cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.21430/m37fyk2i9o
title: Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types (see companion study SDY1658)

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/m38dlilkd5
title: B-Lymphocyte Immunotherapy in Islet Transplantation (CIT-05) and Extended Follow Up after Islet Transplantation in Type 1 Diabetes (CIT-08)

description: CIT-05: Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with the immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. CIT-08: The purpose of this protocol is to collect long-term follow-up information on the safety and efficacy of islet transplantation in CIT subjects after their completion in their CIT parent study.
DOI: 10.21430/m38ed12jye
title: INDIGO HLA  and KIR part 1

description: High resolution HLA and KIR typing in five CNS-related diseases.
DOI: 10.21430/m38fvnpezc
title: Effects of tissue localization on Natural Killer (NK) cell phenotypic and functional diversity

description: This study characterizes human Natural Killer (NK) cells across multiple lymphoid and mucosal tissues from individual organ donors using high-dimensional flow cytometry and whole transcriptome analysis.
DOI: 10.21430/m39q379sfj
title: Study of Antithymocyte Globulin for Treatment of New-onset T1DM (START)

description: Antithymocyte globulin (e.g., Thymoglobulin) is an antibody preparation that is commonly used to treat and prevent organ transplant rejection. The START trial aims to determine whether antithymocyte globulin (ATG) treatment can halt the progression of newly diagnosed type 1 diabetes when given within 12 weeks of disease diagnosis.
DOI: 10.21430/m3ajsrnm6b
title: Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria gastrointestinal tract (GI)

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.
DOI: 10.21430/m3ald4rxie
title: A Research Trial of Aralast in New Onset Diabetes (RETAIN) (ITN041AI)

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.
DOI: 10.21430/m3am77xtu7
title: Maternal gut microbiota reflecting poor diet quality is associated with sPTB

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 α-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 α-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
DOI: 10.21430/m3avn5hgtn
title: Influenza / S. aureus Superinfection

description: Infection of mice with Influenza virus, S. aureus, or both
DOI: 10.21430/m3awcqnwdw
title: Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH) (ASC01)

description: Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a serious, life-threatening manifestation of systemic sclerosis (SSc), an autoimmune disease of the connective tissue characterized by scarring (fibrosis) and atrophy of the skin, joints and tendons, skeletal muscles, and internal organs, and immunological disturbances. One-year survival for patients with SSc-PAH ranges from 50-81%. There is currently no cure for SSc-PAH and treatment is limited to vasodilator therapy used in all forms of PAH. In recent studies, immunotherapy was shown to be effective in treating SSc-interstitial lung disease, another serious, life-threatening manifestation of SSc. In addition, there are compelling pre-clinical data and anecdotal clinical reports that suggest modulation of the immune system may be an effective strategy for treating SSc-PAH. To test this approach, this trial will determine if rituximab, an immunotherapy, has a marked beneficial effect on clinical disease progression, with minimal toxicity, in patients with SSc-PAH when compared to placebo.
DOI: 10.21430/m3bzb4p8ci
title: Longitudinal profiling of respiratory and systemic immune responses in severe COVID-19

description: We examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls.
DOI: 10.21430/m3ceh2a7zf
title: Optimization of NULOJIX (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)

description: This study is a multicenter, prospective, randomized (1:1), open-label, Phase II study to compare a NULOJIX (belatacept) based immunosuppressive regimen to a CNI-based regimen in recipients of SPK. Subjects will be consented and enrolled until a total of 60 subjects are randomized.
DOI: 10.21430/m3ci9dvm22
title: Vaccine Efficay and Placebo Cohorts with Malaria Natural History Groups 2 & 3: Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium falciparum NF54

description: Double-blind, randomized, placebo-controlled trial that started on 01 April 2016 to assess the safety, tolerability and protective efficacy of PfSPZ Vaccine against naturally occurring infection. The start of the study was dependent on the safety and tolerability results of the pilot study. The PfSPZ Vaccine targeted dose was 1.8x10^6 PfSPZ, or the highest tolerable dose determined from the Pilot Study (Arm 1c, 1d). Arm 2 (n=60) was the targeted vaccine dose arm and received 3 doses of PfSPZ Vaccine (1.8x106) via DVI on Days 1, 57, 113. Arm 3 (n=60) was the placebo-controlled arm and received 3 doses of normal saline (NS) via DVI on Days 1, 57, 113. All volunteers received antimalarial treatment prior to vaccination #1 and vaccination #3. All subjects were assessed by thick blood smear (TBS) every 2 weeks after the 3rd dose until week 24 and as indicated for symptoms.
DOI: 10.21430/m3cwcoqdnw
title: Unique transcriptomic landscapes identified in isPTB  and infectiion-PTB/AHC

