DR54 DataRelease
Release Date: December 2024
New Studies: 34
Updated Studies: 8
New Studies
| SDY1882: Human airway epithelial response to RV-C is coordinated between infected and uninfected cells | |||||||
| Status: | New | ||||||
| Description: | Human airway epithelial response to RV-C is coordinated between infected and uninfected cells | ||||||
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| DOI: | 10.21430/M3ZIREBFAY | ||||||
| Subjects: | 3 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2210: Adaptive Immune Response to WNV | ||||||||||
| Status: | New | |||||||||
| Description: | The Collaborative Cross mouse model was used to capture a wide range of cellular and cytokine responses to West Nile virus infection at 7,12,21, and 28 days post infection. This model a high level of genetic diversity and has been shown to recapitulate humen response to this infection. | |||||||||
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| DOI: | 10.21430/M3G4YQNJ68 | |||||||||
| Subjects: | 1486 | |||||||||
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| Publications: | None | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2397: Multimodal hierarchical classification of CITE-seq data | ||||||||||
| Status: | New | |||||||||
| Description: | Single-cell RNA sequencing (scRNA-seq) is invaluable for profiling cellular heterogeneity and dissecting transcriptional states, but transcriptomic profiles do not always delineate subsets defined by surface proteins, as in cells of the immune system. Cellular Indexing of Transcriptomes and Epitopes (CITE-seq) enables simultaneous profiling of single-cell transcriptomes and surface proteomes; however, accurate cell type annotation requires a classifier that integrates this multimodal data. Here, we describe MultiModal Classifier Hierarchy (MMoCHi), a marker-based approach for classification, reconciling gene and protein expression without reliance on reference atlases. We benchmark MMoCHi using sorted T lymphocyte subsets and annotate a cross-tissue human immune cell dataset. MMoCHi outperforms leading transcriptome-based classifiers and multimodal unsupervised clustering in its ability to identify immune cell subsets that are not readily resolved and to reveal novel subset markers. MMoCHi is designed for adaptability and can integrate CITE-seq annotation of cell types and developmental states across diverse lineages, tissues, or individuals. | |||||||||
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| DOI: | 10.21430/M3JCDJ1TU0 | |||||||||
| Subjects: | 3 | |||||||||
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| Publications: | None | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2716: NHP SRI CiToxLAB TBI 4Gy longitudinal study | |||||||
| Status: | New | ||||||
| Description: | Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects in peripheral whole blood of 4 Gy total body irradiation at the molecular level over a series of days after exposure. | ||||||
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| DOI: | 10.21430/M3VKQ9A72L | ||||||
| Subjects: | 8 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2761: Cellular mechanisms associated with sub-optimal immune responses to SARS-CoV-2 bivalent booster vaccination in patients with Multiple Myeloma | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Spike binding IgG antibody levels were measured by spike binding ELISA and neutralization capacity was assessed by SARS-CoV-2 multi-cycle microneutralization assays. Spike specific T-cell function was also assessed. Flow cytometry was performed, on a subset of samples, to identify immune cell subsets associated with lack of humoral antibodies. | ||||||||||||
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| DOI: | 10.21430/M3KF4UNHV8 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY2772: T Cell Response Against Chlamydia (TRAC)_PBMC CyTOF | |||||||
| Status: | New | ||||||
| Description: | Manuscript Abstract: Chlamydia trachomatis (CT) is the causative agent of chlamydia, the most common bacterial sexually transmitted infection (STI) in the United States despite effective antibiotics. Understanding natural immunity to CT is crucial to inform vaccine design. This study aimed to identify immune cell populations and functional features associated with reduced risk of CT reinfection. PBMCs were collected from 82 CT-exposed women tested for CT and other STIs upon enrollment, and repeatedly over 1 year of follow-up. Immune responses were profiled by mass cytometry. Women with CT at enrollment exhibited higher frequencies of CD4+ effector memory T cells (TEM) than uninfected women. Specifically, Th2, Th17, and Th17 DN CD4 TEM were increased. However, functional features indicated diminished expression of T cell activation and differentiation markers, underscoring weaknesses of natural immunity that could be addressed by vaccine design. Comparing responses in women who remained follow-up negative (FU-) to those who were reinfected (FU+), higher frequencies of Th1, Th17, and Th17 DN CD4 T cells were observed in FU- women. Conversely, Th2 CD4 T cells were increased in FU+ women. Furthermore, markers of T cell memory and Th17 lineage were increased on T cells among FU- women. These data indicate that peripheral T cells exhibit distinct features associated with natural immunity to CT. Notably, the highly plastic