Associations of Historical Redlining With BMI and Waist Circumference in Coronary Artery Risk Development in Young Adults.

Introduction: Historical maps of racialized evaluation of mortgage lending risk (i.e., redlined neighborhoods) have been linked to adverse health outcomes. Little research has examined whether living in historically redlined neighborhoods is associated with obesity, differentially by race or gender. Methods: This is a cross-sectional study to examine whether living in historically redlined neighborhoods is associated with BMI and waist circumference among Black and White adults in 1985-1986. Participants' addresses were linked to the 1930s Home Owners' Loan Corporation maps that evaluated mortgage lending risk across neighborhoods. The authors used multilevel linear regression models clustered on Census tract, adjusted for confounders to estimate main effects, and stratified, and interaction models by (1) race, (2) gender, and (3) race by gender with redlining differentially for Black versus White adults and men versus women. To better understand strata differences, they compared Census tract-level median household income across race and gender groups within Home Owners' Loan Corporation grade. Results: Black adults (n=2,103) were more likely than White adults (n=1,767) to live in historically rated hazardous areas and to have higher BMI and waist circumference. Redlining and race and redlining and gender interactions for BMI and waist circumference were statistically significant (p<0.10). However, in stratified analyses, the only statistically significant associations were among White participants. White participants living in historically rated hazardous areas had lower BMI (ß=-0.63 [95% CI= -1.11, -0.15]) and lower waist circumference (ß=-1.50 [95% CI= -2.62, -0.38]) than those living in declining areas. Within each Home Owners' Loan Corporation grade, residents in White participants' neighborhoods had higher incomes than those living in Black participants' neighborhoods (p<0.0001). The difference was largest within historically redlined areas. Covariate associations differed for men, women, Black, and White adults, explaining the difference between the interaction and the stratified models. Race by redlining interaction did not vary by gender. Conclusions: White adults may have benefitted from historical redlining, which may have reinforced neighborhood processes that generated racial inequality in BMI and waist circumference 50 years later.

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

Food Insecurity Among Aging Supplemental Nutrition Assistance Program Participants and Eligible Nonparticipants in Two Predominantly Low-Income Black Neighborhoods: Implications for Supplemental Nutrition Assistance Program Enrollment and Outreach for Older Adults.

BACKGROUND: The Supplemental Nutrition Assistance Program (SNAP) plays a critical role in alleviating poverty and food insecurity. Despite these benefits, many older Americans who are eligible for SNAP do not participate in the program. Few studies have explored household factors and food insecurity outcomes associated with nonparticipation among older Black Americans. OBJECTIVES: The study aim was to explore changes in food insecurity and related financial hardship outcomes between 2020 and 2021 among SNAP participants, eligible nonparticipants, and ineligible nonparticipants; compare reasons for not participating in SNAP; and to compare household factors associated with SNAP nonparticipation. METHODS: Longitudinal design examining data from 2020 and 2021 to assess changes in food insecurity over the course of the coronavirus disease 2019 pandemic. PARTICIPANTS/SETTING: Participants were 528 adults (aged 30 to 97 years) in households randomly selected from a listing of all residential addresses in two predominantly Black neighborhoods with lower incomes in Pittsburgh, PA, and surveyed between March to May 2020 and May to December 2021. MAIN OUTCOME MEASURES: Food security was measured using the validated 6-item US Department of Agriculture Adult Food Security Survey Module. STATISTICAL ANALYSES PERFORMED: Findings are based on a descriptive analysis of food security and related indicators. Statistical testing was performed to assess differences between SNAP participation status and individual characteristics, food security, and financial hardship using Wald F test for continuous measures and Pearson χ2 test for categorical measures. A multivariable linear model was used to assess the association of SNAP participation and eligibility status with change in food insecurity. RESULTS: In cross-sectional analyses of 2021 data, no differences were observed between SNAP participants and eligible nonparticipants for food insecurity, food bank use, mean weekly food spending per person, and difficulty paying for basics. However, with respect to changes in food insecurity over the course of the pandemic, SNAP participants experienced a greater improvement in mean food security scores between 2020 and 2021 (-0.52 reduction in mean food insecurity score or a 16% improvement in food security; P ≤ 0.05) relative to SNAP-eligible nonparticipants. Perceived ineligibility (71.3%) and perceived lack of need (23%) were the most common reasons for not participating in SNAP. CONCLUSIONS: More than one-third of SNAP participants and eligible nonparticipants experienced food insecurity and financial hardship. However, there were differences in the changes in food insecurity between these groups.

