19385 results for "Cheap fc 26 coins Buyfc26coins.com is official EA Sports partner for FC 26 coins That was the fastest delivery ever..fxB4"

in 17.06 milliseconds.

• Systems Analysis of the PfSPZ Vaccine in Kenyan Infants

  The PfSPZ vaccine is a candidate vaccine targeting the Plasmodium falciparum parasite, which is the cause of the most lethal type of human malaria. This study used de-identified blood samples collected from 316 infants aged 5 to 12 months (inclusive) enrolled in a Phase 2, randomized, placebo-controlled trial (NCT02687373) of the PfSPZ malaria vaccine, conducted in a region of western Kenya where malaria transmission is high and perennial. The study began in July, 2016, after peak malaria transmission, and was completed in August, 2018. In this study, three doses of the PfSPZ Vaccine (4.5x105 PfSPZ, 9.0x105 PfSPZ, and 1.8x106 PfSPZ) were tested against a normal saline placebo comparator. In all four groups, doses were administered in 3 doses at 0, 8, and 16 weeks by direct venous inoculation. Vaccine efficacy was determined at 3, 6, and 12 months of follow-up after the third immunization. RNA was extracted from whole blood collected in PAXgene tubes before PfSPZ immunization, and two weeks after the third (final) dose, from 262 children for which sufficient material was available at both time points (82% of 316 enrolled children; 525 samples). RNA was depleted of globin and ribosome transcripts before library generation and sequencing on the Illumina NovaSeq platform. RNA-seq expression data was analyzed to determine blood transcriptional signatures, before and after PfSPZ vaccine immunization, that predicts sterile protection from naturally occurring P. falciparum infection or delayed parasitemia at 3 months post-immunization. Gene expression data will also be correlated to P. falciparum-specific IgG antibody and cellular responses to identify possible molecular correlates of vaccine-induced immunogenicity

  Study phs002196

• DSRCT RNA genomic sequencing

  Purpose: To further understand the molecular pathogenesis of desmoplastic small round cell tumor (DSRCT), a rare but often fatal malignancy occurring primarily in young males, we used next-generation RNA sequencing to investigate the gene expression profiles intrinsic to this disease.Experimental Design: RNA from DSRCT tumor samples were obtained from the Cooperative Human Tissue Network biorepository. RNA sequencing was completed using the Illumina HiSeq 2000 system. Presence of the EWSR1-WT1 fusion was verified using both RNA-sequencing and PCR. Validation studies, including WT1 ChIP-seq, RNA sequencing, and EWS-WT1 knockdown experiments, were performed on an established DSRCT cell line, JN-DSRCT-1. Protein expression of clinically relevant genes determined by RNA sequencing was confirmed using immunohistochemistry. A panel of immune signature genes was also evaluated to identify possible immune therapeutic targets. Results: We analyzed the RNA from 14 tumor samples, of which two were confirmed negative for the diagnostic EWSR1-WT1 translocation. Principal component analysis of the sequencing data indicated that fusion-negative and fusion-positive tumors are transcriptionally distinct entities. Overlapping the significant ChIP-seq peaks with genes found to be highly expressed in the RNA sequencing data revealed that IGF2 and FGFR4 were both highly expressed, and targets of the EWS-WT1 fusion gene. This finding has potential clinical relevance for targeted therapeutic intervention. In addition, we identified the immune checkpoints CD200 and CD276 as potentially targetable genes whose expression is independent of the EWS-WT1 fusion gene in vitro.Conclusions: Despite the transcriptional complexity of this disease, we were able to identify IGF2, FGFR4, CD200, and CD276 as potential therapeutic targets for patients suffering from DSRCT.

  Study EGAS00001002770

• Large Scale Genotyping of Psychiatric Disorders

  Psychiatric disorders cause enormous human suffering and cost to society. The goal of this project is to elucidate the genetics of psychiatric disorders through a large consortium effort and genome-wide genotyping. The Psychiatric Genomics Consortium (PGC) (https://www.med.unc.edu/pgc) is an international consortium to pursue genome-wide analyses of common psychiatric disease. The PGC was founded in 2007 to unite investigators from around the world to conduct mega-analyses of individual genome-wide genotype data for schizophrenia (SCZ), bipolar disorder (BIP), autism (AUT), attention-deficit hyperactivity disorder (ADHD), and major depressive disorder (MDD). Subsequently, the PGC has expanded to include Tourette syndrome (TS), obsessive-compulsive disorder (OCD), eating disorders (ED), post-traumatic stress disorder (PTSD), and substance abuse (SUD). The PGC partnered with Illumina to develop the PsychChip, a custom GWAS array aimed at capturing common variation genome-wide for imputation, rare coding variation drawn from the exome chip and dense genotypes for loci with suggestive evidence for association across the initial PGC analyses of SCZ, MDD, BPD, ASD and ADHD. Samples (cases, controls, and families) were collected from Institutional Review Board-approved protocols that aim to study the genetics of psychiatric disorders. Genome-wide genotyping was performed at the Broad Institute (Cambridge, MA, USA) and the Mount Sinai School of Medicine Friedman Brain Institute (New York, NY, USA) using the PsychChip or Exome Chip.

