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Community health workers (CHWs) informed students and researcher alike on the Kin Keeper(SM) Cancer Prevention Intervention. Students interested in medicine, guided by faculty, conducted a focus group session with 13 CHWs to find out if the intervention was effective for delivering breast and cervical cancer education. Strengths reported were (1) cultural appropriateness, (2) home visits, (3) CHW resource kits, and (4) increased awareness. The barriers were privacy perceptions and scheduling home visits. Overall, the CHWs indicated that the intervention was effective and flexible enough to accommodate the African American, Latina, and Arab groups of women. [ABSTRACT FROM AUTHOR]

This paper presents the rationale and findings of a feasibility and process study of the Kin Keeper(SM) Cancer Prevention Intervention. An observational cohort study design was implemented with African-American women in synergistic female family relationships. Community health workers (CHWs) from two Michigan public health programs recruited women to serve as 'kin keepers' who in turn recruited their female family members. In total, 161 kin keepers and female family members were sampled. Trained CHWs led kin keepers and family members in learning about breast cancer. Data methods included baseline and post-training administration of a breast cancer literacy assessment, post-training focus groups and review of personal action plans. To validate the feasibility of the process, a linear mixed-effects regression with 97% power was identified and differences in pre-post scores were detected at 5% significance level. Adjusting for family random effects, breast cancer literacy scores increased for all participants recruited (P-value = 0.0004) suggesting that the process was feasible. Analysis of focus groups and action plans indicated that participants valued the instruction and planned to act upon it. This experience with kin keepers and their families offers encouragement that the theoretical model and its community-based delivery can continue to enhance scholarship dedicated to ameliorating health care disparities. [ABSTRACT FROM AUTHOR]

Background: Although African American women have a lower incidence of breast cancer, they suffer a 30% higher age-adjusted mortality. Lower health literacy levels diminish women's ability to engage in cancer prevention and detection activities.Methods: We conducted a focus group with lay health workers, following their completion of structured literacy assessments.Results: The women's performance established the feasibility and acceptability of incorporating literacy assessments. However, the findings identified perceived limits in existing measures and identified attributes that should be included in cancer-focused literacy assessments.Conclusions: A cancer-specific literacy assessment could assist community health workers in measuring women's functional cancer literacy. [ABSTRACT FROM AUTHOR]

Cancer mortality issues for African-American women are undeniably real. It is also apparent that to address the issue of this unequal burden, different intervention approaches are necessary. Employing a family systems approach for African-American women and their families holds benefits for both cancer prevention and cancer treatment. The Kin Keeper Model is based on the premise that the natural ways AfricanAmerican women communicate various health messages to females in their family can be used to influence their cancer prevention and screening behaviors. This paper reports empirical research that demonstrates significant familial influence on African-American women's cancer prevention screening behaviors. Findings indicated that family influence provides insight into the intersection of family altruism with cultural familial decision-making. In addition, the findings underscore the strong influence family has on African-American women's propensity to receive mammogram screening. [ABSTRACT FROM AUTHOR]

This article reports on an evaluation of community cardiovascular disease prevention projects. The evaluation protocol involved u monitoring system for documenting community activities. It showed improvements in cardiovascular disease prevention services, community actions, planned products, and new or modified community programs to prevent cardiovascular disease. Reports from focus group sessions provided analyses of participants' perceived behaviors and satisfaction with eight community-based cardiovascular disease prevention projects in African American communities. Modest improvements in blood pressure, blood cholesterol, dietary intake, and physical activity among u convenience sample of participants in the community were noted. [ABSTRACT FROM AUTHOR]

Sonic hedgehog (Shh) is a morphogen with important roles in embryonic development and in the development of a number of cancers. Its activity is modulated by interactions with binding partners and co-receptors including heparin and heparin sulfate proteoglycans (HSPG). To identify antagonists of Shh/heparin binding, a diverse collection of 34,560 chemicals was screened in single point 384-well format. We identified and confirmed twenty six novel small molecule antagonists with diverse structures including four scaffolds that gave rise to multiple hits. Nineteen of the confirmed hits blocked binding of the N-terminal fragment of Shh (ShhN) to heparin with IC 50 values < 50 μM. In the Shh-responsive C3H10T1/2 cell model, four of the compounds demonstrated the ability to block ShhN-induced alkaline phosphatase activity. To demonstrate a direct and selective effect on ShhN ligand mediated activity, two of the compounds were able to block induction of Gli1 mRNA, a primary downstream marker for Shh signaling activity, in Shh-mediated but not Smoothened agonist (SAG)-mediated C3H10T1/2 cells. Direct binding of the two compounds to ShhN was confirmed by thermal shift assay and molecular docking simulations, with both compounds docking with the N-terminal heparin binding domain of Shh. Overall, our findings indicate that small molecule compounds that block ShhN binding to heparin and act to inhibit Shh mediated activity in vitro can be identified. We propose that the interaction between Shh and HSPGs provides a novel target for identifying small molecules that bind Shh, potentially leading to novel tool compounds to probe Shh ligand function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Japanese encephalitis is a disease caused by the Japanese encephalitis virus (JEV) and is a concern for U.S. military personnel stationed in the Republic of Korea (ROK). The recent literature reports a potential shift from GI to GV as the dominant genotype circulating in east Asia. In the ROK, GV has been reported in a few Culex spp., but not in the main JEV vector, Cx . tritaeniorhynchus . The goal of this surveillance was to shed light on the current knowledge of the epidemiology of JEV in the ROK by analyzing mosquito collection data from three consecutive years, 2021-2023, and molecularly detecting and genotyping JEV in all Culex spp. collected in several military locations across the ROK. In this study, we detected only JEV GI in Cx . tritaeniorhynchus in 2021 samples. In contrast, all 2022 and 2023 positive samples were GV and detected in Cx . bitaeniorhynchus , Cx . orientalis , and Cx . pipiens . Results support a shift in JEV genotype in the ROK and suggest that for GV, Culex spp. other than Cx . tritaeniorhynchus may be playing an important role.

