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BackgroundEpigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac.MethodsBuilding on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women.ResultsChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women.ConclusionsThis study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Undocumented college students in the United States encounter a number of structural barriers to postsecondary education success, including disparate in-state resident tuition (ISRT) policies across the country. Texas, the first state to establish ISRT benefits for undocumented college students, has been a site of tension respective to this issue over the last 20 years. In fact, there have been eight legislative attempts to repeal the state's affirmative ISRT policy. In order to investigate this ongoing ISRT debate in Texas, we used critical discourse analysis methods to analyze the implicit and explicit messages communicated in the policy and surrounding policy discourse. Our conceptual framework, grounded in three constructs of critical whiteness studies including ontological expansiveness, color evasiveness, and individualization, allowed us to uncover whiteness as a pernicious undergirding force within this policy discourse.

Racist and discriminatory federal, state, and local housing policies significantly contribute to disparities in cardiovascular disease incidence and mortality for individuals that self-identify as Black or African American. Here we highlight three key housing policies - "redlining," zoning, and the construction of highways - which have wrought a powerful, sustained, and destructive impact on cardiovascular health in Black/African American communities. Redlining and highway construction policies have restricted access to quality health care, increased exposure to carcinogens such as PM2.5, and increased exposure to extreme heat. At the root of these policy decisions are longstanding, toxic societal factors including racism, segregation, and discrimination, which also serve to perpetuate racial inequities in cardiovascular health. Here, we review these societal and structural factors and then link them with biological processes such as telomere shortening, allostatic load, oxidative stress, and tissue inflammation. Lastly, we focus on the impact of inflammation on the immune system and the molecular mechanisms by which the inflamed immune microenvironment promotes the formation of atherosclerotic plaques. We propose that racial residential segregation and discrimination increases tissue inflammation and cytokine production, resulting in dysregulated immune signaling, which promotes plaque formation and cardiovascular disease. This framework has the power to link structural racism not only to cardiovascular disease, but also to cancer.

The higher education community often views international students through a homogenous lens. To challenge the cultural norms set by the dominant group, researchers need to explore how these norms affect international teaching assistants (ITAs). The following questions guided the current study: (a) How do ITAs construct intersecting identities of teacher and learner that reflect the presence of dominant cultural norms within a predominantly White institution? (b) What strategies do ITAs use to navigate cultural and linguistic power dynamics within a predominantly White institution as they seek to establish authority? We conducted a case study through an intersectionality framework. Findings revealed participants' marginalization, authority, and strategies to overcome oppression. We offer recommendations about power dynamics that require increased institutional support.

Over 90% of breast cancer is cured; yet there remain highly aggressive breast cancers that develop rapidly and are extremely difficult to treat, much less prevent. Breast cancers that rapidly develop between breast image screening are called "interval cancers." The efforts of our team focus on identifying multiscale integrated strategies to identify biologically aggressive precancerous breast lesions. Our goal is to identify spatiotemporal changes that occur prior to development of interval breast cancers. To accomplish this requires integration of new technology. Our team has the ability to perform single cell in situ transcriptional profiling, noncontrast biological imaging, mathematical analysis, and nanoscale evaluation of receptor organization and signaling. These technological innovations allow us to start to identify multidimensional spatial and temporal relationships that drive the transition from biologically aggressive precancer to biologically aggressive interval breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology Cancer > Genetics/Genomics/Epigenetics.

During puberty, a woman's breasts are vulnerable to environmental damage ("window of vulnerability"). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures.

Background: Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2‐negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity. Methods: In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68). Results: We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple‐negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression. Conclusion: This retrospective, real‐world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes. [ABSTRACT FROM AUTHOR]

The anti-critical race theory movement has caused educators strife and fear nationally. In these current socio-political times, faculty are navigating unprecedented experiences of racism as they teach and research critical race theory. Through our work, we examined 40 faculty experiences challenging legislation at a national, state, and institutional level. We present recommendations for practice and policy that resist the surveillance experienced during this socio-political backlash. [ABSTRACT FROM AUTHOR]

