bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical Research on Impacting Load and Structural Response for a Model Experiment of High-Speed Craft
Authors: Liu Weiqin , Qin Yuxin , Hu Yuchen , Vladimir Nikola , Xu Shuangxi , Wu Yigang 
Published: March 2024

Abstract
High-speed craft typically utilizes hydroplane boat-type and large power engine to obtain high-speed in water. However, these designs result in significant hydrodynamic nonlinearities, including slamming, wetness, sliding, and dolphin effect. As a result, high-speed craft exhibits complex impact load characteristics and structural responses, which have garnered considerable attention from ship mechanics researchers. This paper studies impacting load and structural response of a high-speed craft by means of numerical approach that combines computational fluid dynamics (CFD) and finite element method (FEM). A model experiment of high-speed craft is selected to simulate impact load and structural response. The craft model consists of two ship bodies and a keel beam, and a number of pressure sensors and strain gaugesare arranged to capture the impacting pressure and vertical bending moment (VBM). A numerical fluid-structure interaction (FSI) approach is employed to investigate the model experiment of the high-speed craft by coupling CFD and FEM. CFD is utilized to solve the hydrodynamics of the high-speed craft. Dynamics of fluid-body interaction (DFBI) and overset grid algorithm are employed to accurately simulate the motion of the craft. Dynamic FEM is used to calculate structural response of high-speed craft, structural VBM is obtained. Two-way FSI is employed to realize coupling of CFD and FEM. This involves iterating the wave pressures and structural displacement to make progress. Ultimately, the numerical results and experimental results, which encompass impacting pressure, craft motion, and VBM, are compared and analyzed, demonstrating a high degree of agreement. Numerical methods can be employed to analyze the impacting load and structural response for high-speed craft.
Specific interaction between Group B
Streptococcus
CC17 hypervirulent clone and phagocytes
Authors: Bourrel Anne-Sophie , Picart Amandine , Fernandez Jose-Carlos , Hays Constantin , Mignon Virginie , Saubaméa Bruno , Poyart Claire , Fouet Agnès , Tazi Asmaa , Guignot Julie 
Published: March 2024

ABSTRACT

Streptococcus agalactiae
also named Group B
Streptococcus
(GBS) is the most significant pathogen causing invasive infections, such as bacteremia and meningitis, in neonates. Worldwide epidemiological studies have shown that a particular clonal complex (CC) of capsular serotype III, the CC17, is strongly associated with meningitis in neonates and is therefore, designated as the hypervirulent clone. Macrophages are a permissive niche for intracellular bacteria of all GBS clones. In this study, we deciphered the specific interaction of GBS CC17 strains with macrophages. Our study revealed that CC17 strains are phagocytosed at a higher rate than GBS non-CC17 strains by human monocytes and macrophages both in cellular models and in primary cells. CC17-enhanced phagocytosis is due to an initial enhanced-attachment step to macrophages mediated by the CC17-specific surface protein HvgA and the PI-2b pilus (Spb1). We showed that two different inhibitors of scavenger receptors (fucoidan and poly(I)) specifically inhibited CC17 adhesion and phagocytosis while not affecting those of non-CC17 strains. Once phagocytosed, both CC17 and non-CC17 strains remained in a LAMP-1 positive vacuole that ultimately fuses with lysosomes where they can survive at similar rates. Finally, both strains displayed a basal egress which occurs independently from actin and microtubule networks. Our findings provide new insights into the interplay between the hypervirulent GBS CC17 and major players of the host’s innate immune response. This enhanced adhesion, leading to increased phagocytosis, could reflect a peculiar capacity of the CC17 lineage to subvert the host immune defenses, establish a niche for persistence or disseminate.
Harms and Benefits Inventory (HBI): initial validation of a novel assessment of perceived harms and benefits of firearm policies and practices
Authors: Grasso Damion , Raissian Kerri M , Doucette L , McGuire Austen Bradley , Dineen Jennifer Necci 
Published: March 2024

