cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.21430/m3jl1iwxgz
title: The association between vaginal bacterial composition and miscarriage

description: To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages, the study conducted prospective profiling on 161 pregnancies by using 16S rRNA gene?based metataxonomics from 5 weeks? gestation in pregnancies ending in miscarriage (78) or uncomplicated term deliveries (83) matched for age, gestation and body mass index. Relative vaginal bacteria abundance, diversity and richness were measured and compared among cohorts. RESULTs: Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding. Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.?depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies.
DOI: 10.21430/m3kaq17awd
title: PLA2G6 in attenuating ferroptosis

description: The study found that spontaneous preterm birth (SPTB) is associated with ferroptosis and that inhibition of GPX4 causes ferroptotic injury in primary human trophoblasts and during mouse pregnancy. Importantly, the role for the phospholipase PLA2G6, known to metabolize Hp-PE to lyso-PE and oxidized fatty acid, was uncovered in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hypoxia/reoxygenation injury in vivo. Together, ferroptosis signaling and the role for PLA2G6 in attenuating trophoblastic ferroptosis in the human and mouse placenta was identified, which provided mechanistic insights into the ill-defined placental lipotoxicity that may inspire PLA2G6-targeted therapeutic strategies
DOI: 10.21430/m3kwdr5vts
title: Response of human MDDCs to HIV

description: ATAC-seq measurements of human MDDCs following infection with HIV
DOI: 10.21430/m3liq1cwan
title: Systemic Immunological Effects of Influvac Tetra Vaccination

description: A proteomics study to identify the systemic changes induced by a tetravalent influenza vaccine.
DOI: 10.21430/m3lk4advd1
title: Charge-Altering Releasable Transporters Enable Specific Phenotypic Manipulation Of Resting Primary Natural Killer Cells

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.
DOI: 10.21430/m3lmdegz3w
title: Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children

description: KSPZV1 Part 1 is a single center, age de-escalating, dose-escalating, randomized, double-blind, placebo-controlled trial enrolling malaria-exposed Kenyan children ages 5 months to 9 years at the time of first vaccination. One or two doses of the radiation-attenuated sporozoite-based PfSPZ Vaccine (8 per group) or normal saline placebo (4 per group) were administered by DVI at up to 5 different dosing levels using a staggered, dose-escalating design. Dosages include: 1.35 x10^5, 2.7 x10^5 (lowest two doses only in the two younger age groups), 4.5 x10^5, 9.0 x10^5, and 1.8 x10^6 PfSPZ in 13 cohorts of 12 participants each (3 dose cohorts among 5–9-year-olds, 5 among 1–5-year-olds, and 5 among 5–12-month-olds).
DOI: 10.21430/m3lnuwu2lk
title: Th1 Polarization of JIA Synovial Fluid T Cells

description: We sought to determine the immunophenotype of joint-infiltrating CD4+ T cells as well as the stability of Tregs in oligo JIA. This was done through the use of flow cytometry, bulk and single-cell RNA sequencing, DNA methylation studies, and Treg suppression assays. We show that CD4+ T cells in SF, including Tregs, are predominantly Th1-polarized. Disease extension is associated with a greater proportion of IFN?-expressing CD4+ T cells in the joint. Importantly, Th1-skewed SF Tregs in oligo JIA maintain Treg identity and suppressive functionality. Our findings suggest that inhibiting the Th1 pathway and enhancing Treg function may be key in controlling arthritic flares in oligo JIA.
DOI: 10.21430/m3lqg9jffs
title: Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells

description: We studied the response of primary DCs to the prototypical persistent DNA virus, human cytomegalovirus (CMV). Recognition of live infected cells is a mechanism of virus detection by pDCs that elicits a unique antiviral immune response.
DOI: 10.21430/m3lqiyecmj
title: Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19

description: Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. The adaptive immune system responds to pathogens in an antigen-specific manner to develop protective immunity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects, and compared the response in unexposed controls
DOI: 10.21430/m3ls8zvwmd
title: T cell immune signature of whole cell vs acellular pertussis vaccination in healthy individuals

description: T cell immune signature of whole cell vs acellular pertussis vaccination as well as priming in healthy individuals
DOI: 10.21430/m3luwfe0ds
title: Cervicovaginal Microbiota and Local Immune Response Modulate the Risk of Spontaneous Preterm Delivery

description: From a cohort of 2000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Using innovative Bayesian modeling of cervicovaginal microbiota, seven bacterial taxa were significantly associated with increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of alpha-defensin-2 lowered the risk of sPTB associated with cervicovaginal microbiota in an ethnicity-dependent manner. Surprisingly, even in Lactobacillus spp. dominated cervicovaginal microbiota, low ?-defensin-2 was associated with increased risk of sPTB.
DOI: 10.21430/m3mmuwivmu
title: Broad dysregulation of innate immunity and hematopoiesis distinguishes mild from severe COVID-19

