bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract CT161: GP2 immune response a predictor of recurrence in a phase IIb study evaluating HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with breast cancer
Authors: Patel Snehal S. , McWilliams David B. , Patel Mira S. , Thompson Jaye , Daugherty F. Joseph 
Published: June 2022

Abstract
The authors did not submit an updated abstract. The original abstract should be considered final.
Citation Format: Snehal S. Patel, David B. McWilliams, Mira S. Patel, Jaye Thompson, F. Joseph Daugherty. GP2 immune response a predictor of recurrence in a phase IIb study evaluating HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT161.
Abstract LB018: Clonal evolution and lineage choice driven by IRF4 in zebrafish T-cell lymphoma model
Authors: Amanda Stella , Tan Tze King , Ong Jolynn Zu Lin , Theardy Madelaine Skolastika , Wong Regina Wan Ju , Huang Xiao Zi , Ali Muhammad Zulfaqar , Yan Li , Gong Zhiyuan , Inagaki Hiroshi , Foo Ee Yong , Pang Brendan , Tan Soo Yong , Iida Shinsuke , Sanda Takaomi 
Published: June 2022

Abstract
IRF4 is a master regulator of immunity and is also frequently overexpressed in mature lymphoid neoplasms. Here, we demonstrate the stage-specific oncogenicity of IRF4 in vivo, its potential effects on T-cell development and clonal evolution using a zebrafish model. IRF4-transgenic zebrafish develop aggressive tumors with massive infiltration of abnormal lymphocytes that spread to distal organs. Many late-stage tumors are mono- or oligoclonal, and tumor cells can expand in recipient animals after transplantation, demonstrating their malignancy. Mutation of p53 significantly accelerates tumor onset, increases penetrance, and results in tumor heterogeneity. Unexpectedly, single-cell RNA-sequencing reveals that majority of tumor cells are double-negative T-cells, many of which express tcr-γ that became dominant as the tumors progress, whereas double-positive T-cells are largely diminished. Gene expression and enhancer profiling demonstrates that gata3, mycb and several genes that were previously not implicated in cancers including lrrn1, patl1 and psip1 are specifically upregulated in tumors, while genes responsible for T-cell differentiation including cxcr4b, id3 and cd8a are repressed. IRF4-driven tumors are sensitive to treatment with the BRD inhibitor (JQ1).
Citation Format: Stella Amanda, Tze King Tan, Jolynn Zu Lin Ong, Madelaine Skolastika Theardy, Regina Wan Ju Wong, Xiao Zi Huang, Muhammad Zulfaqar Ali, Li Yan, Zhiyuan Gong, Hiroshi Inagaki, Ee Yong Foo, Brendan Pang, Soo Yong Tan, Shinsuke Iida, Takaomi Sanda. Clonal evolution and lineage choice driven by IRF4 in zebrafish T-cell lymphoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB018.
Abstract LB052: Melanoma-secreted amyloid beta suppresses neuroinflammation and promotes brain metastasis
Authors: Kleffman Kevin , Levinson Grace , Rose Indigo V. , Blumenberg Lili , Shadaloey Sorin A. , Dhabaria Avantika , Wong Eitan , Galán-Echevarría Francisco , Karz Alcida , Argibay Diana , Von-Itter Richard , Floristán Alfredo , Baptiste Gillian , Eskow Nicole , Tranos James , Chen Jenny , de Miera Eleazar C. Vega Saenz , Call Melissa , Rogers Robert , Jour George , Wadghiri Youssef Zaim , Osman Iman , Li Yue Ming , Mathews Paul , Demattos Ronald , Ueberheide Beatrix , Ruggles Kelly , Liddelow Shane A. , Schneider Robert J. , Hernando Eva 
Published: June 2022

