RESUMEN
BACKGROUND: In 2014, the Preston Medical Library underwent a radical change, moving from an academic office building to the main floor of a regional medical center. While the library had previously served the public, health information requests have substantially increased in volume due to the new location. Researchers analyzed request data to see if the service's reach has expanded to counties that previously had not used the service, to see which counties have requested the most health information, and to ascertain whether more requests are from counties with higher poverty rates. CASE PRESENTATION: Each health information request is logged with the subject nature and patron contact information. Consumer health request data were downloaded from the library database. Names and other identifying data were removed. Request forms were sorted and reviewed by zip code and county, comparing number of requests as well as poverty levels. Tableau was utilized to create maps, visually showing patron concentrations and poverty levels. CONCLUSIONS: There were 3,141 health information requests from September 21, 2014, to May 31, 2019. The majority of requests were from local counties. Requests were also received from counties that had not been previously reached and counties with elevated poverty levels. Collecting data on patron interactions is not only critical for institutional reporting, but also for community outreach. Understanding that data require taking additional steps to filter the information, assess local demographics, and customize library services. Researchers anticipate being able to better tailor services to the community based on the results.
Asunto(s)
Información de Salud al Consumidor/estadística & datos numéricos , Hospitales , Bibliotecas Médicas/estadística & datos numéricos , Mercadotecnía , Humanos , Conducta en la Búsqueda de Información , TennesseeRESUMEN
Cancer stem-like cells are hypothesized to be the major tumor-initiating cell population of human cutaneous squamous cell carcinoma (cSCC), but the landscape of molecular alterations underpinning their signaling and cellular phenotypes as drug targets remains undefined. In this study, we developed an experimental pipeline to isolate a highly enriched CD133+CD31-CD45-CD61-CD24- (CD133+) cell population from primary cSCC specimens by flow cytometry. The CD133+ cells show enhanced stem-like phenotypes, which were verified by spheroid and colony formation in vitro and tumor generation in vivo Gene expression profiling of CD133+/- cells was compared and validated, and differentially expressed gene signatures and top pathways were identified. CD133+ cells expressed a repertoire of stemness and cancer-related genes, including NOTCH and NOTCH1-mediated NF-κB pathway signaling. Other cancer-related genes from WNT, growth factor receptors, PI3K/mTOR, STAT pathways, and chromatin modifiers were also identified. Pharmacologic and genetic targeting of NOTCH1, IKKα, RELA, and RELB modulated NF-κB transactivation, the CD133+ population, and cellular and stemness phenotypes. Immunofluorescent staining confirmed colocalization of CD133+ and IKKα expression in SCC tumor specimens. Our functional, genetic, and pharmacologic studies uncovered a novel linkage between NOTCH1, IKKα, and NF-κB pathway activation in maintaining the CD133+ stem SCC phenotypes. Studies investigating markers of activation and modulators of NOTCH, IKK/NF-κB, and other pathways regulating these cancer stem gene signatures could further accelerate the development of effective therapeutic strategies to treat cSCC recurrence and metastasis. Mol Cancer Ther; 17(9); 2034-48. ©2018 AACR.
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Carcinoma de Células Escamosas/genética , Quinasa I-kappa B/genética , FN-kappa B/genética , Células Madre Neoplásicas/metabolismo , Receptor Notch1/genética , Neoplasias Cutáneas/genética , Antígeno AC133/genética , Antígeno AC133/metabolismo , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Diaminas/farmacología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Quinasa I-kappa B/metabolismo , Masculino , Ratones Desnudos , FN-kappa B/metabolismo , Receptor Notch1/antagonistas & inhibidores , Receptor Notch1/metabolismo , Transducción de Señal/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Tiazoles/farmacología , Trasplante HeterólogoRESUMEN
DNA microarray technology has become a powerful tool in the arsenal of the molecular biologist. Capitalizing on high precision robotics and the wealth of DNA sequences annotated from the genomes of a large number of organisms, the manufacture of microarrays is now possible for the average academic laboratory with the funds and motivation. Microarray production requires attention to both biological and physical resources, including DNA libraries, robotics, and qualified personnel. While the fabrication of microarrays is a very labor-intensive process, production of quality microarrays individually tailored on a project-by-project basis will help researchers shed light on future scientific questions.
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Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Animales , Diseño de Equipo , Técnicas Genéticas , Humanos , RobóticaRESUMEN
Understanding the language encrypted in the gene regulatory regions of the human genome is a challenging goal for the genomic era. Although customary extrapolations from steady-state mRNA levels have been effective, deciphering these regulatory codes will require additional empirical data sets that more closely reflect the dynamic progression of molecular events responsible for inducible transcription. We describe an approach using chromatin immunoprecipitation to profile the kinetic occupancy of the transcriptional coactivator and histone acetyltransferase p300 at numerous mitogen-induced genes in activated T cells. Comparison of these profiles reveals a class of promoters that share common patterns of inducible expression, p300 recruitment, dependence on selective p300 domains, and sensitivity to histone deacetylase inhibitors. Remarkably, this class also shares an evolutionarily conserved promoter composition and structure that accurately predicts additional human genes with similar functional attributes. This "reverse genomic" approach will have broad application for the genome-wide classification of promoter structure and function.