bluuebunny/crossref_metadata_2025 huggingface dataset:
Vagal preganglionic axons arborize in the myenteric plexus into two types: nitrergic and non-nitrergic postganglionic motor pools?
Authors: Jaffey D. M. , McAdams J. L. , Baronowsky E. A. , Black D. , Powley T. L.
Published: January 2023

Vagal preganglionic neurons innervate myenteric ganglia. These autonomic efferents are distributed so densely within the ganglia that it has been impractical to track individual vagal axons through the myenteric plexus with tracer labeling. To evaluate whether vagal efferent axons evidence selectivity, particularly for nitrergic or non-nitrergic myenteric neurons within the plexus, we limited the numbers and volumes of brainstem dextran biotin tracer injections per animal. Reduced labeling and the use of immunohistochemistry generated cases in which some individual axons could be distinguished and traced in three dimensions (Neurolucida) within and among successive (up to 46) myenteric ganglia. In the myenteric plexus of all stomach regions, the majority (∼86%) of vagal efferents were organized into two distinct subtypes. One subtype (∼24% of dextran-labeled efferents, designated “primarily nitrergic”) selectively contacted and linked—both within and between ganglia—nitric oxide synthase positive (nNOS+) neurons into presumptive motor modules. A second subtype (∼62% of efferents, designated “primarily non-nitrergic”) appeared to selectively contact and link—both within and between ganglia—non-nitrergic enteric neurons into a second type of effector ensemble. A third candidate type (∼14% of labeled preganglionics), appeared to lack “nitrergic selectivity” and to contact both nNOS+ and nNOS− enteric neurons. In addition to the quantitative assessment of the efferent axons in stomach, qualitative observations of the proximal duodenum indicated similar selective vagal efferent projections, in proportions comparable with those evaluated in the stomach. Limited injections of tracer, three-dimensional (3-D) tracing of individual axons, and histochemistry of myenteric neurons might distinguish additional efferent phenotypes.
A Mechanism Exploration for the Yi‐Fei‐San‐Jie Formula against Non‐Small‐Cell Lung Cancer Based on UPLC‐MS/MS, Network Pharmacology, and In Silico Verification
Authors: Hu Leihao , He Canfeng , Mo Aier , Zhan Xingkai , Yang Caizhi , Guo Wei , Sun Lingling , Su Weiwei , Lin Lizhu
Published: January 2023

Non‐small‐cell lung cancer (NSCLC) is one of the most prevalent cancers worldwide. A Yi‐Fei‐San‐Jie formula (YFSJF), widely used in NSCLC treatment in south China, has been validated in clinical studies. However, the pharmacological mechanism behind it remains unclear. In this study, 73 compounds were identified using ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS), with 58 enrolled in network pharmacology. The protein‐protein interaction network, functional enrichment analysis, and compound‐target‐pathway network were constructed using 74 overlapping targets from 58 drugs and NSCLC. YFSJF has many targets and pathways in the fight against NSCLC. PIK3R1, PIK3CA, and AKT1 were identified as key targets, and the PI3K/AKT pathway was identified as the key pathway. According to the Human Protein Atlas (THPA) database and the Kaplan–Meier Online website, the three key targets had varying expression levels in normal and abnormal tissues and were linked to prognosis. Molecular docking and dynamics simulations verified that hub compounds have a strong affinity with three critical targets. This study revealed multiple compounds, targets, and pathways for YFSJF against NSCLC and suggested that YFSJF might inhibit PIK3R1, PIK3CA, and AKT1 to suppress the PI3K/AKT pathway and play its pharmacological role.
Fecal Microbiota Transplantation Research over the Past Decade: Current Status and Trends
Authors: Hao Shaodong , Yang Shanshan , Zhang Naiwei , Cheng Hongjie
Published: January 2023

Background. Fecal microbiota transplantation (FMT) is a current research hotspot, with a surge in the output of publications over the past decade. This study dedicates to the exploration of the research status and highlights significant themes and future trends in FMT research with the aid of bibliometric analysis. Methods. FMT publications from 2012 to 2021 were retrieved on August 12, 2022, using the SCI-Expanded of Web of Science (WoS). The Bibliometrix in R program, Microsoft Office Excel, VOSviewer, and CiteSpace were utilized for bibliometrics and visual analysis, revealing the main publications, journals, countries, agencies, authors, and keywords distribution in FMT research. Results. There were 2,931 papers included. FMT research presented a growing trend from 2012 to 2021. The countries with the most publications and contributions in FMT area were China and the United States. The high-yield institutions were Harvard University, Udice French Research Universities, and the University of California System. The primary authors were Nieuwdorp Max, Allegretti Jessica R, and Kassam Zain. Frontiers in Microbiology and Science were the top-ranked journals in publications and total citations, respectively. The important topics primarily included FMT-related mechanisms and the usage of FMT in Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disease, neurological disorders, and psychiatric disorders. Future research would primarily concentrate on neurological disorders, chemotherapy and immunotherapy for malignant tumors, and FMT-related consensus and guidelines. Conclusion. With the help of bibliometric analysis, we were able to obtain the understanding of the status and trends of global FMT-related research. The field of FMT is undergoing tremendous progress, and our findings can guide clinical researchers’ and practitioners’ future work in the rapidly evolving field of FMT.
Comparison of Pregnancy Outcomes of History‐Indicated and Ultrasound‐Indicated Cervical Cerclage: A Retrospective Cohort Study
Authors: Ikechebelu Joseph Ifeanyichukwu , Dim Cyril Chukwudi , Okpala Boniface Chukwuneme , Eleje George Uchenna , Joe-Ikechebelu Ngozi N. , Malachy Divinefavour Echezona , Nnoruka Chinedum Mark , Nwajiaku Louis Anayo , Okam Princeston Chukwuemeka , Albert Innocent Chigozie , Okpala Augusta Nkiruka , Igbodike Emeka Philip
Published: January 2023

