Search

Interest in using internet search data, such as that from the Google Health Trends Application Programming Interface (GHT-API), to measure epidemiologically relevant exposures or health outcomes is growing due to their accessibility and timeliness. Researchers enter search term(s), geography, and time period, and the GHT-API returns a scaled probability of that search term, given all searches within the specified geographic-time period. In this study, we detailed a method for using these data to measure a construct of interest in 5 iterative steps: first, identify phrases the target population may use to search for the construct of interest; second, refine candidate search phrases with incognito Google searches to improve sensitivity and specificity; third, craft the GHT-API search term(s) by combining the refined phrases; fourth, test search volume and choose geographic and temporal scales; and fifth, retrieve and average multiple samples to stabilize estimates and address missingness. An optional sixth step involves accounting for changes in total search volume by normalizing. We present a case study examining weekly state-level child abuse searches in the United States during the coronavirus disease 2019 pandemic (January 2018 to August 2020) as an application of this method and describe limitations.

Economic hardship may lead to a wide range of negative outcomes, including violence. However, existing literature on economic hardship and violence is limited by reliance on official reports of violence and conflation of different measures of economic hardship. The goals of this study are to measure how violence-related injuries are associated with five measures of county-level economic shocks: unemployment rate, male mass layoffs, female mass layoffs, foreclosure rate, and unemployment rate change, measured cross-sectionally and by a 1-year lag. This study measures three subtypes of violence outcomes (child abuse, elder abuse, and intimate partner violence). Yearly county-level data were obtained on violence-related injuries and economic measures from 2005 to 2012 for all 87 counties in Minnesota. Negative binomial models were run regressing the case counts of each violence outcome at the county-year level on each economic indicator modeled individually, with population denominator offsets to yield incidence rate ratios. Crude models were run first, then county-level socio-demographic variables and year were added to each model, and finally fully-adjusted models were run including all socio-demographic variables plus all economic indicators simultaneously. In the fully-adjusted models, a county’s higher foreclosure rate is the strongest and most consistently associated with an increase in all violence subtypes. Unemployment rate is the second strongest and most consistent economic risk factor for all violence subtypes. Lastly, there appears to be an impact of gender specific to economic impacts on child abuse; specifically, male mass-lay-offs were associated with increased rates while female mass-lay-offs were associated with decreased rates. Understanding the associations of different types of economic hardship with a range of violence outcomes can aid in developing more holistic prevention and intervention efforts.

All Supplementary data figures and legends. Supplementary Figure 1. In Silico analysis of RUNX1 expression in human kidney cancer. Supplementary Figure 2. Knockdown of RUNX1 with shRNA causes a growth defect in two ccRCC cell lines. Supplementary Figure 3. RUNX1 deletion in 786-O* cells and orthotopic xenograft. Supplementary Figure 4. Principle component analysis. Gene expression variances between control (786-O pX, Red) and RUNX1 CRISPR cells (786-O A1, yellow and 786-O A3, purple). Supplementary Figure 5. Heterozygous deletion of RUNX2 in a GEM model of kidney cancer does not affect survival.

RNAseq data set

The recurring association of specific genetic lesions with particular types of cancer is a fascinating and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where, although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown protumorigenic role for the RUNX genes in this disease setting. Analysis of patient tumor biopsies together with loss-of-function studies in preclinical models established the importance of RUNX1 and RUNX2 in ccRCC. Patients with high RUNX1 (and RUNX2) expression exhibited significantly poorer clinical survival compared with patients with low expression. This was functionally relevant, as deletion of RUNX1 in ccRCC cell lines reduced tumor cell growth and viability in vitro and in vivo. Transcriptional profiling of RUNX1-CRISPR–deleted cells revealed a gene signature dominated by extracellular matrix remodeling, notably affecting STMN3, SERPINH1, and EPHRIN signaling. Finally, RUNX1 deletion in a genetic mouse model of kidney cancer improved overall survival and reduced tumor cell proliferation. In summary, these data attest to the validity of targeting a RUNX1-transcriptional program in ccRCC.Significance:These data reveal a novel unexplored oncogenic role for RUNX genes in kidney cancer and indicate that targeting the effects of RUNX transcriptional activity could be relevant for clinical intervention in ccRCC.

Supplementary Table 1. The relationship between RUNX2 and clinico-pathological characteristics of kidney cancer in the TMA study.

PURPOSE: Childhood and adult adversities occur more frequently among women and persons of colour, possibly influencing racial/ethnic disparities in substance use behaviours. This study investigates how childhood and adult adversities cluster together by race/ethnicity and how these adversity clusters predict binge drinking, tobacco, e-cigarette, and marijuana use in women. METHODS: Latent class analysis (LCA) was used in a combined sample from the 2015 and 2018 Minnesota College Student Health Survey to identify clusters of childhood adversities plus highly correlated adult adversities among Asian, Black, Latina, and White women aged 18-25. The LCA method allowed unique clusters of adversity to emerge from these data, stratified by race/ethnicity. Each substance use outcome was regressed on each adversity cluster across each race/ethnicity group. RESULTS: A seven-cluster model was selected for White women, a five-cluster model for Black women, and four-cluster models for Asian and Latina women. Differences across racial/ethnic clusters included the presence of a lifetime sexual assault only cluster in the White, Black, and Asian women that did not exist among Latina women. Across all racial/ethnic groups and substance use outcomes, the high adversity cluster exhibited the greatest risk. Significant racial/ethnic disparities were observed across several substance use behaviours; these were narrowed substantially among women with fewer adversities. CONCLUSIONS: In this study, subtyping women according to their histories of adversity revealed differences in substance use risk. The reduced substance use disparities found among those with lower adversities suggest that prevention of adversities may advance health equity.

