Neural mechanism underlying depressive-like state associated with social status loss.

Downward social mobility is a well-known mental risk factor for depression, but its neural mechanism remains elusive. Here, by forcing mice to lose against their subordinates in a non-violent social contest, we lower their social ranks stably and induce depressive-like behaviors. These rank-decline-associated depressive-like behaviors can be reversed by regaining social status. In vivo fiber photometry and single-unit electrophysiological recording show that forced loss, but not natural loss, generates negative reward prediction error (RPE). Through the lateral hypothalamus, the RPE strongly activates the brain's anti-reward center, the lateral habenula (LHb). LHb activation inhibits the medial prefrontal cortex (mPFC) that controls social competitiveness and reinforces retreats in contests. These results reveal the core neural mechanisms mutually promoting social status loss and depressive behaviors. The intertwined neuronal signaling controlling mPFC and LHb activities provides a mechanistic foundation for the crosstalk between social mobility and psychological disorder, unveiling a promising target for intervention.

American Cancer Society's report on the status of cancer disparities in the United States, 2023.

In 2021, the American Cancer Society published its first biennial report on the status of cancer disparities in the United States. In this second report, the authors provide updated data on racial, ethnic, socioeconomic (educational attainment as a marker), and geographic (metropolitan status) disparities in cancer occurrence and outcomes and contributing factors to these disparities in the country. The authors also review programs that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. There are substantial variations in risk factors, stage at diagnosis, receipt of care, survival, and mortality for many cancers by race/ethnicity, educational attainment, and metropolitan status. During 2016 through 2020, Black and American Indian/Alaska Native people continued to bear a disproportionately higher burden of cancer deaths, both overall and from major cancers. By educational attainment, overall cancer mortality rates were about 1.6-2.8 times higher in individuals with ≤12 years of education than in those with ≥16 years of education among Black and White men and women. These disparities by educational attainment within each race were considerably larger than the Black-White disparities in overall cancer mortality within each educational attainment, ranging from 1.03 to 1.5 times higher among Black people, suggesting a major role for socioeconomic status disparities in racial disparities in cancer mortality given the disproportionally larger representation of Black people in lower socioeconomic status groups. Of note, the largest Black-White disparities in overall cancer mortality were among those who had ≥16 years of education. By area of residence, mortality from all cancer and from leading causes of cancer death were substantially higher in nonmetropolitan areas than in large metropolitan areas. For colorectal cancer, for example, mortality rates in nonmetropolitan areas versus large metropolitan areas were 23% higher among males and 21% higher among females. By age group, the racial and geographic disparities in cancer mortality were greater among individuals younger than 65 years than among those aged 65 years and older. Many of the observed racial, socioeconomic, and geographic disparities in cancer mortality align with disparities in exposure to risk factors and access to cancer prevention, early detection, and treatment, which are largely rooted in fundamental inequities in social determinants of health. Equitable policies at all levels of government, broad interdisciplinary engagement to address these inequities, and equitable implementation of evidence-based interventions, such as increasing health insurance coverage, are needed to reduce cancer disparities.

American Cancer Society's report on the status of cancer disparities in the United States, 2021.

In this report, the authors provide comprehensive and up-to-date US data on disparities in cancer occurrence, major risk factors, and access to and utilization of preventive measures and screening by sociodemographic characteristics. They also review programs and resources that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. The overall cancer death rate is 19% higher among Black males than among White males. Black females also have a 12% higher overall cancer death rate than their White counterparts despite having an 8% lower incidence rate. There are also substantial variations in death rates for specific cancer types and in stage at diagnosis, survival, exposure to risk factors, and receipt of preventive measures and screening by race/ethnicity, socioeconomic status, and geographic location. For example, kidney cancer death rates by sex among American Indian/Alaska Native people are ≥64% higher than the corresponding rates in each of the other racial/ethnic groups, and the 5-year relative survival for all cancers combined is 14% lower among residents of poorer counties than among residents of more affluent counties. Broad and equitable implementation of evidence-based interventions, such as increasing health insurance coverage through Medicaid expansion or other initiatives, could substantially reduce cancer disparities. However, progress will require not only equitable local, state, and federal policies but also broad interdisciplinary engagement to elevate and address fundamental social inequities and longstanding systemic racism.

