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Triple-negative breast cancer (TNBC) is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype), with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM) and mesenchymal stem-like (MSL) subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype) into four (TNBCtype-4) tumor-specific subtypes (BL1, BL2, M and LAR) and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50) or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively). Collectively, we provide pre-clinical data that could inform clinical trials designed to test the hypothesis that improved outcomes can be achieved for TNBC patients, if selection and combination of existing chemotherapies is directed by knowledge of molecular TNBC subtypes.

By 2030 more people in the United States will be older than age sixty-five than younger than age five. Our health care system is unprepared for the complexity of caring for a heterogenous population of older adults-a problem that has been magnified by the coronavirus disease 2019 (COVID-19) pandemic. Here, as part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2021 initiative, we identify six vital directions to improve the care and quality of life for all older Americans. The next administration must create an adequately prepared workforce; strengthen the role of public health; remediate disparities and inequities; develop, evaluate, and implement new approaches to care delivery; allocate resources to achieve patient-centered care and outcomes, including palliative and end-of-life care; and redesign the structure and financing of long-term services and supports. If these priorities are addressed proactively, an infrastructure can be created that promotes better health and equitable, goal-directed care that recognizes the preferences and needs of older adults.

Growing evidence suggests a low engagement in advance care planning (ACP) among ethnic minorities in the U.S. The purpose of this study was to synthesize findings from prior research about ACP among ethnic minorities. An extensive literature search was conducted using multiple electronic databases. After applying inclusion criteria, 26 studies were included. Four categories of facilitators and barriers to ACP were identified: (1) Socio-demographic factors, (2) health status, literacy and experiences, (3) cultural values, and (4) spirituality. Socio-demographic factors showed inconsistent findings regarding their association with ACP engagement. Worse health status and knowledge about ACP are common facilitators across ethnic minority groups, whereas mistrust toward the health care system was a barrier only for Blacks. Collectivistic cultural values influenced ACP engagement among Latinos and Asian Americans; however, spirituality/religion played an important role among Blacks. The implications for culturally competent approaches to promote ACP and future research directions are discussed.

Access to breast screening mammogram services decreased during the COVID-19 pandemic. Our objectives were to estimate: 1) the COVID-19 affected period, 2) the proportion of pandemic-associated missed or delayed screening encounters, and 3) pandemic-associated patient attrition in screening encounters overall and by sociodemographic subgroup. We included screening mammogram encounter EPIC data from 1-1-2019 to 12-31-2022 for females ≥40 years old. We used Bayesian State Space models to describe weekly screening mammogram counts, modeling an interruption that phased in and out between 3-1-2020 and 9-1-2020. We used the posterior predictive distribution to model differences between a predicted, uninterrupted process and the observed screening mammogram counts. We estimated associations between race/ethnicity and age group and return screening mammogram encounters during the pandemic among those with 2019 encounters using logistic regression. Our analysis modeling weekly screening mammogram counts included 231,385 encounters (n = 127,621 women). Model-estimated screening mammograms dropped by >98% between 03-15-2020 and 05-24-2020 followed by a return to pre-pandemic levels or higher with similar results by race/ethnicity and age group. Among 79,257 women, non-Hispanic (NH) Asians, NH Blacks, and Hispanics had significantly (p < .05) lower odds of screening encounter returns during 2020-2022 vs. NH Whites with odds ratios (ORs) from 0.70 to 0.91. Among 79,983 women, those 60-69 had significantly higher odds of any return screening encounter during 2020-2022 (OR = 1.28), while those ≥80 and 40-49 had significantly lower odds (ORs 0.77, 0.45) than those 50-59 years old. A sensitivity analysis suggested a possible pre-existing pattern. These data suggest a short-term pandemic effect on screening mammograms of ~2 months with no evidence of disparities. However, we observed racial/ethnic disparities in screening mammogram returns during the pandemic that may be at least partially pre-existing. These results may inform future pandemic planning and continued efforts to eliminate mammogram screening disparities.

The U.S. Surgeon General and others have emphasized a critical need to address COVID-19 misinformation to protect public health. In St. Louis, MO, we created iHeard STL, a community-level misinformation surveillance and response system. This paper reports methods and findings from its first year of operation. We assembled a panel of over 200 community members who answered brief, weekly mobile phone surveys to share information they heard in the last seven days. Based on their responses, we prioritized misinformation threats. Weekly surveillance data, misinformation priorities, and accurate responses to each misinformation threat were shared on a public dashboard and sent to community organizations in weekly alerts. We used logistic regression to estimate odds ratios (ORs) for associations between panel member characteristics and misinformation exposure and belief. In the first year, 214 panel members were enrolled. Weekly survey response rates were high (mean = 88.3% ± 6%). Exposure to a sample of COVID-19 misinformation items did not differ significantly by panel member age category or gender; however, African American panel members had significantly higher reported odds of exposure and belief/uncertain belief in some misinformation items (ORs from 3.4 to 17.1) compared to white panel members. Our first-year experience suggests that this systematic, community-based approach to assessing and addressing misinformation is feasible, sustainable, and a promising strategy for responding to the threat of health misinformation. In addition, further studies are needed to understand whether structural factors such as medical mistrust underly the observed racial differences in exposure and belief.

