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Objectives/Goals: To develop and implement a centralized Smartsheet-based portfolio to streamline data collection, coordination, and reporting of NJ ACTS Workforce Development programs, improving efficiency, transparency, and alignment with CTSA translational science goals. Methods/Study Population: NJ ACTS Workforce Development programs, including digital badges, seminars, workshops, and internships, were mapped into a unified Smartsheet platform. Program participation, training metrics, and milestone data were integrated through automated workflows and real-time dashboards, enabling seamless tracking and analysis. Data collection templates and standardized reporting tools were co-designed with program managers to ensure consistency across domains. Continuous user feedback informed iterative refinements to improve usability and data integrity. Results/Anticipated Results: Early results of the Smartsheet portfolio have reduced administrative workload, standardized reporting, and enhanced transparency across programs. Real-time dashboards now track learner progress, completion rates, and cross-program engagement. Early adoption indicates improved collaboration among stakeholders and stronger alignment with CTSA goals and performance metrics. Anticipated outcomes include sustained efficiency gains, improved accountability, and scalable use across institutional partners. Discussion/Significance of Impact: A centralized Smartsheet platform supports coordinated management of training initiatives, enabling data-driven decision-making, continuous improvement, and replicable models for translational workforce development across the CTSA consortium.

Objectives/Goals: To implement and evaluate a Smartsheet-based system that centralizes management, tracking, and credentialing for the NJ ACTS Clinical Research Coordinator digital badging program, improving efficiency, data integration, and measurable workforce development outcomes. Methods/Study Population: The NJ ACTS CRC digital badging program was integrated into a Smartsheet platform designed to unify data across JotForm, Qualtrics, REDCap, Canvas LMS, and Accredible. Automated workflows track learner enrollment, module completion, and credential issuance in real time. Participants include CRCs and trainees across academic and clinical settings. The platform’s dashboards and automated reports support continuous monitoring, feedback collection, and competency validation. Data from initial cohorts were analyzed to assess usability, process efficiency, and accuracy of training metrics across systems. Results/Anticipated Results: Integration of Smartsheet has improved onboarding efficiency, reduced administrative burden, and enhanced visibility into learner progress. Automated credentialing through Accredible provides timely recognition of competencies. Early results demonstrate increased completion rates and more consistent tracking across partner sites. The unified system enables data-driven decision-making and facilitates the scalable expansion of CRC training efforts within and beyond NJ ACTS institutions. Discussion/Significance of Impact: Smartsheet integration enhances the infrastructure for digital badging and workforce tracking, providing a replicable and scalable model to standardize CRC training nationally and advance competency-based education in translational science.

CD4 T cells are necessary to control intracellular bacterial infections, but the role of sex in these infections is poorly understood. Here we show that upon challenge with Salmonella, a model intracellular bacterium, more male mice succumb to infection than females, despite having more Salmonella specific CD4 T cells at later infection stages. Upon infecting mice lacking CD4 T cells, survival differences reverse, which suggests that female and male CD4 T cells play opposing roles during infection. Transfer of purified CD4 T cells from either sex into CD4 deficient mice restores survival in females but decreases survival in males. Decreasing the hormone 17β-estradiol in females induces a more severe male-like phenotype. Exogenous 17β-estradiol induces both inflammatory and suppressive cytokines in CD4 T cells from infected female mice and restores the protective function of T cells during infection. These findings reveal a sex difference in CD4 T cell behavior during intracellular bacterial infection.

