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Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions, including serving as messenger RNAs that are translated into peptides. Here we describe circular RNAs generated by human polyomaviruses (HPyVs), some of which encode variants of the previously described alternative large T antigen open reading frame (ALTO) protein. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N6-methyladenosine (m6A) modified. The translation of MCPyV circALTOs into ALTO protein is negatively regulated by MCPyV-generated miRNAs in cultured cells. MCPyV ALTO expression increases transcription from some recombinant promoters in vitro and upregulates the expression of multiple genes previously implicated in MCPyV pathogenesis. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation in MCPyV-negative cells. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and infected tissues and express proteins that have the potential to modulate the infectious and tumorigenic properties of these viruses.

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SDCT spectral reconstructions demonstrate similar performance to those of dsDECT in discriminating UA from non-UA stones in a phantom model.

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PIK3CA-related disorders include vascular malformations, potential overgrowth of various tissues, limb abnormalities, disordered soft tissue, and/or fatty hyperplasia that often leads to significant morbidity. Alpelisib, a targeted inhibitor of p110α, an enzyme encoded by the PIK3CA gene, has demonstrated success in a cohort of patients with PIK3CA-driven overgrowth syndromes. We describe the clinical course of 2 pediatric patients treated with alpelisib under the Novartis Managed Access Program. Both patients, though clinically distinct, demonstrate improvements in overgrowth volumes/extent, function of their affected limb, and quality of life, without significant adverse effects after prolonged treatment.

eratinocyte carcinoma (KC), also known as nonmelanoma skin cancer, refers to basal cell carcinoma and squamous cell carcinoma. The incidence rates of KC are much lower among people with skin of color compared with people who identify as non-Hispanic White. 1 However, KCs in individuals with skin of color can be associated with worse outcomes owing to a higher risk for tumor invasion, metastasis, atypical clinical presentations, and delays in diagnosis compared with non-Hispanic White populations. 2 Ultraviolet exposure is the strongest modifiable risk factor associated with KC, but studies establishing this association have been primarily in non-Hispanic White populations. To date, and to our knowledge, there has been no comprehensive systematic review examining the association between UV exposure and KC among individuals with skin of color. Methods Personnel, Protocol, and RegistrationThe systematic review team included 5 reviewers (E.K., F.C.P.S.L., M.A., J.P., and A.S.A.) and 1 health sciences librarian (R.B.) from the University of Texas Libraries. The systematic review was registered on March 8, 2021, in the PROSPERO database (CRD42021234735). We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. This research project was considered by The University of Texas at Austin Institutional Review Board as non-human participant research, and approval was not required.IMPORTANCE Ultraviolet radiation exposure is an important modifiable risk factor for keratinocyte carcinoma (KC) in fair-skinned non-Hispanic White populations; however, the evidence for this relationship in darker-skinned populations is less certain.OBJECTIVE To assess and synthesize the published data concerning the association between UV exposure and the risk of KC in individuals with skin of color.EVIDENCE REVIEW PubMed, Cochrane, and Web of Science databases were searched from database origin through January 2022. Studies deemed eligible included UV exposure as a risk factor for KC in individuals with skin of color, defined as any race other than non-Hispanic White, Fitzpatrick skin types IV to VI, or tanning ability of rarely or never burns. The UV index, irradiance, latitude, history of phototherapy, history of sunburn, or occupational exposure were used as measures of exposure. The Oxford Centre for Evidence-Based Medicine guidelines were used to assess evidence quality.FINDINGS A total of 72 716 articles appeared in the search. After duplicate removal, 29 393 database records were screened, 454 full-text articles were assessed, a forward and reverse citation search was performed, and 12 articles, with clinical data spanning the years 1990 to 2019, met inclusion criteria. More than 32 970 KCs in individuals with skin of color were included. Eight studies found no association between UV exposure and KC, while 4 studies showed a positive association. Study types included 1 ecological study, 9 cohort studies, and 2 case-control studies. The quality of the studies was rated from moderate to low...

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