bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 893: Studying the impact of CNVs on expression at single-cell resolution in HGSOC using autoencoders
Authors: Falco Matias Marin , Närhi Teemu , Erkan Erdogan Pekcan , Hynninen Johanna , Vähärautio Anna 
Published: March 2024

Abstract
High-grade serous ovarian cancer (HGSOC) is one of the most lethal gynecological malignancies. Lack of common targetable oncogenic mutations has complicated the development of directed therapies to combat emerging resistance. This malignancy is mainly characterized by the mutation of gene TP53, which promotes genome instability for the emergence of extensive copy number variations (CNVs). However its impact on gene expression at the single-cell level is not well understood. In this study, we aim to investigate the effect of CNVs on transcriptomic signatures by taking advantage of variational autoencoders (VAE) ability for dimensionality reduction, unsupervised learning and feature extraction. The use of VAEs is becoming more popular for the analysis of scRNAseq data, and scVI is one of the most versatile VAE applications performing wide variety of tasks. Here, we used single-cell RNA sequencing (scRNA-seq) data from 90 longitudinal samples of 64 HGSOC patients and inferred CNVs in each cell using inferCNV, an established computational pipeline. Then, we modified scVI algorithm to allow the VAE to reconstruct CNVs from a latent space originated from gene expression profiles and viceversa. Our models were capable of reconstructing CNV profiles accurately from expression data and also remove batch effect. From these models we could observe how, after the integration of genomic information, the latent clusters produced from the transcriptomic space were influenced by the amplifications or deletions of certain genomic regions. Moreover, some of these clusters were characterized by the alteration of important oncogenes in HGSOC, such as KRAS and CCNE1, and allowed us to focus on the transcriptomic consequences of their amplifications. With the results from the approach presented here, we gained a more comprehensive picture of the impact of genomic alterations on HGSOC. As future work, we plan to validate of this results on external cohorts and link the identified signatures to clinically relevant features such as prognosis or chemotherapy response.
Citation Format: Matias Marin Falco, Teemu Närhi, Erdogan Pekcan Erkan, Johanna Hynninen, Anna Vähärautio. Studying the impact of CNVs on expression at single-cell resolution in HGSOC using autoencoders [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 893.
Abstract 906: Large-scale surface protein abundance prediction from single-cell transcriptomes with a zero-shot model and its applications to cancer research
Authors: Chen Ruoqiao , Chen Bin , Zhou Jiayu 
Published: March 2024

Abstract
We develop SPIDER, a zero-shot model which can predict the abundance for a large scale (&gt;2,000) of surface proteins from single-cell transcriptomes in various contexts. This is to overcome the challenges in current single-cell protein abundance quantification tools (e.g., flow cytometry, CITE-seq) and computational models (e.g., totalVI, Seurat, cTPnet), where routinely only &lt;300 surface proteins can be quantified or predicted. Comprehensive benchmarking on four external validation sets shows that the prediction accuracy of SPIDER outperforms other state-of-the-art methods including Seurat, totalVI, and cTPnet, with a prediction accuracy elevated as much as 42.5% in new contexts. We further conduct case studies in cancers by applying SPIDER to predict the abundance of &gt;2,500 surface proteins on scRNA-seq datasets of hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (RCRLM), where the predicted surface protein abundance data is analyzed to demonstrate the broad downstream applications of SPIDER including facilitating cell type annotation, disease biomarker/target identification, and cell-cell interaction (CCI) inference. For instance, in these datasets we find that SPIDER can reveal (novel) disease biomarkers that are overlooked by solely observing transcript expression, such as CD44/PIK3IP1 in hepatocytes/γδ2 T cells as a positive/negative HCC biomarker, demonstrating the capability of SPIDER to compensate for the limitations in the RNA modality. In conclusion, we propose the SPIDER model which can provide valuable information on the abundance of a large scale of surfaceomes in single cells, and can be further used to gain new insights into cancers via promoting cell type annotation, disease biomarker/target identification, and CCI inference.
Citation Format: Ruoqiao Chen, Bin Chen, Jiayu Zhou. Large-scale surface protein abundance prediction from single-cell transcriptomes with a zero-shot model and its applications to cancer research [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 906.
Abstract 947: A nanodroplet cell processing platform for identifying synergistic drug combinations for neuroblastoma treatment in TH-MYCN transgenic mice
Authors: Liao Yen-Tzu , Yu Zhi-Kai , Kuo Ching-Te , Hsu Wen-Ming , Huang Yi-Xun , Lee Hsinyu 
Published: March 2024

