bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 767: The role of abdominal obesity in the association between obesity and prostate cancer: A U.S. population-based cross-sectional study NHANES 2001-2020
Authors: Ahmed Anwar E. , Martin Callista B. , Dahman Bassam , Kern Sean Q. , Chesnut Gregory T. 
Published: March 2024

Abstract
Background: Research suggests inconsistent evidence regarding the association between general obesity and prostate cancer among men in the United States. This study aimed to examine whether the association between general obesity and prostate cancer is influenced by abdominal obesity.
Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), 2001-2020, a nationally representative survey. The analysis was restricted to 16,703 non-Hispanic men (10,683 White and 6,020 Black). General obesity was defined by a body mass index of 30 kg/m2 or greater and abdominal obesity was defined by a waist circumference of 102 cm or greater. Respondents were classified into four mutually exclusive groups according to the body fat indicators: 1) presence of both general and abdominal obesity, 2) abdominal obesity without general obesity, 3) general obesity without abdominal obesity, and 4) none of the two (the reference group).
Results: The overall prevalence of prostate cancer was 2.25% (95% CI: 2.0-2.5%). Men with abdominal obesity without general obesity have significantly higher prevalence of prostate cancer (4.28%) compared to men with both abdominal obesity and general obesity (2.23%), men with neither abdominal obesity or general obesity (1.70%), and men with general obesity without abdominal obesity (0.18%), P &lt;.0001. Black men with abdominal obesity without general obesity have the highest prevalence of prostate cancer (7.21%), followed by White men with abdominal obesity without general obesity (4.10%). With and without adjusting for age and education, men with abdominal obesity without general obesity had significantly higher odds of prostate cancer, regardless of ethnicity. Black men with both abdominal obesity and general obesity had significantly higher odds of prostate cancer. General obesity without abdominal obesity was inversely associated with prostate cancer in White men but not in Black men.
Conclusions: This study illustrates that waist circumference is a potential classifier of prostate cancer as it shows variation in prevalence of prostate cancer by general obesity within the same and different racial and ethnic groups.
Citation Format: Anwar E. Ahmed, Callista B. Martin, Bassam Dahman, Sean Q. Kern, Gregory T. Chesnut. The role of abdominal obesity in the association between obesity and prostate cancer: A U.S. population-based cross-sectional study NHANES 2001-2020 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 767.
Abstract 770: The innate immune system response to malignancy- under the radar
Authors: Tobi Martin , Talwar Harvinder , McVicker Benita 
Published: March 2024

Abstract
It has become clear that many cancers evade detection by, for example, silencing of immune checkpoints. Re-activation of the immune armamentarium by checkpoint inhibitors has improved survival in many types of cancer. However, we still are unable to gauge the response of the innate immune system (InImS) to incipient malignancy. The InImS is likely both a sentient early warning system and an immediately deployed cancer combatant. We describe a potential marker that quantifies the innate immune system response to multiple deadly tumors. Methods: We obtained a database of patients at high risk of colorectal neoplasia and prospectively noted those who contracted cancer on follow up. We contrasted the historic, premorbid biomarker response from the time of enrolment, primarily using the FERAD ratio. This was obtained by dividing the ferritin blood concentration by the denominator of fecal shedding of a Paneth cell marker, p87. We also compared the FERAD response to the absolute neutrophil:lymphocyte ratio (NLR), a known prognostic biomarker, and also the available, known PDL-1 response for each group of cancers. Results: We found that certain groups of cancers historically had very low FERAD ratios while others were high. Using FERAD ratios for lung, gastric, non-Hodgkin’s lymphoma, melanoma, thyroid, renal, and head and neck cancers, there is a significant inverse correlation between survival and FERAD (r=-0.8;p&lt;0.025) which is similar to that of NLR (r=-0.7;p&lt;0.035). For prostate cancer, breast, colorectal cancer (CRC), leukemia/MDS, there is a direct correlation between survival and FERAD (r=0.99;p&lt;0.002). There is also an inverse relationship between NLR and PDL-1 response rates (r=-0.8;p&lt;0.04). An observed mild positive trend for FERAD PDL-1 response rates may bode well for melanoma, lung, head and neck and renal cancers. Conclusions: Since p87 could be manipulated by dietary means to affect the FERAD ratio favorably, this could be incorporated into more effective chemotherapy regimens and result in better cancer treatment outcomes. Hepatocellular cancer (HCC) and CRC-liver metastasis appear to be immunological outliers. This will need an additional unique approach such as TIGIT intervention therapy (Zheng et al.. Immune checkpoint targeting TIGIT in HCC. Am J Transl Res. 2020). This may allow modulation of the immune response based on FERAD, NLR ratios, and other considerations of mutational burden and genetic mutations, in patients with selected cancers.
Citation Format: Martin Tobi, Harvinder Talwar, Benita McVicker. The innate immune system response to malignancy- under the radar [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 770.
Abstract 777: Notch signaling dependent chemoresistance in racial disparity in ER+ breast cancer
Authors: Singh Shailesh , Das Megha , Chakrabarti Rumela 
Published: March 2024

