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Ownership in the League of Ireland: why Irish professional football clubs are transitioning to the co-operative model

ABSTRACT The League of Ireland (LOI) is the Republic of Ireland’s top tier of professional football. In the 2022/2023 season, six of the nineteen clubs in the LOI were owned and governed as co-operative organizations. This paper identifies the key motivating factors behind the emergence and development of co-operative clubs in the LOI. To achieve this, semi-structured interviews were conducted with board members of five co-operative clubs in the LOI and with two key stakeholder organizations. The research found that the co-operative model was adopted by supporters and communities as a last resort option following decades of financial distress and poor corporate governance under the investor-owned model. This paper argues that the co-operative model has succeeded in saving numerous clubs from the brink of financial collapse and the model could be considered by other clubs in the LOI as a viable alternative model of ownership.

The impact of artificial intelligence on corporate greenwashing: evidence from the Chinese listed firms

PurposeThis paper investigates the impact of AI penetration rate on the degree of corporate greenwashing and aims to assess the potential of AI in enhancing firms' environmental performance and reducing false disclosures.Design/methodology/approachThis study employs a year and firm fixed-effects model to analyze data from Chinese listed firms from 2012 to 2022. We use the low-carbon city pilot as a quasi-natural experiment to address endogeneity concerns and conduct a series of robustness tests, including adding control variables and transforming the model.FindingsThe results of this paper show that the application of AI can inhibit firms' greenwashing behavior, with green innovation activities further enhancing this inhibitory effect. In state-owned firms and those with Party Organizations, the inhibitory effect of AI on corporate greenwashing is more significant. This reduction in greenwashing is more likely to be observed in firms that are heavily influenced by Confucian culture, receive higher public attention regarding their environmental impact, face less market competition, suffer from more serious pollution and face less financial constraints.Originality/valueWe propose a new research perspective that offers novel insights into promoting the green development of firms by revealing the potential of AI in reducing their greenwashing behavior. Corporate boards can explore specific strategies for applying AI to monitor, prevent and correct greenwashing, thereby enhancing corporate environmental performance and social responsibility.

Politics of school evaluation during quality assurance policy implementation in selected secondary schools in Dodoma, Tanzania

Purpose This study aims to examine the nature and extent of political dynamics (power struggles and contestations) among internal and external school stakeholders in the school evaluation processes and their influence on the objectivity and consistency of evaluations. Design/methodology/approach This study used a purposive sampling method to examine seven secondary schools in Dodoma Region, which were key in piloting the School Quality Assurance (SQA) policy implementation in 2018. The selected schools were government boarding institutions with long histories, managed by School Management Teams and Governing Boards that influenced school decision-making. These schools had regular SQA visits and produced School Self-Evaluation and Whole-School Evaluation reports, which served as the primary data sources. Data were analysed using a method that involved sorting, coding, identifying patterns and applying theory to interpret the findings. The analysis focused on discrepancies and power dynamics in school evaluations, particularly how internal and external evaluators’ roles were represented in the reports. Ethical considerations were ensured through confidentiality, pseudonymizing participants and obtaining clearance from relevant authorities. This study’s reliability and trustworthiness were enhanced through consistent data collection protocols, a transparent coding framework and triangulation of sources. This research offers insights into the politics of SQA policy implementation, highlighting tensions and power dynamics in school evaluations and revealing gaps between policy and practice. Findings This study identifies the SQA policy discourses that were tools and sites of power struggles and contestations among internal and external evaluators in all six quality domains. These political dynamics impacted the objectivity and consistency of evaluation outcomes due to subjectivity among evaluators. Internal evaluation had a positive image by offering higher quality indicators than external evaluation in most case study schools. Research limitations/implications Policy documents provide a high-level overview, often missing the nuanced realities of school implementation. While updated periodically, they may not reflect current practices or challenges. These documents typically present an idealized vision of education, which might not align with actual outcomes. Analysing them alone can overlook the perspectives of teachers, students, parents and other stakeholders directly impacted by the policies. Informal practices and adaptations in response to policy directives may not be documented, and the interpretation of such documents can vary widely, leading to subjective analysis. In addition, policy documents lack empirical data on the effectiveness and impact of the policies. Practical implications This study highlights the need for clear and consistent evaluation criteria to reduce discrepancies between internal and external evaluators. It also underscores the importance of training and support for school-based evaluators to ensure reliable assessments. Moreover, this study calls for addressing political dynamics influencing evaluation objectivity, ensuring that evaluations genuinely reflect school performance. Finally, the findings advocate for involving all stakeholders in the evaluation process to enhance transparency and accountability. Social implications This study has important social implications. It reveals how political dynamics can affect the fairness and transparency of school evaluations, potentially impacting stakeholders’ trust in the education system. This study highlights the need for equitable and unbiased evaluation practices to ensure that all schools are fairly assessed and supported. This can lead to better educational outcomes, as schools receive appropriate feedback and resources. Moreover, involving community members in the evaluation process can foster greater accountability and community engagement in educational development. Originality/value This study provides original value by addressing the intersection of political dynamics and educational evaluation. It uniquely examines how power struggles and political influences affect the objectivity and consistency of quality assurance practices. By highlighting discrepancies between internal and external evaluators, this study offers fresh insights into the challenges of implementing educational policies. This research contributes to the broader discourse on educational reform by advocating for more transparent and equitable evaluation processes, thereby enhancing policy effectiveness and educational outcomes.