PURPOSE: Despite recommendations from the World Health Organization and the American Academy of Pediatrics to exclusively breastfeed infants for their first 6 months of life, 75% of women do not meet exclusive breastfeeding guidelines and 60% do not meet their own breastfeeding goals. Numerous observational studies have linked maternal psychological distress (e.g., perceived stress, anxiety, depression) with non-optimal breastfeeding outcomes, such as decreased proportion and duration of exclusive breastfeeding. The physiological mechanisms underlying these associations, however, remain unclear. METHODS: For this narrative review, we evaluated the evidence for relationships between maternal psychological distress and lactation and breastfeeding outcomes in pregnancy and postpartum and the possible physiological mechanisms that facilitate these relationships. We searched PubMed using the following terms: “stress”, “anxiety”, “depression”, “breastfeeding”, and “lactation”. A further hand-search was conducted to ensure a thorough review of the literature. FINDINGS: Among the studies examined, methods used to assess maternal psychological distress were not uniform, with some studies examining perceived distress via a variety of validated tools and others measuring biological measures of distress, such as cortisol. Evidence supports a role for psychological distress in multiple breastfeeding outcomes, including delayed secretory activation and decreased duration of exclusive breastfeeding. One physiological mechanism proposed to explain these relationships is that psychological distress may impair the release of oxytocin, a hormone that plays a critical role in milk ejection during lactation. Continued impairment of milk ejection may lead to decreased milk production due to incomplete emptying of the breast during each feed. Maternal distress may also yield elevated levels of serum cortisol and decreased insulin sensitivity, which are associated with decreased milk production. The relationship between psychological distress and breastfeeding is likely to be bidirectional, however, in that breastfeeding appears to reduce maternal distress, again possibly via their effects on the pleasure/reward and calming effects of oxytocin on the mother. This suggests interventions to support lactation and breastfeeding goals in women who score high on measures of psychological distress would be beneficial for both maternal and infant well-being. IMPLICATIONS: Evidence to date suggests that maternal psychological distress may impair lactation and breastfeeding outcomes, but stronger study designs and rigorous assessment methods are needed. A better understanding of the physiological mechanisms leading to impaired lactation may assist in the development of early interventions for mothers experiencing distress. In addition, stress-reducing programs and policies should be investigated for their potential to improve breastfeeding outcomes.

Cancer cells are softer than the normal cells, and metastatic cells are even softer. These changes in biomechanical properties contribute to cancer progression by facilitating cell movement through physically constraining environments. To identify properties that enabled passage through physical constraints, cells that were more efficient at moving through narrow membrane micropores were selected from established cell lines. By examining micropore-selected human MDA MB 231 breast cancer and MDA MB 435 melanoma cancer cells, membrane fluidity and nuclear elasticity were excluded as primary contributors. Instead, reduced actin cytoskeleton anisotropy, focal adhesion density and cell stiffness were characteristics associated with efficient passage through constraints. By comparing transcriptomic profiles between the parental and selected populations, increased Ras/MAPK signalling was linked with cytoskeleton rearrangements and cell softening. MEK inhibitor treatment reversed the transcriptional, cytoskeleton, focal adhesion and elasticity changes. Conversely, expression of oncogenic KRas in parental MDA MB 231 cells, or oncogenic BRaf in parental MDA MB 435 cells, significantly reduced cell stiffness. These results reveal that MAPK signalling, in addition to tumour cell proliferation, has a significant role in regulating cell biomechanics. This article has an associated First Person interview with the first author of the paper., Highlighted Article: Selection for tumour cells that efficiently pass through narrow diameter microporous membranes reveals a prominent role for MAPK signalling in regulating cell elasticity.

Junia N de Brito,1 Jessica K Friedman,1 Rebecca L Emery,2 Dianne Neumark-Sztainer,1 Jerica M Berge,3 Susan M Mason1 1Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA; 2Department of Family Medicine and Biobehavioral Health, University of Minnesota, Duluth, MN, USA; 3Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, MN, USACorrespondence: Junia N de BritoDivision of Epidemiology and Community Health, University of Minnesota, 1300 S 2nd St, Suite 300, Minneapolis, MN, 55455, USATel +1 612-624-1818Email nogue013@umn.eduBackground: The coronavirus disease 2019 (COVID-19) pandemic increased mothers’ caregiving demands, potentially placing them at increased risk for reduced engagement in healthful behaviors and high psychological distress.Purpose: The purpose of this study was to describe perceived changes in moderate-vigorous physical activity (MVPA) and sedentary behaviors and the prevalence of different measures of psychological distress (depressive and anxiety symptoms, perceived stress, and positive and negative affect) among mothers. We also evaluated the associations of perceived change in MVPA and sedentary behaviors with measures of psychological distress.Methods: We conducted a cross-sectional survey with 317 mothers living with children (0– 20 years old) at home. Mothers self-reported perceived changes in MVPA and sedentary behaviors from before the pandemic to during COVID-19 stay-at-home orders and early reopening, and levels of depression and anxiety symptomatology, perceived stress, and positive and negative affect during the pandemic.Results: Compared to pre-pandemic levels, 39% of mothers reported engaging less in MVPA, and 63% reported engaging in more sedentary activities. One-quarter and 31% of mothers reported moderate/severe depressive and anxiety symptoms, respectively, and 78% medium/high levels of perceived stress. Adjusted linear regression analyses revealed that reduced MVPA and increased sedentary behaviors were associated with high average scores of depressive and anxiety symptoms, perceived stress, negative affect, and low scores of positive affect.Conclusion: A large proportion of mothers reported being less physically active and more engaged in sedentary behaviors, which were associated with increases in psychological distress. Clinical and public health intervention efforts should consider how to improve mothers’ physical and mental health as the country emerges from this crisis.Keywords: COVID-19, mothers, physical activity, stress, depression, anxiety