Racial and socioeconomic disparities in lung cancer screening in the United States: A systematic review.

Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer deaths. Lung cancer screening (LCS) reduces NSCLC mortality; however, a lack of diversity in LCS studies may limit the generalizability of the results to marginalized groups who face higher risk for and worse outcomes from NSCLC. Identifying sources of inequity in the LCS pipeline is essential to reduce disparities in NSCLC outcomes. The authors searched 3 major databases for studies published from January 1, 2010 to February 27, 2020 that met the following criteria: 1) included screenees between ages 45 and 80 years who were current or former smokers, 2) written in English, 3) conducted in the United States, and 4) discussed socioeconomic and race-based LCS outcomes. Eligible studies were assessed for risk of bias. Of 3721 studies screened, 21 were eligible. Eligible studies were evaluated, and their findings were categorized into 3 themes related to LCS disparities faced by Black and socioeconomically disadvantaged individuals: 1) eligibility; 2) utilization, perception, and utility; and 3) postscreening behavior and care. Disparities in LCS exist along racial and socioeconomic lines. There are several steps along the LCS pipeline in which Black and socioeconomically disadvantaged individuals miss the potential benefits of LCS, resulting in increased mortality. This study identified potential sources of inequity that require further investigation. The authors recommend the implementation of prospective trials that evaluate eligibility criteria for underserved groups and the creation of interventions focused on improving utilization and follow-up care to decrease LCS disparities.

Genetic modifiers of body mass index in individuals with cystic fibrosis.

To identify modifier loci underlying variation in body mass index (BMI) in persons with cystic fibrosis (pwCF), we performed a genome-wide association study (GWAS). Utilizing longitudinal height and weight data, along with demographic information and covariates from 4,393 pwCF, we calculated AvgBMIz representing the average of per-quarter BMI Z scores. The GWAS incorporated 9.8M single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) > 0.005 extracted from whole-genome sequencing (WGS) of each study subject. We observed genome-wide significant association with a variant in FTO (FaT mass and Obesity-associated gene; rs28567725; p value = 1.21e-08; MAF = 0.41, ß = 0.106; n = 4,393 individuals) and a variant within ADAMTS5 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 5; rs162500; p value = 2.11e-10; MAF = 0.005, ß = -0.768; n = 4,085 pancreatic-insufficient individuals). Notably, BMI-associated variants in ADAMTS5 occur on a haplotype that is much more common in African (AFR, MAF = 0.183) than European (EUR, MAF = 0.006) populations (1000 Genomes project). A polygenic risk score (PRS) calculated using 924 SNPs (excluding 17 in FTO) showed significant association with AvgBMIz (p value = 2.2e-16; r2 = 0.03). Association between variants in FTO and the PRS correlation reveals similarities in the genetic architecture of BMI in CF and the general population. Inclusion of Black individuals in whom the single-gene disorder CF is much less common but genomic diversity is greater facilitated detection of association with variants that are in LD with functional SNPs in ADAMTS5. Our results illustrate the importance of population diversity, particularly when attempting to identify variants that manifest only under certain physiologic conditions.

Economic mobility and parents' opportunity hoarding.

Creating opportunities for people to achieve socioeconomic mobility is a widely shared societal goal. Paradoxically, however, achieving this goal can pose a threat to high-socioeconomic-status (SES) people as they look to maintain their privileged positions in society for both them and their children. Two studies evaluate whether this threat manifests as "opportunity hoarding" in which high-SES parents adopt attitudes and behaviors aimed at shoring up their families' access to valuable educational and economic resources. The current paper provides converging evidence for this hypothesis across two studies conducted with 2,557 American parents. An initial correlational study demonstrated that believing that socioeconomic mobility is possible was associated with high-SES parents being more inclined to attempt to secure valuable educational and economic resources for their children, even when doing so came at the cost of low-SES families. Specifically, high-SES parents with stronger beliefs in socioeconomic mobility exhibited decreased support for redistributive policies and viewed engaging in discrete behaviors that would unfairly advantage their children (e.g., allowing them to misrepresent their identities on school and job applications) as more acceptable relative to both low-SES parents with similar beliefs and high-SES parents who were less optimistic about socioeconomic mobility. A subsequent experimental study established these relationships causally by comparing parents' responses to different types of socioeconomic mobility. Together, the current findings merge insights across psychology and economics to deepen understandings of the processes through which societal inequities emerge and persist, especially during times of apparently abundant opportunity.

