DR38 DataRelease
Release Date: 02/24/2021
SDY1591: Th17 reprograming of T cells in systemic juvenile idiopathic arthritis | |||||||
Status: | New | ||||||
Description: | Systemic juvenile idiopathic arthritis (sJIA) begins with fever, rash, and high-grade systemic inflammation but commonly progresses to a persistent afebrile arthritis. The basis for this transition is unknown. To evaluate a role for lymphocyte polarization, we characterized T cells from patients with acute and chronic sJIA. | ||||||
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DOI: | 10.21430/M3129QBMS5 | ||||||
Subjects: | 69 | ||||||
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Clinical Assessments: | None |
SDY1596: Licensed BCG formulations differ markedly in innate immune activation | ||||||||||
Status: | New | |||||||||
Description: | Bacille Calmette-Gurin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across the globe generating formulations that may differ in clinical efficacy. Innate immune recognition of live BCG contributes to immunogenicity suggesting that differences in BCG viability may contribute to divergent activity of licensed formulations. | |||||||||
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DOI: | 10.21430/M3QX318KNW | |||||||||
Subjects: | 28 | |||||||||
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Publications: | None | |||||||||
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Clinical Assessments: | None |
SDY1620: Treated HIV infection induces alterations in phenotype but not HIV-specific function of peripheral blood natural killer cells | |||||||||
Status: | New | ||||||||
Description: | Natural killer (NK) cells are the predominant antiviral cells of the innate immune system, and may play an important role in acquisition and disease progression of HIV. While untreated HIV infection is associated with distinct alterations in the peripheral blood NK cell repertoire, less is known about how NK phenotype is altered in the setting of long-term viral suppression with antiretroviral therapy (ART), as well as how NK memory can impact functional responses. As such, we sought to identify changes in NK cell phenotype and function using high-dimensional mass cytometry to simultaneously analyze both surface and functional marker expression of peripheral blood NK cells in a cohort of ART-suppressed, HIV+ patients and HIV- healthy controls. | ||||||||
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DOI: | 10.21430/M30J52ENN6 | ||||||||
Subjects: | 20 | ||||||||
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Clinical Assessments: | None |
SDY1625: Double Expressor Assessment | ||||||||||
Status: | New | |||||||||
Description: | Determine the frequency of double expressor lymphocytes of frozen PBMCs from T1D patients and health controls through flow cytometry. | |||||||||
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DOI: | 10.21430/M3Z5UFK8GC | |||||||||
Subjects: | 28 | |||||||||
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Publications: | None | |||||||||
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Clinical Assessments: | None |
SDY1647: CD16 is upregulated in HIV-exposed seronegative women and may mediate enhanced antibody-dependent cytotoxicity | |||||||||
Status: | New | ||||||||
Description: | Performed a mass cytometry-based screen of NK cell receptor expression patterns in healthy controls and HIV-exposed seronegative women individuals and then focused mechanistic studies on the expression CD16 | ||||||||
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DOI: | 10.21430/M3HV2PQM3C | ||||||||
Subjects: | 30 | ||||||||
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Clinical Assessments: | None |
SDY1660: Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH) (ASC01) | ||||||||||
Status: | New | |||||||||
Description: | This prospective, double-blind, placebo-controlled, multi-center, randomized trial will evaluate the effect of rituximab on disease progression in subjects with SSc-PAH receiving concurrent stable-dose standard medical therapy with a prostanoid, endothelin receptor antagonist, and/or phosphodiesterase 5 (PDE-5) inhibitor. The study will focus on assessment of clinical response and safety measures longitudinally. In addition, the effects of treatment with rituximab on the underlying immune mechanisms associated with B-cell dysregulation and pathogenic autoantibody response in this disease will be investigated. 