bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1307: Community-driven support platform BlueHQ: An innovative solution to address the needs of patients with colorectal cancer
Authors: Newcomer Kimberly Lynn 
Published: March 2024

Abstract
Background: Colorectal cancer (CRC) is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. To manage the disease, patients and caregivers turn to various tools and resources for financial assistance, information dissemination, emotional and peer support, and treatment planning, among other critical issues and needs they face. The Colorectal Cancer Alliance (the Alliance) created BlueHQ to provide patients and caregivers with a resource solution encompassing all potential areas of need.
Methods: A survey aimed at understanding needs, barriers, and quality improvement opportunities was disseminated via the Alliance's Blue Hope Nation community for two weeks and by email. One hundred sixty-seven colorectal cancer patients and forty caregivers of colorectal cancer patients completed the survey.
Results: Patients and caregiver respondents report reliance on external tools and resources to manage disease and support information. Of the support methods, patient respondents reported using social media (46.11%); notebooks, journals, and planners (45.41%); online articles (44.91%); the Blue Hope Nation Facebook group (41.32%); cancer discussion boards (35.33%); and spiritual or religious advice (29.94%). Patients sought financial assistance, local peer support and groups, and mental health help to minimize diagnosis-related stressors. To provide more efficient care and limit stress, the community suggested financial help, communication and support from other patients and caregivers, and informational resources.
Conclusions: These survey results are consistent with other published learnings about patient and caregiver reliance on support tools and highlight the myriad resources that patients and caregivers currently use for managing CRC. BlueHQ is a support solution that provides patients and caregivers with access to information and resources tailored to users’ specified profiles, including molecular characteristics of the tumor. Users can also store documents and information from healthcare encounters, creating a longitudinal record and tracking disease progression. In the age of precision oncology, BlueHQ ensures patients and users are presented with personalized educational materials and multimedia resources to help manage their disease and bridge the gaps in patient support. BlueHQ was explicitly designed to connect the CRC community to the latest therapeutic and clinical research resources to improve outcomes and quality of life for all CRC patients.
Citation Format: Kimberly Lynn Newcomer. Community-driven support platform BlueHQ: An innovative solution to address the needs of patients with colorectal 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 1307.
Abstract 140: Distinct pathways regulated by activated β-Catenin and YAP in hepatoblastoma pathogenesis
Authors: Liao Weiting , Chen Xin 
Published: March 2024

Abstract
Hepatoblastoma (HB) is a rare, yet the most common primary malignant hepatic liver in children. A significantly portion of children with HB have tumors that are not resected at diagnosis, leading to the dismal prognosis in these patients. Concomitant YAP and β-catenin activation could be seen 80% of HB. The signaling pathways regulated by YAP and β-catenin in HB pathogenesis remain unclear. Here, we engineered a inducible HB murine model using hydrodynamic injection to deliver transposon plasmids encoding constitutive YAP and doxycycline (Dox) inducible ΔN90-β-Catenin (Yap/TRE-β-Catenin). When fed with Dox, HB formed rapidly in the mice. Upon Dox withdraw, HB regressed over the long term. We analyzed gene expression patterns in mouse HB lesions upon short term Dox withdrawal, i.e, tumors still existed yet ΔN90-β-Catenin was turned off. This approach assisted to identify genes regulated by the activated β-Catenin in HB tumors. We compared these genes with the previously identified YAP regulated genes and found the distinct gene expression programs regulated by YAP and β-Catenin in HB. Specifically, YAP off down-regulated Hippo pathway and up-regulated metabolism-related pathways, whereas β-Catenin off down-regulated protein export, DNA replication pathway and up-regulated immune-related pathways. Finally, we identified ONECUT1 as a gene down-regulated by activated β-Catenin in HB. ONECUT1 expression was down-regulated in human HBs, and co-expression of ONECUT1 strongly suppressed Yap/β-Catenin HB formation in mice. Mechanically, ONECUT1 could regulate proliferation-related downstream signaling. Altogether our studies demonstrated that suppression of activated CTNNB1 mutations could repress HB progression in vivo, and we identified distinct pathways regulated by activated β-catenin and YAP in HB. Suppression of ONECUT1 expression by β-catenin is a key genetic event leading to HB formation.
Citation Format: Weiting Liao, Xin Chen. Distinct pathways regulated by activated β-Catenin and YAP in hepatoblastoma pathogenesis [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 140.
Abstract 1411: Cell-type-specific transcriptomic immune aging clocks reveal clinically relevant associations with chronic illnesses including cancer
Authors: Gurevich-Schmidt Yael , Wang Kun , Wu Di , Madan Sanna , Gopalan Vishaka , Sinha Sanju , Wang Binbin , Dhruba Saugato Rahman , Schäffer Alejandro A. , Ruppin Eytan 
Published: March 2024

