RESUMEN
Improving the prevention, detection, and treatment of Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) across racial, ethnic, and other diverse populations is a national priority. To this end, this paper proposes the development of the Standard Health Record for Dementia (SHRD, pronounced "shared") for collecting and sharing AD/ADRD real-world data (RWD). SHRD would replace the current unstandardized, fragmented, or missing state of key RWD with an open source, consensus-based, and interoperable common data standard. This paper describes how SHRD could leverage the best practices of the Minimal Common Oncology Data Elements (mCODETM) initiative to advance prevention, detection, and treatment; gain adoption by clinicians and electronic health record (EHR) vendors; and establish sustainable business and governance models. It describes a range of potential use cases to advance equity, including strengthening public health surveillance by facilitating AD/ADRD registry reporting; improving case detection and staging; and diversifying participation in clinical trials.
Asunto(s)
Enfermedad de Alzheimer , Equidad en Salud , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/prevención & control , Registros Electrónicos de Salud , HumanosRESUMEN
Eph receptors and their membrane-associated ephrin ligands regulate cell-cell interactions during development. The biochemical and biologic functions of this receptor tyrosine kinase family are still being elucidated but include roles in nervous system segmentation, axon pathfinding, and angiogenesis. To isolate murine orthologs of three zebrafish Eph family members (zek1, zek2, and zek3), we have used a degenerate RT-PCR-based cloning method specific for members of the Eph family. Although this method was effective for isolation of Eph receptor cDNAs, including members of both the A and B subfamilies, our results suggested that zek1 may not have a murine ortholog. The isolated cDNAs were also used to generate RNA in situ hybridization probes to examine the expression patterns of murine EphA2, A3, A4, A7, B1, B2, and B4 in 9.5-dpc mouse embryos. In addition to the expected abundant expression of these Eph receptors in the developing CNS and the presence of EphB receptors in vascular tissues, several of the EphA receptors were expressed in discrete regions of the developing vasculature. These results suggest a role for both EphA and EphB receptors in vascular development.
Asunto(s)
Vasos Sanguíneos/embriología , Sistema Nervioso Central/embriología , Clonación Molecular/métodos , Regulación del Desarrollo de la Expresión Génica , Familia de Multigenes , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de la Familia Eph , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas de Pez Cebra , Secuencia de Aminoácidos , Animales , Vasos Sanguíneos/metabolismo , Southern Blotting , Sistema Nervioso Central/metabolismo , ADN Complementario/genética , Evolución Molecular , Femenino , Proteínas Fetales/biosíntesis , Proteínas Fetales/genética , Biblioteca de Genes , Edad Gestacional , Ratones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Hibridación de Ácido Nucleico , Filogenia , ARN Mensajero/análisis , ARN Mensajero/genética , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Vertebrados/genética , Pez Cebra/genéticaRESUMEN
In a search for novel tyrosine kinases involved in vertebrate development, we have isolated cDNAs corresponding to three distinct members of the Eph-family of receptor tyrosine kinases. Whole mount RNA in situ hybridization analysis showed all three genes were most abundantly expressed in the developing nervous system. zek1 (zebrafish Eph-like kinase1) encodes a 981 amino acid polypeptide closely related to the murine Sek1 and Bsk receptors. Cos-1 cells transfected with zek1 produce a 141 kilodalton tyrosine phosphorylated protein which is recognized by antibodies raised against two predicted Zek1 peptides. These antibodies also recognized a protein of the same apparent molecular weight in lysates from zebrafish embryos and adults. Widespread expression of zek1 in the developing brain and neural tube suggested a generalized function of the Zek1 receptor in neuronal cell ontogeny.