1000 mg of rituximab or placebo will be administered as two IV infusions given two weeks apart. Clinical assessments and sample collection will occur at monthly visits through Week 48. If a participant has not recovered B cells by Week 48, B cell studies will be conducted quarterly until reconstitution is documented or for 2 years after initial treatment. This trial will include a sub-study, entitled ""Right Ventricular Response to Rituximab in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension - A Magnetic Resonance Imaging Sub-study"" (RESTORE Sub-study). The objective of the RESTORE sub-study is to evaluate the therapeutic effect of rituximab on the right ventricle of patients with SSc-PAH. Changes in right ventricular end diastolic volume index (RVEDVI) and stroke volume (SV) determined by cardiac MRI will be used as surrogates of right ventricle function and prognosis. Enrollment for the RESTORE sub-study will parallel that of main trial. Twenty patients from each treatment arm, distributed among all participating sites, will be recruited for this sub-study. Each patient will be studied at baseline (i.e. prior to initiation of study drug) and after 24 weeks or at time of discontinuation. In addition to the data collection and testing specified in the main trial, participants in RESTORE will undergo comprehensive cardiac MRI evaluation. All main trial study inclusion and exclusion criteria apply, as well as additional exclusion criteria that pertain only to the RESTORE sub-study: 1) known hypersensitivity to Gadolinium; 2) inability to tolerate or cooperate with MRI; 3) morbid obesity; and 4) presence of metallic objects or pacemakers. | |||||||||
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DOI: | 10.21430/M3AWCQNWDW | |||||||||
Subjects: | 57 | |||||||||
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Assays: | None | |||||||||
Clinical Assessments: | None |
SDY1666: KSHV tropism in B lymphocytes | |||||||
Status: | New | ||||||
Description: | Study of Tonsil Biospecimens via ex vivo infection with KSHV to determine KSHV tropism for B lymphocytes in human tonsil | ||||||
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DOI: | 10.21430/M3QC31XEYE | ||||||
Subjects: | 40 | ||||||
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Publications: | None | ||||||
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Clinical Assessments: | None |
SDY1667: Cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans | |||||
Status: | New | ||||
Description: | Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we demonstrate a range of pre-existing memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease. | ||||
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DOI: | 10.21430/M3R9UGV228 | ||||
Subjects: | 45 | ||||
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Clinical Assessments: | None |
SDY1672: Immune Response to IAV | |||||||
Status: | New | ||||||
Description: | Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of genetic variation, we measured antibody response and weight change after infection with influenza-A virus. | ||||||
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DOI: | 10.21430/M33IIY5ARD | ||||||
Subjects: | 3640 | ||||||
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SDY1696: The interaction between the vaginal microbiome, cervical length and vaginal progesterone treatment for preterm birth risk | |||||||
Status: | New | ||||||
Description: | Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. By using 16S rRNA gene sequencing in women at risk of preterm birth (n?=?161), the study assessed 1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and 2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix. | ||||||
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DOI: | 10.21430/M3I5KIC0BC | ||||||
Subjects: | 228 | ||||||
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Assays: | None | ||||||
Clinical Assessments: | None |
SDY1702: Mid-gestation serum lipidomic profile of PTB are influenced by BMI | |||||||
Status: | New | ||||||
Description: | BMIs is one of risk factors for spontaneous preterm birth (sPTB). To identify BMI-associated metabolic perturbations and potential mid-gestation serum biomarkers of sPTB, the study compared metabolomics/lipidomics in sPTB and FTB (Full term birth) women stratified by BMIs categories: underweight, normal weight, and obese. Technique: combining untargeted metabolomics and lipidomics with targeted metabolic profiling of major regulators of inflammation and metabolism, including oxylipins, endocannabinoids, bile acids and ceramides. Results: 1) underweight/sPTB showed dyslipidemia characterized by elevated phospholipids, unsaturated triglycerides, sphingomyelins, cholesteryl esters and long-chain acylcarnitines. 2) normalweight/sPTB showed altered relative abundance of 14(15)-epoxyeicosatrienoic acid and 14,15-dihydroxyeicosatrienoic acids to other regioisomers at mid-pregnancy. 3) obese/sPTB: showed elevated oxidative stress and dyslipidemia characterized by elevated serum free fatty acids. In conclusion, using metabolomics can distinct BMI-dependent metabolic manifestations among women who had sPTB | ||||||