Abstract
The aging of the immune system has profound implications for individual immune responses, yet precise quantification of immune age remains a challenge. Analyzing single-cell peripheral blood mononuclear cells (PBMC) transcriptomics data from 981 healthy individuals, we developed IMMClock (IMMune Clock), a human immune age clock derived from single cell transcriptomics. IMMClock is the first to accurately assess the age of three major immune cell types, CD8+ T cells, CD4+ T cells and NK cells, at the individual level. Testing the ability of these clocks to capture the dynamic aging process, we show that they reliably predict individuals' chronological ages across seven publicly available single-cell transcriptomics datasets and the large Framingham bulk transcriptomics cohort. IMMClock identifies cell type specific age-related pathways including apoptosis, interferon gamma response, and cytokine response. The application of IMMClock reveals several associations between immune aging of different cell-types and key clinical phenotypes during aging: it recapitulates the established observation of higher immune age in males compared to females and uncovers higher immune age in CD8+ T cells of smokers and individuals with chronic illnesses including cancer. Analyzing cancer patients’ data, IMMClock readings strongly correlate with CD8+ T cell exhaustion levels, and, quite strikingly, highlights an elevated immune age in the tumor microenvironment compared to blood.
Citation Format: Yael Gurevich-Schmidt, Kun Wang, Di Wu, Sanna Madan, Vishaka Gopalan, Sanju Sinha, Binbin Wang, Saugato Rahman Dhruba, Alejandro A. Schäffer, Eytan Ruppin. Cell-type-specific transcriptomic immune aging clocks reveal clinically relevant associations with chronic illnesses including 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 1411.
Abstract 1494: Clonal dominance defines metastatic dissemination in pancreatic cancer
Authors: Ho I-Lin , Li Chieh-Yuan , Wang Fuchenchu , Zhao Li , Liu Jingjing , Yen Er-Yen , Dyke Charles A. , Shah Rutvi , Liu Zhaoliang , Çetin Ali Osman , Citron Francesca , Attanasio Sergio , Giuliani Virgina , Heffernan Tim , Do Kim-Anh , Gargiulo Gaetano , Draetta Giulio , Carugo Alessandro , Lin Ruitao , Viale Andrea 
Published: March 2024

Abstract
Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically-implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination. This model revealed the multifaceted nature of tumor growth, with rapid changes in clonal fitness leading to continuous reshuffling of tumor architecture and alternating clonal dominance as a distinct feature of cancer growth. Regarding dissemination, a large fraction of tumor lineages could be found at secondary sites each having distinctive organ growth patterns as well as numerous undescribed behaviors such as abortive colonization. Paired analysis of primary and secondary sites revealed fitness as major contributor to dissemination. From the analysis of pro- and non-metastatic isogenic subclones, we identified a transcriptomic signature able to identify metastatic cells in human tumors and predict patients’ survival.
Citation Format: I-Lin Ho, Chieh-Yuan Li, Fuchenchu Wang, Li Zhao, Jingjing Liu, Er-Yen Yen, Charles A. Dyke, Rutvi Shah, Zhaoliang Liu, Ali Osman Çetin, Francesca Citron, Sergio Attanasio, Virgina Giuliani, Tim Heffernan, Kim-Anh Do, Gaetano Gargiulo, Giulio Draetta, Alessandro Carugo, Ruitao Lin, Andrea Viale. Clonal dominance defines metastatic dissemination in pancreatic 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 1494.
Abstract 1505: Unraveling diepafitaxis: Investigating ECM stiffness and microarchitecture in tumor spheroid migration
Authors: Chen Hsiang-Pei , Tsai Ya-Chu , Tu Ting-Yuan 
Published: March 2024

