6414 results for "11+1双色球多少钱一注"

in 13.12 milliseconds.

• Tumor-derived exosomes modulate PD-L1 expression in monocytes

  In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell–derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples. Transfer of CLL-derived exosomes or hY4 alone to monocytes resulted in key CLL-associated phenotypes, including the release of cytokines, such as C-C motif chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the expression of PD-L1. These responses were abolished in Toll-like receptor 7 (TLR7)–deficient monocytes, suggesting exosomal hY4 as a driver of TLR7 signaling. Pharmacologic inhibition of endosomal TLR signaling resulted in a substantially reduced activation of monocytes in vitro and attenuated CLL development in vivo. Our results indicate that exosome-mediated transfer of noncoding RNAs to monocytes contributes to cancer-related inflammation and concurrent immune escape via PD-L1 expression.

  Study EGAS00001002377

• Quantitative analysis of a novel DNA hypermethylation panel for lung cancer diagnosis using bronchial specimens

  Non-diagnostic findings in Transbronchial Lung Biopsy (TBLB) and Endobronchial Ultrasound-guided Transbronchial Lung Biopsy (EBUS-TBLB) are not uncommon. A challenge is to improve lung cancer detection by TBLB/EBUS-TBLB. In order to improve the diagnostic yield of bronchoscopy, we used 850K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules.We found that the combination of HOXA7, SHOX2,and SCT methylation analysis has the best diagnostic yield in 123 bronchial washing (sensitivity: 74·1%; AUC: 0·851) and 172 brushing samples (sensitivity: 86·1%; AUC: 0·915). We developed a kit comprising these three genes and validated the kit in 329 unique bronchial washing samples, 397 unique brushing samples, and 179 unique patients with both washing and brushing samples. The diagnostic accuracy of the panel alone in lung cancer diagnosis was 86·9%, 91·2% and 95% in bronchial washing, brushing, and washing+brushing samples, respectively. The panel's sensitivity in combination with cytology, rapid on-site evaluation (ROSE), and histology in lung cancer diagnosis was 90·8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing+brushing samples. Quantitative analysis of the three-gene panel improves lung cancer diagnosis by bronchoscopy.

  Study EGAS00001007089

• Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types

  Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.

  Study EGAS00001007412

• Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types (RNAseq)

  Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.

  Study EGAS00001007428

• NIPT samples for systematic evaluation of NIPT aneuploidy detection software tools

  This dataset contains two sets of samples. The reference sample set consists of a total of 669 samples that had been reported previously to be euploid by the NIPTIFY screening test. The validation sample set is based on a previously published validation study by Zilina et al. (1), consisting of 423 samples, of which 259 were high-risk pregnancies that had undergone diagnostic invasive prenatal analysis (1). All samples were sequenced with Illumina NextSeq 500 platform, producing 85 bp single-end reads with an average per-sample coverage of 0.32× at the University of Tartu, Institute of Genomics Core Facility, according to the manufacturer’s standard protocols, as described previously (1). This study was performed with the approval of the Research Ethics Committee of the University of Tartu (#315/T-13). 1. Zilina O, Rekker K, Kaplinski L, Sauk M, Paluoja P, Teder H, et al. Creating basis for introducing non‐invasive prenatal testing in the Estonian public health setting. Prenat Diagn [Internet]. 2019 Dec 6;39(13):1262-8. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/pd.5578

  Dataset EGAD00001007712

• Single-cell level characterization of B cell depletion and repopulation following rituximab in systemic lupus erythematosus

  Rituximab, a CD20+ B cell depletion therapy, is frequently used in the treatment of systemic lupus erythematosus (SLE). However, variability in patient response highlights the need for a deeper understanding of the underlying immune cell dynamics of B cell depletion and repopulation. In this study, we conducted longitudinal single-cell profiling of nine SLE patients treated with rituximab from pretreatment to up to 15 months post-treatment. These were compared to eight healthy controls. We profiled PBMCs via 10X Genomics single-cell RNA, surface protein (CITE-seq), B cell receptor (BCR), and T cell receptor (TCR) sequencing and sequenced bulk BCR repertoires in parallel. For single cell sequencing, 10 pools were created with an equal number of cells from 4 samples each. Samples collected at different timepoints from the same patient were distributed across different pools to allow demultiplexing of individuals using genotypes captured from the scRNA-seq data. Libraries were pooled using a ratio of GEX:CITE:TCR:BCR=9:2:1:1 and were sequenced across two lanes of the NovaSeq 6000. For bulk BCR sequencing, individual samples were demultiplexed using primer barcodes and paired-end BCR amplicon reads were merged prior to submission; data are provided as unmapped single-end reads.

