bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4222: Glyphosate and AMPA exposure: Associations with dietary intake and other factors
Authors: Lucia Rachel McFarland , Liao Xiyue , Huang Wei-Lin , Forman Danielle , Kim Alexis , Ziogas Argyrios , Norden-Krichmar Trina M. , Goodman Deborah , Alvarez Andrea , Masunaka Irene , Pathak Khyatiben , McGilvrey Marissa , David-Dirgo Victoria , Hegde Apurva , Pirrotte Patrick , Park Hannah Lui 
Published: April 2023

Abstract
Background: Animal and epidemiologic studies suggest that exposure to the weed killer, glyphosate, and its primary metabolite aminomethylphosphonic acid (AMPA), is associated with increased risk for cancer, including breast cancer and non-Hodgkin's lymphoma. The International Agency for Research on Cancer (IARC) has categorized glyphosate as a “probable carcinogen,” yet glyphosate is the most highly used pesticide in the world. Biomonitoring studies assessing levels of human glyphosate and AMPA exposure in the United States have been limited. Thus, we examined urinary levels of these chemicals in a cohort of postmenopausal women residing in Southern California and evaluated associations with demographics, dietary intake, and other behavioral factors.
Methods: 338 postmenopausal women provided two first-morning urine samples and at least one paired 24-hour dietary recall. Participants also reported on demographic and other factors. Urinary glyphosate and AMPA were measured using LC-MS/MS.
Results: Glyphosate was detected in nearly 90% of urine samples and AMPA in 67.2%. Urinary glyphosate and AMPA levels were lower in women who reported high levels of organic eating (p=0.04 and p=0.01, respectively). Urinary glyphosate was lower in women who reported higher levels of physical activity (p=0.03). Multivariate analysis showed that grain consumption, particularly refined grains, was significantly associated with higher urinary glyphosate levels (adjusted p=0.004). Alcohol consumption (adjusted p=0.001) and frequency of eating fast-food (adjusted p=0.006) were associated with higher urinary AMPA levels, while fruit (adjusted p=0.03) and corn (adjusted p=0.008) consumption were associated with lower AMPA.
Conclusions: In the largest study to date examining paired dietary recall data and measurements of urinary glyphosate and AMPA, the vast majority of women sampled had detectable levels. Consumption of certain foods, including grains and alcoholic beverages, were associated with higher urinary levels of glyphosate and AMPA.
Citation Format: Rachel McFarland Lucia, Xiyue Liao, Wei-Lin Huang, Danielle Forman, Alexis Kim, Argyrios Ziogas, Trina M. Norden-Krichmar, Deborah Goodman, Andrea Alvarez, Irene Masunaka, Khyatiben Pathak, Marissa McGilvrey, Victoria David-Dirgo, Apurva Hegde, Patrick Pirrotte, Hannah Lui Park. Glyphosate and AMPA exposure: Associations with dietary intake and other factors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4222.
Abstract 4286: A statistical learning method for simultaneous copy number estimation and subclone clustering with single cell sequencing data
Authors: Xiao Feifei , Qin Fei , Cai Guoshuai 
Published: April 2023

Abstract
The availability of single cell sequencing (SCS) enables us to assess intra-tumor heterogeneity and identify cellular subclones without the confounding effect from mixed cells. Copy number aberrations (CNAs) have been commonly used to identify subclones in SCS data since cells comprising a subpopulation are found to share genetic profile. However, currently available methods may generate spurious results (e.g., falsely identified CNAs) in the procedure of CNA detection, hence diminishing the accuracy of subclones identification from a large complex cell population. In this study, we developed a CNA detection method based on a fused lasso model, referred to as FLCNA, which can simultaneously identify subclones in single cell DNA sequencing (scDNA-seq) data. Spike-in simulations were conducted to evaluate the clustering and CNA detection performance of FLCNA benchmarking to existing copy number estimation methods (SCOPE, HMMcopy) in combination with commonly used clustering methods. FLCNA was also applied to a real scDNA-seq dataset with breast cancer and clusters identified using FLCNA showed clearly different genomic variation patterns. In conclusion, FLCNA provided superior performance in subclone identification and CNA detection with scDNA-seq data.
Citation Format: Feifei Xiao, Fei Qin, Guoshuai Cai. A statistical learning method for simultaneous copy number estimation and subclone clustering with single cell sequencing data. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4286.
Abstract 4308: Cancer as a disease of information
Authors: Goldstein Adam Julian 
Published: April 2023

