The prevalence and nature of somatic copy number alterations (CNAs) in breast epithelium and their role in tumor initiation and evolution remain poorly understood. Using single-cell DNA sequencing (49,238 cells) of epithelium from BRCA1 and BRCA2 carriers or wild-type individuals, we identified recurrent CNAs (for example, 1q-gain and 7q, 10q, 16q and 22q-loss) that are present in a rare population of cells across almost all samples (n = 28). In BRCA1/BRCA2 carriers, these occur before loss of heterozygosity (LOH) of wild-type alleles.
View Article and Find Full Text PDFThe matrix effect limits the accuracy of quantitation of the otherwise popular metabolomics technique liquid chromatography coupled to mass spectrometry (LC-MS). The gold standard to correct for this phenomenon, whereby compounds coeluting with the analyte of interest cause ionization enhancement or suppression, is to quantify an analyte based on the peak area ratio with an isotopologue added to the sample as an internal standard. However, these stable isotopes are expensive and sometimes unavailable.
View Article and Find Full Text PDFHow cell-to-cell copy number alterations that underpin genomic instability in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer, remains understudied. Here, by applying scaled single-cell whole-genome sequencing to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences.
View Article and Find Full Text PDFIntroduction: Partial thickness burns not undergoing surgical excision are treated with topical silver products including silver sulfadiazine (SSD) and Mepilex Ag. Skin allograft is a more costly alternative that acts as definitive wound coverage until autogenous epithelialization. Economic constraints and the movement toward value-based care demand cost and outcome justification prior to adopting more costly products.
View Article and Find Full Text PDFMotivation: Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator.
Results: We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis.
Background: Metabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological, and many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, data repositories, and data analysis tools.
View Article and Find Full Text PDFMetabolomics has become a crucial phenotyping technique in a range of research fields including medicine, the life sciences, biotechnology and the environmental sciences. This necessitates the transfer of experimental information between research groups, as well as potentially to publishers and funders. After the initial efforts of the metabolomics standards initiative, minimum reporting standards were proposed which included the concepts for metabolomics databases.
View Article and Find Full Text PDFThe possible presence of matrix effect is one of the main concerns in liquid chromatography-mass spectrometry (LC-MS)-driven bioanalysis due to its impact on the reliability of the obtained quantitative results. Here we propose an approach to correct for the matrix effect in LC-MS with electrospray ionization using postcolumn infusion of eight internal standards (PCI-IS). We applied this approach to a generic ultraperformance liquid chromatography-time-of-flight (UHPLC-TOF) platform developed for small-molecule profiling with a main focus on drugs.
View Article and Find Full Text PDFBackground: Autologous split-thickness skin grafting has been proven to provide the best cosmetic and functional outcome after cutaneous burn injuries and thus is the standard of care. Clinical observations have shown that female burn patients frequently have greater difficulty choosing a donor site than do male burn patients. However, there is a lack of data characterizing donor-site preferences among women with burns.
View Article and Find Full Text PDFBackground: The purpose of this study was to assess the cost-effectiveness of five standardized procedures for breast reconstruction to delineate the best reconstructive approach in postmastectomy patients in the settings of nonirradiated and irradiated chest walls.
Methods: A decision tree was used to model five breast reconstruction procedures from the provider perspective to evaluate cost-effectiveness. Procedures included autologous flaps with pedicled tissue, autologous flaps with free tissue, latissimus dorsi flaps with breast implants, expanders with implant exchange, and immediate implant placement.
The standard treatment of partial-thickness burns includes topical silver products such as silver sulfadiazine (SSD) cream and enclosed dressings including silver-impregnated foam (Mepilex Ag; Molnlycke Health Care, Gothenburg, Sweden) and silver-laden sheets (Aquacel Ag; ConvaTec, Skillman, NJ). The current state of health care is limited by resources, with an emphasis on evidence-based outcomes and cost-effective treatments. This study includes a decision analysis with an incremental cost-utility ratio comparing enclosed silver dressings with SSD in partial-thickness burn patients with TBSA less than 20%.
View Article and Find Full Text PDFBackground: Laser-assisted indocyanine green angiography is a U.S. Food and Drug Administration-approved technology used to assess tissue viability and perfusion.
View Article and Find Full Text PDFBackground: The use of acellular dermal matrix has allowed for single-stage immediate breast reconstruction after mastectomy at a significantly decreased cost compared with two-stage expander/implant reconstruction. The use of a pedicled autologous dermal flap in the same fashion as acellular dermal matrix in women with larger, ptotic breasts has also allowed for single-stage immediate breast reconstruction with similarly low complication rates and without the added procedural cost of using acellular dermal matrix. There have been no prior studies evaluating whether the added procedural cost for acellular dermal matrix is cost-effective relative to using an autologous dermal flap in single-stage immediate breast reconstruction following mastectomy.
View Article and Find Full Text PDFUnlabelled: Identification of metabolites using high-resolution multi-stage mass spectrometry (MS(n)) data is a significant challenge demanding access to all sorts of computational infrastructures. MetiTree is a user-friendly, web application dedicated to organize, process, share, visualize and compare MS(n) data. It integrates several features to export and visualize complex MS(n) data, facilitating the exploration and interpretation of metabolomics experiments.
View Article and Find Full Text PDFJ Cosmet Laser Ther
June 2005
There are various treatment modalities for acne vulgaris including topical and oral therapy as well as microdermabrasion and chemical peels. Recently, there has been an emergence of novel laser and light sources as a means for treating acne vulgaris. This article will review the advances of laser and light sources in the treatment of acne vulgaris.
View Article and Find Full Text PDFThere are numerous treatments for cellulite including topical, surgical, laser and other therapies. Many of these treatments are expensive. Part of the difficulty in treating cellulite arises from our incomplete understanding of this phenomenon.
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