From medical school through residency applications: Puerto Ricans may face ignorance and prejudice.

It is not that unusual to find that Americans are unaware that Puerto Rico is a territory of the United States, and, like them, Puerto Ricans are U.S citizens enjoying the same liberties, freedoms, and rights. It may be less expected to face such incognizance or ignorance within the medical community as careers in medicine offer healthcare professionals the opportunity to serve patients spanning race, ethnicity, gender, sexual orientation, religion, and other demographic differences. Unfortunately, some of the personal experiences of the primary author have prompted us to cull four personal narratives of Puerto Rican individuals (Boricuas), who comprise 20.8% of the Hispanic, Latino, or Spanish Origin applicants to U.S. medical schools, during various early stages of a medical career. Of course, these personal anecdotes, offered in response to just a few general questions about recent experiences of bias in medical applications or in early training, do not indicate pervasive bias. Similarly, these instances may be more common than people in the medical community would prefer to believe. In the brief narratives that follow, Boricuas at different junctures in their medical educations highlight the bias that they have faced and their reactions to it. We present this information with the hope of promoting awareness of potential biases at different stages of medical education.

Solving Problems Due to Hurricane Maria and COVID-19: CT Trends in Puerto Rico Before, During, and Beyond Public Health Crises.

Our objective was to evaluate the impact of recent public health crises on radiology CT services in Puerto Rico. We gathered and analyzed CT statistics from 2 of Puerto Rico's major private hospital groups and obtained monthly data from January 2016 to March 2021. We quantified short- and long-term impacts of Hurricane Maria (September 2016-August 2017, September 2017-August 2018, September 2018-August 2019) and COVID-19 (April 2019-March 2020, April 2020-March 2021) by calculating month-to-month and year-to-year percentage differences for each hospital and all hospitals combined for the dates leading up to, in the immediate aftermath, and following these major events. Despite short-term effects throughout September from Hurricane Maria, there were no noticeable year-to-year differences in the total number of CT studies performed. Both March and April 2020 highlighted the instantaneous impact caused by COVID-19; these months contributed less than 6% of the total yearly scans performed between April 2019 and March 2020 and April 2020-March 2021 for all the hospitals individually. Hurricane Maria exerted a short-term impact on CT studies performed throughout September 2017. COVID-19 also demonstrated immediate yet prolonged effects on the number of CT studies performed with all 3 hospitals reporting decreases between a full pandemic year and the year prior. Our results support fortifying medical and societal infrastructure to better prepare for future natural and public health disasters, particularly in Puerto Rico and similarly resourced areas, to maintain steady, if somewhat diminished, radiology services such as CT for regular and emergency purposes.

Sox2 induces glioblastoma cell stemness and tumor propagation by repressing TET2 and deregulating 5hmC and 5mC DNA modifications.

DNA methylation is a reversible process catalyzed by the ten-eleven translocation (TET) family of enzymes (TET1, TET2, TET3) that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Altered patterns of 5hmC and 5mC are widely reported in human cancers and loss of 5hmC correlates with poor prognosis. Understanding the mechanisms leading to 5hmC loss and its role in oncogenesis will advance the development of epigenetic-based therapeutics. We show that TET2 loss associates with glioblastoma (GBM) stem cells and correlates with poor survival of GBM patients. We further identify a SOX2:miR-10b-5p:TET2 axis that represses TET2 expression, represses 5hmC, increases 5mC levels, and induces GBM cell stemness and tumor-propagating potential. In vivo delivery of a miR-10b-5p inhibitor that normalizes TET2 expression and 5hmC levels inhibits tumor growth and prolongs survival of animals bearing pre-established orthotopic GBM xenografts. These findings highlight the importance of TET2 and 5hmC loss in Sox2-driven oncogenesis and their potential for therapeutic targeting.

A Sox2:miR-486-5p Axis Regulates Survival of GBM Cells by Inhibiting Tumor Suppressor Networks.

Glioblastoma multiforme (GBM) and other solid malignancies are heterogeneous and contain subpopulations of tumor cells that exhibit stem-like features. Our recent findings point to a dedifferentiation mechanism by which reprogramming transcription factors Oct4 and Sox2 drive the stem-like phenotype in glioblastoma, in part, by differentially regulating subsets of miRNAs. Currently, the molecular mechanisms by which reprogramming transcription factors and miRNAs coordinate cancer stem cell tumor-propagating capacity are unclear. In this study, we identified miR-486-5p as a Sox2-induced miRNA that targets the tumor suppressor genes PTEN and FoxO1 and regulates the GBM stem-like cells. miR-486-5p associated with the GBM stem cell phenotype and Sox2 expression and was directly induced by Sox2 in glioma cell lines and patient-derived neurospheres. Forced expression of miR-486-5p enhanced the self-renewal capacity of GBM neurospheres, and inhibition of endogenous miR-486-5p activated PTEN and FoxO1 and induced cell death by upregulating proapoptotic protein BIM via a PTEN-dependent mechanism. Furthermore, delivery of miR-486-5p antagomirs to preestablished orthotopic GBM neurosphere-derived xenografts using advanced nanoparticle formulations reduced tumor sizes in vivo and enhanced the cytotoxic response to ionizing radiation. These results define a previously unrecognized and therapeutically targetable Sox2:miR-486-5p axis that enhances the survival of GBM stem cells by repressing tumor suppressor pathways. SIGNIFICANCE: This study identifies a novel axis that links core transcriptional drivers of cancer cell stemness to miR-486-5p-dependent modulation of tumor suppressor genes that feeds back to regulate glioma stem cell survival.