Abstract
Background: Metastasis, accounting for up to 90% of cancer-related deaths, remains one of the least understood aspects of cancer progression. Recent research has shifted focus from solely biological hallmarks to the physical characteristics of cancer, such as the stiffness and microarchitecture of the extracellular matrix (ECM), which play pivotal roles in metastatic advancement. We previously introduced the concept of 'diepafitaxis' to describe a unique mechanism driving the interface-mediated tropism of tumor spheroids at matrix-surface boundaries. This phenomenon suggests that cancer cells preferentially migrate along a 2D 'interfacial' track formed by heterogeneous 3D ECM structures, facilitating invasion and dispersion. However, the exact mechanisms by which interfacial components, stiffness, and structural attributes influence cell movement remain debated. To investigate this, we have developed a microfluidic chip with a precisely controlled stiffness of the hydrogel matrix-matrix interface (MMI), aiming to shed light on specific diepafitatic behaviors.
Method: We developed a polydimethylsiloxane (PDMS)-based microfluidic chip using a traditional photolithographic process. This chip features three channels, with the center channel designed to precisely control various MMI stiffness combinations: stiff vs soft (t-o), stiff vs stiff (t-t) and soft vs soft (o-o). MDA-MB-231 breast cancer spheroids (BCS), representing an in vitro tumor model, were embedded in the top gel. We observed the dynamic behavior of these cancer spheroids over a 24-h period using differential interference contrast (DIC) microscopy.
Result: The study revealed that BCS exhibited more pronounced dispersion in a soft homogeneous ECM compared to a stiff ECM in 3D environments. Interestingly, when BCS were near an MMI, a stiffer MMI (t-t) significantly enhanced BCS invasiveness and single-cell migration, more so than t-o, and notably more than o-o. We previously described this phenomenon as '2.5D migration,' where cells migrate in a ventral 2D manner within a sandwiched 3D gel structure. This diepafitatic behavior was further analyzed for its response to gravitational effects and the influence of chemotaxis, induced by introducing VEGF on one side of the microfluidic channel.
Conclusion: Conclusively, our study demonstrates that the stiffness and structure of the ECM, particularly at MMI, significantly influence the invasive behavior and migration patterns of BCS, underscoring the critical role of mechanical microenvironments in cancer metastasis.
Citation Format: Hsiang-Pei Chen, Ya-Chu Tsai, Ting-Yuan Tu. Unraveling diepafitaxis: Investigating ECM stiffness and microarchitecture in tumor spheroid migration [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 1505.
Abstract 1555: Nuclear accumulation of cell surface programmed cell death ligand 1 promotes metastatic outgrowth in triple-negative breast cancer cells
Authors: Gohara Yuma , Tomonobu Nahoko , Kinoshita Rie , Yamamoto Kenichi , Murata Hitoshi , Sakaguchi Masakiyo 
Published: March 2024