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DOI: | 10.21430/M3QKUPQS46 | ||||||
Subjects: | 0 | ||||||
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Assays: | None | ||||||
Clinical Assessments: | None |
SDY1707: Maternal plasma miRNAs as potential biomarkers for detecting risk of SGA | |||||||
Status: | New | ||||||
Description: | Small-for-gestational-age fetuses (SGA) (birthweight <10th centile) are at high risk for stillbirth or long-term adverse outcomes. To identify maternal plasma miRNAs as potential biomarkers for detecting risk of SGA, the study sampled 29 women (16 delivered normally grown babies and 13 delivered SGA (birthweight <5th centile)) and determined their plasma miRNA profiles (~800 miRNAs) by using the Nanostring nCounter miRNA assay. The comparative analysis between SGA and normal groups identified seven miRNAs at 12?14+6 weeks gestation. Four of these were technically validated by RT-qPCR. Differential expression of two miRNA markers; hsa-miR-374a-5p (p = 0?0176) and hsa-let-7d-5p (p = 0?0036), were validated in an independent population of 95 women (SGA n = 12, Control n = 83). In the validation cohort, which was enriched for SGA cases, the ROC AUCs were 0?71 for hsa-miR-374a-5p, and 0?74 for hsa-let-7d-5p, and 0?77 for the two combined | ||||||
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DOI: | 10.21430/M3QPGX9UYA | ||||||
Subjects: | 0 | ||||||
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Assays: | None | ||||||
Clinical Assessments: | None |
SDY1710: Early Prediction of Preeclampsia via Machine Learning | |||||||
Status: | New | ||||||
Description: | An early prediction model for preeclampsia was developed with the use of machine learning methods that analyzed all available clinical and laboratory data during routine prenatal visits. Using the elastic net algorithm, a subset of the most informative features from all variables can be automatically identified. The obtained prediction model for preeclampsia yielded an area under the curve of 0.79 (95% confidence interval, 0.75?0.83), sensitivity of 45.2%, and false-positive rate of 8.1%. The prediction model for early-onset preeclampsia achieved an area under the curve of 0.89 (95% confidence interval, 0.84?0.95), true-positive rate of 72.3%, and false-positive rate of 8.8%. | ||||||
Program/Contract: |
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DOI: | 10.21430/M3G6ZCU1UC | ||||||
Subjects: | 0 | ||||||
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Assays: | None | ||||||
Clinical Assessments: | None |
SDY1712: Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria gastrointestinal tract (GI) | |||||||
Status: | New | ||||||
Description: | We have a mutually beneficial relationship with the trillions of microorganisms inhabiting our gastrointestinal tract. However, maintaining this relationship requires recognizing these organisms as affable and restraining inflam- matory responses to these organisms when encountered in hostile settings. How and when the immune system develops tolerance to our gut microbial members is not well understood. We identify a specific preweaning inter- val in which gut microbial antigens are encountered by the immune system to induce antigen-specific tolerance to gut bacteria. For some bacterial taxa, physiologic encounters with the immune system are restricted to this inter- val, despite abundance of these taxa in the gut lumen at later times outside this interval. Antigen-specific tolerance to gut bacteria induced during this preweaning interval is stable and maintained even if these taxa are encountered later in life in an inflammatory setting. However, inhibiting microbial antigen encounter during this interval or ex- tending these encounters beyond the normal interval results in a failure to induce tolerance and robust antigen- specific effector responses to gut bacteria upon reencounter in an inflammatory setting. Thus, we have identified a defined preweaning interval critical for developing tolerance to gut bacteria and maintaining the mutually bene- ficial relationship with our gut microbiota. | ||||||
Program/Contract: |
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DOI: | 10.21430/M3AJSRNM6B | ||||||
Subjects: | 18 | ||||||
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Publications: | None | ||||||
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Assays: | None | ||||||
Clinical Assessments: | None |
SDY1722: Perturbation of ILF3 in Human MDDCs | |||||||
Status: | New | ||||||