Background. Cervical cerclage is the procedure of choice for preventing preterm delivery due to cervical insufficiency. The indication for its application may be based on the woman’s reproductive history, findings at ultrasound, or clinical findings on vaginal examination. Pregnancy outcomes from these indications are variable according to the available literature. Objective. To compare the effectiveness and reproductive outcomes (miscarriage, preterm birth rates, and birth weights) of McDonald’s cervical cerclage after history‐indicated and ultrasound‐indicated cervical cerclage in pregnant women. Methods. The retrospective cohort study was conducted at Life International Hospital Awka, Nigeria and Life Specialist Hospital Nnewi, Nigeria. Pregnant women, who had a McDonald’s cervical cerclage performed due to either history or ultrasound indication between January 1, 2011, and December 31, 2020, were included in the study. Women with multiple pregnancies and those with physical examination‐indicated or emergency cerclages were excluded. The main outcome measures included the prevalence of cervical cerclage, miscarriage, and preterm delivery rates. Outcomes were compared between groups with the chi‐square test, Fisher’s exact test, or Student’s t test. p value of < 0.5 was set as significant value. Results. Overall, during the study period, 5392 deliveries occurred in the study sites, of which 103 women had a history‐indicated or ultrasound‐indicated cervical cerclage. This resulted in a 1.91% prevalence rate for history‐indicated and ultrasound‐indicated cervical cerclage. Of these, 68 (66%) had history indicated, while 35 (34%) had ultrasound‐indicated cerclage. There was no difference in the sociodemographic characteristics of both groups. Both groups had similar miscarriage rates: 1.18 in 1000 and 1.04 in 1000 deliveries, respectively (RR 1.160, 95% CI: 0.3824 to 3.5186, p = 0.793). There was more preterm delivery in history‐indicated cerclage than ultrasound‐indicated cervical cerclage (26.50% vs. 17.10%; p = 0.292), though the difference was not statistically significant. The ultrasound group had a higher average birthweight than the history group (2.67 ± 0.99 vs. 2.53 ± 0.74). However, this difference was not statistically significant. Conclusion. The effectiveness and reproductive outcomes (miscarriage, preterm birth rates, and birth weights) of pregnant women with cervical cerclage due to history‐indicated and ultrasound‐indicated cervical cerclage appear similar. When needed, cervical cerclage should be freely applied for cervical insufficiency, irrespective of the type of indication.
Abstract A013: Patterns of heterolocalism among Chinese immigrants in Philadelphia
Authors: Batterson Ella , Tseng Marilyn , Walton Emily C. , Egleston Brian , Zhong Julia , Li Minzi , Fang Carolyn
Published: January 2023

Residence in an immigrant enclave has been linked to lower risk for some cancers but higher risk of late-stage diagnosis. In part, these patterns may be explained by the cultural, institutional, and social resources in immigrant enclaves that protect against ill health. Modern communication and transportation can facilitate “exposure” to immigrant enclaves as resource hubs, while individuals may reside in more racially integrated neighborhoods. This process of heterolocalism is underexplored in its relationship to cancer risk. The current study compares residents and non-residents of Chinese immigrant enclaves in Philadelphia with respect to distances traveled for various activities. Participants were 520 Chinese immigrant men and women aged 35-65 y. Interviews conducted 9/18-01/20 included questions on residence and usual locations of five types of activities: employment, grocery shopping, religious services, healthcare, and leisure. Participants were categorized as residing in a traditional (n=167), emerging (n=202), or non-enclave (n=151) neighborhood depending on the co-ethnic density of their census tract and adjacent tracts. We used ArcGIS to geocode participants’ residences and activity locations and conducted spatial analyses to examine distances traveled to these activities. Results indicated that residents of traditional enclaves stayed within or near their residential neighborhoods for grocery shopping, religious services, and leisure activities (median distances all <1 mi), although they traveled further for employment (median 2.5 mi) and healthcare (median 1.9 mi). Based on non-parametric Kruskal-Wallis tests, traditional enclave residents traveled the shortest median distances to all activities (all p<0.001). In contrast, non-enclave residents traveled the furthest for groceries (median 2.9 mi), religious services (median 8.2 mi), and leisure (median 3.2 mi) (all p<0.001). Mapped travel patterns indicate that many non-enclave residents travelled to enclave areas for these activities. Our findings suggest that heterolocalism is a means by which immigrants maintain co-ethnic connections. They also suggest the importance of understanding enclave ‘exposure’ beyond place of residence to clarify the relationships between immigrant enclaves and cancer outcomes.