Advancing Business Ethical Standards: Unpacking the Synergistic Influence of Governance Structures and CSR Engagement on Corporate Integrity in BRICS Countries

ABSTRACTIn a global business environment where ethical lapses increasingly undermine corporate credibility, can enhanced governance mechanisms and CSR engagement drive ethical corporate behavior? This study explores the intricate relationship between corporate governance attributes and Business Ethical Practices (BEP), examining how CSR engagement moderates this relationship across 386 manufacturing firms in the BRICS countries from 2010 to 2022. Grounded in Stakeholder and Agency Theories, the research investigates three core governance strands: diversity, structural, and process attributes. Using the Generalized Method of Moments (GMM) estimator, the findings reveal that gender diversity and age diversity positively influence BEP, while national diversity has a negative association, raising concerns about the alignment of foreign board members with local ethical standards. Board independence and board size significantly enhance ethical practices, while CEO duality negatively affects BEP, emphasizing the importance of independent oversight. Among process attributes, board meetings and board tenure positively contribute to BEP, while meeting attendance shows a negative association, suggesting that mere presence without meaningful participation may not guarantee ethical outcomes. Notably, CSR engagement amplifies positive governance effects and mitigates negative influences, reinforcing its critical role as a governance enhancer. Heterogeneity analyses across manufacturing types (Job Shop, Batch, Continuous Process, and Mass Production) confirmed the consistency of these findings. Furthermore, robustness tests, including cluster analysis, sensitivity analysis, and endogeneity controls, validated the reliability of the results. The study provides targeted policy recommendations advocating for stronger diversity mandates, deeper CSR integration, and enhanced ethical training, while the practical implications emphasize the importance of comprehensive governance frameworks for long‐term ethical sustainability.

299. Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for Central Nervous System Infections: Clinical Factors Associated with Increased Diagnostic Yield

Abstract Background Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) can improve diagnostic yields in central nervous system (CNS) infections, but the most beneficial clinical indications have yet to be defined.Table 1.Factors evaluated by univariate analysis associated with a positive CSF mNGS test*P-value in bold are considered statistically significant (P < 0.05) Methods We analyzed CSF mNGS results and associated clinical, demographic, and laboratory metadata from a cohort of patients for whom mNGS testing was performed at University of California, San Francisco (UCSF) from 2016 to 2023. We assessed by chart-review positive CSF mNGS results that established definitive diagnoses of CNS infections in the cohort. We then used univariate and multivariate logistic regression analysis to identify clinical factors that were associated with positive mNGS results.Figure 1.Significant clinical factors associated with mNGS positivity selected by multivariate analysis.The odds ratio and associated confidence intervals are plotted for each row (clinical factors).*, P < 0.05; **, P < 0.01; ***, P < 0.001; NS, non-significant. Results Of 1,164 mNGS tests, 133 were positive for CNS infection-causing pathogens. By univariate analysis (Table 1), factors including hospitalization (P = 0.009), intensive care unit (ICU) admission (P = 0.02), immunosuppressed status (P < 0.0001), clinical meningitis or meningoencephalitis (P < 0.0001), and abnormal CNS imaging (P = 0.004) were significantly associated with a positive mNGS result. In contrast, demographic variables, including age, sex, race, and ethnicity, were not. For CSF, early mNGS testing performed by hospital day 7 (P < 0.002), elevated protein (P = 0.005), and low glucose (P = 0.001) were associated with a positive mNGS result, whereas the presence of red blood cells (P = 0.77), pleocytosis (P = 0.17), and neutrophil or lymphocyte predominance (P = 0.24) were not. Significant factors selected by multivariate analysis include ICU stay (OR = 1.8, 95%CI[1.2, 1.9]), acute abnormalities on imaging (OR = 2.3, 95%CI[1.3, 4.2]), early mNGS testing within 7 days of admission (OR = 2.8, 95%CI[1.5, 5.2]), meningitis or meningoencephalitis (OR = 10.7, 95%CI[1.4, 82.7] and OR = 14.4, 95%CI[1.9, 112.1]), and immunosuppressed status (OR = 4.3 95%CI[2.7, 7.0]) (Figure 1). Conclusion This study identified key factors for predicting positive CSF mNGS results that will be incorporated into a predictive scoring system to identify clinical scenarios for which testing is clinically indicated to maximize diagnostic yield. Real-time scoring metric will enhance diagnostic stewardship and optimize the cost-effectiveness of CSF mNGS testing. Disclosures Charles Chiu, MD, PhD, Abbott Laboratories, Inc: Grant/Research Support|Biomeme: Advisor/Consultant|Biomeme: Board Member|BiomeSense: Advisor/Consultant|BiomeSense: Board Member|Delve Bio: Advisor/Consultant|Delve Bio: Board Member|Delve Bio: Grant/Research Support|Flightpath Biosciences: Advisor/Consultant|Flightpath Biosciences: Board Member|Mammoth Biosciences: Advisor/Consultant|Mammoth Biosciences: Board Member|Pathogen detection using next generation sequencing: US patent 11380421|Poppy Health: Advisor/Consultant|Poppy Health: Board Member

298. Host Response Profiling from Clinical Metagenomic Sequencing Data for Diagnosis of Central Nervous System Infections