Abstract
Brain metastasis is a significant cause of morbidity and mortality in multiple cancer types and represents an unmet clinical need. The mechanisms that mediate metastatic cancer growth in the brain parenchyma are largely unknown. Melanoma, which has the highest rate of brain metastasis among common cancer types, is an ideal model to study how cancer cells adapt to the brain parenchyma. Our unbiased proteomics analysis of melanoma short-term cultures revealed that proteins implicated in neurodegenerative pathologies are differentially expressed in melanoma cells explanted from brain metastases compared to those derived from extracranial metastases. We showed that melanoma cells require amyloid beta (Aβ) for growth and survival in the brain parenchyma. Melanoma-secreted Aβ activates surrounding astrocytes to a prometastatic, anti-inflammatory phenotype and prevents phagocytosis of melanoma by microglia. Finally, we demonstrate that pharmacological inhibition of Aβ decreases brain metastatic burden. Our results reveal a novel mechanistic connection between brain metastasis and Alzheimer’s disease - two previously unrelated pathologies, establish Aβ as a promising therapeutic target for brain metastasis, and demonstrate suppression of neuroinflammation as a critical feature of metastatic adaptation to the brain parenchyma.
Citation Format: Kevin Kleffman, Grace Levinson, Indigo V. Rose, Lili Blumenberg, Sorin A. Shadaloey, Avantika Dhabaria, Eitan Wong, Francisco Galán-Echevarría, Alcida Karz, Diana Argibay, Richard Von-Itter, Alfredo Floristán, Gillian Baptiste, Nicole Eskow, James Tranos, Jenny Chen, Eleazar C. Vega Saenz de Miera, Melissa Call, Robert Rogers, George Jour, Youssef Zaim Wadghiri, Iman Osman, Yue Ming Li, Paul Mathews, Ronald Demattos, Beatrix Ueberheide, Kelly Ruggles, Shane A. Liddelow, Robert J. Schneider, Eva Hernando. Melanoma-secreted amyloid beta suppresses neuroinflammation and promotes brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB052.
Abstract LB073: Improving early career faculty research programs: Underrepresented Biomedical Researcher Scholars Program
Authors: Murray Debra , Fernbach Susan 
Published: June 2022

Abstract
According to the U.S. Department of Education in Fall 2018, full-time faculty in degree-granting postsecondary institutions were ~40% White males; 35% White females; 7% Asian/Pacific Islander males; 5% Asian/Pacific Islander females; and 3% each Black males, Black females, Hispanic males, and Hispanic females.1 Under-representation is one of the barriers to success for African American and Hispanic faculty. Barriers to women’s career advancement from underrepresented groups in academic medicine, science, and engineering and obtaining external research funding support for African American faculty do not occur in a vacuum and co-exist with barriers to research productivity overall.2 This data establishes the necessity of increasing representation, creating more accessible research opportunities, building networks, mentoring relationships in STEM-related fields, obtaining a diverse scientific workforce, and ensuring the success of all underrepresented in biomedical research (UBR) trainees and early career faculty. The All of Us Evenings with Genetics (AoUEwG) Research Program provides training to support Early Career Faculty and Senior Postdoctoral fellowship in cancer research. This engagement program includes Evenings With Genetics seminars, where regional and national campus audiences will be introduced to research opportunities available through the All of Us research hub; the Underrepresented Biomedical Researcher Faculty Summit UBRFS), where summit attendees will take part in using the All of Us research hub and receive data science training and professional development; and the UBRFS Scholars Program, where conference participants will receive yearlong support after the summit, including monthly multidisciplinary research team meetings, quarterly meetings, and mentor support. The AoUEwG Research Program aims to increase research productivity among UBR early career faculty and support their promotion to the next career level.
Citation Format: Debra Murray, Susan Fernbach. Improving early career faculty research programs: Underrepresented Biomedical Researcher Scholars Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB073.
Abstract LB190: Modulation of SPI1 transcriptional program contributes to the preclinical anti-tumor activity of SMARCA4/SMARCA2 ATPase inhibitors in AML
Authors: Sandoval Gabriel J. , Feldman Katharine , Topal Sal , Adam Ammar , Wu Hsin-Jung , Sappal Darshan , Soares Luis M. , Lahr David L. , Xu Lan , Vaswani Rishi G. , Muwanguzi Jordana , Huang Liyue , Piel Jessica , Collins Mike , Chan Ho Man , Thomenius Michael J. , Bellon Steven F. , Kruger Ryan G. , Decicco Carl P. , Centore Richard C. , Hentemann Martin 
Published: June 2022