Citation Format: Ella Batterson, Marilyn Tseng, Emily C. Walton, Brian Egleston, Julia Zhong, Minzi Li, Carolyn Fang. Patterns of heterolocalism among Chinese immigrants in Philadelphia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A013.
Abstract A039: Factors associated with reconstruction rates in breast cancer patients after mastectomy: Investigating disparities at a private versus safety net hospital
Authors: Norman Thomas , Hwang Lindsay , Ye Jason
Published: January 2023

Purpose: Despite post-mastectomy reconstruction being associated with improved body image, self-confidence, and quality of life, some evidence suggests that race, income, and insurance are associated with decreased rates of reconstruction. The purpose of this study was to evaluate the rates and factors associated with reconstruction after mastectomy at our institution’s private hospital (PH) and government safety net hospital (SNH). Methods: This retrospective study included 158 women (95 PH, 63 SNH) with unilateral, invasive, node-positive breast cancer who underwent surgery (mastectomy), chemotherapy, and radiotherapy in 2008–2019. We recorded age, race, preferred language, hospital, type of insurance, tumor features, and cancer treatment. Results: The median patient age was 52 (range, 27–83) years. Of the 158 patients, 60 underwent reconstruction: 52 (54.7%) at PH and 8 (12.7%) at SNH. Chi-squared tests identified age, race, language, insurance, and hospital as factors associated with reconstruction. In univariable regression analysis, these factors were associated with a higher odds of reconstruction: PPO insurance (OR 2.71, 95% CI 1.15–6.35) and treatment at PH (OR 10.48, 95% CI 4.71–23.32). Lower odds of reconstruction were associated with older age (age > 52 years: OR 0.47, 95% CI 0.25–0.87), Hispanic ethnicity (OR 0.22, 95% CI 0.10–0.50), Spanish as preferred language (OR 0.27, 95% CI 0.13–0.56), Medi-Cal HMO (OR 0.07, 95% CI 0.01–0.60), and being uninsured (OR 0.27, 95% CI 0.08–0.92). In multivariable analysis, only age remained significant: the odds of reconstruction were decreased in patients older than 52 years (OR 0.38, 95% CI 0.17–0.87). Conclusion: In women with unilateral, invasive, node-positive breast cancer, reconstruction after mastectomy was more frequent at our institution’s PH than at our SNH. Age, race, language, insurance, and hospital were associated with reconstruction after breast cancer resection in univariable analysis, but only age remained significantly associated with reconstruction in multivariable analysis. These results suggest that while demographic or socioeconomic factors may limit access to reconstruction after mastectomy, these factors are not as important as patient age.

Citation Format: Thomas Norman, Lindsay Hwang, Jason Ye. Factors associated with reconstruction rates in breast cancer patients after mastectomy: Investigating disparities at a private versus safety net hospital [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A039.
Abstract B034: Cancer Health Awareness through Screening and Education (CHANGE): Community health engagement
Authors: Vernon Marlo M. , Jones Samantha , Coughlin Steven , Moore Justin X. , Heboyan Vahe , Tingen Martha
Published: January 2023

Purpose The goal of the CHANGE project is to provide a sustainable model of evidence-based cancer awareness through education – with an emphasis on prevention and early detection behaviors. Methods: Residents of a public housing community were invited to participate in a 4-week education program on breast, prostate, and colorectal cancer, including modifiable risk factors of obesity and tobacco use, screening eligibility, and participation in clinical trials. Each session was led by trained research staff, and lasted approximately one hour. A community site survey was also conducted among 20% of the residents to evaluate community cancer knowledge and screening behaviors. A community advisory board was established to support program implementation and advise on choosing a cancer risk-reducing environmental change. Results: 14 adult participants (7 men and 7 women, 86% African American) completed baseline measurements. 10 participants received a relevant health history notification, which means they were positive for one of the following which put them in the "higher risk" category: Due for one of the following screenings Breast, Colorectal or Prostate; Had family history of cancer; Tobacco use; Overweight/obese - 1 male was referred to the GCC Tobacco Cessation Program. All eligible participants were navigated to local cancer screening providers and will be followed up at 3 months.Community site survey results indicated a need for improved access to fresh fruits and vegetable access. Community advisory board participants and community resources collaborated to provide locally grown fresh fruits and vegetables to the public housing community's internal market. 1 Discussion: This sample represents those most at risk for cancer in the Augusta, GA area. This project will impact health equity by emphasizing a comprehensive approach to care through community environmental change and individual changes in knowledge and risk-reducing behaviors. Additional sites will be enrolled in the program through the end of 2022.