The health risk of social disadvantage is transplantable into a new host.

Low socioeconomic status (SES) is a risk factor for mortality and immune dysfunction across a wide range of diseases, including cancer. However, cancer is distinct in the use of allogeneic hematopoietic cell transplantation (HCT) as a treatment for hematologic malignancies to transfer healthy hematopoietic cells from one person to another. This raises the question of whether social disadvantage of an HCT cell donor, as assessed by low SES, might impact the subsequent health outcomes of the HCT recipient. To evaluate the cellular transplantability of SES-associated health risk, we analyzed the health outcomes of 2,005 HCT recipients who were transplanted for hematologic malignancy at 125 United States transplant centers and tested whether their outcomes differed as a function of their cell donor's SES (controlling for other known HCT-related risk factors). Recipients transplanted with cells from donors in the lowest quartile of SES experienced a 9.7% reduction in overall survival (P = 0.001) and 6.6% increase in treatment-related mortality within 3 y (P = 0.008) compared to those transplanted from donors in the highest SES quartile. These results are consistent with previous research linking socioeconomic disadvantage to altered immune cell function and hematopoiesis, and they reveal an unanticipated persistence of those effects after cells are transferred into a new host environment. These SES-related disparities in health outcomes underscore the need to map the biological mechanisms involved in the social determinants of health and develop interventions to block those effects and enhance the health of both HCT donors and recipients.

DNA methylation near MAD1L1, KDM2B, and SOCS3 mediates the effect of socioeconomic status on elevated body mass index in African American adults.

Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI. Using data from African American adults from the Atherosclerosis Risk in Communities (ARIC) Study (n = 2664, mean age = 57 years), education, income, and occupation were used to create a composite SES score at visit 1 (1987-1989). We conducted two methylation-wide association analyses to identify associations between SES (visit 1), BMI and cytosine-phosphate-guanine (CpG) sites measured at a subsequent visit (1990-1995). We then utilized structural equation modeling (SEM) to test whether identified sites mediated the association between earlier SES and BMI in sex-stratified models adjusted for demographic and risk factor covariates. Independent replication and meta-analyses were conducted using the Jackson Heart Study (JHS, n = 874, mean age 51 years, 2000-2004). Three CpG sites near MAD1L1, KDM2B, and SOCS3 (cg05095590, cg1370865, and cg18181703) were suggestively associated (P-value < 1.3×10-5) in ARIC and at array-wide significance (P-value < 1.3×10-7) in a combined meta-analysis of ARIC with JHS. SEM of these three sites revealed significant indirect effects in females (P-value < 5.8×10-3), each mediating 7%-20% of the total effect of SES on BMI. Nominally significant indirect effects were observed for two sites near MAD1L1 and KDM2B in males (P-value < 3.4×10-2), mediating -17 and -22% of the SES-BMI effect. These results provide further evidence that epigenetic modifications may be a potential pathway through which SES may "get under the skin" and contribute to downstream health disparities.

BertTCR: a Bert-based deep learning framework for predicting cancer-related immune status based on T cell receptor repertoire.

The T cell receptor (TCR) repertoire is pivotal to the human immune system, and understanding its nuances can significantly enhance our ability to forecast cancer-related immune responses. However, existing methods often overlook the intra- and inter-sequence interactions of T cell receptors (TCRs), limiting the development of sequence-based cancer-related immune status predictions. To address this challenge, we propose BertTCR, an innovative deep learning framework designed to predict cancer-related immune status using TCRs. BertTCR combines a pre-trained protein large language model with deep learning architectures, enabling it to extract deeper contextual information from TCRs. Compared to three state-of-the-art sequence-based methods, BertTCR improves the AUC on an external validation set for thyroid cancer detection by 21 percentage points. Additionally, this model was trained on over 2000 publicly available TCR libraries covering 17 types of cancer and healthy samples, and it has been validated on multiple public external datasets for its ability to distinguish cancer patients from healthy individuals. Furthermore, BertTCR can accurately classify various cancer types and healthy individuals. Overall, BertTCR is the advancing method for cancer-related immune status forecasting based on TCRs, offering promising potential for a wide range of immune status prediction tasks.

