Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women but less is known about BBD in African American women. As African American women suffer from disproportionate mortality due to breast cancer, special focus on pathologic characteristics that may influence disease risk is warranted. Benign breast biopsies from African American women were identified by the University Pathology Group (Detroit, MI). African American women of ages 20 to 84 years, who underwent a breast biopsy from 1997 to 2000, were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit Surveillance Epidemiology and End Results (SEER) program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD. A total of 1,406 BBD biopsies from African American women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed nonproliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were more than three-fold more likely to develop breast cancer as compared with women who had nonproliferative disease [relative risk (RR) 3.29, 95% confidence interval (CI) 1.21-8.93]. Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and potentially improved survival.
While there is a rich history of studies involving robots and individuals with autism spectrum disorders (ASD), few of these studies have made substantial impact in the clinical research community. In this paper we first examine how differences in approach, study design, evaluation, and publication practices have hindered uptake of these research results. Based on ten years of collaboration, we suggest a set of design principles that satisfy the needs (both academic and cultural) of both the robotics and clinical autism research communities. Using these principles, we present a study that demonstrates a quantitatively measured improvement in human-human social interaction for children with ASD, effected by interaction with a robot.
BACKGROUND COVID-19 has spread worldwide since late 2019, with an unprecedented case count and death toll globally. Health care personnel (HCP), first responders, and other essential and frontline workers (OEWs) are at increased risk of SARS-CoV-2 infection because of frequent close contact with others. OBJECTIVE The Arizona Healthcare, Emergency Response, and Other Essential Workers Study (AZ HEROES) aims to examine the epidemiology of SARS-CoV-2 infection and COVID-19 illness among adults with high occupational exposure risk. Study objectives include estimating the incidence of SARS-CoV-2 infection in essential workers by symptom presentation and demographic factors, determining independent effects of occupational and community exposures on incidence of SARS-CoV-2 infection, establishing molecular and immunologic characteristics of SARS-CoV-2 infection in essential workers, describing the duration and patterns of real-time reverse transcription–polymerase chain reaction (rRT-PCR) positivity, and examining postvaccine immunologic response. METHODS Eligible participants include Arizona residents aged 18 to 85 years who work at least 20 hours per week in an occupation involving regular direct contact (ie, within 3 feet) with others. Recruitment goals are stratified by demographic characteristics (50% aged 40 years or older, 50% women, and 50% Hispanic or American Indian), by occupation (40% HCP, 30% first responders, and 30% OEWs), and by prior SARS-CoV-2 infection (with up to 50% seropositive at baseline). Information on sociodemographics, health and medical history, vaccination status, exposures to individuals with suspected or confirmed SARS-CoV-2 infection, use of personal protective equipment, and perceived risks are collected at enrollment and updated through quarterly surveys. Every week, participants complete active surveillance for COVID-like illness (CLI) and self-collect nasal swabs. Additional self-collected nasal swab and saliva specimens are collected in the event of CLI onset. Respiratory specimens are sent to Marshfield Laboratories and tested for SARS-CoV-2 by rRT-PCR assay. CLI symptoms and impact on work and productivity are followed through illness resolution. Serum specimens are collected every 3 months and additional sera are collected following incident rRT-PCR positivity and after each COVID-19 vaccine dose. Incidence of SARS-CoV-2 infections will be calculated by person-weeks at risk and compared by occupation and demographic characteristics as well as by seropositivity status and infection and vaccination history. RESULTS The AZ HEROES study was funded by the US Centers for Disease Control and Prevention. Enrollment began on July 27, 2020; as of May 1, 2021, a total of 3165 participants have been enrolled in the study. Enrollment is expected to continue through December 1, 2021, with data collection continuing through at least April 2022, contingent upon funding. CONCLUSIONS AZ HEROES is unique in aiming to recruit a diverse sample of essential workers and to prospectively follow strata of SARS-CoV-2 seronegative and seropositive adults. Survey results combined with active surveillance data on exposure, CLI, weekly molecular diagnostic testing, and periodic serology will be used to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, assess the intensity and durability of immune responses to natural infection and COVID-19 vaccination, and contribute to the evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/28925