Citation Format: Marlo M. Vernon, Samantha Jones, Steven Coughlin, Justin X. Moore, Vahe Heboyan, Martha Tingen. Cancer Health Awareness through Screening and Education (CHANGE): Community health engagement [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B034.
Abstract B037: Effective recruitment strategies utilized in the midst of a COVID-19 pandemic to examine dietary practices and colorectal cancer screening practices of Blacks in New York City
Authors: Johnson Cicely K. , Ma Grace X. , Leung May May , Ogunwobi Olorunseun O.
Published: January 2023

African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the U.S. Factors that may be contributing to these high rates, however, remain poorly understood. Specifically, this study assessed the relationship between dietary habits and colorectal cancer screening behavior and intent among individuals who identify as Black, with their ethnicity as African-American, Caribbean, and African. There are many factors that influence dietary habits, and a salient factor is culture. Many studies have experienced challenges recruiting in communities of color for various reasons. The purpose of this presentation is to describe recruitment methods utilized for this study in the midst of the COVID-19 pandemic, and to discuss challenges, strategies that were implemented and lessons learned that can inform and improve future recruitment efforts. Effective recruitment strategies included partnership, consistent engagement, and meeting people in places where they frequent and felt comfortable. Utilizing faith-based locations, barbershops, hair salons, and pivotal community locations allowed individuals to trust the researchers, and also eliminated the need to retain study subjects over a period of time, due to on-site data collection. Though our findings are limited to Black families in predominantly minority neighborhoods, we have identified successful strategies for this specific high-risk population and potentially similar others.

Citation Format: Cicely K. Johnson, Grace X. Ma, May May Leung, Olorunseun O. Ogunwobi. Effective recruitment strategies utilized in the midst of a COVID-19 pandemic to examine dietary practices and colorectal cancer screening practices of Blacks in New York City [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B037.
Abstract B074: Evaluating nursing knowledge and readiness in providing care for post-9/11 veterans in civilian healthcare settings: A quality improvement project
Authors: Simoni Chelsey , Ratliff Jack
Published: January 2023

Over three-million military service members deployed overseas in support of the post-9/11 Global War on Terror since 2001. Of those, 7,057 have been killed in action, 30,177 have committed suicide, 279,652 died from ill-defined and unknown medical causes, and 520,966 have been diagnosed with cancer. Post-9/11 veterans are 192.75% more likely to be diagnosed with cancer when compared to their civilian counterparts and are more likely to utilize civilian providers (75%) than the Department of Veterans Affairs for health care concerns. The purpose of this quality improvement project is to investigate the level of nurse knowledge, beliefs, and perceptions related to providing health care to post-9/11 veterans in civilian care settings. A descriptive project design with a 15-question survey was implemented. The survey was sent to registered nurses practicing in civilian care settings. A sample of 537 registered nurses practicing in civilian care settings responded. Findings included that 93% incorrectly chose mental health conditions as the most likely occurring condition in post-9/11 veterans, while 7% correctly chose medical illnesses as most prevalent. Nurse respondents reported a perceived prevalence of post-traumatic stress occurring more often than cancer and malignancies at a ratio of 19:1. These findings highlight the high potential for cognitive biases which may lead to misdiagnoses and delayed diagnoses in post-9/11 veterans presenting for care with medical symptoms, furthering the need for education. This quality improvement project revealed significant gaps in civilian nurses’ clinical knowledge in screening, assessing, identifying, treating, and recommending resources for post-9/11 veterans and medical-related conditions.

Citation Format: Chelsey Simoni, Jack Ratliff. Evaluating nursing knowledge and readiness in providing care for post-9/11 veterans in civilian healthcare settings: A quality improvement project [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B074.
Abstract B082: Collaboration strategies to involve Black women’s perspectives in community engaged breast cancer research
Authors: Edmonds Megan C.
Published: January 2023

Purpose: While advancements in treatment and genomic research in breast cancer are on the rise, breast cancer (BC) disparities continue to widen. Black women disproportionately have the worst prognosis and survival rates from BC compared to all racial/ethnic groups of women. Community engagement and dissemination of disparities focused research may help mitigate poor outcomes among Black women. The goal of this study was to build sustainable research-partnerships with community-based organizations to promote guideline concordant breast cancer surveillance behaviors among Black breast cancer survivors. Methods: Several partnerships were formed to conduct breast cancer research among Black women. Community building and communication tools were developed and evaluated to help shape and sustain meaningful research working relationships with breast cancer focused community organizations. Results: Partnerships were commonly established from shared goals and missions. Frequent communication and strength-based activities were key tenants in developing impactful partnerships and research initiatives. From these partnerships a breast cancer campaign, web-based communication platform and rich secondary and qualitative data were collected from a community cohort of Black and White breast cancer survivors (N=266). Conclusion: Communication tools, iterative goal settings and community engaged approaches were essential in launching several research initiatives and outreach to Black women. To date our collaboration practices have resulted in novel and increased recruitment efforts that provide implications for research participation from Black women.