Abstract
SPI1 (PU.1) is an ETS family transcription factor that plays a critical role in hematopoietic development and differentiation. Regulation of SPI1 expression has also been implicated in Acute Myeloid Leukemia (AML) oncogenesis, though its mechanism is incompletely understood. Previously we have identified and characterized a series of novel dual inhibitors of the SMARCA4/SMARCA2 ATPases (also referred to as BRG1/BRM), critical components of the BAF (mSWI/SNF) family of chromatin remodeling complexes; and FHD-286, a related SMARCA4/SMARCA2 ATPase inhibitor, is currently being explored clinically for the treatment of metastatic uveal melanoma and AML (NCT04879017 and NCT04891757). Here we show that AML cell lines are sensitive to BAF ATPase inhibition, resulting in both cell cycle arrest and apoptosis. We demonstrate that BAF ATPase inhibition primarily affects the SPI1 transcriptional profile by regulating SPI1 genomic occupancy at various enhancer elements, resulting in downregulation of key target genes. Using in vivo mouse models of AML, we demonstrate dose-dependent tumor growth inhibition and pharmacodynamic modulation of SPI1 target genes. Together, these data suggest that modulation of SPI1 function may, in part, provide a mechanistic basis for the clinical development of FHD-286 in AML.
Citation Format: Gabriel J. Sandoval, Katharine Feldman, Sal Topal, Ammar Adam, Hsin-Jung Wu, Darshan Sappal, Luis M. Soares, David L. Lahr, Lan Xu, Rishi G. Vaswani, Jordana Muwanguzi, Liyue Huang, Jessica Piel, Mike Collins, Ho Man Chan, Michael J. Thomenius, Steven F. Bellon, Ryan G. Kruger, Carl P. Decicco, Richard C. Centore, Martin Hentemann. Modulation of SPI1 transcriptional program contributes to the preclinical anti-tumor activity of SMARCA4/SMARCA2 ATPase inhibitors in AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB190.
Abstract LB536: Newly established CAR-T target antigen luciferase reporter cell lines facilitate CAR-T development
Authors: Foulke John , Fera Brian Della , Chen Luping , Tian Fang 
Published: June 2022

Abstract
Adoptive T cell therapy is a type of immunotherapy in which T cells are genetically modified to fight tumors. It has emerged as an exciting new approach for cancer treatment. Chimeric antigen receptor (CAR)-T cells have displayed remarkable efficacy in treating malignant cancers, particularly liquid tumors. CAR-T cells have proven to be a new type of ’living’ therapeutic by harnessing the patients' immune system to recognize specific tumor associated antigens and redirect the engineered T cells to more specifically target tumor cells. A large number of research efforts have been put into developing new CAR structures to increase the scope of targeted cancers and anti-tumor efficacy. Evaluating the biofunction of CAR-T cells in vitro often involves a series of labor-intensive co-culture experiments and immunoassays. Reproducibility also remains a challenge during the validation of new CAR-T cells due to donor-to-donor variation and other factors. In this study, we present a panel of luciferase reporter tumor cell lines that can be utilized to examine the function of CAR-T cells. The panel of selected human tumor cell lines naturally express high levels of CAR-T target antigens on cell surface, such as CD19, CD20 and Her2. After introduction of a Lenti-LUC2 luciferase reporter into the parental cell lines, single cell cloning was performed to isolate stable clones with high luciferase expression. To verify the performance of the target Luciferase reporter cell lines, we used commercially available CAR-T cells expressing CD19, CD20, HER2 and empty vector-transduced T cells as controls in co-culture experiments. The cytotoxicity of the CAR-T cells against target tumor cells was measured using both a luciferase assay and the xCELLigence potency assay. Our results demonstrate that the luciferase reporter system is a relatively simple, robust, and highly sensitive means to measure biological processes. The luciferase reporter cell lines provide an advantage in measuring target cell killing without having to use radioactive 51Cr release assay or pre-labeling the cells in CAR-T functional evaluation. In addition, these reporter cell lines were characterized and authenticated using cell morphology, growth kinetics, and STR analysis. The expression stability of both the target antigen and luciferase was verified by comparing the low passage and the high passage reporter cells. In summary, the well-characterized CAR-T target antigen luciferase reporter cell lines from ATCC provide excellent tools for studying CAR-T biofunction and validating new CAR-T agents for cancer immunotherapy.
Citation Format: John Foulke, Brian Della Fera, Luping Chen, Fang Tian. Newly established CAR-T target antigen luciferase reporter cell lines facilitate CAR-T development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB536.
Abstract LB545: Structure, dynamics and consequences of replication stress-induced structural variants in hepatocellular carcinoma
Authors: Bayard Quentin , Cordier Pierre , Péneau Camille , Imbeaud Sandrine , Hirsch Theo Z. , Renault Victor , Nault Jean-Charles , Blanc Jean-Frédéric , Calderaro Julien , Desdouets Chantal , Zucman-Rossi Jessica , Letouzé Eric 
Published: June 2022