The COVID-19 pandemic has led to unemployment, school closures, movement restrictions, and social isolation, all of which are child abuse risk factors. Our objective was to estimate the effect of COVID-19 shelter in place (SIP) policies on child abuse as captured by Google searches. We applied a differences-in-differences design to estimate the effect of SIP on child abuse search volume. We linked state-level SIP policies to outcome data from the Google Health Trends Application Programming Interface. The outcome was searches for child abuse-related phrases as a scaled proportion of total searches for each state-week between December 31, 2017 and June 14, 2020. Between 914 and 1512 phrases were included for each abuse subdomain (physical, sexual, and emotional). Eight states and DC were excluded because of suppressed outcome data. Of the remaining states, 38 introduced a SIP policy between March 19, 2020 and April 7, 2020 and 4 states did not. The introduction of SIP generally led to no change, except for a slight reduction in child abuse search volume in weeks 8-10 post-SIP introduction, net of changes experienced by states that did not introduce SIP at the same time. We did not find strong evidence for an effect of SIP on child abuse searches. However, an increase in total search volume during the pandemic that may be differential between states with and without SIP policies could have biased these findings. Future work should examine the effect of SIP at the individual and population level using other data sources.

Urban, low-income, African American children and parents report lower quality primary care and face negative social determinants of health. High-quality well-child care is critical for this population. The purpose of this qualitative study was to compare and contrast parent and health care provider experiences of well-child care for urban, low-income, African American families to better understand the complex factors involved in care quality and health outcomes. Two data sets were analyzed using conventional content analysis, parent focus group data, and provider interviews. After analysis, results were sorted into similar categories, and convergence coding was completed to identify areas of agreement, partial agreement, dissonance, and silence. Thirty-five parents took part in four focus groups, and nine providers were interviewed. Following convergence coding, five categories and 31 subcategories were identified. The five categories included: social determinants of health, sources of advice and support, challenges with the healthcare system, parent-provider relationships, and anticipatory guidance topics. Triangulation demonstrated convergence between parents and providers understanding of the concepts and functions of well-child care, however the prominence and meaning varied within each category and sub-category. The variance in agreement, areas of silence, and dissonance shed light on why the population reports lower overall quality primary care.

Substantial evidence suggests that economic hardship causes violence. However, a large majority of this research relies on observational studies that use traditional violence surveillance systems that suffer from selection bias and over-represent vulnerable populations, such as people of color. To overcome limitations of prior work, we employed a quasi-experimental design to assess the impact of the Great Recession on explicit violence diagnoses (injuries identified to be caused by a violent event) and proxy violence diagnoses (injuries highly correlated with violence) for child maltreatment, intimate partner violence, elder abuse, and their combination. We used Minnesota hospital data (2004–2014), conducting a difference-in-differences analysis at the county level (n = 86) using linear regression to compare changes in violence rates from before the recession (2004–2007) to after the recession (2008–2014) in counties most affected by the recession, versus changes over the same time period in counties less affected by the recession. The findings suggested that the Great Recession had little or no impact on explicitly identified violence; however, it affected proxy-identified violence. Counties that were more highly affected by the Great Recession saw a greater increase in the average rate of proxy-identified child abuse, elder abuse, intimate partner violence, and combined violence when compared with less-affected counties.

Introduction: Substantial cross-sectional evidence exists supporting an association between high body mass index (BMI) during childhood and increased cardiometabolic risk factors. However, less is known about longitudinal associations of child BMI trajectories with biomarkers of cardiometabolic risk. The objective of this study was to (1) identify distinct BMI trajectories during childhood from ages 2-11 years and (2) evaluate the association of these BMI trajectories with biomarkers of cardiometabolic risk at ages 7-11 years. Methods: The analytic sample included 338 children living in low-income and racially/ethnically diverse households who participated in the NET-Works randomized intervention trial and the NET-Works 2 prospective follow-up study. BMI was measured at baseline (when children were 2-4 years of age) and again at 1-, 2-, 3- and 5-year follow-up visits. Percent of the 95 th percentile of BMI (%BMIp95) was the BMI metric calculated at each time point. At the 5-year follow-up visit, children (aged 7 to 11 years) completed assessments for carotid to anterior tibial artery pulse wave velocity (PWV), C-reactive protein (CRP), leptin, adiponectin, and oxidized low-density lipoprotein (oxLDL). Group-based trajectory modeling was used to identify child %BMIp95 trajectory groups. Adjusted linear regressions evaluated the associations between %BMIp95 trajectory groups and PWV, CRP, leptin, adiponectin, and oxLDL. Results: We identified two trajectory groups: (1) 75% of children had a moderate-decreasing trajectory (baseline BMI was below the 95th percentile of BMI and followed a moderate-decreasing trajectory over time), and (2) 25% had a marked-increasing trajectory (baseline BMI was above the 95th percentile of BMI and followed a steep increase over time). Relative to children in the moderate-decrease trajectory group, children in the marked-increase trajectory group had higher mean adjusted CRP (3.3 mg/L, 95% CI [1.6, 4.9]) and leptin (62.5 ng/mL, 95% CI [44.0, 80.9]), and lower levels of adiponectin (-1.4 μg/mL, 95% CI [-2.5, -0.1]). Differences in PWV and oxLDL were small and not statistically significant. Conclusions: Two unique BMI trajectories were observed among children living in low-income and racially/ethnically diverse households. Compared to children with steady BMI decrease over time, those with steady BMI increase over time had a higher baseline BMI and adverse inflammatory and adipokine profiles later in childhood. However, we found no evidence of differences in arterial stiffness, which could develop later in adolescence or adulthood. This study provides additional objective evidence supporting the importance of early-life tracking of BMI using the %BMIp95 metric and lifestyle interventions to reduce the risk of obesity and emerging cardiometabolic risk during childhood.

Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show, using MDA-MB-231 cells as a model, that the plasticity of at least some metastatic breast cancer cells is dependent on the transcriptional co-regulator CBFβ. We demonstrate that CBFβ is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells. We subsequently show, using an inducible CBFβ system, that the MET can be reversed, thus demonstrating the plasticity of CBFβ-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose expression is dependent on CBFβ. Finally, we demonstrate that loss of CBFβ inhibits the ability of metastatic breast cancer cells to invade bone cell cultures and suppresses their ability to form bone metastases in vivo. Together our findings demonstrate that CBFβ can determine the plasticity of the metastatic cancer cell phenotype, suggesting that its regulation in different micro-environments may play a key role in the establishment of metastatic tumours.

Background: Breast cancer screening practices and the influence of clinical guidelines or recommendations are well documented for physicians, but little is known about the screening practices of nonphysician providers (physician assistants and advanced practice registered nurses). The seven breast cancer screening guidelines or recommendations on the use of mammography have the most variation for screening average-risk women 40–49 years of age. Therefore, to better understand the practices of nonphysicians, this study will compare the practices of physicians with nonphysician providers for women 40–49 years of age. Materials and Methods: Minnesota physicians and nonphysicians were e-mailed an anonymous cross-sectional survey, which asked primary care providers about their mammography screening practices for average-risk women 40–44 and 45–49 years of age and to rate the influence of seven breast cancer screening recommendations on the use of mammography in their practice. Comparisons across providers' demographic and professional characteristics were conducted using chi-squared and Fisher's exact tests, as appropriate, and multivariate logistic regression analyses. Results: Of the respondents who practiced primary care (193 physicians, 50 physician assistants, and 197 advanced practice registered nurses), 66.7% reported recommending mammography for women at ages 40–44 and 77.2% recommended mammography for women at ages 45–49. Nonphysician providers were more likely to recommend screening in both these age groups (p

Summary Loss of p53 function contributes to the development of many cancers. While cell-autonomous consequences of p53 mutation have been studied extensively, the role of p53 in regulating the anti-tumor immune response is still poorly understood. Here, we show that loss of p53 in cancer cells modulates the tumor-immune landscape to circumvent immune destruction. Deletion of p53 promotes the recruitment and instruction of suppressive myeloid CD11b+ cells, in part through increased expression of CXCR3/CCR2-associated chemokines and macrophage colony-stimulating factor (M-CSF), and attenuates the CD4+ T helper 1 (Th1) and CD8+ T cell responses in vivo. p53-null tumors also show an accumulation of suppressive regulatory T (Treg) cells. Finally, we show that two key drivers of tumorigenesis, activation of KRAS and deletion of p53, cooperate to promote immune tolerance., Graphical Abstract, Highlights • Tumor-specific loss of p53 delays tumor rejection in immune-competent hosts • p53 loss increases myeloid infiltration through enhanced cytokine secretion • The increase in Treg cells in response to loss of p53 is independent of Kras mutation • Kras mutations coordinate with p53 loss to regulate myeloid recruitment, TP53 is one of the most frequently mutated genes in cancer; however, its significance in controlling tumor-immune crosstalk is not fully understood. Blagih et al. highlight a key role for tumor-associated loss of p53, a common oncogenic event, in regulating myeloid and T cell responses.

BACKGROUND The COVID-19 pandemic has created environments with increased risk factors for household violence, such as unemployment and financial uncertainty. At the same time, it led to the introduction of policies to mitigate financial uncertainty. Further, it hindered traditional measurements of household violence. OBJECTIVE Using an infoveillance approach, our goal was to determine if there were excess Google searches related to exposure to child abuse, intimate partner violence (IPV), and child-witnessed IPV during the COVID-19 pandemic and if any excesses are temporally related to shelter-in-place and economic policies. METHODS Data on relative search volume for each violence measure was extracted using the Google Health Trends application programming interface for each week from 2017 to 2020 for the United States. Using linear regression with restricted cubic splines, we analyzed data from 2017 to 2019 to characterize the seasonal variation shared across prepandemic years. Parameters from prepandemic years were used to predict the expected number of Google searches and 95% prediction intervals (PI) for each week in 2020. Weeks with searches above the upper bound of the PI are in excess of the model’s prediction. RESULTS Relative search volume for exposure to child abuse was greater than expected in 2020, with 19% (10/52) of the weeks falling above the upper bound of the PI. These excesses in searches began a month after the Pandemic Unemployment Compensation program ended. Relative search volume was also heightened in 2020 for child-witnessed IPV, with 33% (17/52) of the weeks falling above the upper bound of the PI. This increase occurred after the introduction of shelter-in-place policies. CONCLUSIONS Social and financial disruptions, which are common consequences of major disasters such as the COVID-19 pandemic, may increase risks for child abuse and child-witnessed IPV.