Citation Format: Megan C. Edmonds. Collaboration strategies to involve Black women’s perspectives in community engaged breast cancer research [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B082.
Abstract B109: Depression is a risk factor for noncompliance with antiviral medication treatment among Asian Americans with chronic hepatitis B
Authors: Zhu Di , Bracy Danny , Lu Wenyue , Zhu Lin , Handorf Elizabeth , Tan Yin , Yeh Ming-chin , Nguyen Minhhuyen T. , Ma Grace X.
Published: January 2023

Introduction: Asian Americans is a Hepatitis B (HBV) disparity population who only account for 6% of the US population but experience a 60% burden of having HBV, which is associated with 75% of hepatocellular carcinoma (HCC). Adherence to HBV medication is a practical approach to prevent liver cancer. However, limited studies have been conducted on the impacts of depression on HBV medication adherence among underserved Asian American HBV patients. Methods: This study utilized 12-m follow up data from a randomized controlled clinical trial aimed at improving long-term adherence to HBV medication adherence. Eligible Asian American HBV patients were recruited from the Greater Philadelphia Area and New York City. HBV medication adherence was assessed using the 8-Item Morisky Medication Adherence Scale (MMAS-8), and depression was measured with Patient Health Questionnaire-9 (PHQ-9). We conducted OLS regression to examine the association between depression and medication adherence among participants who reported that they were taking antiviral medication for their chronic hepatitis B condition. Results: Among 154 participants (118 Chinese and 36 Vietnamese), 43.57% were female, and 56.49% were male. Nearly all the participants reported having health insurance (92.21%) and having a physician to visit regularly (95.21%). Bivariate analysis showed that depression was negatively significantly associated with medication adherence score (r=-0.55, p<0.001). Multivariable analysis revealed that a higher level of depressive symptoms at baseline significantly predicted poor medication adherence (log odds: -0.16, 95% CI: 4.02-6.89), with other covariates controlled for. In addition, study arm and ethnicity were significant predictors of medical adherence as well. Conclusion: The findings suggest that depression level has significant impacts on medication adherence. This indicates the need for mental health monitoring for CHB patients on antiviral. There are needs for culturally sensitive clinical and community interventions to improve mental health status and medication adherence among this vulnerable population. In addition, we will discuss the successes and challenges in the participant recruitment and intervention implementation process of this study.

Citation Format: Di Zhu, Danny Bracy, Wenyue Lu, Lin Zhu, Elizabeth Handorf, Yin Tan, Ming-chin Yeh, Minhhuyen T. Nguyen, Grace X. Ma. Depression is a risk factor for noncompliance with antiviral medication treatment among Asian Americans with chronic hepatitis B [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B109.
Abstract C005: Social determinants and environmental exposures and their localized contribution to risk of cancer mortality
Authors: McCormack Kara
Published: January 2023

When considering environmental exposures and/or social determinants of health (SDOH), data are typically available by counties, zip codes or census tracts. We consider two quantitative challenges in this setting when modeling cancer outcomes. The first is that multiple, potentially highly correlated exposures may contribute to risk. The second is that the spatial correlation of such features may not follow the original models designed for disease risk mapping. While several conditional autoregressive (CAR) models are typically utilized (Besag et al. (1991), Leroux et al. (1999), Stern and Cressie (1999)), a critical drawback is that they impose a global level of autocorrelation across the study area, presuming areas nearest each other are most similar. Spatial data may actually include step changes in the risk surface, indicative of more complex patterns either due to physical barriers and/or social isolation. Thus, identifying these step changes is of interest, as they may reflect the underlying complexity of the relationship between environmental exposures, SDOH and cancer mortality. We consider a two-step model to explore how clusters of environmental exposures and SDOH may be able to identify boundaries in the risk surface of cancer outcomes. In the first step, we estimate clusters of exposures using Bayesian profile regression, a nonparametric approach based on Dirichlet process mixture methods. In the second step, we model cancer mortality using locally adaptive spatial smoothing with the clusters as dissimilarity metrics (Lee and Mitchell, 2012). Several diagnostic tools are used to assess convergence in each step. With this work, we bridge the gap between incorporating mixtures of correlated exposures with the identification of localized areas with elevated risk of cancer mortality. We apply this approach to a nationwide database of county-level breast cancer mortality, utilize environmental exposure data from the National Air Toxics Assessment and assess SDOH from the American Community Survey.

