1073 results for "2025年12月600642股价走势分析"

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• A Phase 2 Study of Tipifarnib in Large Granular Lymphocyte (LGL) Leukemia

  LGL leukemia can be divided into three subsets including the following: αβ or γδT-LGL and NK-LGL leukemia. All three subtypes will be enrolled using a two-stage design. The primary endpoint of the study is assessment of overall clinical response. Correlative laboratory studies will be performed aimed at determining the mechanism of response to treatment. Thirteen participants will be accrued in the first stage at a dose of 300 mg BID administered intermittently every other week (i.e., 7 days on and 7 days off). If there are two or more responders, the protocol will be extended to a second stage of the study and accrual will be extended to 25 evaluable participants. Allowing for 10% rate of ineligibility due to unexpected events and dropout, we will accrue 14 patients in the first stage and 27 patients in total. Participants that withdraw from the study for reason unrelated to toxicity, will be replaced. There are two potential stopping rules for toxicity. If 3 or more participants out of the 13 enrolled in the first stage experiences grade IV neurotoxicity, the study will be stopped due to excessive toxicity. Dose reductions have been incorporated for hematologic toxicity. Treatment of T and NK LGL leukemia with immunosuppressive agents such as low-dose methotrexate generally require from four to six months for a clinical response and sometimes much longer. Therefore, in participants who show clinical improvement with less than grade three toxicity, tipifarnib treatment will be continued for as many as four additional months (12 months total). After the first 8 months, response will be assessed. The protocol treatment will be discontinued in participants with progression of disease. A long-term follow up will be performed for five years in patients that receive a complete clinical response. The long-term follow up will consist of vital signs, weight, CBCs, serum chemistries, and physical examination at six month intervals.

  Study phs000594

• Center for Education and Drug Abuse Research (CEDAR)

  Under its programmatic name, the Center for Education and Drug Abuse research (CEDAR), this Center of Excellence project was completed in 2015. The CEDAR sample consists of 775 nuclear families comprising an adult male (proband), his spouse/mate, and their biological child who is 10-12 years of age at recruitment. This child is designated as index child (IC), and is followed through age 30. Minimal exclusionary criteria were applied to maximize the sample's representativeness. Follow-up evaluations on ICs were conducted at ages 14, 16, 19, 22, 25, 27 and 30. Interim questionnaires were mailed annually beginning at age 20. CEDAR utilizes the family/high-risk paradigm. The offspring thus comprise high average risk (HAR) and low average risk (LAR) groups, constituting the majority of the CEDAR children sample: 250 HAR males, 100 HAR females, 250 LAR males and 94 LAR females. The remainder of the IC sample, 50 males and 31 females, are the offspring of fathers who have a lifetime non-SUD psychiatric dis-order. The follow-up rate from baseline to the final assessment is ~65%. The cohort of children is 76% White and 22% Black. The representation of females among ICs is lower than males, due to the later start of recruit-ment (2nd funding cycle; the study originally focused on males). The CEDAR genetic study has been augmented by the inclusion of its sample into the whole-genome genotyping effort conducted under the Genes, Environment and Development Initiative (GEDI). DNA from the blood samples of target children (index cases) and their siblings submitted to the NIDA Genetics Depository a Rutgers University was obtained and genotyped on Illumina Human660W-Quad Beadchips, with a high average genotyping rate of 99.8%. The sample comprised 158 females and 271 males (37 and 63 %), ~70:30 European- and African- American, with approximately 1:1 ratio of children of affected fathers and normal controls.

