Aberrant methylation of genomic DNA has been reported in many cancers. Specific DNA methylation patterns have been shown to provide clinically useful prognostic information and define molecular disease subtypes with different response to therapy and long-term outcome. Osteosarcoma is an aggressive malignancy for which approximately half of tumors recur following standard combined surgical resection and chemotherapy. No accepted prognostic factor save tumor necrosis in response to adjuvant therapy currently exists, and traditional genomic studies have thus far failed to identify meaningful clinical associations. We studied the genome-wide methylation state of primary tumors and tested how they predict patient outcomes. We discovered relative genomic hypomethylation to be strongly predictive of response to standard chemotherapy. Recurrence and survival were also associated with genomic methylation, but through more site-specific patterns. Furthermore, the methylation patterns were reproducible in three small independent clinical datasets. Downstream transcriptional, in vitro, and pharmacogenomic analysis provides insight into the clinical translation of the methylation patterns. Our findings suggest the assessment of genomic methylation may represent a strategy for stratifying patients for the application of alternative therapies.
Background
Though the proportion of women in medical schools has increased, gender disparities among those who pursue research careers still exists. In this study, we seek to better understand the main factors contributing to the existing gender disparities among medical students choosing to pursue careers in medical research.
Methods
A secondary cross-sectional cohort analysis of previously published data was conducted using a 70-item survey that was sent to 16,418 medical students at 32 academic medical centers, and was IRB exempt from the need for ethical approval at the University of Illinois at Chicago and the University of Pennsylvania. Data was collected from September 2012 to December 2014. Survey results were analyzed using chi-square tests and Cramer’s V to determine gender differences in demographic characteristics (training stage, race/ethnicity, marital status, parental status, financial support, and parental career background), career sector choice, career content choice, specialty choice, foreseeable career obstacles, and perceptions about medical research careers.
Results
Female respondents were more likely to be enrolled in MD-only programs, while male respondents were more likely to be enrolled in MD/PhD programs. More male students selected academia as their first-choice career sector, while more female respondents selected hospitalist as their first-choice career sector. More female respondents identified patient care and opportunities for community service as their top career selection factors, while more male respondents identified research and teaching as their top career selection factors. Student loan burden, future compensation, and work/life balance were the most reported obstacles to pursuing a career in medical research.
Conclusions
There are many factors from a medical student’s perspective that may contribute to the existing gender disparities in pursuing a career in medical research. While much progress has been made in attracting nearly equal numbers of men and women to the field of medicine, active efforts to bridge the gap between men and women in medical research careers are needed.
INTRODUCTION: In this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD. METHODS: We inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We used in vivo two-photon imaging to measure capillary stalling, penetrating arteriole flow, and vascular inflammation. We also characterized short-term memory function and gene expression changes in cerebral microvessels. RESULTS: We found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways. DISCUSSION: Oxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target.
Telemedicine utilization among otolaryngologists was rare prior to the COVID-19 pandemic. We sought to understand rates of telemedicine utilization by otolaryngologists amid unprecedented changes in care delivery during the pandemic. Using Medicare Physician/Supplier Procedure Summary data, we performed a retrospective cross-sectional analysis of telemedicine services provided to Medicare beneficiaries by otolaryngologists in 2020. The total number of services and amount of reimbursement received by otolaryngologists for telemedical care increased by 52,989% and 73,147% in 2020 relative to 2019: 139,094 vs 262 services and $9.9 million vs $13,536, respectively. The mean telemedicine revenue per otolaryngologist offset only 8.8% ($9304.69) of losses from the reduction in mean in-person revenue between 2019 and 2020. Further research will be necessary to inform successful adoption of telemedicine within our field amid the ongoing COVID-19 pandemic.
This discussion seeks to highlight the ability of poetry to combat loneliness, a growing public health problem with significant negative health outcomes that potentially impact millions of Americans. We argue that poetry can play a very relevant role and have an impact in medicine. Through a brief literature review of previous studies on poetry in medicine, we demonstrate that poetry can not only combat loneliness but can also play important roles in helping patients, physicians, and other healthcare professionals/providers. Because of the COVID-19 pandemic, we believe now is the perfect opportunity to utilize poetry because the benefits can be experienced even in solitude, which is why this is such a timely and pertinent issue today.
CONCLUSIONS:These results demonstrate that even in the absence of numeric data such as Step 1 scores and publication metrics, the written language in LORs can stratify applicants. This work suggests that highly descriptive and positive adjectives such as "bright" and "excellent" are important keywords for evaluators to include in LORs to indicate applicant strength. Finally, plastic surgery programs may consider using machine learning algorithms to assess LORs, not only to save residency programs time but also to mitigate individual reviewer bias.
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