Abstract
PD-L1 presented on the cancer cell surface is well known for its role in immune checkpoint regulation by interacting with PD-1 on immune cells. On the other hand, it has been reported that PD-L1 is localized in the cancer cells’ nuclei, where the nuclear PD-L1 (nPD-L1) is conducive to cancer outgrowth and motility. However, there has yet to be reported about the mechanistic insight into the event. In this study, we, therefore, aimed to clarify still unidentified points in the nPD-L1-mediated event. Our efforts revealed that the upregulation is induced by a functional suppression of nuclear protein X (tentative name), which we identified as a novel binding protein with nPD-L1 at its cytoplasmic tail. Their nuclear interaction also abolished an aggressive cancer proclivity, epithelial-mesenchymal transition (EMT). The mechanism is helpful to the complex nature of PD-L1 in plural cancer cell behaviors.
Citation Format: Yuma Gohara, Nahoko Tomonobu, Rie Kinoshita, Kenichi Yamamoto, Hitoshi Murata, Masakiyo Sakaguchi. Nuclear accumulation of cell surface programmed cell death ligand 1 promotes metastatic outgrowth in triple-negative breast cancer cells [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 1555.
Abstract 1561: Identification of tumor-associated macrophages promoting early-stage metastasis during peritoneal dissemination in gastric cancer
Authors: Kawase Wataru , Hiroshima Yukihiko , Hashimoto Itaru , Onuma Shizune , Furuta Mitsuhiro , Machida Nozomu , Oshima Takashi , Miyagi Yohei 
Published: March 2024

Abstract
Peritoneal dissemination (PD) is the most frequent metastasis pattern in gastric cancer (GC) and is a significant predictor of poor prognosis. However, the mechanisms underlying PD formation remain unclear, and a PD-specific signature has not been identified. PD development is thought to be influenced by various changes occurring in GC tumor cells and immune cells present in the peritoneal cavity. We previously performed RNA-seq analysis of cell components in cytology-positive (CY1) gastric cancer ascites. The results suggested that tumor-associated macrophages (TAMs) infiltrate the abdominal cavity together with GC tumor cells and might be involved in PD development. In this study, we aimed to identify the specific TAMs responsible for promoting metastasis during the early stage of PD in GC. We demonstrated the abundant presence of TAMs in CY1 GC ascites using flow cytometry analysis and identified several genes that were significantly expressed in CY1 TAMs using single-cell RNA-seq analysis. Furthermore, we evaluated the potential of these genes to serve as therapeutic targets for the treatment of PD in GC.
Citation Format: Wataru Kawase, Yukihiko Hiroshima, Itaru Hashimoto, Shizune Onuma, Mitsuhiro Furuta, Nozomu Machida, Takashi Oshima, Yohei Miyagi. Identification of tumor-associated macrophages promoting early-stage metastasis during peritoneal dissemination in gastric 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 1561.
Abstract 1572: POU5F1B is a human-restricted ROCK inhibitor-sensitive oncoprotein that restructures membrane nanodomains to increase cell adhesion
Authors: Simó-Riudalbas Laia , Offner Sandra , Abrami Laurence , Unterauer Eduard M. , Duc Julien , Planet Evarist , Jungmann Ralf , van der Goot Gisou , Trono Didier 
Published: March 2024

Abstract
Evolution confers new species with distinctive biological features, which can translate in purely mechanistic speciation or in novel phenotypic traits. POU5F1B arose by retrotransposition of POU5F1 (OCT4) in the last common ancestor of modern Hominoidae. Its human product is endowed with oncogenic properties, notably promoting gastrointestinal cancer growth and metastasis. Here, we reveal that the oncogenic action of POU5F1B requires ubiquitination of lysine residues found only in the human protein. This post-translational modification is essential for POU5F1B to localize to the cytoplasm and become acylated by the DHHC17 palmitoyltransferase. This leads to POU5F1B association with detergent-resistant membrane subdomains, where it triggers the accumulation of integrins and signaling molecules, and to a stimulation of cell focal adhesion. Finally, we determined that POU5F1B stability is critically dependent on ROCK, a crucial regulator of cytoskeletal dynamics and cell motility.
Citation Format: Laia Simó-Riudalbas, Sandra Offner, Laurence Abrami, Eduard M. Unterauer, Julien Duc, Evarist Planet, Ralf Jungmann, Gisou van der Goot, Didier Trono. POU5F1B is a human-restricted ROCK inhibitor-sensitive oncoprotein that restructures membrane nanodomains to increase cell adhesion [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 1572.
Abstract 1615: Balanced molecular feature selection unveils universally tumor-lineage informative methylation sites in colorectal cancer
Authors: Li Xuan Cindy , Liu Yuelin , Schäffer Alejandro A. , Mount Stephen M. , Sahinalp Süleyman C. 
Published: March 2024

