Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence ...associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profiles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profiles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fixed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis.
Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically significant negative correlation between methylation profiles and gene expression in the panel of breast cancer cell lines. Subnetwork enrichment of these genes has identified 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed methylation patterns between the basal and luminal subtypes.
Our results indicate that the proposed computational protocol is a viable platform for identifying epigenetically regulated genes. Our protocol has generated a list of predictors including COL1A2, TOP2A, TFF1, and VAV3, genes whose key roles in epigenetic regulation is documented in the literature. Subnetwork enrichment of these predicted markers further suggests that epigenetic regulation of individual genes occurs in a coordinated fashion and through common regulators.
Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense ...study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1α isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.
Abstract
Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires ...expertise in both imaging methodology—with specific adaptations to imaging of the heart—as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.
Graphical Abstract
Graphical abstract
Left top: Increasing demand for non-invasive cardiovascular imaging as illustrated for England. Data are challenging to collect across Europe, but trends would be expected to be similar in many European countries. Bottom left: Longstanding history of cardiovascular imaging in the management of cardiovascular disease. Right: Components driving competency-based cardiac imaging offered by the European Society of Cardiology and the European Association of Cardiovascular Imaging of the ESC.
Iron is critical for fetal development. Neonates of obese women may be at risk for poor iron status at birth as a result of maternal inflammation-driven overexpression of hepcidin.
The objective of ...this study was to determine differences in placental transfer of oral iron (57Fe) and expression of placental transferrin receptor 1 (TFR1) and ferroportin (FPN) mRNA and protein and their association with maternal and neonatal iron-related parameters, including maternal hepcidin, among women with and without prepregnancy (PP) obesity.
57Fe ingested during the third trimester of pregnancy was recovered in venous umbilical cord blood among 20 PP obese BMI (in kg/m2): 30.5–43.9 and 22 nonobese (BMI: 18.5–29.0) women aged 17–39 y. Placental TFR1 and FPN mRNA and protein expression were quantified via qPCR and Western blot. Maternal and neonatal markers of iron status and regulation, as well as inflammation, were measured. Descriptive and inferential statistical tests (e.g., Student t test, Pearson correlation) were used for data analysis.
There was no difference in cord blood enrichment of 57Fe or placental mRNA or protein expression of TFR1 or FPN among the women with and without PP obesity. Maternal hepcidin was not correlated with cord blood enrichment of 57Fe or placental FPN mRNA or protein expression. Maternal log ferritin (corrected for inflammation) was inversely correlated with log percent enrichment of 57Fe in cord blood (partial r = –0.50; P < 0.01, controlled for marital status) and protein expression of TFR1 (r = –0.43; P = 0.01).
Placental iron trafficking did not differ among women with and without PP obesity. Findings reinforce the importance of maternal iron stores in regulating placental iron trafficking.
Highlights • The PowerPlex® Fusion 6C System is a new 6-dye, 27-locus, STR multiplex. • A multisite study following SWGDAM guidelines was completed for the multiplex. • Results demonstrate the ...robustness of design and suitability for forensic use.
People with sickle cell disease frequently use complementary and integrative therapies to cope with their pain, yet few studies have evaluated their effectiveness. The 3-arm, 3-site pragmatic Hybrid ...Effectiveness-implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain (GRACE) has 3 priorities: (1) evaluate guided relaxation and acupuncture to improve pain control; (2) determine the most appropriate and effective treatment sequence for any given patient based on their unique characteristics; and (3) describe the processes and structures required to implement guided relaxation and acupuncture within health care systems.
