Objective To determine the relative correlations of Twitter and Google Search user trends concerning smell loss with daily coronavirus disease 2019 (COVID-19) incidence in the United States, compared to other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. To describe the effect of mass media communications on Twitter and Google Search user trends. Study Design Retrospective observational study. Setting United States. Subjects and Methods Google Search and “tweet” frequency concerning COVID-19, smell, and nonsmell symptoms of COVID-19 generated between January 1 and April 8, 2020, were collected using Google Trends and Crimson Hexagon, respectively. Spearman coefficients linking each of these user trends to COVID-19 incidence were compared. Correlations obtained after excluding a short timeframe (March 22 to March 24) corresponding to the publication of a widely read lay media publication reporting anosmia as a symptom of infection was performed for comparative analysis. Results Google searches and tweets concerning all nonsmell symptoms (0.744 and 0.761, respectively) and COVID-19 (0.899 and 0.848) are more strongly correlated with disease incidence than smell loss (0.564 and 0.539). Twitter users tweeting about smell loss during the study period were more likely to be female (52%) than users tweeting about COVID-19 more generally (47%). Tweet and Google Search frequency pertaining to smell loss increased significantly (>2.5 standard deviations) following a widely read media publication linking smell loss and SARS-CoV-2 infection. Conclusions Google Search and tweet frequency regarding fever and shortness of breath are more robust indicators of COVID-19 incidence than anosmia. Mass media communications represent important confounders that should be considered in future analyses.
Purpose:
Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood.
Experimental Design:
Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC). Twenty-eight additional HPV oropharyngeal cancer (HPVOPC) tumors from The Cancer Genome Atlas (TCGA) project were analyzed as a separate validation cohort. Genomic, transcriptomic, proteomic, computational, and functional analyses of HPVOPC were applied to these datasets.
Results:
Our analysis revealed circular, oncogenic DNA in nearly all HPVOPC, with circular human and human–viral hybrid ecDNA present in over a third of HPVOPC and viral circular DNA in remaining tumors. Hybrid ecDNA highly express fusion transcripts from HPV promoters and HPV oncogenes linked to downstream human transcripts that drive oncogenic transformation and immune evasion, and splice multiple, diverse human acceptors to a canonical SA880 viral donor site. HPVOPC have high E6*I expression with specific viral oncogene expression pattern related to viral or hybrid ecDNA composition.
Conclusions:
Nonchromosomal circular oncogenic DNA is a dominant feature of HPVOPC, revealing an unanticipated link between HPV and ecDNA that leverages the power of extrachromosomal inheritance to drive HPV and somatic oncogene expression.
ISSOs are caused by diverse pathologies. Given the considerable rates of neoplastic disease and cranial neuropathies, patients affected by an ISSO should be monitored closely and treated aggressively. Prompt surgical intervention, with either diagnostic or therapeutic intent, is often indicated.
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