12450 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

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• Whole genome and transcriptome analysis of a sporadic and recurring parathyroid carcinoma

  Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.

  Study EGAS00001000484

• Profiling the unique protective properties of intracranial arterial endothelial cells

  Cardiovascular disorders, like atherosclerosis and hypertension, are increasingly known to be associated with vascular cognitive impairment (VCI). In particular, intracranial atherosclerosis is one of the main causes of VCI, although plaque development occurs later in time and is structurally different compared to atherosclerosis in extracranial arteries. Recent data suggest that endothelial cells (ECs) that line the intracranial arteries may exert anti-atherosclerotic effects due to yet unidentified pathways. To gain insights into underlying mechanisms, we isolated post-mortem endothelial cells from both the intracranial basilar artery (BA) and the extracranial common carotid artery (CCA) from the same individual (total of 15 individuals) with laser capture microdissection. RNA sequencing revealed a distinct molecular signature of the two endothelial cell populations of which the most prominent ones were validated by means of qPCR. Our data reveal for the first time that intracranial artery ECs exert an immune quiescent phenotype. Secondly, genes known to be involved in the response of ECs to damage (inflammation, differentiation, adhesion, proliferation, permeability and oxidative stress) are differentially expressed in intracranial ECs compared to extracranial ECs. Finally, Desmoplakin (DSP) and Hop Homeobox (HOPX), two genes expressed at a higher level in intracranial ECs, and Sodium Voltage-Gated Channel Beta Subunit 3 (SCN3B), a gene expressed at a lower level in intracranial ECs compared to extracranial ECs, were shown to be responsive to shear stress and/or hypoxia. With our data we present a set of intracranial-specific endothelial genes that may contribute to its protective phenotype, thereby supporting proper perfusion and consequently may preserve cognitive function. Deciphering the molecular regulation of the vascular bed in the brain may lead to the identification of novel potential intervention strategies to halt vascular associated disorders, such as atherosclerosis and vascular cognitive dysfunction.

  Study EGAS00001004479

• Prevention and Early Treatment of Acute Lung Injury Network - Vitamin D to Improve Outcomes by Leveraging Early Treatment (PETAL VIOLET-BioLINCC)

  Data Access NOTE: Please refer to the "Authorized Access" section below regarding accessing data through the BioData Catalyst ecosystem. The data from this accession is not available for download through dbGaP. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from PETAL VIOLET include Plasma and Whole Blood. Please note that use of biospecimens in genetic research is subject to a tiered consent. Specimens may not be used to produce commercial products.Objectives: To evaluate the effect of short-term vitamin D supplementation on mortality among critically ill patients with a vitamin D deficiency.Background: Observational data indicate that vitamin D deficiency is common among critically ill patients and constitutes a potentially modifiable risk factor associated with longer lengths of stay in the hospital and intensive care unit (ICU), lung and other organ injury, prolonged mechanical ventilation, and death. In a previous phase 2 trial, vitamin D supplementation administered to vitamin D-deficient, critically ill patients was associated with lower observed mortality than placebo at 28 days and at 6 months. Because of the need for a larger, phase 3 trial, the PETAL-VIOLET study was initiated to determine if early administration of high-dose vitamin D3 would reduce all-cause mortality among critically ill patients with a vitamin D deficiency.Participants: 1360 patients underwent randomization, 690 were assigned to the vitamin D group and 668 were assigned to the placebo group. Of the 1078 patients confirmed to have a vitamin D deficiency by liquid chromatography-tandem mass spectrometry (LC-MS-MS), 538 had been assigned to the vitamin D group and 540 had been assigned to the placebo group.Design: PETAL-VIOLET was a multicenter, double-blind, placebo-controlled, phase 3 trial. Patients were enrolled within 12 hours after the clinician's decision to admit the patient to the ICU from the emergency department, hospital ward, operating room, or outside facility. Patients were tested for vitamin D deficiency, with a threshold of plasma 25-hydroxyvitamin D level of less than 20 ng per milliliter. Patients were randomly assigned in a 1:1 ratio, stratified according to site, to receive either a single enteral (administered orally or through a nasogastric or orogastric tube) dose of 540,000 IU of vitamin D3 or matched placebo, in liquid form, administered within 2 hours after randomization.Conclusions: After the first interim analysis, the data and safety monitoring board recommended that the trial be stopped for futility.A single 540,000 IU enteral dose of vitamin D3 administered early during critical illness rapidly corrected vitamin D deficiency but did not provide an advantage over placebo with respect to mortality or other clinically important end points.

