bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 7423: BATCH-FLEX: Feature-level equalization of x-batch in heterogeneous cancer data
Authors: Davis Joshua , Obermayer Alyssa , Duong Thac , Hesterberg Rebecca , Wang Xuefeng , Teng Mingxiang , Grass G. Daniel , Shaw Timothy 
Published: March 2024

Abstract
Purpose: Develop a shiny application to help integrate cancer datasets and guide researchers in selecting an appropriate method of correction for their technical artifacts.
Description: Integrative analysis of heterogeneous expression data remains challenging due to variations in platform, RNA quality, sample processing, and other unknown technical effects. As the field performs omics profiling of samples from cancer patients and murine models, there is the need for harmonizing, identifying, and correcting these technical effects to ensure robust analysis on the treatment and conditional effects of the underlying genetics or biological events. However, selecting and implementing different approaches for removing unwanted batch effects can be a time-consuming and tedious process, especially for more biologically focused investigators. In this project, we present Shiny BATCH-FLEX, a Shiny app to rapidly visualize batch correction by established batch correction methods such as ComBat, Mean Centering, ComBatSeq, and Limma RemoveBatchEffect. With BATCH-FLEX, users can visualize the contribution of variance of a factor before and after correction using principal component analysis, relative log expression plots, heatmaps, and explanatory variables. Users can also save all plots and matrices as a single ZIP file for further downstream analysis.
Results: As a proof of concept, we assessed BATCH-FLEX using simulated data generated from a linear model framework introduced by Gagnon-Bartsch and Speed, which assumes that gene expression measurements can be distilled to a combination of the biological signal, systemic nose, and random noise. BATCH-FLEX was able to successfully identify and remove the introduced effect using each of the batch correction methods listed above. Next, we evaluated BATCH-FLEX using a comprehensive collection of bladder cancer data consisting of microarray data from 13 studies spanning 1452 samples. Following the cleaning of study-dependent noise, BATCH-FLEX was successful in revealing the heterogeneity among bladder cancer based on known sample type annotations.
Conclusion: We have developed BATCH-FLEX, a tool for oncologic researchers to rapidly assess, select, and implement commonly used batch correction methods. This tool is available at https://github.com/shawlab-moffitt/BATCH-FLEX. Our integrative web portal of a Bladder Cancer Resource for Translational Science (BEACON) will also be shared at the meeting.
Citation Format: Joshua Davis, Alyssa Obermayer, Thac Duong, Rebecca Hesterberg, Xuefeng Wang, Mingxiang Teng, G. Daniel Grass, Timothy Shaw. BATCH-FLEX: Feature-level equalization of x-batch in heterogeneous cancer data [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 7423.
Abstract 7567: In-depth mass cytometry analysis reveals different immune cell composition of unique molecular subtypes in extensive stage small-cell lung cancer
Authors: Li Yuekang , Qu Jingjing , Wu Binggen , Shen Qian , Sun Wenjia , Chen Lijun , Wang Bo , Ying Lixiong , Zhou Jianya , Zhou Jianying 
Published: March 2024

Abstract
Background: A novel molecular subtype classification was fashionable for small cell lung cancer (SCLC). However, the distribution of SCLC molecular subtype classification in Chinese patients were unknown, especially extensive stage (ES)-SCLC. It should validate and define their associated microenvironments across subtypes in ES-SCLC.
Method: We used immunohistochemical (IHC) to evaluate SCLC markers of the subtypes including ASCL1, NEUROD1, POU2F3, SCLC-A/N/P in 135 ES-SCLC tumors. Peripheral blood of 24 ES-SCLC patients was test by mass cytometry using time-of-flight (CyTOF) to evaluate the differences in immune subsets regard to the subtype tumor microenvironment (TME). Validation was performed using flow cytometry and multiplex IF.
Results: ASCL1, NEUROD1, POU2F3, and Inflamed were account for 60.7%, 28.9%, 7.4%, and 18.5% of SCLC tumors, respectively. Significant intratumoral heterogeneity was observed with 15.6% of the tumors being both positive for SCLC-A and -N subtype markers, respectively. The SCLC-I type possessed more CD8+ T-cells infiltration and had higher frequency an ‘inflamed’ immunophenotyped. CyTOF data showed greater CD161+CD127+CD8+T cells proportion in SCLC-I than SCLC-N subtypes before and after anti-immunotherapy. Furthermore, we validated that lung tissue of SCLC-I were infiltrated more CD161+CD127+CD8+T cells compared to SCLC-N subpopulation(P=0.0281). Flow cytometry further showed the stronger immune activation of CD161+CD127+CD8+T cells in SCLC-I types induced higher expression of GZMB and GNLY and lower-expression of T-cell exhaustion markers PD-1,TIGIT and LAG3 in comparison with SCLC-N types. We further confirmed that the high level of CD161+CD127+CD8+T associated with a favorable treatment response and prolonged overall survival.
Conclusion: The present study validated the molecular subtypes in ES-SCLC patients. Furthermore, SCLC-I subtype has longer PFS and OS than SCLC-A, -N and -P patients. Our research not only provides an insight into the immune landscape of ES-SCLC but also sheds light on a special subset of CD161+CD127+CD8+T cells with prognostic and therapeutic significance.
Citation Format: Yuekang Li, Jingjing Qu, Binggen Wu, Qian Shen, Wenjia Sun, Lijun Chen, Bo Wang, Lixiong Ying, Jianya Zhou, Jianying Zhou. In-depth mass cytometry analysis reveals different immune cell composition of unique molecular subtypes in extensive stage small-cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7567.
Abstract 7591: Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib
Authors: Ghandali Maryam , Srinivasan Praveen , Xia Yutong , Wong Eric T. , Sobol Robert W. , zhou Lanlan , Carneiro Benedito A. , Graff Stephanie L. , El-Deiry Wafik S. 
Published: March 2024

