14977 results for "cancer studies using rna-seq"

in 17.39 milliseconds.

• Foregut Microbiome and Risk of Gastric Intestinal Metaplasia, and Gastric Cancer Risk

  The study is composed of two sub-studies. The first study, conducted by NYU Grossman School of Medicine, is a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. Shotgun metagenomic sequencing using oral wash samples from the 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs were conducted. The other study, conducted by Vanderbilt University Medical Center, is a prospective case-control study on the oral microbiome and gastric cancer risk, utilizing shotgun metagenomic sequencing data of pre-diagnostic buccal samples from 319 Asians, 118 African Americans and 51 European Americans. This study includes data from three population-based studies: the Southern Community Cohort Study (SCCS), the Shanghai Women's Health Study (SWHS), and the Shanghai Men's Health Study (SMHS). The SWHS and SMHS include 74,941 women aged 40-70 years and 61,480 men aged 40-74 years, respectively, who were permanent residents of Shanghai and recruited to the cohorts between 1997 and 2006. The SCCS is an ongoing prospective cohort study, including ~86,000 participants recruited during 2002 and 2009 from 12 Southeastern states. Nearly 67% of study participants are African Americans (AAs) and the remaining are European American (EA) subjects.

  Study phs002566

• Bulk RNAseq - Calprotectin in vitro effects on human early hematopoiesis

  To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform. Bulk RNAseq 4 conditons : -Control - Calprotectin - IL-6 - Calprotectin+IL-6

  Study EGAS50000000454

• Investigating immunopathological signatures associated with COVID-19 severity post Omicron

  The aim of this study was to investigate the type and duration of protective immunity alongside immunopathological signatures associated with COVID-19 severity. RNA sequencing was performed using the Illumina Stranded mRNA Prep Ligation kit to investigate the protein coding transcriptome of PBMC cells. T cell receptor (TCR) repertoire profiling was performed with the TakaraBio SMART-Seq Human TCR (with UMIs) on PBMC cells to investigate the depth and persistence of SARS-CoV-2 targeting TCRs. The cohort (n=20) consisted of 10 non-hospitalised and 10 Hospitalised individuals with samples analysed 3 months post positive SARS-CoV-2 PCR.

  Study EGAS50000000926

• Transcriptome analysis of endometrial organoids derived from patients with Mayer-Rokitansky-Küster-Hauser syndrome

  The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. The cause of the disease is still enigmatic. Here, we developed organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically they share great similarity between healthy control organoids and are fully hormone responsive. Transcriptome analysis using RNA-seq identified possible disease-causing pathways altered in MRKH patients during development of the female reproductive tract. Thus, the organoid cultures provide a powerful research model for further insight into disease-causing alterations.

  Study EGAS00001005908

• Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression

  Leiomyosarcoma (LMS) is a smooth muscle-derived mesenchymal cancer commonly found to have recurrent loss of tumor suppressor genes and a poorly defined oncogenic program. Empiric cytotoxic chemotherapy is the standard systemic treatment for LMS, and while more targeted and effective therapies are urgently needed, insights into therapeutic vulnerabilities in LMS have been limited by available preclinical models. We generated a panel of LMS patient-derived xenograft (PDX) models and evaluated fidelity to their tumors of origin using RNA sequencing and ultra-low passage whole-genome sequencing (ULP-WGS). Data available at dbGaP include RNA sequencing and ULP-WGS of primary tumors and early and late passages of PDX. 

  Study phs002587

• RNA-seq in insulinomas

  RNA-seq datasets in human insulinoma samples

  Dataset EGAD50000000462

• Transcriptome of insulinomas

  Characterization of the transcriptome of insulinomas by RNA-seq.

  Study EGAS50000000320

• RNA-Seq data for Juvenile Pilocytic Astrocytomas

  RNA-Seq data for 9 JPA samples.

  Dataset EGAD00001009043

• Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases. Cancer Discovery doi: 10.1158/2159-8290. PMID: 30787016 PMCID: PMC6497554

  The BAM files for WES and RNA seq used in the article "Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases." on cancer Discovery 2019. PMID: 30787016 PMCID: PMC6497554. Authors : Grant M Fischer, ..., Michael A Davies.