Th17 lineage appears to contribute to protection. Addressing these immune nuances could promote efficacy of CT vaccines. T Cell Response against Chlamydia (TRAC) Study Cohort (246 participants): This cohort was composed of mainly young (median age, 21 years; range, 18-35 years), single (89%), African American (66%) women determined to be at high risk for the acquisition of Chlamydia trachomatis. Criteria indicating high-risk status included: greater than 3 sexual partners in the previous 6 months, less than or equal to 14 years of age at sexual debut, history of pelvic inflammatory disease (PID), or presentation to the recruitment site with any of the following: presence of mucopurulent cervicitis on exam, or sexual contact with a partner known to be infected with C. trachomatis or Neisseria gonorrhoeae or non-gonococcal non-chlamydial urethritis. Women with a diagnosis of PID according to the Centers for Disease Control and Prevention guidelines were excluded. Additional exclusion criteria were pregnancy, uterine procedure or miscarriage in the preceding 60 days, menopause, hysterectomy, antibiotic therapy in the preceding 14 days, and allergy to study medications. TRAC participants were enrolled into a longitudinal study designed to investigate T cell responses important for protection from ascending or incident chlamydial infection. Women were recruited from the Allegheny County Health Department's Sexually Transmitted Diseases Clinic, Magee-Womens Hospital (MWH) Ambulatory Care Clinic, and the Reproductive Infectious Disease Research Unit at MWH in Pittsburgh PA. Participants provided informed consent at the time of enrollment and agreed to attend follow-up visits and to complete questionnaires regarding obstetric/gynecologic history, behavioral practices, sex exposure, contraceptive methods, and symptoms regarding according to study protocols. Clinical, histological, and microbiological testing was performed, and blood and endometrial samples were obtained for cell suspension and DNA and RNA upon enrollment. Additional cervical and vaginal samples were also obtained for microbiome-related investigation. Patients in this cohort were assessed for infection and blood was obtained at follow-up visits scheduled 1, 4, 8, and 12 months from enrollment. Overall rate of chlamydial infection in this cohort is 67%. Within the cohort, 76% completed at least 3 follow-up visits, and 57% completed all. Endometrial biopsy tissue was evaluated histologically for disease by two pathologists blinded to the study design. | ||||||
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| DOI: | 10.21430/M3ODFAXIG5 | ||||||
| Subjects: | 82 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2774: Functional Analysis of Complement Variants in a Genotyped iPSC Epithelial Cell Model System | |||||||
| Status: | New | ||||||
| Description: | Our goal is to assess the complement pathway in differentiated RPE cells with different complement genotypes. | ||||||
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| DOI: | 10.21430/M3591TGDDJ | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2775: Functional Analysis of Complement Variants in a Genotyped iPSC Epithelial Cell Model System | |||||||
| Status: | New | ||||||
| Description: | To study complement expression in ARPE cells exposed to H2O2. | ||||||
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| DOI: | 10.21430/M3AJN8WRWH | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2841: 35th Multicenter Airway Research Collaboration (MARC-35): airway metagenome endotyping in infancy | |||||||||||||
| Status: | New | ||||||||||||
| Description: | In a multicenter prospective cohort study of infants (age <1 year) hospitalized for bronchiolitis, we sought to identify airway metagenome endotypes associated with the development of childhood asthma. From nasopharyngeal aspirate (NPA) samples collected at hospitalization, we extracted total genomic DNA and constructed libraries. Metagenomic shotgun sequencing of library pools was performed on the Illumina NovaSeq6000 platform (San Diego, USA), using paired-end chemistries with the read length of 2x150b. We conducted taxonomy profiling using MetaPhlAn3 and functional profiling of the microbial community using HUMAnN3. Using similarity network fusion clustering approach, we identified five distinct metagenome-host genome endotypes and examined their association with the risk of developing asthma by age six years. Compared to infants with classic bronchiolitis (endotype A), endotype E infants had a significantly higher risk for developing asthma. The pathway analysis showed that endotype E had enriched microbial pathways and host pathways. Additionally, endotype E had a significantly higher proportion of neutrophils. | ||||||||||||
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| DOI: | 10.21430/M35OND33V5 | ||||||||||||
| Subjects: | 0 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY2851: Prevaccination Response to an Influenza Vaccine | |||||||
| Status: | New | ||||||
| Description: | Analysis of pre and postvaccination serum glycomes antibody responses in adults. A Glycomic analysis may help predict immune response to vaccination and the specfic glycoforms of the immune proteins. | ||||||
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| DOI: | 10.21430/M3EKUYE19K | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2852: Metabolome baseline discriminates to the influenza vaccination | ||||||||||