Aberrant activation of hedgehog (Hh) signaling has been implicated in various cancers. Current FDA-approved inhibitors target the seven-transmembrane receptor Smoothened, but resistance to these drugs has been observed. It has been proposed that a more promising strategy to target this pathway is at the GLI1 transcription factor level. GANT61 was the first small molecule identified to directly suppress GLI-mediated activity; however, its development as a potential anti-cancer agent has been hindered by its modest activity and aqueous chemical instability. Our study aimed to identify novel GLI1 inhibitors. JChem searches identified fifty-two compounds similar to GANT61 and its active metabolite, GANT61-D. We combined high-throughput cell-based assays and molecular docking to evaluate these analogs. Five of the fifty-two GANT61 analogs inhibited activity in Hh-responsive C3H10T1/2 and Gli-reporter NIH3T3 cellular assays without cytotoxicity. Two of the GANT61 analogs, BAS 07019774 and Z27610715, reduced Gli1 mRNA expression in C3H10T1/2 cells. Treatment with BAS 07019774 significantly reduced cell viability in Hh-dependent glioblastoma and lung cancer cell lines. Molecular docking indicated that BAS 07019774 is predicted to bind to the ZF4 region of GLI1, potentially interfering with its ability to bind DNA. Our findings show promise in developing more effective and potent GLI inhibitors.

•Situating engagement within the experience and priorities of survivors will enhance translational research and health equity.•The TRUST framework provides a guide to expand opportunities for community engagement in cardio-oncology for multiple constituents and across the care continuum.•Training community members as cardio-oncology champions may promote stakeholder representation.•Community connectors can support bidirectional engagement and support for survivors as they transition from active treatment., Competing Interests: Dr Sheppard is supported by the National Cancer Institute, Community Outreach and Engagement (PI: P30CA016059); the American Cancer Society (RSG-19-182-01-CPPB), which focuses on “Improving Communication and Adherence in Black Breast Cancer Survivors”; and the NCI Community Oncology Research Program (NCORP) (UG1CA189869), which is focused on the “VCU Massey Minority/Underserved NCI Community Oncology Research Program.” Dr Sutton is supported by the National Cancer Institute (R00CA256038). Dr Guha is supported by the American Heart Association-Strategically Focused Research Network Grant in Disparities in Cardio-Oncology (#847740, #863620) and the Department of Defense Prostate Cancer Research Program’s Physician Research Award (#HT94252310158). None of these funds supported this work. Dr Guha has an academic consulting relationship with Pfizer and Novartis; and his institution has received research funding from Sumitomo Pharma; however, there is no conflict of interest in submitting this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Genomic islands (GIs) are mobile genetic elements that integrate site-specifically into bacterial chromosomes, bearing genes that affect phenotypes such as pathogenicity and metabolism. GIs typically occur sporadically among related bacterial strains, enabling comparative genomic approaches to GI identification. For a candidate GI in a query genome, the number of reference genomes with a precise deletion of the GI serves as a support value for the GI. Our comparative software for GI identification was slowed by our original use of large reference genome databases (DBs). Here we explore smaller species-focused DBs., Results: With increasing DB size, recovery of our reliable prophage GI calls reached a plateau, while recovery of less reliable GI calls (FPs) increased rapidly as DB sizes exceeded ~500 genomes; i.e., overlarge DBs can increase FP rates. Paradoxically, relative to prophages, FPs were both more frequently supported only by genomes outside the species and more frequently supported only by genomes inside the species; this may be due to their generally lower support values. Setting a DB size limit for our SMAll Ranked Tailored (SMART) DB design speeded runtime ~65-fold. Strictly intra-species DBs would tend to lower yields of prophages for small species (with few genomes available); simulations with large species showed that this could be partially overcome by reaching outside the species to closely related taxa, without an FP burden. Employing such taxonomic outreach in DB design generated redundancy in the DB set; as few as 2984 DBs were needed to cover all 47894 prokaryotic species., Conclusions: Runtime decreased dramatically with SMART DB design, with only minor losses of prophages. We also describe potential utility in other comparative genomics projects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To examine if racial differences in cardiovascular health (CVH) are associated with cardiovascular disease (CVD) disparities among women with breast and gynecologic cancers., Sample & Setting: The sample consisted of 252 Black women and 93 White women without a self-reported history of cancer or CVD who developed a breast or gynecologic malignancy. Women who developed CVD before their cancer diagnosis were excluded., Methods & Variables: CVH was classified using metrics of the American Heart Association's Life's Simple 7 framework. Metrics were summed to create a total CVH score (0-7). Associations among race, ideal CVH (score of 5-7), and CVD incidence following cancer diagnosis were estimated with Cox proportional hazards models., Results: Ideal CVH was similar between Black women (33%) and White women (37%). Race and CVH were not associated with CVD incidence., Implications for Nursing: In a small sample of women diagnosed with breast and gynecologic cancers, racial disparities in CVH and CVD incidence were not observed. Additional investigation of potential confounders relating to social determinants of health tied to the construct of race is warranted.

