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BACKGROUND: The research community has historically failed to enroll diverse groups of participants in dementia clinical trials. A unique aspect of dementia care research is the requirement of a study partner, who can attest to the care recipients clinical and functional capacity. The aim of this study is to assess racial and ethnic differences and the importance of various trial considerations among dementia caregivers, in their decision to participate in clinical research as study partners. METHOD: We embedded a vignette about a hypothetical dementia clinical trial in a nationally representative survey of U.S. dementia caregivers, oversampling non-Hispanic Black and Hispanic caregivers. Dementia caregivers were asked about their willingness to participate in the trial with their care recipient and rated the importance of nine considerations in hypothetical decisions to participate. Caregiver demographic characteristics were analyzed as predictors of trial participation in a base demographic model. In a second reasons model caregiver demographic characteristics and the rated importance of the nine considerations were separately analyzed as predictors; both models used survey-weighted logistic regression. RESULT: The sample consisted of 610 dementia caregivers, including 156 non-Hispanic Black and 122 Hispanic caregiver participants. In the base demographic model, hypothetical trial participation was negatively associated with older caregiver age (OR (odds ratio) = 0.72, p =

Pregnancies ending before 26 weeks contribute 1% of births but 40% of infant deaths in the United States. The rate of these periviable births to non-Hispanic (NH) Black women exceeds four times that for NH whites. Small male periviable infants remain most likely to die. NH white periviable males weigh more than their NH Black counterparts. We argue that male infants born from twin gestations, in which one fetus died in utero (i.e., the vanishing twin syndrome), contribute to the disparity. We cannot directly test our argument because vanishing typically occurs before clinical recognition of pregnancy. We, however, describe and find associations that would emerge in vital statistics were our argument correct. Among male periviable singleton births from 288 monthly conception cohorts (January 1995 through December 2018), we found an average NH white advantage of 30 grams (759 grams versus 729 grams). Consistent with our argument, however, cohorts signaling relatively few survivors of the vanishing twin syndrome showed no disparity.

Protein biomarkers are associated with mortality in cardiovascular disease, but their effect on predicting respiratory and all-cause mortality is not clear. We tested whether a protein risk score (protRS) can improve prediction of all-cause mortality over clinical risk factors in smokers. We utilized smoking-enriched (COPDGene, LSC, SPIROMICS) and general population-based (MESA) cohorts with SomaScan proteomic and mortality data. We split COPDGene into training and testing sets (50:50) and developed a protRS based on respiratory mortality effect size and parsimony. We tested multivariable associations of the protRS with all-cause, respiratory, and cardiovascular mortality, and performed meta-analysis, area-under-the-curve (AUC), and network analyses. We included 2232 participants. In COPDGene, a penalized regression-based protRS was most highly associated with respiratory mortality (OR 9.2) and parsimonious (15 proteins). This protRS was associated with all-cause mortality (random effects HR 1.79 [95% CI 1.31-2.43]). Adding the protRS to clinical covariates improved all-cause mortality prediction in COPDGene (AUC 0.87 vs 0.82) and SPIROMICS (0.74 vs 0.6), but not in LSC and MESA. Protein-protein interaction network analyses implicate cytokine signaling, innate immune responses, and extracellular matrix turnover. A blood-based protein risk score predicts all-cause and respiratory mortality, identifies potential drivers of mortality, and demonstrates heterogeneity in effects amongst cohorts.

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

BackgroundThe purpose of our study was to understand the relationship between sociodemographic factors and adherence to the MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension] Intervention for Neurodegenerative Delay) diet in a demographically diverse national population-based sample of 9-12-year-olds in the US.MethodsWe analyzed data from the Adolescent Brain and Cognitive Development (ABCD) Study (Year 1, N = 8333). Multivariable linear regression analysis was used to identify associations between MIND diet score and sociodemographic factors, including race/ethnicity, household income, parent education level, age, sex, and sexual minority status.ResultsCompared to White adolescents, Latino adolescents showed the greatest adherence to the MIND diet. Boys had lower adherence to the MIND diet than girls. Lower household income was associated with lower adherence to the MIND diet. Older age was associated with lower adherence to the MIND diet. Sexual minorities had a lower adherence to the MIND diet when compared to their heterosexual counterparts.DiscussionFemale sex, Latino ethnicity, Asian and Black race, high household income, heterosexual sexual orientation, and younger age were associated with higher adherence to the MIND diet. These sociodemographic differences can inform targeted screening and counseling for clinicians and public health organizations among diverse adolescent populations.Impact statementSociodemographic disparities in diet quality have been documented, but none have explored adherence to the MIND (Mediterranean-DASH [Dietary Approaches to Stop Hypertension] Intervention for Neurodegenerative Delay) diet in early adolescence. In this demographically diverse sample of 9-12-year-old early adolescents in the U.S., we found notable and nuanced sociodemographic disparities in adherence to the MIND diet. Sociodemographic factors associated with higher adherence to the MIND diet included female sex, Latino ethnicity, high household income, heterosexual sexual orientation, and younger age.

Healthy adipose tissue is essential for normal physiology. There are 2 broad types of adipose tissue depots: brown adipose tissue (BAT), which contains adipocytes poised to burn energy through thermogenesis, and white adipose tissue (WAT), which contains adipocytes that store lipids. However, within those types of adipose, adipocytes possess depot and cell-specific properties that have important implications. For example, the subcutaneous and visceral WAT confers divergent risk for metabolic disease. Further, within a depot, different adipocytes can have distinct properties; subcutaneous WAT can contain adipocytes with either white or brown-like (beige) adipocyte properties. However, the pathways that regulate and maintain this cell and depot-specificity are incompletely understood. Here, we found that the transcription factor KLF15 is required for maintaining white adipocyte properties selectively within the subcutaneous WAT. We revealed that deletion of Klf15 is sufficient to induce beige adipocyte properties and that KLF15s direct regulation of Adrb1 is a critical molecular mechanism for this process. We uncovered that this activity is cell autonomous but has systemic implications in mouse models and is conserved in primary human adipose cells. Our results elucidate a pathway for depot-specific maintenance of white adipocyte properties that could enable the development of therapies for obesity and associated diseases.

