RESUMO
Purpose: The aim of this research is to describe the use of the social media platform, Instagram, by academic ophthalmology residency programs in the United States over time and consider the impact of the COVID-19 pandemic on ophthalmology's social media presence. Methods and Subjects: This cross-sectional study was conducted online by reviewing the publicly accessible Instagram accounts of all accredited US academic ophthalmology residency programs. Main Outcomes and Measures: Number of US ophthalmology residency programs with an affiliated Instagram account were analyzed by year of creation. The content of the top six accounts with the most followers was analyzed by evaluating amount of engagement within defined post categories. Results: Of the 124 ophthalmology residency programs, 78 (62.9%) were identified as having an affiliated Instagram account, 60 accounts (48.4%) were created during the years 2020 or 2021, and 62 (50.0%) accounts focused specifically on promoting the residency training program. Of the top six accounts with the most followers, post categories that received the most engagement were "Medical" and "Group Photo", while those that received the least engagement were "Department Bulletin" and "Miscellaneous." User engagement on posts as measured by likes and comments increased across multiple post categories after January 2020. Conclusion: Social media presence of ophthalmology residency programs on Instagram increased substantially in 2020 and 2021. As a result of the COVID-19 pandemic restricting in-person interactions, residency programs have used alternative platforms to reach applicants. Given the increasing use of such applications, social media will likely continue to become an important aspect of professional engagement in ophthalmology.
RESUMO
AIM: Elevated Src-Family tyrosine kinase (SFK) activity drives carcinogenesis in vivo and elevated SFK activity is found ubiquitously in human cancers. Although human squamous cell carcinomas (SCCs) demonstrate increased SFK activity, in silico analysis of SCCs demonstrates that only 0.4% of lesions contain mutations that could potentially increase SFK activity; similarly, a low frequency of activating SFK mutations is found in other major cancers. These findings indicate that SFK activation in cancers likely is not due to activating mutations but alternative mechanisms. To evaluate potential alternative mechanisms, we evaluated the selectivity of c-Cbl and Srcasm in downregulating native and activated mutant forms of SFKs. MATERIALS AND METHODS: We co-transfected native and activated forms of Src and Fyn with c-Cbl and Srcasm into HaCaT cells and monitored the ability of Srcasm and c-Cbl to downregulate native and activated forms of SFKs by Western blotting. The mechanism of downregulation was probed using mutant forms of Srcasm and c-Cbl and using proteosomal and lysosomal inhibition. RESULTS: The data indicate that Srcasm downregulates native Fyn and Src more effectively than c-Cbl, whereas c-Cbl preferentially downregulates activated SFK mutants, including Fyn Y528F, more effectively than Srcasm. Srcasm downregulates SFKs through a lysosomal-dependent mechanism while c-Cbl utilizes a proteosomal-dependent mechanism. CONCLUSION: Given the rarity of activating SFK mutations in human cancer, these data indicate that decreasing Srcasm level/function may represent a mechanism for increasing SFK activity in SCC and other human tumors.
RESUMO
Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma. Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser captured microdissection of human SCCIS and the adjacent epidermis to isolate genomic DNA and RNA for next-generation sequencing. Whole-exome sequencing identified UV-signature mutations in multiple genes, including NOTCH1-3 in the epidermis and SCCIS and oncogenic TP53 mutations in SCCIS. Gene families, including SLFN genes, contained UV/oxidative-signature disruptive epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1,166 differentially expressed genes; the top five enriched gene ontology biological processes included (i) immune response, (ii) epidermal development, (iii) protein phosphorylation, (iv) regulation of catalytic activity, and (v) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. NEURL1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.