| Status: | New | |||||||||
| Description: | Computational analysis of baseline metabolic differences were conducted to increase the response to inactivated fluzone vaccination in ferrets and humans. The demographic samples of the subjects were assessed and measured via seroconversion via HAI from plasma samples. Overall the metabolic profiles could separate the high-risk responders from the high-risk no-responders. | |||||||||
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| DOI: | 10.21430/M3YJDHQZ3T | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY2853: Broadly neutralizing antibodies target a haemagglutinin anchor epitope | ||||||||||||||||||||||
| Status: | New | |||||||||||||||||||||
| Description: | To investigate the specificities of HA-specific antibodies, we generated 358 mAbs from plasmablasts and HA+ memory B cells (MBCs) isolated from volunteers who were vaccinated against or naturally infected with seasonal influenza viruses or were participants in a phase I clinical trial of a chimeric HA (cHA) vaccine. | |||||||||||||||||||||
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| DOI: | 10.21430/M3XDGOCNIZ | |||||||||||||||||||||
| Subjects: | 70 | |||||||||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||||||||
| SDY2854: COBRA HA plus RDOTAP | |||||||
| Status: | New | ||||||
| Description: | Mice were vaccinated with COBRA HA plus RDOTAP and assessed for immune responses | ||||||
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| DOI: | 10.21430/M3N6U92SLZ | ||||||
| Subjects: | 391 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2855: Vinyl Sulfone ACE-Dextran MP | |||||||
| Status: | New | ||||||
| Description: | Vinyl Sulfone MP expressing COBRA elicits broadly reactive antibodies | ||||||
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| DOI: | 10.21430/M3BTBYSD3X | ||||||
| Subjects: | 60 | ||||||
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| Assays: | None | ||||||
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| SDY2858: Glycomics of Cervicovaginal Fluid from Women at Risk of Preterm Birth | |||||||
| Status: | New | ||||||
| Description: | In the present study, we substantially expanded the scope of our investigations to describe global and temporal N- and O-glycomics of CVF samples (n = 60) collected from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Of the pregnant women, 15 delivered preterm and 21 at term. Our expanded glycomics analyses included identification of terminal glycotopes displayed on extended polylacNAc antennae, which are expected to act as more accessible ligands for lectins compared to counterparts on non-extended antennae. Many CVF samples were remarkably rich in glycan epitopes widely considered to be unique hallmarks of cancer and viral glycosylation. Complementary functional analyses revealed quantitative differences in glycan epitope expression associated with bacterial composition and concentrations of cytokines, matrix metalloproteinases (MMP) and complement proteins. Longitudinal glycomic studies of two women who delivered extreme preterm showed substantial changes in expression of immune-active glycan epitopes shortly before delivery. In contrast, glycomes remained stable into the third trimester for women who delivered at term. We also present an analysis strategy designed to address issues of overlapped isotopic peaks from multiple glycans commonly found in the high mass range of the complex CVF N-glycome. This approach facilitated accurate high-speed data annotation and quantitation enabling the construction of N-glycan, O-glycan and glycotope libraries, which are provided as open access repositories | ||||||
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| DOI: | 10.21430/M3DQG5NP4U | ||||||
| Subjects: | 40 | ||||||
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| SDY2859: H3N2 Infection | |||||||
| Status: | New | ||||||
| Description: | Ferrets were infected with H3N2 with examination of how pH and lung cells interact | ||||||
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| DOI: | 10.21430/M3Z5IB547W | ||||||
| Subjects: | 60 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2860: mRNA-1273 and Ad26.COV2.S vaccines protect against B.1.621 variant of SARS-CoV-2 | |||||||||||
| Status: | New | ||||||||||
| Description: | Here, we evaluated in mice and hamsters the efficacy of a pre-clinical version of the Moderna mRNA vaccine (mRNA-1273) and the Johnson and Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. | ||||||||||
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| DOI: | 10.21430/M3AAMROV11 | ||||||||||
| Subjects: | 414 | ||||||||||
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| SDY2863: Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike | |||||||
| Status: | New | ||||||
| Description: | Here, human sera and monoclonal antibodies were used to examine SARS-CoV-2 Omicron subvariant BA.2.86's antigenicity. | ||||||
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| DOI: | 10.21430/M3K2IUTNPS | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
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| SDY2873: Preclinical evaluation of a universal inactivated influenza B vaccine based on the mosaic hemagglutinin-approach | ||||||||||
| Status: | New | |||||||||