Aims: To explore how emerging adult-aged women self-manage their sexual and reproductive health and to generate a grounded theory of these self-management processes., Design: Grounded theory methods using a constructivist approach., Methods: Between September 2019 and September 2020, 18- to 25-years-old women (n = 13) were recruited from a 4-year university, a 2-year community college, and neighbourhoods surrounding the institutions of higher education. Individual interviews were transcribed verbatim and qualitatively analysed using a constant comparative method and inductive coding., Results: The theory purports that core processes of sexual and reproductive health self-management used by the women in this study included both passive and (re)active processes. These processes expanded upon and/or maintained the women's accessible sexual and reproductive health knowledge, behaviour and beliefs, defined as the sexual and reproductive health repertoire. The processes appeared to be cyclical and were often initiated by a catalysing event or catalyst and resulted in conversations with confidantes, or trusted individuals. A catalyst was either resolved or normalized by expanding or maintaining the sexual and reproductive health repertoire., Conclusion: The resulting theory, EMeRGE Theory, offers insight into the complex and cyclical processes emerging adult-aged women use to simultaneously develop and adapt their foundational sexual and reproductive health knowledge, behaviours and beliefs., Implications for the Profession And/or Patient Care: This explication of emerging adult-aged women's sexual and reproductive health self-management processes can be used by nurses and nurse researchers to better address this population's unique health needs., Impact: The EMeRGE Theory provides valuable guidance for future exploratory and intervention research aimed at improving the health and well-being of emerging adult-aged women., Reporting Method: The authors adhered to the Consolidated Criteria for Reporting Qualitative studies (COREQ) in preparation of this publication., Patient or Public Contribution: No patient or public contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Adding sequences into an existing (possibly user-provided) alignment has multiple applications, including updating a large alignment with new data, adding sequences into a constraint alignment constructed using biological knowledge, or computing alignments in the presence of sequence length heterogeneity. Although this is a natural problem, only a few tools have been developed to use this information with high fidelity., Results: We present EMMA (Extending Multiple alignments using MAFFT--add) for the problem of adding a set of unaligned sequences into a multiple sequence alignment (i.e., a constraint alignment). EMMA builds on MAFFT--add, which is also designed to add sequences into a given constraint alignment. EMMA improves on MAFFT--add methods by using a divide-and-conquer framework to scale its most accurate version, MAFFT-linsi--add, to constraint alignments with many sequences. We show that EMMA has an accuracy advantage over other techniques for adding sequences into alignments under many realistic conditions and can scale to large datasets with high accuracy (hundreds of thousands of sequences). EMMA is available at https://github.com/c5shen/EMMA ., Conclusions: EMMA is a new tool that provides high accuracy and scalability for adding sequences into an existing alignment., (© 2023. The Author(s).)

Purpose: Black women often experience poorer breast cancer-related outcomes and higher mortality than white women. A contributor to this disparity may relate to the disproportionate burden of cancer treatment-related cardiovascular (CV) toxicities. The objective of this review is to identify studies that report racial differences in CV toxicity risk., Methods: Medline and Embase were searched for studies that assessed CV toxicities as the outcome(s) and included Black and White women with breast cancer. Studies were selected based on inclusion/exclusion criteria and through the use of multiple reviewers., Results: The review included 13 studies following a review of 409 citations and 49 full-text articles. All studies were retrospective and 8/13 utilized data from the Surveillance, Epidemiology, and End Results-Medicare linked database. Trastuzumab was the most frequently studied treatment. The proportion of Black women in these studies ranged from 5.5 to 63%. A majority of studies reported a higher risk of CV toxicity amongst Black women when compared to white women (93%). Black women had up to a two times higher risk of CV toxicity (HR, 2.73 (CI, 1.24 to 6.01)) compared to white women. Only one study evaluated the role of socioeconomic factors in explaining racial differences in CV toxicity; however, the disparity remained even after adjusting for these factors., Conclusions: There is a critical need for more longitudinal studies that evaluate multilevel factors (e.g., psychosocial, biological) that may help to explain this disparity., Implications for Cancer Survivors: Black cancer survivors may require additional surveillance and mitigation strategies to decrease disproportionate burden of CV toxicities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2 high ESCC., Design: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays., Results: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as potential NRF2 inhibitors with minimal cytotoxicity at specified concentrations. We then validated two of these compounds, pyrimethamine and mitoxantrone, by demonstrating their dose- and time-dependent inhibitory effects on the expression of NRF2 and its target genes in two NRF2 Mut human ESCC cells (KYSE70 and KYSE180). RNAseq and qPCR confirmed the suppression of global NRF2 signaling by these two compounds. Mechanistically, pyrimethamine reduced NRF2 half-life by promoting NRF2 ubiquitination and degradation in KYSE70 and KYSE180 cells. Expression of an Nrf2 E79Q allele in mouse esophageal epithelium (Sox2CreER;LSL-Nrf2 E79Q/+ ) resulted in an NRF2 high phenotype, which included squamous hyperplasia, hyperkeratinization, and hyperactive glycolysis. Treatment with pyrimethamine (30 mg/kg/day, p.o.) suppressed the NRF2 high esophageal phenotype with no observed toxicity., Conclusion: We have identified and validated pyrimethamine as an NRF2 inhibitor that may be rapidly tested in the clinic for NRF2 high ESCC., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The natural assemblage of a symbiotic bacterial microbiome (bacteriome) with microalgae in marine ecosystems is now being investigated as a means to increase algal productivity for industry. When algae are grown in open pond settings, biological contamination causes an estimated 30% loss of the algal crop. Therefore, new crop protection strategies that do not disrupt the native algal bacteriome are needed to produce reliable, high-yield algal biomass. Bacteriophages offer an unexplored solution to treat bacterial pathogenicity in algal cultures because they can eliminate a single species without affecting the bacteriome. To address this, we identified a highly virulent pathogen of the microalga Nannochloropsis gaditana , the bacterium Bacillus safensis , and demonstrated rescue of the microalgae from the pathogen using phage. 16S rRNA amplicon sequencing showed that phage treatment did not alter the composition of the bacteriome. It is widely suspected that the algal bacteriome could play a protective role against bacterial pathogens. To test this, we compared the susceptibility of a bacteriome-attenuated N. gaditana culture challenged with B. safensis to a N. gaditana culture carrying a growth-promoting bacteriome. We showed that the loss of the bacteriome increased the susceptibility of N. gaditana to the pathogen. Transplanting the microalgal bacteriome to the bacteriome-attenuated culture reconstituted the protective effect of the bacteriome. Finally, the success of phage treatment was dependent on the presence of beneficial bacteriome. This study introduces two synergistic countermeasures against bacterial pathogenicity in algal cultures and a tractable model for studying interactions between microalgae, phages, pathogens, and the algae microbiome., Competing Interests: JC and CS employer has filed a patent application on biotic countermeasures for algae crop protection. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Humphrey, Mackenzie, Lobitz, Schambach, Lasley, Kolker, Ricken, Bennett, Williams, Smallwood and Cahill.)

