14662 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

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• Rare Genetic Steroid Disease Consortium (GSD) Apparent Mineralocorticoid Excess (AME) Syndrome Natural History Clinical Protocol

  The objective of this project is to observe the natural history of apparent mineralocorticoid excess (AME). AME is a rare monogenic hypertensive disease first described by the Principal Investigator, Dr. Maria I. New, in 1977 [1], for which the first mutation in the causative HSD11B2 gene was reported by her group in 1995. [2] Little is known about the progression of this rare hypertensive disorder, which is defined by the presence of hypertension in conjunction with low renin, low to absent levels of the mineralocorticoid aldosterone, elevated urinary cortisol/cortisone metabolite ratio 5β-tetrahydrocortisol (THF) + allo-THF/ tetrahydrocortisone (THE) (i.e., THF+αTHF/THE) and the presence of mutations in the HSD11B2 gene on both alleles. The range of symptoms reflecting progressive end-organ damage is wide in the small number of affected individuals studied to date. It is important to develop accurate information on the longitudinal pattern of progression (natural history) of AME not only because it may improve the care of affected individuals, but also because it may serve as a platform for understanding the role of mineralocorticoid excess in other forms of low-renin hypertension, which constitute 40% of all forms of hypertension. In this study, we will recruit as widely as possible through the Rare Diseases Clinical Research Network (RDCRN) to identify individuals with the triad of low renin, low aldosterone, and elevated urinary THF+αTHF/THE and confirm their disorder as AME by molecular genetic testing of the HSD11B2 gene. We will gather clinical and biochemical data yearly for the duration of the grant. We will describe phenotype and genotype at diagnosis and follow the progression or regression of symptoms over time under standard treatment, with rigorous review of end organs potentially damaged by chronic hypertension. Finally, we will study the natural history of the carriers of HSD11B2 mutations, i.e., the heterozygote relatives of the probands, in order to ascertain evidence of existing or developing hypertension and resulting end-organ damage. This will be the first rigorous study of AME heterozygotes. The participant accrual for AME-affected patients and the carriers of HSD11B2 mutations will be at least two years, but as long as seven years.

  Study phs000603

• Changes in Oral and Gut Microbiota and Incidence and Severity of Patient-Reported Symptoms in Pre- and Post-Kidney Transplant Patients

  This novel prospective cohort explores the relationships between oral and fecal microbiome features (alpha and beta diversity, differential relative abundances of bacterial taxa, and functional genes) and the incidence and severity of psychoneurological symptoms (e.g., pain, fatigue, depression, anxiety, and sleep disturbance) before and after patients receive a kidney transplant from a live donor. Thirty-five subjects provided fecal and saliva specimens for shotgun metagenomic sequencing of gut and oral microbiomes at 3 timepoints: 1) within 4 weeks prior to the transplant surgery (at end-stage kidney disease), 2) 1-3 weeks after the transplant surgery, and 3) at 3 months after the transplant (after restoration of kidney function). Subjects were enrolled between October, 2018, to November, 2021, and all study visits were completed by March, 2022. Data collected includes: Demographic (age, biological sex at birth, race/ethnicity, marital status); clinical data (body mass index, dialysis status, type of dialysis, high vs. low risk immune-suppression protocol, antibiotics during study period); laboratory data (serum creatinine; estimated glomerular filtration rate; serum blood urea nitrogen; immunosuppression trough levels), and outcome data (symptoms such as pain interference, pain intensity, fatigue, anxiety, depression, sleep disturbance, acute rejection, delayed graft failure, graft loss, post-transplant infections, and health-related quality of life). Incidence and severity of symptoms, including pain interference, pain intensity, fatigue, sleep dysfunction, and anxiety/depression-like symptoms, were measured using the Patient Reported Outcome Measurement Systems (PROMIS) 57 v2.1. Health related quality of life was assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF v1.3). The objective of this longitudinal study is to characterize changes in microbial features at baseline, before restoration of kidney function, and over time, after restoration of kidney function via kidney transplantation, and to identify relationships between microbiome features and transplant outcomes (rejection, infection, delayed graft function, graft failure), symptom burden, and health-related quality of life. Shotgun metagenomic sequencing of the oral and gut microbiomes will allow a higher-resolution examination of the gut microbiome compared to 16S rRNA gene amplicon sequencing, and will provide direct evidence of metabolic capabilities of the microbiota. This approach will allow us to explore the dynamic nature of symptom burden, and the effects of demographic and clinical variables on the oral and gut microbiomes before and after restoration of kidney function.