Abstract
Neuroblastoma is the most common pediatric extracranial solid tumor and contributes to more than 15% of child mortality. It is characterized by extreme heterogeneity and high-risk tumors often resulting in poor prognosis. Currently, chemotherapy is a prevailing standard treatment for neuroblastoma. However, it is plagued by multiple challenges such as drug resistance and debilitating side effects. Synergistic drug combination is proposed as an innovative approach to potentially improve clinical outcomes of single-agent chemotherapy. We propose a novel approach to screen for effective chemo-synergistic drug combinations using Bioinspired nanodroplet processing (BioNDP) screening platform. This platform overcomes the limitations of conventional drug screening approaches, including the requirement for large cell numbers and the low translation rate from bench to bedside. In this study, we utilize TH-MYCN transgenic mice, a well-known genetically engineered mouse model of neuroblastoma that recapitulates critical genetic and clinical aspects of high-risk MYCN-amplified neuroblastoma. With its genetically homogeneous background and spontaneous tumor development, TH-MYCN mice offer a valuable comparison to traditional xenograft mouse models. We have also developed an optimal procedure of primary murine tumor isolation using both negative and positive selection approaches. The purity of the isolated cells was verified with GD2 expression, one of well-known marker of neuroblastoma. In addition, we have successfully identified an effective drug combination of cyclophosphamide, doxorubicin, and vincristine, using primary neuroblastoma tumor samples derived from TH-MYCN transgenic mice as a target. The in vitro synergistic effect of primary mouse tumor cell cytotoxicity was confirmed by using luminescent cell viability assay. Further in vivo experiments have demonstrated the therapeutic efficacy of this selected drug combination in suppressing tumor growth and improving survival rate in all TH-MYCN transgenic mice treated. To sum up, we aim to establish a future patient-centric paradigm by which minimal primary cell samples from a personalized biopsy of patients may undergo drug screening, leading to the identification of a tailored drug combination. The BioNDP platform we developed may become a pivotal resource for personalized therapy to ensure a faster and more efficient treatment strategy for patients.
Citation Format: Yen-Tzu Liao, Zhi-Kai Yu, Ching-Te Kuo, Wen-Ming Hsu, Yi-Xun Huang, Hsinyu Lee. A nanodroplet cell processing platform for identifying synergistic drug combinations for neuroblastoma treatment in TH-MYCN transgenic mice [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 947.
Abstract 994: Single analyte profiling of the mutational, immune and microbiome landscape in african american colon cancer patients
Authors: Gurjao Carino , Chan Edmond , Lee Michael J. , Hangai Sho , Rabadan Raul , Korem Tal , Hibshoosh Hanina , Izar Benjamin 
Published: March 2024

Abstract
Colorectal cancer (CRC) disproportionately affects African American (AA) patients who experience a higher incidence and mortality than any other demographic groups in the United States. Yet molecular profiling in this population is scarce. Here, we performed whole-exome sequencing (WES) of 342 immediately snap-frozen tissues comprising AA CRC and matched, distant normal colon and identified distinct genomic drivers, DNA signatures, and, surprisingly, mosaic pathogenic mutations that are not present in the patient-matched CRC. We inferred T cell infiltration and tissue-resident microbiome (TR-M) directly from WES, enabling integrative analyses. Compared to normal colon, T cell infiltration is strongly decreased in tumours with microsatellite stability (MSS), while microsatellite unstable (MSI) and Polymerase Epsilon (POLE) mutant tumours had similar levels, suggesting immune evasion in MSS rather than increased T cell infiltration in MSI/POLE-mutants. Analyses of matched normal and tumour tissues revealed the evolving TR-M at unprecedented granularity and identified distinct niches of interactions with genomic and tumour-microenvironmental features. Together, this study represents the largest comprehensive genomic analysis of CRC in AA and provides a framework for performing a multi-layered analysis from a single analyte, thus, affording a cost-effective approach to expedite medical discoveries in underrepresented ancestries.
Citation Format: Carino Gurjao, Edmond Chan, Michael J. Lee, Sho Hangai, Raul Rabadan, Tal Korem, Hanina Hibshoosh, Benjamin Izar. Single analyte profiling of the mutational, immune and microbiome landscape in african american colon cancer patients [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 994.
Abstract 999: Clinical trial matchmaking: Connecting sites to sponsors
Authors: Griffin Lyndsey , Shivakumar Latha , Boehmer Leigh , Dodson Savannah , Plotkin Elana , Pal Sumanta , Benson Al B. 
Published: March 2024