  Study phs003879

• Proteogenomic discovery of a novel class of cancer antigens by HLA ligandome analysis of colon cancer tissues

  CD8+ T cells recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathological conditions such as cancer. Recent advances in proteogenomic analysis of HLA ligandomes have demonstrated that cells present a subset of cryptic peptides derived from non-coding regions of the genome; however, the roles of cryptic HLA ligands in tumor immunity remain unknown. In the present study, we comprehensively and quantitatively investigated the HLA class I ligandome of a set of human colorectal cancer (CRC) and matched normal tissues, showing that cryptic translation products account for a small fraction of the HLA class I ligandome and serve as antigens for patient T cell surveillance against colon cancer.

  Study JGAS000280

• Duplexseq of the interstrand crosslinks_WGS

  One of the most dangerous forms of DNA damage are interstrand crosslinks (ICLs), which covalently crosslink the two strands of the DNA double helix. The repair of these lesions is crucial for cellular survival due to their ability to block transcription and DNA replication. Initially, the major pathway that has been described in ICL repair involves a network of 22 genes that are mutated in a severe human genetic disease known as Fanconi Anemia (FA). Using synthetic lethality screens in the near-haploid human HAP1 cell line, we recently identified two potentially novel regulators of ICL repair, C1orf112 and THAP12. Loss of C1orf112 and THAP12 causes hypersensitivity to ICL-inducing DNA damaging agents, such as Mitomycin C (MMC). Additionally, C1orf112-depleted cells show elevated levels of micronuclei and accumulation of DNA damage in S-phase. To better understand how C1orf112 and THAP12 mediate the repair of ICLs, we want to perform mutational signature analysis, using the BotSeq method. Therefore, WT, C1orf112 and THAP12 knockout cells were cultured in vehicle or MMC treated conditions for 10 days and the genomic DNA was isolated. FANCA and FANCD2 knockout cells are taken along as controls in this experimental setting. . This dataset contains all the data available for this study on 2023-04-20.

  Dataset EGAD00001010298

• Methylome profiling of Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) and a patient derived cell-line model

  Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using the twist human methylome panel.

  Dataset EGAD50000000040

• BCL11B Enhancer Hijacking by t(14;16)(q32;q24) Translocation Defines a Novel High-Risk Subtype of T-ALL

  We performed integrated analysis of pediatric and adult T-ALL and mixed phenotype acute leukemias (MPALs) by whole-genome and whole-transcriptome sequencing.

  Study EGAS50000001254

• Congenital mesoblastic nephroma and infantile fibrosarcoma

  The genetic basis of many rare childhood cancers remains unknown. These include a spectrum of infant soft tissue tumors without canonical gene fusions, encompassing congenital mesoblastic nephroma (CMN) of the kidney and infantile fibrosarcoma (IFS). Here, we integrated whole genome and transcriptome sequencing and identified diagnostic markers and novel therapeutic strategies.

  Dataset EGAD00001003885

• Fecal microbiome of T2D patients undergoing semaglutide or empagliflozin treatment

  The gut microbiome has been shown to be affected by the use of many human-targeted medications, and the interaction can be bidirectional. This has been clearly demonstrated for type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described. We investigated the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyzed whether the pre-treatment gut microbiome can predict the treatment efficacy. Twenty subjects (10 women and 10 men) were enrolled in the study between November 2019 and January 2023 from the University of Tartu Hospital, Tartu, Estonia. All participants had been diagnosed with type 2 diabetes. The study group taking semaglutide included 6 women and 4 men, and the group prescribed empagliflozin included 4 women and 6 men. Gut microbiome fecal samples donated at four timepoints (Baseline, Month 1, Month 3; Month 12) were studied using 16S ribosomal RNA gene sequencing and analysis.

  Dataset EGAD50000000756

• PAS Pedigrees: Identification of novel genetic variants contributing to cardiovascular disease in pedigrees with premature atherosclerosis.

  The heritability of CVD has been estimated to be between 40 and 55%. Due to the low MAF, PAS-causing mutations cannot be identified by indirect genotyping because their presence cannot be inferred from common haplotypes, as has been done successfully to uncover common risk variants by GWAS. It has been shown by Ng et al that the causative gene for rare syndromes can be unequivocally identified by sequencing the exomes of only four cases and eight controls. We expect exome sequencing to result in a high number of mutations and non-causitive coding variants.

  Study EGAS00001000052