Abstract Though alcohol consumption has been implicated in the pathogenesis of oropharyngeal cancer, the molecular mechanism for the pathogenesis of alcohol-related oropharyngeal cancer is poorly understood. In our study, we sought to identify key microRNAs (miRNA), piwi-interacting RNAs (piRNA), and long non-coding RNAs (lncRNA) dysregulated by ethanol, as well as its known carcinogenic metabolite acetaldehyde, to determine the role these non-coding RNAs (ncRNA) play in the pathogenesis and progression of oropharyngeal cancer. Using next generation sequencing analysis, we analyzed the non-coding RNA of head and neck squamous cell carcinoma (HNSCC) patients. In order to further investigate these ncRNAs, we exposed a panel of normal oral epithelial cell lines (OKF4, OKF 6) to 0.1%, 0.3%, and 1.0% ethanol for 4 weeks to represent social drinkers, moderate drinkers, and heavy drinkers respectively, and performed qPCR arrays to determine alcohol regulation of piRNAs and lncRNAs in vitro. We identified a panel of 5 piRNAs, 6 lncRNAs, 8 miRNAs and that were dysregulated consistently in vitro and clinically between alcohol drinkers and those who are non-drinkers. The five piRNAs (piR 25894, piR 35373, piR 266308, piR 34946, and piR 58510) were upregulated between parental cells and the alcohol-treated derivatives in both clinical and in-vitro data, and further investigation may elucidate their role as oncogenes. SAF and Zeb2Nat, two lncRNAs implicated in oncogenesis, exhibited the highest fold change, and the stem cell genes Nanog and Oct-4, and the epithelial-to-mesenchymal transition (EMT) gene Vimentin, were also upregulated through ethanol treatment, thus suggesting that SAF and Zeb2Nat are important in the pathogenesis of alcohol-induced oropharyngeal cancers by promoting expression of the EMT phenotype and stemness. Ectopic expression of miR-30a-5p and miR-934 resulted in increased expression of the stem cell genes, CD44, Oct3/4, Nanog, BMI-1. Forced expression of these miRNAs also resulted in increased proliferation, increased invasion, and inhibition of cisplatin-induced apoptosis, signifying the malignant transformation of normal oral cells. Identification of key ncRNAs differentially expressed in alcohol-related oropharyngeal cancer may reveal important steps in the initiation and progression of oropharyngeal cancer. These key ncRNAs may also serve as indicators and therapeutic targets for more effective treatments of alcohol-associated oropharyngeal cancer. Citation Format: Maarouf A. Saad, Elizabeth Kim, Vicky Yu, Jonjei Ku, Selena Z. Kuo, Hao Zheng, Elham Rahimy, Jessica Wang-Rodriguez, Weg M. Ongkeko. Alcohol-dysregulated non-codingRNAs in the pathogenesis of oropharyngeal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3556. doi:10.1158/1538-7445.AM2014-3556
Understanding the relative risk of SARS-CoV-2 infection across occupations can inform guidance to protect workers and communities. Less is known about infection risk for first responders and other essential workers than for health care personnel.
Objective
To compare the prevaccination incidence of SARS-CoV-2 infection among first responders and other essential workers with incidence among health care personnel.
Design, Setting, and Participants
This was a prospective cohort study of health care personnel, first responders, and other essential workers in Arizona from July 20, 2020, to March 14, 2021. Participants were seronegative at enrollment, had frequent direct contact with others at work, worked at least 20 hours per week, and submitted weekly nasal swab specimens for real-time reverse transcriptase polymerase chain reaction analysis. Data analyses were performed from April 19, 2021, to June 4, 2021.
Exposures
Occupation was the primary exposure of interest. Confounders assessed were sociodemographic characteristics, health status, community exposure, and work exposure.
Main Outcomes and Measures
Crude incidence of SARS-CoV-2 infection was defined as the sum of first positive SARS-CoV-2 infections in participants divided by person-weeks at risk. Negative binomial regression was used to model SARS-CoV-2 infection by occupation to estimate unadjusted and adjusted incidence rate ratios (IRRs). The least absolute shrinkage and selection operator (LASSO) method was used to generate a parsimonious multivariable model.
Results
The study cohort comprised 1766 Arizona workers (mean age [SD], 43.8 [11.1] years; 1093 [61.9%] female; 401 [22.7%] were Hispanic and 1530 [86.6%] were White individuals) of whom 44.2% were health care personnel, 22.4% first responders, and 33.4% other essential workers. The cohort was followed up for 23 393 person-weeks. Crude incidence of SARS-CoV-2 infection was 6.7, 13.2, and 7.4 per 1000 person-weeks at risk for health care personnel, first responders, and other essential workers, respectively. In unadjusted models, first responders had twice the incidence of infection as health care personnel (IRRs, 2.01; 95% CI, 1.44-2.79). While attenuated, this risk remained elevated in adjusted LASSO-optimized models (IRR, 1.60; 95% CI, 1.07-2.38). Risk of infection among other essential workers was no different than for health care personnel in unadjusted or adjusted models.
Conclusions and Relevance
This prospective cohort study found that first responders had a higher incidence of SARS-CoV-2 infection than health care personnel, even after adjusting for potential confounding factors. Given their frequent contact with each other and with the public and their high rates of SARS-CoV-2 infection, the safety challenges for first responders warrant greater public health attention and research.
Alcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype. Using RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC. From RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934. Alcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC.