Abstract
Breast cancer is the most common cancer in women worldwide, and the fifth leading cause of cancer-related deaths globally. Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, is usually treated with surgery, chemotherapy, and radiation. Tumor Treating Fields therapy are FDA-approved for the treatment of glioblastoma (GBM) and malignant pleural mesothelioma (MPM).TT Fields use alternating electric fields to inhibit tumor growth through mitotic disruption, cellular damage, integrated stress response activation, and immune mechanisms and inhibit cell proliferation, induce cell death, and cause cell cycle arrest.TT Fields can induce BRCAness and when combined with PARP inhibition, this combination may result in synthetic lethality. We explored the effect of TTFields on two TNBC cell lines MDA-MB436 (BRCA1-mutant, p53-null) and MDA-MB468 (BRCA1 wild-type, p53-mutant) treated with TTFields (150 kHz) for 24 hours. Western blot analysis showed elevation of p21 independent of p53 mutational status. We examined the combination of PARP inhibitor (Talazoparib) with TTFields in MDA-MB468 cells to determine the effect of the combination in BRCA wild-type cancer cells. Western blot analysis showed p21 upregulation after 24 hours in combination without an increase in p53. p21 acts as a G1-checkpoint protein and loss of p21 expression has been observed in a high percentage of human breast cancer cells. Our results suggest a rational and potentially effective therapy that could be further developed and used for the treatment of breast cancer. Our ongoing studies are exploring potential mechanisms of synergy between PARP inhibitor Talazoparib and TTFields using various TNBC models, and the effect of the combination on cell cycle arrest in cell culture and in vivo.
Citation Format: Maryam Ghandali, Praveen Srinivasan, Yutong Xia, Eric T. Wong, Robert W. Sobol, Lanlan zhou, Benedito A. Carneiro, Stephanie L. Graff, Wafik S. El-Deiry. Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib [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 7591.
Abstract 879: The AVERON Notebook to discover druggable cancer dependencies through the mutant-directed protein-protein interactions
Authors: Chen Hongyue (Nicole) , Yeung Sean , Revennaugh Brian , Fu Haian , Ivanov Andrey A. 
Published: March 2024

Abstract
Cancer is a devastating disease that takes more than 10 million lives every year. The genomic alterations, such as mutations in cancer driver genes, can disrupt the essential networks of protein-protein interactions (PPIs), dysregulating major oncogenic pathways and inducing the transformation. While some mutations can disrupt existing PPIs, others can create neomorph PPIs (neoPPIs), which are unnatural for wild-type counterparts. Discovery of such mutant-created neoPPIs is vital for understanding the molecular mechanisms of mutant-driven tumorigenesis and developing new personalized clinical strategies in cancer. However, systematic experimental interrogation of the clinical significance and biological functions of neoPPIs is highly challenging. To address this critical challenge, we develop a novel computational platform called AVERON Notebook for identifying new Actionable Vulnerabilities Enabled by Rewired Oncogenic Networks. The AVERON employs specially designed algorithms and statistical techniques to i) Assess and compare the levels of neoPPIs in cancer patients; ii) Examine their impact on clinical outcomes; iii) Identify distinctive sets of signature genes and oncogenic pathways regulated by individual neomorph PPIs; and iv) Discover clinically significant neoPPI-regulated genes with available clinical compounds and approved drugs. Together, the AVERON Notebook provides a powerful tool for exploring the functional consequences of tumor-driving mutations mediated through the neoPPI networks and sheds new light on previously unexplored clinically actionable dependencies enabled by neomorph PPIs in cancer patients. The AVERON Notebook is freely available onGitHub: https://github.com/aivanovlab/averon_notebook and Code Ocean: https://doi.org/10.24433/CO.7986101.v1
Acknowledgments: This work was supported in part by NCI’s Informatics Technology for Cancer Research (ITCR) Program (R21CA274620, A.A.I.), Mary Kay Foundation Grant for Cancer Research (A.A.I), NCI Emory Lung Cancer SPORE (P50CA217691, H.F.), NCI P01CA257906 (H.F.), Career Enhancement Program (A.A.I., P50CA217691), Winship Cancer Institute (NIH 5P30CA138292).
Citation Format: Hongyue (Nicole) Chen, Sean Yeung, Brian Revennaugh, Haian Fu, Andrey A. Ivanov. The AVERON Notebook to discover druggable cancer dependencies through the mutant-directed protein-protein interactions [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 879.
Abstract 89: Comprehensive cell based bioassay approaches for characterization, and clinical development of therapeutic agonistic antibodies for cancer immunotherapy and autoimmune diseases
Authors: Chari Venkatesh , Lin-Jones Jennifer , Yang Luhan , Lamerdin Jane E. , Agrawal Gaurav 
Published: March 2024