Author(s): Chenkai Wu [sup.1] , Kimlin Tam Ashing [sup.2] , Veronica C. Jones [sup.3] , Lisa Barcelo [sup.4] Author Affiliations: (1) School of Biological and Population Health Sciences, Oregon State [...], While individual-level determinants of health, such as education and income, have been well documented among breast cancer survivors, little is known about the role of neighborhood context on survivorship outcomes among this population. The present study examined the association of neighborhood stress with multiple health outcomes among ethnic minority breast cancer survivors (BCS). A mixed-methods approach was used to recruit 320 African-American and Hispanic BCS who were 26-89 years and lived in metropolitan Los Angeles, CA. Neighborhood stress was assessed by six items taken from the Life Stress Scale. Health outcomes included (1) self-rated health, measured by the Short-Form-36 Health Survey, (2) number of comorbidities (0-14), (3) depressive symptoms, assessed by the Center for Epidemiological Studies-Depression scale, and (4) psychological difficulties. Greater neighborhood stress was significantly associated with poorer self-reported health (adjusted [beta] = -.22, 95% confidence interval [CI] -.40, -.05), greater number of comorbidities (adjusted risk ratio = .19, 95% CI .07, .30), more depressive symptoms (adjusted [beta] = .10, 95% CI .06, .15), and a higher likelihood of psychological difficulties (adjusted odds ratio = 2.28, 95% CI 1.51, 3.45) among ethnic minority BCS. These findings underscored the importance of taking neighborhood context into account in examining the determinants of health, survivorship, and quality of life outcomes among cancer patients. Our findings may inform population health, health services, and interventions addressing neighborhood and individual-level factors to promote post treatment health and survivorship outcomes as well as to identify high-risk patients, especially among medically vulnerable communities.

Work Reimagined: Uncovering Your Calling. By Richard J. Leider and David A. Shapiro. Oakland, CA: Berrett-Koehler Publishers, 2015, 155 pp., $16.95 paperback. In this time of global pandemic, one would [...]

Introduction: Cancer inequity is one of the most critical public health issues faced by ethnic minorities and people of lower socioeconomic status. The disparate burden of cancer is caused by poor access to care and inadequate delivery of cancer treatment, as well as comorbid and co-occurring conditions. Diabetes is a common and serious comorbid condition of cancer. Methods: To better understand diabetes prevalence among diverse cancer patients, this study analyzed and described characteristics of cancer patients with diabetes from local-level Service Planning Area (SPA) data using City of Hope Comprehensive Cancer Center data, and United States national-level data from The National Health Interview Survey. Results: Findings from national level data showed that patients in racial/ethnic minority groups had a higher occurrence of being diagnosed with diabetes, especially for non-Hispanic Blacks (OR=1.76, 95% CI=1.51, 2.03) and Hispanic/ Latino individuals (OR=1.34, 95% CI=1.18, 1.52). Cancer patients who are older, ethnic minority, overweight/obese and with lower educational levels were more likely to have co-occurring diabetes. SPA-level patient data found similar results. Discussion: In response to our findings and other reports, clinicians and health system including health coverage organizations should routinely assess cancer patients for cooccurring chronic illnesses, in particular diabetes. Interventions improving coordinated care that integrates oncology, endocrinology and primary care, targeting cancer patients -especially racial/ethnic minorities, overweight/obese, and older patients who are at increased risk for diabetes - ought to be considered as best practice Whole Person care. With coordinated care management, ethnic disparities in cancer may be better addressed and reduced. Additionally, policymakers can contribute by enacting policies improving access to and coverage of integrated oncology, chronic disease prevention, and associated specialty care i.e., endocrinology to equalize quality care for ethnic minority, lower educated, overweight/obese and older cancer patients who are more likely to suffer greater comorbidity, and inadequate oncology and coordinated care to reduce disparities. [ABSTRACT FROM AUTHOR]

Invasive alien species (IAS) are a key driver of global biodiversity loss. Reducing their spread and impact is a target of the Sustainable Development Goals (SDG target 15.8) and of the EU IAS Regulation 1143/2014. The use of citizen science offers various benefits to alien species' decision-making and to society, since public participation in research and management boosts awareness, engagement and scientific literacy and can reduce conflict in IAS management. We report the results of a survey on alien species citizen science initiatives within the framework of the European Cooperation in Science and Technology (COST) Action Alien-CSI. We gathered metadata on 103 initiatives across 41 countries, excluding general biodiversity reporting portals, spanning from 2005 to 2020, offering the most comprehensive account of alien species citizen science initiatives on the continent to date. We retrieved information on project scope, policy relevance, engagement methods, data capture, data quality and data management, methods and technologies applied and performance indicators such as the number of records coming from projects, the numbers of participants and publications. The 103 initiatives were unevenly distributed geographically, with countries with a tradition of citizen science showing more active projects. The majority of projects were contributory and were run at a national scale, targeting the general public, alien plants and insects, and terrestrial ecosystems. These factors of project scope were consistent between geographic regions. Most projects focused on collecting species presence or abundance data, aiming to map presence and spread. As 75% of the initiatives specifically collected data on IAS of Union Concern, citizen science in Europe is of policy relevance. Despite this, only half of the projects indicated sustainable funding. Nearly all projects had validation in place to verify species identifications. Strikingly, only about one third of the projects shared their data with open data repositories such as the Global Biodiversity Information Facility or the European Alien Species Information Network. Moreover, many did not adhere to the principles of FAIR data management. Finally, certain factors of engagement, feedback and support, had significant impacts on project performance, with the provision of a map with sightings being especially beneficial. Based on this dataset, we offer suggestions to strengthen the network of IAS citizen science projects and to foster knowledge exchange among citizens, scientists, managers, policy-makers, local authorities, and other stakeholders. [ABSTRACT FROM AUTHOR]

