Methylation alterations of CpG islands, CpG island shores and first exons are key events in the formation and progression of human cancer, and an increasing number of differentially methylated regions and genes have been identified in breast cancer. Recent studies of the breast cancer methylome using deep sequencing and microarray platforms are providing a novel insight on the different roles aberrant methylation plays in molecular subtypes of breast cancer. Accumulating evidence from a subset of studies suggests that promoter methylation of tumor-suppressor genes associated with breast cancer can be quantified in circulating DNA. However, there is a paucity of studies that examine the combined presence of genetic and epigenetic alterations associated with breast cancer using blood-based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor for breast cancer that has been measured in lymphocytes. We isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL. Methylation of at least one gene was found in 49% of the cases compared to 20% of the controls. Three of the four genes had receiver characteristic operator curve values of ≥0.50: MAL (0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promoter methylation was associated with breast cancer and inversely associated with DRC. This is the first evidence of a significant association between genetic and epigenetic alterations in breast cancer using blood-based tests. The potential diagnostic utility of these biomarkers and their relevance for breast cancer risk prediction should be examined in larger cohorts.
This review recognized moderate evidence in favor of TT interventions in balance and stroke rehabilitation programs. With TT, intensity may be a more critical factor than specificity and may offer additional carryover to recovery parameters of postural control and balance, beyond gait performance. It is recommended that clinicians utilizing TT incorporate objective measures of balance to assess the potential for skill transference and improvements in balance. Higher quality studies and additional research are needed to denote critical parameters by which improvements in balance may be optimized.
Clinically useful molecular tools to triage women for a biopsy upon referral to colposcopy are not available. We aimed to develop a molecular panel to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher lesions (CIN2
Several genomic epidemiology tools have been developed to track the public and population health impact of SARS-CoV-2 community spread worldwide. A SARS-CoV-2 Variant of Concern (VOC) B.1.1.7, known as 501Y.V1, which shows increased transmissibility, has rapidly become the dominant VOC in the United States (US). Our objective was to develop an evidenced-based genomic surveillance algorithm that combines RT-PCR and sequencing technologies to identify VOCs. Deidentified data were obtained from 508,969 patients tested for COVID-19 with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA certified clinical laboratories in Puerto Rico (n=86,639) and in three CLIA certified clinical laboratories in the US (n=422,330). TaqPath data revealed a frequency of S Gene Target Failure (SGTF) >47% for the last week of March 2021, in both Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021.The weekly SGTF rate in US samples was high (>8%) from late December to early January, and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico is concurrent with a sharp increase in VOCs among all SARS-CoV-2 sequences from Puerto Rico uploaded to GISAID (n=461). B.1.1.7 frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021. The exponential increase in SGTF and B.1.1.7 prevalence in Puerto Rico and US requires an urgent response. According to the proposed evidence-based algorithm, approximately 50% of all positive samples should be managed as potential B.1.1.7 carriers with VOC quarantine and contact tracing protocols while their lineage is confirmed by WGS in surveillance laboratories. Patients infected with VOCs should be effectively triaged for isolation, contact tracing and follow-up treatment purposes.
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