The aim of this study was to utilize a computational methodology based on Gene Reversal Rate (GRR) scoring to repurpose existing drugs for a rare and understudied cancer: inflammatory breast cancer (IBC). This method uses IBC-related gene expression signatures (GES) and drug-induced gene expression profiles from the LINCS database to calculate a GRR score for each candidate drug, and is based on the idea that a compound that can counteract gene expression changes of a disease may have potential therapeutic applications for that disease. Genes related to IBC with associated differential expression data (265 up-regulated and 122 down-regulated) were collated from PubMed-indexed publications. Drug-induced gene expression profiles were downloaded from the LINCS database and candidate drugs to treat IBC were predicted using their GRR scores. Thirty-two (32) drug perturbations that could potentially reverse the pre-compiled list of 297 IBC genes were obtained using the LINCS Canvas Browser (LCB) analysis. Binary combinations of the 32 perturbations were assessed computationally to identify combined perturbations with the highest GRR scores, and resulted in 131 combinations with GRR greater than 80%, that reverse up to 264 of the 297 genes in the IBC-GES. The top 35 combinations involve 20 unique individual drug perturbations, and 19 potential drug candidates. A comprehensive literature search confirmed 17 of the 19 known drugs as having either anti-cancer or anti-inflammatory activities. AZD-7545, BMS-754807, and nimesulide target known IBC relevant genes: PDK, Met, and COX, respectively. AG-14361, butalbital, and clobenpropit are known to be functionally relevant in DNA damage, cell cycle, and apoptosis, respectively. These findings support the use of the GRR approach to identify drug candidates and potential combination therapies that could be used to treat rare diseases such as IBC., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

We examined whether resilience modified associations between allostatic load (AL), a physiological indicator of coping with repeated stressors, and cardiovascular disease (CVD) among 2758 African Americans in the Jackson Heart Study. Baseline AL was quantified using biological measures of metabolic, cardiovascular, and immune markers. We constructed a multidimensional resilience measure using validated questionnaires for social support, social networks, religious experiences, and optimism. Participants were followed until 2016 for stroke, coronary heart disease (CHD), and heart failure (HF). We used multivariable-adjusted, sex-stratified Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between dichotomous AL and CVD. High AL was associated with CHD among women (HR = 1.73, 95% CI = 1.00, 2.99) and HF among women (HR = 1.52, 95% CI = 0.98, 2.37) and men (HR = 2.17, 95% CI = 1.28, 3.68). Among women, resilience did not modify the AL-CVD relationship. Among men, we observed higher stroke risk among men with low resilience (HR = 2.21, 95% CI = 0.94, 5.22) and no association among those with high resilience. Counterintuitively, high AL was associated with greater HF (HR = 5.80, 95% CI = 2.32, 14.47) in the subgroup of men with high resilience. Future studies addressing different facets of resilience are needed to elucidate underlying mechanisms for CVD prevention among African Americans., (© 2022. W. Montague Cobb-NMA Health Institute.)

Resilience, thriving in the face of adversity, is a critical component of well-being in African American women. However, traditional definitions and approaches to operationalize resilience may not capture race- and gender-related resilience experiences of African American women. A more complete conceptualization of resilience may help facilitate future investigation of the mechanisms through which resilience influences health in this group. Our team conducted a scoping review of the literature published during twenty years, between 2000 and 2019, on resilience and health in African American women. We included a multidisciplinary set of databases (PubMed, CINAHL, PsycINFO, Scopus, Social Work Abstracts, Sociological Abstracts, Academic Search Premier). Using Covidence software a multi-step review process was conducted; 904 abstracts were initially screened for eligibility, 219 full-text studies were screened in stage two, and 22 remaining studies were reviewed for extraction. The studies reviewed revealed limitations of unidimensional approaches to conceptualizing/operationalizing resilience in African American women. The review highlighted culturally-relevant components of resilience including spirituality/religion, strength, survival, active coping, and social support. Findings highlight the importance of operationalizing resilience as a multidimensional construct so it can be optimally included in research designed to investigate the quality of life, cardiovascular risk, and other health outcomes in African American women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Little is known about whether a breast or gynecologic cancer diagnosis increases long-term cardiovascular disease (CVD) risk among Black females. The purpose of this study was to determine whether a breast or gynecologic cancer diagnosis is associated with CVD risk and identify determinants of subsequent CVD risk among Black females with an incident breast or gynecologic cancer diagnosis., Methods: Using the Southern Community Cohort Study data from 2002-2016, this study was designed to analyze CVD incidence among Black females without cancer or CVD at enrollment. Cox proportional hazards regression models with or without covariates were used to explore the relationship between a breast or gynecologic cancer diagnosis and CVD risk among women without cancer as well as without CVD at enrollment (N=11,486). In addition, Cox proportional hazards regression models, excluding those who developed CVD before breast and gynecologic cancer diagnosis and those with other types of cancers, were used to assess determinants of CVD risk among breast and gynecologic cancer survivors., Results: Of 11,486 Black females, 531 developed a breast or gynecological cancer (4.6%) over a median follow-up of 140 months (interquartile range: 123-159 months). Compared to women without cancer, women with a breast or gynecological cancers had greater than 20% higher risk of incident CVD during the follow-up period. Without adjusting for covariates, positive association between CVD risk and breast cancer was observed (hazard ratio (HR) = 1.24; 95% confidence interval (CI) = 1.11 - 1.39; p < 0.001); as well as between CVD risk and a gynecological cancer (HR = 1.23; 95% CI = 1.03 - 1.46; p = 0.021). Yet, after adjusting for covariates, CVD risk was only significantly associated with breast cancer (p = 0.001) but not gynecologic cancer. In cancer case-only analyses, CVD risk was significantly increasing with age (p < 0.05)., Conclusions: Like study populations of predominantly White females, our results suggest that, adjusting for covariates, Black females possess a higher risk of CVD following a breast cancer diagnosis compared to women who did not develop breast cancer. Our results suggest a need for active CVD surveillance in the cancer survivorship phase., (Copyright © 2023. Published by Elsevier Inc.)

