bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-204: Oncogenic Ras signaling requires serine protease hepsin to induce invasive breast cancer phenotype
Authors: Pant Shishir Mani , Tervonen Topi , Belitskin Denis , Englund Johanna , Verschuren Emmy , Kovanen Panu , Klefstrom Juha 
Published: September 2020

Abstract
Invasive cancer growth occurs when epithelial tumor cells individually or collectively detach from the primary tumor and migrate into the adjacent healthy tissue. This process starts a gradual tumor progression that may lead to life-threatening metastatic disease. Hepsin is a type II transmembrane serine protease that is frequently overexpressed in breast, prostate, and other epithelial cancers. It promotes tumor progression through activating growth factors and disrupting cell-cell and cell-basement membrane (BM) junctions. Although hepsin participates in pericellular cancer degradome, the oncogenic upstream mechanisms that activate hepsin in cancer are not well known. We found that oncogenic Ras proteins by activating MAPK pathway signaling alter the ratio of hepsin and HAI-1 to increase the proteolytic activity of hepsin. In 3D epithelial culture models of Ras-driven cancer, depletion of hepsin by shRNA restored desmosomes, BM defects, and glandular morphology but not the apical polarity. Mechanistically, Ras-MAPK pathway affected hepsin/HAI-1 via two distinct downstream pathways: Hepsin protein was stabilized via Ras-induced and heat shock transcription factor-1-mediated stress pathway, whereas HAI-1 was down-regulated by Ras via tumor suppressor LKB1 and PI3K-dependent pathways. Altogether, the results suggest that abnormal activation of Ras-MAPK pathway elevates hepsin activity to execute early steps of breast cancer invasion.
Citation Format: Shishir Mani Pant, Topi Tervonen, Denis Belitskin, Johanna Englund, Emmy Verschuren, Panu Kovanen, Juha Klefstrom. Oncogenic Ras signaling requires serine protease hepsin to induce invasive breast cancer phenotype [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-204.
Abstract LB-209: Integrative analysis of recurrent-metastatic progression in high-risk human papillomavirus cervical carcinomas
Authors: Choi Youn Jin , Jung Yu Yeon 
Published: September 2020

Abstract
Purpose: The acquisition of recurrent/metastatic potential by a tumor cell defines a critical step of malignant progression. However, the understanding of metastatic progression at the molecular level is scarce for cervical carcinomas (CES).
Materials and Methods: In this study, we performed comprehensive genomic, transcriptomic and viral profiling of five pairs of primary (CES-P) and matched recurrent/metastatic tumors (CES-R/M) with high risk human papillomavirus.
Results: Whole exome sequencing revealed mutation features of CES-R/M such as elevated mutation burdens and prevalent copy number alterations compared to their matched CES-P. A relative deficit of APOBEC-related mutation signatures accompanying the transcriptional down-regulation of APOBEC3A was also observed for CES-R/M. Mutations on genes encoding epigenetic regulators were also commonly observed as CES-R/M-specific alterations. Immunoprofiling and gene set analysis further revealed that CES-P were enriched with transcripts representing activated anticancer immunity such as cytolytic scores and interferon-gamma pathway but CES-R/M showed the up-regulation of genes involved in epithelial-mesenchymal transition and angiogenesis. Viral capture sequencing also revealed the hotspots of viral integration such as 12q13. Moreover, we found that the transcriptional upregulation of POSTN and downregulation of APOBEC3A were associated with unfavorable clinical outcomes in CES.
Conclusions: The comprehensive genomic and transcriptomic profiling of a rare cohort including CES-R/M identified metastases-specific features to advance the molecular understanding into the CES metastatic progression with potential clinical implication.
Citation Format: Youn Jin Choi, Yu Yeon Jung. Integrative analysis of recurrent-metastatic progression in high-risk human papillomavirus cervical carcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-209.
Abstract LB-234: Development of HER2 targeted HSP90 inhibitors delivery system
Authors: Lim Kwangsuk , Hong Yudong , Won Young-Wook 
Published: September 2020