description: Our understanding of protective vs. pathologic immune responses to Coronavirus disease 2019 (COVID-19) is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. We further demonstrate that emergency granulopoiesis is a prominent feature of fatal COVID-19. Notably, we do not identify substantial immune perturbations in mild COVID-19 in either protein expression, RNA expression, or chromatin regulation, implying that mild disease is characterized by absent or rapidly resolved systemic immune responses. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 such as neutrophil hyperactivation that may provide targets for therapeutic intervention such as inhibiting neutrophil function through ligation of neutrophil inhibitory receptors.
DOI: 10.21430/m3nww7is3o
title: Computational discovery of therapeutic candidates for preventing preterm birth

description: Few therapeutic methods exist for preventing preterm birth (PTB). In the US, progesterone (P4) supplementation is the only FDA-approved drug for use in preventing recurrent spontaneous PTB. However, P4 has limited effectiveness (only 1/3 of cases). To identify repositioning drug candidates, the study used a rank-based pattern-matching strategy to compare the differential gene expression signature for PTB to differential gene expression drug profiles in the Connectivity Map database and assigned a reversal score to each PTB-drug pair. Eighty-three drugs, including P4, were identified. Many of these compounds have been evaluated in the context of pregnancy, with 13 belonging to pregnancy category A or B ? indicating no known risk in human pregnancy. The drug lansoprazole (a proton-pump inhibitor) with a strong reversal score and a good safety profile was selected for validation in LPS-induced inflammation mouse model. The result showed a significant increase in fetal viability by lansoprazole compared with controls
DOI: 10.21430/m3nzoj19rm
title: Integrated modeling of metabolome, proteome, and immunome trajectories predicts labor onset

description: To predict labor onset, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry for metabolomics, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. A stacked generalization algorithm to the multiomic dataset was applied to build and independently validate an integrated predition model. The model with the top 45 features resulted in the prediction in Pearson R=0.85 ( training set) and 0.81 (test set), respectively. The study found the surge in steroid hormone metabolites 2 to 4 weeks before labor coincided with dynamic changes in plasma protein concentrations and immune cell responses.
DOI: 10.21430/m3o03jfgi6
title: Alloantibodies in Pediatric Heart Transplantation (CTOTC-04)

description: The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients.
DOI: 10.21430/m3o1zsrr7p
title: Modified CyTOF Helios Injector Can Improve Data Quality

description: Evaluating data quality and inter-instrument variability of the Helios Mass Cytometer using a modified injector and sample acquisition protocol
DOI: 10.21430/m3ocs4vqwy
title: Flow Cytometry of T cells from HAARVI COVID-19 Cohort

description: FCS and workspace files from ICS and Surface Marker Staining Experiments
DOI: 10.21430/m3odkgm8o5
title: An Inflammatory Cytokine Signature Predicts Covid-19 Severity And Survival

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.
DOI: 10.21430/m3pc6gt19o
title: Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes

description: Based on 10,734 mother?infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, the study constructed haplotype genetic scores using SNPs known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). And tested associations between these haplotype genetic scores and birth outcomes (gestational duration, birth weight). In addition, constructed the infant-specific birth weight genetic scores to examine the effects of fetal growth on gestational duration and maternal phenotypes during pregnancy. The conclusions of the study are that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes
DOI: 10.21430/m3qc31xeye
title: KSHV tropism in B lymphocytes

description: Study of Tonsil Biospecimens via ex vivo infection with KSHV to determine KSHV tropism for B lymphocytes in human tonsil
DOI: 10.21430/m3qck8h0yh
title: A comparative CyTOF analysis of resected-tumor samples from human GBM patients and mouse GBM-tumors (see companion study SDY1637)

description: Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. We generated distinct imageable syngeneic mouse GBM-tumor models and utilized RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identified immunologically-inert and active syngeneic tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells, resident macrophages and fewer eosinophils and SiglecF+ macrophages. To mimic the clinical settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decrease in resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM patients and mouse GBM-tumors showed stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.
DOI: 10.21430/m3qkupqs46
title: Mid-gestation serum lipidomic profile of PTB are influenced by BMI

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
DOI: 10.21430/m3qkw63fpo
title: Tumor Immune Microenvironment of mIDH1 and wtIDH1 Glioma GEMMs

description: The tumor immune cell compartment of mIDH1 and wtIDH1 glioma models.
DOI: 10.21430/m3qpgx9uya
title: Maternal plasma miRNAs as potential biomarkers for detecting risk of SGA

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
DOI: 10.21430/m3quum0902
title: gso32 infected with Mtb

description: Gene expression analysis of gso32 bone marrow derived macrophages treated with IFNbeta and/or infected with live or heat killed Mycobacterium tuberculosis
DOI: 10.21430/m3qx318knw
title: Licensed BCG formulations differ markedly in innate immune activation