Undergraduate leadership education prepares students for meaningful roles in various aspects of civic and professional life. In this article, the authors explore the contextual facets of undergraduate academic leadership programs and courses utilizing the Sustainable Development Goals (SDGs) as a framework for addressing local and global challenges through leadership education and development at two higher education institutions. Each example is described contextually followed by promising classroom practices embedded through the use of the SDG framework., (© 2023 Wiley Periodicals, LLC.)

Objective: Emerging adult-aged (EA;18-25 years) women have disproportionately high rates of unintended pregnancy and sexually transmitted infections compared to other women of reproductive age. Little is known about how EA women define and prioritize various aspects of sexual and reproductive health. The purpose of this study was to identify EA women determined definitions of sexual and reproductive health., Methods: Between September 2019 and September 2020, 13 women were interviewed about their sexual and reproductive health. Interview transcripts were used to conduct qualitative content analysis., Results: Definitions provided by participants were grouped according to three distinct thematic categories, Being Safe, Healthcare as a Tool, and Mind-Body Connection. Being Safe included using condoms and taking steps to prevent sexually transmitted infections. Healthcare as a Tool referred to utilization of healthcare services (e.g., an annual exam) to manage sexual and reproductive health. Mind-Body Connection included acknowledgement of both the physical and mental aspects of sexual and reproductive health, as well as awareness of physical and emotional discomfort related to it. These categories highlight EA women's holistic definitions of sexual and reproductive health., Conclusions: Healthcare providers and researchers can use the holistic sexual and reproductive health definitions endorsed by EA women in this study as a starting point for creating and delivering sexual and reproductive healthcare and counseling that is developmentally appropriate and sensitive to population-specific needs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cervical cerclage has been used for decades to reduce preterm birth. The Shirodkar and McDonald cerclage are the most commonly used techniques with no current consensus on the preferred technique., Objective: To compare the efficacy of the Shirodkar and McDonald cerclage techniques in preventing preterm birth., Search Strategy: Studies were sourced from six electronic databases and reference lists., Selection Criteria: Studies including women with a singleton pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique that ran comparative analyses between the two techniques., Data Collection and Analysis: The primary outcome was preterm birth before 37 weeks, with analyses at 28, 32, 34 and 35 weeks. Secondary data were also collected on neonatal, maternal and obstetric outcomes., Main Results: Seventeen papers were included: 16 were retrospective cohort studies and one was a randomised controlled trial. The Shirodkar technique was significantly less likely to result in preterm birth before 37 weeks than the McDonald technique (relative risk [RR] 0.91, 95% CI 0.85-0.98). This finding was supported by a statistically significant reduction in rates of preterm birth before 35, 34 and 32 weeks, PPROM, difference in cervical length, cerclage to delivery interval, and an increase in birthweight in the Shirodkar group. No difference was seen in preterm birth rates <28 weeks, neonatal mortality, chorioamnionitis, cervical laceration or caesarean section rates. The RR for preterm birth prior to 37 weeks was no longer significant when sensitivity analyses were performed removing studies with a serious risk of bias. However, similar analyses removing studies that utilised adjunctive progesterone strengthened the primary outcome (RR 0.83, 95% CI 0.74-0.93)., Conclusion: Shirodkar cerclage reduces the rate of preterm birth prior to 35, 34 and 32 weeks' gestation when compared with McDonald cerclage; however, the overall quality of the studies in this review is low. Further, large, well-designed randomised controlled trials are required to address this important question to optimise care for women who may benefit from cervical cerclage., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Satellites such as phage-induced chromosomal islands (PICIs) are mobile genetic elements relying on helper phages for their mobilization, through trans-regulatory interactions. We discovered a PICI with a more intimate cis- regulatory configuration, integrated within a late gene of its helper prophage. This helper-embedded PICI (HE-PICI) configuration delays expression of the interrupted helper late gene until the satellite excises and provides passive helper-driven components to both HE-PICI replication and late transcription. Upon induction of a helper-satellite composite, precise excision of the entire composite was observed, followed by composite replication, then satellite excision. We mapped 491 additional HE-PICIs to one of 14 sites in cognates of phage lambda late genes. Associated integrases form a single phylogenetic clade with subclades respecting the 14 site groups, exhibiting repeated tropism for prophage late genes as new integration sites evolve. Four ordered zones in a general gram-negative PICI genome organization are: an integration zone encoding integrase and AlpA, a dynamic zone encoding members of the Bro-N network of domain-swapping DNA-interactive proteins and immunity repressor RNAs, a replication zone, and a dynamic late zone in which clusters as large as 17 consecutive helper prophage late genes have been captured. Helper-embedded satellites present new dimensions in satellite/helper relationships., (© The Author(s) 2023. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

The emergence of drug-resistant pathogens necessitates the development of new countermeasures. In this regard, the introduction of probiotics to directly attack or competitively exclude pathogens presents a useful strategy. Application of this approach requires an understanding of how a probiotic and its target pathogen interact. A key means of probiotic-pathogen interaction involves the production of small molecules called natural products (NPs). Here, we report the use of whole-cell matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry to characterize NP production by candidate probiotics (mouse airway microbiome isolates) when co-cultured with the respiratory pathogen Burkholderia. We found that a Bacillus velezensis strain inhibits growth of and elicits NP production by Burkholderia thailandensis. Dereplication of known NPs detected in the metabolome of this B. velezensis strain suggests that a previously unannotated bioactive compound is involved. Thus, we present the use of whole-cell MALDI as a broadly applicable method for screening the NP composition of microbial co-cultures; this can be combined with other -omics methods to characterize probiotic-pathogen and other microbe-microbe interactions., (© 2023 Wiley-VCH GmbH.)