Abstract
The causes and symptoms of cancer are often described in physical terms, for example as DNA mutations leading to increased cell proliferation. These understandings have been immensely informative, but physical changes are only one of several ways to understand what cancer is and why it behaves the way it does. An alternative perspective builds upon Claude Shannon's work in information theory, and sees cancer as a result of missing, noisy, and/or distorted information. In this talk I summarize existing research and discuss the implications for understanding cancer as a disease of information. I then explain how detecting and treating cancer look different when viewed through this lens. In particular, I discuss how this approach offers the hope for rehabilitating cancer cells by restoring expected information flows, in contrast to some current treatments which exacerbate information disruptions.
Citation Format: Adam Julian Goldstein. Cancer as a disease of information. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4308.
Abstract 4311: Using multiomics analysis to identify dysregulated transcription factors in non-small cell lung cancer (NSCLC) to drive the expression of a cancer-activated synthetic biomarker
Authors: Zhang Yue Wendy , Rudina Shireen , Wodziak Dariusz , Xia Chloe , Louie Maggie , Park Albert , Suhy David 
Published: April 2023

Abstract
Early detection of cancer is an important driver of increased survival, quality of life and reduced healthcare costs. Earli is developing a highly sensitive, orthogonal approach that uses a genetic construct that usurps dysregulated pathways and actively forces cancer cells to drive the expression of a detectable ‘synthetic’ biomarker. Identification of abnormally elevated transcription factors (TF) in cancer is crucial when developing a cancer-activated expression platform. Evaluating TF function in a genome wide fashion is a challenge, especially since TF activity is not solely reflected by just its RNA expression or even by protein abundance, but also its post-translational modification including phosphorylation. In this study, we use the publicly available multiomics dataset from Clinical Proteomic Tumor Analysis Consortium (CPTAC) which includes RNA-seq based transcriptional profiling, MS based protein abundance and phosphorylation from 211 paired tumor and normal adjacent samples derived from NSCLC patients. Performing Multiomics Factor Analysis (MOFA) analysis, we identified a short list of 34 dysregulated TFs in NSCLC that displayed high expression levels in at least two of the three omics platforms relative to normal tissues, six of which scored highly across all three. A subset of candidate TF binding sequences were subcloned as multimers into expression constructs with a basal promoter and empirically evaluated in multiple cancer cell lines, including patient-derived xenograft (PDX) cell lines and normal cell lines.Transfection experiments demonstrated that these novel chimeric synthetic promoters could produce robust levels of expression in PDX-derived cell lines that was 10-20x higher than expression mediated by known cancer-activated promoters such as the endogenous survivin (BIRC5) promoter. Furthermore, levels achieved were only 3-4 fold lower than a control EF-1a promoter, one of the strongest promoters, typically used to drive constitutive expression in mammalian cells. Currently, a small subset of these chimeric constructs is being tested in murine tumor models and in large animal cancer models such as oncopigs. These experiments will further drive the development of this approach for use in early cancer detection.
Citation Format: Yue Wendy Zhang, Shireen Rudina, Dariusz Wodziak, Chloe Xia, Maggie Louie, Albert Park, David Suhy. Using multiomics analysis to identify dysregulated transcription factors in non-small cell lung cancer (NSCLC) to drive the expression of a cancer-activated synthetic biomarker. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4311.
Abstract 4318: Cancer cell communication with macrophages prevents T cell activation during emergence of cell cycle therapy resistance
Authors: Griffiths Jason I. , Cosgrove Patrick A. , Castaneda Eric Medina , Nath Aritro , Chen Jinfeng , Adler Frederick R. , Chang Jeffrey T. , Khan Qamar J. , Bild Andrea H. 
Published: April 2023