Background The COVID-19 pandemic has created environments with increased risk factors for household violence, such as unemployment and financial uncertainty. At the same time, it led to the introduction of policies to mitigate financial uncertainty. Further, it hindered traditional measurements of household violence. Objective Using an infoveillance approach, our goal was to determine if there were excess Google searches related to exposure to child abuse, intimate partner violence (IPV), and child-witnessed IPV during the COVID-19 pandemic and if any excesses are temporally related to shelter-in-place and economic policies. Methods Data on relative search volume for each violence measure was extracted using the Google Health Trends application programming interface for each week from 2017 to 2020 for the United States. Using linear regression with restricted cubic splines, we analyzed data from 2017 to 2019 to characterize the seasonal variation shared across prepandemic years. Parameters from prepandemic years were used to predict the expected number of Google searches and 95% prediction intervals (PI) for each week in 2020. Weeks with searches above the upper bound of the PI are in excess of the model’s prediction. Results Relative search volume for exposure to child abuse was greater than expected in 2020, with 19% (10/52) of the weeks falling above the upper bound of the PI. These excesses in searches began a month after the Pandemic Unemployment Compensation program ended. Relative search volume was also heightened in 2020 for child-witnessed IPV, with 33% (17/52) of the weeks falling above the upper bound of the PI. This increase occurred after the introduction of shelter-in-place policies. Conclusions Social and financial disruptions, which are common consequences of major disasters such as the COVID-19 pandemic, may increase risks for child abuse and child-witnessed IPV.

Background: Cervical cancer rates have declined since the implementation of cervical cancer screening methods such as Pap tests. However, Pap tests are still underutilized by many minority women due to limited awareness about human papillomavirus (HPV) and cervical cancer, difficulties accessing health care services, and cultural or religious beliefs. HPV self-sampling has been proposed as an alternative to overcome some of these barriers. This study aimed to assess awareness, self-efficacy, and preferences of HPV self-sampling among racially- and ethnically-diverse women. Methods: From May – November 2021, women, ages 30-65 years old, were recruited in person and virtually to complete an online survey. The survey included 15 sociodemographic questions and five outcome measures related to HPV self-sampling: (1) awareness of test; (2) self-efficacy to conduct test; (3) location preference of test (clinic vs. home); 4) collector preference for screening strategy (self-collected vs. clinician-collected); and 5) preference of cervical cancer screening strategy (HPV self-sampling vs. Pap test). Modified Poisson regression was conducted to assess exploratory associations between sociodemographic variables and each outcome measure; relative risks were adjusted for age. Results: A total of 420 women completed the online survey, of which 32.4% identified as non-Hispanic white, 22.2% as Hispanic, 12.6% as Black/African American, 28.3% as Asian, 1.9% as American Indian/Alaskan Native, and 1.4% as more than two races. The majority of women had not heard of HPV self-sampling (93.5%) but reported high self-efficacy (75.3%). Women also reported higher preferences for completing an HPV test in the clinic (52.2%) and for performing a self-collected HPV test themselves (58.7%) yet would choose a traditional Pap test over HPV self-sampling (56.0%). Conclusion: The low level of HPV self-sampling awareness, across all racial and ethnic groups, suggests a strong opportunity to promote widespread educational efforts around this new tool. While many women, including those that are racially- and ethnically-diverse, still prefer the Pap test, the biggest barrier to their potential uptake of HPV self-sampling is a strong reliance on provider expertise. Future research should leverage the provider role in HPV self-sampling interventions as well as explore the feasibility of home-based or clinic-based HPV self-sampling approaches. Citation Format: Serena Xiong, Rahel Ghebre, Shalini Kulasingam, Susan M. Mason, Rebekah J. Pratt, DeAnn Lazovich. Exploring factors associated with preferences for human papillomavirus (HPV) self-sampling among racially-and ethnically-diverse women: a cross-sectional study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P026.

Various types of stressors are associated with maladaptive eating, but how the stressor of everyday discrimination (e.g., less respect, poorer service) relates to maladaptive eating and adaptive eating remains unclear. We examined everyday discrimination as a predictor of maladaptive and adaptive eating. Data were collected in a population-based study, Eating and Activity over Time (N = 1410, ages 18-30). Everyday discrimination was categorized as none, low, moderate, or high. Outcomes included maladaptive eating (i.e., overeating and binge eating) and adaptive eating (i.e., intuitive eating and mindful eating). Modified Poisson regressions estimated the prevalence ratios (PRs) for overeating and binge eating associated with everyday discrimination. Linear regressions estimated associations between everyday discrimination and intuitive and mindful eating scores. After adjustment for age, ethnicity/race, gender, and socioeconomic status, moderate and high levels of discriminatory experiences were each associated with a significantly greater prevalence of binge eating (PR = 2.2, [95% CI = 1.3-3.7] and PR = 3.1, [95% CI = 2.0-4.7], respectively) and lower intuitive (β = -0.4, [95% CI = -0.7, -0.2] and β = -0.5 [95% CI = -0.8, -0.3], respectively), and mindful eating scores (β = -0.3, [95% CI = -0.6, -0.1] and β = -0.5 [95% CI = -0.8, -0.3], respectively) compared to young adults with no discriminatory experience. Public health efforts to prevent maladaptive eating and encourage the adoption of adaptive eating should consider the potential contribution of everyday discrimination and the need to advocate for equity and inclusion.