Abstract
Breast cancer (BCa) is the leading cause of cancer related death in women worldwide. The most common BCa subtype is the Estrogen/Progesterone receptor (ER+/PR+) luminal subtype, comprising up to 75% of all newly diagnosed BCa. Although these patients show initial benefit with chemotherapy and endocrine therapy, however, 40-50% of them eventually don’t respond to treatment due to resistance. Thus, the need for additional targeted therapies for this large subset of ER+ BCa patients is critical. Based on recent studies, it is observed that Afro-American (AA) patients experience substantially higher BCa mortality (40% more) than White American (WA) women in ER+ breast cancer. Unfortunately, the cause behind this difference in mortality in AA patients is not well understood. Notch signaling is a highly conserved intercellular communication mechanism critical for many cellular processes and is composed of several receptors and ligands. Recent data show that Notch receptors are overexpressed in hormone treatment refractory ER− patients of (Afro-American) AA origin, hinting connection of Notch signaling to racial disparity in breast cancer. Notch signaling is also identified in several metabolic disorders involving fatty acids and other lipids. However, function of Notch signaling in context of chemoresistance in AA ER+ breast cancer is still unknown. Using single cell sequencing, we found that chemo-resistant AA ER+ breast cancer patient samples have a distinct Notch signature enriched subpopulations in tumor cells, which was missing in WA patients. Notch signaling happens through juxtacrine signaling of ligand/receptor signaling. Further analysis in tumor microenvironment shows lipid enriched tumor associated macrophages, which are Notch dependent, suggesting potential crosstalk between lipid heavy tumor-macrophages and tumor cells, which may drive the chemoresistance in AA patients. Further analysis using patient derived explants, an attractive new tool for drug efficacy testing in ex vivo, we found that chemotherapy itself increases Notch signaling in the tumors. Ongoing studies involving scRNAseq, untargeted lipidomics and chemo-resistant PDE will delineate the precise mechanism of action between tumor cells and tumor associated lipid heavy macrophages in context of Notch signaling in chemo-resistant AA ER+ breast cancer.
Citation Format: Shailesh Singh, Megha Das, Rumela Chakrabarti. Notch signaling dependent chemoresistance in racial disparity in ER+ breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 777.
Abstract 842: Maize consumption and circulating aflatoxin B1 levels in Mexican adults
Authors: Lajous Martin , Solis-Martinez Obed , Monge Adriana , Groopman John , McGlynn Katherine A. , Romero Martin , Batis Carolina , Lamadrid-Figeuroa Hector , Riojas-Rodriguez Horacio 
Published: March 2024

Abstract
Objective: To estimate the impact of maize consumption on aflatoxin B1 [AFB1] levels, a potent carcinogen, in Mexican adults living in south and eastern Mexico.
Methods: Study participants were women and men ≥40 years of age living in five high hepatocellular carcinoma burden states who participated in Mexico’s 2018 National Health and Nutrition Survey, a stratified, multi-stage, and cluster survey probability sampling household survey that is representative of the Mexican population. We estimated the consumption of maize intake in grams per day using a previously validated semi-quantitative food frequency questionnaire with a time reference of the previous seven days. We determined circulating AFB1-albumin lysine adduct [AFB1-lys] levels in serum using liquid chromatography. Guided by subject-matter knowledge we fit multivariable linear regression models that considered the survey design and included age, sex, residence, ethnicity, education, socioeconomic status, and foods known to be contaminated with aflatoxins including peanuts, rice, dried chili, milk, and cheese.
Results: Among the 915 participants, median maize consumption was 307 grams per day [Q1-Q3: 165 - 554]. Maize tortillas contributed 80% of the total maize consumption. The median maize tortillas consumption was 252 grams per day [Q1-Q3: 120 - 462], approximately 8 tortillas per day. Prevalence of AFB1-lys detection was 92% and median levels were 0.127 pg/µL [Q1-Q3: 0.052 - 0.449]. After adjusting for factors that may affect aflatoxin levels, for every 100 grams of maize consumption AFB1-lys levels were 7.4% [β: 0.071, 95% CI: 0.030 - 0.112] higher. And for every tortilla consumed [30 g of maize], we observed a 2.0% [β: 0.020, 95% CI: 0.006 - 0.034] higher level of circulating AFB1-lys.
Conclusion: These findings indicate that maize and maize tortillas may be an important source of AFB1 exposure in the Mexican population. Mexico requires effective public health interventions to mitigate exposure to AFB1.
Citation Format: Martin Lajous, Obed Solis-Martinez, Adriana Monge, John Groopman, Katherine A. McGlynn, Martin Romero, Carolina Batis, Hector Lamadrid-Figeuroa, Horacio Riojas-Rodriguez. Maize consumption and circulating aflatoxin B1 levels in Mexican adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 842.
Abstract 85: Immunomics of immune-deficient mouse models before and after CD34 humanization
Authors: Luche Hervé , Hadjem Lilia , Mello Marielle , Canavese Priscilla , Angelis Fabien , Joachim Anais , Bouilly Sylvie , Guinut Frédéric , Fiore Frederic , Malissen Bernard , Zarubica Ana , Corcuff Erwan 
Published: March 2024