Participants (N = 366) are being recruited and randomized 1:1:1 to one of 2 intervention groups or usual care. The acupuncture intervention group receives 10 sessions over approximately 5 weeks. The guided relaxation intervention group receives access to video sessions ranging from 2 to 20 min each viewed daily over 5 weeks. The usual care group receives the standard of clinical care for sickle cell disease. Participants are re-randomized at 6 weeks depending on their pain impact score. Assessments occur at 6 weeks, 12 weeks, and 24 weeks. The primary outcome is the change in pain impact score and secondary measures include opioid use, anxiety, depression, sleep, pain catastrophizing, substance use, global impression of change, constipation, and hospitalizations. The GRACE study uses the Consolidated Framework for Implementation Research to plan, execute, and evaluate the associated implementation processes.
The results from GRACE will represent a critical step toward improving management of pain affecting patients with sickle cell disease.
ClinicalTrials.gov Identifier: NCT04906447.
Adolescents and young adults are vulnerable to developing mental distress. However, evidence suggests that more than half of the young people with symptoms of depression and anxiety overcome their ...distress within a year. However, there is little research on the exact resources that young people use and help them to recover. The aim of this study was to explore how arts activities can support the recovery of young people engaged with arts organizations in Bogota.
We recruited 38 participants from two arts organizations in Bogotá and conducted six focus groups embedded within artistic workshops. The type of activities in the workshops varied reflecting the different teaching methods of the two organizations. The focus group discussions were recorded and analyzed using thematic analysis.
Five themes explained how arts activities can help young people participating in artistic organizations to overcome mental distress: i) allowing the expression of emotions; ii) helping to manage and transform emotions; iii) distracting from problems; iv) facilitating social support and relationships; and v) contributing to the identity of young people.
For young people who participate in artistic organizations, the arts are a resource for overcoming negative emotions such as anxiety, depression, and sadness. The beneficial role of arts activities includes different process of managing, expressing, and distracting from distress, and it differs depending on whether arts are perceived as a professional vocation or a hobby.
The formation of silver nanostructures (AgNSs) with different crystals morphology in porous SiO2/p-Si templates by the electroless wet-chemical method at temperatures between 20 and 50 °C and ...surface-enhanced Raman scattering (SERS) was investigated. It was found that optimized dendritic silver architectures contain a significant number of localized “hot spots.” We show that well-reproducible AgNSs provide a significantly enhanced Raman signal of Nile blue dye molecules up to 10−6 M by using different excitation wavelengths (473, 532, and 633 nm). Based on our observations, the well-organized AgNSs can act as efficient surfaces for SERS as well as (bio)-sensor applications.
Background. Influenza outbreaks have been reported among travelers, but attack rates and incidence are unknown. Methods. A cohort study was conducted. Travelers to subtropical and tropical countries ...recruited at the University of Zurich Travel Clinic (Switzerland), January 1998 to March 2000, were investigated with pre- and posttravel assessment of hemagglutination inhibition and by questionnaire. Results. Among 1450 travelers recruited who completed questionnaires and provided serum samples before departure, 289 (19.9%) reported febrile illness during or after traveling abroad; of these, 211 (73.0%) provided paired serum samples. Additionally, paired serum samples were collected from 321 frequency-matched afebrile control subjects among the remaining 1161 subjects of the study population. Seroconversion for influenza virus infection was demonstrated in 40 (2.8%) of all travelers; 18 participants (1.2%) had a ⩾4-fold increase in antibody titers. This corresponds to an incidence of 1.0 influenza-associated events per 100 person-months abroad. Among the 211 febrile participants, 27 (12.8%) had seroconversion, 13 (6.2%) with a ⩾4-fold increase; among the 321 afebrile control subjects, 13 (4.0%) had seroconversion, 5 (1.6%) with a ⩾4-fold increase. Twenty-five seroconverters (62.5%; P = .747) acquired influenza outside of the European epidemic season. Sixteen patients (40.0%) sought medical attention either abroad or at home, and 32 (80.0%) were asymptomatic at the time of completion of the survey. Conclusions. This survey indicates that influenza is the most frequent vaccine-preventable infection among travelers to subtropical and tropical countries. Infections occur mainly outside the domestic epidemic season, and they have a considerable impact. Pretravel vaccination should be considered for travelers to subtropical and tropical countries.
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