Objectives: To determine if there was excess mortality in Alberta, Canada during the coronavirus disease 2019 (COVID-19) pandemic, to confirm if excess mortality affected all age groups equally, and to determine what proportions of excess deaths were directly related to COVID-19 and non-pharmaceutical drug poisoning., Methods: Weekly all-cause data used to estimate excess mortality were modelled against the pre-pandemic period (January 2015-February 2020). Age-adjusted weekly mortality rates for March 2020 to December 2021 were compared with the preceding 5 years., Results: From March 2020 to December 2021, there was an 11% excess mortality rate, corresponding to an average of 265 monthly excess deaths (maximum >30%). COVID-19-related deaths ( n =3202) accounted for 54.9% of total excess deaths ( n =5833) that occurred in the 22-month period. The increase in all-cause excess deaths was proportionately higher, and with significantly greater numbers, in younger age groups. Significant increases in monthly drug poisoning deaths occurred from March 2020 to April 2021, with a total of 1819 deaths. Eight hundred and 25 excess drug poisoning deaths, representing 25.4% of total all-cause excess deaths, occurred, mainly among those aged 25-60 years. Overall, 54.9% of all excess deaths were directly related to COVID-19 and 25.4% were related to drug poisoning., Conclusions: There was a significant increase in all-cause mortality during the COVID-19 pandemic. Although older adults are more likely to die of COVID-19, a massive increase in non-COVID-19-related mortality was observed among younger people. These factors should be considered in public policy decisions on epidemic/pandemic management., (© 2022 The Author(s).)

Background: Gibson assembly and assembly-in-yeast are strategies to create long synthetic DNAs from diverse fragments, for example, when engineering bacteriophage genomes. Design for these methods requires terminal sequence overlaps in the fragments, determining the order of assembly. Design to rebuild a genomic fragment that is too long for a single PCR presents a puzzle since some candidate joint regions cannot yield satisfactory primers for the overlap. No existing overlap assembly design software is open-source, and none explicitly supports rebuilding., Methods: We describe here bigDNA software that solves the rebuilding puzzle by recursive backtracking, with options to remove or introduce genes; it also tests for mispriming on the template DNA. BigDNA was tested with 3082 prophages and other genomic islands (GIs), from 20 to 100 kb, and the synthetic Mycoplasma genitalium genome., Results: Rebuilding assembly design succeeded for all but ∼1% of GIs., Conclusion: BigDNA will speed and standardize assembly design., Competing Interests: No competing financial interests exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Objective: To determine whether vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy and normal mid-gestation cervical length. Study design: Databases were searched (from inception to December 2020) with the search terms "progesterone" and "premature birth" or "preterm birth". Studies were screened and included if they assessed vaginal progesterone compared to placebo in women with normal cervical length. Data were pooled and synthesized in a meta-analysis using a random effects model. Data sources : MEDLINE and Embase databases. Study synthesis: Following PRISMA screening guidelines, data from 1127 women across three studies were available for synthesis. All studies had low risk of bias and were of high quality. The primary outcome was sPTB <37 weeks, with secondary outcomes of sPTB <34 weeks. Vaginal progesterone did not significantly reduce sPTB before 37 weeks, or before 34 weeks with a relative risk (RR) of 0.76 (95% CI 0.37-1.55, p  = .45) and 0.51 (95% CI 0.12-2.13, p  = .35), respectively. Conclusions: Vaginal progesterone does not decrease the risk of sPTB in high-risk singleton pregnancies with a normal mid-gestation cervical length.

Columbus, Ohio is one of the more prosperous, well-educated, and progressive cities in the United States. However, it ranks as the second worst life expectancy at birth, has a census tract wealth gap (27-year disparity), and one of the higher infant mortality rates in the country. These data suggest that there are likely several high-risk, vulnerable neighborhoods in Columbus with residents experiencing disparate and adverse outcomes. Illustrative of this fact are studies that have examined the social processes and mechanisms through which neighborhood contexts are at the forefront, including exposures to chemical stressors such as particulate matter (PM 2.5 ) as well as non-chemical stressors including violence, social determinants of health, zoning, and land use policies. It is documented that disparate and adverse outcomes are magnified in the vulnerable neighborhoods on the Near East Side as compared to Columbus city proper, Franklin County and/or the state of Ohio. As such, we developed a nuanced community engagement framework to identify potential environmental hazards associated with adverse pregnancy outcomes in those census tracts. The refined framework uses a blended version of traditional community-based participatory research (CBPR) models and is referred to as E 6 , Enhancing Environmental Endeavors via e-Equity, Education, and Empowerment.

Background: Obese women have higher risk of aggressive breast tumors and distant metastasis. However, obesity has rarely been assessed in association with metastasis in diverse populations., Methods: In the Carolina Breast Cancer Study Phase 3 (2008-2013), waist-to-hip ratio (WHR), body mass index (BMI), and molecular subtype [PAM50 risk-of-recurrence (ROR) score] were assessed. Obesity measures were evaluated in association with metastasis within five years of diagnosis, overall and stratified by race and ROR score. Absolute risk of metastasis and risk differences between strata were calculated using the Kaplan-Meier estimator, adjusted for age, grade, stage, race, and ER status. Relative frequency of metastatic site and multiplicity were estimated in association with obesity using generalized linear models., Results: High-WHR was associated with higher risk of metastasis (5-year risk difference, RD, 4.3%; 95% confidence interval, 2.2-6.5). It was also associated with multiple metastases and metastases at all sites except brain. The 5-year risk of metastasis differed by race (11.2% and 6.9% in Black and non-Black, respectively) and ROR score (19.5% vs. 6.6% in high vs. low-to-intermediate ROR-PT). Non-Black women and those with low-to-intermediate ROR scores had similar risk in high- and low-WHR strata. However, among Black women and those with high ROR, risk of metastasis was elevated among high-WHR (RDBlack/non-Black = 4.6%, RDHigh/Low-Int = 3.1%). Patterns of metastasis were similar by BMI., Conclusions: WHR is associated with metastatic risk, particularly among Black women and those with high-risk tumors., Impact: Understanding how risk factors for metastasis interact may help in tailoring care plans and surveillance among patients with breast cancer., (©2022 American Association for Cancer Research.)