Description: | MDDCs were transduced with lentiviral constructs expressing mRNA coding for various isoforms of ILF3 or isoforms lacking specific domains. | ||||||
Program/Contract: |
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DOI: | 10.21430/M3GS4EP88P | ||||||
Subjects: | 7 | ||||||
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Publications: | None | ||||||
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Clinical Assessments: | None |
SDY1723: gso32 infected with Mtb | |||||||
Status: | New | ||||||
Description: | Gene expression analysis of gso32 bone marrow derived macrophages treated with IFNbeta and/or infected with live or heat killed Mycobacterium tuberculosis | ||||||
Program/Contract: |
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DOI: | 10.21430/M3QUUM0902 | ||||||
Subjects: | 8 | ||||||
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Publications: | None | ||||||
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Clinical Assessments: | None |
SDY1725: Response of human MDDCs to HIV | |||||||
Status: | New | ||||||
Description: | Chromatin accessibility was measured by ATAC-seq in human MDDCs following infection with HIV-GFP at several time points over the first 48 hours. | ||||||
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DOI: | 10.21430/M3KWDR5VTS | ||||||
Subjects: | 3 | ||||||
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Clinical Assessments: | None |
SDY1732: Maternal gut microbiota reflecting poor diet quality is associated with sPTB | |||||||
Status: | New | ||||||
Description: | The study conducted comparative analysis in case-control datasets on the data of fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. Results: 1) A decrease in ?-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. 2) Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P < 0.01). The most significant fecal metabolite module (FDR-adjusted P = 0.008) was dominated by DHA and EPA. 3) A low-fiber, high-fat diet in the late second trimester is strongly associated with the development of SPTB. Conclusions: Reduced ?-diversity of the gut microbiota and higher excretion of omega-3 (n?3) fatty acids in stool may provide a novel biomarker signature predicting SPTB in women with a low-fiber, high-fat diet. Further investigation of these markers in a larger sample is needed for validation | ||||||
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DOI: | 10.21430/M3AM77XTU7 | ||||||
Subjects: | 47 | ||||||
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Clinical Assessments: | None |
SDY1737: A Research Trial of Aralast in New Onset Diabetes (RETAIN) (ITN041AI) | |||||||
Status: | New | ||||||
Description: | The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's normal ability to fight infection and respond to injuries) that affects the cells thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). All subjects enrolled in this study have new-onset T1DM (diagnosis of T1DM within 100 days of Visit 0; T1DM diagnosis fulfilling American Diabetes Association standard T1DM criteria). The focus of Part I of this trial (NCT01183468) is pharmacokinetics (PK), pharmacodynamics (PD) and safety. Upon completion of Part I, including a satisfactory safety review, enrollment in Part II (NCT01183455, Phase II Clinical Trial) will begin. | ||||||
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DOI: | 10.21430/M3ALD4RXIE | ||||||
Subjects: | 16 | ||||||
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Assays: | None | ||||||
Clinical Assessments: | None |
SDY1738: Multiomics Characterization of PTB in Low- and Middle-Income Countries | |||||||||
Status: | New | ||||||||
Description: | This study analyzed multiomics data of plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries. The comparative analysis of Cell-free transcriptomics, urine metabolomics, and plasma proteomics between term and preterm birth concluded that major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets | ||||||||
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DOI: | 10.21430/M32WAWRYE2 | ||||||||
Subjects: | 81 | ||||||||
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Clinical Assessments: | None |
SDY472: Plasmablast response to inactivated and live attenuated influenza vaccines (TIV3/TIV3 ID) in SLVP021 2013 | |||||||||
Status: | Updated | ||||||||
Description: | The aim of this study is to compare the response to different formulations of licensed influenza vaccines. The type of seasonal influenza vaccination(s) received independently by volunteers in the year(s) since their last study visit will not impact eligibility. Volunteers will be assigned into one of three vaccine groups (intramuscular trivalent inactivated influenza vaccine (TIV); live attenuated influenza vaccine (LAIV- given year 1 only) or intradermal TIV, based on the type of study vaccine they received in 2010, 2011, 2012, or 2013. All participants will receive a single dose of their assigned seasonal influenza vaccine. Volunteers will complete 3 study visits at Day 0, Day 6-8 and Day 24-32. | ||||||||