Abstract
Preclinical tumor oncology research relies historically on the analysis of mouse or human tumor cell lines implanted onto severely immune-deficient mouse models carrying nude, SCID or Rag mutations on different genetical background (C57Bl/6N, BalbC, NMRI, CB17 or NOD). These lines harbor defects in several leukocyte lineages among which Tc, Bc and NKc might be affected. Humanized mice are emerging models that have been transplanted with human cells or tissues (and/or equipped with human transgenes). Currently, the most advanced strains are the nonobese diabetic, severe combined immunodeficiency (NOD-SCID) mouse with complete disruptions in the interleukin-2 (IL-2) common γ-chain (IL2R γ null) receptor (NSG) and BALB/c Rag2−/− IL2R γ null SirpaNOD mice (BRGS).1 Neonate or juvenile chimera are reconstituted in NSG, BRGS or B6 RGS with CD34+ hematopoietic progenitor cell (HPCs) from human cord blood yielding robust engraftment of a human immune system (HIS).. We genetically modified the mouse genome introducing mutations involved in Tc, Bc and NKc development. We then immuno-phenotyped over 23 lines of mouse mutants produced from the same animal house to minimize the impact of microbiota on innate immune cell populations. High content cytometry analysis of several organs was performed in a standardized manner before and after humanization. The resource obtained of these immunotypes was used to highlight similarities and differences among these lines across several genetical background and will help in selecting the most appropriate model to use for tumor implantation and CD34 or PBMC humanization.
Citation Format: Hervé Luche, Lilia Hadjem, Marielle Mello, Priscilla Canavese, Fabien Angelis, Anais Joachim, Sylvie Bouilly, Frédéric Guinut, Frederic Fiore, Bernard Malissen, Ana Zarubica, Erwan Corcuff. Immunomics of immune-deficient mouse models before and after CD34 humanization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 85.
Abstract 852: Measuring the level of knowledge and awareness about radon in Northeast Tennessee
Authors: Al ksir Kawther , Stanifer Stacy , Quinn Megan , Mamudu Hadii , Slawson Deborah 
Published: March 2024

Abstract
Introduction: Radon, a radioactive gas found in soil and rocks, is the second leading cause of lung cancer in the United States (1). Despite its significant health risks, radon awareness and knowledge remain low (2). In Tennessee, where geological factors contribute to elevated radon levels, understanding the levels of awareness and knowledge about radon is crucial (3). This study focuses on Northeast Tennessee, an area known for its high radon concentrations.
Methods: This cross-sectional study, conducted from September to November 2023, aims to assess radon awareness and knowledge among participants from seven Northeast Tennessee health councils. These councils play a critical role in public health initiatives and provide access to individuals actively involved in health-related discussions. A convenience sample of 150 participants was chosen from an email listserv of 650 health council members. Participants, aged 18 or older, affiliated with the health councils in the study area, and physically present in the US, were eligible to participate. Demographic data, radon knowledge and awareness were assessed. Additional questions evaluated information sources, concern levels, and willingness to inform the community about radon.
Conclusion: This research addresses a significant knowledge gap regarding radon awareness and knowledge in Northeast Tennessee, an area with unique geological factors that elevate radon exposure risks. The study's findings will contribute to the development of targeted educational campaigns and interventions, ultimately promoting awareness and proactive measures to mitigate radon exposure in the region. With the potential to inform policy and public health efforts, this study holds the promise of reducing the health risks associated with radon in Northeast Tennessee.
Citation Format: Kawther Al ksir, Stacy Stanifer, Megan Quinn, Hadii Mamudu, Deborah Slawson. Measuring the level of knowledge and awareness about radon in Northeast Tennessee [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 852.
Abstract 858: A functional atlas of cancer mutation-rewired protein interactome networks
Authors: Agrawal Anjali , McGrail Daniel , Sahni Nidhi , Yi S. Stephen 
Published: March 2024