Abstract
In the era of precision medicine, performing comparative analysis over diverse patient populations is a fundamental step toward tailoring healthcare interventions. However, the critical aspect of equitably selecting molecular features across multiple patients is often overlooked. To address this challenge, we introduce FALAFL (FAir muLti-sAmple Feature seLection), a novel algorithmic approach based on integer linear programming. FALAFL is designed to bridge the gap between molecular feature selection and algorithmic fairness, ensuring a balanced selection of molecular features across different patient samples.
We have applied FALAFL to the problem of selecting lineage-informative CpG sites within a cohort of 9 colorectal cancer patients subjected to low-coverage single-cell methylation sequencing. Our results demonstrate that FALAFL excels at rapidly determining the optimal set of CpG sites, which are well covered by cells across the vast majority of the patients, while ensuring that each patient contributes a similar number of sites to the final selection. An analysis of the FALAFL-selected CpG sites reveals that their lineage informativeness exhibits a strong association across diverse patient profiles, suggesting the non-stochasticity and universality of methylation changes in tumor evolution. Furthermore, these universally lineage-informative sites exhibit subclonal level alterations in the colorectal cancer primary tumors and are strongly associated with lineage-specific gene expression patterns.
By integrating equity considerations into the molecular feature selection process, FALAFL is poised to propel equitable healthcare data science practices and advance our understanding of cancer and other complex diseases.
Citation Format: Xuan Cindy Li, Yuelin Liu, Alejandro A. Schäffer, Stephen M. Mount, Süleyman C. Sahinalp. Balanced molecular feature selection unveils universally tumor-lineage informative methylation sites in colorectal 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 1615.
Abstract 1648: RB represses cohesin-dependent loop formation and activates E2F-independent transcription
Authors: Lee Hanjun , Gkotinakou Ioanna-Maria , Krishnan Badri , Dyson Nicholas J. , Lawrence Michael S. , Sanidas Ioannis 
Published: March 2024

Abstract
The retinoblastoma protein (RB) suppresses the activity of the E2F transcription factor family, controlling cellular proliferation. Recent studies, however, indicate that RB's role in chromatin organization, which is not yet fully understood, might be distinct from this E2F-dependent regulation. Employing chromosome conformation capture at a single nucleosome resolution, we identified RB as a cell cycle-regulated repressor of cohesin-dependent loop formation at topologically associating domain (TAD) boundaries. RB depletion increased the number and size of cohesin-dependent loops and strengthened topologically associating domains (TADs). This phenomenon was specific to the G1 phase and was not observed in the S phase, indicating that this novel RB function is regulated by the cell cycle. Mechanistically, RB showed extensive colocalization with cohesin in the human genome, and it impacted cohesin’s distribution on the chromatin. Active RB reduced cohesin from RB-bound TAD boundaries and decreased cohesin activity therein, as assessed by the increased K105/106 acetylation of the cohesin subunit SMC3. This led to reduced insulation in chromosome conformation capture assays. Importantly, by weakening the insulation activity of the adjacent insulators, RB non-canonically enhanced the expression of non-E2F target genes salient for cell adhesion and extracellular matrix organization. When RB was lost, cells showed a more rapid cellular detachment rate and an elevated migration rate, indicating that this novel RB function controls specific transcriptional programs rather than arbitrary genes to regulate the process of cell adhesion and migration. Overall, we conclude that RB has a central role in the interplay between cell cycle and chromatin organization, by repressing the cohesin-dependent loop formation at TAD boundaries. This RB function safeguards E2F-independent transcriptional programs driven by active enhancers and helps maintain cellular adhesion to the extracellular matrix.
Citation Format: Hanjun Lee, Ioanna-Maria Gkotinakou, Badri Krishnan, Nicholas J. Dyson, Michael S. Lawrence, Ioannis Sanidas. RB represses cohesin-dependent loop formation and activates E2F-independent transcription [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 1648.