Abstract
Heat shock protein 90 (HSP90) plays a crucial role in the survival and growth of cancer cells by improvement of the stability and activity of many signaling proteins such as Akt, Raf-1 and HER2/neu. HSP90 inhibitors (HSP90i) such as geldamanycin (GM), AUY922 and STA-9090 have been developed for inhibition of multiple signaling pathways that are initiated by HSP90. Although geldanamycin derivatives (GM) which is the first class of HSP90 inhibitors were disappointing in the initial clinical trials, these studies have shown promise in patients with HER2 positive cancers. To improve anticancer efficacy of HSP90i, HER2 targeted HSP90i delivery system (HER2-HBD) was constructed because of difficulty in chemical modification of HSP90i. HER2-HBD consist of HER2 scFv and HSP90i binding domain, was expressed from 293 cells. This system could incorporate HSP90i into recombinant antibody fusion protein based on biological binding affinity. HER2-HBD and HSP90i was spontaneously formed HER2-HBD/HSP90i complex. HER2-HBD/HSP90i complex specifically delivered HSP90i into HER2 positive cancer cell and reduced cancer cell growth in vitro and in vivo test. HER2-HBD recombinant system based on biological affinity between HSP90i and HBD was not required chemical reaction to conjugate antibody and drug. This system might be useful targeted delivery systems for HSP90i without tailored conjugation method to develop antibody-drug conjugate (ADC) and also applied to develop targeted delivery systems for biological inhibitor drugs.
Citation Format: Kwangsuk Lim, Yudong Hong, Young-Wook Won. Development of HER2 targeted HSP90 inhibitors delivery system [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-234.
Abstract LB-246: Venice: A new algorithm for finding marker genes of single-cell populations in tumor microenvironment
Authors: Pham Son , Vuong Hy , Truong Thao 
Published: September 2020

Abstract
Most widely used tools for finding marker genes insingle-cell data(SeuratT/NegBinom/Poisson, CellRanger, EdgeR, limmatrend) rely on a conventional definition of differentially expressed genes from bulk RNA-seq: genes with different means of expression values . However, in single-cell data (e.g., cell populations in tumor microenvironments), a cell population can be a mixture of many cell types/cell states, hence the mean expression of genes cannot represent the whole population. In addition, these tools assume that the gene expression of a population belongs to a specific family of distribution. This assumption is often violated in single-cell data. In this work, we define marker genes of a cell population as genes that can be used to distinguish cells in the population from cells in other populations. Besides log-fold change, we devise anew metric to classify genes into up-regulated, down-regulated, and transitional states. In a benchmark for finding up-regulated and down-regulated genes, our tool outperforms all compared methods, including Seurat, ROTS, scDD, edgeR, MAST, limma, normal t-test, Wilcoxonand Kolmogorov-Smirnov test. Our method is much faster than all compared methods, therefore, it enables interactive analysis for large single-cell data sets in BioTuring Browser (https://bioturing.com/bbrowser).
Citation Format: Son Pham, Hy Vuong, Thao Truong. Venice: A new algorithm for finding marker genes of single-cell populations in tumor microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-246.
Abstract LB-254: The effectiveness of healthcare professional training on the legal issues impacting individuals diagnosed with cancer to improve patient quality of life
Authors: Morales Joanna , Bryant Monica 
Published: September 2020

