Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5+ stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1+ stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease. These PDS3 phenotypic traits are evident across numerous bulk and single-cell datasets, and demark a series of subtle biological states that are currently under-represented in pre-clinical models and are not identified using existing subtyping classifiers.

What Are Your Patients Reading Online About Soft-tissue Fillers? An Analysis of Internet Information.

BACKGROUND: Soft-tissue fillers are increasingly being used for noninvasive facial rejuvenation. They generally offer minimal downtime and reliable results. However, significant complications are reported and patients need to be aware of these as part of informed consent. The Internet serves as a vital resource to inform patients of the risks and benefits of this procedure. METHODS: Three independent reviewers performed a structured analysis of 65 Websites providing information on soft-tissue fillers. Validated instruments were used to analyze each site across multiple domains, including readability, accessibility, reliability, usability, quality, and accuracy. Associations between the endpoints and Website characteristics were assessed using linear regression and proportional odds modeling. RESULTS: The majority of Websites were physician private practice sites (36.9%) and authored by board-certified plastic surgeons or dermatologists (35.4%) or nonphysicians (27.7%). Sites had a mean Flesch-Kincaid grade level of 11.9 ± 2.6, which is well above the recommended average of 6 to 7 grade level. Physician private practice sites had the lowest scores across all domains with a notable lack of information on complications. Conversely, Websites of professional societies focused in plastic surgery and dermatology, as well as academic centers scored highest overall. CONCLUSIONS: As the use of soft-tissue fillers is rising, patients should be guided toward appropriate sources of information such as Websites sponsored by professional societies. Medical professionals should be aware that patients may be accessing poor information online and strive to improve the overall quality of information available on soft-tissue fillers.