  Study phs001413

• Knoll et al Identification of drug candidates targeting monocyte reprogramming in people living with HIV

  Introduction People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics layers. Methods Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation was performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. Results Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Moreover, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. Discussion These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes.

  Study EGAS00001007460

• Heart Failure Network - Effectiveness of Ultrafiltration in Treating People with Acute Decompensated Heart Failure and Cardiorenal Syndrome (HFN CARRESS - BioLINCC)

  ObjectiveThe CARRESS trial examined the effectiveness of ultrafiltration compared with a strategy of diuretic-based stepped pharmacologic therapy on renal function and weight loss in patients with heart failure who have worsening renal function and persistent congestion.BackgroundAcute cardiorenal syndrome is defined as worsening renal function in patients with acute decompensated heart failure. It occurs in 25 to 33% of patients and is associated with poor outcomes. Current heart failure treatments focus on removing excess fluid buildup, however administration of intravenous diuretics may contribute to worsening renal function. Venovenous ultrafiltration is one alternative therapy that may be effective in patients with acute decompensated heart failure complicated by acute cardiorenal syndrome and persistent congestionSubjectsA total of 188 patients were randomized.DesignHospitalized subjects were randomly assigned to receive either ultrafiltration therapy or pharmacologic therapy. Ultrafiltration was performed at a fluid-removal rate of 200 ml per hour and loop diuretics were discontinued for the duration of the intervention. The addition of intravenous vasodilators or positive inotropic agents was prohibited, unless they were deemed to be necessary as rescue therapy. Patients assigned to stepped pharmacologic therapy received intravenous diuretics to manage congestion and maintain a urine output of 3 to 5 liters per day. In both groups, the assigned treatment strategy was to be continued until the signs and symptoms of congestion in the patient were reduced as much as possible. The primary end points were baseline changes in serum creatinine and weight as assessed at 96 hours after treatment assignment.ConclusionsThe use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function, and there was a similar amount of weight loss between the two groups. Ultrafiltration was associated with a higher rate of adverse events (Bart, et al., 2012, PMID: 23131078).

  Study phs003510

• DNA Methylomic Profiling of Preeclampsia Across Pregnancy

  Preeclampsia (PE) is a hypertensive, multi-system disorder of pregnancy that significantly impacts maternal and infant morbidity/mortality across the globe, as it increases risk of cardiovascular disease and remains a leading killer of women and babies. Despite PE's significant impact on morbidity/mortality, there are no clinically reliable biomarkers that predict PE. DNA methylation, a dynamic regulator of gene expression, represents a mechanism that is known to be impacted by the environment. Because PE stems from a dysfunctional placenta that releases debris into the maternal circulation, we hypothesized that the in-vivo environment created by the dysfunctional placenta will impact DNA methylation in the maternal circulation, and that these blood-based methylation profiles would serve as a systemic biomarker of the maternal response to placental dysfunction. Our overall objective of this pilot study was to longitudinally characterize DNA methylation profiles across the three trimesters of pregnancy in the maternal blood at time points before and after clinically overt PE using a targeted (endoglin and endoglin-related genes) and a discovery-based approach. For this pilot study, 28 normotensive control participants and 28 PE case participants enrolled in the NICHD funded pregnancy study entitled Prenatal Exposures and Preeclampsia Prevention: Mechanisms of Preeclampsia and the Impact of Obesity (PEPP3; P01HD30367) were 1:1 frequency matched on self-reported race, pre-pregnancy BMI, smoking history, and gestational age at sample collection. Methylation data were collected with the Infinium® MethylationEPIC Beadchip. Methylation assay data collection were carried out at Johns Hopkins University Genetic Resources Core Facility, The SNP Center, Baltimore, MD, USA.

  Study phs001937

• A Genomic Approach to Warfarin Dose Prescription in Admixed Caribbean Hispanics