| Description: | Here, the investigators present the preclinical evaluation of a novel universal influenza B virus vaccine based on recombinant mosaic hemagglutinin-based (mHA) viruses. | |||||||||
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| DOI: | 10.21430/M3AW2YFNC7 | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2884: SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence. | ||||||||||||||||||
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| DOI: | 10.21430/M37CVKBIH8 | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2885: Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey | ||||||||||
| Status: | New | |||||||||
| Description: | Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized. Methods: In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion that were identified following COVID-19 illness. We used medical record and survey data to estimate the prevalence of ME/CFS-like illness based on self-reported symptoms congruent with the 2015 Institute of Medicine ME/CFS criteria. History of COVID-19 was based on a positive SARS-CoV-2 nucleic acid amplification test or ICD-10 diagnosis code in the medical record, or self-report of prior COVID-19 on a survey. Results: Of 2,745,374 adults in the eligible population, an estimated 45,892 (95% confidence interval [CI]: 32,869, 58,914) or 1.67% (CI 1.20%, 2.15%) had ME/CFS-like illness. Among those with ME/CFS-like illness, an estimated 14.12% (CI 3.64%, 24.6%) developed the illness after COVID-19. Among persons who had COVID-19, those with ME/CFS-like illness after COVID-19 were more likely to be unvaccinated and to have had COVID-19 before June 1, 2021. All persons with ME/CFS-like illness had significant impairment in physical, mental, emotional, social, and occupational functioning compared to persons without ME/CFS-like illness. Conclusions: In a large, integrated health system, 1.67% of adults had ME/CFS-like illness and 14.12% of all persons with ME/CFS-like illness developed it after COVID-19. Though COVID-19 did not substantially increase ME/CFS-like illness in the KPNC population during the study time period, ME/CFS-like illness nevertheless affects a notable portion of this population and is consistent with estimates of ME/CFS prevalence in other populations. Additional attention is needed to improve awareness, diagnosis, and treatment of ME/CFS. | |||||||||
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| DOI: | 10.21430/M3W8ISVK9N | |||||||||
| Subjects: | 0 | |||||||||
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| SDY2886: Modeling the transmission mitigation impact of testing for infectious diseases | |||||||
| Status: | New | ||||||
| Description: | A fundamental question of any program focused on the testing and timely diagnosis of a communicable disease is its effectiveness in reducing transmission. Here, we introduce testing effectiveness (TE)-the fraction by which testing and post-diagnosis isolation reduce transmission at the population scale-and a model that incorporates test specifications and usage, within-host pathogen dynamics, and human behaviors to estimate TE. Using TE to guide recommendations, we show that today's rapid diagnostics should be used immediately upon symptom onset to control influenza A and respiratory syncytial virus but delayed by up to two days to control omicron-era severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, while rapid tests are superior to reverse transcription quantitative polymerase chain reaction (RT-qPCR) to control founder-strain SARS-CoV-2, omicron-era changes in viral kinetics and rapid test sensitivity cause a reversal, with higher TE for RT-qPCR despite longer turnaround times. Last, we illustrate the model's flexibility by quantifying trade-offs in the use of post-diagnosis testing to shorten isolation times. | ||||||
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| DOI: | 10.21430/M3RBDLZNHW | ||||||
| Subjects: | 0 | ||||||
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| SDY2887: SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to inhibit nucleocytoplasmic transport | |||||||||||||||
| Status: | New | ||||||||||||||
| Description: | The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) accessory protein Orf6 works as an interferon antagonist, in part, by inhibiting the nuclear import activated p-STAT1, an activator of interferon-stimulated genes, and the export of the poly(A) RNA. Insight into the transport regulatory function of Orf6 has come from the observation that Orf6 binds to the nuclear pore complex (NPC) components: Rae1 and Nup98. To gain further insight into the mechanism of Orf6-mediated transport inhibition, we examined the role of Rae1 and Nup98. We show that Rae1 alone is not necessary to support p-STAT1 import or nuclear export of poly(A) RNA. Moreover, the loss of Rae1 suppresses the transport inhibitory activity of Orf6. We propose that the Rae1/Nup98 complex strategically positions Orf6 within the NPC where it alters FG-Nup interactions and their ability to support nuclear transport. In addition, we show that Rae1 is required for normal viral protein production during SARS-CoV-2 infection presumably through its role in supporting Orf6 function. | ||||||||||||||
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| DOI: | 10.21430/M32AVMRPB7 | ||||||||||||||
| Subjects: | 0 | ||||||||||||||