Abstract Background Clinical metagenomic next-generation sequencing (mNGS) testing of cerebrospinal fluid (CSF) increases diagnostic yield for suspected central nervous system (CNS) infections. Nevertheless, up to 45% of cases remain unknown despite extensive testing and 6 months of follow-up. We developed artificial intelligence-machine learning (AI-ML) classification models (classifiers) based on RNA gene expression / host response data from CSF mNGS testing to enhance diagnostic performance.Figure 1.An artificial intelligence machine learning classifier. (A) Schematic illustration of the different steps to generate the sub-classifiers then integrated into a consensus classifier. (B) The parasitic sub-classifier was generated using the "leave-one-out" algorithm due to the low sample numbers. (C) Performance metrics of the main classifiers. Methods From June 2016 and April 2023, 464 CSF mNGS results from UCSF patients with a confirmed viral (n=175), bacterial (n=91), fungal (n=44), or non-infectious (n=155) diagnosis were randomly divided into training and test subsets in an 80:20 ratio (Figure 1A). Clinicians adjudicated their confidence in the final diagnosis based on blinded medical chart review and laboratory test results. Gene (feature) selection was carried out using high-confidence samples, followed by 50-fold cross-validation. All possible pairwise comparisons were performed to generate sub-classifiers which were then integrated into a consensus classifier. Performance metrics were obtained by running the consensus classifier on the independent test subset. A separate classifier was developed for parasitic infections (n=24) using a “leave-one-out” algorithm to assess performance (Figure 1B). Classifier results were displayed as a score ranging from 0 to 10, corresponding to specificities of ≤70% to ≥99%.Figure 2.Differentially expressed gene analysis with pair-wise comparison between sub-classifiers. Left panel shows genes selected by the LASSO (least absolute shrinkage and selection operator) algorithm, and right panel the pathway/function these genes. Results Classifier accuracy based on the test set was 83%, with individual area under the curve (AUC) scores ranging from 0.88-0.93 for each category (Figure 1C). The function of the selected genes corresponded well with the category (Figure 2). Classifier examples include patients with (i) culture-negative CNS tuberculosis, (ii) persistent Toxoplasma gondii infection despite 19 days of treatment, (iii) a rare autoimmune syndrome, and (iv) a chronic enterovirus infection misclassified as an atypical bacterial infection, suggesting that acute and chronic host response profiles differ (Figure 3).Figure 3.Classifier examples. (i) culture-negative CNS tuberculosis, (ii) persistent Toxoplasma gondii infection despite 19 days of treatment, (iii) a rare autoimmune syndrome, and (iv) a chronic enterovirus infection misclassified as an atypical bacterial infection. Conclusion Host response profiling with AI-ML classifiers complements mNGS testing and can enhance diagnostic yield for unexplained CNS syndromes. Disclosures Charles Chiu, MD, PhD, Abbott Laboratories, Inc: Grant/Research Support|Biomeme: Advisor/Consultant|Biomeme: Board Member|BiomeSense: Advisor/Consultant|BiomeSense: Board Member|Delve Bio: Advisor/Consultant|Delve Bio: Board Member|Delve Bio: Grant/Research Support|Flightpath Biosciences: Advisor/Consultant|Flightpath Biosciences: Board Member|Mammoth Biosciences: Advisor/Consultant|Mammoth Biosciences: Board Member|Pathogen detection using next generation sequencing: US patent 11380421|Poppy Health: Advisor/Consultant|Poppy Health: Board Member

P-1861. Increased Disease Severity in Experimental Clostridioides difficile Infection is Associated with Increased Levels of Fecal Toxin

Abstract Background Clostridioides difficile is a toxin-producing bacteria that is the most common cause of nosocomial diarrhea. The CDC estimates that there are around 500,000 infections caused by C. difficile each year and has declared that the bacteria is an urgent public health threat . The production of toxin is thought to be the primary driver of disease pathogenesis. To understand the relationship between toxin and disease severity, we analyzed the correlation between clinical and histopathologic scores and toxin amount using a murine model. Real Time Cellular Analysis utilizing Aligent Systems. (A) Single well view of well before (left) and after (right) addition of HT-29 cells. Cellular impedance is measured using electron flow from the negative terminal to the positive terminal. Increased cell proliferation and adhesion to the bottom of the well leads to increased cellular impedance. (B) Example graphic of real-time cellular index tracing. (C) Experimental real-time cellular index tracing of fecal samples and toxin standards. Methods Young (6- to 8-week-old), specific-pathogen-free mice were treated with 10 days of Cefoperazone to render them susceptible to C. difficile infection. Mice were given an oral gavage of either water, C. difficile VPI10463 spores, or C. difficile 630g spores. We monitored mice throughout the experiment for posture, coat, diarrheal signs, activity, and weight change to determine clinical score. At the time of sacrifice, tissue was collected and histopathologic scores were determined based on edema, epithelial damage, and inflammatory cell infiltration. Cytokines were measured using a customized Luminex panel. Real time cellular analysis was utilized to quantify the amount of toxin present in mouse fecal samples. Statistical analysis was completed in R. Pearson’s product-moment correlations for the relation of log(toxin) amount and individual components of clinical score Results There was a strong, positive correlation between clinical score and toxin. When further analyzed, we found that the weight loss component of clinical score was most correlated with toxin amount (Table 1). Additionally, there was a strong, positive correlation between total histopathologic score and toxin (Figure 2). We found that all components of total histopathologic score were strongly correlated with toxin. We found multiple cytokines were correlated with toxin (Table 2). Histopathology (A) Scatterplot showing total histopathologic score (based on edema, epithelial damage, and inflammatory cell infiltration of the cecum and colon) and log(toxin) amount. Total histopathologic score has a strong, positive, correlation with log(toxin) amount (r=0.653). (B) Histopathology representative of mice without C. difficile infection. (C) Histopathology representative of mice with C. difficile infection. Conclusion Increased toxin present in fecal samples was found to be correlated with severity of disease. Previous work established a predictive model of CDI utilizing cytokines. We expect that the relationship between toxin and disease severity is mediated by the host immune response. Understanding the relationship between toxin and disease severity could be helpful in predicting CDI prognosis and helpful in guiding therapy. Pearson’s product-moment correlations for the relation of log(toxin) amount and individual cytokines. Disclosures Vincent B. Young, MD, PhD, Aimmune: Honoraria|American Society for Microbiology: Board Member|Debiopharm: Advisor/Consultant|Peggy Lillis Foundation: Board Member|University of Oklahoma COBRE: Advisor/Consultant|Vedanta: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant|Vedanta Bioscience: Grant/Research Support Krishna Rao, MD, MS, Vedanta: Advisor/Consultant

P-2258. Characterizing real world infection risk in multiple myeloma patients receiving teclistamab