  Warfarin is an oral anticoagulant and one of the most used drugs in the world accounting for up to 1.5% of prescriptions globally. Warfarin inhibits vitamin K epoxide reductase complex 1 (VKORC1), an enzyme responsible for the vitamin K recycling that is required for the activation of clotting factors. Warfarin is prescribed at an average dose of 5 mg/day for most of the indications but significant inter-patient variability has been observed. Single nucleotide variations at the VKORC1 (GeneID: 79001) and CYP2C9 (GeneID: 1559) genes alone explain from 28 to 35% of variability in warfarin dose requirements and up to 56% when clinical factors (age, gender, body surface area, diabetes and heart valve) are incorporated into regression analysis. However, genetic-guided dosing algorithms are mostly derived from studies in Europeans. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. VKORC1 (GeneID: 79001) and CYP2C9 (GeneID: 1559), the most important genetic predictors of warfarin response, were sequenced using Next Generation sequencing. Other candidate genes in DMET Plus Assay were assessed to identify genetic variants with relevance in warfarin dose requirements among Puerto Ricans. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis that were confirmed with univariate and conditioned regressions. Accordingly, patients were stratified based on stable warfarin doses as sensitive (<4 mg/day), control (4-6 mg/day) and resistant (>6 mg/day). Genetic variants associated with warfarin response among the study cohort were used to perform a multivariate regression analyses to develop a genetic-guided dosing algorithm tailored for Puerto Ricans. The CYP2C9rs2860905 SNP was found to be strongly associated with warfarin dose requirements in Puerto Ricans. The CYP2C9 rs2860905 SNP tags four haplotypes that represent the trihybrid admixture of Puerto Ricans. Therefore, haplotypes harboring the rs2860905 variant are more informative in predicting warfarin dose among Puerto Ricans than the common single segregating SNPs (i.e., CYP2C9*2 and CYP2C9*3) relevant to Europeans. DMET Plus array confirmed the strong association of VKORC1 (GeneID: 79001) and CYP2C9 (GeneID: 1559) with warfarin dose requirements, but also identified other polymorphisms in CES2 (GeneID: 8824) and ABCB1 (GeneID: 5243) associated with warfarin resistance (>6 mg/day). Ancestry analysis showed that Puerto Ricans from Veteran Affairs Caribbean Healthcare System (VACHS) using warfarin had higher Native American proportions than Puerto Ricans from the 1000 Genomes project; however, this difference was not significant. Incorporation of rs2860905 in a regression model (R2=0.60 MSE=0.38) that also included additional genetic predictors (i.e., VKORC1-1639G>A; CYP2C9 rs1856908; ABCB1 rs10276036; CES2 rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2=0.132 versus 0.023 and 0.007, respectively, p<0.001). Interestingly, deep vein thrombosis and diabetes were found associated with high warfarin dose requirements among Puerto Ricans. Our results support the use of CYP2C9 rs2860905 along with other genetic markers [e.g., VKORC1(GeneID: 79001 )] and clinical covariates to predict warfarin dose in Puerto Ricans. Although our findings need further replication, this study contributes to the field of Pharmacogenetics and to improve anticoagulation therapy among Puerto Ricans.

  Study phs001496

• Next Generation Mendelian Genetics: Familial Hemophagocytic Lymphohistiocytosis

  The NHGRI Next Generation Mendelian Genetics project uses exome resequencing to identify variants in unsolved Mendelian diseases. Familial hemophagocytic lymphohistiocytosis (fHLH) is a serious immune disorder that results from defective cytotoxic lymphocyte function. Autosomal recessive mutations in PFP1, UNC13D, STX11, STBP2, or RAB27, and hemizygous mutations in SH2D1A or BIRC4, account for known causes of the disease, but 30-70% of patients in North America lack a known genetic etiology. This project was designed to identify additional genetic abnormalities from HLH patients. The exome sequences of four unrelated individuals with a diagnosis of HLH, but without mutations in genes known to cause disease, were obtained by massively parallel DNA sequencing.

  Study phs000537

• International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN)

  The genetic makeup of an individual strongly influences the risk of developing systemic lupus erythematosus (SLE). The identification of genes that predispose an individual to SLE will lead to earlier and better diagnosis, better treatments, and possibly prevention. To this end, the International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) was formed in 2005 and is composed of lupus researchers who agreed to pool their knowledge and resources to search for genes that predispose to lupus. Eight laboratories contributed DNA samples for genotyping at the Broad Institute and association with SLE was performed by the Data Coordinating Center (Wake Forest University), as part of a four stage study design. Stages one and two of this design were graciously funded by the Alliance for Lupus Research (www.lupusresearch.org). In this stage of the study, approximately 767 SLE patients (cases) were compared to approximately 383 non-SLE patients (controls) for differences among the Illumina HumanHap300. The affected individuals are all females of European decent. 82% of the cases are the index case from multiplex pedigrees for SLE and the remaining 18% have self-reported first degree relatives with SLE. A detailed summary of the methods and results can be found in the manuscript in Nature Genetics February 2008 by SLEGEN "Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants ITGAM, PXK, KIAA1542 and other loci". (Please see also Study Accession: phs000202.v1.p1)

  Study phs000216

• Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration.

  The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines revealed a unique form of structural variation, termed heterocateny here, characterized by heterogeneous, interrelated, and repetative patterns of concatemerized virus and host DNA segments. Evidence of heterocateny was detected in extrachromosomal and/or intrachromosomal DNA in all cases. Unique breakpoint sequences shared across structurally heterogeneous virus-host concatemers within each cancer facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that unstable virus and virus-host concatemers in ecDNA or integrated form mediate insertion into and excision from chromosomes, capture, rearrangement, and rolling-circle amplification of host DNA, and chromosomal rearrangements. The data indicate that heterocatena is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intra-tumoral heterogeneity and clonal evolution.

  Study EGAS00001006652