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| SDY2888: Perspectives of patients undergoing neoadjuvant chemotherapy for breast cancer during the COVID‐19 pandemic | ||||||||||
| Status: | New | |||||||||
| Description: | Background: The COVID‐19 pandemic resulted in a lapse in routine health care and cancer screenings for many individuals. This study sought to improve our understanding of the impact of the COVID‐19 pandemic on women being treated for breast cancer, both in general, and specifically related to their diagnosis. Methods: Semi‐structured interviews were conducted between August 2021 and February 2022 with women who were receiving neoadjuvant chemotherapy for early‐stage breast cancer at the Stefanie Spielman Comprehensive Breast Center in Columbus, Ohio. Interviews were recorded and transcribed verbatim. Transcripts were coded using deductive dominant thematic analysis and inductive coding that allowed for categorization of data as well as identification of emergent themes. Results: Data collected from our 19 interviews revealed that the COVID‐19 pandemic posed important challenges for breast cancer patients including fear of COVID‐19 infection and feelings of isolation. Most interviewees noted they had been vaccinated against COVID‐19 because of a desire to protect themselves and others from getting sick. Some women also expressed concerns about having delayed their screening mammograms due to the pandemic. Several patients described unexpected positive aspects of the pandemic such as being able to spend more time with family and having the ability to continue working because of the option to work from home during their cancer treatment. Conclusions: Our findings provide important insight about the impact of COVID‐19 on breast cancer patients. We highlight the positives that have been reported because of the pandemic, as well as the need to address delayed breast cancer screening. | |||||||||
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| DOI: | 10.21430/M3YV5LJQYT | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
| Clinical Assessments: | None | |||||||||
| SDY2889: Learning and Predicting from Dynamic Models for COVID-19 Patient Monitoring | |||||||
| Status: | New | ||||||
| Description: | COVID-19 has challenged health systems to learn how to learn. This paper describes the context, methods and challenges for learning to improve COVID-19 care at one academic health center. Challenges to learning include: (1) choosing a right clinical target; (2) designing methods for accurate predictions by borrowing strength from prior patients' experiences; (3) communicating the methodology to clinicians so they understand and trust it; (4) communicating the predictions to the patient at the moment of clinical decision; and (5) continuously evaluating and revising the methods so they adapt to changing patients and clinical demands. To illustrate these challenges, this paper contrasts two statistical modeling approaches - prospective longitudinal models in common use and retrospective analogues complementary in the COVID-19 context - for predicting future biomarker trajectories and major clinical events. The methods are applied to and validated on a cohort of 1,678 patients who were hospitalized with COVID-19 during the early months of the pandemic. We emphasize graphical tools to promote physician learning and inform clinical decision making. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3U1359IJE | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY2890: Selective suppression of de novo SARS-CoV-2 vaccine antibody responses in patients with cancer on B cell-targeted therapy | |||||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||||
| Description: | We assessed vaccine-induced antibody responses to the SARS-CoV-2 ancestral virus and Omicron variant before and after booster immunization in 57 patients with B cell malignancies. Over one-third of vaccinated patients at the pre-booster time point were seronegative, and these patients were predominantly on active cancer therapies such as anti-CD20 monoclonal antibody. While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the overall booster benefit was disproportionately evident in patients already seropositive and not receiving active therapy. While ancestral virus- and Omicron variant-reactive antibody levels among individual patients were largely concordant, neutralizing antibodies against Omicron tended to be reduced. Interestingly, in all patients, including those unable to generate detectable antibodies against SARS-CoV-2 spike, we observed comparable levels of EBV- and influenza-reactive antibodies, demonstrating that B cell-targeting therapies primarily impair de novo but not preexisting antibody levels. These findings support rationale for vaccination before cancer treatment. | ||||||||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M330CLD4LU | ||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||
| SDY2891: Detection of SARS-CoV-2 Antibodies in Immunoglobulin Products | ||||||||||
| Status: | New | |||||||||