Understanding the acceptability of long-acting injectable antiretroviral therapy (LAI-ART) among people with HIV (PWH), especially priority populations, is essential for effective implementation. We conducted semi-structured interviews with patients in three Ryan White-funded HIV clinics in San Francisco, Chicago, and Atlanta. We employed maximal variation sampling across age, gender, race, ethnicity, and time living with HIV and oversampled for individuals with suboptimal clinical engagement. An 8-step hybrid deductive and inductive thematic analysis approach guided data analysis. Between August 2020 and July 2021, we conducted 72 interviews. Median age was 46 years; 28% were ciswomen, 7% transwomen, 44% Black/African-American and 35% Latinx, 43% endorsed a psychiatric diagnosis, 35% were experiencing homelessness/unstable housing, and 10% had recent substance use. Approximately 24% were sub-optimally engaged in care. We observed a spectrum of LAI-ART acceptability, ranging from enthusiasm to hesitancy to rejection. We also characterized four emergent orientations towards LAI-ART: innovator, pragmatist, deliberator, and skeptic. Overall, the majority of participants expressed favorable initial reactions towards LAI-ART. Most approached LAI-ART pragmatically, but acceptability was not static, often increasing over the course of the interview. Participants considered their HIV providers as essential for affirming personal relevance. HIV stigma, privacy concerns, and medical mistrust had varied impacts, sometimes facilitating and other times hindering personal relevance. These findings held across priority populations, specifically young adults, cis/trans women, racial/ethnic minorities, and individuals with suboptimal clinical engagement. Further research is needed to explore the transition from hypothetical acceptance to uptake and to confirm the actual benefits and drawbacks of this treatment.

Associations of total testosterone (T) and calculated free T with cardiovascular disease (CVD) remain poorly understood. Particularly how these associations vary according to race and ethnicity in a nationally representative sample of men. Data included 7058 men (≥20 years) from NHANES. CVD was defined as any reported diagnosis of heart failure (HF), coronary artery disease (CAD), myocardial infarction (MI), and stroke. Total T (ng/mL) was obtained among males who participated in the morning examination. Weighted multivariable-adjusted logistic regression models were conducted. We found associations of low T (OR = 1.57, 95% CI = 1.17-2.11), low calculated free T (OR = 1.53, 95% CI = 1.10-2.17), total T (Q1 vs Q5), and calculated free T (Q1 vs Q5) with CVD after adjusting for estradiol and SHBG. In disease specific analysis, low T increased prevalence of MI (OR = 1.72, 95% CI = 1.08-2.75) and HF (OR = 1.74, 95% CI = 1.08-2.82), but a continuous increment of total T reduced the prevalence of CAD. Similar inverse associations were identified among White and Mexican Americans, but not Blacks (OR = 0.93, 95% CI = 0.49-1.76). Low levels of T and calculated free T were associated with an increased prevalence of overall CVD and among White and Mexican Americans. Associations remained in the same direction with specific CVD outcomes in the overall population.

ObjectivesLow-cost debt can potentially enhance wealth and indirectly benefit health, yet Black Americans disproportionately lack this type of debt, which may constrain their ability to accumulate wealth throughout their lives and across generations. Our objectives are to develop a novel debt-asset measure, use it to quantify the Black-White differential in debt-asset profiles, and estimate its contribution to the racial gap in cognition.MethodsUsing the Health and Retirement Study (1998-2020), we grouped individuals based on debt and asset information during the preretirement period of ages 55-61, including the absence of debt and the relative amount of debt compared to assets. Linear mixed models were used to examine the extent to which cognition in later life (ages 62-80) differs across these debt-asset profiles and its role in explaining the racial disparity in cognition.ResultsCompared with Whites, Blacks were more likely to fall into categories characterized by high debt-to-asset ratio (DAR) or limited asset ownership. Low-asset nonborrowers displayed the poorest cognition, followed closely by high-DAR borrowers. The Black-White differential in debt-asset profiles contributed to the racial gap in cognition.DiscussionThere were 2 unfavorable debt-asset profiles: high debt relative to assets and little or no debt due to a lack of assets, which was more prevalent among Blacks than Whites. We discuss how institutional and structural racism shapes Black-White disparities in debt-asset profiles, such as limited access to borrowing opportunities, thereby contributing to health inequalities, including cognition.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

BACKGROUND: We evaluated smoking differences across nativity and race/ethnicity among women diagnosed with breast cancer. METHODS: In our Northern Californian pooled population of 5,653 [670 Asian, 690 Hispanic, and 4,300 non-Hispanic White (White)] women diagnosed with breast cancer, we evaluated smoking differences across nativity, race/ethnicity, and acculturation and effect modification of nativity by race/ethnicity and education. RESULTS: Foreign-born women currently smoked less than US-born women [odds ratio (OR) = 0.46, 95% confidence limit (CL): 0.29-0.72]. Hispanic (OR = 0.50; 95% CL: 0.32-0.78) women currently smoked less than White women. Among those who ever smoked (n = 2,557), foreign-born women smoked 5.23 fewer pack-years (PY) than US-born women (95% CL: -2.75 to -7.70). Furthermore, Asian (-4.60, 95% CL: -0.81 to -8.39) and Hispanic (-6.79, 95% CL: -4.14 to -9.43) women smoked fewer PY than White women. Associations were generally suggestive of greater smoking with greater acculturation (immigration age, US years, survey language). Finally, associations for nativity differed by education but not race/ethnicity, with a higher likelihood of smoking in US-born women only among those with less than a bachelors degree (OR = 2.84, 95% CL: 2.15-3.77; current smoking: P = 0.01, PY: P = 0.05). CONCLUSIONS: Asian and Hispanic (vs. White) and foreign-born (vs. US-born) breast cancer survivors reported fewer smoking behaviors. Smoking differences across nativity and education were driven by higher rates of smoking in US-born women with lower educational attainment. IMPACT: Smoking behavioral patterns were similar among breast cancer survivors and the general population, informing potential smoking interventions.

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

IntroductionDepressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear.MethodsAsian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity.ResultsHigher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function.DiscussionDepressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups.HighlightsWe examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies. METHODS: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array. Global ancestry proportions were estimated using ADMIXTURE, and local ancestry was estimated using RFMIXv2.0. We investigated associations between lupus nephritis, age at onset, and autoantibody status with both global and local ancestry proportions within the Major Histocompatibility Complex region. RESULTS: Our results showed small effect sizes that did not meet the threshold for statistical significance for global or local ancestry proportions in either African American or Mestizo patients with SLE who presented with the clinical manifestations of interest compared with those who did not. CONCLUSION: These findings suggest that local genetic ancestry within the Major Histocompatibility Complex region is not a major contributor to these SLE manifestations among patients with SLE from admixed populations.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

We examine whether the COVID-19 pandemic was associated with changes to daily activity limitations due to poor physical or mental health and whether those changes were different within and between gendered and racialized groups. We analyze 497,302 observations across the 2019 and 2020 waves of the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System survey. Among White men and women, the COVID-19 pandemic was associated with fewer days of health-related activity limitations and decreased frequent activity limitation (≥14 days in the past month) compared to the prepandemic period. By contrast, Latina and Black women experienced increased days of activity limitation and greater likelihood of frequent activity limitation, and these changes were significantly different than for White women. These findings are robust to the inclusion of structural inequality measures and demonstrate how systemic racism and sexism likely exacerbate a myriad of pandemic-related health problems.