Citation Format: Kara McCormack. Social determinants and environmental exposures and their localized contribution to risk of cancer mortality [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C005.
Abstract C024: Study of therapeutic effects of polyisoprenylated cysteinyl amide inhibitors on lung cancer cells of Black American patients using 3D-printed alveolar models
Authors: Belony Nadine L. , Ren Bing , Pham Phuc , Gregory Matthew , Puente Pablo E. , Lamango Nazarius S. , Offringa Ite A. , Huang Yong
Published: January 2023

Lung cancer is one of the top five deadliest cancers, and Black Americans have a higher mortality rate when compared to White Americans. Lung adenocarcinoma (LUAD) is the most common histological lung cancer subtype in all population groups including Blacks. Unfortunately, there are no in vitro model systems to study lung cancer and its treatments for Black subjects. Herein we aim to utilize three-dimensional (3D) printing to develop an in vitro three-dimensional (3D) alveolar model using a lung adenocarcinoma cell line from a Black patient (NCI-H23). The developed model is further utilized to study the therapeutic effects of potential LUAD therapeutic agents, polyisoprenylated cysteinyl amide inhibitors (PCAIs), which target and disrupt the RAS-mediated signaling pathway. KRAS is the most commonly mutated oncogene in LUAD in Blacks, and is mutated in NCI-H23 cells. For comparison, hAEC-FT-C7 cells, which are immortalized human alveolar epithelial cells and do not carry the KRAS mutation, will also be used separately to print the alveolar models and test the effects of PCAIs. The experimental results will be further compared to those using two-dimensional (2D) models to better understand the therapeutic effects of PCAIs on Black LUAD. The resulting knowledge will help design better treatments for ethnically/racially diverse patients in whom the RAS signaling pathway is frequently altered.

Citation Format: Nadine L. Belony, Bing Ren, Phuc Pham, Matthew Gregory, Pablo E. Puente, Nazarius S. Lamango, Ite A. Offringa, Yong Huang. Study of therapeutic effects of polyisoprenylated cysteinyl amide inhibitors on lung cancer cells of Black American patients using 3D-printed alveolar models [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C024.
Abstract C041: FAN1 splice variant as a possible risk variant for African American hereditary breast cancer and understanding its role in tumorigenesis
Authors: Glover Sheniqua R. , Sams Cierla McGuire , Bishop Madison , LoBue Troy , Mcneely Issac , Merner Nancy D.
Published: January 2023

Recognizing African American health and research disparities, there is a need to better understand African American breast cancer risk. Our group has established the Alabama Hereditary Cancer Cohort to aid in identifying risk variants associated with African American hereditary breast cancer. We have identified several suspected risk variants using next-generation sequencing technologies, including a low-frequency African American-specific splicing variant in FANCD2/FANCI-associated nuclease 1 (FAN1). FAN1 is an exo/endonuclease involved in DNA inter-strand crosslinking repair. There has been speculation that FAN1 could be a breast cancer susceptibility gene because FAN1 is in the Fanconi Anemia pathway with known breast cancer susceptibility genes, BRCA1 and BRCA2. This splicing variant, FAN1 c.3057+1G>A, does not interfere with the coded protein, but alters the donor splice site of exon 14, adding 34 bases to the beginning of the 3’ untranslated region. Interestingly, it has an allele frequency of 3.6% in the general African American population but was found in 5.1% of African American breast cancer cases in the Alabama Hereditary Cancer Cohort. Extremely rare in European Americans overall; it was not detected in any European American breast cancer cases. Functionalizing FAN1 c.3057+1G>A and other identified mutations is important to demonstrate pathogenicity. Our group uses prime editing to introduce variants of interest into selected cell lines. Prime editing is an innovative gene-editing technique that can introduce base substitutions, insertions, and deletions into the genome without the need for double-stranded DNA breaks or donor DNA. Upon gene-editing, cell proliferation, invasion, migration, and other cellular characteristics that contribute to tumorigenesis are investigated. Overall, it is imperative to identify African-American breast cancer risk variants and understand how they play a role in disease pathogenesis, leading to better risk assessment and novel therapeutics.

Citation Format: Sheniqua R. Glover, Cierla McGuire Sams, Madison Bishop, Troy LoBue, Issac Mcneely, Nancy D. Merner. FAN1 splice variant as a possible risk variant for African American hereditary breast cancer and understanding its role in tumorigenesis [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C041.
Abstract C044: A case and control genetic profile of tissue and serum in African American men
Authors: Harlemon Maxine S. , Bollag Roni , Terris Martha , Millena Ana Cecilia , Bowen Nathan , Odero-Marah Valerie
Published: January 2023