  Study phs002199

• Plasma MicroRNA Signatures of Aging

  Background. MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as biological aging indicator and their associations with health outcomes using population-level data. Methods. We quantified plasma expression levels of 2,083 extracellular microRNAs using targeted RNA-sequencing in 2,684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1,930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge –a composite score of age and nine multi-system blood biomarkers–, the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets. Results. We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (ntraining=1158, ntest=772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (nvalidation=754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with ten-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. Conclusions. This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.

  Study EGAS00001008117

• Inflammatory Bowel Disease Exome Sequencing Study

  The Broad Institute and Massachusetts General Hospital (MGH) are launching a new initiative to perform large-scale exome sequencing in inflammatory bowel disease (Crohn's disease and ulcerative colitis). Given the considerable unmet therapeutic need in inflammatory bowel disease (IBD), the recent emergence of rapid and efficient genome sequencing technologies and the compelling evidence for the role of genetics in these disorders have motivated the founding of a collaborative sequencing effort geared toward the discovery of high-impact genetic variants influencing IBD risk that can serve as guides to future therapeutic development and diagnostic tools. The initiative will be directed by experienced IBD researchers from MGH and the Broad Institute but aims to develop a collaborative exome sequencing network that will partner with researchers worldwide. Two large pilot exome sequencing projects are being launched immediately as part of this initiative based on established genetic study designs that enrich for the discovery of rare, high-impact risk and protective variants. 1) Early-onset pediatric IBD: a major focus of the work will surround full-exome sequencing of the earliest-onset childhood IBD cases. It has long been recognized in many diseases that penetrant genetic risk factors are much more likely to be found in cases with unusually early onset. The Broad Institute has completed more than 50,000 exomes in the past two years; and their technical expertise in generating and processing such sequencing data, along with population genetic variation patterns from these experiments, will provide a foundation for obtaining the best outcome in the interpretation of these cases. Samples with IBD onset before 6 years of age - and in some cases going up to age 10 - collected by IBD researchers around the world are welcomed for inclusion in this study. 2) Adult-onset IBD case-control study: Genetic mapping has provided dramatic insights into IBD pathogenesis in recent years, but a substantial amount of heritability - in particular the role of strong-acting rare mutations - is yet to be elucidated. To deliver those insights, IBD cases with an unusually low burden of known genetic risk factors (particularly emphasizing those with positive family history and/or from isolated or enriched populations) will be contrasted with population controls that have an extremely high burden of known IBD risk factors, enhancing discovery of critical protective variants that may provide the best clues for therapeutic development. This project will also be initiated as an international collaboration, particularly among researchers with sample sets with Immunochip genotyping that will enable the immediate genetic identification of these enriched target populations. This project will be supported by the NHGRI Large-Scale Sequencing Program, with all generated data made publicly available to the research community through standard NIH databases.

  Study phs001076

• LITS

  Difference in gene expression values between case and control, log2 values. Blood transcriptome from women participating in the Norwegian Women and Cancer study (NOWAC) Post-genome Cohort taken up to eight years before brest cancer diagnosis. Illumina HumanWG-6 version 3 or Illumina HumanHT-12 expression bead chip, combined on identical nucleotide universal identifiers.

  Dataset EGAD00010001400

• Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocarcinogenesis

  This study contain the WGS and WEX aligned bam files and RNA-seq fastq files for human liver tumors.

  Dataset EGAD00001006426

• Colon cancer amplicon targeted sequencing study contaning WBCs, primary tumor tissue and plasma samples

  This dataset consists of amplicon targeted NGS paired-end raw data (FASTQ R1 and R2) obtained from 148 colon cancer patients. Specifically, we have 148 primary tumor tissue samples, 148 white blood cell samples, and 118 plasma samples collected at baseline.

  Dataset EGAD50000000084

• Dac for "MediMer: A versatile do-it-yourself peptide-receptive MHC class I multimer platform for tumor neoantigen-specific T cell detection"

  Dac for the Study "MediMer: A versatile do-it-yourself peptide-receptive MHC class I multimer platform for tumor neoantigen-specific T cell detection" registered for Frank Momburg, f.momburg@dkfz-heidelberg.de Marten Meyer, marten.meyer@dkfz-heidelberg.de

  Dac EGAC50000000064

• Progressive multifocal leukoencephalopathy (PML)

  We generated RNAseq, ATACseq, Multiomics and CITEseq for patients with Progressive multifocal leukoencephalopathy (PML) to profile the chromatin accessibility, transcriptional profiles and surface proteins at single-cell level.

  Study EGAS50000000139

• Genomic analyses (WES, RNAseq, scRNAseq and scTCRseq) of triple negative breast cancer evolution

  This study explores the evolution of tumor and blood immune microenvironment and related mechanisms that shape breast cancer progression.

  Dataset EGAD50000000117