| Description: | Background: For patients with primary antibody deficiency, the first line of therapy is replacement with immunoglobulin (Ig) products. Prior to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, Ig products did not contain antibodies with specificity for this virus, and there have been limited data on the antibodies present in the Ig products in current use. Objective: To quantitatively examine SARS-CoV-2 antibodies in current Ig products. Methods: We examined 142 unique lots of 11 different Ig products intended for intravenous and/or subcutaneous delivery for IgG-binding activities against recombinant SARS-CoV-2 receptor binding domain, spike, and nucleocapsid proteins by enzyme-linked immunosorbent assays. In addition, to assess functionality, 48 of these unique lots were assessed for their ability to inhibit the variants SARS-CoV-2 Ancestral, Alpha, Beta, Delta, and Omicron spike binding to angiotensin-converting enzyme 2 (ACE2). Results: Significantly increased antibody values were observed for products manufactured after the year 2020 (expiration dates 2023-2024), as compared with Ig products before 2020 (prepandemic). Sixty percent and 85% of the Ig products with expiration dates of 2023 and 2024 were positive for antibody to SARS-CoV-2 proteins, respectively. The area under the curve values were significantly higher in products with later expiration dates. Later dates of expiration were also strongly correlated with inhibition of ACE2-binding activity; however, a decline in inhibition activity was observed with later variants. Conclusions: Overall, more recent Ig products (expiration dates 2023-2025) contained significantly higher binding and inhibition activities against SARS-CoV-2 proteins, compared with earlier, or prepandemic products. Normal donor SARS-CoV-2 antibodies are capable of inhibiting ACE2-binding activities and may provide a therapeutic benefit for patients who do not make a robust vaccine response. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3KII4T7U2 | |||||||||
| Subjects: | 0 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2892: Evaluation of Next-Generation H3 Influenza Vaccines in Ferrets Pre-Immune to Historical H3N2 Viruses | ||||||||||
| Status: | New | |||||||||
| Description: | This study examined the role that pre-existing immunity plays on influenza virus vaccination. Ferrets were infected with historical A(H3N2) influenza viruses isolated from either the 1970's, 1980's, or 1990's and then vaccinated with computationally optimized broadly reactive antigens (COBRA) or wild-type (WT) influenza virus like particles (VLPs) expressing hemagglutinin (HA) vaccine antigens to examine the expansion of immune breadth. Vaccines with the H3 COBRA HA antigens had more cross-reactive antibodies following a single vaccination in all three pre-immune regimens than vaccines with WT H3 HA antigens against historical, contemporary, and future drifted A(H3N2) influenza viruses. The H3 COBRA HA vaccines also induced antibodies capable of neutralizing live virus infections against modern drifted A(H3N2) strains at higher titers than the WT H3 HA vaccine comparators. | |||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3OMOXT8LZ | |||||||||
| Subjects: | 79 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY2893: Influenza breakthrough infection in vaccinated mice is characterized by non-pathological lung eosinophilia. | |||||||||
| Status: | New | ||||||||
| Description: | The authors previously reported a dose-dependent recruitment of eosinophils to the lungs of mice vaccinated with alum-adjuvanted trivalent inactivated influenza vaccine (TIV) following a sublethal, vaccine-matched H1N1 challenge. Herein, the authors conducted the investigations to phenotype the lung eosinophils observed in their model of influenza breakthrough infection. | ||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3CQYI1X4U | ||||||||
| Subjects: | 40 | ||||||||
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| Clinical Assessments: | None | ||||||||
| SDY2894: Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection. | ||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M37UTNWVVA | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2895: Quantitative assessment of multiple pathogen exposure and immune dynamics at scale | |||||||||||||||||||||||||
| Status: | New | ||||||||||||||||||||||||
| Description: | Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development. | ||||||||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3MKY6KRR3 | ||||||||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||||||||
| SDY2896: Microfluidic Immuno-Serolomic Assay Reveals Systems Level Association with COVID-19 Pathology and Vaccine Protection | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | How to develop highly informative serology assays to evaluate the quality of immune protection against coronavirus disease-19 (COVID-19) has been a global pursuit over the past years. Here, a microfluidic high-plex immuno-serolomic assay is developed to simultaneously measure 50 plasma or serum samples for 50 soluble markers including 35 proteins, 11 anti-spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This assay demonstrates the quintuplicate test in a single run with high throughput, low sample volume, high reproducibility and accuracy. It is applied to the measurement of 1012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein analysis reveals distinct immune mediator modules that exhibit a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies or receiving B cell depletion therapy. Serological analysis identifies that COVID-infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which can be associated with limited clonotype diversity and functional deficiency in B cells. These findings underscore the importance to individualize immunization strategies for these high-risk patients and provide an informative tool to monitor their responses at the systems level. | |||||||||||||||