description: The study compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB (idiopathic spontaneous preterm birth) between 28–36 weeks gestation and healthy term placentas. Transcriptomic analyses revealed a unique expression signature for isPTB, which included three upregulated IGF binding proteins (IGFBP1, IGFBP2, and IGFBP6), supporting a role for aberrant IGF signaling in isPTB, and secondary signatures of inflammatory markers including TNC, C3, CFH, and C1R, which have been associated with placental maturity. In contrast, the expression signature of the PTB-infection cohort included upregulation of proliferative genes along with cell cycling and mitosis pathways. Together, these data suggest an isPTB molecular signature of placental hypermaturity, likely contributing to the premature activation of inflammatory pathways associated with birth and providing a molecular basis for idiopathic spontaneous birth
DOI: 10.21430/m3czdhcxkv
title: T and B cell responses to SARS-CoV-2 coronavirus

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.
DOI: 10.21430/m3e5ced0hu
title: Host Determinants Of Protection Against Tuberculosis In Adolescents

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.
DOI: 10.21430/m3e5ldnf4k
title: Steroid and Tacrolimus Avoidance Using NULOJIX (Belatacept) in Renal Transplantation (CTOT-16)

description: This trial is a phase 2 prospective, multi-center, open-label study of renal transplantation assessing the safety and efficacy of a steroid-free, calcineurin inhibitor-free, belatacept-based immunosuppressive regimen.
DOI: 10.21430/m3ej9n4nc2
title: Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children

description: KSPZV1 Part 2 is a single center, randomized, double-blind, placebo-controlled trial enrolling 336 malaria-exposed Kenyan children ages 5 to 12 months at the time of first vaccination. Subjects were randomized to 1 of 4 groups in a 1:1:1:1 ratio to receive 3 doses at 8-week intervals of either 4.5 x10^5, 9.0 x10^5, or 1.8 x10^6 PfSPZ or normal saline as a control.
DOI: 10.21430/m3etfanv1o
title: Sex differences in immune responses to SARS-CoV-2 (Companion study to SDY1655)

description: In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. ** THE DATA FOR THIS STUDY IS CONTAINED IN SDY1655 **.
DOI: 10.21430/m3fe77i3xs
title: Critical ACE2 Determinants of SARS-CoV-2 and Group 2B Coronavirus Infection and Replication

description: Through molecular modeling and empirical in vitro validation, the study identified 5 key amino acid differences between murine and human ACE2 that mediate SARS-CoV-2 infection, generating a chimeric humanized murine ACE2. Additionally, the study examined the ability of the generated humanized murine ACE2 receptor to permit infection by an additional preemergent group 2B coronavirus, WIV-1, providing evidence for the potential pan-virus capabilities of this chimeric receptor.
DOI: 10.21430/m3fq76h3ig
title: Transcriptome and Regulatory Maps of Decidua-derived Stromal Cells Inform Gene Discovery in Preterm Birth

description: This study generated extensive transcriptional and chromatin annotations of decidua-derived stromal cells and then utilized a computational framework to analyze this information in conjunction with results from a genome-wide association study of gestation duration in 56,384 women. This resulted in a significant enrichment of heritability estimates in functional noncoding regions in stromal cells, as well as in the discovery of additional loci associated with gestational duration and target genes of associated loci.
DOI: 10.21430/m3fvw3z3tn
title: Immune Cell Repertoires in Breast Cancer Patients after Adjuvant Chemotherapy