Developmental exposure to organophosphate flame retardants (OPFRs) is a public health concern due to their endocrine-disrupting potential. We examined perinatal exposure to tris(1,3-dichloro-2-propyl) phosphate, triphenyl phosphate, and tricresyl phosphate in mice. Adult male and female offspring were assessed for memory and anxiety-like behavior. Dopamine and norepinephrine were quantified in the hippocampus and prefrontal cortex (PFC), and bulk RNA sequencing was conducted for the hippocampus. OPFR-treated females in high ovarian hormone states spent less time in the open field test (OFT) center, the Y-maze unknown arm, and with the displaced object in spatial object recognition (SOR) indicating increased anxiety-like behavior and impaired spatial memory. These females also illustrated improved memory on the short-term Barnes maze, and a trending improvement in the novel object recognition test. Females in low ovarian hormone states, demonstrated a trend in center OFT exploration. OPFR-treated males displayed disruption in memory in the SOR and the short- and long-term Barnes maze. Perinatal OPFR reduced hippocampal dopamine in males and altered prefrontal dopamine in females in a hormone-dependent manner. OPFR-treated females in high ovarian hormones states demonstrated a trending decrease in PFC norepinephrine. Perinatal OPFR treatment caused differential gene expression in 121 individual genes and alteration to functional modules related to RNA processing, cellular metabolism, and extracellular organization. Hormone status also affected gene OPFR-induced altered expression, with similarity between males and high ovarian hormone state females. Our findings suggest that perinatal OPFR exposure causes widespread, sex specific, and hormone dependent disruptions in behavior, neurochemistry, and gene expression in adulthood. Anxiety-like behavior in OPFR-treated females varied with ovarian hormone statusHigh ovarian hormone OPFR females showed task-dependent changes in memoryMales displayed impaired spatial memory following perinatal OPFR treatmentPerinatal OPFR modifies hippocampal and prefrontal dopamine and norepinephrineOPFR treatment altered individual gene and functional gene module expression.

Semipermeable polymeric anion exchange membranes are essential for separation, filtration and energy conversion technologies including reverse electrodialysis systems that produce energy from salinity gradients, fuel cells to generate electrical power from the electrochemical reaction between hydrogen and oxygen, and water electrolyser systems that provide H 2 fuel. Anion exchange membrane fuel cells and anion exchange membrane water electrolysers rely on the membrane to transport OH − ions between the cathode and anode in a process that involves cooperative interactions with H 2 O molecules and polymer dynamics. Understanding and controlling the interactions between the relaxation and diffusional processes pose a main scientific and critical membrane design challenge. Here quasi-elastic neutron scattering is applied over a wide range of timescales (10 0 –10 3  ps) to disentangle the water, polymer relaxation and OH − diffusional dynamics in commercially available anion exchange membranes (Fumatech FAD-55) designed for selective anion transport across different technology platforms, using the concept of serial decoupling of relaxation and diffusional processes to analyse the data. Preliminary data are also reported for a laboratory-prepared anion exchange membrane especially designed for fuel cell applications. Semipermeable polymeric anion exchange membranes are essential for separation, filtration and energy conversion technologies such as fuel cells. Quasi-elastic neutron scattering is now used to disentangle water, polymer relaxation and OH − diffusional dynamics in a commercially available membrane.

Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs), such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor κB (NFκB). Our objective was to determine the effect of IκK-16, a selective blocker of inhibitor of kappa-B kinase (IκK), on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-α and IL-10 production (P < 0.05). miR-155 and miR-138 levels were significantly upregulated at 17 h in the impaired monocyte (P < 0.05). Notably, IκK-16 decreased miR-155 expression with a corresponding dose-dependent decrease in TNF-α and IL-10 production (P < 0.05), and impaired monocyte function was associated with increased miR-155 and miR-138 expression. In the context of IκK-16 inhibition, miR-155 mimics increased TNF-α production, while miR-155 antagomirs decreased both TNF-α and IL-10 production. These data demonstrate that IκK-16 treatment attenuates the monocyte inflammatory response, which may occur through a miR-155-mediated mechanism, and that IκK-16 is a promising approach to limit the magnitude of an excessive innate inflammatory response to LPS.

