DR36 DataRelease
Release Date: 09/30/2020
| SDY1434: Steroid and Tacrolimus Avoidance Using NULOJIX (Belatacept) in Renal Transplantation (CTOT-16) | |||||||
| Status: | New | ||||||
| Description: | Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. Transplant recipients have to take anti-rejection medications to prevent their immune system (the body's natural defense system against illness) from rejecting their new kidney. Most patients who receive a kidney transplant must take these anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work. The purpose of this study is to determine if NULOJIX (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the transplanted kidney from damage. The researchers also want to learn more about the safety of this treatment and the long term health of the transplanted kidney. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3E5LDNF4K | ||||||
| Subjects: | 70 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1603: Investigating the natural killer cell response to acute dengue infection. | ||||||||||
| Status: | New | |||||||||
| Description: | Performed a mass cytometry screen of the expression of NK cell receptors and their ligands in acute dengue patients and healthy controls. | |||||||||
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| DOI: | 10.21430/M3HGK1QHHW | |||||||||
| Subjects: | 91 | |||||||||
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| Publications: | None | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY1630: Effects of tissue localization on Natural Killer (NK) cell phenotypic and functional diversity | |||||||
| Status: | New | ||||||
| Description: | Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigated how tissue localization regulates the development and function of human Natural Killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 59 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation and function across age and between diverse individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen and lungs, exhibiting shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity prevail in lymph nodes and intestines, exhibiting tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, while mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. | ||||||
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| DOI: | 10.21430/M38FVNPEZC | ||||||
| Subjects: | 78 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1633: SR Tacrolimus Safety and PK Study in Healthy Subjects | |||||||
| Status: | New | ||||||
| Description: | This is a single-center, nonrandomized, open-label, first-in-human study to assess the safety and pharmacokinetic (PK) profile of sustained-release (SR) tacrolimus, which will be administered as a single dose of 0.1 mg/kg by subcutaneous (SC) injection in 8 healthy subjects. Following a screening period, eligible subjects will be admitted to the clinical research unit (CRU). On Day 1 subjects will receive a single injection of SR tacrolimus. Subjects will remain at the CRU for at least 24-hours postdose for collection of serial blood samples for PK analysis and safety monitoring until discharge on Day 2. Subjects will return to the clinic for PK and safety evaluations for 60 days postdose. | ||||||
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| DOI: | 10.21430/M3W2VVIN1S | ||||||
| Subjects: | 8 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1634: Charge-Altering Releasable Transporters Enable Specific Phenotypic Manipulation Of Resting Primary Natural Killer Cells | |||||||
| Status: | New | ||||||
| Description: | Natural killer (NK) cells are capable of rapid and robust cytotoxicity, making them excellent tools for immunotherapy. However, their recalcitrance to standard transfection techniques has limited both mechanistic studies and clinical applications. Current approaches for NK cell manipulation rely on viral transduction or methods requiring NK cell activation, which can alter NK cell function. Here, we report that non-viral Charge-Altering Releasable Transporters (CARTs) efficiently transfect primary human NK cells with mRNA without relying on NK cell activation. | ||||||
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| DOI: | 10.21430/M3LK4ADVD1 | ||||||
| Subjects: | 4 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1640: T and B cell responses to SARS-CoV-2 coronavirus | |||||||
| Status: | New | ||||||
| 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 | ||||||
| SDY1648: Sex differences in immune responses to SARS-CoV-2 (Companion study to SDY1655) | |||||||
| Status: | New | ||||||
| Description: | Patients who were admitted to the Yale-New Haven Hospital between March 18th and May 9th, 2020 and were positive for SARS-CoV-2 by RT-PCR from nasopharyngeal and/or oropharyngeal swabs were enrolled through the IMPACT biorepository study. Among total 198 patients enrolled in IMPACT study this period, we obtained freshly-isolated peripheral blood mononuclear cells (PBMCs), plasma, nasopharyngeal swabs or saliva samples from in total 93 patients for the present study. Nasopharyngeal swabs and saliva samples for virus RNA assessment along with blood samples were collected on the day of enrollment. Plasma and PBMCs were isolated from whole blood and plasma was used for titer measurements of SARS-CoV-2 spike S1 protein specific IgG and IgM antibodies (anti-S1 IgG and IgM) and cytokine/chemokine measurements. Freshly isolated PBMCs were stained and analyzed by flow cytometry analyses. A subset (n = 54) of study participants donated blood, nasopharyngeal swabs, and saliva longitudinally. To compare the immune phenotype between sexes, two sets of data analyses were performed in parallel, baseline and longitudinal. As a control group, COVID-19 uninfected health care workers (HCWs) from Yale-New Haven Hospital were enrolled. | ||||||
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| DOI: | 10.21430/M3ETFANV1O | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1654: Single-cell transcriptomics of human T cells | |||||||
| Status: | New | ||||||
| Description: | Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease. | ||||||
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| DOI: | 10.21430/M3XI6TNA0K | ||||||
| Subjects: | 8 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1655: Longitudinal Analyses Reveal Immunological Misfiring in Severe COVID-19 (Companion study to SDY1648) | |||||||||||
| Status: | New | ||||||||||
| Description: | Longitudinal analyses of COVID-19 patients revealed increasingly dysregulated and sustained inflammatory immune responses in severe disease compared to moderate disease. Maladaptive immune profiles included persistent type 1, type 2 and type 3 cytokines, as well as a mix of monocyte-related chemokines, and growth factors. Unbiased clustering of patients based on these measurements linked worse clinical outcomes to greater dysregulation in the immune response. | ||||||||||
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| DOI: | None | ||||||||||
| Subjects: | 202 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY1662: An Inflammatory Cytokine Signature Predicts Covid-19 Severity And Survival | |||||||
| Status: | New | ||||||
| Description: | Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-a, and IL-1b in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. | ||||||
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| DOI: | 10.21430/M3ODKGM8O5 | ||||||
| Subjects: | 2340 | ||||||
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