Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic ...pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture.
This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment.
The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis.
ClinicalTrials.gov, ID: NCT03125304 . Registered on 30 April 2017.
Abstract
A typical cancer somatic mutation identification workflow involves using a standard human reference genome for aligning the sequencing reads and annotating the uncovered somatic variants. ...The completeness and the correctness of the reference genome, and the haplotype representations may all impact the sequencing read alignments and subsequent somatic variant identifications. However, the exact impacts of the underlying references being used on somatic mutation analysis has not been investigated. In this study, we selected 3 human reference genomes, including GRCh38, T2TCHM13, and a personalized genome (PG) that was derived from a normal cell line, and 12 tumor normal paired replicates of Illumina short read sequencing data for the HCC1395 breast cancer cell line and a matched normal cell line, and aim to illustrate and quantify the effects of the reference genomes on the accuracy of somatic SNV/SV mutation detection using various somatic variant callers. Our analysis shows that the use of a personalized haplotype-specific genome assembly, rather than an unrelated genome such as GRCh38 or T2TCHM13 as a reference, not only improves read alignments for short-read sequencing data but also ameliorates the detection accuracy of somatic SNVs and SVs. While most somatic mutation calls are identical or equivalent, we identify GRCh38 and T2TCHM13 specific somatic mutations that may need to be avoided for further pursuit of incorrect treatment options. We uncover novel somatic mutations only when personalized genome assembly is used as a reference, some of which overlap with genes involving with pathways related to cancer invasion and metastasis (e.g., CDH23, ST14 etc.). The predicted somatic SVs are found more precise. Such results may provide additional interventional target choices for patients, researchers or clinicians, and physicians to look into further for personalized patient care.
Citation Format: Chunlin Xiao, Valerie Schneider. Assessment of human reference genomes on cancer somatic mutation detection in tumor-normal paired reference samples using whole genome short-read sequencing data abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2033.
Abstract
DNA N6-methyladenine (m6A) modification has been found widely presented in the human genome, and genome-wide DNA methylation profiling in cancer may reveal epigenetic signatures with ...significant clinical outcomes. Whole genome sequencing data from PacBio single-molecule real-time (SMRT) system provides signals for identifying the presence of m6A in human genomic DNA. We identified 343,199 m6A modification sites with an average density of 122 per Mb in the HCC1395 breast cancer cell line, whereas 722,303 m6A modification sites with average density of 257 per Mb were observed in a matched normal HCC1395BL cell line, meaning that the total number and the average density of m6A methylation sites in the cancer cell line were reduced more than 50% than that in normal cell line. Only small fraction of the methylation sites was found to be shared between the two cell lines, indicating that significant de-methylation (loss) and new methylation (gain) events occurred in HCC1395 cancer cells. A broad distribution of m6A methylation sites across autosomal chromosomes was observed, but the density of m6A methylation sites on chromosome X was extremely low for both HCC1395 and HCC1395BL cell lines. In contrast, the m6A densities on chromosome 7 and chromosome 22, particularly on their q-arms, from HCC1395 were substantially higher (hypermethylation) than other autosomal chromosomes, suggesting that copy number variations may be associated with these chromosomal regions. Most of the m6A methylation sites were located in intergenic and intronic regions, whereas only about 2~3% of the m6A methylation sites were situated in exonic regions, and 12% on ncRNAs. Understanding the genome-wide distinction of DNA methylation between cancer and matched normal cell lines makes it possible to ask more targeted questions and further investigate the role of methylation in cancer.
Citation Format: Chunlin Xiao, Valerie Schneider. Genome-wide profiling of DNA N6-methylation from a breast cancer and a matched normal cell lines abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3743.
Even though considerable efforts have been applied toward self-healing materials, construction of a reversible network in a nonpolar elastomer with a high strength and self-healing behavior is still ...a considerable challenge. Herein, a novel method to construct a dual ionic network for natural rubber (NR)-based carboxylate ionomers with a high self-healing efficiency through an anionic mechanism is demonstrated. Maleic anhydride (MAH) was grafted with NR by an anionic mechanism to construct the first ionic network, with n-butyllithium as the metallization reagent. Subsequently, zinc dimethacrylate (ZDMA) reacted with the MAH-modified NR, and the second ionic network was constructed. Additionally, scanning electron microscopy analyses showed that the grafting of MAH improved the dispersity of ZDMA in NR, resulting in a stronger reinforcing effect. Compared to the reported ZDMA-based self-healing elastomers, the dual ionic network exhibited a better reinforcing effect with a high self-healing efficiency of 75% in full-cut mode. This concept offers a novel inspiration to design high-performance self-healing elastomers.
The complete sequence of a human genome Nurk, Sergey; Koren, Sergey; Rhie, Arang ...
Science (American Association for the Advancement of Science),
04/2022, Volume:
376, Issue:
6588
Journal Article
Peer reviewed
Open access
Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining ...8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.
Increasing evidence has shown that the dysregulation of miRNAs is involved in the pathogenesis of retinoblastoma (RB). This present study was aimed to investigate the significance of miR-375 in RB ...progression, and the underlying mechanism.
The miR-375 expression was detected by RT-PCR. CCK-8 assay and transwell assays were used to measure RB cell viability, migration, and invasion. The downstream gene of miR-375 was verified by luciferase reporter assay. Western blot was applied to detect the related proteins of MAPK1/MAPK3 signalling pathway.
MiR-375 was decreased significantly in RB tissues, and its down-regulation was associated with the poor prognosis of RB patients. Over-expression of miR-375 inhibited RB cell proliferation, migration, and invasion. More importantly, miR-375 modulated ERBB2 expression negatively, and ERBB2 was confirmed as the target of miR-375. Moreover, ERBB2 overturned the inhibitory effect of miR-375 mimic on the progression of RB. MiR-375 mimic suppressed RB progression via inhibiting the activation of MAPK1/MAPK3 signalling pathway.
MiR-375 inhibited RB progression through targeting ERBB2 and suppressing MAPK1/MAPK3 signalling pathway, which might be a new target for the clinical treatment strategy.
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple ...populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 ...release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina. We performed single-nucleotide variant (SNV) and short insertion and deletion (INDEL) discovery and generated a comprehensive set of structural variants (SVs) by integrating multiple analytic methods through a machine learning model. We show gains in sensitivity and precision of variant calls compared to phase 3, especially among rare SNVs as well as INDELs and SVs spanning frequency spectrum. We also generated an improved reference imputation panel, making variants discovered here accessible for association studies.
The 1000 Genomes Project was launched as one of the largest distributed data collection and analysis projects ever undertaken in biology. In addition to the primary scientific goals of creating both ...a deep catalog of human genetic variation and extensive methods to accurately discover and characterize variation using new sequencing technologies, the project makes all of its data publicly available. Members of the project data coordination center have developed and deployed several tools to enable widespread data access.
PDF
