Study design and data analysis basics modules and least confident with the Submitting an Institutional Review Board protocol and Presenting your summer research modules. Post-module survey responses demonstrated increased learning compared to pre-module results for all modules and learning objectives (p < 0.0001). “This module met my needs” was endorsed 91.4% of the time. The median score for the final quiz that consisted of 25 multiple-choice questions was 23. Thematic analysis of open-ended post-module survey responses identified multiple strengths and opportunities for improvement in course content and instructional methods. These data demonstrate that residents benefit from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions, final quiz scores were high, and open-ended responses highlighted opportunities for additional resident learning.