  Study EGAS00001006798

• Genome-Wide Association Study of Leprosy and Dapsone Hypersensitivity Syndrome (DHS) in Chinese population

  Leprosy GWAS (1) Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). Due to M. leprae's narrow host range and an inability to be cultured in vitro, the biological investigation of this disease has been difficult. Host genetic factors have been suggested to play an important role in disease development, but few have been identified. In this study, we attempted to identify the host genetic factors by performing a two-stage genome-wide association study (GWAS) in Chinese population. The initial genome-wide scan was done by genotyping 706 patients and 1225 controls using the Illumina HumanHap610 BeadChip, and the follow-up study was performed by genotyping 93 SNPs in three independent samples consisting of 3254 cases and 5955 controls. We identified significant association (P < 10-10) within six genes CCDC122 (13q14), C13orf31 (13q14), NOD2(16q12), TNFSF15 (9q32), HLA-DR (6p21) and RIPK2 (8q21), and suggestive association (P = 5.68x10-6) within LRRK2 (12q12). We also revealed suggestive evidence for C13orf31, LRRK2, NOD2 and RIPK2 to show stronger association in the multibacillary form than the paucibacillary form of leprosy. Our findings highlight the importance of the innate immune response, particularly NOD2-mediated signaling, in leprosy and suggests a new therapeutic target for leprosy. DHS GWAS Dapsone (DDS), as both an antibiotic and an anti-inflammatory agent, has been widely used for preventing and treating pathogen-caused infectious diseases and chronic inflammatory diseases. Currently, about 0.5-3.6% of individuals treated with DDS develop severe dapsone hypersensitivity syndrome (DHS) and the mortality rate is up to about 11-13%. However, until now, no tests are available to predict the risk of DHS. To identify the genetic risk factors of DHS, we performed a two-stage GWAS in Chinese population. In this study, the initial genome-wide scan was done by genotyping 39 DHS cases and 833 controls using Illumina Human 660W-Quad Beadchips and imputed human leukocyte antigen (HLA) molecules. Validation was performed by genotyping 24 SNPs using the Sequenom MassARRAY platform in additional 31 DHS cases and 1,089 controls through genotyping and 32 four-digit HLA-B alleles in an independent series of 37 DHS cases and 201 controls through Roche 454 sequencing. We identified significant association (OR =6.18, P = 3.84x10-13) with SNP rs2844573, which located between the HLA-B and MICA loci. HLA-B*13:01 was confirmed to be a strong risk factor for DHS (OR = 20.53, P = 6.84x10-25) and responsible for the association at rs2844573. The presence of HLA-B*13:01 had a sensitivity of 85.5% and specificity of 85.7% as a predictor for DHS, and its absence can reduce the risk by 7 fold (from 1.4% to 0.2%). HLA-B*13:01 is strongly associated with the development of DHS and can be used as a risk predictor of DHS in the individuals of Chinese and other Asian populations. Leprosy GWAS (2) This is a three-stage GWAS of leprosy in the Chinese population. The genome-wide discovery analysis involved two independent data sets: the new unpublished data set by genotyping 842 leprosy patients and 925 controls from northern and southern China using the Human660w-quad beadchips and a previously published GWAS data set of 706 leprosy cases, 1,225 healthy controls and 4,362 individuals with immune-related diseases as population controls from northern China of Chinese Han descent. Further validation studies were performed in two stages in a total of 6,765 cases and 9,505 controls from Chinese Han and minority descent in multiple areas of China, similar to the discovery stage. From this study, we discovered six new susceptibility loci with a combined P-value from discovery and validation stage surpassing genome-wide significance, including BATF3 at 1q32.3, CDH18 at 5p14.3, DEC1 at 9q32, EGR2 at 10q21.3, CCDC88B at 11q13.1 and CIITA at 16p13.13. Our current study has advanced the genetic understanding of leprosy by substantially increasing the number of confirmed