Abstract
By corrupting signals for growth and survival, evolving cancer cells can engineer the tumor microenvironment (TME) to promote treatment resistance. However, the specific interactions between malignant and non-malignant cells that predispose drug resistance and their changes during treatment remain widely unknown. Here we examine the composition, communication, and phenotypic diversity of tumor-associated cell populations in serial biopsies from early-stage ER+ breast cancers. We used single-cell RNA sequencing to profile over 400 thousand malignant and non-malignant cells from patient tumor samples obtained before, during and after treatment. The patients received either endocrine therapy (letrozole) alone or in combination with a CDK4/6 cell cycle inhibitor (ribociclib). Our analyses reveal that cancer cells from ribociclib-resistant tumors stimulate macrophage differentiation towards an immune-suppressive phenotype through upregulation of a diversity of cytokines and growth factors. The macrophage phenotype shift leads to reduced crosstalk with cytotoxic T-cells via IL-2/15/18 receptors, diminishing T-cell activation and recruitment. These results indicate that cancer communications promoting an immune-cold TME predispose tumors to develop CDK4/6 cell cycle inhibitor resistance, and that the beneficial effects of blocking cancer cell proliferation must be balanced against their inhibitory effect on immune cell division and activation. An optimal treatment strategy will require coupling the prevention of cancer division with activation of an effective cytotoxic T-cell response.
Citation Format: Jason I. Griffiths, Patrick A. Cosgrove, Eric Medina Castaneda, Aritro Nath, Jinfeng Chen, Frederick R. Adler, Jeffrey T. Chang, Qamar J. Khan, Andrea H. Bild. Cancer cell communication with macrophages prevents T cell activation during emergence of cell cycle therapy resistance. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4318.
Abstract 4322: AI assisted detection and characterization of tertiary lymphoid structures in patients with colorectal cancer
Authors: Burg Samantha , Hart Nathaniel , Powers Astin , Zhang Wenjun 
Published: April 2023

Abstract
Tertiary Lymphoid Structures (TLSs) are ectopic immune cell aggregates that form in response to abnormal physiology and inflammation. TLS presence in the tumor environment has been associated with positive clinical outcomes and response to immune checkpoint inhibition therapy. Using a fluorescent multiplex panel consisting of Pan-cytokeratin (PanCK), Programmed Death Ligand-1 (PD-L1), cluster of differentiation (CD) 8, CD3, and CD68 we developed a HALO-based artificial intelligence (AI) classifier to detect TLSs in colorectal cancer (CRC) tissue. In conjunction with cell-type and spatial analyses, we used the AI TLS classifier to characterize several features of the TLS and peri-TLS environment. We trained the AI classifier using 51 examples of TLSs from 8 patients, and applied it to images of 21 CRC patient tissues. TLSs were detected in 9/21 patient samples. We then used cellular detection and spatial analysis to characterize features of the TLS, including the germinal center (GC), T cell zone and peri-TLS area. We detected a higher cell density (Mean=12250 ±2039 SD; cells/mm2) within the interior of AI-detected GCs relative to the 1st 200 μm outside of the AI-defined GC border (8005±1870). In addition, we examined the spatial distribution of CD3+ and CD8+ T cells relative to the TLS GC. We found elevated CD3+ cell density in the interior of the GC (5784±1649) and within 200 μm of the GC border (5126±2239) which decreased at distances &gt;200 μm from the GC border. We found CD8+ density to be elevated within the 1st 200 μm of the GC border (1903±1182) and declined 400 μm away from the GC border (963±828). The spatial distribution of T cells surrounding an area of high cell density is indicative of a T cell zone surrounding germinal center. Further analysis of the AI-detected TLS GCs indicated that PD-L1+ cell density was highest within the germinal center (355± 534;9) relative to the exterior of the germinal center (1st 150μm outside germinal center:276± 441). We created an AI classifier that can detect TLS(s) within patient tissue in the absence of a B-cell marker and confirmed that our AI classifier was detecting TLSs by characterizing canonical features of TLSs. Further exploration of the TLS and peri-TLS area may offer insights into immune-tumor interaction within the tumor microenvironment, and paired detection of TLSs in a clinical cohort with outcome data may predict patient response to immune checkpoint inhibitor therapy.
Citation Format: Samantha Burg, Nathaniel Hart, Astin Powers, Wenjun Zhang. AI assisted detection and characterization of tertiary lymphoid structures in patients with colorectal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4322.
Abstract 4340: HLA-B44 motif neoepitope is associated with a favorable tumor immune microenvironment and predicts ICB response in NSCLC
Authors: Li Rui , Fares Charlene M. , Grogan Tristan R. , Zhang Tianhao , Li Debory , Theisen Matthew , Velez Maria A. , Brodrick Paige M. , Lind-Lebuffe Jackson P. , Radwan Yazeed , Ayzenberg Gregory A. , Elashoff David , Liu Bin , Lisberg Aaron E. , Cumming Amy L. , Garon Edward B. 
Published: April 2023