IntroductionUnderstanding gun owners’ perceptions of potential firearm policies’ harms and benefits is critical to successful policy development and implementation. We used national survey data to develop and validate a novel instrument, the Harms and Benefits Inventory (HBI), for policy-makers and advocates to better consider the citizen perspective.MethodWe conducted a nationally representative survey of American gun owners and non-owners (N=2007) using the Social Science Research Solutions probability panel. The survey included 31 candidate HBI items and questions about gun ownership and exposure, storage and carry behaviours, policy positions, and sociodemographic characteristics. Exploratory factor analyses (EFAs) were conducted on HBI items from a randomly selected subsample (N=1003) and then tested with a confirmatory factor analysis (CFA) on data from the second half of the sample (N=1004).ResultsThe best-fitting EFA model was upheld in the CFA and included 21 items with 5 underlying factors. Underlying factors included: (1) firearm regulation, cost and accessibility, (2) special restrictions, (3) permit and education, (4) relaxed restrictions and (5) and hobby and sport. Internal consistency was good to excellent within each of the five scales. Validity was supported by correlations between HBI scales and survey questions.DiscussionFindings support the validity of the HBI in assessing perceptions of potential harms and benefits of firearm policies and practices. Understanding perceptions of potential harms and benefits of gun policies at the time of development or implementation can improve uptake and reduce unintended consequences of these policies.
Abstract 1: Biomarkers of response and acquired resistance to TIL-ACT in solid tumors
Authors: Robinson Welles , Castro Andrea , Al-Bakir Maise , Gartner Jared J. , Chamberlain Christopher Aled , Kverneland Anders H. , Borch Troels H. , Svane Inge Marie , Donia Marco , Robbins Paul , Litchfield Kevin 
Published: March 2024

Abstract
Background: Cancer immunotherapy has revolutionized cancer treatment in the last decade. However, most patients either do not respond to immunotherapy or eventually relapse so there is a need to identify biomarkers of response and understand mechanisms of resistance. Most biomarker studies have analyzed patients treated with immune checkpoint inhibitors (CPI) therapy while the few studies of adoptive cell transfer of tumor infiltrating lymphocytes (TIL-ACT) have analyzed relatively small patient cohorts.
Methods: To systematically identify biomarkers of response and resistance to TIL-ACT, we collected published and unpublished whole-exome and transcriptomic data for tumors from 400 patients treated with TIL-ACT from five tumor types across four institutions and processed these datasets using a standardized bioinformatic pipeline.
Results: To identify biomarkers of response in pre-treatment tumors, we analyzed previously reported biomarkers and performed biomarker discovery in our cohorts. For the subset of 200 patients with T cell reactivities identified from the infusion products and fresh tumor, we refined our biomarkers to include neo-antigen reactivities in addition to identifying both mutational processes and transcriptional signatures associated with neo-antigens reactivity. To identify mechanisms of acquired resistance to TIL-ACT, we analyzed 15 patients with paired pre- and post-treatment tumors and found multiple mechanisms of immune evasion specific to infused reactive T cells including loss of heterozygosity of the HLA allele presenting the neo-antigen, genomic loss of the neo-antigen and inactivation of interferon-gamma signaling pathway.
Conclusions: In summary, we will present the biomarkers landscape of TIL-ACT therapy including differences between histology and across treatment modalities to improve our understanding of the mechanisms of treatment response.
Citation Format: Welles Robinson, Andrea Castro, Maise Al-Bakir, Jared J. Gartner, Christopher Aled Chamberlain, Anders H. Kverneland, Troels H. Borch, Inge Marie Svane, Marco Donia, Paul Robbins, Kevin Litchfield. Biomarkers of response and acquired resistance to TIL-ACT in solid tumors [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 1.
Abstract 1004: Establishing lung adenocarcinoma cell lines to mitigate lung cancer health disparities
Authors: Lugo Sofia , Leon Christopher , Gladstone Matthew , Yan Chunli , Lamango Nazarius S. , Offringa Ite A. , Ofosu-Asante Kweku , Huang Yong , Mensah-Mamfo Justin K. 
Published: March 2024