Abstract
Background: Oncology programs may encounter many challenges engaging in clinical trials. The Association of Community Cancer Center’s (ACCC) Community Oncology Research Institute (ACORI) conducted a survey to gather insights on barriers to clinical trial provision and implementation, patient recruitment, and identifying resources to support cancer programs.
Methods: A survey of 29 questions was administered via Qualtrics. The survey focused on research-naïve sites (i.e., sites with little to no clinical research experience). Survey recipients were identified from ACCC’s membership database, and the survey was open from May 5 to October 10, 2023. One survey response was captured per program.
Results: Of the 350 respondents, most were physicians, investigators, or oncology fellows (20%), directors/administrators (16%), patient navigators (12%), and APPs (12%). Responding programs were categorized as a comprehensive community cancer program (28%), community practice (26%), or academic medical center (21%). Eighty percent of respondents indicated their program currently conducts clinical research. The most common challenges included: patient recruitment (40%), limited staffing (36%), limited clinician time (32%), and lack of training in research administration and conduct (25%). The top 3 resources desired were communication about clinical research opportunities (65%), connections to clinical trial sponsors (49%), and clinical research coordinator training (41%).
Conclusions: Survey results showed a clear need for improved communication regarding clinical research opportunities, connections to clinical trial sponsors, and education around clinical trial implementation. Data from this survey will be used to match sites with trial sponsors, especially sites that serve patients with cancer from under resourced geographic, socioeconomic, racial, and ethnic groups. Future efforts will seek to engage clinical trial sponsors in improving trial engagement and feasibility, workforce support, training, and clinical mentorship.
Citation Format: Lyndsey Griffin, Latha Shivakumar, Leigh Boehmer, Savannah Dodson, Elana Plotkin, Sumanta Pal, Al B. Benson. Clinical trial matchmaking: Connecting sites to sponsors [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 999.
An IRF2-Expressing Oncolytic Virus Changes the Susceptibility of Tumor Cells to Antitumor T Cells and Promotes Tumor Clearance
Authors: Shao Lulu , Srivastava Rashmi , Delgoffe Greg M. , Thorne Stephen H. , Sarkar Saumendra N. 
Published: March 2024

Abstract
IFN regulatory factor 1 (IRF1) can promote antitumor immunity. However, we have shown previously that in the tumor cell, IRF1 can promote tumor growth, and IRF1-deficient tumor cells exhibit severely restricted tumor growth in several syngeneic mouse tumor models. Here, we investigate the potential of functionally modulating IRF1 to reduce tumor progression and prolong survival. Using inducible IRF1 expression, we established that it is possible to regulate IRF1 expression to modulate tumor progression in established B16-F10 tumors. Expression of IRF2, which is a functional antagonist of IRF1, downregulated IFNγ-induced expression of inhibitory ligands, upregulated MHC-related molecules, and slowed tumor growth and extended survival. We characterized the functional domain(s) of IRF2 needed for this antitumor activity, showing that a full-length IRF2 was required for its antitumor functions. Finally, using an oncolytic vaccinia virus as a delivery platform, we showed that IRF2-expressing vaccinia virus suppressed tumor progression and prolonged survival in multiple tumor models. These results suggest the potency of targeting IRF1 and using IRF2 to modulate immunotherapy.
Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020
Authors: Cutri Raffaello M. , Lin Joshua , Wilson Melissa L. , Doherty Joni K. , Pan Dorothy W. 
Published: March 2024

Introduction: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings. Methods: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences. Results: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients’ insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals. Conclusions: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery.
The penetration of robotic technology, task content routinisation and job satisfaction: Evidence from China
Authors: Du Yuhong , Shahiri Hazrul , Wei Xiahai 
Published: March 2024