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.
DOI: 10.21430/m3r2hhaq4q
title: Synovial fibroblast positional identity controlled by inductive Notch signaling underlies pathologic damage in inflammatory arthritis

description: The synovium is a mesenchymal tissue composed mainly of fibroblasts with a lining and sublining that surrounds the joints. In rheumatoid arthritis (RA), the synovial tissue undergoes marked hyperplasia, becomes inflamed and invasive and destroys the joint1,2. Recently, we and others found that a subset of fibroblasts located in the sublining undergoes major expansion in RA and is linked to disease activity 35. However, the molecular mechanism by which these fibroblasts expand in RA remains unknown. Here, we identified a critical role for NOTCH3 signaling in the differentiation of perivascular and sublining CD90(THY1)+ fibroblasts. Using single cell RNA-sequencing and mixed cell micromass organoids, we found that NOTCH3 signaling drives both transcriptional and spatial gradients in fibroblasts emanating from vascular endothelial cells outward. In active RA, NOTCH3 and NOTCH target genes are markedly upregulated in synovial fibroblasts. Importantly, genetic deletion of Notch3 or monoclonal antibody-blockade of NOTCH3 signaling attenuates inflammation and prevents joint damage in inflammatory arthritis. Our results indicate that synovial fibroblasts exhibit positional identity regulated by endothelium-derived Notch signaling and that this stromal crosstalk pathway underlies inflammation and pathology in inflammatory arthritis.
DOI: 10.21430/m3r9ugv228
title: Cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

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.
DOI: 10.21430/m3rbu82mnr
title: Natural killer cell repertoire and function in HIV-1 persistence

description: Samples taken from people living with HIV-1 on long-term ART over the course of 50 weeks were profiled by CyTOF using antibody panels focused on natural killer cell receptors and ligands
DOI: 10.21430/m3sb6g69p1
title: Relaxed constraint and functional divergence of PGR

description: To resolve existing conflicting data on progesterone receptor gene (PGR) evolution, the study assembled a dataset of 119 Eutherian PGRs and used a suite of maximum likelihood-based methods to characterize the strength and direction of selection acting on PGR. The result shows that PGR evolved rapidly in the human lineage (as well as other Catarrhine primates), which likely reflects an episode of relaxed selection intensity rather than positive selection. Coincident with the episode of relaxed selection intensity, ancestral sequence resurrection and functional tests indicate that the major human PR isoforms (PR-A and PR-B) evolved divergent functions in the human stem-lineage. These results suggest that the regulation of progesterone signaling by PR-A and PR-B may also have diverged in the human lineage and that non-human animal models of progesterone signaling may not faithfully recapitulate human biology
DOI: 10.21430/m3smnpg422
title: Unconventional ST2- and CD127-negative lung ILC2 populations are induced by the fungal allergen Alternaria

description: Group 2 innate lymphoid cells (ILC2s) have been recognized for their ability to drive type 2 responses in experimental animal models in the absence of T cells. Mice intranasally challenged with Alternaria alternata, a fungal allergen associated with severe asthma and fatal exacerbations in humans, potently activates ILC2s via the IL-33/ST2 (IL-33R) axis to robustly secrete type 2 cytokines. Animal models, including Alternaria-induced lung inflammation in mice, have given us critical insight into pathways of ILC2 regulation that appear to apply to ILC2 responses in human disease.7 Thus, accurate identification of ILC2s in the lungs of mice is critical to future understanding of their biology and contribution to allergic disease. We assessed whether the conventional ILC2 identification markers ST2 and CD127.
DOI: 10.21430/m3tnvqxr7i
title: Safety groups 1A & 1B: Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium falciparum NF54

description: Single dose safety assessment in 10 adult subjects in Mali – 5 subjects immunized with 4.5x10^5 PfSPZ by DVI and 5 subjects immunized with 9.0x10^5 PfSPZ by DVI.
DOI: 10.21430/m3tsuaj9ma
title: Vaccine Safety and Placebo Groups Arm 1C & 1D with CHMI: Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium falciparum NF54

description: Three injections by DVI on days 1, 57 and 113 of 1.8x10^6 PfSPZ of PfSPZ Vaccine to each of 30 subjects – 15 pretreated with artesunate amodiaquine and 15 not pretreated. Subjects underwent CHMI via PfSPZ Challenge DVI approximately 21 days following the third injection (vaccination #3) in addition to 15 unvaccinated subjects to serve as infectivity controls. Subjects were followed for 28 days after CHMI. Assessment of parasitemia and malaria related clinical symptoms began on Day 6 post CHMI and continued daily until the first microscopic detection of parasitemia (positive blood smear). Subjects were seen in the clinic once daily until a positive blood smear was obtained or until the 27th day post CHMI. Standard treatment with Coartem (artemether-lumefantrine) was initiated upon diagnosis of P. falciparum. All subjects in this group had the option of receiving a booster dose of PfSPZ Vaccine prior to transmission season in 2016.