Abstract
Lung cancer remains the leading cause of cancer death worldwide and is a pronounced source of cancer health disparities. Black/African American (B/AA) individuals demonstrate the highest lung cancer death rates when compared to other ethnic/racial groups. B/AA males exhibit a 15% higher lung cancer death rate and a 12% higher lung cancer incidence when compared to White males. Lung adenocarcinoma (LUAD) is the most common histological subtype in all races including B/AA. To study lung cancer and its related disparities, essential tools such as lung cancer cell lines are important; they can be used for molecular studies of lung cancer development, progression, development of new therapies and pre-clinical drug testing. We reviewed the literature (Leon et al. 2023, Frontiers in Oncology, Vol. 13, p. 1187585, 2023) and identified only 30 unique B/AA cell lines out of ~800 cell lines available, with the majority of cell lines being from White and Asian patients. Moreover, only 6 B/AA cell lines were derived from patients with LUAD. We are in the process of developing additional LUAD cell lines from patients as well as alveolar epithelial cell lines that can be used to model LUAD development. In addition, we are generating multiple independent isogenic cell line variants from existing lung cancer cell line NCI-H23, derived from a B/AA male patient harboring a KRASG12C heterozygous mutation. We are using CRISPR/Cas-9-based genome editing to replace the KRASG12C mutation with other KRAS mutations found in B/AA patients, including KRASG12V, KRASG12D, KRASG12A, and KRASG13C. We will perform whole genome sequencing to exclude off target effects of the CRISPR engineering. We will use isogenic cell lines to test the efficacy of polyisoprenylated cysteinyl amide inhibitors (PCAIs) and other drugs on cell lines bearing the different KRAS mutations. PCAIs were developed to target cells carrying mutant KRAS. Our efforts will provide tools to limit cancer health disparities and serve as a foundation for future research.
Supported by grants U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH)/National Cancer Institute (NCI) and the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI.
Citation Format: Sofia Lugo, Christopher Leon, Matthew Gladstone, Chunli Yan, Nazarius S. Lamango, Ite A. Offringa, Kweku Ofosu-Asante, Yong Huang, Justin K. Mensah-Mamfo. Establishing lung adenocarcinoma cell lines to mitigate lung cancer health disparities [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 1004.
Abstract 1094: Utilizing CRISPR-Cas13 as a novel functional genomics tool to characterize PAX3-FOXO1 in alveolar rhabdomyosarcoma
Authors: Zhao Andrea , Brown Lauren M. , Fareh Mohamed , Ekert Paul G. 
Published: March 2024

Abstract
Background: CRISPR-Cas13 (Cas13) is an RNA editing system that can knockdown gene transcripts with higher efficiency and specificity than RNA interference technologies. We are exploring the utility of Cas13 as a robust novel functional genomics tool to understand the biology of the PAX3-FOXO1(P3F1) gene fusion in alveolar rhabdomyosarcoma (ARMS). Our goal is to identify gene dependencies and novel druggable targets. [LB1]
Aim: This study aims to functionally characterize P3F1 in paediatric cancer cell lines using Cas13. [LB2]
Methods & Results: Transient transfection and viral transduction of Cas13 vector systems were used to demonstrate that Cas13 knockdown of target gene expression can be achieved in ARMS cell lines. We developed guides to specifically target P3F1 expression and tested their efficiency in HEK293T cells. Cas13 function was validated with a mCherry knockdown proof-of-concept expression in the ARMS cell lines Rh5 and Rh30. 90-95% knockdown efficiency was seen over three independent experiments. Ten P3F1 breakpoint targeting guides were designed and screened first in a HEK293T P3F1 overexpression model to select optimal high efficiency targeting guides. The highest efficiency targeting guide showed a GFP reduction of 70% in three independent experiments. High-efficiency Cas13 guides were taken forward into Rh5 cells to knockdown endogenous P3F1 expression which were validated by western blotting and RT-PCR. Western blots of Cas13 sorted Rh5 cells showed that guide 1150 was able to knockdown P3F1 protein expression by ~70%.
Discussion/Conclusion: These findings demonstrate the high efficiency and specificity of the Cas13 system to silence P3F1, and other oncogenic fusion drivers. Further studies will utilize Cas13 to characterize the molecular and cellular consequences of P3F1 gene-silencing in patient-derived ARMS cell lines.
Citation Format: Andrea Zhao, Lauren M. Brown, Mohamed Fareh, Paul G. Ekert. Utilizing CRISPR-Cas13 as a novel functional genomics tool to characterize PAX3-FOXO1 in alveolar rhabdomyosarcoma [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 1094.
Abstract 1130: Leveraging the IVIS imaging technologies for drug potency testing in orthotopic and metastatic tumor models
Authors: Huang Jingqi , Jin Jing , Duan Hongchen , Yang Xueqin , Jin Wenhao , Zhang Yiming , Zhang Lihui , Xu Gaoyang , Xie Liya , Li Wentao 
Published: March 2024