Purpose Commonly-used violence surveillance systems are biased towards certain populations due to overreporting or over-scrutinized. Hospital discharge data may offer a more representative view of violence, through use of proxy codes, i.e. diagnosis of injuries correlated with violence. The goals of this paper are to compare the trends in violence in Minnesota, and associations of county-level demographic characteristics with violence rates, measured through explicitly diagnosed violence and proxy codes. It is an exploration of how certain sub-populations are overrepresented in traditional surveillance systems. Methods Using Minnesota hospital discharge data linked with census data from 2004 to 2014, this study examined the distribution and time trends of explicit, proxy, and combined (proxy and explicit) codes for child abuse, intimate partner violence (IPV), and elder abuse. The associations between county-level risk factors (e.g., poverty) and county violence rates were estimated using negative binomial regression models with generalized estimation equations to account for clustering over time. Results The main finding was that the patterns of county-level violence differed depending on whether one used explicit or proxy codes. In particular, explicit codes suggested that child abuse and IPV trends were flat or decreased slightly from 2004 to 2014, while proxy codes suggested the opposite. Elder abuse increased during this timeframe for both explicit and proxy codes, but more dramatically when using proxy codes. In regard to the associations between county level characteristics and each violence subtype, previously identified county-level risk factors were more strongly related to explicitly-identified violence than to proxy-identified violence. Given the larger number of proxy-identified cases as compared with explicit-identified violence cases, the trends and associations of combined codes align more closely with proxy codes, especially for elder abuse and IPV. Conclusions Violence surveillance utilizing hospital discharge data, and particularly proxy codes, may add important information that traditional surveillance misses. Most importantly, explicit and proxy codes indicate different associations with county sociodemographic characteristics. Future research should examine hospital discharge data for violence identification to validate proxy codes that can be utilized to help to identify the hidden burden of violence.

Background Sexual and physical abuse are risk factors for binge eating and overeating, but few studies have examined association of the identity of the perpetrator with survivors' risk of binge eating and overeating. Purpose To examine the risk of binge eating and overeating by (1) type of abuse and identity of the perpetrators and (2) cumulative abuse experiences/perpetrators. Methods Data came from Eating and Activity over Time (N = 1407; ages 18–30 during 2017–2018). Sexual abuse perpetrators included family members, non-family members, and intimate partners. Physical abuse perpetrators included family members and intimate partners. Cumulative abuse experiences were defined as the number of types of abuse experienced. Modified Poisson regressions were used to examine the risk of binge eating (overeating with loss of control) and overeating (without loss of control), by (1) abuse type and perpetrator and (2) cumulative abuse experiences. Results Abuse was more strongly associated with binge eating than overeating. For binge eating, risk factors included familial and intimate partner sexual abuse (RR = 1.48 [95% CI = 1.01–2.17] and 2.41, [95% CI = 1.70–3.41], respectively) and physical abuse (RR = 1.84, [95% CI = 1.33–2.53] and 1.95, [95% CI = 1.35–2.81], respectively), after adjustment for sociodemographic variables. For overeating, associations with physical abuse were close to the null, and those with sexual abuse were modest, with wide CIs that overlapped the null. Abuse experiences were cumulatively associated with binge eating, but not overeating. Conclusion Assessment of identity of the perpetrator, and cumulative abuse experiences/perpetrators may assist in identifying people at the greatest risk of binge eating.

Introduction Childhood physical, sexual, and emotional abuse are linked to adult obesity, and little is known about what protective factors might mitigate this association. Methods Data from female (n=4,247) and male (n=1,982) participants in the longitudinal Growing Up Today cohort study from 1996 to 2013 were used to examine whether factors found to promote mental health resilience after abuse also operate as buffers (modifiers) of the abuse–weight status association. At ages 20–25 years, participants were asked about their history of child abuse before age 18 years. Potential resilience factors (modifiers) included childhood family SES, neighborhood safety, supportive relationships with adult nonfamily members, quality of maternal relationship, family structure, religious service attendance, and prayer/meditation. Associations between child abuse and BMI at ages 25–32 years were modeled using linear regression, adjusted for sociodemographic variables and baseline BMI. Potential modifiers were tested with interaction terms. Analyses were run in 2019–2020. Results Severe abuse was associated with 0.9 kg/m2 (95% CI=0.5, 1.2) higher adult BMI than no abuse, corresponding to a 46% increased risk of obesity (95% CI=1.28, 1.67). Less severe abuse was not significantly associated with BMI (β=0.1, 95% CI= −0.2, 0.4). There were no significant interactions between modifiers and abuse. Conclusions Factors previously found to promote resilience to mental health sequelae after abuse did not modify the association of severe child abuse with higher weight status.

Adverse experiences, such as childhood abuse and other violence victimization, are associated with problematic eating. However, whether different types of adversity relate to both maladaptive and adaptive eating behaviors is unclear. This study examined the associations of different adverse experiences with maladaptive (i.e., overeating and binge eating) and adaptive (i.e., intuitive eating and mindful eating) eating by gender. Data were derived from the EAT-2018 (Eating and Activity over Time) study (N = 1411, aged 18–30 years in 2017–2018). Modified Poisson regressions were used to examine the associations between adverse experiences and the prevalence of maladaptive eating. Linear regressions were used to examine the associations between adverse experiences and adaptive eating scores. Each adverse experience was associated with greater prevalence of maladaptive eating and lower adaptive eating scores. Among women, intimate partner sexual violence was strongly associated with more overeating (PR = 2.1 [95% CI = 1.4–3.1]) and binge eating (PR = 2.4 [95% CI = 1.5–3.9]), and less mindful eating (β = −0.6, [95% CI = −0.8, −0.3]); being attacked, beaten, or mugged was most associated with less intuitive eating (β = −0.5, [95% CI = −0.8, −0.2]). Among men, being attacked, beaten, or mugged was strongly associated with more overeating (PR = 2.1 [95% CI = 1.2–3.5]) and binge eating (PR = 3.2 [95% CI = 1.6–6.5]); intimate partner physical violence was strongly associated with less intuitive eating (β = −0.6, [95% CI = −0.9, −0.2]); childhood emotional abuse was strongly associated with less mindful eating (β = −0.8, [95% CI = −1.0, −0.5]). To improve eating behaviors, adverse life experiences and the potential impact on maladaptive and adaptive eating should be considered.