Abstract
Immune check point blockade (ICB) has recently transformed the treatment of non-small cell lung (NSCLC). However, the majority of patients do not respond to ICB. For ICB to be effective, tumor neoantigens need to be presented in a human leukocyte antigen (HLA) class I-restricted manner. Recent studies by our group and others have shown that HLA-B44 supertype is associated with extended survival in patients treated with ICB. Herein, we hypothesize that HLA-B44-specific motif neoepitopes generate an active tumor immune microenvironment and a favorable ICB response in NSCLC. Utilizing the TCGA database, we found that nearly half of the NSCLC patients have at least one HLA-B44 allele, of whom 36.8% and 37.3% of patients harbor at least one B44 motif neoepitope in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC), respectively. In a pooled analysis of patients with LUAD and LUSC, gene expression of PD-L1, CTLA-4, LAG-3, CXCL9, CXCL10, CXCL13, CD8A and cytolytic gene signature (includes GZMA and PRF1) is elevated in patients with B44 motif neoepitopes compared to those without motif neoepitopes. Immune cell component analysis showed increased infiltration of Th1, Th2 and CD8 T cells in LUAD and regulatory and CD8 T cells in LUSC. Although a linear regression model revealed a positive correlation between tumor mutational burden (TMB) and number of B44 motif neoepitopes, pooled analysis of LUAD and LUSC with similar TMB showed significant elevation of CTLA-4, LAG3, CXCL10 and a trend of increased expression of CXCL9 in motif patients. Upon investigation of possible immune editing, we found a significantly higher proportion of genes containing B44 neoepitope downregulated at the RNA level both in LUAD and LUSC. Lastly, we showed that combining B44 motif with either PD-L1 or TMB improved prediction of progression-free survival in NSCLC patients treated with ICB. In summary, we demonstrate that HLA-B44 motif neoepitopes are associated with a favorable tumor immune microenvironment and can serve as a potential biomarker for ICB benefit in NSCLC patients.
Citation Format: Rui Li, Charlene M. Fares, Tristan R. Grogan, Tianhao Zhang, Debory Li, Matthew Theisen, Maria A. Velez, Paige M. Brodrick, Jackson P. Lind-Lebuffe, Yazeed Radwan, Gregory A. Ayzenberg, David Elashoff, Bin Liu, Aaron E. Lisberg, Amy L. Cumming, Edward B. Garon. HLA-B44 motif neoepitope is associated with a favorable tumor immune microenvironment and predicts ICB response in NSCLC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4340.
Abstract 4375: A bootstrapping method to optimize go/no-go decisions from single-arm, signal-finding studies in oncology
Authors: Mohan Aparna , Dutta Raunak , Buros-Novik Jacqueline , Akala Omobolaji , Topp Brian Gregory 
Published: April 2023