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

Recent studies in brown adipose tissue (BAT) described a unique subpopulation of mitochondria bound to lipid droplets (LDs), which were termed PeriDroplet Mitochondria (PDM). PDM can be isolated from BAT by differential centrifugation and salt washes. Contrary to BAT, this approach has so far not led to the successful isolation of PDM from white adipose tissue (WAT). Here, we developed a method to isolate PDM from WAT with high yield and purity by an optimized proteolytic treatment that preserves the respiratory function of mitochondria. Using this approach, we show that, contrary to BAT, WAT PDM have lower respiratory and ATP synthesis capacities compared with WAT cytoplasmic mitochondria (CM). Furthermore, by isolating PDM from LDs of different sizes, we found a negative correlation between LD size and the respiratory capacity of their PDM in WAT. Thus, our new isolation method reveals tissue-specific characteristics of PDM and establishes the existence of heterogeneity in PDM function determined by LD size.

White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1's function during differentiation. These findings underscore PATZ1's regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development.

INTRODUCTION: The deaf and hard of hearing (DHH) community experiences lower cancer screening rates than the general population. Cancer worry and fatalism can influence cancer screening, along with race, and the interaction of intrinsic factors with DHH health behavior needs to be investigated. OBJECTIVES: The study examines the association of the intersection of race and hearing status with cancer worry and fatalism. METHODS: This study analyzed cross-sectional survey data from NCI HINTS-ASL (for DHH adults) and NCI HINTS (for hearing adults). Multivariable logistic regression models were used to assess (i) the association of race-hearing status intersection with cancer worry and fatalism, as well as (ii) the relationship between hearing status and outcomes within each race. RESULTS: The study found that the overall interaction between race and hearing status was significantly associated with both high cancer worry and fatalism, with African American (AA)/Black and Asian/Other having higher odds of worry [1.17 (0.83, 1.64); 1.19 (0.85, 1.66), respectively] and other groups having lower worry than White hearing (P < 0.0001), and all deaf having less concern about cancer fatalism (P < 0.0001). Within each racial group, White DHH respondents had lower odds of cancer worry [aOR (95% CI): 0.72 (0.58, 0.91); P < 0.01] and fatalism [0.55 (0.46, 0.67); P < 0.0001] compared to White hearing respondents, while DHH AA/Black [1.89 (1.06, 3.37); P = 0.03], Asian/Other [2.39 (1.06, 3.37); P = 0.03], and Hispanic [1.95 (1.18, 3.22); P < 0.01] respondents had significantly higher odds of cancer worry and lower odds of cancer fatalism [Black: 0.50 (0.23, 1.09); P = 0.07; Asian/Other: [0.68 (0.42, 1.09); P = 0.10]; Hispanic: [0.69 (0.40, 1.17)]; P = 0.16] compared to their hearing counterparts. CONCLUSION: DHH individuals have different odds of experiencing cancer worry and fatalism compared to their hearing counterparts. Inclusion of individuals with sensory disabilities in a larger cancer study sample enriches the diversity of perspectives, ensuring that the findings reflect a broader range of experiences and needs. More research into contributory factors in the signing DHH population is needed.

A simple and rapid method that is not based on race and ethnicity for classifying people with skin of color is of paramount importance in dermatology. The currently used Fitzpatrick classification of sun-reactive skin types is inadequate. Newer scales that have been used in immigration surveys and sociology studies are not applicable in the office setting. A new, non-racial and non-ethnic, colorimetric scale for skin of color has recently been proposed that is simple to perform. The scale has five colors: very light beige (skin color type 1), light brown (skin color type 2), medium brown (skin color type 3), dark brown (skin color type 4) and very dark brown (skin color type 5); an individual with white skin, such as in albinism, would have a skin color type 0 in this classification. In conclusion, the colorimetric scale enables the rapid classification of individuals with skin of color and allows for accurate assessment of skin cancer risk, more appropriate management of cosmetic dermatologic procedures and aesthetic devices, and enhanced ability for focused counseling regarding hair products, skin care interventions, and color-targeted makeup based on the person's skin tone.

BACKGROUND: Black-White racial disparities in cancer mortality are well-documented in the US. Given the estimated shortage of oncologists over the next decade, understanding how access to oncology care might influence cancer disparities is of considerable importance. We aim to examine the association between oncology provider density in a county and Black-White cancer mortality disparities. METHODS: An ecological study of 1048 US counties was performed. Oncology provider density was estimated using the 2013 National Plan and Provider Enumeration System data. Black:White cancer mortality ratio was calculated using 2014-2018 age-standardized cancer mortality rates from State Cancer Profiles. Linear regression with covariate adjustment was constructed to assess the association of provider density with (1) Black:White cancer mortality ratio, and (2) cancer mortality rates overall, and separately among Black and White persons. RESULTS: The mean Black:White cancer mortality ratio was 1.12, indicating that cancer mortality rate among Black persons was on average 12% higher than that among White persons. Oncology provider density was significantly associated with greater cancer mortality disparities: every 5 additional oncology providers per 100 000 in a county was associated with a .02 increase in the Black:White cancer mortality ratio (95% CI: .007 to .03); however, the unexpected finding may be explained by further analysis showing that the relationship between oncology provider density and cancer mortality was different by race group. Every 5 additional oncologists per 100 000 was associated with a 1.6 decrease per 100 000 in cancer mortality rates among White persons (95% CI: -3.0 to -.2), whereas oncology provider density was not associated with cancer mortality among Black persons. CONCLUSION: Greater oncology provider density was associated with significantly lower cancer mortality among White persons, but not among Black persons. Higher oncology provider density alone may not resolve cancer mortality disparities, thus attention to ensuring equitable care is critical.