Ethanol exposure during the early stages of embryonic development can lead to a range of morphological and behavioral differences termed fetal alcohol spectrum disorders (FASDs). In a zebrafish model, we have shown that acute ethanol exposure at 8-10 hr postfertilization (hpf), a critical time of development, produces birth defects similar to those clinically characterized in FASD. Dysregulation of the Sonic hedgehog (Shh) pathway has been implicated as a molecular basis for many of the birth defects caused by prenatal alcohol exposure. We observed in zebrafish embryos that shh expression was significantly decreased by ethanol exposure at 8-10 hpf, while smo expression was much less affected. Treatment of zebrafish embryos with SAG or purmorphamine, small molecule Smoothened agonists that activate Shh signaling, ameliorated the severity of ethanol-induced developmental malformations including altered eye size and midline brain development. Furthermore, this rescue effect of Smo activation was dose dependent and occurred primarily when treatment was given after ethanol exposure. Markers of Shh signaling (gli1/2) and eye development (pax6a) were restored in embryos treated with SAG post-ethanol exposure. Since embryonic ethanol exposure has been shown to produce later-life neurobehavioral impairments, juvenile zebrafish were examined in the novel tank diving test. Our results further demonstrated that in zebrafish embryos exposed to ethanol, SAG treatment was able to mitigate long-term neurodevelopmental impairments related to anxiety and risk-taking behavior. Our results indicate that pharmacological activation of the Shh pathway at specific developmental timing markedly diminishes the severity of alcohol-induced birth defects., (© 2022 Wiley Periodicals LLC.)

Competing Interests: SSL has consulted for AbbVie, Gilead Sciences, Justice Canada (HCV file). All other authors declared no competing interests. We express gratitude to the communities across Alberta who have collaborated in the ECHO programme, as well as the advisory committee in shaping and supporting this collaborative approach. We acknowledge the ECHO programme is located on Treaty 6, 7, and 8, and on Métis Nation of Alberta Region 3 lands. KPRD, KPW, AL, and HC are Indigenous peoples. Total HCV treatment data for Alberta were kindly provided by IQVIA (Kirkland, QC, Canada).

Aggressive breast cancer variants, like triple negative and inflammatory breast cancer, contribute to disparities in survival and clinical outcomes among African American (AA) patients compared to White (W) patients. We previously identified the dominant role of anti-apoptotic protein XIAP in regulating tumor cell adaptive stress response (ASR) that promotes a hyperproliferative, drug resistant phenotype. Using The Cancer Genome Atlas (TCGA), we identified 46-88 ASR genes that are differentially expressed (2-fold-change and adjusted p-value < 0.05) depending on PAM50 breast cancer subtype. On average, 20% of all 226 ASR genes exhibited race-related differential expression. These genes were functionally relevant in cell cycle, DNA damage response, signal transduction, and regulation of cell death-related processes. Moreover, 23% of the differentially expressed ASR genes were associated with AA and/or W breast cancer patient survival. These identified genes represent potential therapeutic targets to improve breast cancer outcomes and mitigate associated health disparities., (© 2022. The Author(s).)

Background: Indigenous populations experience higher rates of hepatitis C virus (HCV) infections in Canada. The Extension for Community Health Outcomes+ (ECHO+) telehealth model was implemented in Alberta to support HCV screening and treatment, using Zoom technology to support Indigenous patient access to specialist care closer to home. Our goal was to expand this program to more Indigenous communities in Alberta, using various Indigenous-led or co-designed methods., Methods: The ECHO+ team implemented a Two-Eyed Seeing framework, incorporating Indigenous wholistic approaches alongside Western treatment. This approach works with principles of respect, reciprocity, and relationality. The ECHO+ team identified Indigenous-specific challenges, including access to liver specialist care, HCV awareness, stigma, barriers to screening and lack of culturally relevant approaches., Results: Access to HCV care via this program significantly increased HCV antiviral use in the past 5 years. Key lessons learned include Indigenous-led relationship building and development of project outputs in response to community needs influences impact and increases relevant changes increasing access to HCV care. Implementation of ECHO+ was carried out through biweekly telehealth sessions, problem solving in partnership with Indigenous communities, increased HCV awareness, and flexibility resulting from the impacts of COVID-19., Conclusion: Improving Indigenous patient lives and reducing inequity requires supporting local primary health care providers to create and sustain integrated HCV prevention, diagnosis, treatment, and support services within a culturally safe and reciprocal model. ECHO+ uses telehealth and culturally appropriate methodology and interventions alongside multiple stakeholder collaborations to improve health outcomes for HCV., Competing Interests: SS Lee received consulting or advisory board fees from AbbVie, Gilead, Intercept, Janssen, and Merck, and speaker honoraria from AbbVie, Gilead, London Drugs, Lupin, Merck, and Pendopharm. The other authors have nothing to disclose., (Copyright © 2022 Canadian Association for the Study of the Liver.)