Community Investments and Diet-Related Outcomes: A Longitudinal Study of Residents of Two Urban Neighborhoods.

INTRODUCTION: Investments in historically oppressed neighborhoods through food retail, housing, and commercial development are hypothesized to improve residents' health, nutrition, and perceptions of their neighborhood as a place to live. Although place-based development (e.g., housing, retail, business assistance) is happening in many communities, there is little evidence of the long-term correlates of multiple investments such as health and nutrition among residents. METHODS: A quasi-experimental longitudinal study was conducted using a cohort of randomly sampled households in two low-income, predominantly African American neighborhoods in Pittsburgh, PA, with surveys assessing residents' food insecurity, perception of their neighborhood as a place to live, perception of access to healthy foods, and dietary outcomes in 2011 and seven years later (2018), with an interim assessment in 2014. Analyses conducted in 2022 compared changes among residents of one neighborhood which had 2.6 times the investments over a 7-year period with changes among residents of a socio-demographically similar neighborhood that received fewer investments. RESULTS: It was found that residents in the neighborhood receiving substantial investments demonstrated statistically significant improvements in neighborhood satisfaction (12.6% improvement compared with a 2.2% decrease) and perceived access to healthy food (52% improvement compared with 18.2% improvement), and marginally significant change in food security (14% compared with 4.8% improvement) compared with residents in the neighborhood receiving fewer investments. CONCLUSIONS: Multiple place-based investments in neighborhoods can potentially induce positive change for residents in health and nutrition outcomes.

Police Bias and Low Relatability and Diet Quality: Examining the Importance of Psychosocial Factors in Predominantly Black Communities.

How police bias and low relatability may contribute to poor dietary quality is poorly understood. In this cross-sectional study, we analyzed data from 2021 from a cohort of n = 724 adults living in predominantly Black communities in Pittsburgh, Pennsylvania; these adults were mostly Black (90.6%), low-income (median household income $17,500), and women (79.3%). We estimated direct and indirect paths between police mistrust and dietary quality (measured by Healthy Eating Index (HEI)-2015) through perceived stress, community connectedness, and subjective social status. Dietary quality was poor (mean HEI-2015 score was 50) and mistrust of police was high: 78% of participants either agreed or strongly agreed that something they say might be interpreted as criminal by the police due to their race/ethnicity. Police bias and low relatability was associated with lower perceived social status [Formula: see text]= - 0.03 (95% confidence interval [CI]: - 0.05, - 0.01). Police bias and low relatability was marginally associated with low dietary quality ß = - 0.14 (95% CI: - 0.29, 0.02). Nineteen percent of the total association between police bias and low relatability and lower dietary quality ß = - 0.16 (- 0.01, - 0.31) was explained by an indirect association through lower community connectedness, or how close respondents felt with their community [Formula: see text] Police bias and low relatability may play a role in community connection, social status, and ultimately dietary disparities for Black Americans. Addressing police bias and low relatability is a continuing and pressing public health issue.

Identifying homologous recombination deficiency in breast cancer: genomic instability score distributions differ among breast cancer subtypes.