Childhood maltreatment (abuse and neglect) is associated with a range of negative outcomes, but a gap remains in understanding of how specific maltreatment types, particularly neglect and non-familial sexual abuse, relate to health and behavior. This study examined the association of neglect and sexual abuse (both familial and non-familial), as well as familial physical and emotional abuse, with: depressive mood and eating disorders; tobacco and marijuana use; and BMI ≥ 25 kg/m

Adverse childhood experiences (ACEs) include childhood abuse, neglect, and household substance abuse. Childhood abuse is a risk factor for disordered eating (DEB). Less well established are associations of childhood neglect and household substance abuse with DEB, and little research has examined ACE associations with DEB in middle adulthood. The objective of this study was to examine associations between ACEs and DEBs among middle-aged adults and examine sex differences. ACEs prior to age 18 were retrospectively assessed in the Coronary Artery Risk Development in Young Adults study in 2000-2001 (N = 3340, ages 32 to 46). DEB outcomes (i.e., concerns about weight and shape, anxiety about eating or food, unhealthy weight control behaviors, chronic dieting, overeating, and binge eating) were assessed in 1995-1996 (ages 27 to 41). Modified Poisson regressions estimated risk ratios (RRs) for associations of a history of any ACE, each ACE, and cumulative ACEs with DEB outcomes. Among women, emotional abuse, physical neglect, and emotional neglect were each modestly associated with most DEBs (RRs = 1.21-1.35, 1.21-1.45, and 1.23-1.41 across DEBs, respectively) after adjustment for sociodemographic variables, BMI, and depressive symptoms. A cumulative ACE score was associated with all DEBs in a stepwise manner (p for trend ≤0.05) except concerns about weight and shape and overeating. Among men, emotional abuse was most consistently related to the majority of DEBs (RRs = 1.23-1.92); household substance abuse was modestly associated with overeating (RR = 1.26, 95% CI = 1.04-1.53). ACEs were cumulatively associated with unhealthy weight control behaviors, overeating, and binge eating (p for trend0.01).

Urban, low-income, African American children and parents report lower quality primary care and face negative social determinants of health. High-quality well-child care is critical for this population. The purpose of this qualitative study was to compare and contrast parent and health care provider experiences of well-child care for urban, low-income, African American families to better understand the complex factors involved in care quality and health outcomes.Two data sets were analyzed using conventional content analysis, parent focus group data, and provider interviews. After analysis, results were sorted into similar categories, and convergence coding was completed to identify areas of agreement, partial agreement, dissonance, and silence.Thirty-five parents took part in four focus groups, and nine providers were interviewed. Following convergence coding, five categories and 31 subcategories were identified. The five categories included: social determinants of health, sources of advice and support, challenges with the healthcare system, parent-provider relationships, and anticipatory guidance topics.Triangulation demonstrated convergence between parents and providers understanding of the concepts and functions of well-child care, however the prominence and meaning varied within each category and sub-category. The variance in agreement, areas of silence, and dissonance shed light on why the population reports lower overall quality primary care.

International travel is popular worldwide, yet its implications for sexual and reproductive health are not fully understood. Few studies have examined the contextual factors that shape women's sexual and contraceptive behaviors-and thus, their risk of unintended pregnancy and sexually transmitted infections (STIs)-while traveling outside their home country. In this qualitative study, female university students with recent (n = 25) or upcoming (n = 19) travel outside the U.S. completed semi-structured interviews from October 2015 to March 2017. Transcripts were analyzed for themes related to contraceptive and sexual behaviors: (1) participants' pre-travel expectations of sex; (2) the circumstances surrounding sexual encounters with men while traveling; (3) negotiation about condom and contraception use with partners; and (4) factors affecting contraceptive adherence. Participants generally expected to be abstinent during travel, citing myriad rationales that included personal values, no perceived opportunities for sex, and the nature of the trip. Some travelers had unexpected sexual encounters, involving health-protecting behaviors and risk-taking (e.g., unprotected sex, substance use). New sexual partnerships were fueled by increased attention from men, situational disinhibition, and perceived heightened intimacy. International travel brought many contraceptive considerations (adequacy of supplies, access to refrigeration, time zone differences, etc.) as well as obstacles that triggered contraceptive lapses and discontinuation. Pill users described the most challenges, while travelers using intrauterine devices expressed appreciation for their maintenance-free contraception. This study suggests complex associations between international travel and young women's sexual and reproductive health. Some travelers were more vulnerable to situational risk factors, while others may have been more insulated. We identify potential intervention opportunities via clinical services, education, and policy to reduce young women's risk of adverse sexual and reproductive health outcomes while traveling abroad. We urge greater recognition of and conversations about contraceptive lapse and unintended pregnancy as potential health risks for female travelers of reproductive age, just as clinical guidelines acknowledge travel-associated STI.