Risk factors of cytokine release syndrome: stress, catecholamines, and beyond.

Cytokine release syndrome (CRS) is a severe clinical syndrome marked by drastic elevation of inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF). Despite the current empirical therapeutic strategies, prediction of CRS onset and identification of high-risk individuals are not satisfactory due to poor understanding of the mechanisms underlying CRS-related immune dysfunction and risk factors for CRS. Recent studies have suggested that conditions such as stress, obesity, diabetes, and hypertension may contribute to the development of CRS. Here, we discuss potential connections between these conditions and CRS pathogenesis, with a focus on stress hormone catecholamine-mediated effects, hoping that the design of CRS therapeutic approaches ensues from a renewed perspective.

Deportations and departures: Undocumented Mexican immigrants' return migration during three presidential administrations.

This study examines changes in the sociodemographic patterns of deportation and voluntary return of undocumented immigrants from the United States to Mexico during three US presidential administrations (2001 to 2019) with different immigration policies. Most previous studies examining these migration flows for the United States as a whole have relied exclusively on counts of deportees and returnees, thereby ignoring changes over the past 20 y in the characteristics of the undocumented population itself, i.e., the population at risk of deportation or voluntary return. We estimate Poisson models based on two data sources that permit us to compare changes in the sex, age, education, and marital status distributions of both deportees and voluntary return migrants with the corresponding changes in the undocumented population during the Bush, Obama, and Trump administrations: the Migration Survey on the Borders of Mexico-North (Encuesta sobre Migración en las Fronteras de México-Norte) for counts of deportees and voluntary return migrants and the Current Population Survey's Annual Social and Economic Supplement for estimated counts of the undocumented population living in the United States. We find that whereas disparities by sociodemographic characteristics in the likelihood of deportation generally increased beginning in Obama's first term, sociodemographic disparities in the likelihood of voluntary return generally decreased over this period. Despite heightened antiimmigrant rhetoric during the Trump administration, the changes in deportation and voluntary return migration to Mexico among the undocumented during Trump's term were part of a trend that began early in the Obama administration.

Heterogeneity of depression across the socioeconomic spectrum.

Why is lower socioeconomic status associated with higher rates of depression? And, is the surplus of depression at lower SES just more of the same type as depression found at higher levels, or is it distinctive? We addressed these questions by examining the relations among SES, amygdala volume, and symptoms of depression in healthy young adults. Amygdala volume, a risk factor for depression, does not synergize with SES in a diathesis-stress relation, nor does it mediate the relation of SES to depression. Rather, SES and amygdala volume are independent, additive risk factors. They are also associated with different depression symptoms and, whereas perceived stress fully mediates the relation of SES to depression, it has no relation to amygdala volume. These findings suggest heterogeneity of depression across the socioeconomic spectrum, with implications for treatment selection as well as for future genetic and brain studies.

Everyday language input and production in 1,001 children from six continents.

Language is a universal human ability, acquired readily by young children, who otherwise struggle with many basics of survival. And yet, language ability is variable across individuals. Naturalistic and experimental observations suggest that children's linguistic skills vary with factors like socioeconomic status and children's gender. But which factors really influence children's day-to-day language use? Here, we leverage speech technology in a big-data approach to report on a unique cross-cultural and diverse data set: >2,500 d-long, child-centered audio-recordings of 1,001 2- to 48-mo-olds from 12 countries spanning six continents across urban, farmer-forager, and subsistence-farming contexts. As expected, age and language-relevant clinical risks and diagnoses predicted how much speech (and speech-like vocalization) children produced. Critically, so too did adult talk in children's environments: Children who heard more talk from adults produced more speech. In contrast to previous conclusions based on more limited sampling methods and a different set of language proxies, socioeconomic status (operationalized as maternal education) was not significantly associated with children's productions over the first 4 y of life, and neither were gender or multilingualism. These findings from large-scale naturalistic data advance our understanding of which factors are robust predictors of variability in the speech behaviors of young learners in a wide range of everyday contexts.