PURPOSE: A 3-biomarker homologous recombination deficiency (HRD) score is a key component of a currently FDA-approved companion diagnostic assay to identify HRD in patients with ovarian cancer using a threshold score of ≥ 42, though recent studies have explored the utility of a lower threshold (GIS ≥ 33). The present study evaluated whether the ovarian cancer thresholds may also be appropriate for major breast cancer subtypes by comparing the genomic instability score (GIS) distributions of BRCA1/2-deficient estrogen receptor-positive breast cancer (ER + BC) and triple-negative breast cancer (TNBC) to the GIS distribution of BRCA1/2-deficient ovarian cancer. METHODS: Ovarian cancer and breast cancer (ER + BC and TNBC) tumors from ten study cohorts were sequenced to identify pathogenic BRCA1/2 mutations, and GIS was calculated using a previously described algorithm. Pathologic complete response (pCR) to platinum therapy was evaluated in a subset of TNBC samples. For TNBC, a threshold was set and threshold validity was assessed relative to clinical outcomes. RESULTS: A total of 560 ovarian cancer, 805 ER + BC, and 443 TNBC tumors were included. Compared to ovarian cancer, the GIS distribution of BRCA1/2-deficient samples was shifted lower for ER + BC (p = 0.015), but not TNBC (p = 0.35). In the subset of TNBC samples, univariable logistic regression models revealed that GIS status using thresholds of ≥ 42 and ≥ 33 were significant predictors of response to platinum therapy. CONCLUSIONS: This study demonstrated that the GIS thresholds used for ovarian cancer may also be appropriate for TNBC, but not ER + BC. GIS thresholds in TNBC were validated using clinical response data to platinum therapy.

Obesity-associated changes in molecular biology of primary breast cancer.

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients' body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.

Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL.

Translesion DNA synthesis (TLS) facilitates replication over damaged or difficult-to-replicate templates by employing specialized DNA polymerases. We investigate the effect on spontaneous mutagenesis of three main TLS control mechanisms: REV1 and PCNA ubiquitylation that recruit TLS polymerases and PRIMPOL that creates post-replicative gaps. Using whole-genome sequencing of cultured human RPE-1 cell clones, we find that REV1 and Polymerase ζ are wholly responsible for one component of base substitution mutagenesis that resembles homologous recombination deficiency, whereas the remaining component that approximates oxidative mutagenesis is reduced in PRIMPOL-/- cells. Small deletions in short repeats appear in REV1-/-PCNAK164R/K164R double mutants, revealing an alternative TLS mechanism. Also, 500-5,000 bp deletions appear in REV1-/- and REV3L-/- mutants, and chromosomal instability is detectable in REV1-/-PRIMPOL-/- cells. Our results indicate that TLS protects the genome from deletions and large rearrangements at the expense of being responsible for the majority of spontaneous base substitutions.

Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP.

PURPOSE: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points. METHODS: The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at surgery, bilateral and multifocal diseases, correlative tissue collection, and US Food and Drug Administration regulatory considerations were contemplated. RESULTS: The working group recommends a preferred definition of pathologic complete response (pCR) as the absence of residual invasive cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0 per AJCC staging). Residual cancer burden should be a secondary end point to facilitate future assessment of its utility. Alternative end points are needed for hormone receptor-positive disease. Time-to-event survival end point definitions should pay particular attention to the measurement starting point. Trials should include end points originating at random assignment (event-free survival and overall survival) to capture presurgery progression and deaths as events. Secondary end points adapted from STEEP 2.0, which are defined from starting at curative-intent surgery, may also be appropriate. Specification and standardization of biopsy protocols, imaging, and pathologic nodal evaluation are also crucial. CONCLUSION: End points in addition to pCR should be selected on the basis of clinical and biologic aspects of the tumor and the therapeutic agent investigated. Consistent prespecified definitions and interventions are paramount for clinically meaningful trial results and cross-trial comparison.

Two for the GOES: Exploring Gambling Outcome Expectancies Scores Across Mixed and Offline-Only Gamblers in Relation to Problem Gambling Risk Status.

As online gambling becomes more prevalent, understanding the motives of online gamblers has become a key focus for research and practice. The aim of this study was to understand differences in gambling-related outcome expectancies between mixed (both online and offline) gamblers and offline-only gamblers, by incorporating gambling harm risk categories from the problem gambling severity index (PGSI). This study comprised a secondary data analysis of the 2015 Northern Territory Gambling Prevalence and Wellbeing Survey. A sample of 1207 individuals in the Northern Territory who had reported gambling at least once in the previous 12 months were used in the analyses. General linear and structural equation modelling were used to ascertain differences in gambling outcome expectancies, in relation to gambling modality (i.e., mixed, offline-only) and PGSI scores. Mixed gamblers tended to score higher on all outcome expectancies than their offline-only counterparts. Outcome expectancy scores were higher in individuals in higher-risk PGSI categories. The escape outcome expectancy was dependent on both modality and risk category. Invariance testing of a low and problem gambling risk subsample revealed differential relationships for both the escape and excitement outcome expectancies for mixed and offline-only gamblers. The results provide an important contribution to the existing literature regarding motivation and outcome expectancies in relation to gambling modality and problem gambling severity. The findings highlight the importance of considering both gambling outcome expectancies and modality when considering problem gambling.