Abstract
Assessing anti-tumor drug potency is significantly enhanced using orthotopic and metastasis mouse tumor models. These models imitate the tumor's native environment, biological complexities, and challenges of drug delivery via blood perfusion, thereby providing a high predictive value for clinical outcomes. In this poster, we demonstrate how the IVIS optical imaging technology is employed to determine the effects of two drugs on two tumor models: •The KRAS (G12C) inhibitor, AMG510, was evaluated on the luciferase-expressing Miapaca-2 pancreatic orthotopic model •The third-generation EGFR inhibitor, AZD9291, was tested on the luciferase-expressing NIC-H1975 intracranial metastatic model Both drugs showed significant anti-tumor activity. In addition to potency testing, each drug was administered in single doses for pharmacodynamic analysis, evaluating pERK/ERK and DUSP6 levels. The pERK levels decreased after treatment, which is in line with the mechanism of action of the inhibitors. Our research illustrates that IVIS imaging offers a robust method for monitoring anti-tumor activity of drugs in orthotopic and metastatic tumor models, empowering scientists to assess new drug candidates by using biologically relevant animal models.
Citation Format: Jingqi Huang, Jing Jin, Hongchen Duan, Xueqin Yang, Wenhao Jin, Yiming Zhang, Lihui Zhang, Gaoyang Xu, Liya Xie, Wentao Li. Leveraging the IVIS imaging technologies for drug potency testing in orthotopic and metastatic tumor models [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 1130.
Abstract 118: Development of a novel murine model, NCG-M/hIL15, for enhanced post-HSC transplantation immunoreconstruction
Authors: Wang Huiyi , Xing Jun , Fan Jialu , Fan Yuan , Zhao Jing , Gao Xiang , Ju Cunxiang 
Published: March 2024

Abstract
Advances in the field of immunology and hematopoietic stem cell (HSC) transplantation have prompted the development of murine models that faithfully recapitulate human immune responses. We present the NCG-M/hIL15 model, an innovative advancement in the realm of preclinical research, addressing two key challenges associated with existing models: the limited capacity for human natural killer (NK) cell regeneration in NCG-M and the suboptimal reconstitution of T cells, myeloid lineage cells in NCG-hIL15 mice.
Compared to the conventional NCG-M model, the NCG-M/hIL15 model demonstrates a significant improvement in its ability to regenerate human NK cells post-HSC transplantation. This advancement offers a valuable tool for studying NK cell biology, immune surveillance, and antitumor responses.
Furthermore, when compared to the NCG-hIL15 model, the NCG-M/hIL15 model outperforms in the reconstitution of human T cells and myeloid lineage cells, contributing to a more comprehensive simulation of human immune responses. The overall survival of mice in this model is notably stable, further enhancing its utility for long-term immunological studies.
The NCG-M/hIL15 model not only advances our understanding of human immune responses but also has significant implications for the development of novel immunotherapies and the preclinical evaluation of HSC transplantation strategies. This novel murine model offers a more accurate representation of the human immune system, with the potential to expedite the development of innovative therapeutic interventions. We present this model as a valuable addition to the preclinical research toolkit, promising a deeper understanding of immunology and a brighter future for clinical applications.
Citation Format: Huiyi Wang, Jun Xing, Jialu Fan, Yuan Fan, Jing Zhao, Xiang Gao, Cunxiang Ju. Development of a novel murine model, NCG-M/hIL15, for enhanced post-HSC transplantation immunoreconstruction [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 118.
Abstract 1219: In vivo delivery of CRISPR-Cas9 using lipid nanoparticles enables ATAD3A gene depletion to enhance RAS-targeted therapy
Authors: Chen Fanghui , Lang Liwei , Li Yamin , Zheng Wei , Teng Yong 
Published: March 2024