Prostate cancer is the most common non-cutaneous cancer among men. A man with 1,2 or 3 first degree relatives with prostate cancer, has a 2,5, and 11-fold increased risk of developing prostate cancer. The heritability rate of prostate cancer is 58%. African American men have the highest incidence and mortality rate of prostate cancer in American. Men of African descent, globally, are more likely to die from prostate cancer than any other ancestral groups. We performed Immunohistochemistry(IHC) and RNA seq analysis on African American tissue and serum samples, with a focus on HMGA2, which has been shown promote EMT, invasion, and metastasis in cancer. Acknowledgements: These studies were supported by NIH/NIMHD U54MD007590 and U54MD013376. Our sample set included 3 benign and 2 prostate cancer tumors from African Americans. IHC markers showed HMGA2 staining within epithelial cells of the prostate cancer tissue. This result validates studies that show that distinct subtypes of prostate cancer may arise from luminal and basal epithelial cell types. RNA seq results showed HMGA to be non-significantly down-regulated in tumor samples. The most differentially expressed (DE) gene, however, was SNORD116-18. Studies have shown SNORD116-18 expression to be associated with chronic lymphocytic leukemia in distinguishing prognostic groups. This finding may be a pathway of interest for further studies. RNA seq of serum gave homogeneous results, however, gene set enrichment analysis of the most differentially expressed genes within the serum showed overlap with inflammation pathways gene for upregulated DE genes and Methylation Pathway for downregulated DE genes. Further analysis on more samples from African Americans tissue and serum will be used to validate findings.

Citation Format: Maxine S. Harlemon, Roni Bollag, Martha Terris, Ana Cecilia Millena, Nathan Bowen, Valerie Odero-Marah. A case and control genetic profile of tissue and serum in African American men [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C044.
Abstract C049: Investigating cancer racial disparities through TCGA transcriptomic and proteomic database
Authors: Lei Brian , Saxena Anjana
Published: January 2023

In the United States, epidemiological studies have highlighted a disparity in cancer incidence and outcome rates between racial groups. This disparity is attributed to numerous factors, including gene polymorphisms, differences in lifestyle and environmental exposures, and socioeconomic factors. Although an abundance of tumor molecular data exists, the effect of race on gene expression signatures often remains unexplored. In this project, we investigated racial molecular differences in tumors of 10 carcinoma types. We used publicly available data from The Cancer Genome Atlas (TCGA) in conjunction with online analysis tools to identify patterns of differential gene expression in tumors obtained from 4,112 White, Black/African American, and Asian patients. We identified race-dependent expression of numerous genes whose mRNA transcript levels were significantly correlated with patient survival outcomes. A small subset of these genes was differentially expressed in multiple carcinomas, including genes involved in cell cycle progression such as CCNB1, CCNE1, CCNE2, and FOXM1. This suggests that cell cycle dysregulation is a major culprit in the health disparity. In contrast, genes such as transcriptional factor ETS1 and apoptotic gene BAK1 were differentially expressed and clinically significant only in specific cancer types. In numerous cancer types we also observed race-dependent regulation of cancer-relevant biological pathways, especially DNA repair mechanisms. This large-scale pan-cancer study refines our understanding of the molecular basis for the cancer racial health disparity and can help inform the use of novel biomarkers in clinical settings as well as the future development of precision therapies.

Citation Format: Brian Lei, Anjana Saxena. Investigating cancer racial disparities through TCGA transcriptomic and proteomic database [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C049.
Abstract C060: Investigating the clinical relevance in prostate cancer of the serum biomarkers PVT1 exons 4A, 4B and 9 across risk levels and ethnicity/race
Authors: Levine Fayola , Asante-Asamani Emmanuel , Pal Gargi , Liss Michael , Ogunwobi Olorunseun
Published: January 2023

Chromosome 8q24 is of particular importance for cancer susceptibility. Located in this region is the Plasmacytoma Variant Translocation 1 (PVT1) gene, a long noncoding RNA that has been implicated in multiple cancers including prostate cancer. Amplification of the PVT1 gene locus is a common event in many malignant diseases and is associated with poor clinical outcomes. The pioneering role of PVT1, and its alternatively spliced transcripts, as a cancer biomarker is progressively becoming established. We have demonstrated that copy numbers of PVT1 exons 4A, 4B and 9 is quantifiable in cancer cells, tissue, and serum from cancer patients. In this study, we assessed clinically annotated serum samples from 40 prostate cancer patients to investigate the clinical relevance of PVT1 exons 4A, 4B, and 9 as a biomarker across cancer risk levels and ethnicity/race. Explorative data analysis for the development of composite score for prostate cancer was performed using Kruskal-Wallis Rank Sum Test. We observed significantly higher copy numbers of PVT1 exons 4B and 9 across all races (White, Black and Hispanic) and Blacks and Hispanics when compared to the control. Additionally, using a 3-level cancer risk rating assessment in which 0 = healthy, 1 = low risk and 2 = high risk, we observed that PVT1 exon 9 may distinguish between cancerous and noncancerous cases across all races, but may not help distinguish between indolent and aggressive cancer cases. Notably, PVT1 exon 4B may help distinguish between indolent and aggressive cancer cases for Blacks and Hispanics. The results of this study suggest that using PVT1 exon 4B or 9 may identify cancer regardless of ethnicity/race, and that utilization of serum PVT1 exon 4B copy number may help distinguish between indolent and aggressive prostate cancer in Blacks and Hispanics.