IntroductionAlthough adverse childhood experiences (ACEs) have been positively associated with adiposity, few studies have examined long-term race-specific ACE-BMI relationships.MethodsA Black and White all-women cohort (N=611; 48.6% Black) was followed between 1987 and 1997 from childhood (ages 9-10 years) through adolescence (ages 19-20 years) to midlife (ages 36-43 years, between 2015 and 2019). In these 2020-2022 analyses, the interaction between race and individual ACE exposures (physical abuse, sexual abuse, household substance abuse, multiple ACEs) on continuous BMI at ages 19-20 years and midlife was evaluated individually through multivariable linear regression models. Stratification by race followed as warranted at α=0.15.ResultsRace only modified ACE-BMI associations for sexual abuse. Among Black women, sexual abuse was significantly associated with BMI (Badjusted=3.24, 95% CI=0.92, 5.57) at ages 19-20 years and marginally associated at midlife (Badjusted=2.37, 95% CI= -0.62, 5.35); among White women, corresponding associations were null. Overall, having ≥2 ACEs was significantly associated with adolescent BMI (Badjusted=1.47, 95% CI=0.13, 2.80) and was marginally associated at midlife (Badjusted=1.45, 95% CI= -0.31, 3.22). This was similarly observed for physical abuse (adolescent BMI: Badjusted=1.23, 95% CI= -0.08, 2.54; midlife BMI: Badjusted=1.03, 95% CI= -0.71, 2.78), but not for substance abuse.ConclusionsDirect exposure to certain severe ACEs is associated with increased BMI among Black and White women. It is important to consider race, ACE type, and life stage to gain a more sophisticated understanding of ACE-BMI relationships. This knowledge can help strengthen intervention, prevention, and policy efforts aiming to mitigate the impacts of social adversities and trauma on persistent cardiometabolic health disparities over the lifecourse.

INTRODUCTION: Identifying people at high risk of Alzheimer's disease (AD) dementia allows for timely intervention, which, if successful, will result in preventing or delaying the onset of the disease. METHODS: Utilizing data from the Chicago Health and Aging Project (CHAP; n = 2130), we externally evaluated four risk‐prediction models for AD dementia, including Cardiovascular Risk Factors, Aging, and Dementia (CAIDE), Australian National University Alzheimer's Disease Risk Index (ANU‐ADRI), Brief Dementia Screening Indicator (BDSI), and Dementia Risk Score (DRS), in Black or African American and White adults. RESULTS: BDSI had the highest discriminate abilities for AD dementia (c‐statistics of 0.79 in Black and 0.77 in White adults), followed by ANU‐ADRI, within the age range and follow‐up period of the original development cohort. CAIDE had the lowest discriminating power (c‐statistic ≤0.55). With increasing follow‐up periods (i.e., 10–15 years), the discrimination abilities for all models declined. DISCUSSION: Because of racial disparities in AD dementia and longer preclinical and prodromal stages of disease development, race‐specific models are needed to predict AD risk over 10 years. Highlights: Utilizing risk‐prediction models to identify individuals at higher risk of Alzheimer's disease (AD) dementia could benefit clinicians, patients, and policymakers. Clinicians could enroll high‐risk individuals in clinical trials to test new risk‐modifiable treatments or initiate lifestyle modifications, which, if successful, would slow cognitive decline and delay the onset of the disease.Current risk‐prediction models had good discriminative power during the first 6 years of follow‐up but decreased with longer follow‐up time.Acknowledging the longer preclinical phase of AD dementia development and racial differences in dementia risk, there is a need to develop race‐specific risk‐prediction models that can predict 10 or 20 years of risk for AD and related dementias. [ABSTRACT FROM AUTHOR]

Point-of-care tools to assess advanced liver fibrosis, including the NFS, BARD, FIB-4, and APRI, are of major interest due to their noninvasive nature. However, these tools have not been investigated extensively in the Latina population. Given that the highest rate of NAFLD in Latinos and the most severe presentation of non-alcoholic fatty liver disease (NAFLD) is more common in women, we hypothesize that ethnicity may play a role in predicting liver fibrosis, particularly in women. We determined whether ethnicity alone or in association with other parameters can predict the severity of fibrosis in women with NAFLD when included in four tools. We retrospectively included 562 Latina and 133 White Caucasian women with a history of NAFLD. Associations between ethnicity and liver fibrosis severity using the four fibrosis predictor models were studied using backward selection multinomial logistic regression. Latina women compared to White showed lower body mass index (p\0.001), higher HbA1c (p\0.001), lower prevalence of bariatric surgery (p\0.001), lower likelihood to smoke (p = 0.003), and higher prevalence of chronic kidney disease stages 3-5 (p = 0.01). Some clinical variables were associated with fibrosis but not univocally in each tool. We did not find differences in the outcome of the four models when holding all other factors and examining ethnicity alone between Latina and White women. Although we did not include data on liver histology, this is the first study examining the role of ethnicity in predicting the severity of fibrosis using established noninvasive scores and documenting no association between Latina ethnicity and the severity of fibrosis in women with NAFLD. [ABSTRACT FROM AUTHOR]

Despite the prominence of the weathering hypothesis as a mechanism underlying racialized inequities in morbidity and mortality, the life course social and economic determinants of Black-White disparities in biological aging remain inadequately understood. This study uses data from the Health and Retirement Study (n = 6,782), multivariable regression, and Kitagawa-Blinder-Oaxaca decomposition to assess Black-White disparities across three measures of biological aging: PhenoAge, Klemera-Doubal biological age, and homeostatic dysregulation. It also examines the contributions of racial differences in life course socioeconomic and stress exposures and vulnerability to those exposures to Black-White disparities in biological aging. Across the outcomes, Black individuals exhibited accelerated biological aging relative to White individuals. Decomposition analyses showed that racial differences in life course socioeconomic exposures accounted for roughly 27% to 55% of the racial disparities across the biological aging measures, and racial disparities in psychosocial stress exposure explained 7% to 11%. We found less evidence that heterogeneity in the associations between social exposures and biological aging by race contributed substantially to Black-White disparities in biological aging. Our findings offer new evidence of the role of life course social exposures in generating disparities in biological aging, with implications for understanding age patterns of morbidity and mortality risks.