Students' consumption of high and low nutrition foods and reduced plate waste by schools' wellness-related policies and garden program participation.

BACKGROUND: Participation in school-based programs that may support children's nutritious dietary behaviours varies across schools. We examined school participation in wellness-related policies, school-based garden programs and students' dietary behaviours. METHODS: Among matching schools who did and did not participate in school-based garden programs, we analysed the lunches of 80 Pittsburgh Public Schools (PPS) students in 1st, 2nd, 6th and 7th grades during Autumn 2019 using digital food photography. We also acquired school wellness policy data. Using cross-sectional linear regression, we estimated the association between school-based garden programming, wellness-related policies and dietary outcomes, adjusting for grade. RESULTS: School's implementation of nutrition services policies was negatively associated with energy wasted from lunch ( ß = - 44.7 , p = 0.01 ${\rm{\beta }}=-44.7,{p}=0.01$ ). The number of semesters the students' school had participated in the garden program was positively associated with students' whole grain consumption ( ß = 0.07 , p < 0.001 ${\rm{\beta }}=0.07,{p}\lt 0.001$ ). CONCLUSIONS: Cross-sectional associations suggest that schools that are more engaged in wellness policies and garden programs may provide environments that are more supportive of students' nutrition than in other schools.

Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER+/luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.

Multi-dimensional Profiles of Risk and Their Association with Obesity-Severity in Low-Income Black Women.

Multi-level risk factors underlie disproportionate obesity rates among Black women. Latent class analysis of multi-level risk and protective factors among low-income Black women (n = 917) in 2011 (Pittsburgh, PA). Data were collected via in-person survey, interviewer-assisted online dietary recalls, and from 2011 crime records. Multinomial logistic regression estimated cross-sectional associations between latent classes and obesity severity derived from measured anthropometry. Latent class analysis identified four groups of women according to their motivations and intentions to be healthy, socioeconomic and health burden, and neighborhood risk: Class 1 = Very high burden (n = 283), Class 2 = Health motivated, low burden, low neighborhood risk (n = 231), Class 3 = High burden and high neighborhood risk (n = 106), and Class 4 = Low burden and low neighborhood risk (n = 297). Class 3 = High burden and high neighborhood risk women had the highest severe obesity risk. Multi-level strategies may support low-income Black women women's resilience to obesity who face neighborhood-level and socioeconomic stressors.

What Is Associated with Changes in Food Security among Low-Income Residents of a Former Food Desert?

Lack of geographic access to foods has been postulated as a cause for food insecurity, which has been linked to poor nutrition, obesity, and chronic disease. Building on an established cohort of randomly selected households from a low-income, predominantly Black neighborhood, we examined household food security, distance to where study participants reported doing their major food shopping, and prices at stores where they shopped. Data from the Pittsburgh Hill/Homewood Research on Eating, Shopping, and Health study for years 2011, 2014 and 2018 was limited to residents of the neighborhood that began as a food desert (i.e., low access to healthy foods), but acquired a full-service supermarket in 2013. We calculated descriptive statistics and compared study participants in the former food desert neighborhood whose food security improved to those whose food security did not improve across survey waves. We estimated cross sectional linear regressions using all waves of data to assess food security level among study participants. Distance to major food shopping store was positively associated with food security (p < 0.05) while food-store prices were not significantly associated with food security. Findings suggest that for predominantly low-income residents, food secure individuals traveled further for their major food shopping.

Spatial genomics maps the structure, nature and evolution of cancer clones.

Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1-3. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive4,5. Here, to address this need, we developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers. Applying the base-specific in situ sequencing workflow to eight tissue sections from two multifocal primary breast cancers revealed intricate subclonal growth patterns that were validated by microdissection. In a case of ductal carcinoma in situ, polyclonal neoplastic expansions occurred at the macroscopic scale but segregated within microanatomical structures. Across the stages of ductal carcinoma in situ, invasive cancer and lymph node metastasis, subclone territories are shown to exhibit distinct transcriptional and histological features and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.

Association of the Healthy, Hunger-Free Kids Act of 2010 With Body Mass Trajectories of Children in Low-Income Families.

Importance: Implemented in 2012, the Healthy, Hunger-Free Kids Act of 2010 (HHFKA) increased nutritional requirements of the National School Lunch Program (NSLP) to reverse the potential role of the NSLP in childhood obesity. Objective: To evaluate whether associations between the free or reduced-price NSLP and body mass growth differed after implementation of the HHFKA. Design, Setting, and Participants: This cohort study used data from 2 nationally representative cohorts of US kindergarteners sampled in 1998 to 1999 and 2010 to 2011 and followed up for 6 years, through grade 5, in the Early Childhood Longitudinal Study Kindergarten Class of 1998-1999 (ECLS-K:1999, in 2003-2004) and Kindergarten Class of 2010-2011 (ECLS-K:2011, in 2015-2016). In total, 5958 children were selected for analysis from low-income families eligible for the free or reduced-price NSLP (household income <185% of the federal poverty level) who attended public schools and had no missing data on free or reduced-price NSLP participation or on body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) at kindergarten or grades 1 and 5. Data were analyzed from January 1 to September 7, 2021. Exposures: Cross-cohort comparison of before vs after implementation of the HHFKA for free or reduced-price NSLP participation at kindergarten and grades 1 and 5. Main Outcomes and Measures: Body mass index difference (BMID) from obesity threshold was the difference in BMI units from the age- and sex-specific obesity thresholds (95th percentile) and is sensitive to change at high BMI. Multigroup models by cohort included weights to balance the distribution of the 2 cohorts across a wide range of covariates. A Wald test was used to assess whether associations differed between the cohorts. Results: In the final analysis, 3388 children in ECLS-K:1999 (1696 girls [50.1%]; mean [SD] age at baseline, 74.6 [4.3] months) and 2570 children in ECLS-K:2011 (1348 males [52.5%]; mean [SD] age at baseline, 73.6 [4.2] months) were included. The best fitting model for BMID change by free or reduced-price NSLP participation across the cohorts included fixed and time-varying associations. Before HHFKA implementation, grade 5 free or reduced-price NSLP participants had higher BMID, adjusted for their prior BMID trajectory, than nonparticipants (ß = 0.54; 95% CI, 0.27-0.81). After HHFKA implementation, this association was attenuated (ß = -0.07; 95% CI, -0.58 to 0.45), and grade 5 associations were different across cohorts (χ21 = 4.29, P = .04). Conclusions and Relevance: In this cohort study using cross-cohort comparisons, children from low-income families who participated in the free or reduced-price NSLP had a higher likelihood of progression to high BMI that was no longer observed after HHFKA implementation. This finding suggests that the HHFKA may have attenuated the previous association of the NSLP with child obesity disparities.

Estimates of the Nutritional Impact of Non-Participation in the National School Lunch Program during COVID-19 School Closures.

The COVID-19 pandemic resulted in widespread school closures, reducing access to school meals for millions of students previously participating in the US Department of Agriculture (USDA) National School Lunch Program (NSLP). School-prepared meals are, on average, more nutritious than home-prepared meals. In the absence of recent data measuring changes in children's diets during the pandemic, this article aims to provide conservative, back-of-the-envelope estimates of the nutritional impacts of the pandemic for school-aged children in the United States. We used administrative data from the USDA on the number of NSLP lunches served in 2019 and 2020 and nationally representative data from the USDA School Nutrition and Meal Cost Study on the quality of school-prepared and home-prepared lunches. We estimate changes in lunchtime calories and nutrients consumed by NSLP participants from March to November 2020, compared to the same months in 2019. We estimate that an NSLP participant receiving no school meals would increase their caloric consumption by 640 calories per week and reduce their consumption of nutrients such as calcium and vitamin D. Because 27 to 78 million fewer lunches were served per week in March-November 2020 compared to the previous year, nationally, students may have consumed 3 to 10 billion additional calories per week. As students return to school, it is vital to increase school meal participation and update nutrition policies to address potentially widening nutrition disparities.