Background African Americans have a disproportionate burden of hypertension and comorbid disease. Pharmacogenetic markers of blood pressure response have yet to be defined clearly. This study explores the association between G-protein-coupled receptor kinase type 4 (GRK4) variants and blood pressure response to metoprolol among African Americans with early hypertensive nephrosclerosis. Methods Participants from the African American Study of Kidney Disease and Hypertension (AASK) trial were genotyped at three GRK4 polymorphisms: R65L, A142V, and A486V. A Cox proportional hazards model, stratified by gender, was used to determine the relationship between GRK4 variants and time to reach a mean arterial pressure (MAP) of 107 mm Hg, adjusted for other predictors of blood pressure response. Potential interactions between the three polymorphisms were explored by analyzing the effects of gene haplotypes and by stratifying the analysis by neighboring sites. Results The hazard ratio with 95% confidence interval by A142V among men randomized to a usual MAP (102–107 mm Hg) was 1.54 (1.11–2.44; P = 0.0009). The hazard ratio by A142V with R65/L65 or L65/L65 was 2.14 (1.35–3.39; P = 0.001). Haplotype analyses were consistent but inconclusive. There was no association between A142V and blood pressure response among women. Conclusions Results suggest a sex-specific relationship between GRK4 A142V and blood pressure response among African-American men with early hypertensive nephrosclerosis. Men with a GRK4 A142 were less responsive to metoprolol if they had a GRK4 L65 variant. The effect of GRK4 variants and blood pressure response to metoprolol should be studied in larger clinical trials. American Journal of Hypertension 2009; doi:10.1038/ajh.2008.341

Purpose: To explore the association between CYP3A4 and CYP3A5 gene polymorphisms and blood pressure response to amlodipine among participants from the African-American Study of Kidney Disease and Hypertension Trial randomized to amlodipine (n = 164). Methods: Cox proportional hazards models were used to determine the risk of reaching a target mean arterial pressure (MAP) of ≤107 mm Hg by CYP3A4 (A–392G and T16090C) and CYP3A5 (A6986G) gene polymorphisms, stratified by MAP randomization group (low or usual) and controlling for other predictors for blood pressure response. Results: Women randomized to a usual MAP goal with an A allele at CYP3A4 A–392G were more likely to reach a target MAP of 107 mm Hg. The adjusted hazard ratio (AA/AG compared to GG) with 95% confidence interval was 3.41 (1.20–9.64; p = 0.020). Among participants randomized to a lower MAP goal, those with the C allele at CYP3A4 T16090C were more likely to reach target MAP: The adjusted hazard ratio was 2.04 (1.17–3.56; p = 0.010). After adjustment for multiple testing using a threshold significance level of p = 0.016, only the CYP3A4 T16090C SNP remained significant. CYP3A5 A6986G was not associated with blood pressure response. Conclusions: Our findings suggest that blood pressure response to amlodipine among high-risk African-Americans appears to be determined by CYP3A4 genotypes, and sex specificity may be an important consideration. Clinical applications of CYP3A4 genotype testing for individualized treatment regimens warrant further study.

Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs), such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor [kappa]B (NF[kappa]B). Our objective was to determine the effect of I[kappa]K-16, a selective blocker of inhibitor of kappa-B kinase (I[kappa]K), on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-[alpha] and IL-10 production (P < 0.05). miR-155 and miR-138 levels were significantly upregulated at 17 h in the impaired monocyte (P < 0.05). Notably, I[kappa]K-16 decreased miR-155 expression with a corresponding dose-dependent decrease in TNF-[alpha] and IL-10 production (P < 0.05), and impaired monocyte function was associated with increased miR-155 and miR-138 expression. In the context of I[kappa]K-16 inhibition, miR-155 mimics increased TNF-[alpha] production, while miR-155 antagomirs decreased both TNF-[alpha] and IL-10 production. These data demonstrate that I[kappa]K-16 treatment attenuates the monocyte inflammatory response, which may occur through a miR-155-mediated mechanism, and that I[kappa]K-16 is a promising approach to limit the magnitude of an excessive innate inflammatory response to LPS.

Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, SARS-CoV-2, and HIV. Herein, we developed a highly modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, TLR7/8a adjuvants and their mixtures. These various TLRa-SNP adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could improve the design of vaccines for and dramatically impact modern vaccine development.Competing Interest StatementE.A.A, B.S.O, and J.B. are listed as inventors on a pending patent application. N.P.K. is a cofounder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. The King lab has received unrelated sponsored research agreements from Pfizer and GSK. All other authors declare no conflicts of interest.Footnotes* We revised Figures 1-7 and additional experiments added.