genetic susceptibility loci. Leprosy GWAS (3) To discover additional leprosy susceptibility loci, we carried out a large-scale three-stage GWAS analysis of leprosy in Chinese population. The genome-wide discovery analysis (Stage 1) involved a new GWAS data set of 1,197 leprosy cases and 1,426 controls from northern and southern China conducted by using Illumina Omni Zhonghua chips with 900,015 single-nucleotide polymorphisms (SNPs), two published GWAS dataset (GWAS2 data set including 706 leprosy cases, 1,225 healthy controls genotyped by Illumina HumanHap610 beadchips, GWAS3 data set including 842 leprosy patients and 925 controls from northern and southern China genotyped by the Human660w-quad beadchips). Further validation studies were performed in two stages in a total of 5,413 cases and 9,771 controls from Chinese Han descent in multiple areas of China. In this study, we identified four novel associations at genome-wide significance (P < 5 x 10-8), all of which can indicate candidate genes within the susceptibility loci, SYN2 (3p25.2), BBS9 (7p14.3), CTSB (8p23.1) and MED30 (8q24.11), through a differential gene expression and eQTL analysis. Altogether, these findings have provided new insight and significantly expanded our understanding of the genetic basis of leprosy. Leprosy GWAS (4) In this study, we attempted to systematically investigate the contribution of protein-coding variants to leprosy susceptibility by performing a three-stage genome-wide association study (GWAS) of protein-coding variants in Chinese population. The initial genome-wide scan was done by genotyping 1,670 persons affected by leprosy and 2,321 controls using the Illumina Infinium Human Exome Beadchips (v1.0).The validation study was performed by genotyping 39 SNPs in an additional 3,169 leprosy patients and 9,814 healthy controls from the northern region of China, and the replication study was performed by genotyping eight SNPs in three independent samples from the southern regions of China consisting of 2,231 cases and 2,266 controls. We identified significant association (P < 1.23 x 10-6) within seven genes FLG (Gene ID: 2312), IL23R (Gene ID: 149233), CARD9 (Gene ID: 64170), NCKIPSD (Gene ID: 51517), TYK2 (Gene ID: 7297), SLC29A3 (Gene ID: 55315), IL27 (Gene ID: 246778). Our findings discover novel involvement of skin barrier and endocytosis/phagocytosis/autophagy, besides known innate and adaptive immunity, in the pathogenesis of leprosy, highlight the merits of protein coding variant studies for complex diseases. Here, the summary statistics from the five genome-wide association analyses were published.

  Study phs000217

• ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas

  We have sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas

  Study EGAS00000000075

• Prediction of DNA Repair Inhibitor Response in Short Term Patient-Derived Ovarian Cancer Organoids

  In this study, 34 ovarian tumor organoids generated from 23 patients underwent paired DNA damage repair defect functional analyses and whole exome sequencing analysis to compare genetic mutational status to DNA repair functional capacity. 22 of the patients had high grade serous cancer and 1 of the patients had low grade serous cancer. A normal control, fresh parent tumor, and cells from the organoid culture generated from the parent tumor underwent whole exome sequencing analysis and the data from the sequencing analysis is provided here.

  Study phs001685

• A Genome-Wide Association Study for Post-bronchodilator Lung Function in Children with Asthma

  In this study, we conducted a genome-wide association study (GWAS) of post-bronchodilator (BD) FEV1 (forced expiratory volume in 1 second) and FEV1/FVC (forced vital capacity) in Puerto Rican children with asthma. From September 2003 to June 2010, we recruited 618 Puerto Rican children with asthma, which was defined as physician diagnosed asthma and at least one episode of wheezing in the previous year. The recruited children include 267 from public schools in Hartford, Connecticut and 351 from randomly selected households in San Juan, Puerto Rico.

  Study phs001216