The inheritance of social status: England, 1600 to 2022.

A lineage of 422,374 English people (1600 to 2022) contains correlations in social outcomes among relatives as distant as 4th cousins. These correlations show striking patterns. The first is the strong persistence of social status across family trees. Correlations decline by a factor of only 0.79 across each generation. Even fourth cousins, with a common ancestor only five generations earlier, show significant status correlations. The second remarkable feature is that the decline in correlation with genetic distance in the lineage is unchanged from 1600 to 2022. Vast social changes in England between 1600 and 2022 would have been expected to increase social mobility. Yet people in 2022 remain correlated in outcomes with their lineage relatives in exactly the same way as in preindustrial England. The third surprising feature is that the correlations parallel those of a simple model of additive genetic determination of status, with a genetic correlation in marriage of 0.57.

Global trends in emotional distress.

In this study, we examined emotional distress using annual representative survey data from 1.53 million individuals surveyed in 113 countries from 2009 to 2021. Participants reported whether they had experienced worry, sadness, stress, or anger during a lot of the previous day. Within-country estimates showed that the prevalence of feelings of emotional distress increased from 25 to 31% between 2009 and 2021, with those with low levels of education and income experiencing the largest increases in distress. On a global level, the pandemic period was characterized by an initial increase in distress in 2020 followed by recovery in 2021.

Negative energy balance hinders prosocial helping behavior.

The internal state of an animal, including homeostatic requirements, modulates its behavior. Negative energy balance stimulates hunger, thus promoting a range of actions aimed at obtaining food. While these survival actions are well established, the influence of the energy status on prosocial behavior remains unexplored. We developed a paradigm to assess helping behavior in which a free mouse was faced with a conspecific trapped in a restrainer. We measured the willingness of the free mouse to liberate the confined mouse under diverse metabolic conditions. Around 42% of ad libitum-fed mice exhibited a helping behavior, as evidenced by the reduction in the latencies to release the trapped cagemate. This behavior was independent of subsequent social contact reward and was associated with changes in corticosterone indicative of emotional contagion. This decision-making process was coupled with reduced blood glucose excursions and higher Adenosine triphosphate (ATP):Adenosine diphosphate (ADP) ratios in the forebrain of helper mice, suggesting that it was a highly energy-demanding process. Interestingly, chronic (food restriction and type 2 diabetes) and acute (chemogenetic activation of hunger-promoting AgRP neurons) situations mimicking organismal negative energy balance and enhanced appetite attenuated helping behavior toward a distressed conspecific. To investigate similar effects in humans, we estimated the influence of glycated hemoglobin (a surrogate of long-term glycemic control) on prosocial behavior (namely charity donation) using the Understanding Society dataset. Our results evidenced that organismal energy status markedly influences helping behavior and that hypothalamic AgRP neurons are at the interface of metabolism and prosocial behavior.

Conservation successes and challenges for wide-ranging sharks and rays.

Overfishing is the most significant threat facing sharks and rays. Given the growth in consumption of seafood, combined with the compounding effects of habitat loss, climate change, and pollution, there is a need to identify recovery paths, particularly in poorly managed and poorly monitored fisheries. Here, we document conservation through fisheries management success for 11 coastal sharks in US waters by comparing population trends through a Bayesian state-space model before and after the implementation of the 1993 Fisheries Management Plan for Sharks. We took advantage of the spatial and temporal gradients in fishing exposure and fisheries management in the Western Atlantic to analyze the effect on the Red List status of all 26 wide-ranging coastal sharks and rays. We show that extinction risk was greater where fishing pressure was higher, but this was offset by the strength of management engagement (indicated by strength of National and Regional Plan of Action for sharks and rays). The regional Red List Index (which tracks changes in extinction risk through time) declined in all regions until the 1980s but then improved in the North and Central Atlantic such that the average extinction risk is currently half that in the Southwest. Many sharks and rays are wide ranging, and successful fisheries management in one country can be undone by poorly regulated or unregulated fishing elsewhere. Our study underscores that well-enforced, science-based management of carefully monitored fisheries can achieve conservation success, even for slow-growing species.

