bluuebunny/crossref_metadata_2025_split huggingface dataset:
492. Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of Aging and HIV-infection
Authors: Zapata Heidi , Kumar Archit , Wang Jiawei , Shaw Albert , Zhou Haowen , Radcliffe Christopher , Barakat Lydia A , Wyk Brent Vander , Allore Heather , Zhao Hongyu , Tsang Sui , Manager Data , Mohanty Subhasis 
Published: December 2022

Abstract

Background
Dectin-1 is an innate immune pattern recognition receptor that recognizes and binds b-1,3/1,6 glucans on fungal pathogens.

Methods
We evaluated Dectin-1 function in innate immune cells (Monocytes and Dendritic cells) in a cohort of HIV-positive and HIV-negative young and older adults (n= 81). PBMCs were stimulated with whole glucan particles (1,3/1,6-b-glucan, WGP), a specific Dectin-1 agonist and analyzed via intracellular cytokine staining (ICS) and multicolor flow cytometry of monocytes and dendritic cells. Sorted CD14+ CD16+ monocytes stimulated with WGP and subjected to RNA-seq analysis.

Results
Stimulation of monocytes with β-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-a, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-a production. This increase in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-a and coagulation response that was already increased at baseline, and a persistent IFN-α and IFN-γ response. HIV-older adults also demonstrated an activated dendritic cell signature and M1 macrophage signature upon stimulation that was not seen in young individuals. Pathways upregulated in all cohorts were the signaling pathways MTORC-1, hypoxia pathway (pathways involved in trained immunity) and the unfolded protein response. Of note MTORC-1 signaling was upregulated at baseline in HIV-Older adults.

Conclusion
Overall, our study demonstrates that increased age and HIV-infection can affect the function of Dectin-1 and lead to a distinct inflammatory signature. Dectin-1 stimulation in HIV-Older adults led to a more pro-inflammatory phenotype that was demonstrated through both protein and gene expression. Dectin-1 induced inflammation in HIV-infected individuals may be contributing to the pro-inflammatory environment that is seen in the setting of both aging and HIV-infection.

Disclosures
All Authors: No reported disclosures.
506. Neonatal CD8+ T Cells Demonstrate PD-1 Dependent Impairment Following Human Metapneumovirus Infection
Authors: Eddens Taylor , Parks Olivia , Zhang Yu , Williams John 
Published: December 2022

Abstract

Background
Human metapneumovirus (HMPV) is a leading cause of pediatric acute respiratory illness, accounting for 14.2 million acute lower respiratory tract infections and 500,000 hospitalizations per year in children less than 5 years of age globally. Infants and neonates are particularly susceptible to severe HMPV disease. Our prior studies in adult mice demonstrated CD8+ T cells were critical for clearance of HMPV infection, although these cells show impaired function due to PD-1:PD-L1 signaling. However, the immune system in the neonatal lung skews towards an anti-inflammatory and tolerogenic response when compared to adults. We therefore sought to explore the roles CD8+ T cell and PD-1 signaling in neonatal mice to recapitulate the population at highest risk.

Methods
C57BL/6 or Pdcd1-/- pups were infected intranasally with 1.0x106 PFU/g of a clinical isolate of HMPV (TN94-49) on day of life 4-6. Viral burden was assessed via plaque assay and cellular responses were characterized by multispectral flow cytometry.

Results
HMPV infection led to stunted weight gain in pups compared to mock-infected controls. HMPV-infected neonatal mice had a robust innate immune response comprised of neutrophils, CD103+ dendritic cells, and interstitial macrophages, all of which demonstrated upregulation of PD-L1. From an adaptive perspective, neonatal mice mounted an antigen-specific CD8+ T cell response and resolved HMPV infection by day 8 post-infection. Similar to our prior studies in adult mice, neonatal CD8+ T cells upregulated expression of several inhibitory receptors, such as PD-1, LAG-3, and TIM-3. Neonatal CD8+T cells demonstrated limited effector cytokine production, such as IFN-γ and granzyme B, following ex vivo stimulation with a class I HMPV-specific peptide. Pdcd1-/- mice (lacking PD-1) also mounted an antigen-specific CD8+ T cell response, but had markedly increased production of IFN-γ and granzyme B.