Faced with a surge in labour costs, companies are strongly incentivised by local governments’ aggressive promotion to embrace robotic technology, triggering intense media debates. This, in turn, inevitably shapes workers’ attitudes towards their current jobs and brings uncertainty about their future workplace. This study investigates the connection between robotisation, routinisation and job satisfaction in China’s labour market. The results show that there is an observed positive relationship between an individual’s job satisfaction and exposure to robots in the local labour market, which may be related to the overwhelming benefits of these new technologies about certain work dimensions. However, fear of automation is not groundless. Our findings show that job satisfaction decreased with an increase in the routinisation of task content, particularly in areas that are increasingly exposed to robot adoption. This supports the routine-biased technological change hypothesis, which connects technology-induced unemployment with job routinisation. JEL Classification: J28, O33
Leading Resilient, Purpose-Oriented Networks Through Change
Authors: Cooper Katherine R. , Wang Rong , Harris Jack L. , Miles Joshua Paul , Shumate Michelle 
Published: March 2024

Background: Conveners are crucial in coordinating interorganizational partnerships, particularly purpose-oriented networks. However, their roles may shift from initially recruiting organizational partners to overseeing and sustaining a network through periods of change. Extensive research has focused extensively on these early stages of the interorganizational venture, but less scholarship has focused on how conveners respond to critical changes over time and the implications of convener actions in sustaining resilient networks. Purpose: This research explores the convener’s role in purpose-oriented network formation and change management and offers implications for creating resilient purpose-oriented networks. Research Design: The study conducts qualitative analysis of interviews conducted with cross-sector, purpose-oriented networks at two points in time to explore how conveners organize networks and respond to change. Study Sample: This study draws on two waves of interview data collected from the conveners of 26 cross-sector collaborative networks focused on education reform in the United States. Data Collection and/or Analysis: Interviews with conveners of 26 networks were analyzed through attribute and provisional coding to study the network’s composition and activity, perceptions of the problem and reasons for network. A second round of interviews was later collected and analyzed to explore what changes emerged after a network’s initial convening and how conveners responded to those changes through provisional and magnitude coding. Results: Findings reveal different magnitudes of change experienced by the networks (e.g., incremental, radical, and in-between) that influenced convener responses to those changes. Additionally, networks were found to have two founding orientations: problem- and solution-oriented. Networks founded with a problem orientation were more resilient than those founded with a solution orientation, partly because of the repertoire of activities in which their conveners engaged. Conclusions: Conveners play a critical role both in founding purpose-oriented networks and in leading them through change. This study suggests the concept of founding orientations to explore the different frames purpose-oriented networks may adopt and offer insights as to how those orientations influence network reactions to change. Findings pertaining to founding orientation, network change, and convener response offer theoretical and practical implications for building resilient networks.
Delay in Referral to Specialty Care in Patients with Spondyloarthropathy and Psoriatic Arthritis in India: IRA Database Report
Authors: Chandrashekara S  , Shenoy Padmanabha , Kumar Uma , Pandya Sapan , Ghosh Alakendu , Khare Apurva , Dudam Rajkiran , Danda Debashish , Goswami Rudra Prosad 
Published: March 2024

Aim: The present study is intended to evaluate the factors influencing the diagnostic and rheumatology care referral delay in patients with spondyloarthropathy (SpA) and psoriatic arthritis (PsA) in India. Materials and methods: The independent prospective, multicentre, observational study collected data from 8 centres across India through the database created by the Indian Rheumatology Association (IRA). Modified Prasad scale was used for socio-economic classification based on the patient’s income. The data of PsA and SpA were analysed separately, and the causes were compared using t-test for continuous variables and chi-square and Fisher’s exact tests for categorical variables. Results: The mean referral delay noted for PsA and SpA subjects were 16.3±34.35 and 17.48±33.59 (IQR 24 and 34) months, respectively. Majority of the PsA patients and about 65% of SpA subjects reported a lack of awareness of the rheumatology specialty as the major reason for the delay. Another major reason was management by other specialists instead of rheumatologists (65% and 74% respectively). Approximately 8% of patients in both disease groups had no faith in modern care due to perceived elevated risk of adverse effects. SpA patients with improved socio-economic status had a higher proportion of subjects seeking specialty care. A direct association was noted between professional skill and early access to specialty care for both PsA and SpA patients. Conclusion: The lack of awareness of rheumatology as a specialty and patients being managed by other specialties are the two major reasons for delayed referral of SpA and PsA. Additionally, a patient’s economic and skill level can influence their ability to access specialty care.