Abstract
Background: Phase Ib, single-arm trials are common in oncology development. Since these trials are not powered for statistical significance, Go/No-Go decisions are largely driven by observed trends in ORR relative to historic control. Here we develop a bootstrapping method to systematically compare secondary endponts, such as the waterfall plot, to historic control data. In addition, we identify an actionable Go threshold and estimate the expected false positive and false negative rates associated with that threshold.
Method: A proprietary mathematical model was used to simulate thousands of single-arm trials (n = 30) with a combination of pembrolizumab and a novel agent with miserable (Rx0), modest (Rx1), moderate (Rx2) or magnificent (Rx3) efficacy. A bootstrapping method was used to compare waterfall plots from these trials to a simulated Phase III pembrolizumab monotherapy control arm (n = 511).
Results: The bootstrapping method provides a visualization of the observed waterfall plot for the single-arm combination trial relative to the range of possible outcomes from historic control data (5th, median, 95th percentile). The method also provides a score reflecting the probability that the observed data is different from the historic control. An ROC analysis showed a strong ability to separate drugs with modest (AUROC = 83%), moderate (AUROC = 96%) and magnificent combination efficacy (AUROC = 99%) from drugs with miserable efficacy. The method was shown to effectively move drugs with a range of efficacy through an in-silico pipeline while rejecting drugs without combination efficacy.
Conclusion: This bootstrapping method allows comparisons of secondary endpoints from early clinical trials to historic control data. The visualization is intuitive, and the quantification provides an actionable Go-threshold. The method also provides an estimate of the risk associated with that recommendation. We suggest incorporation of this as a component of Go/No-Go decision making in early oncology trials.
Citation Format: Aparna Mohan, Raunak Dutta, Jacqueline Buros-Novik, Omobolaji Akala, Brian Gregory Topp. A bootstrapping method to optimize go/no-go decisions from single-arm, signal-finding studies in oncology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4375.
Abstract 4397: Chemotherapy-induced peripheral neuropathy and falls in cancer survivors relate to digital balance and gait impairments
Authors: Shah Vrutangkumar , Muzyka Daniel , Guidarelli Carolyn , Sowalsky Kristen , Winters-Stone Kerri M. , Horak Fay B. 
Published: April 2023

Abstract
Background and Aim: Standing postural sway and gait tests with body-worn inertial sensors provide a multitude of objective, digital balance, and gait measures that represent several different domains controlling mobility. However, it is not clear which domains of balance or gait best reflect the impact of treatment-induced peripheral neuropathy on mobility or differentiate fall risk in cancer survivors. This study aimed to determine which domains of balance and gait differed between cancer survivors who reported 1) symptoms of peripheral neuropathy versus asymptomatic survivors and 2) falls in the previous six months versus non-fallers.
Methods: Both postural sway during 30 seconds of quiet stance and gait characteristics from the Instrumented Time-Up-and-Go test (ITUG) were recorded with six synchronous inertial sensors (Opals by APDM Wearable Technology, a Clario company). The sensors were placed on both shanks and wrists, and one on the lumbar spine and sternum in 425 female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used first to identify independent domains of mobility from 14 balance and gait measures for subsequent analysis.
Results: PCA analysis revealed 5 independent domains (PC1: Sway amplitude, PC2: Gait pace; PC3: Sway frequency; PC4: Gait spatial-temporal and PC5: Turning) that accounted for 81% of the variance of performance across the participants. Cancer survivors who reported neuropathy showed a significantly higher sway frequency (PC3) than asymptomatic survivors. Cancer survivors who reported falls showed a significantly larger sway area (PC1) and slower gait pace (PC2) than non-fallers.
Conclusions: Wearable sensor instrumentation from short balance and gait tests capture objective digital gait and balance outcomes reflective of treatment-related neuropathy and fall risk in women treated with chemotherapy for cancer. Wearable sensors could be used for oncology clinical trials to assess the impact of cancer treatment and symptom mitigation strategies to limit changes in mobility that might lead to excess falls in people with cancer.
Citation Format: Vrutangkumar Shah, Daniel Muzyka, Carolyn Guidarelli, Kristen Sowalsky, Kerri M. Winters-Stone, Fay B. Horak. Chemotherapy-induced peripheral neuropathy and falls in cancer survivors relate to digital balance and gait impairments. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4397.