  Study phs001649

• Regulatory Changes in Glioblastoma Brain Tumors and Xenografts Wave 1

  Non-coding elements in our genomes that play critical roles in complex disease are frequently marked by highly unstable RNA species. Sequencing nascent RNAs attached to an actively transcribing RNA polymerase complex can identify unstable RNAs, including those templated from gene-distal enhancers (eRNAs). However, nascent RNA sequencing techniques remain challenging to apply in some cell lines and especially to intact tissues, limiting broad applications in fields such as cancer genomics and personalized medicine. Here we report the development of chromatin run-on and sequencing (ChRO-seq), a novel run-on technology that maps the location of RNA polymerase using virtually any frozen tissue sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in 23 human glioblastoma (GBM) brain tumors and patient derived xenografts. Remarkably, >90,000 distal enhancers discovered using the signature of eRNA biogenesis within primary GBMs closely resemble those found in the normal human brain, and diverge substantially from GBM cell models. Despite extensive overall similarity, 12% of enhancers in each GBM distinguish normal and malignant brain tissue. These enhancers drive regulatory programs similar to the developing nervous system and are enriched for transcription factor binding sites that specify a stem-like cell fate. These results demonstrate that GBMs largely retain the enhancer landscape associated with their tissue of origin, but selectively adopt regulatory programs that are responsible for driving stem-like cell properties. We also identified enhancers and their associated transcription factors that regulate genes characteristic of each known GBM subtype, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.

  Study phs001646

• Center for Common Disease Genomics [CCDG] - Cardiovascular: ENGAGE Atrial Fibrillation-TIMI 48

  This study is a part of NHGRI's Center for Common Disease Genomics, which is a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Current estimates anticipate that the CCDG program will sequence approximately 140K whole genomes and 225K whole exomes during the life of the project. The Cardiovascular Disease working group of the CCDG considered five diseases: early-onset coronary artery disease (EOCAD), stroke, atrial fibrillation, congestive heart failure and type 2 diabetes. Atrial fibrillation will affect between 6-12 million individuals in the US by 2050. AF also is associated with increased risks of stroke, dementia, heart failure, death, and high health care costs. Many risk factors for AF have been identified, including advancing age, cardiovascular disease (CVD), and CVD risk factors. However, there is little knowledge how to prevent AF. Furthermore, therapies for AF are only partially effective, and are themselves associated with substantial morbidity. Previously, heritable forms of AF have been considered rare; yet in the last decade, it has been established that AF, and in particular early-onset forms of AF, are heritable. Genome-wide association studies (GWAS) provide a powerful tool to identify common variants underlying disease risk. The AFGen Consortium currently consists of investigators from more than 25 studies with >20,000 individuals with AF and >100,000 without AF. In the latest analyses, 14 loci have been identified for AF1. Broadly, the loci implicate genes related to cardiopulmonary development, cardiac-expressed ion channels, and cell signaling molecules.Source: https://ccdg.rutgers.edu/sites/default/files/CCDG_CVD_EOAF_FINAL_w_link.pdfFor this study, The Broad Institute of MIT and Harvard generated genetic data for 13,667 individuals from the ENGAGE AF-TIMI 48 clinical trial run by Brigham and Women's Hospital TIMI study group using whole exome sequencing and whole genome genotyping (Infinium Global Screening Array); all cases with atrial fibrillation.