IntroductionIncreasing racial/ethnic diversity in the United States calls for methodological approaches that capture participants who identify with multiple racial/ethnic groups. Existing approaches are oriented toward large samples (N > 500); yet, we do not know how effective these approaches are with more common smaller convenience samples. We explored how several approaches were associated with the sample distribution of racial/ethnic groups and ethnic identity using a small convenience sample.MethodsIn 2017, 320 U.S. adolescents (Mage  = 16.04 years, SDage  = 1.33; 59% female) responded to an open-ended question regarding their racial/ethnic group(s) in a cross-sectional survey. Seventy-five (23%) adolescents identified with multiple racial/ethnic groups. Remaining adolescents identified solely with the Asian/Hawaiian Native/Pacific Islander (19%), Black/African American (3%), European American (21%), Latinx (34%), or Native American/Alaska Native (

BACKGROUND: We evaluated diagnostic mammography among women with a breast lump to determine whether performance varied across racial and ethnic groups. METHODS: This study included 51,014 diagnostic mammograms performed between 2005 and 2018 in the Breast Cancer Surveillance Consortium among Asian/Pacific Islander (12%), Black (7%), Hispanic/Latina (6%), and White (75%) women reporting a lump. Breast cancers occurring within 1 year were ascertained from cancer registry linkages. Multivariable regression was used to adjust performance statistic comparisons for breast cancer risk factors, mammogram modality, demographics, additional imaging, and imaging facility. RESULTS: Cancer detection rates were highest among Asian/Pacific Islander [per 1,000 exams, 84.2 (95% confidence interval (CI): 72.0-98.2)] and Black women [81.4 (95% CI: 69.4-95.2)] and lowest among Hispanic/Latina women [42.9 (95% CI: 34.2-53.6)]. Positive predictive values (PPV) were higher among Black [37.0% (95% CI: 31.2-43.3)] and White [37.0% (95% CI: 30.0-44.6)] women and lowest among Hispanic/Latina women [22.0% (95% CI: 17.2-27.7)]. False-positive results were most common among Asian/Pacific Islander women [per 1,000 exams, 183.9 (95% CI: 126.7-259.2)] and lowest among White women [112.4 (95% CI: 86.1-145.5)]. After adjustment, false-positive and cancer detection rates remained higher for Asian/Pacific Islander and Black women (vs. Hispanic/Latina and White). Adjusted PPV was highest among Asian/Pacific Islander women. CONCLUSIONS: Among women with a lump, Asian/Pacific Islander and Black women were more likely to have cancer detected and more likely to receive a false-positive result compared with White and Hispanic/Latina women. IMPACT: Strategies for optimizing diagnostic mammography among women with a lump may vary by racial/ethnic group, but additional factors that influence performance differences need to be identified. See related In the Spotlight, p. 1479.

PurposeTo compare baseline mental health symptoms and gender affirmation between Black/Latine versus White transgender/nonbinary youth (BLTY vs. WTY) and examine relationships between gender affirmation and mental health symptoms, and whether associations differed by race/ethnicity subgroup.MethodsBaseline data were analyzed from the gender-affirming hormone cohort of the Trans Youth Care United States Study-a 4-clinic site, observational study. Mental health symptoms assessed included depression, suicidality, and anxiety. Gender affirmation measures included the parental acceptance subscale from the perceived Parental Attitudes of Gender Expansiveness Scale-Youth Report; non-affirmation, internalized transphobia, and community connectedness subscales from the Gender Minority Stress and Resilience Measure-Adolescent; and self-reported living full time in affirmed gender. Fisher exact tests and independent sample t tests compared mental health symptoms and gender affirmation between subgroups. Logistic regression analyses evaluated associations between gender affirmation and mental health symptoms. Interaction analyses assessed differences in associations between subgroups.ResultsThe sample (mean age 16 years, range 12-20 years) included 92 BLTY (35%) and 170 WTY (65%). Subgroups had comparable prevalence of depression and anxiety symptoms. WTY had higher prevalence of lifetime suicidality (73% vs. 59%; p = .02). There were no differences in gender affirmation. Among the whole sample, higher parental acceptance decreased odds of depression symptoms. Not living in affirmed gender increased odds of depression symptoms. Higher non-affirmation and internalized transphobia increased odds of depression and anxiety symptoms and suicidality. Associations did not vary by subgroup.DiscussionBLTY and WTY had comparable mental health symptoms. For both subgroups, gender affirmation decreased odds of those symptoms.

Preterm birth is a leading cause of perinatal morbidity and mortality. There are significant racial disparities in the rates of preterm delivery in the United States, with Black individuals at disproportionately higher risk than their White counterparts. Although low-dose aspirin is currently under investigation for reducing the rates of preterm delivery, limited data are available on how the use of low-dose aspirin might affect racial and ethnic disparities in the rates of preterm delivery. Our group and others have shown that low-dose aspirin decreases spontaneous preterm delivery in low-risk parturients. This study aimed to examine whether the relationship between low-dose aspirin and the risk of spontaneous preterm delivery is modified by race and ethnicity. This was a secondary analysis of a randomized clinical trial examining low-dose aspirin for preeclampsia prevention in low-risk nulliparous individuals. The parent trial defined low risk as the absence of preexisting hypertension or other medical comorbidities. Participants received 60-mg aspirin or placebo between 13 and 25 weeks of gestation. Here, multiple pregnancies, fetal anomalies, terminations or abortions at

Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1-dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

PurposeThe National Heart, Lung and Blood Institute Growth and Health Study (NGHS) prospectively collected anthropometric, biospecimens, clinical, health behaviour and psychosocial measures associated with cardiovascular disease from childhood to young adulthood. The aim of the current study was to assess the impact of stress, dysregulated eating and social genomic biomarkers on cardiometabolic risk factors among the original participants now in midlife and their children.ParticipantsBeginning in 1987-1988, NGHS recruited black and white girls (age 9-10 years) from socioeconomically diverse backgrounds from from three sites: Cincinnati, Ohio; Washington, DC; and Western Contra Costa County, California (N=2379) and followed them for 10 years. The study maintained an 89% retention rate. The current study is 30 years after the start of the original study and focused on the participants of California (n=887) and their children aged 2-17 years. We re-enrolled 624 of 852 eligible participants (73%): 49.2% black and 50.8% white. The mean age was 39.5 years. Among the 645 eligible biological children, 553 were enrolled; 49% black and 51% white, with 51.5% girls and 48.5% boys. The mean age was 9.3 years.Findings to dateLongitudinal analysis of adolescent drive for thinness predicted higher scores for drive for thinness during midlife, which was indirectly associated with greater adult body mass index through adult drive for thinness. Latent trajectory modelling of adolescent growth over 10 years found that women with persistently high weight trajectory had twice the odds of having children who met the definition for obesity compared with the persistently normal group, adjusting for adult weight.Future plansNew studies on neighbourhood socioeconomic status, food insecurity and additional biomarkers of chronic stress, microbiome and accelerated ageing (ie, telomere length and epigenetic clock) are underway. We are developing a 10-year follow-up to understand changes in ageing biomarkers of the participants and their children.Trial registration numberNCT00005132.