Abstract
A cancer diagnosis may carry with it a variety of legal issues, including insurance coverage, government benefits, and consumer rights. These legal issues can cause people unnecessary worry, confusion, and stress, and can be overwhelming. The Insurance and Finance Intensive is focused on providing healthcare professionals tools to proactively identify the presence of cancer-related legal, health insurance, and financial issues facing their patients. Additionally, the training helps health care professionals to offer referrals to appropriate legal and related resources, once those issues are identified. Oncology healthcare professionals participated in an eight-hour comprehensive training. Attendees were provided with substantive information about cancer-related legal issues, such as identifying health insurance options, navigating disability insurance and appeals, and managing finances. A follow-up survey was sent to all past intensive attendees to measure the effectiveness of the training and to address any lingering questions and difficult case studies. Ninety-four percent of survey respondents strongly agreed or agreed that the information provided by the training helped them reduce the stress and anxiety of their patients and their families. Ninety-two percent of survey respondents strongly agreed or agreed that the information provided by the training improved the quality of life of their patients and their families. The Insurance & Finance Intensive successfully provided health care professionals with valuable information on the practical and legal issues that impact individuals diagnosed with cancer. It is recommended that more healthcare professionals participate in this training to improve the quality of life of their patients beyond diagnosis.
Citation Format: Joanna Morales, Monica Bryant. The effectiveness of healthcare professional training on the legal issues impacting individuals diagnosed with cancer to improve patient quality of life [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-254.
Abstract LB-264: Biodynamic chemotherapy selection in breast cancer patients
Authors: An Ran , Turek John , Nolte David , Loesch David , Morgan Travis 
Published: September 2020

Abstract
Purpose: Biodynamic signatures (temporal patterns of microscopic motion within a three-dimensional tumor explant) offer a phenomic biomarker that is highly predictive for therapeutic response. The purpose of this study is to evaluate predictive accuracy of a biodynamic drug response classifier in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods: Consecutive breast cancer patients from 4 institutions were screened for enrollment in a prospective observational study (NCT03164863). Treatment-naïve needle biopsies were delivered to a central laboratory where biodynamic signatures were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received NAC per institutional guidelines and were followed through surgical intervention. A four-point classifier was trained to predict pathologic complete response (CR) then prospectively validated. Results: Among patients completing neoadjuvant treatment and surgical intervention, 33% (24 of 72) achieved CR. The biodynamic classifier predicted CR with 96% sensitivity and 97% negative predictive value. Biodynamically “favored” (scoring ≥ 3) and “strongly favored” (scoring 4) regimens produced CR at rates of 56% (23 of 41) and 73% (19 of 26), respectively. Only 3% of patients (1 of 31) achieved CR from regimens scoring 1 or 2. Area under the receiver operating curve (AUC) was 87% (95% CI: 75% to 93%, p &lt;.0001), with similar performance across all subtypes and therapy cohorts (range: 84% to 89%). Performance of the classifier on training and validation patients was statistically equivalent. Conclusion: Biodynamic scoring accurately predicts response in breast cancer patients receiving NAC and holds promise to substantially improve management of these patients.
Chemotherapy response distribution by biodynamic scoreBiodynamic ScoreNo ResponsePartial ResponseComplete ResponseTotal111 (58%)7 (37%)1 (5%)1922 (17%)10 (83%)0 (0%)1231 (7%)10 (67%)4 (27%)1540 (0%)7 (27%)19 (73%)26Totals14 (19%)34 (47%)24 (33%)72
Citation Format: Ran An, John Turek, David Nolte, David Loesch, Travis Morgan. Biodynamic chemotherapy selection in breast cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-264.
Abstract LB-272: T-cell clonal dynamics determined by high resolution TCR-β sequencing in recipients of allogeneic hematopoietic cell transplantation
Authors: Gittelman Rachel M. , Leick Mark , DeFilipp Zachariah , Ritz Jerome , Yusko Erik , Sanders Catherine , Robins Harlan 
Published: September 2020