Abstract
Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole genome sequencing to explore in-depth the nature of structural variants (SVs) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC display frequent intra- and inter-chromosomal templated insertion cycles (TIC) likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are close in the 3D genome organization. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induces continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics and consequences of SV accumulation in tumors with oncogene-induced replication stress.
Citation Format: Quentin Bayard, Pierre Cordier, Camille Péneau, Sandrine Imbeaud, Theo Z. Hirsch, Victor Renault, Jean-Charles Nault, Jean-Frédéric Blanc, Julien Calderaro, Chantal Desdouets, Jessica Zucman-Rossi, Eric Letouzé. Structure, dynamics and consequences of replication stress-induced structural variants in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB545.
Downwind Development in a Stationary Band Complex Leading to the Secondary Eyewall Formation in the Simulated Typhoon Soudelor (2015)
Authors: Zhu Xue-Song , Yu Hui , Wang Yuqing 
Published: June 2022

Abstract
Previous studies have demonstrated the importance of the downwind development of a rainband in secondary eyewall formation (SEF) in tropical cyclones. However, the details of the transition from rainbands to a secondary eyewall are not well understood. This study examined the convection onset in the early stage of SEF in the numerically simulated Typhoon Soudelor (2015). Results show that the convection onset in the SEF region was associated with the organization of a stationary band complex (SBC), which resulted from the outward propagation of inner rainbands and downwind propagation of secondary rainbands, with convection enhanced in the downwind sector of the SBC. The outward propagation of the inner rainbands involved the mesoscale pressure perturbations-induced unbalanced boundary layer dynamics, which were responsible for the radial outflow above the boundary layer inflow and the related secondary circulation on the inward side of the rainband. In the downwind propagation, secondary rainbands evolved into stratiform precipitation in the downshear-left quadrant, where mesoscale descending inflow continuously occurred and transported low equivalent potential temperature (θe) and dry air downward and downwind, leading to a decrease in low-level θe on the outward side of the rainband. A balanced state of the cold pool dynamics was finally reached in the downwind sector of the SBC between the supergradient-induced vertical wind shear and the low-θe-induced cold pool, resulting in the convection enhancement. Our results strongly suggest that both the unbalanced dynamics and rainband processes were essential in the early stage of SEF.

Significance Statement
The purpose of this study is to better understand how spiral rainbands evolve into a stationary rainband complex (SBC), and the physical processes responsible for the convection enhancement in the downwind sector of the SBC. This is important because it is this downwind convective enhancement that leads to the secondary eyewall formation (SEF). Our results provide the details of the transition from rainbands to a secondary eyewall and suggest that both the unbalanced boundary layer dynamics and rainband processes are essential in the early stage of SEF.
Impact of Optimally Growing Initial Errors on the Mesoscale Predictability of Heavy Precipitation Events along the Mei-Yu Front in China
Authors: Ke Jiaying , Mu Mu , Fang Xianghui 
Published: June 2022