Despite the growing cultural diversity worldwide, there is scarce research on how socialization processes prepare youth to respond to increasing multicultural demands and the degree to which these socialization opportunities inform youth academic functioning. This study used a person-centered approach to identify profiles or niches based on the degree and consistency of multicultural socialization experiences across school, peer, and family settings and to examine the associations between identified niches and markers of academic functioning (i.e., emotional and behavioral academic engagement, academic aspirations and expectations) in a sample of adolescents (N = 717; Mage = 13.73 years). Participants (49.9% girls) were from the U.S. Southwest and represented multiple ethno-racial backgrounds (31.8% Hispanic/Latinx, 31.5% Multiethnic, 25.7% White, 7.3% Black or African American, 1.4% Asian American or Pacific Islander, 1.4% American Indian or Alaska Native, and 1% Arab, Middle Eastern, or North African). Six distinct multicultural socialization niches were identified. Three niches had similar patterns across school-peer-family but ranged in the degree of socialization. The cross-setting similar higher socialization niche (Niche 6) demonstrated greater socialization than the cross-setting similar moderate (Niche 5) and lower socialization (Niche 4) niches, which had moderate and lower socialization, respectively. Three niches demonstrated cross-setting dissimilarity which ranged in the type of cross-setting contrast and the degree of socialization. The cross-setting dissimilar school contrast socialization niche (Niche 3) had greater dissimilarities between socialization opportunities in the school setting compared to the peer and family settings and demonstrated the lowest levels of socialization of all niches. The other two niches, the cross-setting dissimilar peer contrast (Niche 1) and greater peer contrast socialization (Niche 2) niches had larger dissimilarities between socialization opportunities in the peer setting than the school and family settings. In the former, however, the contrast was lower, and socialization ranged between very low to low. In the latter, the contrast was higher and socialization ranged from very low to moderate. Most adolescents were in the cross-setting similar lower socialization niche or in the cross-setting dissimilar niches. Adolescents in the cross-setting similar higher multicultural socialization demonstrated greater emotional and behavioral academic engagement than adolescents in most of the other niches. Adolescents in the cross-setting dissimilar school contrast niches demonstrated lower emotional and behavioral academic engagement and lower academic expectations than adolescents in some of the other niches. The results emphasize the collective role of school, peer, and family multicultural socialization on emotional and behavioral academic engagement.

Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation in gene regulation. Remarkably, targeted DNA demethylation at the Pparg promoter restored its transcription. In conclusion, TET3 significantly governs adipogenesis and diet-induced adipose expansion by regulating key target genes in APCs.

In the United States (US), pressure ulcers affect ≤3 million people and costs exceed 26.8 billion US dollars in spending. To examine trends in primary pressure ulcer (PPU) hospitalization mortality, length of hospital stay (LOS), and inflation-adjusted charges (IAC) in the US from 2005 to 2014 by race/ethnicity. We secondarily examined the relationship between race/ethnicity with PPU mortality, LOS, and IAC with race/ethnicity. This cross-sectional study used Nationwide Inpatient Sample (NIS) data from 2005 to 2014. The study sample included all hospitalizations with the designated ICD-9-CM code of 707.20-25 (pressure ulcer). There was a notable decline in PPU hospitalization from 11.5% to 7.77 % between 2005 and 2014. The mean mortality decreased from 2.32% to 1.12% (P < .001), the mean LOS declined from 9.39 days (P < .001), and the mean IAC per hospitalization decreased from $30,935 to $29,432 (P < .001). Positive changes observed in mortality, LOS, and IAC trends were consistent across different racial and ethnic groups. The results of multivariable logistic and linear regression analyses revealed that Black patients (β = 0.68, 95% CI 0.36-1.01, P < .001) and patients belonging to the Other race/ethnic category (β = 0.93, 95% CI 0.18-1.69) had longer hospital stays compared to their White counterparts. Regarding IAC, Black patients (β = 2846, 95% CI 1254-4439, P < .005), Hispanic patients (β = 6527, 95% CI 4925-8130), and patients from the Other race/ethnic category (β = 3473, 95% CI 1771-5174) had higher IAC for PPU treatment compared to their White counterparts. PPU hospitalization discharges, as well as hospitalization mortality, LOS, and IAC, decreased during the study period, however, our findings revealed disparities in PPU outcomes among different racial/ethnic groups. Implications of the findings are discussed.

BACKGROUND: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC

IntroductionThe aim of this study was to evaluate the association of cardiovascular health (CVH) with cognitive outcomes, including incident Alzheimer's dementia, rate of cognitive decline, and measures of brain injury and structure.MethodsThis study consisted of 1702 Black or African American and White participants living in the south side of Chicago, Illinois, and enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. CVH was based on seven risk factors, including diet, physical activity, body mass index, smoking, dyslipidemia, hypertension, and diabetes.ResultsIn a multivariable-adjusted model, CVH was associated with a lower risk of Alzheimer's dementia. The hazard ratio per 1 additional point in CVH score was 0.84 (95% CI 0.76, 0.94). CVH was also associated with a slower rate of cognitive decline and less volume (injury) in white matter hyperintensities.DiscussionPromoting CVH in communities with Black residents may lower the future risk of Alzheimer's dementia.

Gentrification, a racialized and profit-driven process in which historically disinvested neighborhoods experience an influx of development that contributes to the improvement of physical amenities, increasing housing costs, and the dispossession and displacement of existing communities, may influence the risk of severe maternal morbidity (SMM). Leveraging a racially diverse population-based sample of all live hospital births in California between 2006 and 2017, we examined associations between neighborhood-level gentrification and SMM. SMM was defined as having one of 21 procedures and diagnoses, as described in the SMM index developed by Centers for Disease Control and Prevention. We compared three gentrification measures to determine which operationalization best captures aspects of gentrification most salient to SMM: Freeman, Landis 3-D, and Urban Displacement Project Gentrification and Displacement Typology. Descriptive analysis assessed bivariate associations between gentrification and birthing peoples characteristics. Overall and race and ethnicity-stratified mixed-effects logistic models assessed associations between gentrification and SMM, adjusting for individual sociodemographic and pregnancy factors while accounting for clustering by census tract. The study sample included 5,256,905 births, with 72,718 cases of SMM (1.4%). The percentage of individuals living in a gentrifying neighborhood ranged from 5.7% to 11.7% across exposure assessment methods. Net of individual and pregnancy-related factors, neighborhood-level gentrification, as measured by the Freeman method, was protective against SMM (OR = 0.89, 95% CI: 0.86-0.93); in comparison, gentrification, as measured by the Gentrification and Displacement Typology, was associated with greater risk of SMM (OR = 1.18, 95% CI: 1.14-1.23). These associations were significant among non-Hispanic White, non-Hispanic Black, and Hispanic individuals. Findings demonstrate that gentrification plays a role in shaping the risk of SMM among birthing people in California. Differences in how gentrification is conceptualized and measured, such as an emphasis on housing affordability compared to a broader characterization of gentrifications multiple aspects, may explain the heterogeneity in the directions of observed associations.