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DOI: | 10.21430/M3KHTSSSN7 | ||||||||
Subjects: | 24 | ||||||||
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Clinical Assessments: | None |
SDY1381: Host Determinants Of Protection Against Tuberculosis In Adolescents | |||||||||||
Status: | Updated | ||||||||||
Description: | The bacterium that causes tuberculosis (TB), Mycobacterium tuberculosis (M.tb), has infected one quarter of the world's population. Infection occurs when the pathogen is inhaled, following exposure to a patient with lung TB. 10% of infected persons progress to disease, while 90% never do. We don't understand why some people develop disease, while others do not: this is the focus of this application. To address protection against TB, we have established a cohort of 6,363 South African adolescents. 53% were infected with M.tb at baseline. During 2 years of follow-up, 76 of these participants developed TB disease. As blood was collected and stored every 6 months, we have a unique opportunity to compare host responses between adolescents who developed disease and those who have remained healthy. We will have two approaches to defining protection. Our first focus will be on T cells, which are immune cells shown to be critical for protection against TB. Current assays focus on limited aspects of the T cell response, but have not been successful in defining protection. We have devised a new paradigm - we hypothesize that a model including multiple T cell functional attributes plus their regulation by multiple immune cells will define protection. We propose that relative "immune quiescence", i.e., an optimal but relatively silent immune response, is associated with protection. We and others have preliminary data to suggest that too much inflammation, or too much activation of the immune system, may be detrimental. The rationale for our second focus is that our knowledge of host control of M.tb infection remains incomplete - we therefore propose an unbiased approach that will facilitate discovery of novel pathways involved in protection. We will assess genome-wide gene expression in blood cells, including purified immune cell populations, to delineate new pathways involved in protection. Our preliminary studies of protection against TB in infants have shown the incredible power of this approach. The longitudinal nature of the adolescent cohort, and state-of-the-art bioinformatic approaches, afford unique muscle for uncovering host determinants of protection. We will immediately validate findings by studying further groups of adolescents, from the same cohort. This will be followed by mechanistic studies aimed at understanding how newly described markers may act to protect us against TB. Knowledge of host determinants of protection against TB disease could impact TB control in many ways. For example, targeted prophylactic therapy for infected persons could be implemented, as well as rapid clinical testing of novel TB vaccines. Knowledge gained will also stimulate development of new vaccines and drugs against TB. | ||||||||||
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DOI: | 10.21430/M3E5CED0HU | ||||||||||
Subjects: | 150 | ||||||||||
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Clinical Assessments: | None |
SDY1618: Superior mouse eosinophil depletion in vivo targeting transgenic Siglec-8 instead of endogenous Siglec-F: mechanisms and pitfalls | |||||||
Status: | Updated | ||||||
Description: | We uncovered shortcomings when using certain antibodies that target Siglec-F to deplete mouse eosinophils, while administration of anti-Siglec-8 antibody to Siglec-8 transgenic mice works well. | ||||||
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DOI: | 10.21430/M348T28T35 | ||||||
Subjects: | 12 | ||||||
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Clinical Assessments: | None |
SDY1640: T and B cell responses to SARS-CoV-2 coronavirus | |||||||
Status: | Updated | ||||||
Description: | Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide megapools, circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified. Anti-SARS-CoV-2 IgG, IgM and IgA titers against the spike protein were determined. | ||||||
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DOI: | 10.21430/M3CZDHCXKV | ||||||
Subjects: | 40 | ||||||
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Clinical Assessments: | None |