Abstract Background Teclistamab is an anti-B-cell maturation antigen (BCMA) bispecific antibody used in relapsed, refractory multiple myeloma (MM) that induces durable responses but is associated with high rates of infectious complications. Real world data are needed to further characterize infection risk in patients receiving teclistamab.Table 1.Patient characteristics between infected and non-infected patients Methods A retrospective single-center study of teclistamab treated patients with relapsed, refractory MM from 1/1/2023 to 11/20/2023. Patients received teclistamab according to a step-up dosing regimen, with Day 0 defined as first step-up dose. The primary objective was to report the incidence, type, and timing of infection. Differences in demographics and clinical characteristics were described between infected and non-infected patients.Table 2.Patient outcomes on teclistamab between infected and non-infected patients Results 19 patients received teclistamab; median age 72 years, 73.7% white, and 26.3% with Karnofsky performance status ≥ 80 (Table 1). 11 (57.9%) patients developed infections and 5 had more than one infection. There were 3 bacteremias, 6 other bacterial infections (urinary tract infection, pneumonia, cholangitis, osteomyelitis, sinusitis), 6 respiratory viral infections, and 2 cytomegalovirus (CMV) reactivations. There were no documented infections with herpes simplex virus, varicella zoster virus, Pneumocystis jirovecii, or fungal pathogens. The median time to any infection was 17 days (range 2, 266), with a median of 20 days (range 2, 123) to bacterial infection and 31 days (range 3, 266) to viral infection (Figure 1). Patient characteristics and antimicrobial prophylaxis strategies were largely similar between infected and non-infected patients (Table 1). There was a nonsignificant trend toward increased immune effector cell-associated neurotoxicity syndrome (ICANS) and increased use of steroids in the infected group. 10 patients in the infected group discontinued teclistamab (p=0.013) and 3 died (p=0.108, Table 2).Figure 1.Cumulative incidence of any infection (A), bacterial infection (B), and viral infection (C). Conclusion The incidence of infection was high amongst patients receiving teclistamab and increased with time. Individuals with infections were more likely to discontinue teclistamab. Further data are needed to inform guidance regarding infection prevention strategies and criteria for teclistamab interruption or discontinuation in this MM population with few other treatment options. Disclosures Kevin Rakszawski, MD, AstraZeneca: Speakers Bureau|Pfizer: Speakers Bureau Seema Naik, MD, ADC Therapeutics: Advisor/Consultant|ADC Therapeutics: Board Member|ADC Therapeutics: Honoraria|Janssen: Advisor/Consultant|Janssen: Board Member|Janssen: Honoraria|Onclive: Honoraria|Onclive: Speaker

P-2099. A Novel Anaerobic Activity Index to define the “anti-anaerobic” spectrum of antimicrobials

Abstract Background While necessary for the treatment of anaerobic infections, use of antibiotics with anaerobic activity may be associated with poor patient outcomes including graft-versus host disease after bone marrow transplant and mortality in critically ill patients. However, we lack a uniform method to assess the relative anaerobic activity of antibiotics and have poor definitions of what it means for antimicrobials to be “anti-anaerobic”. Methods A PubMed search using terms “microbial sensitivity test”, “anti-bacterial agents” and “bacteria, anaerobic” yielded 575 papers published between January 2013-2024 (Figure 1). Papers with < 100 isolates, non-human isolates, or without antimicrobial susceptibility testing (AST) were excluded. AST for an average of 17,709 anaerobic clinical isolates per antimicrobial from 56 publications were summarized. Anaerobes were categorized into 11 groups based on the literature (Table 1). For 16 commonly used antibiotics, values of 0, 1, or 2 were awarded for each group of anaerobes for average published susceptibility of ≤ 10%, 11-89.4%, and ≥ 89.5%, respectively, and tallied to create a composite score (0-22, Score A). Three alternative scores were created based on different susceptibility cutoffs (Scores B-D; Table 2).Table 1:Groups of anaerobes for which antimicrobial susceptibility was scored Results In Anaerobic Activity Index Score A, scores ranged from 11 for moxifloxacin to 22 for tigecycline, meropenem, and imipenem (Table 2). Anaerobic Activity Index scores were plotted against the Antibiotic Spectrum Coverage (ASC), a previously published antibiotic “broad” spectrum score (Figure 2). Varying susceptibility thresholds affected estimated anaerobic activity for some antibiotics, including clindamycin and vancomycin, but overall, there was good agreement across all scores (A-D). Moxifloxacin had the lowest overall scores due to high rates of resistance across all groups of anaerobes. Conclusion Antibiotic broad-spectrum scores have been proposed, but no valid score exists and no score assessing anaerobic activity has been developed. An Anaerobic Activity Index may improve the definition of “anti-anaerobic” antimicrobials for clinical care and research. Further studies are needed to validate this index as a potential tool to evaluate the effect of anaerobic antibiotic exposure on clinical outcomes. Disclosures Vincent B. Young, MD, PhD, Aimmune: Honoraria|American Society for Microbiology: Board Member|Debiopharm: Advisor/Consultant|Peggy Lillis Foundation: Board Member|University of Oklahoma COBRE: Advisor/Consultant|Vedanta: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant|Vedanta Bioscience: Grant/Research Support David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

428. Severe Acute Respiratory Syndrome Coronavirus 2 Household Transmission during the Omicron Era in Massachusetts: A Prospective, Case-Ascertained Study using Genomic Epidemiology

Abstract Background Households are a major setting for SARS-CoV-2 infections, but there remains a lack of knowledge regarding the dynamics of viral transmission, particularly in the setting of pre-existing SARS-CoV-2 immunity and evolving variants.Table 1.SARS-CoV-2 Secondary Attack Rates (SAR) Methods We conducted a prospective, case-ascertained household transmission study in the greater Boston area in March-July 2022. Anterior nasal swabs, along with clinical and demographic data, were collected for 14 days. Nasal swabs were tested for SARS-CoV-2 by PCR. Whole genome sequencing was performed on high-titer samples.Figure 1.Trial profile Results We enrolled 33 households in a primary analysis set, with a median age of participants of 25 years old (range 2-66), 98% of whom had received at least 2 doses of a COVID-19 vaccine. 58% of households had a secondary case during follow up and the secondary attack rate (SAR) for contacts was 39%. We further examined a strict analysis set of 21 households that had only 1 PCR+ case at baseline, finding an SAR of 22.5%. Genomic epidemiology further determined that there were multiple sources of infection for household contacts, including the index case and outside introductions. When limiting estimates to only highly probable transmissions given epidemiologic and genomic data, the SAR was 18.4%.Figure 2.Household diagram(A) Individual households are labeled with a 3-letter identifier and represented with grey boxes. Households in both the primary and strict analysis sets are shown. Each member of the household is shown within the grey box, with their outcome color-coded as described in the legend. (B) Phylogenetic map of positive samples. Conclusion Household contacts of a person newly diagnosed with COVID-19 are at high risk for SARS-CoV-2 infection in the following 2 weeks. This is, however, not only due to infection from the household index case, but also because the presence of an infected household member implies increased SARS-CoV-2 community transmission.Figure 3.Viral load curves and transmission plots by household in the strict analysis set(A) Households where transmission was determined to be highly probable are shown. (B) Households where transmission was determined to be unlikely are shown. (C) Households that did not yield sufficient sequencing data are shown. Disclosures Michael Springer, Ph. D., Nexus laboratories: Advisor/Consultant|Nexus laboratories: Stocks/Bonds (Private Company)|Rhinostics: Board Member|Rhinostics: Ownership Interest|Rhinostics: Stocks/Bonds (Private Company) Pardis C. Sabeti, MD, PhD, Danaher Corporation: Board Member|Danaher Corporation: Stocks/Bonds (Public Company)|Delve Bio: Co-founder|Delve Bio: Ownership Interest|NextGenJane: former SAB member, investor|NextGenJane: Ownership Interest|Polaris Genomics: investor|Polaris Genomics: Ownership Interest|Sherlock Biosciences: Patents for CRISPR-based and microfluidic based diagnostics licensed|Sherlock Biosciences: Co-founder|Sherlock Biosciences: Ownership Interest