The mobilome of a microbe, i.e., its set of mobile elements, has major effects on its ecology, and is important to delineate properly in each genome. This becomes more challenging for incomplete genomes, and even more so for metagenome-assembled genomes (MAGs), where misbinning of scaffolds and other losses can occur. Genomic islands (GIs), which integrate into the host chromosome, are a major component of the mobilome. Our GI-detection software TIGER, unique in its precise mapping of GI termini, was applied to 74,561 genomes from 2,473 microbial species, each species containing at least one MAG and one isolate genome. A species-normalized deficit of ∼1.6 GIs/genome was measured for MAGs relative to isolates. To test whether this undercount was due to the higher fragmentation of MAG genomes, TIGER was updated to enable detection of split GIs whose termini are on separate scaffolds or that wrap around the origin of a circular replicon. This doubled GI yields, and the new split GIs matched the quality of single-scaffold GIs, except that highly fragmented GIs may lack central portions. Cross-scaffold search is an important upgrade to GI detection as fragmented genomes increasingly dominate public databases. TIGER2 better captures MAG microdiversity, recovering niche-defining GIs and supporting microbiome research aims such as virus-host linking and ecological assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mageeney, Trubl and Williams.)

Purpose: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC., Methods: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis., Results: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies., Conclusion: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance., (© 2022. The Author(s).)

Purpose: Black women have a 40% increased risk of breast cancer-related mortality. These outcome disparities may reflect differences in tumor pathways and a lack of targetable therapies for specific subtypes that are more common in Black women. Hepatocyte growth factor (HGF) is a targetable pathway that promotes breast cancer tumorigenesis, is associated with basal-like breast cancer, and is differentially expressed by race. This study assessed whether a 38-gene HGF expression signature is associated with recurrence and survival in Black and non-Black women., Methods: Study participants included 1957 invasive breast cancer cases from the Carolina Breast Cancer Study. The HGF signature was evaluated in association with recurrence (n = 1251, 171 recurrences), overall, and breast cancer-specific mortality (n = 706, 190/328 breast cancer/overall deaths) using Cox proportional hazard models., Results: Women with HGF-positive tumors had higher recurrence rates [HR 1.88, 95% CI (1.19, 2.98)], breast cancer-specific mortality [HR 1.90, 95% CI (1.26, 2.85)], and overall mortality [HR 1.69; 95% CI (1.17, 2.43)]. Among Black women, HGF positivity was significantly associated with higher 5-year rate of recurrence [HR 1.73; 95% CI (1.01, 2.99)], but this association was not significant in non-Black women [HR 1.68; 95% CI (0.72, 3.90)]. Among Black women, HGF-positive tumors had elevated breast cancer-specific mortality [HR 1.80, 95% CI (1.05, 3.09)], which was not significant in non-Black women [HR 1.52; 95% CI (0.78, 2.99)]., Conclusion: This multi-gene HGF signature is a poor-prognosis feature for breast cancer and may identify patients who could benefit from HGF-targeted treatments, an unmet need for Black and triple-negative patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although Black American mothers and infants are at higher risk for morbidity and mortality than their White counterparts, the biological mechanisms underlying these phenomena remain largely unknown. To investigate the role that lifetime stressor exposure, perceived stressor severity, and systemic inflammatory markers might play, we studied how these factors were interrelated in 92 pregnant Black American women. We also compared inflammatory marker levels for women who did versus did not go on to give birth preterm. During the early third trimester, women completed the Stress and Adversity Inventory for Adults to assess the stressors they experienced over their lifetime. Women also provided blood samples for plasma interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α quantification. Preterm births were identified by medical record review. Controlling for relevant covariates, there were significant positive associations between average levels of both overall and acute perceived stressor severity and plasma IL-1β levels. Controlling for perceived stress at assessment and exposure to racial discrimination did not affect these results. Mediation models revealed that exposure to more chronic stressors was related to higher plasma IL-1β levels, as mediated by higher average levels of overall perceived stressor severity. Exposure to fewer acute stressors was related to higher plasma IL-1β levels, as mediated by higher average levels of acute perceived stressor severity. Finally, women who went on to give birth preterm had higher levels of plasma IL-6. These data thus highlight the potential importance of assessing and addressing lifetime stressor exposure among mothers before and during maternal-infant care., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study examined consumption proportions and factors associated with sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and 100% fruit juice (FJ) consumption. We recruited Non-Hispanic Black ( n = 136) and White ( n = 192) low-income overweight or obese pregnant women aged 18 to 46 years (mean = 25.7 years) from the Special Supplemental Nutrition Program for Women, Infants, and Children clinics in Michigan, USA. Independent variables included weight status, trimester, smoking, stress, education, employment, race, and age. Dependent variables were high (consuming ≥ 1 serving/day) versus low consumptions of SSB, ASB, and 100% FJ. Multivariate logistic regression modeling was performed to examine factors associated with beverage consumption. Out of the sample, 48.2%, 6.7%, and 31.3% reported high SSB, ASB, and 100% FJ consumption, respectively. SSB consumption was associated with smoking (OR: 3.77, p < 0.001), education (OR: 0.57, p = 0.03), and race (OR: 1.69, p = 0.03). Artificially sweetened beverage consumption was not associated with any factors examined. One hundred percent FJ consumption was associated with stress (OR: 0.90, p = 0.03) and race (OR: 4.48, p < 0.001). Clinicians may advocate for reductions in SSB and 100% FJ consumption tailored to client consumption characteristics.

Over the last three decades, increased attention has been given to the representation of historically underrepresented groups within the landscape of pivotal clinical trials. However, recent events (i.e., coronavirus pandemic) have laid bare the potential continuation of historic inequities in available clinical trials and studies aimed at the care of broad patient populations. Anecdotally, cardiovascular disease (CVD) has not been immune to these disparities. Within this review, we examine and discuss recent landmark CVD trials, with a specific focus on the representation of Blacks within several critically foundational heart failure clinical trials tied to contemporary treatment strategies and drug approvals. We also discuss solutions for inequities within the landscape of cardiovascular trials. Building a more diverse clinical trial workforce coupled with intentional efforts to increase clinical trial diversity will advance equity in cardiovascular care., (Copyright © 2021. Published by Elsevier B.V.)