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2.
Health Equity ; 5(1): 124-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33778315

RESUMO

Purpose: Refugees and asylum seekers have unique and complex needs related to their experiences of forced displacement and resettlement. Cultural competence is widely recognized as important for the provision of effective and equitable services for refugee populations. However, the delivery of culturally appropriate services-including health care and social services-is often complicated by unclear definitions and operationalization of cultural competence. Further, the unique needs and priorities of people from refugee backgrounds are under-addressed in the cultural competence literature. This scoping review seeks to synthesize the peer-reviewed literature examining cultural competence in refugee service settings. Methods: A systematic search of four databases (EBSCO, Proquest, Scopus and Google Scholar) identified 26 relevant peer-reviewed studies for analysis. Results: A range of approaches to cultural competence were identified at the level of individual providers and organizations. Conclusion: We identified a need for greater refugee participation and perspectives in the practice of cultural competence, increased conceptual clarity and greater recognition of structural barriers. We call for further rigorous research that critically examines the concept of cultural competence and its meaning and relevance to refugee populations.

4.
Acta Neuropathol Commun ; 6(1): 48, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880060

RESUMO

Genomic characterization has begun to redefine diagnostic classifications of cancers. However, it remains a challenge to infer disease phenotypes from genomic alterations alone. To help realize the promise of genomics, we have performed a quantitative proteomics investigation using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and 41 tissue samples spanning the 4 genomically based subgroups of medulloblastoma and control cerebellum. We have identified and quantitated thousands of proteins across these groups and find that we are able to recapitulate the genomic subgroups based upon subgroup restricted and differentially abundant proteins while also identifying subgroup specific protein isoforms. Integrating our proteomic measurements with genomic data, we calculate a poor correlation between mRNA and protein abundance. Using EPIC 850 k methylation array data on the same tissues, we also investigate the influence of copy number alterations and DNA methylation on the proteome in an attempt to characterize the impact of these genetic features on the proteome. Reciprocally, we are able to use the proteome to identify which genomic alterations result in altered protein abundance and thus are most likely to impact biology. Finally, we are able to assemble protein-based pathways yielding potential avenues for clinical intervention. From these, we validate the EIF4F cap-dependent translation pathway as a novel druggable pathway in medulloblastoma. Thus, quantitative proteomics complements genomic platforms to yield a more complete understanding of functional tumor biology and identify novel therapeutic targets for medulloblastoma.


Assuntos
Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Meduloblastoma/genética , Meduloblastoma/metabolismo , Proteínas de Neoplasias/genética , Proteogenômica/métodos , Cromatografia Líquida , Metilação de DNA , Feminino , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Proteoma , RNA Mensageiro , Espectrometria de Massas em Tandem
5.
Oncotarget ; 6(16): 14584-95, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-25970789

RESUMO

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Cerebelares/genética , Meduloblastoma/genética , Proteômica/métodos , Linhagem Celular Tumoral , Neoplasias Cerebelares/patologia , Humanos , Espectrometria de Massas , Meduloblastoma/patologia , Fatores de Risco
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