Abstract
Somatic mutations in cancer can exert effects on protein-protein interactions (PPIs), leaving some wild-type (WT) interactions perturbed while others unperturbed. The type of PPI perturbations can be used to link the mutation to its phenotypic effects. Here, we apply a technique known as functional variomics to characterize PPI profile changes for around 1,000 cancer missense mutations. Remarkably, our results reveal 5 distinct classes (edgotypes) of mutations: mutations losing PPIs compared to WT (edgetic), gaining PPIs (gain), gaining & losing PPIs (gain/loss), losing all PPIs (quasi-null), and those that do not perturb PPIs (quasi-WT). Notably, gastroenterological cancers have a greater proportion of edgetic mutations, whereas reproductive cancers have a greater proportion of gain edgotype mutations, demonstrating the link between edgotype and cancer type. We further show that more severe cancer stages are associated with interaction-perturbing mutation edgotypes, and the gain/loss edgotype is the most deleterious of all. In addition, pathway enrichment analysis suggests that the edgotypes are predictive of biological effects. For example, mutation edgotypes with loss of interactions are involved in apoptotic process and DNA damage repair, consistent with the expected loss of such functions in cancer. Meanwhile, gain edgotype is linked with cell division and G2/M transition. To our knowledge, this represents the first attempt to perform systematic interactome profiling for cancer mutations. As our results can reveal specific phenotypic attributes and biological functions that are altered for different PPI profiles, our functional platform is important for cancer precision medicine. Our study strengthens the link between genotypes and phenotypes while illustrating the significance of edgotypes in complex disease modeling.
Citation Format: Anjali Agrawal, Daniel McGrail, Nidhi Sahni, S. Stephen Yi. A functional atlas of cancer mutation-rewired protein interactome networks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 858.
Abstract 897: Synthetic lethality screening with Recursive Feature Machines
Authors: Radhakrishnan Adityanarayanan , Cai Cathy , Weir Barbara A. , Moy Christopher , Uhler Caroline 
Published: March 2024

Abstract
Synthetic lethality refers to the concept that simultaneous perturbation of gene pairs leads to cell death but individual perturbation does not. Synthetically lethal gene pairs (SL pairs) provide a potential avenue for selective targeting of cancer cells based on underlying genetic vulnerabilities. The rise of large scale gene perturbation screens such as the Cancer Dependency Map (DepMap) offers the opportunity to identify SL pairs automatically using machine learning. Yet, a key difficulty in using machine learning models for this task is the lack of labeled data in the form of known SL pairs. Thus, prior approaches framed SL pair identification as a feature learning problem where the goal is to identify the genomic features most influential for predicting low cellular viability under a gene knockout. These prior approaches have primarily utilized random forests since these machine learning models are one of the only nonlinear models for which feature importances are provided explicitly. On the other hand, if we could identify features learned by state-of-the-art models on screening tasks such as kernel machines, we would be better powered in finding SL pairs. In this work, we present a computationally efficient and effective pipeline for SL pair screening built on a recently developed class of feature learning kernel machines known as Recursive Feature Machines (RFMs). We show that our pipeline more accurately recovers experimentally verified SL pairs than prior work including the best model from the DepMap portal and previous random forest based approaches (see the table below). Moreover, our pipeline identifies several new candidate SL pairs for further analysis, opening new avenues for targeting genetic vulnerabilities in cancer.
Rank of verified SL pairs across unsupervised methods (lower is better with a minimum value of 1). Experimentally Verified SL Pairs Pearson Correlation PARIS DepMap RFMs (Ours) SMARCA2/SMARCA4 1 1 1 1 ARID1A/ARID1B 1 1 1 1 STAG1/STAG2 1 1 1 1 CREBBP/EP300 1 1 1 1 VPS4A/VPS4B 7 &gt; 10 5 1 DDX17/DDX5 4 1 1 1 ENO1/ENO2 &gt; 10 1 1 1 SMARCC1/SMARCC2 &gt; 10 1 1 1 UBB/UBC &gt; 10 1 &gt; 10 1 MAGOH/MAGOHB 1 1 1 1 FAM50A/FAM50B 1 1 1 1
Citation Format: Adityanarayanan Radhakrishnan, Cathy Cai, Barbara A. Weir, Christopher Moy, Caroline Uhler. Synthetic lethality screening with Recursive Feature Machines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 897.