Conclusion
These data demonstrate that PD-1 signaling on CD8+ T cells constrains the antiviral response in a novel model of neonatal respiratory viral infection. Understanding the mechanisms that inhibit neonatal anti-viral responses could present opportunities for novel therapeutic strategies for common infections with high morbidity and mortality in neonates and infants.

Disclosures
John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant.
508. Prevalence of nasopharyngeal colonization by Staphylococcus aureus in adults with chronic diseases in Colombia.
Authors: Lozada Julian , Ibáñez-Prada Elsa D D , Serrano-Mayorga Cristian C , Fuentes Yuli V , Bustos Ingrid G G , Mendez Lina , Crispin Ana M , Reyes Luis Felipe F 
Published: December 2022

Abstract

Background
Staphylococcus aureus is a significant cause of morbidity and mortality worldwide. It is responsible for many infections, especially soft tissues, and bacteremia. S. aureus is also a commensal microorganism in humans, usually found in the nasopharynx. Colonized subjects, especially adults with comorbidities, have a higher risk of developing clinical infections such as community-acquired pneumonia (CAP). Some researchers have hypothesized that nasopharyngeal colonization is the etiology that could predict the etiology of CAP. Therefore, the objective of this study was to establish the prevalence of nasopharyngeal colonization by S. aureus in adults with comorbidities in a Colombian cohort.

Methods
This was a multicenter prospective cohort study in 3 centers in Colombia, conducted between December 2020 and March 2021. Patients older than 18 years with a diagnosis of chronic disease were included. Subjects with evidence or diagnosis of CAP before 90 days and subjects admitted to hospitalization during the last seven days were excluded. Nasopharyngeal aspirate (NPA) sampling in each participant according to WHO guidelines. A seeding of 100 ¼L of NPA by counting method on blood agar. The colonies in these cultures were identified by MALDI-TOF.

Results
NPAs were obtained in 810 subjects. S. aureus was isolated in 16.9% [137/810] of participants, with an average concentration of 148 CFU/100 µL [IQR 1 – 5500]. All the obtained colonies were confirmed by MALDI-TOFF. Patients had a mean age of 61.4 years [IQR 26 – 98], and 48.7% [67/137] were women. All of the subjects presented at least one comorbidity (51,1% [70/137] Arterial hypertension, 21,9% [30/137] chronic kidney disease, 16,8% [23/137] Diabetes and Heart failure). Notably, only 5.8% [8/137] developed pneumonia during the first six months of follow-up.

Conclusion
Our results confirm that S. aureus is a prevalent microorganism that colonizes the nasopharynx in adults with comorbidities. We will follow up with the patients for two years to determine if the nasopharyngeal colonization due to S. aureus is a risk factor for developing CAP.

Disclosures
All Authors: No reported disclosures.
510. Secretory IgA in the Vaginal Mucosa Inhibits Herpes Simplex Virus Infection
Authors: Fong Valerie , Hunte Richard , Keller Marla J , Herold Betsy , Herold Betsy 
Published: December 2022

Abstract

Background
HSV2 increases HIV risk and is twice as common among women. We previously showed that cervicovaginal secretions exhibit innate anti-HSV2 activity that was lower in adolescents and women with HIV-- conditions associated with vaginal dysbiosis and increased HSV shedding. Our current study aims to test the hypothesis that vaginal dysbiosis is associated with low anti-HSV activity and to explore the molecules and mechanisms that contribute.