  Study phs002774

• ImmunAID

  The ImmunAID study is a multi-center research program aimed at improving the diagnosis and understanding of systemic autoinflammatory diseases. The study integrates immunological, and molecular data from patients across several European cohorts. Its objective is to identify biomarkers and biological pathways that characterize disease mechanisms and help differentiate between inflammatory conditions. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779295. The project has generated genomic datasets, which are available through the European Genome-phenome Archive (EGA). In addition, it has produced several non-genomic datasets, listed below. All datasets have been fully anonymized in accordance with applicable ethical and regulatory frameworks. These non-genomic data are available upon request. To request access to these datasets, please contact: immunaid2024@gmail.com Your request will be studied by the Data Access Committee, and data will be made available upon approval. Non-genomic datasets available: Flow cytometry (general immune phenotype) — Dataset ID: ICKD2021569, size: 23 GB, 342 patients Somascan proteomics data — Dataset ID: ICKD2021570, size: 59 MB, 444 patients ELISA panel (Ferritin, CRP, HO1, IL-1B, IL-6, IL-8, IL-10, IL-12, IL-18, IFN-γ, TNF-α) — Dataset ID: ICKD2021571, size: 295 KB, 439 patients Mass spectrometry (MS/MS) — Dataset ID: ICKD2021572, size: 1.8 TB, 447 patients ELISA (CRP/ SAA) — Dataset ID: ICKD2021573, size: 321 KB, 443 patients Flow cytometry (inflammasome activity) — Dataset ID: ICKD2021574, size: 899 KB, 307 patients Plasma lipidomics — Dataset ID: ICKD2021575, size: 1.1 MB, 427 patients Urine lipidomics — Dataset ID: ICKD2021576, size: 833 KB, 368 patients ELISA (alarmins) — Dataset ID: ICKD2021577, size: 129 KB, 108 patients ELISA (IL-18 / IL-1) — Dataset ID: ICKD2021578, size: 271 KB, 330 patients Flow cytometry (NK cell alterations) — Dataset ID: ICKD2021579, size: 14 GB, 216 patients Chemokine measurements — Dataset ID: ICKD2021580, size: 489 KB, 404 patients Luminex (multiple analyte measurements) — Dataset ID: ICKD2021581, size: 759 KB, 369 patients

  Study EGAS50000001393

• POU4F3 mutation screening in Japanese hearing loss patients.

  A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands) to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants) were successfully identified in 15 probands (2.5%) among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants in POU4F3 were a common cause of autosomal dominant HL.

  Study JGAS000093

• Gene expression signatures associated with chronic endometritis revealed by RNA sequencing

  Chronic endometritis (CE) is a persistent inflammatory condition of the endometrium characterized by the infiltration of plasma cells. CD138 immunohistochemistry is considered to improve the CE diagnosis rate. Using the number of CD138-positive cells equal or greater than five as a diagnostic criterion for CE, we identified 24 CE and 33 non-CE cases among women with infertility. We conducted RNA-sequencing analysis for these 57 cases in total as an attempt to elucidate the molecular pathogenesis of CE and to search for new biomarkers for CE. By comparing CE and non-CE groups, we identified 20 genes upregulated in the endometria of CE patients, including 12 immunoglobulin-related genes and eight non-immunoglobulin genes as differentially expressed genes. The eight genes were MUC5AC, LTF, CAPN9, MESP1, ACSM1, TVP23A, ALOX15, and MZB1. By analyzing samples in the proliferative and secretory phases of the menstrual cycle separately, we also identified four additional non-immunoglobulin genes upregulated in CE endometria: CCDC13 by comparing the samples in the proliferative phase, and OVGP1, MTUS2, and CLIC6 by comparing the samples in the secretory phase. Although the genes upregulated in CE may serve as novel diagnostic markers of CE, many of them were upregulated only in a limited number of CE cases showing an extremely high number of CD138-positive cells near or over one hundred. Exceptionally, TVP23A was upregulated in the majority of CE cases regardless of the number of CD138-positive cells. The upregulation of TVP23A in the endometria of CE cases may reflect the pathophysiology of a cell-type or cell-types intrinsic to the endometrium rather than the accumulation of plasma cells. Our data, consisting of clinical and transcriptomic information for CE and non-CE cases, helped us identify gene expression signatures associated with CE.