P-60. Lineage dynamics are not the major drivers of Streptococcus pneumoniae serotype 3 vaccine escape

Abstract Background Streptococcus pneumoniae serotype 3 (Spn3) is included in the pneumococcal 13-valent conjugate vaccine (PCV13) but carriage and invasive disease persist worldwide. Previous work showed that the prevalent clonal complex 180 (CC180) of Spn3 is comprised of 3 genetically distinct lineages: clade Iα, Iβ, and II; a post-PCV13 shift towards increased incidence of clade II strains with a concomitant decrease in clade Iα and 1β incidence has been observed in the United States, England, and Wales. It was hypothesized that PCV13 is controlling clade Iα and 1β but not clade II, resulting in clade II expansion and ultimately rendering the vaccine ineffective against Spn3. It is imperative to test this hypothesis in other regional contexts given the implications on vaccine design and efficacy. Therefore, our group assessed the dynamics of Spn3 population structure and PCV13 in Portugal. Prevalence of Spn3 clonal complexes before and after the introduction of PCV13 in Portugal Methods We whole-genome sequenced 501 Spn3 strains from Portugal and analyzed over 1400 Spn3 whole genome sequences from published datasets for global comparisons. Phylogenetic tree construction, clade identification, clonal complex typing, and annotation of antimicrobial resistance (AMR) and virulence genes was used to evaluate changes in bacterial genetics. Prevalence of Spn3 clades before and after the introduction of PCV13 in Portugal Results Consistent with previous work, the prevalence of clonal complexes significantly changed before and after the introduction of PCV13 in Portugal (p=4.94-12): CC180 increased from 29% of Spn3 strains to 65%. The prevalence of lineages also changed (p=2.33-13): clade Iα increased from 21% to 54% of Spn3 strains, while clade II was not detected pre-PCV13 but increased to only 5% post-PCV13. This contrasts with studies conducted elsewhere. The phylogenetic distribution of AMR alleles is similar across different regions, so altered antibiotic fitness does not explain the continued success of clade Iα over clade II in Portugal. Conclusion Our data suggests clade II is not the global driver of Spn3 PCV13 vaccine escape as clade Iα remains dominant in Portugal. Current work aims to determine if clade Iα allelic variants augment virulence and thus competitive fitness against clade II in Portugal. Informed vaccine design requires an understanding of the region-specific bacterial population structure and genetic features to optimize efficacy. Disclosures Richard Malley, MD, Amplitude Therapeutics: Board Member|Corner Therapeutics: Board Member|GSK: Advisor/Consultant|Merck: Advisor/Consultant Mario Ramirez, PhD, GSK: Advisor/Consultant|Merck Sharp and Dohme: Advisor/Consultant|Pfizer: Honoraria

P-99. Comparative Analysis of False Positive Results in Low and High Risk U.S. Populations: New Access HIV Ag/Ab combo Assay vs. Abbott ARCHITECT HIV Ag/Ab Combo Assay

Abstract Background The fully automated 4th gen HIV Ag/Ab combo assay by Beckman Coulter, Inc. on the DxI 9000 Access Immunoassay analyzer allows for separate reporting of HIV-1 p24 Ag and HIV-1/HIV-2 Ab results, with a time to first result of ̴30 minutes and a sample volume of 60µL. To evaluate its performance, a U.S. multisite study was conducted to compare the Access HIV Ag/Ab combo assay with the ARCHITECT HIV Ag/Ab Combo assay. False positive rates were assessed in low and high risk U.S. populations with unknown HIV status by comparing the new Access HIV Ag/Ab combo assay with the ARCHITECT HIV Ag/Ab Combo assay.1 Footnotes Methods The evaluation tested 6,981 low risk and 799 high risk samples (adult, pregnant, pediatric) at 3 clinical trial sites. Following the CDC recommended algorithm, samples that initially tested reactive were subjected to duplicate testing, if repeatedly reactive, were further confirmed using the HIV 1/2 differentiation assay (Geenius HIV-1/2 Supplemental Assay, Bio-Rad), and the HIV-1 RNA PCR Assay (Aptima HIV-1 Quantitative Dx Assay, Hologic, Inc).2 Results The Access HIV Ag/Ab combo assay showed a lower incidence of false positive results (n=25) in the low risk group with a specificity of 99.6% (n=6981; 95% CI: 99.5-99.8%) compared to the ARCHITECT HIV Ag/Ab Combo assay (n=87) with a specificity of 98.8% (n=6981; 95% CI: 98.5-99.0%). Similarly, in the high risk group, the Access HIV Ag/Ab combo assay yielded fewer false positive results (n=1) with a specificity of 99.9% (n=799; 95% CI: 99.3-100.0%) than the ARCHITECT HIV Ag/Ab Combo assay (n=11) with a specificity of 98.6% (n=799; 95% CI: 97.6-99.2%). Conclusion Falsely reactive HIV test results can have significant consequences for patients and healthcare providers. Selecting an appropriate HIV assay with high sensitivity and specificity is essential. This study provides evidence that the Access HIV Ag/Ab combo assay is an attractive alternative to the ARCHITECT HIV Ag/Ab Combo assay with fewer false positive results, suggesting improved accuracy in identifying HIV infections in both low and high risk U.S. populations. Disclosures Fred S. Apple, PhD, Mindray: Advisor/Consultant|Werfen: Advisor/Consultant Robert H. Christenson, PhD, DABCC, FADLM, FACC, Beckman Coulter: Advisor/Consultant|Beckman Coulter: Grant/Research Support|Beckman Coulter: Honoraria|Becton Dickinson: Advisor/Consultant|Becton Dickinson: Grant/Research Support|Becton Dickinson: Honoraria|QuidelOrtho: Advisor/Consultant|QuidelOrtho: Grant/Research Support|QuidelOrtho: Honoraria|Roche Diagnostics: Advisor/Consultant|Roche Diagnostics: Board Member|Roche Diagnostics: Grant/Research Support|Roche Diagnostics: Honoraria|Siemens Healthineers: Advisor/Consultant|Siemens Healthineers: Board Member|Siemens Healthineers: Grant/Research Support|Siemens Healthineers: Honoraria