Abstract
Targeting mitochondrial oncoproteins presents a new concept in developing effective cancer therapeutics. ATAD3A is a nuclear-encoded mitochondrial enzyme that contributes to mitochondrial dynamics, cholesterol metabolism, and signal transduction. Our previous study has demonstrated elevated expression of ATAD3A in head and neck squamous cell carcinoma (HNSCC) primary tissues and cultured cell lines. Loss of function suppresses HNSCC cell growth and elicits tumor regression in orthotopic tumor-bearing mice. Mechanistically, ATAD3A interacts with ERK1/2 in the mitochondria of HNSCC cells in the presence of VDAC1, and the ATAD3A-ERK1/2 signaling axis drives HNSCC development in a RAS-independent fashion. CRISPR-Cas9 has revolutionized genome engineering and has been intensively used to modify cancer-associated genes. However, challenges remain as CRISPR editing components must be transported into cells to exert their function. There is a need to explore effective in vivo delivery systems to accelerate the clinical use of CRISPR-Cas9. As no drug is available to target ATAD3A directly, we developed CRISPR-based ATAD3A-targeting nanodrugs by loading Cas9 mRNA and anti-ATAD3A sgRNAs into lipid nanoparticles (LNPs) that have become clinically acceptable delivery system due to low toxicity and high delivery efficacy and biocompatibility. As expected, treatment tongue tumors established in NSG mice with LNP-sgATAD3A remarkably repressed tumor growth. Most interestingly, the addition of LNP-sgATAD3A to the RAS inhibitor salirasib potentiated anticancer activity for HNSCC compared with the efficacy resulting from single-arm treatment. These novel and significant findings demonstrate a novel approach to inhibiting ATAD3A in tumor cells and provide a possible therapeutic strategy to enhance the success of multimodality therapy in cancer patients.
Citation Format: Fanghui Chen, Liwei Lang, Yamin Li, Wei Zheng, Yong Teng. In vivo delivery of CRISPR-Cas9 using lipid nanoparticles enables ATAD3A gene depletion to enhance RAS-targeted therapy [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 1219.
Abstract 1265: Comparison of mortality- vs. stage-based endpoints in randomized trials of cancer screening: A systematic review with implications for multi-cancer screening trials
Authors: Feng Xiaoshuang , Zahed Hana , Onwuka Justina , Johansson Mattias , Etzioni Ruth , Callister Matthew E. , Robbins Hilary A. 
Published: March 2024

Abstract
Background: Randomized controlled trials (RCTs) assessing the endpoint of late-stage cancer incidence, rather than the gold-standard of cancer-specific mortality, are proposed for evaluation of multi-cancer early detection tests.
Methods: We conducted a systematic review to assess whether stage-based endpoints can provide a valid alternative for mortality-based endpoints (registration: PROSPERO CRD42023411132). We searched PubMed to identify RCTs of cancer screening interventions published in English before January 20, 2023. Inclusion required that RCTs report, by study arm, numbers of cancer-specific deaths and cancer cases distinguishable between stages I-II vs. III-IV. Data extraction was done by 2 separate reviewers and included the numbers of cancer cases, deaths, and participants by study arm. For each trial, we calculated the percentage reduction in the cumulative (a) late-stage cancer incidence and (b) cancer-specific mortality between the intervention and control arms. We compared these two endpoints based on Pearson correlation coefficients, fixed-effects meta-analysis, and binary statistical significance.
Results: We analyzed 41 trials ranging in size from 2,500 to 409,000 participants. Correlation between the reduction in cancer-specific mortality vs. stage III-IV cancer was strong for lung (Pearson’s ρ=0.92, n=12), breast (ρ=0.70, n=6), and ‘other’ cancers (ρ=0.69, n=8) but weak for colorectal (ρ=0.39, n=11) and prostate cancers (ρ&lt;0, n=4). The overall correlation by fixed-effects meta-analysis across cancer types was 0.71 (95%CI=0.47-0.86) (I2=0.55). In larger trials, there was a smaller deviation between the observed reduction in cancer-specific mortality and that predicted, by cancer type, based on the trial’s reduction in stage III-IV cancer (p=0.02). Of 12 trials demonstrating a statistically significant reduction in stage III-IV cancer incidence (p&lt;0.05), 5 also showed reduced cancer-specific mortality (42%).
Conclusions: In screening RCTs, reductions in late-stage cancer vs. cancer-specific mortality are correlated, but with important differences by cancer type. Screening interventions that reduce late-stage cancer incidence do not necessarily reduce cancer-specific mortality.
Citation Format: Xiaoshuang Feng, Hana Zahed, Justina Onwuka, Mattias Johansson, Ruth Etzioni, Matthew E. Callister, Hilary A. Robbins. Comparison of mortality- vs. stage-based endpoints in randomized trials of cancer screening: A systematic review with implications for multi-cancer screening trials [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 1265.