Many epidemiological studies have examined associations between birth defects (BDs) and pediatric malignancy over the past several decades. Our objective was to conduct a systematic literature review of studies reporting on this association. We used librarian-designed searches of the PubMed Medline and Embase databases to identify primary research articles on pediatric neoplasms and BDs. English language articles from PubMed and Embase up to 10/12/2015, and in PubMed up to 5/12/2017 following an updated search, were eligible for inclusion if they reported primary epidemiological research results on associations between BDs and pediatric malignancies. Two reviewers coded each article based on the title and abstract to identify eligible articles that were abstracted using a structured form. Additional articles were identified through reference lists and other sources. Results were synthesized for pediatric cancers overall and for nine major pediatric cancer subtypes. A total of 14,778 article citations were identified, of which 80 met inclusion criteria. Pediatric cancer risk was increased in most studies in association with BDs overall with some notable specific findings, including increased risks for CNS tumors in association with CNS abnormalities and positive associations between rib anomalies and several pediatric cancer types. Some children born with BDs may be at increased risk for specific pediatric malignancy types. This work provides a foundation for future investigations that are needed to clarify specific BD types predisposing toward malignancy and possible underlying causes of both BDs and malignancy.

To investigate food democracy and health disparities in the New York City (NYC) trans fat policy process. Texts from semi-structured interviews, public testimony and comments on the policy were analysed using categorization and thematic coding. A priori content analysis for themes of food democracy was followed by open, axial and selective coding for sub-themes on health disparities. Data and method triangulation and respondent validation were used to establish data dependability, trustworthiness and representativeness. NYC. Interviews from a purposive, snowballed sample of thirty-three participants included restaurateurs, scientists, health and consumer advocates, consumers and policy makers. Additionally, 261 pages of transcript from public testimony of fifty-three participants and a purposive sample of public comments on the policy from a pool of 2157 were analysed. Principles of food democracy involving inclusive citizenship, access to information, collaborative participation and focus on collective good were well represented in the data. Additionally, sub-themes linked to health disparities included: government responsibility for fairer access to healthier foods; recognition that people made choices based on circumstances; concern for vulnerable groups; and outrage with a food industry viewed as unconcerned for public health. Principles of food democracy present in the successful process of adoption of the 2006 NYC trans fat policy addressed nutrition-related health. Food democracy is a contemporary food system and policy approach with potential for public health benefits in reducing nutrition-related health disparities.

Mineral and hydrocarbon extraction and infrastructure are increasingly significant drivers of forest loss, greenhouse gas emissions, and threats to the rights of forest communities in forested areas of Amazonia, Indonesia, and Mesoamerica. Projected investments in these sectors suggest that future threats to forests and rights are substantial, particularly because resource extraction and infrastructure reinforce each other and enable population movements and agricultural expansion further into the forest. In each region, governments have made framework policy commitments to national and cross-border infrastructure integration, increased energy production, and growth strategies based on further exploitation of natural resources. This reflects political settlements among national elites that endorse resource extraction as a pathway toward development. Regulations that protect forests, indigenous and rural peoples’ lands, and conservation areas are being rolled back or are under threat. Small-scale gold mining has intensified in specific locations and also has become a driver of deforestation and degradation. Forest dwellers’ perceptions of insecurity have increased, as have documented homicides of environmental activists. To explain the relationships among extraction, infrastructure, and forests, this paper combines a geospatial analysis of forest loss overlapped with areas of potential resource extraction, interviews with key informants, and feedback from stakeholder workshops. The increasing significance of resource extraction and associated infrastructure as drivers of forest loss and rights violations merits greater attention in the empirical analyses and conceptual frameworks of Sustainability Science.

Systematic analysis of cancer-associated mutations in the blood cells of healthy individuals. Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. The Cancer Genome Atlas (TCGA) provides a unique resource for comprehensive discovery of mutations and genes in blood that may contribute to the clonal expansion of hematopoietic stem/progenitor cells. Here, we analyzed blood-derived sequence data from 2,728 individuals from TCGA and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia and/or lymphoma-associated genes, and nine were recurrently mutated ( DNMT3A , TET2 , JAK2 , ASXL1 , TP53 , GNAS , PPM1D , BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant events that cause clonal hematopoietic expansion.