94. Efficacy of SCY-247, a Second-generation Triterpenoid Antifungal, in Three Murine Models of Invasive Fungal Infections

Abstract Background There are limited treatment options for invasive fungal infections (IFIs) with broad-spectrums of activity that can be delivered both orally and intravenously. SCY-247 is a second-generation novel triterpenoid antifungal in development. It has broad-spectrum activity covering yeasts, molds and dimorphic fungi, including azole- and echinocandin-resistant strains and can be given orally or intravenously. Recent in vivo murine efficacy studies were performed with SCY-247 and results from 3 studies demonstrating activity against Candida and Mucorales are presented.Table 1:Study Methodology Details Methods The in vivo activity of SCY-247 was assessed in murine models of invasive candidiasis (IC) caused by C. albicans and C. glabrata and a murine model of pulmonary mucormycosis (PM) caused by R. delemar. In each model, SCY-247 was administered by oral gavage, twice daily (BID), for seven days with doses ranging from 5 to 48 mg/kg. Efficacy endpoints included changes in tissue fungal burden (CFU) and/or survival. Details are shown in Table 1. Results SCY-247 demonstrated potent in vivo activity in all three murine IFI models. In each dose-dependent responses based on the primary endpoints of fungal burden and/or survival were observed. Significant reductions in kidney fungal burden vs placebo (P < 0.01) were observed at doses ≥10 mg/kg against C. albicans and at doses ≥16 mg/kg against C. glabrata; significant reductions in lung fungal burden (P < 0.01) were also observed in the C. glabrata model at doses ≥32 mg/kg. Bioanalysis demonstrated SCY-247 preferentially distributed to kidney and lung tissues versus plasma and reductions in C. glabrata fungal burden correlated with dose and exposure. Against pulmonary mucormycosis, treatment with SCY-247 at doses ≥32 mg/kg resulted in prolonged survival (P < 0.05) and reductions in both lung and brain fungal burden vs placebo (P < 0.05). Conclusion SCY-247 demonstrated significant in vivo activity in murine models of invasive candidiasis and pulmonary mucormycosis, and the antifungal responses correlated with dose and exposure. Disclosures Steve Wring, PhD, SCYNEXIS, Inc.: Advisor/Consultant Katyna Borroto-Esoda, MS, Scynexis Inc: Advisor/Consultant Nathan P. Wiederhold, PharmD, BioMerieux: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mycovia: Grant/Research Support|Scynexis: Grant/Research Support|Sfunga: Grant/Research Support Ashraf S. Ibrahim, PhD, SCYNEXIS, Inc.: Advisor/Consultant|SCYNEXIS, Inc.: Grant/Research Support David A. Angulo, MD, SCYNEXIS, Inc.: Board Member|SCYNEXIS, Inc.: SCYNEXIS, INC Officer and Board Member, SCYNEXIS Patents|SCYNEXIS, Inc.: Stocks/Bonds (Public Company)

P-1063. SCY-247: A Second-generation IV/Oral Triterpenoid Antifungal with Extensive Tissue Distribution and Pharmacokinetics, and Low Drug-Drug Interaction Potential

Abstract Background SCY-247 is an IV/oral second-generation triterpenoid anti-fungal for systemic fungal infections including multidrug resistant pathogens. Here we present translational data for nonclinical pharmacokinetics (PK) including dose-related tissue disposition in a murine C. glabrata model and correlation to reductions in fungal burden. Further, in vitro CYP450 interactions were evaluated to assess potential for clinical drug-drug interactions (DDIs). Methods The PK of SCY-247 was determined in rats and dogs. Plasma and tissue exposures were compared to reductions in kidney and lung fungal burden in a model of invasive C. glabrata. Neutropenic mice were infected IV with C. glabrata (∼108 yeast cells/mouse) and sacrificed on Day +7. Potential for inhibiting or inducing CYP450 isoforms was assessed in vitro using methods supportive of an FDA Investigational New Drug (IND) Application. Results SCY-247 has low clearance (∼10% liver blood flow) with half-life ≥15 hours following oral and IV administration to rat and dog consistent with once-daily administration in humans. Volume of distribution is ∼3 L/kg supportive of extensive tissue distribution. Exposure increased on repeat administration. Solubility of oral SCY-247 as a salt is >30 mg/mL at gastric pH consistent with rapid dissolution in the stomach and rapid absorption - as demonstrated by an early Tmax (0.5-2hr) following oral administration. In a murine model of C. glabrata infection, SCY-247 demonstrated dose-related increases in exposure and corresponding reduction in fungal burden (right figure panel) with higher distribution in kidney and lung tissue compared to plasma (left figure panel). In vitro, SCY-247 did not induce human CYP450s 1A2, 2B6 or 3A4. The IC50 values for inhibition of human 2C9, 2C19 and 3A isoforms were >20 μM ( >10-fold higher than the anticipated clinical Cmax) supportive of low risk of DDI’s for these isoforms. Conclusion SCY-247 has demonstrated dose- and tissue-related exposure reductions in fungal burden, PK consistent with once daily dosing to humans and low risk for CYP450-related DDIs. Disclosures Steve Wring, PhD, SCYNEXIS, Inc.: Advisor/Consultant Katyna Borroto-Esoda, MS, Scynexis Inc: Advisor/Consultant Nathan P. Wiederhold, PharmD, BioMerieux: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mycovia: Grant/Research Support|Scynexis: Grant/Research Support|Sfunga: Grant/Research Support David A. Angulo, MD, SCYNEXIS, Inc.: Board Member|SCYNEXIS, Inc.: SCYNEXIS, INC Officer and Board Member, SCYNEXIS Patents|SCYNEXIS, Inc.: Stocks/Bonds (Public Company)