Methods
Cervicovaginal lavage (CVL) (10 ml normal saline wash) was collected from 20 women who presented with clinical bacterial vaginosis (BV) (Day 0) and then 1 and 4 weeks after completing a 7-day oral metronidazole course; parent study results were reported (PMID 34003290). Anti-HSV2 activity of CVL (diluted 1:4) was determined by plaque reduction assay. CVL IgG, IgA, cytokines and antimicrobial peptides were quantified by ELISA or multiplex Luminex and select microbiota by quantitative real-time PCR. CVL was enriched for IgA and IgG using protein L (binds all Ig) and Protein G (binds only IgG). HSV-specific antibodies in CVL were assessed by ELISA. Statistical analyses including Spearman correlation coefficients (SCC) were performed with GraphPad Prism version 9.1.2 software.

Results
Anti-HSV2 activity of CVL was highly variable at Day 0 (mean 18.6% SD 36.7) and trended to increase after treatment (mean 22.56% SD 33.8). The anti-HSV2 activity correlated positively with Nugent scores (SCC= -0.28, p= 0.03) and qPCR levels of BV-associated microbes (SCC = -0.2 to -0.3, p&lt; -0.1) but positively with IgA (r= 0.49, p&lt; 0.01) and IgG (r= 0.33, p= 0.01). IgA and IgG were isolated from pools of CVL with high inhibitory activity greater than 40% (n= 8). The anti-HSV2 activity mapped to the IgA fraction (56.5% inhibition) compared to the IgG or non-Ig fraction (0% inhibition) even though, as expected, the CVL concentration of IgG was higher than IgA (8.3μg/mL vs 4.9 μg/mL). The anti-HSV2 activity did not correlate with HSV-specific Ig in CVL.

Conclusion
Our findings suggest that secretory vaginal IgA contributes to innate anti-HSV2 activity and may trap viral particles to prevent viral entry. We speculate that sialidases, which cleave IgA and are elaborated by BV-associated microbiota, contribute to the low anti-HSV2 activity observed in high-risk cohorts.

Disclosures
Betsy Herold, MD, Viracor (Eurofins): Advisor/Consultant|X-Vax, Technologies: Advisor/Consultant|X-Vax, Technologies: Grant/Research Support|X-Vax, Technologies: Serve on Scientific Advisory Board for X-Vax, Technologies and receiving reserach funding for related worl. Betsy Herold, MD, Viracor (Eurofins): Advisor/Consultant|X-Vax, Technologies: Advisor/Consultant|X-Vax, Technologies: Grant/Research Support|X-Vax, Technologies: Serve on Scientific Advisory Board for X-Vax, Technologies and receiving reserach funding for related worl.
515. Comparing Different Delivery Methods of Fecal Microbiota Transplantation
Authors: Lee Eun Hwa , Lee Ki Hyun , Kim Jinnam , Ju Lee Se , Kim Jung Ho , Ahn Jin Young , Jeong Su Jin , Ku Nam Su , Yeom Joon-sup , Choi Jun Yong 
Published: December 2022

Abstract

Background
The increasing prevalence of multi-drug resistant organism (MDRO) carriage imposes significant medical challenges by increasing healthcare costs. Since MDRO carriage impacts treatment outcome and prognosis, many decolonization strategies were proposed but were not as effective as expected. Recently, fecal microbiota transplantation (FMT) has been discussed as a novel and effective method of MDRO decolonization. In this study, we compared the effectiveness of different FMT delivery methods to find suitable methods and optimize the success rate of decolonization for the patients with MDRO carriage.

Methods
In this prospective cohort study, we enrolled patients with MDRO carriage from 2018 to 2021. Patients received FMT via one of the four following methods; oral capsule, esophagogastroduodenoscopy, colonoscopy, or gastric tube. FMT delivery method was chosen according to the medical condition or eligibility for oral diet. The participants were followed up for one year. Decolonization and recolonization with MDRO were determined by the follow-up stool cultures. Microbiome analysis was done to assess the successful restoration of the gut microbiome.