ObjectiveTo describe patient approaches to navigating their probability of a vaginal birth after cesarean (VBAC) within the context of prediction scores generated from the original Maternal-Fetal Medicine Units' VBAC calculator, which incorporated race and ethnicity as one of six risk factors.MethodsWe invited a diverse group of participants with a history of prior cesarean delivery to participate in interviews and have their prenatal visits recorded. Using an open-ended iterative interview guide, we queried and observed these individuals' mode-of-birth decisions in the context of their VBAC calculator scores. We used a critical and feminist approach to analyze thematic data gleaned from interview and visit transcripts.ResultsAmong the 31 participants who enrolled, their self-identified racial and ethnic categories included: Asian or South Asian (2); Black (4); Hispanic (12); Indigenous (1); White (8); and mixed-Black, -Hispanic, or -Asian background (4). Predicted VBAC success probabilities ranged from 12% to 95%. Participants completed 64 interviews, and 14 prenatal visits were recorded. We identified four themes that demonstrated a range of patient-led approaches to interpreting the probability generated by the VBAC calculator: 1) rejecting the role of race and ethnicity; 2) reframing failure, finding success; 3) factoring the physical experience of labor; and 4) modifying the probability for VBAC.ConclusionOur findings demonstrate that a numeric probability for VBAC may not be highly valued or important to all patients, especially those who have strong intentions for VBAC. Black and Hispanic participants challenged the VBAC calculator's incorporation of race and ethnicity as a risk factor and resisted the implication it produced, especially that their bodies were less capable of achieving a vaginal birth. Our findings suggest that patient-led approaches to assessing and interpreting VBAC probability may be an untapped resource for achieving a more person-centered, equitable approach to counseling.

PurposeThe incidence of Ewing sarcoma varies according to race and ethnicity, and genetic susceptibility is known to affect disease risk. Apart from these factors, the etiology of Ewing sarcoma is largely unknown.MethodsWe compared the birth characteristics of a population-based series of 556 Ewing sarcoma cases born in California in 1978-2015 and diagnosed in 1988-2015 with those of 27,800 controls selected from statewide birth records and frequency-matched to cases on the year of birth, using multivariable logistic regression models. We also assessed whether Ewing sarcoma clustered within families.ResultsCompared to non-Hispanic White subjects, Black (odds ratio [OR] = 0.07, 95% confidence interval [CI] 0.03-0.18), Asian (OR = 0.57, 95% CI 0.41-0.80), and Hispanic (OR = 0.73, 95% CI 0.62-0.88) individuals had a significantly lower risk of Ewing sarcoma. Race and ethnicity differences were more profound for metastatic Ewing sarcoma. Birthweight was also identified as a significant risk factor (OR = 1.09, 95% CI 1.00-1.18 for each 500 g increase in birthweight). A separate family-based cancer clustering analysis did not suggest any strong role for familial predisposition alleles.ConclusionsThis population-based study with minimal selection bias provides support for a role of accelerated fetal growth in the etiology of Ewing sarcoma in addition to more precise estimates of racial and ethnic variations in disease risk. This comparatively large analysis of birth characteristics and Ewing sarcoma in a multiethnic population should stimulate further investigations into genetic and environmental causes.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

OBJECTIVE: To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort. METHODS: NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non-SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random-effects regressions. Five- and 10-year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling. RESULTS: A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non-SLE NP events, predicted annual, 5-, and 10-year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5-fold higher and indirect costs 1.3-fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non-SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs. CONCLUSION: Patients with new/ongoing SLE or non-SLE NP events incurred higher direct and indirect costs.

PurposeThe purpose of this study was to assess differences in COVID-19 vaccine willingness and uptake between rural and nonrural adults, and within rural racial-ethnic groups.MethodsWe utilized data from the COVID-19's Unequal Racial Burden online survey, which included 1,500 Black/African American, Latino, and White rural adults (n = 500 each). Baseline (12/2020-2/2021) and 6-month follow-up (8/2021-9/2021) surveys were administered. A cohort of nonrural Black/African American, Latino, and White adults (n = 2,277) was created to compare differences between rural and nonrural communities. Multinomial logistic regression was used to assess associations between rurality, race-ethnicity, and vaccine willingness and uptake.FindingsAt baseline, only 24.9% of rural adults were extremely willing to be vaccinated and 28.4% were not at all willing. Rural White adults were least willing to be vaccinated, compared to nonrural White adults (extremely willing: aOR = 0.44, 95% CI = 0.30-0.64). At follow-up, 69.3% of rural adults were vaccinated; however, only 25.3% of rural adults who reported being unwilling to vaccinate were vaccinated at follow-up, compared to 95.6% of adults who were extremely willing to be vaccinated and 76.3% who were unsure. Among those unwilling to vaccinate at follow-up, almost half reported distrust in the government (52.3%) and drug companies (46.2%); 80% reported that nothing would change their minds regarding vaccination.ConclusionsBy August 2021, almost 70% of rural adults were vaccinated. However, distrust and misinformation were prevalent among those unwilling to vaccinate at follow-up. To continue to effectively combat COVID-19 in rural communities, we need to address misinformation to increase COVID-19 vaccination rates.