Background: In this phase II clinical trial, we evaluated the efficacy of the nonanthracycline combination of carboplatin and nab‐paclitaxel in early stage triple‐negative breast cancer (TNBC). Patients and Methods: Patients with newly diagnosed stage II–III TNBC (n = 69) were treated with neoadjuvant carboplatin (area under the curve 6) every 28 days for four cycles plus nab‐paclitaxel (100 mg/m2) weekly for 16 weeks. Pathological complete response (pCR) and residual cancer burden (RCB) were analyzed with germline mutation status, tumor‐infiltrating lymphocytes (TILs), TNBC molecular subtype, and GeparSixto immune signature (GSIS). Results: Sixty‐seven patients were evaluable for safety and response. Fifty‐three (79%) patients experienced grade 3/4 adverse events, including grade 3 anemia (43%), neutropenia (39%), leukopenia (15%), thrombocytopenia (12%), fatigue (7%), peripheral neuropathy (7%), neutropenia (16%), and leukopenia (1%). Twenty‐four patients (35%) had at least one dose delay, and 50 patients (72%) required dose reduction. Sixty‐three (94%) patients completed scheduled treatment. The responses were as follows: 32 of 67 patients (48%) had pCR (RCB 0), 10 of 67 (15%) had RCB I, 19 of 67 (28%) had RCB II, 5 of 67 (7%) had RCB III, and 1 of 67 (2%) progressed and had no surgery. Univariate analysis showed that immune‐hot GSIS and DNA repair defect (DRD) were associated with higher pCR with odds ratios of 4.62 (p =.005) and 4.76 (p =.03), respectively, and with RCB 0/I versus RCB II/III with odds ratio 4.80 (p =.01). Immune‐hot GSIS was highly correlated with DRD status (p =.03), TIL level (p <.001), and TNBC molecular subtype (p <.001). After adjusting for age, race, stage, and grade, GSIS remained associated with higher pCR and RCB class 0/I versus II/III with odds ratios 7.19 (95% confidence interval [CI], 2.01–25.68; p =.002) and 8.95 (95% CI, 2.09–38.23; p =.003), respectively. Conclusion: The combination of carboplatin and nab‐paclitaxel for early stage high‐risk TNBC showed manageable toxicity and encouraging antitumor activity. Immune‐hot GSIS is associated with higher pCR rate and RCB class 0/1. This study provides an additional rationale for using nonanthracycline platinum‐based therapy for future neoadjuvant trials in early stage TNBCs. Clinical trial identification number: NCT01525966 Implications for Practice: Platinum is an important neoadjuvant chemotherapy agent for treatment of early stage triple‐negative breast cancer (TNBC). In this study, carboplatin and nab‐paclitaxel were well tolerated and highly effective in TNBC, resulting in pathological complete response of 48%. In univariate and multivariate analyses adjusting for age, race, tumor stage and grade, "immune‐hot" GeparSixto immune signature (GSIS) and DNA repair defect (DRD) were associated with higher pathological complete response (pCR) and residual cancer burden class 0/1. The association of immune‐hot GSIS with higher pCR holds promise for de‐escalating neoadjuvant chemotherapy for patients with early stage TNBC. Although GSIS is not routinely used in clinic, further development of this immune signature into a clinically applicable assay is indicated. Metastatic triple‐negative breast cancer is associated with poor clinical outcomes, largely due to a lack of effective targeted therapy. This article reports the results of a phase II trial evaluating the efficacy of neoadjuvant carboplatin plus nab‐paclitaxel in patients with stage II–III triple‐negative breast cancer. [ABSTRACT FROM AUTHOR]

Fumarase does not catalyse 18O exchange between (2S, 3R)-tartrate and solvent water, nor does it catalyse ²H or ³H exchange into (2S)-fluorosuccinate from isotopically labelled water. Both of these substrate analogues are good competitive inhibitors of fumarase. This lack of isotopic exchange provides prima facie evidence against the stepwise carbenium ion and carbanion mechanisms. This, together with evidence from the literature, suggests that the fumarase-catalysed dehydration of (2S)-malate occurs by a concerted mechanism in which breaking of the C-OH bond is much further advanced than that of the C-H bond in the transition state. [ABSTRACT FROM AUTHOR]

A personal narrative is presented which explores the author's experience of traveling to San Luis de Monteverde, Costa Rica in March 2014 under an environmental sustainability course.