  Dataset EGAD00001005046

• Tracing early predictors of glioma evolution under therapy

  Clonal evolution drives cancer progression and therapeutic resistance. Recent studies revealed divergent longitudinal trajectories in gliomas, but early molecular traits steering post-treatment cancer evolution remain unclear. We analyzed sequencing data of 544 initial-recurrent adult diffuse glioma pairs to identify genomic and transcriptomic early predictors of tumor evolution in each molecular subtype.

  Study EGAS00001006894

• Additional RNA-seq, ChIP-seq, and ATAC-seq files for PCGP SJERG

  This dataset contains RNA-seq, ATAC-seq, and ChIP-seq samples from the SJERG cohort. We applied ChIP-Seq for Dux4 on two B-cell ALL cell-lines(REH, Nalm6) along with INPUT. ATAC-Seq on two B-cell ALL cell-lines(REH, Nalm6) and xenograft of a B-cell ALL patient(ERG000016).

  Dataset EGAD00001002654

• Adipose Tissue Omics In Obesity

  This project used a multi-omics approach to study the adipose tissue transcriptome in humans with and without obesity. Our human cohort included males and females between the ages of 18-80 who underwent elective abdominal surgery at the University of Michigan and the Ann Arbor Veterans Affairs Healthcare System.Patients with advanced cancer or immuncompromised status were excluded. Visceral adipose tissue (VAT/omental) and subcutaneous adipose tissue (SAT/abdominal wall) were collected from subjects with obesity (BMI>=35) at the beginning of elective surgical procedures, placed on ice, and transported back to the laboratory for immediate processing. For adipose tissue stromal cells (ASC) isolation, adipose tissue was digested with Type II collagenase (2 mg/mL in PBS/2% BSA) at 37oC, 60min, centrifuged at 250 rcf, and the stromal-vascular cell pellet was retrieved, plated overnight, and the adherent cells passaged three times to enrich for ASC, which were then frozen in DMEM/F12, 15% fetal calf serum, and 10% DMSO in liquid nitrogen until use. Single nuclear sequencing was performed on preparations from intact adipose tissue. Bulk RNA sequencing and single cell sequencing were performed on ASC isolated from intact adipose tissue and cultured in 2D and 3D culture systems. We currently apply bulk, single cell, and single nuclear sequencing analyses to these tissues. One component of this project studies single nuclear sequencing in nuclei isolated from intact adipose tissues from human subjects with obesity, focusing on depot comparisons (VAT vs. SAT). This cohort also permits comparisons of adipose tissue transcriptomes between male and female subjects, controlling for age and BMI. Primary findings to date include identification of multiple ASC, adipocyte, and endothelial cell (EC) subpopulations, T-cell, and macrophage (MAC) populations that are in concordance with and expand upon other published datasets. Of two dominant ASC subpopulations, one (inflammatory-mesothelial, IM- ASC) is present in VAT, but absent in SAT, while the other (fibroadipogenic, FA-ASC) is present in both VAT and SAT. We identified multiple EC subtypes with features of lymphatic, venous, and arterial EC, and a PRDM16 expressing population with features of an EC progenitor. Immune cell populations match recent experimental validation of lipid-activated macrophage (LAM) phenotypes, TIM4 macrophages, and a prominent population of MRC1/CD206+ resident AT macrophages with expression signatures related to glucocorticoid activation. These data support depot-specific differences in ASC subpopulations and previously unrecognized EC heterogeneity within human AT, with the potential to shed light on functional differences in AT depot and disease state. Planned future studies include ATAC-Seq and other omics analyses. Another component of this project studies transcriptional responses of ASC in vitro to various stimuli, including different matrix environments. Current data includes bulk RNA Sequencing of human ASC from VAT and SAT differentiated into mature adipocytes in hydrogels of differing stiffness (3%, 5%, 10%) to define transcriptional responses to matrix environments of different stiffness. Primary findings to date include enrichment of adipogenesis and lipid and oxidative metabolic gene pathways in adipocytes in 5% relative to 3% hydrogels, while fibrotic gene pathways have been enriched in 3% hydrogels. These data demonstrate that intermediate density matrix promotes a more adipogenic, less fibrotic adipocyte phenotype geared towards increased lipid and aerobic metabolism. Planned future studies include expansion of intact tissues from our cohort studied with single nuclear sequencing, as well as further study of ASC responses in vitro to different biologic stimuli, including different matrix environments.

