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Resistance to endocrine therapy agents has presented a clinical obstacle in the treatment of hormone-dependent breast cancer. Our laboratory has initiated a study of microRNA regulation of signaling pathways that may result in breast cancer progression on aromatase inhibitors (AI). Microarray analysis of hormone refractory cell lines identified 115 differentially regulated microRNAs, of which 49 microRNAs were believed to be hormone-responsive. A group of microRNAs were inversely expressed in the AI-resistant lines versus LTEDaro and tamoxifen-resistant. We focused our work on hsa-miR-128a which was hormone-responsive and selectively up-regulated in the letrozole-resistant cell lines. Human miR-128a was predicted to target the TGFβ signaling pathway and indeed sensitivity to TGFβ was compromised in the letrozole-resistant cells, as compared to parental MCF-7aro. Human miR-128a was shown to negatively target TGFβRI protein expression by binding to the 3'UTR region of the gene. Inhibition of endogenous miR-128a resulted in resensitization of the letrozole-resistant lines to TGFβ growth inhibitory effects. These data suggest that the hormone-responsive miR-128a can modulate TGFβ signaling and survival of the letrozole-resistant cell lines. To our knowledge, this is the first study to address the role of microRNA regulation as well as TGFβ signaling in AI-resistant breast cancer cell lines. We believe that in addition to estrogen-modulation of gene expression, hormone-regulated microRNAs may provide an additional level of post-transcriptional regulation of signaling pathways critically involved in breast cancer progression and AI-resistance.

Although incarcerated adults are at elevated risk of dying from cancer, little is known about cancer screening in carceral settings. This study compared stage-specific incidence of screen-detectable cancers among incarcerated and recently released people with the general population, as a reflection of screening practices. We calculated the age- and sex-standardized incidence ratios (SIR) for early- and late-stage cancers for incarcerated and recently released adults compared to the general Connecticut population between 2005 and 2016. Our sample included 143 cancer cases among those incarcerated, 406 among those recently released, and 201 360 in the general population. The SIR for early-stage screen-detectable cancers was lower among incarcerated (SIR = 0.28, 95% CI = 0.17 to 0.43) and recently released (SIR = 0.69, 95% CI = 0.51 to 0.88) individuals than the general population. Incidence of late-stage screen-detectable cancer was lower during incarceration (SIR = 0.51, 95% CI = 0.27 to 0.88) but not after release (SIR = 1.32, 95% CI = 0.93 to 1.82). Findings suggest that underscreening and underdetection of cancer may occur in carceral settings. [ABSTRACT FROM AUTHOR]

Introduction: Stigma has inhibited public health practitioners' influence during the COVID-19 pandemic. We explore the experienced and anticipated stigma of people affiliated with a large university in the United States, using the Health Stigma and Discrimination Framework. Methods: We conducted a qualitative secondary substudy of 20 people who tested SARS-CoV-2 positive and 10 who tested negative in the summer of 2020, selected from a study of 3,324 university students and employees. Findings: No participants reported anticipated stigmatization prior to testing positive. However, eight of 20 participants recounted stigma marking (being marked by COVID-19 diagnosis or membership in a "high-risk" group) or manifestations of stigma after testing positive, including feelings of guilt or shame, and concerns about being judged as selfish or irresponsible. Three described being denied services or social interactions as a result of having had COVID-19, long after their infectiousness ended. Participants noted that clear public health messaging must be paired with detailed scientific information, rather than leaving people to resort to non-experts to understand the science. Discussion: Public health messaging designed to mitigate spread of SARS-CoV-2 and protect the community may perpetuate stigma and exacerbate inequities. As a result, people may avoid testing or treatment, mistrust public health messaging, or even use risk-increasing behavior as coping mechanisms. Implications for Practice: Intentional use of language that promotes equity and deters discrimination must be high priority for any COVID-19-related public health messaging. Partnership with community leaders to co-create programs and disseminate messaging is a critical strategy for reducing stigma, especially for historically mistreated groups. [ABSTRACT FROM AUTHOR]

This article explores the use of natural language processing (NLP) techniques to identify incarceration status in electronic health records (EHR) in emergency department settings. The study developed and validated NLP models to accurately identify incarceration status from clinical notes, which could potentially help address health disparities and tailor interventions for individuals with a history of incarceration. The study found that the Clinical-Longformer NLP model was effective in accurately identifying incarceration history, although it had limitations in distinguishing temporal labels. It is important to approach patients in a non-judgmental manner and confirm incarceration history before offering resources to avoid stigma. The NLP model can serve as a screening tool, but manual confirmation is recommended to avoid false positives or misplacements of electronic labels in patient files. [Extracted from the article]