Abstract
Delayed reconstitution of the immune system after allogeneic hematopoietic cell transplantation (HCT) is a long-recognized complication. Specifically, loss of T-cell diversity has been implicated in infectious complications, graft-versus-host disease (GVHD), and disease relapse. We performed serial high-resolution next generation sequencing using the immunoSEQ® Assay (Adaptive Biotechnologies, Seattle, WA) to characterize the TCRβ locus in 99 HCT recipients in the first 3 months after transplant. Transplant donor type included unrelated (n=57) and related (n=42) donors. Conditioning regimen intensity included reduced intensity (n=55) and myeloablative (n=44). We measured T-cell fraction, clonality, and richness in the donor and at days +15, +30, +50 and +100 post-transplant in the recipient, and correlated metrics to clinical variables. In agreement with prior studies, we found that although absolute T-cell numbers recover relatively quickly after transplant, repertoire diversity remains diminished. Restricted diversity was associated with conditioning intensity, use of ATG, and donor type. Increased T-cell clonal expansion at Day +30 compared to the donor sample was associated with the incidence of acute GVHD (HR=1.11, p=5x10-5). Even after exclusion of the twelve patients who had experienced acute GVHD by day +30, the association between acute GVHD and clonal expansion persisted (HR=1.098, p=0.041), indicating that clonal expansion preceded the development of acute GVHD. Our results indicate the importance of early post-transplant sampling and highlight T-cell clonal expansion as a potential novel biomarker for GVHD which warrants further study.
Citation Format: Rachel M. Gittelman, Mark Leick, Zachariah DeFilipp, Jerome Ritz, Erik Yusko, Catherine Sanders, Harlan Robins. T-cell clonal dynamics determined by high resolution TCR-β sequencing in recipients of allogeneic hematopoietic cell transplantation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-272.
Abstract LB-354: Immune phenotyping of diverse syngeneic brain tumors identifies critical tumor micro-environmental differences
Authors: Khalsa Jasneet K. , Keegan Joshua W. , Cheng Nina , Driver Joseph , Chaudry Ameen , Bi Wenya Linda , Lederer James A. , Shah Khalid 
Published: September 2020

Abstract
Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Pre-clinical syngeneic mouse models are at the forefront of testing and understanding emerging novel immune based therapies prior to their translation in patients. We generated distinct imageable syngeneic GBM-tumor models and assessed tumor infiltrating immune cells from end-stage tumors by utilizing RNA sequencing, CyTOF (mass Cytometry by Time of Flight) and correlative immunohistochemistry. CyTOF facilitates multiparametric analysis of up to 40 different markers which is useful especially in the case of GBM where number of TILs is limiting. We identified immunologically-inert and active syngeneic tumor types and show that inert tumors have an immune-suppressive phenotype with numerous MDSCs (Ly6C+ CD11b+), exhausted CD8 T cells and fewer eosinophils. To mimic the clinical settings of first line of GBM treatment, we performed tumor resection in an immunologically inert tumor model. We show that tumor-resection invigorates an anti-tumor response via significant increase in CD8+ T cells, monocyte/macrophages and decrease in Ly6G+ myeloid cells. A comparative CyTOF analysis of resected-tumor samples from GBM patients and mouse GBM tumors showed stark similarities in one of the mouse GBM tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.
Citation Format: Jasneet K. Khalsa, Joshua W. Keegan, Nina Cheng, Joseph Driver, Ameen Chaudry, Wenya Linda Bi, James A. Lederer, Khalid Shah. Immune phenotyping of diverse syngeneic brain tumors identifies critical tumor micro-environmental differences [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-354.
Abstract LB-360: Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells
Authors: Wang Jing , Hall Matthew , Bushnell Grace , Decker Joseph , Orbach Sophia , Raghani Ravi , Zhang Yining , Morris Aaron , Ma Jeffery , Kandagatla Pridvi , Jeruss Jacqueline , Shea Lonnie 
Published: September 2020