Results
A total of 57 patients received FMT for MDRO decolonization. The number of patients who received FMT via oral capsule, EGD, colonoscopy, and gastric tubes was 14, 9, 23, and 11. The overall decolonization rate was 69.2%, and the recolonization rate was 19.3%. The colonoscopy group required the shortest time for decolonization, while the EGD group was the longest (24.9 vs. 190.4 days, p-value=0.022). The decolonization rate was the highest in the EGD group (85.7%) and the lowest in the gastric tube group (50.5%). The oral capsule group had a comparable decolonization rate to the EGD group (84.6% vs. 85.7%, p=0.730). The clinical factor associated with decolonization was antibiotic usage after FMT (Odds ratio= 6.810, p-value=0.008). Microbiome analysis data showed improvement in alpha index in the Oral capsule and the EGD group. All four groups showed a reduced proportion of MDRO species after FMT.
Comparison of ACE index of Taxonomic data with different FMT modalities

Conclusion
The oral capsule is an effective FMT method for patients who are tolerable to an oral diet compared to the other conventional methods. Discontinuation of antibiotics after FMT is critical in decolonization.

Disclosures
All Authors: No reported disclosures.
524. An Objective Measure of The Host Response Suggests Social Determinants, Rather than Pathobiology, as a Factor in Disparate Sepsis Outcomes Among Races
Authors: O’Neal Hollis R , Sheybani Roya , Mitchell Miranda , Tse Henry T , Shah Ajay M , Thomas Christopher B 
Published: December 2022

Abstract

Background
Sepsis is a common and costly condition encountered in United States hospitals and Emergency Departments (ED). Studies have shown that the incidence of sepsis and risk of sepsis morbidity and mortality increases with age. With increased efforts on early detection and process of care, in-hospital sepsis deaths have declined; however, racial disparities have been observed in sepsis-related outcomes. The objective of this study was to assess demographic, severity, and outcome differences among septic patients presenting to the ED self-reporting as White vs. Black, and evaluate the potential of an investigational cellular host response test in risk stratifying these subpopulations for risk of poor outcomes.

Methods
The IntelliSep test is an investigational in-vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes from a routine whole blood sample in under 10 minutes. The result is the IntelliSep Index (ISI), ranging between 0.1-10.0, stratified into three discrete interpretation bands of increasing disease severity risk: Green, Yellow, and Red.
Adult patients presenting to the ED with signs or suspicion of infection were prospectively enrolled in four discrete but similar cohorts at multiple sites in the USA (Feb. 2016 – Apr. 2020). All patients had ISI performed and were followed by retrospective chart review for outcome information and sepsis adjudication. Treating clinicians did not have access to assay results, and only those determined to be septic were included in the final analysis.

Results
Of the 150 patients included in the analysis, 92 (61%) were White and 58 (39%) Black. No significant differences were observed in biological sex or severity of illness (Fig). Black subjects were significantly younger (mean difference 8.9 years; p &lt; 0.001) compared to Whites. Independent of race, the ISI correlated with increasing likelihood of adverse sepsis-related outcomes.
Biological sex and APACHE II scores by ISI Interpretation Band for White and Black Study subjects.

Conclusion
The ISI is an objective tool for the quantification of immune activation, and adequately risk-stratifies patients with sepsis for adverse outcomes, independent of race. This finding suggests that social determinants of health, rather than differences in immunobiology, contribute to racial disparities observed in sepsis-related outcomes.

Disclosures
Roya Sheybani, PhD, Cytovale: Employee|Cytovale: Stocks/Bonds Henry T. Tse, PhD, Cytovale: Stocks/Bonds Ajay M. Shah, PhD, Cytovale Inc: Board Member|Cytovale Inc: Ownership Interest|Cytovale Inc: Stocks/Bonds.
549. The Application of Nanopore Sequencing Technology to Characterize Rotavirus Genotypes from Young Children with Diarrhea in the United Arab Emirates
Authors: George Junu , Al-Marzooq Farah , Narchi Hassib , Alsuwaidi Ahmed R 
Published: December 2022

Abstract

Background
In the United Arab Emirates, rotavirus A (RVA) remains a major cause of gastroenteritis in young children despite the universal use of rotavirus vaccines. Monitoring the genetic diversity of circulating strains is essential to better understand the disease burden. Although semi-nested multiplex-PCR is a popular method for RVA genotyping, some clinically significant strains may not be accurately identified by this method. Nanopore sequencing is a third-generation single-molecule sequencing technology that allows for real-time identification of viral and bacterial isolates at competitive costs. This study aims to investigate the use of nanopore sequencing and multiplex-PCR methods to identify RVA genotypes.