  Study phs003390

• Multi-Omic Profiling of Glioma Patient Tumors and Patient-Derived Model Systems

  We have created a resource of transcriptomic (RNAseq), genomic (whole-exome seq), and lipidomic (untargeted shotgun) profiling data from over 175 molecularly diverse glioma tumors and derivative models in orthotopic mouse xenografts and gliomasphere cultures from over 110 unique patient tumor lines. Provided in this dataset are matched bulk RNA and whole-exome paired-end sequencing data from resected gliomas and derived model systems performed on Illumina HiSeq and NovaSeq sequencing instruments. This comprehensive dataset powers multiple studies aiming to derive molecular signatures of intertumoral heterogeneity and perturbation responses in glioma. Through integrative multi-omic analyses in Minami, et al., 2023, PMID: 37236196, we identified that CDKN2A deletion remodels the GBM lipidome and consequently primes CDKN2A-deleted tumors for ferroptosis. Lipidomics data related to this study are publicly available here. In another study, we used a combination of molecular profiling and functional profiling of apoptotic potential to stratify patients into groups with differential vulnerability to the current standard-of-care in gliomas, and in combination with drugs targeting intrinsic apoptosis, largely informed but not limited to TP53 mutation status.

  Study phs003286

• Sputum RNA-Seq from Asthmatic Patients for Microbes and Genes

  RNA-seq files and other data associated with an investigation of the relationship between microbes, genes and immune cells present in the sputum of humans with asthma.

  Study phs002224

• Summary statistics of meta-analysis using two genome-wide association study of inflammatory bowel disease in Koreans.

  Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is thought to develop due to dysregulated mucosal immune responses to gut flora in genetically susceptible individuals. Crohn’s disease (CD) and ulcerative colitis (UC) are the two major subtypes of IBD. To identify additional susceptibility loci for IBD in Asians, we performed meta-analyses using two genome-wide association studies.

  Study EGAS00001005026

• Longitudinal single-cell transcriptomic study in patient-derived xenografts of pediatric T-ALL

  In this study, we conducted single cell full length total RNA sequencing (VASA-seq) on 13 matched pediatric T-ALL PDX samples at initial diagnosis and relapse, along with 5 non-relapsing PDX samples collected at initial diagnosis. We identified a subpopulation of T-ALL cells with stem-like cell features that expands substantially at relapse indicating resistance to first-line therapy. Chemotherapy resistance was further validated through functional testing: Two samples were subjected to in-vitro drug testing, treated with Cytarabine for three days, followed by single-cell transcriptomic analysis using 10x Genomics. Additionally, in-vivo drug testing was conducted on one sample, involving re-engraftment into mice and treatment with a combination of Vincristine, Doxorubicin, and Dexamethasone. Single-cell transcriptomic analysis using 10x Genomics was performed after 0, 15 and 30 days of treatment.

  Study EGAS50000000582

• Single cell RNAseq of PBMC from RCC patients

  Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had >80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.

  Study EGAS00001004451

• single nuclei RNASeq of 5 regions of the human prenatal brain

  Data generated through single nuclei RNA sequencing on 5 regions of the brain (frontal cortex, ganglionic eminence, hippocampus, thalamus and cerebellum) from 3 fetuses (two of 14 and one of 15 post-conception weeks, all female). Tissue was acquired from the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) with ethical approval. snRNA-seq libraries were prepared from ∼10,000 nuclei from each sample using Chromium Single Cell 3ʹ (v3) reagents (10X Genomics). Quality control of libraries was performed using the Agilent 5200 Fragment Analyzer before sequencing on an Illumina NovaSeq 6000 to a depth of at least 865 million (median = 1.01 billion) read pairs per library. Raw sequencing data were converted into FASTQ files. For a full description of data generation, please see Cameron et al, Biological Psychiatry 2022, https://doi.org/10.1016/j.biopsych.2022.06.033.