Abstract
Immune signaling within a metastatic niche drives recruitment and colonization, and the subsequent tumor cell fate within the niche. We employed a biomaterial scaffold as a synthetic metastatic niche to dissect the signals driving the responses within the niche relative to the native metastatic niche, which was the lung in these models. For both the natural and the synthetic niche, Gr-1+ cells secreting S100A8/A9 were the major factors contributing to tumor cell recruitment. Interestingly, upon recruitment, tumor cells in the synthetic niche were observed to undergo senescence and were cleared whereas cells within the native niche accumulated and ultimately proliferated to form macrometastases. The synthetic niche has underlying inflammation due to the foreign body responses (FBR) consisting of N1-polarized Gr1+ myeloid cells, M1-polarizedmacrophage, mature dendritic cells and highly cytotoxic CTLs and NK cells, which were not observed in the lung. Furthermore, we found two proteins (osteopontin and decorin) that are associated with developing FBR greatly improve the cytotoxicity of CTLs and NK cells in the lung from stage 3 breast cancers by increasing their production of Perforin/Granzyme, Fas/TRAIL and IFNr/TNFa. Our results highlight the potential of FBR-associated biomolecules to be used as immune-editing anticancer drugs and also inspire the development of therapeutic implants to actively catch and eradicate metastatic cells.
Citation Format: Jing Wang, Matthew Hall, Grace Bushnell, Joseph Decker, Sophia Orbach, Ravi Raghani, Yining Zhang, Aaron Morris, Jeffery Ma, Pridvi Kandagatla, Jacqueline Jeruss, Lonnie Shea. Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-360.
Biometric authenticator algorithm based on multiresolution analysis
Authors: Kerrache Soumia , Mohammed Beladgham , Aymen Hamza , Ibrahim Kadri 
Published: September 2020

Features extraction is an essential process in identifying person biometrics because the effectiveness of the system depends on it. Multiresolution Analysis success can be used in the system of a person’s identification and pattern recognition. In this paper, we present a feature extraction method for two-dimensional face and iris authentication. Our approach is a combination of principal component analysis (PCA) and curvelet transform as an improved fusion approach for feature extraction. The proposed fusion approach involves image denoising using 2D-Curvelet transform to achieve compact representations of curves singularities. This is followed by the application of PCA as a fusion rule to improve upon the spatial resolution. The limitations of the only PCA algorithm are a poor recognition speed and complex mathematical calculating load, to reduce these limitations, we are applying the curvelet transform. <br /> To assess the performance of the presented method, we have employed three classification techniques: Neural networks (NN), K-Nearest Neighbor (KNN) and Support Vector machines (SVM).<br />The results reveal that the extraction of image features is more efficient using Curvelet/PCA.
Performance analysis of flow-based attacks detection on CSE-CIC-IDS2018 dataset using deep learning
Authors: Farhan Rawaa Ismael , Maolood Abeer Tariq , Hassan Nidaa Flaih 
Published: September 2020

<p>The emergence of the Internet of Things (IOT) as a result of the development of the communications system has made the study of cyber security more important. Day after day, attacks evolve and new attacks are emerged. Hence, network anomaly-based intrusion detection system is become very important, which plays an important role in protecting the network through early detection of attacks. Because of the development in machine learning and the emergence of deep learning field, and its ability to extract high-level features with high accuracy, made these systems involved to be worked with real network traffic CSE-CIC-IDS2018 with a wide range of intrusions and normal behavior is an ideal way for testing and evaluation . In this paper , we test and evaluate our deep model (DNN) which achieved good detection accuracy about 90% .</p>
A hybrid control system for investigating a high level of decision in IoT
Authors: Al-Obaidi Mohanad Ali Meteab , Ali Basim Jamil , H.Ssaud Jamila , Sutikno Tole 
Published: September 2020

<span lang="IN">In the modern world, the search started for cheap and efficient operating system sources has begun can converted to civilian ends</span><span>.</span><span lang="IN"> Internet of Things (IoT) is one of the most realistic applications for remote control and remote management using a wide network.</span><span lang="EN">In this paper, a control system is designed and built to manage and control traffic lights and street lighting systems, as well as turning on/off generators in a small virtual environment.</span><span> This was implemented by designing and building a hybrid electronic circuit that combines the closed-circuit control system and the open circuit system. The closed circuit regulates the system according to the desired condition without operator interaction; while the open circuit operates on demand. This type of a hybrid control system demonstrated its high flexibility by controlling devices and its high efficiency compared to the closed circuit and the open circuit system independently. It also helps reduce the number of maintenance guys and energy consumption as well as the cost.</span>