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| DOI: | 10.21430/M3V3OD75IE | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
| SDY2897: Distinct patterns of SARS-CoV-2 BA.2.87.1 and JN.1 variants in immune evasion, antigenicity, and cell-cell fusion | |||||||||||||||||||
| Status: | New | ||||||||||||||||||
| Description: | The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly, BA.2.87.1 is more resistant to neutralization by XBB.1.5-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines. | ||||||||||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3RPFWUJK6 | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||||||
| SDY2898: Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome | ||||||||||||||||
| Status: | New | |||||||||||||||
| Description: | BACKGROUND: Prolonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation. | |||||||||||||||
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| DOI: | 10.21430/M3LVL6PXK0 | |||||||||||||||
| Subjects: | 0 | |||||||||||||||
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| Clinical Assessments: | None | |||||||||||||||
Updated Studies
| SDY58: Defining signatures for immune responsiveness by functional systems immunology | |||||||||||
| Status: | Updated | ||||||||||
| Description: | Project 2: Immunologic and genomic signatures of response to neuroinvasive or non-neuroinvasive West Nile Virus infection. | ||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3Q6U5GGRT | ||||||||||
| Subjects: | 135 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1644: Urban Environmental Factors and Childhood Asthma (URECA) (ICAC-07) | ||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||
| Description: | The purpose of this study is to determine the way environmental factors (like the components of inner-city household dust) affect immune system development and symptoms of asthma in inner city children. The study is divided into three periods, as the subjects age from birth to 10 years old. Each age bracket will explore different objectives and endpoints. Study Objectives/Hypotheses: Subjects age 0 to 3 years old: Environmental factors in the inner city adversely influence the development of the immune system to promote cytokine dysregulation, allergy, and recurrent wheezing by age 3. Children who have had a viral lower respiratory infection and have developed cytokine dysregulation by age 3 are at increased risk for the development of asthma by age 6. Subjects age 4 to 7 years old: There is a unique pattern of immune development that is driven by specific urban exposures in early life, and this pattern of immune development is characterized by: 1) impairment of antiviral responses and 2) accentuation of Th2-like responses (e.g. cockroach-specific Interleukin-13(IL-13)). The clinical effects of these changes in immune development are frequent virus-induced wheezing and allergic sensitization by 3-4 years of age, and these characteristics synergistically increase the risk of asthma at age 7 years. Subjects age 7 to 10 years old: There are unique combinations of environmental exposures (cockroach allergens, indoor pollutants [Environmental Tobacco Smoke (ETS) and Nitrogen Dioxide (NO2)], lack of microbial exposure), and family characteristics (stress, genetic factors related to innate immunity) that synergistically promote asthma onset, persistence, and morbidity in urban neighborhoods. These exposures and characteristics influence immune expression and lung development during critical periods of growth, resulting in specific asthma phenotypes. Subjects age 10 to 16 years old: To determine the wheezing, asthma and atopy phenotypes in minority children growing up in poor urban neighborhoods as they develop from birth through adolescence. | |||||||||||||||||||||||||||
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| DOI: | 10.21430/M3H1YHLR5Z | |||||||||||||||||||||||||||
| Subjects: | 1218 | |||||||||||||||||||||||||||
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| SDY2187: Microbiome Preterm Birth DREAM Challenge | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description: | Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from raw sequences via an open-source tool, MaLiAmPi. We validated the crowdsourced models on novel datasets representing 331 samples from 148 pregnant individuals. From 318 DREAM challenge participants we received 148 and 121 submissions for our two separate prediction sub-challenges with top-ranking submissions achieving bootstrapped AUROC scores of 0.69 and 0.87, respectively. Alpha diversity, VALENCIA community state types, and composition (via phylotype relative abundance) were important features in the top performing models, most of which were tree based methods. This work serves as the foundation for subsequent efforts to translate predictive tests into clinical practice, and to better understand and prevent preterm birth. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3JMMPMLSP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 764 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Assays: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Assessments: | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SDY2188: Maintenance and residence of immune memory to COVID-19 vaccines in tissues | |||||||||||