Methods
Thirty-three RVA isolates, obtained from stool specimens collected from children less than 5 years old who presented with diarrhea between December 2017 and April 2019, were used for genotyping by PCR and nanopore sequencing. Sixteen isolates were genotyped by Taqman-based qRT-PCR based on VP7 (G) and VP4 (P) genes and genotypes were confirmed by nanopore sequencing in thirteen isolates; three isolates were excluded from nanopore sequencing due to poor RNA quality. Another fifteen isolates were genotyped by the nanopore method alone and two samples were excluded due to poor RNA quality.

Results
The majority of isolates genotyped by qRT-PCR (9 out of 16) were found to harbor VP7 gene of G9 genotype, whereas 5 isolates were of G3 genotype. G12 genotype was rare (2 isolates). For VP4 (P) genotypes, P8 was the most prevalent (8 isolates), followed by P4 (7 isolates), and P6 (1 isolate). When combinations of VP7 and VP4 genotypes are considered, G9P[8] and G9P[4] were the most common genotypes. Nanopore sequencing of 28 isolates revealed G3P8 (29%) as the most prevalent G-P combination, followed by G8P[8] (18%). G9P[8] and G2P[4] were present in 14% of samples. G12P[6] was present in 7% of tested samples. Further, G9P[4], G3P[4], G1P[4], and G4P[2] were detected in 4% of total specimens. One sample was non-typable.

Conclusion
Nanopore sequencing detected various RVA strains among the studied samples including the recently emerging strain, G8P[8]. Using this method in surveillance studies may advance our understanding of the origin, genetic recombination, and burden of disease.

Disclosures
All Authors: No reported disclosures.
569. Utility of the Meningoencephalitis Panel in Modifying Antimicrobial Use in Neonates with Temperature Instability
Authors: Player Brittany , Havens Peter , Mitchell Michelle L , Bushee Glenn , Pan Amy , Huppler Anna R 
Published: December 2022

Abstract

Background
Decisions to discontinue antibiotics in infants undergoing evaluation for central nervous system (CNS) infection can be difficult. Previous reports have associated the use of the meningoencephalitis (ME) PCR panel with decreased hospital stay and antimicrobial use in pediatric and adult patients. However, limited focus has been on infants ≤60-days-old with temperature instability (TI) who undergo evaluation for serious bacterial infection based on age and risk-stratification. We hypothesize use of the ME panel will decrease the duration of antimicrobial use in infants with TI and negative bacterial cultures undergoing evaluation for CNS infection.

Methods
The electronic medical record was queried for patients that met inclusion criteria. Infants ≤60-days-old evaluated for CNS infection due to TI between 1/1/12 – 1/31/22 were included. Exclusion criteria were history of intracranial (IC) devices, previous IC surgery, IC structural or neurovascular abnormalities, or head trauma. A retrospective chart review was performed. We compared length of stay and antimicrobial duration for the groups of patients with the ME panel done versus not done.

Results
A total of 1808 patients with negative bacterial cultures were identified, 96 of whom had the ME panel performed. Patient age, sex, and race were similar between groups. The median hospital length of stay for the patients that had the ME panel done was 64.7 hours as compared to 47.8 hours for those that did not have the ME panel done. The duration of antibacterial therapy was similar when the ME panel was done versus not done. The median duration of therapy for acyclovir was 8.5 when the ME panel was done versus 14.8 hours when it was not done.

Conclusion
When including all patients ≤60-days-old evaluated for TI, use of the ME panel did not lead to a shorter length of hospital stay or duration of empiric antibiotics. However, use of the ME panel decreased duration of therapy in the subset of patients empirically started on acyclovir. Further data analysis will seek to identify patient populations that may most benefit from the use of the ME panel.

Disclosures
All Authors: No reported disclosures.