  Study EGAS00001006537

• Proteogenomic Characterization Unveils Biomarkers Associated With Chemoresistance in Muscle Invasive Bladder Cancer

  Cisplatin-based neoadjuvant chemotherapy (NAC) combined with radical cystectomy has been used as a standard of care for patients with clinically non-metastatic muscle invasive urothelial bladder cancer, but 40-50% patients will benefit from the treatment. Molecular subtypes of muscle invasive bladder cancer (MIBC) provide a possible biomarker roadmap that may help identify patients who may or may not respond to NAC. Recently, by integrating Mass Spectrometry-based proteomics, proteogenomic studies from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) have demonstrated the potential of this approach in prioritizing candidate driver genes and facilitating understanding of the chemotherapy resistance mechanisms. To demonstrate the proteogenomic workflow for investigating the mechanisms underlying chemotherapy resistance in MIBC, we conducted proteogenomic characterization of 46 pre- and 14 post- treatment tumors, including whole exome sequencing (WES), mRNA sequencing, Tandem Mass Tag (TMT)-proteomics, or TMT-phosphoproteomic. These samples were selected from an initial cohort of 143 MIBC tissues and filtered by tumor purity, clinical history, pathological response, and proteomic quality control metrics. The final cohort comprised samples from 53 patients, including 45 with both genomic and proteomic data and 8 with genomic data only.Our multi-omics-based clustering reveals subtypes associated with chemotherapy sensitivity. Protein abundance of a short isoform of ATAD1 and RAF family proteins were identified as biomarkers of chemosensitivity which highlights the importance of proteomics data. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive benefit of combination therapy targeting these proteins. Our data analysis clearly demonstrates that proteogenomic plays an important role in uncovering potential resistance mechanisms that operate only at protein and Post-Translational Modification (PTM) levels. Proteomics data can be accessed through PRIDE with ID PXD060290. RNA-seq and whole-exome sequencing (WES) FASTQ files are archived in the dbGaP database.

  Study phs004049

• bulk RNA-seq data

  a total number of 99 bulk RNA-seq lymphoma samples

  Dataset EGAD50000000631

• SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors

  Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we studied derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids revealed a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently revealed patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 drives patient-specific epigenetic reprogramming underlying MRT tumorigenesis.

  Study EGAS00001007590

• MP2PRT: Genomic and Molecular Characterization of Biomarkers Associated with Tumor Angiogenesis, DNA Repair, and Immunologic Tolerance using Samples from the NRG Oncology Phase 3 Randomized Trial, GOG-0240 (NCT00803062)

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study is one of the selected studies under this program. For this study, genomic characterization (WGS, WXS, Total RNAseq, miRNAseq) has been performed on cervical tumor tissue from patients with advanced disease (persistent, recurrent, and metastatic) and matching germline samples. It is hypothesized that the characterization of these tissues using next generation sequencing will lead to the identification of relevant novel genetic aberrations within the immunologic, DNA repair, and tumor angiogenesis domains that dichotomize the study population into exceptional responders and non-responders to systemic therapy, with a spectrum of response manifesting between the two extremes.

  Study phs002293

• Transcriptome Sequencing PPGL

  RNA library preparation of samples with RNA Integrity Number (RIN) > 5.5 (median 7.1; range 5.6-8.9) was performed as described in the TruSeq Stranded mRNA Library Prep Kit (Illumina, RS-122-2101). Briefly, 0.7-1 µg total RNA PolyA+ fraction was purified and randomly fragmented, converted to double stranded cDNA and processed through subsequent enzymatic treatments of end-repair, dA-tailing, and ligation to adapters. Adapter-ligated library was completed by PCR with Illumina PE primers. The resulting purified cDNA library was applied to an Illumina flow cell for cluster generation and sequenced on an Illumina HiSeq2500 on a 51bp single-read format following manufacturer's protocols. cDNA libraries from FFPE tumors and low integrity RNA’s (RIN<5.5) from FF tumors (median 2.4; range 1-5.5) but % of fragments > 200 nucleotides higher than 20% (median 57.5; range 20-96) were prepared using QuantSeq 3’ mRNA-Seq Library Prep Kit FWD for Illumina (Lexogen, 015) with a UMI Second Strand Synthesis Module for QuantSeq FWD (Lexogen, 081), vendor’s protocol for low input/ low quality/ FFPE RNA using 200-500 ng of total RNA, according to availability, was used as starting material. PCR Add-on Kit for Illumina (Lexogen, 020) was used to adjust the library amplification number of cycles. Libraries were applied to an Illumina flow cell for cluster generation and sequenced on NovaSeq6000. Image analysis, per-cycle basecalling and quality score assignment was performed with Illumina Real Time Analysis software. Demultiplexing of BCL files to FASTQ format was performed with the bcl2fastq Software (Illumina).