In obesity, CD11c+ innate immune cells are recruited to adipose tissue and create an inflammatory state that causes both insulin and catecholamine resistance. We found that ablation of Gnas, the gene that encodes Gαs, in CD11c expressing cells protects mice from obesity, glucose intolerance, and insulin resistance. Transplantation studies showed that the lean phenotype was conferred by bone marrow-derived cells and did not require adaptive immunity. Loss of cAMP signaling was associated with increased adipose tissue norepinephrine and cAMP signaling, and prevention of catecholamine resistance. The adipose tissue had reduced expression of catecholamine transport and degradation enzymes, suggesting that the elevated norepinephrine resulted from decreased catabolism. Collectively, our results identified an important role for cAMP signaling in CD11c+ innate immune cells in whole-body metabolism by controlling norepinephrine levels in white adipose tissue, modulating catecholamine-induced lipolysis and increasing thermogenesis, which, together, created a lean phenotype.Article highlightsWe undertook this study to understand how immune cells communicate with adipocytes, specifically, whether cAMP signaling in the immune cell and the adipocyte are connected. We identified a reciprocal interaction between CD11c+ innate immune cells and adipocytes in which high cAMP signaling in the immune cell compartment induces low cAMP signaling in adipocytes and vice versa. This interaction regulates lipolysis in adipocytes and inflammation in immune cells, resulting in either a lean, obesity-resistant, and insulin-sensitive phenotype, or an obese, insulin-resistant phenotype.

Background and Aim Methods Results Conclusions Esophageal cancer significantly contributes to US cancer mortality, with notable racial disparities. This study aims to provide updated esophageal cancer mortality trends among Black and White adults from 1999 to 2020.CDC‐WONDER was used to identify Black and White adults in the United States from 1999 to 2020. We calculated age‐standardized mortality rates, absolute rate differences, and rate ratios to compare the mortality differences between these populations.From 1999 to 2020 in the United States, there were 303 267 esophageal cancer deaths, with significant racial disparities. The age‐adjusted mortality rate for Black adults fell from 6.52 to 2.62 per 100 000, while for White adults, it declined from 4.19 to 3.97 per 100 000, narrowing the racial mortality gap. Gender‐wise, the study showed a decrease in the mortality rate from 3.31 to 2.29 per 100 000 in Black women, but an increase from 1.52 to 1.99 per 100 000 in White women. Among young men, the rate dropped in Black men from 12.82 to 6.26 per 100 000 but rose in White men from 9.90 to 10.57 per 100 000. Regionally, Black adults in the Midwest and South initially had higher mortality rates than Whites, but this gap reduced over time. By 2020, Black men had lower mortality rates across all regions.Over the last two decades, age‐adjusted esophageal cancer mortality decreased in Black adults but stabilized in White adults, reflecting distinct cancer trends and risk factors. The study highlights the importance of tailored public health strategies for healthcare access and risk factor management. [ABSTRACT FROM AUTHOR]

White light is of great technical interest in many photonic applications. In this work, colloidal solutions containing mutually immiscible green perovskite nanocrystals and red InP quantum dots are developed as color‐conversion (CC) materials for generating white light. By combining the green/red CC materials and a blue top‐emission organic light‐emitting diode as an excitation source, it is possible to generate white light with a range of color temperatures (CTs). The technical approach can be extended to a wide variety of photonic applications where controllable CT is desirable. [ABSTRACT FROM AUTHOR]

Introduction: In honouring the legacy of Jude Byrne's life‐long advocacy for women and mothers who use drugs, this paper presents a case study of a group of women about whom we know little about and hear even less from: women who inject drugs in relatively affluent suburbs. Methods: Based on a 2020 qualitative study of people who inject drugs in an affluent area of Sydney known as 'The Beaches', we use in‐depth interview data to thematically explore the lived experiences of gendered stigma among women who inject drugs. Results: Even when women occupy the 'ideal' social position in terms of class (middle‐class) and race (White) they remain subject to harmful forms of gendered stigma related to injecting drug use. Participants had internalised negative attitudes around injection drug use as a form of failed femininity and, despite being part of 'good' families and neighbourhoods, participants experienced forced child removal. Discussion and Conclusions: Taking the lead from feminist intersectionality scholarship, our data illustrate how stigma and discrimination act as a form of structural violence against women who inject drugs in affluent communities. While the social relations of gender provide some degree of protection by 'performing proximity to Whiteness', gendered stigma and violence persist. [ABSTRACT FROM AUTHOR]

Sympathetic activation during cold exposure increases adipocyte thermogenesis via the expression of mitochondrial protein uncoupling protein 1 (UCP1)1. The propensity of adipocytes to express UCP1 is under a critical influence of the adipose microenvironment and varies between sexes and among various fat depots2-7. Here we report that mammary gland ductal epithelial cells in the adipose niche regulate cold-induced adipocyte UCP1 expression in female mouse subcutaneous white adipose tissue (scWAT). Single-cell RNA sequencing shows that glandular luminal epithelium subtypes express transcripts that encode secretory factors controlling adipocyte UCP1 expression under cold conditions. We term these luminal epithelium secretory factors 'mammokines'. Using 3D visualization of whole-tissue immunofluorescence, we reveal sympathetic nerve-ductal contact points. We show that mammary ducts activated by sympathetic nerves limit adipocyte UCP1 expression via the mammokine lipocalin 2. In vivo and ex vivo ablation of mammary duct epithelium enhance the cold-induced adipocyte thermogenic gene programme in scWAT. Since the mammary duct network extends throughout most of the scWAT in female mice, females show markedly less scWAT UCP1 expression, fat oxidation, energy expenditure and subcutaneous fat mass loss compared with male mice, implicating sex-specific roles of mammokines in adipose thermogenesis. These results reveal a role of sympathetic nerve-activated glandular epithelium in adipocyte UCP1 expression and suggest that mammary duct luminal epithelium has an important role in controlling glandular adiposity.

Chronic white adipose tissue (WAT) inflammation has been recognized as a critical early event in the pathogenesis of obesity-related disorders. This process is characterized by the increased residency of proinflammatory M1 macrophages in WAT. However, the lack of an isogenic human macrophage-adipocyte model has limited biological studies and drug discovery efforts, highlighting the need for human stem cell-based approaches. Here, human induced pluripotent stem cell (iPSC) derived macrophages (iMACs) and adipocytes (iADIPOs) are cocultured in a microphysiological system (MPS). iMACs migrate toward and infiltrate into the 3D iADIPOs cluster to form crown-like structures (CLSs)-like morphology around damaged iADIPOs, recreating classic histological features of WAT inflammation seen in obesity. Significantly more CLS-like morphologies formed in aged and palmitic acid-treated iMAC-iADIPO-MPS, showing the ability to mimic inflammatory severity. Importantly, M1 (proinflammatory) but not M2 (tissue repair) iMACs induced insulin resistance and dysregulated lipolysis in iADIPOs. Both RNAseq and cytokines analyses revealed a reciprocal proinflammatory loop in the interactions of M1 iMACs and iADIPOs. This iMAC-iADIPO-MPS thus successfully recreates pathological conditions of chronically inflamed human WAT, opening a door to study the dynamic inflammatory progression and identify clinically relevant therapies.