Abstract
Based on the conditional nonlinear optimal perturbation (CNOP) approach, the impact of the optimally growing initial errors on the mesoscale predictability of typical mei-yu front heavy precipitation events over eastern China was explored. First, based on a nonlinear optimization system built using the high-resolution Weather Research and Forecasting Model and particle swarm optimization algorithm, the CNOPs for three heavy precipitation cases were obtained. The CNOPs as the optimally growing initial errors caused the largest forecast errors and made the 24-h accumulated precipitation stronger than any other kind of initial errors. Moreover, the CNOPs showed faster growth and saturation than the random errors in space, highlighting the importance of the initial error with specific spatial structure in the meso- and convective-scale processes. Despite different CNOPs having particular spatial structures, the large amplitudes of the CNOPs at lower levels were mainly located in the rainband along the mei-yu front. Although the spectral energies of the CNOPs increased with increasing scales, the forecast error growth for the CNOPs generally followed the well-known three-stage conceptual model. Moreover, the large-scale and large-amplitude initial errors in the CNOPs were the most influential in terms of the forecast quality. This suggests that reducing large-scale initial errors can potentially improve the forecast accuracy. However, the mesoscale predictability of the mei-yu front heavy precipitation events is inherently limited, for which the moist convection was found to be the main reason.
Improving Trendelenburg position effectiveness by varying cardiopulmonary bypass flow
Authors: Ho Raymond , McDonald Charles , Pauls Jo P , Li Zhiyong 
Published: June 2022

Introduction Trendelenburg position (TP) is used to transport gaseous emboli away from the cerebral region during cardiac surgery. However, TP effectiveness has not been fully considered when combined with varying the cardiopulmonary bypass (CPB) flow. This study simulated the supine and TP at different pump flows and assessed the trapped emboli and embolic load entering the aortic arch branch arteries (AABA). Methods A computational fluid dynamics (CFD) approach used a centrally cannulated adult patient-specific aorta model replicating a CPB circuit. Air emboli of 0.1 mm, 0.5 mm, and 1.0 mm ( n = 700 each) were injected into the aorta placed in the supine position (0°) and the TP (−20°) at 2 L/min and 5 L/min. The number of emboli entering the AABA were compared. An aortic phantom flow experiment was performed to validate air bubble behaviour. Results TP at 5 L/min had the lowest 0.1 mm mean (±SD) embolic load compared to the supine 2 L/min (55.3 ± 30.8 vs 64.3 ± 35.4). For both the supine and TP, the lower flow of 2 L/min had the highest number of simulated trapped emboli in higher elevated regions than at 5 L/min (541 ± 185 and 548 ± 191 vs 520 ± 159 and 512 ± 174), respectively. The flow experiment demonstrated that 2 L/min promoted bubble coalescence and high amounts of trapped emboli and 5 L/min transported air emboli away from the AABA. Conclusions TP effectiveness was improved by using CPB flow to manage air emboli. These results provide insights for predicting emboli behaviour and improving emboli de-airing procedures.
CT-based radiomics to distinguish progressive from stable neuroendocrine liver metastases treated with somatostatin analogues: an explorative study
Authors: Staal Femke CR , Taghavi M , Hong Eun K , Tissier Renaud , van Treijen Mark , Heeres Birthe C , van der Zee Dennis , Tesselaar Margot ET , Beets-Tan Regina GH , Maas Monique 
Published: June 2022

Background Accurate response evaluation in patients with neuroendocrine liver metastases (NELM) remains a challenge. Radiomics has shown promising results regarding response assessment. Purpose To differentiate progressive (PD) from stable disease (SD) with radiomics in patients with NELM undergoing somatostatin analogue (SSA) treatment. Material and Methods A total of 46 patients with histologically confirmed gastroenteropancreatic neuroendocrine tumors (GEP-NET) with ≥1 NELM and ≥2 computed tomography (CT) scans were included. Response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST1.1). Hepatic target lesions were manually delineated and analyzed with radiomics. Radiomics features were extracted from each NELM on both arterial-phase (AP) and portal-venous-phase (PVP) CT. Multiple instance learning with regularized logistic regression via LASSO penalization (with threefold cross-validation) was used to classify response. Three models were computed: (i) AP model; (ii) PVP model; and (iii) AP + PVP model for a lesion-based and patient-based outcome. Next, clinical features were added to each model. Results In total, 19 (40%) patients had PD. Median follow-up was 13 months (range 1–50 months). Radiomics models could not accurately classify response (area under the curve 0.44–0.60). Adding clinical variables to the radiomics models did not significantly improve the performance of any model. Conclusion Radiomics features were not able to accurately classify response of NELM on surveillance CT scans during SSA treatment.