ABSTRACT
Research is a crucial aspect of medical advancement, and applicants applying to dermatology often have high research outputs. With United States Medical Licensing Examination (USMLE) Step 1 becoming pass/fail, research productivity may be more emphasized. We primarily sought to assess predictors of medical school research productivity. Class of 2023 dermatology residents publicly listed on Accreditation Council for Graduate Medical Education-accredited programs were included. Their medical school bibliography and demographics were assessed using PubMed and other platforms (eg, Doximity, LinkedIn). By multivariable analysis, students who attended a top 25 medical school (ranked by US News and World Report) or were PhD graduates had significantly higher H-indices, average impact factors, and total years of research activity (P < .01). Top 25 medical school graduates also had significantly higher total peer-reviewed publications, first authorships, and clinical research papers (P < .01). PhD graduates had significantly more clinical research and fewer dermatology-related papers (P < .03). Graduates of osteopathic medical schools had significantly fewer review papers (P = .02). Gender and graduation from an international medical school had no relationship with research productivity. Our study demonstrates a correlation between applicant-specific factors and research productivity. Because the emphasis on research productivity may increase, understanding the mechanisms behind these relationships may guide future dermatology applicants or their mentors.
Subject(s)
Dermatology , Internship and Residency , Humans , United States , Schools, Medical , Education, Medical, Graduate , DemographyABSTRACT
BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring. METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics. RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to resistance. Proteomics identified elevation of downstream Nrf2 targets and the enrichment of enzymes involved in generation of biomass and reducing equivalents, metabolism of glucose, glutathione, NAD(P), and oxoacids. This was accompanied by biochemical and metabolic evidence of an enhanced reductive state dependent on coordinated glucose and glutamine catabolism, associated with reduced energy production and proliferation, despite normal mitochondrial structure and function. CONCLUSIONS: Our analysis identified coordinated metabolic changes associated with CDDP resistance that may provide new therapeutic avenues through targeting of these convergent pathways.