Abstract
Agonistic antibodies are emerging as promising therapeutics for targeting immune checkpoints, particularly those within the TNF Receptor Superfamily, as they play a crucial role in regulating immune cell function, especially in the context of cancer treatment. In addition, there is also a growing focus on the potential of agonistic antibodies to selectively activate co-inhibitory checkpoint receptors. This offers a promising avenue for suppressing inflammation in autoimmune diseases and restoring tolerance in graft-vs-host disease (GvHD) while avoiding the complications of global immunosuppression.
While a substantial number of clinical trials are currently underway for oncology and autoimmune indications, there is a notable scarcity of commercially available assays to support the clinical development of this class of therapeutics, impacting their time-to-clinic. Existing assays frequently fail to accurately assess the agonistic activity of antibodies as they are unable to replicate the necessary physiologically relevant conditions.
In this context, we present several case studies that highlight the pivotal role of cell-based bioassay approaches developed by Eurofins DiscoverX in driving the characterization and clinical development of agonistic antibody therapeutics targeting various checkpoint receptors. Additionally, we discuss our data demonstrating the indispensable role of FcyR-mediated antibody clustering in establishing the otherwise elusive agonistic activity of antibodies.
Citation Format: Venkatesh Chari, Jennifer Lin-Jones, Luhan Yang, Jane E. Lamerdin, Gaurav Agrawal. Comprehensive cell based bioassay approaches for characterization, and clinical development of therapeutic agonistic antibodies for cancer immunotherapy and autoimmune diseases [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 89.
From Motion to Emotion: Visual Pathways and Potential Interconnections
Authors: Puce Aina 
Published: March 2024

Abstract
The two visual pathway description of Ungerleider and Mishkin changed the course of late 20th century systems and cognitive neuroscience. Here, I try to reexamine our laboratory's work through the lens of the Pitcher and Ungerleider new third visual pathway. I also briefly review the literature related to brain responses to static and dynamic visual displays, visual stimulation involving multiple individuals, and compare existing models of social information processing for the face and body. In this context, I examine how the posterior STS might generate unique social information relative to other brain regions that also respond to social stimuli. I discuss some of the existing challenges we face with assessing how information flow progresses between structures in the proposed functional pathways and how some stimulus types and experimental designs may have complicated our data interpretation and model generation. I also note a series of outstanding questions for the field. Finally, I examine the idea of a potential expansion of the third visual pathway, to include aspects of previously proposed “lateral” visual pathways. Doing this would yield a more general entity for processing motion/action (i.e., “[inter]action”) that deals with interactions between people, as well as people and objects. In this framework, a brief discussion of potential hemispheric biases for function, and different forms of neuropsychological impairments created by focal lesions in the posterior brain is highlighted to help situate various brain regions into an expanded [inter]action pathway.
Public engagement with COVID-19 preprints: Bridging the gap between scientists and society
Authors: Henke Justus 
Published: March 2024