description: Adjuvant chemotherapy in breast cancer patients causes immune cell depletion at an age when the regenerative capacity is compromised. Successful regeneration requires the recovery of both quantity and quality of immune cell subsets. Although immune cell numbers rebound within a year post-treatment, it is unclear whether overall compositional diversity is recovered. We investigated the regeneration of immune cell complexity by comparing peripheral blood mononuclear cells from breast cancer patients ranging from one to five years post-chemotherapy with those of age-matched healthy controls using mass cytometry and T cell receptor sequencing. These data revealed universal changes in patients' CD4 T cells that persisted for years and consisted of expansion of TH17-like CD4 memory populations with incomplete recovery of CD4 naive T cells. Conversely, CD8 T cells fully recovered within a year. Mechanisms of T cell regeneration however were unbiased as CD4 and CD8 T cell receptor diversity remained high. Likewise, TEMRAs were not expanded indicating that regeneration was not driven by recognition of latent viruses. These data suggest that while CD8 T cell immunity is successfully regenerated, the CD4 compartment may be irreversibly impacted. Moreover, the bias of CD4 memory towards inflammatory effector cells may impact responses to vaccination and infection.
DOI: 10.21430/m3g6zcu1uc
title: Early Prediction of Preeclampsia via Machine Learning

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%.
DOI: 10.21430/m3gl2sm9xs
title: Establishment of Vaginal Microbiota Composition in Early Pregnancy and its Association with Subsequent Preterm Prelabor Rupture of the Fetal Membrane

description: In this study, we use metataxonomics to longitudinally characterize the vaginal bacterial composition from as early as 6 weeks of gestation in women at high (n?=?38) and low (n?=?22) risk of preterm birth who subsequently experience PPROM and in women delivering at term without complications (n?=?36). Reduced Lactobacillus spp. abundance and high diversity was observed prior to PPROM in 20% and 26% of women at low and high risk of preterm births respectively, but in only 3% of women who delivered at term.
DOI: 10.21430/m3gs4ep88p
title: Perturbation of ILF3 in Human MDDCs

description: MDDCs were transduced with lentiviral constructs expressing mRNA coding for various isoforms of ILF3 or isoforms lacking specific domains.
DOI: 10.21430/m3guqmudwl
title: Maternal and Infant Immune Repertoire Sequencing in PPROM study

description: The study analyzed lymphocyte receptor repertoires in maternal and cord blood from 14 term and 10 preterm deliveries and hypothesized that the high incidence of infection in patients with preterm labor (PTL) may result in specific changes in the TCR and BCR repertoires
DOI: 10.21430/m3h6b9ca5d
title: T cell and chemokine receptor control of CD8 T cell motility after influenza infection

description: CD8 T cells utilize chemokines and antigen signals throughout acute influenza virus infection
DOI: 10.21430/m3h8hwj1ic
title: Endometrial Gland Organoids

description: The study established endometrial gland organoids from decidua isolated from term placental membranes. These organoids express typical markers of glandular epithelia such as E-cadherin, Laminin and Cytokeratin 7, and can be propagated in cell culture through multiple passages. Potential survival factors for the co-culture of organoids and endometrial stromal fibroblasts were identified. These modifications facilitate the generation of patient-specific endometrial gland organoids with known pregnancy outcomes
DOI: 10.21430/m3hgk1qhhw
title: Investigating the natural killer cell response to acute dengue infection.

description: Performed a mass cytometry screen of the expression of NK cell receptors and their ligands in acute dengue patients and healthy controls.
DOI: 10.21430/m3hv2pqm3c
title: CD16 is upregulated in HIV-exposed seronegative women and may mediate enhanced antibody-dependent cytotoxicity

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
DOI: 10.21430/m3i5kic0bc
title: The interaction between the vaginal microbiome, cervical length and vaginal progesterone treatment for preterm birth risk

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.
DOI: 10.21430/m3iancco4a
title: Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection

description: Estimate the ratio of symptomatic to asymptomatic CHIKV infections (S:A ratio), elucidate sign and symptom cooccurrence, characterize the probability of infection and disease occurrence across age, identify risk factors associated with infection and disease outcomes, and quantify differences in the proportions of inapparent CHIKV infections between the Asian CHIKV lineage and the ECSA CHIKV lineage
DOI: 10.21430/m3iv53zsx3
title: The roles of CD103 and CD49a in adherence and motility of CD8 T cells

description: Influenza specific CD8 T cells from influenza infected mice were examined both in vitro and in vivo to characterize the roles that integrins CD103 and CD49a play when they interact with their respective ligands.