Reciprocal relationships among influenza experiences, perceptions, and behavior: Results from a national, longitudinal survey of United States adults.

OBJECTIVE: Our objective was to model the reciprocal relationships of perceived risk of contracting influenza with and without influenza vaccination, vaccination behavior, and reported influenza illness. METHODS: We fit structural equation models to data from a longitudinal survey of adults in the United States collected through the RAND American Life Panel. Data come from fall and spring surveys fielded before and after each of 3 influenza seasons, 2016/2017, 2017/2018, and 2018/2019, for a total of 6 waves. RESULTS: As expected, reported influenza experience was associated with increased perceived influenza risk in subsequent survey waves. Furthermore, perceived risk was associated with subsequent vaccination behavior, such that vaccination was more common for those with higher perceived unvaccinated influenza risk and lower perceived vaccinated influenza risk. Perhaps surprisingly, both elements of perceived risk were also associated with a greater likelihood of subsequent reported influenza illness. This malleability in illness reports may reflect uncertainty, as more respondents reported being sick but being unsure about whether they had influenza than reported certainty that they had influenza. CONCLUSIONS: Interventions that influence perceptions about past experience with influenza, including increased testing and informational campaigns about influenza symptoms, could have unanticipated impacts on perceptions of influenza vaccination and vaccination behavior.

BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1.

Defects in BRCA1, BRCA2 and other genes of the homology-dependent DNA repair (HR) pathway cause an elevated rate of mutagenesis, eliciting specific mutation patterns including COSMIC signature SBS3. Using genome sequencing of knock-out cell lines we show that Y family translesion synthesis (TLS) polymerases contribute to the spontaneous generation of base substitution and short insertion/deletion mutations in BRCA1 deficient cells, and that TLS on DNA adducts is increased in BRCA1 and BRCA2 mutants. The inactivation of 53BP1 in BRCA1 mutant cells markedly reduces TLS-specific mutagenesis, and rescues the deficiency of template switch-mediated gene conversions in the immunoglobulin V locus of BRCA1 mutant chicken DT40 cells. 53BP1 also promotes TLS in human cellular extracts in vitro. Our results show that HR deficiency-specific mutagenesis is largely caused by TLS, and suggest a function for 53BP1 in regulating the choice between TLS and error-free template switching in replicative DNA damage bypass.

Differences in lymphoma patients between chimeric antigen receptor T-cell therapy trials and the general population.

Chimeric antigen receptor (CAR)-T cell therapies appear to be promising treatments for non-Hodgkin's and B-cell lymphoma. However, several CAR-T therapies approved by the US Food and Drug Administration have only been tested for efficacy in relatively few single-arm clinical trials with small sample sizes. We sought to examine the differences between patients in these trials and the general population of patients with non-Hodgkin's and B-cell lymphoma. Five hundred and twenty-two patients from 15 CAR-T trials found in a systematic review and 417,492 patients from the Surveillance, Epidemiology, and End Results (SEER) Program database were compared. CAR-T study participants appeared to be younger (46.7% under 70 years old vs. 42.2%), more male (68.0% vs. 55.7%), and followed for a shorter period of time compared to patients in the SEER population (mean [M] 45.6 months, 95% confidence interval [CI] 17.7 to 63.3 months follow-up vs. M 57.1 months, 95% CI 57.0 to 57.3 months survival). CAR-T study participants may differ significantly from the general population of patients with non-Hodgkin's and B-cell lymphoma. Effectiveness of CAR-T therapies in the general population of lymphoma patients may differ from effectiveness demonstrated in trials. Newly created CAR-T patient registries are essential to establishing population-level effectiveness of the therapies.