Abstract
The surge in preprint server use, especially during the COVID-19 pandemic, necessitates a reexamination of their significance in the realm of science communication. This study rigorously investigates discussions surrounding preprints, framing them within the contexts of systems theory and boundary objects in scholarly communication. An analysis of a curated selection of COVID-19-related preprints from bioRxiv and medRxiv was conducted, emphasizing those that transitioned to journal publications, alongside the associated commentary and Twitter activity. The data set was bifurcated into comments by biomedical experts versus those by nonexperts, encompassing both academic and general public perspectives. Findings revealed that while peers dominated nearly half the preprint discussions, their presence on Twitter was markedly diminished. Yet, intriguingly, the themes explored by these two groups diverged considerably. Preprints emerged as potent boundary objects, reinforcing, rather than obscuring, the delineation between scientific and nonscientific discourse. They serve as crucial conduits for knowledge dissemination and foster interdisciplinary engagements. Nonetheless, the interplay between scientists and the wider public remains nuanced, necessitating strategies to incorporate these diverse discussions into the peer review continuum without compromising academic integrity and to cultivate sustained engagement from both experts and the broader community.
Prevalence, Risk Factors, and Metabolic Characteristics of Metabolically Healthy Obesity in Patients Seeking Bariatric Surgery: A Cohort Study
Authors: Zheng Xuejing , Tian Chenxu , Xu Guangzhong , Du Dexiao , Zhang Nengwei , Wang Jing , Sang Qing , Wuyun Qiqige , Chen Weijian , Lian Dongbo , Wang Dezhong , Amin Buhe , Wang Liang 
Published: March 2024

Background Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight. Objective This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery. Methods A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes. Results Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender ( P = .021) and younger age ( P < .001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%). Conclusion Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population.
How do non-Western authoritarian countries respond to disasters? Structural difference from the pluralistic model
Authors: Oh Namkyung , Ding Minshuai , Kim Yunkwon 
Published: March 2024

Effective coordination, networking, and voluntary civil engagement are crucial for ensuring effective disaster responses. It should be noted, however, that these recommendations are primarily derived from the experiences of Western pluralistic countries. Thus, there has been insufficient consideration given to the applicability of these recommendations to non-pluralistic countries and the ways in which non-Western authoritarian countries navigate the difficulties of coordinating and establishing networks with civil sector organizations. This study broadens the scope of research by examining non-Western authoritarian countries through an analysis of how China responded to the floods of 2020. The results of the study indicate that the Chinese flood response system was primarily government-driven, centralized, and hierarchical. According to the pluralistic model, this arrangement encounters difficulties in integrating resources and information from partners in different sectors and jurisdictions. Consequently, this poses additional challenges to the Chinese disaster response systems. Nevertheless, the study findings reveal that the Chinese system proficiently resolved problems. This was accomplished by flattening the hierarchical structure via innovative interventions and remedying the lack of voluntary civic sector engagement through mass mobilization. Consequently, it would be fallacious to hold that the pluralist model can be effortlessly transplanted to non-Western authoritarian nations without regard for their distinct political, cultural, economic, and social contexts. Points for practitioners To improve disaster response, practitioners should consider adapting hierarchical networks and embracing flexibility. This can be achieved by reducing bureaucratic layers, which enhances effectiveness and encourages innovative interventions for streamlined decision making. It is important to emphasize provincial–local support and mass mobilization, as seen in China, which underscores the need for engaging civil sectors in non-pluralistic contexts. Context-specific approaches are crucial and should consider political, cultural, and social factors. Transforming hierarchical structures into modular networks may improve response.
Use of the GORE Conformable Excluder Device in Highly Angulated Aortic Neck Anatomy: Mid-term Outcomes
Authors: GnanaDev Raja , Malkoc Aldin , Hsu Jeffrey , Behseresht Jason , Tayyarah Majid , Vo Trung D. , Andacheh Iden 
Published: March 2024

Introduction Patients with complex aortic anatomy require meticulous surgical planning to optimize intraoperative and postoperative outcomes. The GORE Excluder Conformable Abdominal Aortic Aneurysm Endoprosthesis (CEXC Device, WL Gore and Associates, Flagstaff, AZ) allows for endovascular treatment of highly angulated and short proximal neck abdominal aortic aneurysms (AAA). Owing to its recent approval, short-term clinical outcomes of this device remain scarce. Report In this report, we present a case series of 3 patients who underwent endovascular aortic repair using the GORE Excluder Conformable device with highly angulated (>70°) aortic neck anatomy. Endografts were deployed in a radiology suite using standard 2D angiography in conjunction with a CYDAR Medical (Wilmington, Delaware) reconstructed 3D overlay. The patients’ ages were 85, 67, and 85 years. The mean abdominal aortic aneurysm diameter in these cases was 6.9 cm. The mean proximal neck length was 2.1 cm, proximal mean neck angulation was 83°. The mean operative time, total fluoroscopy time, and contrast used were 208 minutes, 28.3°minutes, and 94.5 milliliters, respectively. No adjunctive procedures, such as proximal cuff or endo-anchors, were performed at the time of index procedure. Discussion Type Ia endoleak was observed in 1 patient post-operatively but after treatment with an aortic cuff there was no evidence of enlarging aneurysm sac. The GORE Excluder Conformable Endoprosthesis expands access to endovascular management of AAAs. Our early experience with this device demonstrated excellent patient and clinical outcomes in a highly angulated neck anatomy.