  Study JGAS000621

• Molecular analysis of diffuse cerebellar gliomas

  Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients. World Health Organization histological grade at recurrence was mostly stable; it was increased in 2, the same in 9, and decreased in 1 cases. Whole-exome sequencing demonstrated that the rate of shared mutation between the primary and recurrent tumors was relatively low, ranging from 3.2-57.9% (average, 33.3%), indicating a branched evolutionary pattern. The trunk alterations that existed throughout the course were restricted to IDH1 mutation, 1p/19q-codeletion, and TERT promoter mutation, and mutation of the known candidate tumor suppressor genes CIC and FUBP1 were not consistently observed between primary and recurrent tumors. Multiple sampling from different regions within a tumor showed marked intratumoral heterogeneity. Notably, in general, the number of mutations was not significantly different after recurrence, remaining under 100, and no hypermutator phenotype was observed. FUBP1 mutation, loss of chr. 9p21, and TCF12 mutation were among a few recurrent de novo alterations that were found at recurrence, indicating that these events were clonally selected at recurrence but were not enough to enhance malignancy. Genome-wide methylation status, measured by Illumina 450 K arrays, was stable between recurrence and the primary tumor. In summary, although oligodendroglioma displays marked mutational heterogeneity, histological malignant transformation accompanying events such as considerable increase in mutation number and epigenetic profile change were not observed at recurrence, indicating that noticeable temporal and spatial genetic heterogeneity in oligodendrogliomas does not result in rapid tumor progression.

  Study JGAS000106

• Integrated copy number and expression analysis identifies profiles of whole-arm chromosomal alterations and subgroups with favorable outcome in ovarian clear cell carcinomas

  Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism arrays in 57 (31 CCCs, 14 SCs, and 12 ECs) and expression microarrays in 55 epithelial ovarian cancers (25 CCCs, 16 SCs, and 14 ECs), and then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs), significantly lower than for SCs (93%, P < 0.01) and ECs (50%, P = 0.017). The ratio of whole-arm to all CNAs was higher in CCCs (46.9%) than SCs (21.7%) (P < 0.0001). SCs with loss of heterozygosity (LOH) of BRCA1 (85%) also had LOH of NF1 and TP53, and LOH of BRCA2 (62%) coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10) showed more favorable prognosis than the others (CCC-1and CCC-3) (P = 0.041). Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64%) than in CCC-2 (0/10, 0%) (P < 0.01). Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis.

  Study JGAS000022

• Genomic profiling of paediatric high grade gliomas from the HERBY clinical trial

  The HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem high grade glioma (HGG) between the ages of 3-18yrs. 121 patients were randomised with 1yr event-free survival as the primary end-point. Confirmation of HGG diagnosis by reference pathology was mandatory before randomisation, followed by review with five independent expert neuropathologists. We collected specimens from 89 patients consenting to translational research, and performed Sanger sequencing for H3F3A, Illumina 450K BeadArray methylation profiling, and whole exome sequencing and RNA sequencing where possible. 7/89 patients (8%) harboured H3F3A G34R/V mutations, whilst 24/89 (27%) harboured H3F3A K27M, the latter reflecting a high proportion of the novel entity recognised in the 2016 WHO classification of diffuse midline glioma with H3K27M mutation. Both histone mutations conferred a significantly shorter progression-free (p=0.0104) and overall survival (p=0.00159). 450K methylation subtyping additionally identified a number of subgroups in histone wild-type cases. These included infrequent (4/86, 4.6%) cases with IDH1 mutation in older children, further categorised into astrocytic ATRX-mutant (n=3) or 1p19q co-deleted with TERT promoter mutation (n=1). 9/74, (12%) of cases were classified as biologically resembling pleomorphic xanthoastrocytoma (PXA) by methylation profiling, with 5/9 harbouring BRAF V600E mutations and epithelioid histology, and 3/9 NF1 mutation and giant cell features. Three cases had methylation profiles more closely resembling low grade gliomas, though were morphologically high grade, and harboured MAPK dysregulation in two cases, with the third part of an additional infant (&lt;3yrs) cohort. Finally, four cases had a mutational burden several orders of magnitude higher than the rest, with (2197-5332) somatic coding variants/sample reflecting a hypermutator phenotype. These data provide an important insight into the wide biological diversity of ‘HGG’ found in the paediatric age group and allow for a profound refinement of clinical trial interpretation.

  Study EGAS00001002328