P-453. Cardiovascular Risk Scores and Insulin Resistance are Higher with Excess Visceral Abdominal Fat in People with HIV in the Modern Antiretroviral (ART) Era

Abstract Background People with HIV (PWH) are at an increased risk of cardiovascular disease (CVD), even after accounting for traditional risk factors like diabetes and dyslipidemia. Metabolic syndrome, a component of which is central adiposity, is also increasingly prevalent in PWH. Yet, there are few data on the contribution of excess visceral abdominal fat (EVAF) to increased CVD risk in PWH in the modern ART era. Methods We used the Visceral Adiposity Measurement and Observation Study (VAMOS) to investigate how EVAF impacts traditional CVD risk factors and overall CV risk in PWH. VAMOS is a cross-sectional, multi-center observational study in PWH, virologically suppressed for ≥1 year, with BMI ranging from 20 to 40 kg/m2. Participants completed study visits, labs, and an abdominal computed tomography scan in the overnight fasting state. Visceral fat was quantified by a single slice at L4-L5. Growth hormone (GH) levels, HOMA-IR and triglyceride:high-density lipoprotein (TG:HDL) ratios (an alternative measure of insulin resistance, IR) were also analyzed. Relationships with EVAF were assessed by Spearman correlation coefficients and Wilcoxon Two-Sample Tests (EVAF defined as ≥130 cm2). Results Of the 170 participants studied, the majority were white and male with an average age of 54 years. Median visceral fat area was 148 cm2 (94, 218) with an EVAF prevalence of 58%. Participants with EVAF had higher HOMA-IR values (p≤.0001) and higher TG:HDL ratios (p=0.0013) than those without EVAF. There was also a positive correlation between EVAF and HOMA-IR (ρ=0.43, p≤0.0001) and TG:HDL ratio (ρ=0.33, p≤0.0001). Importantly, greater visceral fat area was associated with higher 10-year ASCVD risk (p< 0.0001). To understand a potential driver behind this relationship between EVAF and CV risk, GH levels were explored. Increasing visceral fat surface area was inversely correlated with GH levels (ρ=-0.17, p=0.03); moreover, there were lower GH levels in subjects with EVAF (p=0.05). Conclusion Increased levels of visceral fat relate to increased CV risk scores, as well as the traditional risk factors of IR and lipid levels, which contributes to the heightened risk of CVD in PWH on modern ART regimens. The dynamics between decreased GH levels and EVAF found here support targeting EVAF reduction via the GH axis. Disclosures Karam Mounzer, MD, Epividian: Board Member|Epividian: Honoraria|GS: Advisor/Consultant|GS: Grant/Research Support|GS: Honoraria|Merck: Advisor/Consultant|THERA Technologies: Grant/Research Support|ViiV healthcare: Advisor/Consultant|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria John R. Koethe, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Merck & Co.: Advisor/Consultant|Merck & Co.: Grant/Research Support Jordan Lake, MD, Merck: Advisor/Consultant|Theratechnologies: Advisor/Consultant Mohammed Zogheib, PharmD, MPH, Theratechnologies: Employee Colleen McGary, PhD, Theratechnologies: Employee R Brandon Cash, PharmD, Theratechnologies: Employee

P-1405. Drivers of Unplanned Pregnancy among Women with HIV in the Northern and Southern United States

Abstract Background National estimates from 1986-2015 show that the proportion of unplanned pregnancies among women with HIV (WWH) is high at 78% and that Black/African American women are disproportionately impacted. We aimed to evaluate the prevalence of unplanned pregnancy using a contemporary cohort of pregnant and postpartum WWH (2019-2024), and identify the individual, interpersonal, community and societal factors associated with pregnancy planning.Table 1.Sociodemographic, sociocultural, and psychosocial variables in a cohort of pregnant and postpartum women (2019-2024)Footnote: social support (Likert scale 1=never 5=always), HIV provider trust (Likert scale 1=strongly disagree 5=strongly agree), self-efficacy (additive scale 0=cannot do at all 10=completely certain can do), HIV related stigma (additive 0=never experienced 9=heavily experienced) Methods We performed a secondary data analysis of cross-sectional surveys from an on-going randomized controlled trial testing a peer-led behavioral intervention to improve postpartum retention in HIV care. WWH were recruited from six sites in the northeast and southern US. We used unadjusted and adjusted logistic regression to estimate the association between study outcome, pregnancy planning (“Were you planning to get pregnant?” Yes/No) and individual/interpersonal (self-efficacy, social support, HIV provider trust, HIV related stigma) and community/societal (race, ethnicity, marital status, income, employment) factors.Table 2.Factors associated with pregnancy planning among women with HIV Results To date, a total of 137 women (83% Black, 7% White, 10% Asian, American Indian/Alaska Native, Native Hawaiian/Pacific Islander categorized as other race; 14% Hispanic ethnicity) enrolled in the trial and were included in this analysis. The proportion of unplanned pregnancy was high at 73%. Among WWH with unplanned pregnancy, 90% were Black, 4% were White, 6% were women of other race (p=0.002). While Black women had significantly reduced odds of pregnancy planning (OR 0.18, 95% CI 0.046-0.68), married women (OR=3.33, 95% CI 1.26-8.85), women with higher income (OR=1.27, 95% CI 1.03-1.57) and those with employment (OR 2.33, 95% CI 1.08-5.03) had higher odds of pregnancy planning. In the fully adjusted model, Black race (aOR 0.11 95% CI 0.02 -0.48) was the only factor negatively associated with pregnancy planning. Conclusion Unplanned pregnancy among women with HIV and its disproportionate burden on Black women continues to be an area we have yet to make significant progress. Interventions addressing social determinants of unplanned pregnancy and racial disparities are needed to improve reproductive health care for WWH. Disclosures William R. Short, MD, Gilead: Grant/Research Support|Janssen: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Rachel Scott, MD,MPH,FACOG, DHHS Perinatal Guidelines: Board Member|UW STD Prevention Training Center (UW STD PTC): Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|Vindico CME: Honoraria