  Study EGAS00001006044

• scRNA dataset for 15 samples

  This dataset includes single cell (sc)RNA-seq of N=3 patient-derived xenograft (PDX) samples profiled at baseline (no drug treatment) and N=12 samples from one PDX profiled during the course of treatment (N=1 sample each for 4 treatment arms x 3 timepoints). The dataset includes bam files that have been purged of reads mapping to cells where a majority of the reads from that cell mapped to the mouse genome. All scRNA-seq data were generated using the Chromium Next GEM Single Cell 5' Reagent Kits v2 (Dual Index) from 10X Genomics.

  Dataset EGAD50000001424

• Paired Biopsy Project: West Coast Dream Team

  This project aims to analyze the paired metastatic biopsy samples from patients with metastatic castration-resistant prostate cancer (mCRPC), collected before the initiation of the first-line androgen receptor signaling inhibitor (ARSI) for mCRPC and after radiographic disease progression on that ARSI, to understand the resistance mechanisms. We generated both whole genome sequencing (WGS) and RNA-seq data on these samples. A majority of these samples have been deposited in the public domain along with prior publications, and this project contains the 16 WGS samples that have not yet been deposited.

  Study EGAS50000000327

• bulk Exome-seq of the 5 HCC patients which also have the single cell T cell RNA-seq data

  bulk Exome-seq data of the 5 HCC patinets. Single cell RNA seq data of these patients was under the accession number EGAD00001003337

  Dataset EGAD00001004149

• RNA sequencing from patient-derived intestinal organoids

  RNA from the duodenal organoids was isolated using an RNeasy Kit (Qiagen, Hilden, Germany) following the manufacturer’s instructions. RNA purity and concentration were measured using a NanoDrop One spectrophotometer (NanoDrop Technologies, Wilmington, Delaware, USA). Preparation of the RNA library and transcriptome sequencing was conducted by Novogene Co., LTD (Cambridge, UK). Messenger RNA was purified from total RNA using polyA selection and subjected to library construction. Sequencing was performed on an Illumina platform, and 150 bp paired-end reads were generated.

  Study EGAS50000000338

• RNA-seq of human astroblastomas

  RNA-seq for fusion gene discovery of human astroblastomas

  Dataset EGAD00001009664

• Transcriptomic analysis of the NA-PHER2 clinical trial

  We performed whole transcriptome RNA sequencing on serial tumour biopsies collected at baseline, Day 14, and after completion of all neoadjuvant therapy from the NA-PHER2 trial. Patients received neoadjuvant treatment with the combined regimen of trastuzumab, pertuzumab, palbociclib with or without addition of fulvestrant. Transcriptomic profiles were generated from 143 samples (Baseline n = 53, Day 14 n = 49, Surgery n = 41) corresponding to 53 of the 58 patients enrolled in NA-PHER2 trial (91.4%). RNA sequencing was performed on total RNA samples derived from formalin-fixed, paraffin-embedded (FFPE) tissue sections. RNA-Seq libraries were produced using NEBNext® Ultra™ II Directional RNA Library Prep Kit. The capture was then performed on cDNA libraries with the Twist Human Core Exome Enrichment System according to supplier recommendations (Twist Bioscience). The obtained eluted-enriched DNA samples was then sequenced on an Illumina NovaSeq as paired-end 100bp reads. FASTQ files are provided.

  Dataset EGAD50000000363

• Genomic Analysis of Fibrolamellar Hepatocellular Carcinoma

  Fibrolamellar hepatocellular carcinoma (FL-HCC) is a very rare and distinct subtype of hepatocellular carcinoma that occurs in the previously healthy livers of adolescents and young adults. The low incidence rate has kept FL-HCC an understudied cancer, thus the list of FL-HCC markers is limited and the genetic alterations driving its growth have remained unknown. In order to gain a better understanding of the molecular mechanisms underlying FL-HCC initiation and progression, we performed an in-depth genomic analyses of one tumor followed by immunohistochemistry validation on seven other tumors. We showed the expression of neuroendocrine markers in FL-HCC. In addition, DNA/RNA sequencing revealed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. Through in vitro studies, we demonstrated the oncogenic properties of these fusion transcripts. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease.

  Study phs000828