Citation Format: Fayola Levine, Emmanuel Asante-Asamani, Gargi Pal, Michael Liss, Olorunseun Ogunwobi. Investigating the clinical relevance in prostate cancer of the serum biomarkers PVT1 exons 4A, 4B and 9 across risk levels and ethnicity/race [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C060.
Abstract C065: Kinesin family member C1 (KIFC1/HSET) underlies aggressive disease course in androgen receptor-low triple negative breast cancers
Authors: Wright Nikita , Yate-Ching Yuan , Talisman Tijana , Natarajan Rama , LaBarge Mark , Rida Padmashree , Seewaldt Victoria
Published: January 2023

Quadruple negative breast cancer (QNBC), which refers to triple negative breast cancers (TNBCs) lacking androgen receptor (AR) expression, is now considered to be a highly aggressive BC subtype, with no actionable therapeutic targets. QNBC disproportionately afflicts and impacts patients of African descent. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs, compared to non-TNBCs and European-American (EA) TNBCs. Herein, we analyzed KIFC1 mRNA levels and their associations with clinical features and outcomes among AR-low and AR-high TNBC patients in three distinct publicly-available gene expression datasets and the Breast cancer gene expression database (bc-GenExMiner). We discovered that KIFC1 levels were significantly higher (p<0.05) in AR-low and basal-like TNBCs compared to AR-high and luminal androgen receptor TNBCs, irrespective of stage, grade, tumor size, and lymph node status. We also observed that KIFC1 levels were upregulated in AR-low versus AR-high black and premenopausal TNBC patients (p<0.05). Furthermore, AR levels negatively correlated with KIFC1 levels among TNBC and basal-like TNBC patients (p<0.0001). High KIFC1 levels conferred significantly shorter overall survival (OS), disease-free survival, and distant metastasis-free survival among AR-low and basal-like TNBC patients in Kaplan-Meier analyses (p<0.05). In conclusion, KIFC1 levels may be upregulated in QNBCs and specifically QNBCs of African descent, wherein it may promote poorer outcomes. In addition, therapeutically targeting KIFC1 in these patient subpopulations could significantly mitigate racial disparities in TNBC outcomes.

Citation Format: Nikita Wright, Yuan Yate-Ching, Tijana Talisman, Rama Natarajan, Mark LaBarge, Padmashree Rida, Victoria Seewaldt. Kinesin family member C1 (KIFC1/HSET) underlies aggressive disease course in androgen receptor-low triple negative breast cancers [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C065.
Abstract C107: Racial differences in associations between chemical exposures and cancer-specific mortality
Authors: Nguyen Vy K. , Patel Chirag J. , Jolliet Olivier , Colacino Justin
Published: January 2023

We lack knowledge of environmental drivers (e.g. chemical exposures) of cancer mortality, which is most often due to the development of metastatic disease. Thus, there is a need to identify associations between chemical exposures and cancer mortality to help prioritize chemicals for further toxicological and epidemiological studies. We aimed to characterize how the associations between chemical biomarker levels and cancer-specific mortality differ by race/ethnicity to identify which concentrations are associated with increased risk for cancer death for each race/ethnicity. We studied 241 toxicant biomarkers in 35,132 participants sampled from the US CDC National Health and Nutrition Examination Survey 1999-2014. We deployed a series of Cox proportional hazard models with mortality status for cancer and time to death as the outcome variables and the chemical concentrations as the main predictor for each race/ethnicity. We adjusted for covariates such as age, sex, poverty income ratio, smoking, and comorbidity. For non-Hispanic Black participants, we found that an increase of one standard deviation in methyl paraben, a compound used in personal care product, is associated with a 60% increase in risk for cancer death (FDR-adjusted p-value = 4.22E-04). In addition, increased levels of lead and cadmium are associated with increased cancer mortality risk. The hazard ratio for an increase in one standard deviation of lead is 1.21 (FDR-adjusted value = 7.16E-06) in non-Hispanic Blacks and is 1.14 (FDR-adjusted p-value = 5.71E-04) in non-Hispanic Whites. The hazard ratio for cadmium is 1.37 (FDR-adjusted value = 3.06E-06) in non-Hispanic Blacks and is 1.26 (FDR-adjusted p-value = 9.23E-07) in non-Hispanic Whites. According to the International Agency for Research on Cancer (IARC) and the US National Toxicology Program (NTP), cadmium is a known carcinogen, and lead is a probable carcinogen. Methyl paraben is not even listed as a probable or known carcinogen but shows higher cancer mortality risk compared to those of lead and cadmium. In addition, the effect of methyl paraben on cancer have not been well studied. Thus, our methodology can help identify chemical contributors to cancer mortality for further mechanistic evaluation.

Citation Format: Vy K. Nguyen, Chirag J. Patel, Olivier Jolliet, Justin Colacino. Racial differences in associations between chemical exposures and cancer-specific mortality [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C107.