Urban visual intelligence: Uncovering hidden city profiles with street view images.

A longstanding line of research in urban studies explores how cities can be understood through their appearance. However, what remains unclear is to what extent urban dwellers' everyday life can be explained by the visual clues of the urban environment. In this paper, we address this question by applying a computer vision model to 27 million street view images across 80 counties in the United States. Then, we use the spatial distribution of notable urban features identified through the street view images, such as street furniture, sidewalks, building façades, and vegetation, to predict the socioeconomic profiles of their immediate neighborhood. Our results show that these urban features alone can account for up to 83% of the variance in people's travel behavior, 62% in poverty status, 64% in crime, and 68% in health behaviors. The results outperform models based on points of interest (POI), population, and other demographic data alone. Moreover, incorporating urban features captured from street view images can improve the explanatory power of these other methods by 5% to 25%. We propose "urban visual intelligence" as a process to uncover hidden city profiles, infer, and synthesize urban information with computer vision and street view images. This study serves as a foundation for future urban research interested in this process and understanding the role of visual aspects of the city.

Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress.

Sustained life stress and low socioeconomic status are among the major causes of aging-related diseases and decreased life expectancy. Experimental rodent models can help to identify the underlying mechanisms, yet very few studies address the long-term consequences of social stress on aging. We conducted a randomized study involving more than 300 male mice of commonly used laboratory strains (C57BL/6J, CD1, and Sv129Ev) chosen for the spontaneous aggression gradient and stress-vulnerability. Mice were exposed to a lifelong chronic psychosocial stress protocol to model social gradients in aging and disease vulnerability. Low social rank, inferred based on a discretized aggression index, was found to negatively impact lifespan in our study population. However, social rank interacted with genetic background in that low-ranking C57BL/6J, high-ranking Sv129Ev, and middle-ranking CD1 mice had lower survival, respectively, implying a cost of maintaining a given social rank that varies across strains. Machine learning linear discriminant analysis identified baseline fat-free mass as the most important predictor of mouse genetic background and social rank in the present dataset. Finally, strain and social rank differences were significantly associated with epigenetic changes, most significantly in Sv129Ev mice and in high-ranking compared to lower ranking subjects. Overall, we identified genetic background and social rank as critical contextual modifiers of aging and lifespan in an ethologically relevant rodent model of social stress, thereby providing a preclinical experimental paradigm to study the impact of social determinants of health disparities and accelerated aging.

Striatal and Behavioral Responses to Reward Vary by Socioeconomic Status in Adolescents.

Disparities in socioeconomic status (SES) lead to unequal access to financial and social support. These disparities are believed to influence reward sensitivity, which in turn are hypothesized to shape how individuals respond to and pursue rewarding experiences. However, surprisingly little is known about how SES shapes reward sensitivity in adolescence. Here, we investigated how SES influenced adolescent responses to reward, both in behavior and the striatum-a brain region that is highly sensitive to reward. We examined responses to both immediate reward (tracked by phasic dopamine) and average reward rate fluctuations (tracked by tonic dopamine) as these distinct signals independently shape learning and motivation. Adolescents (n = 114; 12-14 years; 58 female) performed a gambling task during functional magnetic resonance imaging. We manipulated trial-by-trial reward and loss outcomes, leading to fluctuations between periods of reward scarcity and abundance. We found that a higher reward rate hastened behavioral responses, and increased guess switching, consistent with the idea that reward abundance increases response vigor and exploration. Moreover, immediate reward reinforced previously rewarding decisions (win-stay, lose-switch) and slowed responses (postreward pausing), particularly when rewards were scarce. Notably, lower-SES adolescents slowed down less after rare rewards than higher-SES adolescents. In the brain, striatal activations covaried with the average reward rate across time and showed greater activations during rewarding blocks. However, these striatal effects were diminished in lower-SES adolescents. These findings show that the striatum tracks reward rate fluctuations, which shape decisions and motivation. Moreover, lower SES appears to attenuate reward-driven behavioral and brain responses.