Background Problematic relationship to eating and food (PREF) captures a broad range of unhealthy eating behaviors. We previously reported that higher BMI is associated with PREF and graded by the number of PREF endorsed. In this study, we prospectively examined the association between PREF and metabolic syndrome and diabetes. Method Eight PREF behaviors were assessed and summed to form the PREF score in 3800 black and white adults (age 27-41 years) in the Coronary Artery Risk Development in Young Adults Study. Diagnoses of incident metabolic syndrome and diabetes were made through 15 years of follow-up. Logistic regression estimated the association with metabolic syndrome. Proportional hazards regression estimated the association with diabetes. Results The odds ratio of metabolic syndrome was 1.25 per PREF point through 5 years of follow-up (95% CI: 1.17-1.34) and 1.17 per point from 5 to 10 years of follow-up (95% CI: 1.08-1.27). Hazard of diabetes was 1.20 per PREF point through 15 years of follow-up (95% CI: 1.12-1.28). Both associations attenuated after adjustment for BMI. Discussion Among participants with PREF, higher scores associate with metabolic syndrome and diabetes, with partial attenuation after adjustment for BMI. Early identification of PREF in middle-aged adults may reduce the burden of metabolic health outcomes.

The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis., The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch.

The Molecule Interacting with CasL 1 (MICAL1) monooxygenase has emerged as an important regulator of cytoskeleton organization via actin oxidation. Although filamentous actin (F-actin) increases MICAL1 monooxygenase activity, hydrogen peroxide (H2O2) is also generated in the absence of F-actin, suggesting that diffusible H2O2 might have additional functions. MICAL1 gene disruption by CRISPR/Cas9 in MDA MB 231 human breast cancer cells knocked out (KO) protein expression, which affected F-actin organization, cell size and motility. Transcriptomic profiling revealed that MICAL1 deletion significantly affected the expression of over 700 genes, with the majority being reduced in their expression levels. In addition, the absolute magnitudes of reduced gene expression were significantly greater than the magnitudes of increased gene expression. Gene set enrichment analysis (GSEA) identified receptor regulator activity as the most significant negatively enriched molecular function gene set. The prominent influence exerted by MICAL1 on F-actin structures was also associated with changes in the expression of several serum-response factor (SRF) regulated genes in KO cells. Moreover, MICAL1 disruption attenuated breast cancer tumour growth in vivo. Elevated MICAL1 gene expression was observed in invasive breast cancer samples from human patients relative to normal tissue, while MICAL1 amplification or point mutations were associated with reduced progression free survival. Collectively, these results demonstrate that MICAL1 gene disruption altered cytoskeleton organization, cell morphology and migration, gene expression, and impaired tumour growth in an orthotopic in vivo breast cancer model, suggesting that pharmacological MICAL1 inhibition could have therapeutic benefits for cancer patients.

Intuitive eating has been associated with markers of better health in cross-sectional studies, but less is known about long-term associations between intuitive eating and subsequent eating and weight-related behaviors. This study assessed how intuitive eating in early adulthood is related to weight status, dieting, healthy and unhealthy weight control behaviors, and binge eating with loss of control five years later. Young adults (N = 1660) were asked about intuitive eating as part of the 2008–2009 third wave of the Project EAT (Eating and Activity in Teens and Young Adults) longitudinal cohort study. Weight status, dieting, healthy and unhealthy weight control behaviors, and binge eating with loss of control were assessed during both the third (EAT-III: mean age 25.3 ± 1.5) and fourth (EAT-IV mean age 31.1 ± 1.5) waves. In analyses adjusted for sociodemographic characteristics, both male and female intuitive eaters had a lower prevalence of high weight status and lower engagement in dieting, unhealthy weight control behaviors, and binge eating at the 5-year follow-up, compared to non-intuitive eaters. Among women, after additional adjustment for EAT-III values for the respective outcome measures, intuitive eating was unrelated to any of the behaviors studied at 5-year follow-up. Among men, intuitive eating predicted a lower likelihood of engaging in unhealthy weight control behaviors (intuitive eaters: 30.0% vs. non-intuitive: 41.9%, p = 0.002) and binge eating (intuitive eaters: 0.9% vs. non-intuitive: 1.5%, p = 0.046) independent of participating in these behaviors at EAT-III. In a population-based sample of young adults, intuitive eating was associated with better markers of eating and weight-related behaviors five years later, suggesting intuitive eating may have potential long-term benefits.

Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Forster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.

To evaluate female students’ expectations and experiences related to their sexual and reproductive health (SRH) during international travel. Participants: Female students from a US university with ...

Although eating disorder symptoms generally decrease in pregnancy, loss of control eating (LOC), defined by the consumption of food accompanied by a sense of being unable to control what or how much is eaten, often persists and may develop in pregnancy. Given that LOC is associated with higher weight status and psychological distress, it is important to understand factors associated with perinatal LOC. Although childhood traumatic events have been linked to LOC in non-pregnant women, the impact of such events on LOC in pregnancy is unknown. Accordingly, the present study aimed to examine the association between a history of childhood traumatic events and LOC prior to and during pregnancy among a community sample of pregnant women with overweight or obesity. Pregnant women (N = 244) were enrolled in a longitudinal study. Women completed interviews between 12 and 20 weeks gestation to document a history of childhood traumatic events and the presence of LOC in the three months prior to and during their current pregnancy. Women were assessed for LOC monthly for the remainder of pregnancy. Results from a multinomial regression model showed that women with a history of childhood traumatic events had higher odds of engaging in LOC both prior to and during pregnancy (OR = 2.52, 95% CI [1.13, 5.64], p = 0.02) but not during pregnancy only (OR = 1.58, 95% CI [0.87, 2.89], p = 0.39). These findings indicate that women with a history of childhood traumatic events may be especially prone to LOC in the months prior to conception that continues throughout pregnancy.