| Status: | Updated | ||||||||||
| Description: | Vaccines for COVID-19 establish protection through the generation of pathogen-specific antibodies in circulation, but whether cellular stores of memory are maintained in tissues is unclear. Here, we define the localization, phenotype, function, and tissue residency of memory T and B cells generated to COVID-19 mRNA vaccines across blood, lymphoid organs, and lungs from 33 vaccinated organ donors aged 23-82, of whom 50% were previously infected with SARS-CoV-2. We reveal that in all vaccinated donors, Spike (S)-specific memory T cells distribute across multiple sites though most frequently in lymphoid organs and variably express tissue resident markers based on site and infection history. S-reactive memory B cells are mostly localized to lymphoid sites where they exhibit resident phenotypes in all donors. Importantly, tissue-localized memory populations are more stably maintained post-vaccination and over age than circulating populations. Our results show that mRNA vaccines induce durable tissue-localized memory with the potential for robust protection. | ||||||||||
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| DOI: | 10.21430/M3ANYY64LW | ||||||||||
| Subjects: | 107 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY2306: 35th Multicenter Airway Research Collaboration (MARC-35): EWAS analysis of infants | |||||||||||||||||||
| Status: | Updated | ||||||||||||||||||
| Description: | In a multicenter prospective cohort study of infants (age <1 year) hospitalized with bronchiolitis, we profiled their epigenome-wide blood DNA methylation level from blood samples collected during hospitalization to examine the relationship with bronchiolitis severity. Extracted DNA was used to perform DNA methylation profiling using the Illumina Infinium MethylationEPIC BeadChip (Illumina, San Diego, CA). We investigated differentially methylated CpGs (DMCs) for the risk of treatment with positive pressure ventilation (PPV) during the bronchiolitis hospitalization. We identified that blood DNA methylation signatures were associated with bronchiolitis severity and played important roles in tissues, cells, and pathways. | ||||||||||||||||||
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| DOI: | 10.21430/M3265DVD4I | ||||||||||||||||||
| Subjects: | 0 | ||||||||||||||||||
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| Assays: | None | ||||||||||||||||||
| Clinical Assessments: | None | ||||||||||||||||||
| SDY2393: Rhesus H-ARS Dose-Response Relationship | |||||||
| Status: | Updated | ||||||
| Description: | Rhesus macaques (Macaca mulatta) were exposed to total-body irradiation ranging from 500 cGy to 750 cGy at a dose rate of 50 cGy/min from a Co-60 source and were observed for 60 days for mortality and clinical signs. Each group consisted of 4 males and 4 females. Animals were provided with supportive care which included antibiotics, fluids, anti-ulcer, anti-emetics, analgesics, nutritional support, and wound disinfection administered according to pre-determined criteria, but were not provided blood transfusions. Blood was drawn at predetermined time points and blood cells were counted. Note: Day 1 is 24 hours after the day of irradiation, which is designated in the data files as Day -1. There is no Day 0. Keywords: rhesus macaques, radiation, natural history, radiation sickness, hematopoietic, hematology, proteomics, metabolomics | ||||||
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| DOI: | 10.21430/M3ZAEP8Q6S | ||||||
| Subjects: | 48 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2838: Binding and Avidity Signatures of Polyclonal Sera From Individuals With Different Exposure Histories to Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Vaccination, and Omicron Breakthrough Infections. | |||||||
| Status: | Updated | ||||||
| Description: | Here, the investigators explored how different exposures to SARS-CoV-2 infection or vaccination influence the polyclonal immune response. | ||||||
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| DOI: | 10.21430/M3X11RM5CN | ||||||
| Subjects: | 105 | ||||||
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| SDY2856: Mode of Delivery Predicts Postpartum Maternal Leukocyte Telomere Length | |||||||
| Status: | Updated | ||||||
| Description: | Background: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging. Study design: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma). Results: Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p =0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta − 496.1, 95 % confidence interval [CI] − 891.1, − 101.1, p =0.01) and beyond (adjusted beta − 396.8; 95 % CI − 727.2, − 66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction. Conclusion: Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted. | ||||||
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| DOI: | 10.21430/M3SBBP9K9I | ||||||
| Subjects: | 67 | ||||||
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| Assays: | None | ||||||
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