P-1401. Association Between Intimate Partner Violence and Antiretroviral Adherence Among Pregnant Women Living with HIV

Abstract Background Despite increased access to antiretroviral therapy (ART) for women with HIV (WWH), challenges like unaddressed mental health issues and poor postpartum HIV care retention persist. This analysis evaluates whether Intimate Partner Violence (IPV) is related to reduced ART use and adherence, a topic not extensively studied in the US, especially in pregnant WWH. Participant Characteristics and Prevalence of IPV during and before Pregnancy Among Pregnant WWH (N=137) Methods We analyzed secondary data from a multisite US randomized trial of a peer-led behavioral intervention to improve postpartum retention in WWH. Data was collected from the baseline survey: socio-demographic, health, and psychosocial characteristics, using tools such as the Edinburgh Postnatal Depression Scale (EPDS), Adverse Childhood Experiences (ACE) and HIV-related stigma scores, and the WHO Violence Against Women questionnaire to assess IPV. A multivariable logistic regression (MLR) examined associations between IPV timing (lifetime, before or in pregnancy) and type (physical, emotional, or sexual) and ART adherence (self-reported, ≥ 80% of prescribed ART doses in the prior month), adjusting for potential covariates. Forest Plot and Multivariable Logistic Regression of the Association Between IPV and ART Adherence (N = 137) Results A total of 137 pregnant WWH enrolled between March 2020 and March 2024 were included: mean age was 30.5 (SD 5.6); 83% were Black, 14% Hispanic; mean number of pregnancies was 3.31 (SD 2.1); mean number of years with HIV 9.26 (SD 8.7). Twenty women reported not disclosing their HIV status to their partners, 14 due to fear of abandonment, and two due to fear of physical violence. Depression, stigma, and ACEs were prevalent: an EPDS score of ≥ 10 was seen in 45% of women, an ACE score of ≥ 4 in 23%, and 51% reported HIV-related shame. Forty women (29%) reported any lifetime IPV exposure (39, psychological; 13, physical; 4, sexual). Significantly higher EPDS, ACE, and stigma scores were seen in women exposed to IPV (p < 0.02). Physical IPV during pregnancy had the strongest association with decreased ART adherence in pregnancy (aOR=0.10, p=0.02). Psychological IPV and any IPV type during or before pregnancy were also associated with lower odds of adherence in pregnancy. Conclusion We found high IPV rates and a significant negative association with ART adherence among pregnant WWH. These findings highlight the importance to screen for and address IPV in HIV care to improve maternal and child health outcomes. Disclosures William R. Short, MD, Gilead: Grant/Research Support|Janssen: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Rachel Scott, MD,MPH,FACOG, DHHS Perinatal Guidelines: Board Member|UW STD Prevention Training Center (UW STD PTC): Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|Vindico CME: Honoraria

P-2230. Light Transmission-based Quantitation of Bacterial Growth on an Agar Plate

Abstract Background The growth of microorganisms in liquid culture is usually evaluated by measuring light transmission and calculating optical density (OD). We have developed a new thin-film transistor image sensor (1000 x 1000 pixels) to measure light transmission through agar plates (Figure 1). Similar to OD in liquid culture, cells grown on the surface of agar plates scatter light and reduce the intensity of transmitted light as the cells grow. This device captures a single image every 5 minutes, enabling in-depth time-lapse studies of cell growth when combined with digital image analysis. Here we present proof-of-concept studies to apply this growth monitoring system for quantitative growth assessment. Figure 1. Schematic representation of the bacterial growth monitoring system. Methods Escherichia coli cells were spread on a plate count agar plate and the growth was monitored over 745 min using the device. The optical density was calculated in the same way as OD of liquid culture: OD = -log10(I/I0) where I0 and I represent the intensity of incident light and transmitted light, respectively. The intensity of I0 and I was measured pixel by pixel; I0 was defined as the average of the first ten frames; I was defined as the average of the three consecutive frames (n-1, n, n+1) to reduce noise. The pixel size is 100 x 100 μm. Figure 2. Quantitative evaluation of E. coli colony growth on an agar plate. (A) The last (149th) frame was binarized at the threshold of OD 0.02 to extract colony contours. The circled and numbered colonies were analyzed in (B). The numbers along the horizontal and vertical axes represent the pixel positions. (B) The OD values of the central pixels of the colonies were tracked over time. Results Colony contours were extracted from the binary image, at the threshold of OD 0.02, of the last (149th) frame (Figure 2A). Five colonies with the highest and lowest OD were selected and the OD values of their central pixels were plotted over time, showing distinct modes of increase (Figure 2B). Next, one colony (#3) was chosen to analyze whether the OD correlated with colony size. One axis represents the OD of its central pixel. The other represents the number of pixels that showed OD 0.02 or more in the 20 x 20 pixel area surrounding the central pixel. As shown in Figure 3, after approximately 550 min, the cell growing area began to expand in correlation with the continued increase in OD. The binarized images, at the indicated time points, also showed the area expansion. Cell growth Figure 3. Cell growth in a single pixel and colony expansion in a wider area. The colony #3 in Figure 2 was analyzed. Shown are the OD of the central pixel (light green) and the number of the pixels that showed OD 0.02 or more in the 20 x 20 pixel area surrounding the central pixel (dark green). The binarized images, at the indicated time points, also showed the area expansion. Conclusion The light transmission-based growth monitoring system enabled us to quantitatively evaluate growth on the agar plate. The pixel-by-pixel analysis provided detailed information on the colony formation and growth. This system can be used in a broad spectrum of microorganism research and inspection. Disclosures Masakazu Nakajima, B. Engineering, CarbGeM Inc.: Board Member|CarbGeM Inc.: Ownership Interest