bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitators and barriers for vaccination in patients with inflammatory rheumatic musculoskeletal diseases: a prospective cohort study
Authors: Andreica Ioana , Roman Iulia , Redeker Imke , Baraliakos Xenofon , Braun Juergen , Kiltz Uta 
Published: June 2023

IntroductionTo identify facilitators and barriers towards vaccination in general and specifically against pneumococci, influenza and SARS-CoV-2 in patients with rheumatic musculoskeletal diseases (RMD).MethodsBetween February and April 2021, consecutive patients with RMD were asked to complete a structured questionnaire on general knowledge about vaccination, personal attitudes and perceived facilitators and barriers towards vaccination. General facilitators (n=12) and barriers (n=15) and more specific ones for vaccination against pneumococci, influenza and SARS-CoV-2 were assessed. Likert scales had four response options: from 1 (completely disagree) to 4 (completely agree). Patient and disease characteristics, their vaccination records and attitudes towards vaccination against SARS-CoV-2 were assessed.Results441 patients responded to the questionnaire. Knowledge about vaccination was decent in ≥70% of patients, but <10% of patients doubted its effectiveness. Statements on facilitators were generally more favourable than on barriers. Facilitators for SARS-CoV-2 vaccination were not different from vaccination in general. Societal and organisational facilitators were more often named than interpersonal or intrapersonal facilitators. Most patients indicated that recommendations of their healthcare professional would encourage them to be vaccinated—without preference for general practitioner or rheumatologists. There were more barriers towards SARS-CoV-2 vaccination than to vaccination in general. Intrapersonal issues were most frequently reported as a barrier. Statistically significant differences in response patterns to nearly all barriers between patients classified as definitely willing, probably willing and unwilling to receive SARS-CoV-2 vaccines were noted.DiscussionFacilitators towards vaccination were more important than barriers. Most barriers against vaccination were intrapersonal issues. Societal facilitators identified support strategies in that direction.
Dynamical stability in presence of non-minimal derivative dependent coupling of k-essence field with a relativistic fluid
Authors: Bhattacharya Kaushik , Chatterjee Anirban , Hussain Saddam 
Published: June 2023

AbstractIn this paper we investigate a non-minimal, space-time derivative dependent, coupling between the k-essence field and a relativistic fluid using a variational approach. The derivative coupling term couples the space-time derivative of the k-essence field with the fluid 4-velocity via an inner product. The inner product has a coefficient whose form specifies the various models of interaction. By introducing a coupling term at the Lagrangian level and using the variational technique we obtain the k-essence field equation and the Friedmann equations in the background of a spatially flat Friedmann–Lemaitre–Robertson–Walker (FLRW) metric. Explicitly using the dynamical analysis approach we analyze the dynamics of this coupled scenario in the context of two kinds of interaction models. The models are distinguished by the form of the coefficient multiplying the derivative coupling term. In the simplest approach we work with an inverse square law potential of the k-essence field. Both of the models are not only capable of producing a stable accelerating solution, they can also explain different phases of the evolutionary universe.
Abstract 1008: A novel biomarker and therapeutic target for early pancreatic cancer
Authors: Park Min Seok , Jung Kyung Hee , Kim Sang Eun , Lee Yun Ji , Park Sunghyouk , Hong Soon-Sun 
Published: June 2023

Abstract
Purpose: Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established.
Methods: Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic patients) and evaluated according to PC status and stages which was compared with that of CA19-9.
Results: Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic area under the curve (AUC) of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early stage PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995).
Conclusion: Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.
Citation Format: Min Seok Park, Kyung Hee Jung, Sang Eun Kim, Yun Ji Lee, Sunghyouk Park, Soon-Sun Hong. A novel biomarker and therapeutic target for early pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1008.
Abstract 1106: A novel cancer therapy using proton beam; an integrated proton dynamic therapy, iPDT
Authors: Matsui HIrofumi 
Published: June 2023

Abstract
A super-aged society, the prime example of which is Japan, is being flooded with increasing in numerous numbers of aged cancer patients, who often take anti-coagulant medicines to prevent the attacks of ischemic heart diseases and/or strokes. Since they show bleeding tendency induced by the medicines, it’s hard for them to receive surgical operations. Thus, low invasive cancer treatments without bleedings are abundantly desired. In this study, the applicant will establish a new proton therapy, in which a resonance nuclear reaction (RNR) induced by collision of a proton with a stable nitrogen isotope (15N), can be a clue to injure cancer-cells specifically. The LET of the product ions (12C6+, 4He2+) of the 15N RNR is above 50 times in comparison with the LET of proton. To establish the cancer-specific 15N delivery, 15N-aminolevulinic acid (15N-ALA) will be used. This reagent has been already used and obtained regulatory approvals as a diagnostic medicine for the location of the glioblastoma in Japan. In this study, a pair of rat gastric epithelial cells, one is normal cell, and another is cancerous characteristics cells were used. 15N-ALA treated porphyrin fluorescent intensity of these cells will be compared with 14N-ALA treatment. The cells will be irradiated with a proton beam generated by an electrostatic accelerator and 4.43 MeV gamma-rays will be measured to demonstrate the amount of 15N collected specifically in the tumor cells. Such quantitative analysis of 15N in the tumor cells can be a new pre-diagnosis of iPDT.
Citation Format: HIrofumi Matsui. A novel cancer therapy using proton beam; an integrated proton dynamic therapy, iPDT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1106.
Abstract 1175: Systematic profiling of conditional pathway activation as a new class of cancer dependency
Authors: Chang Liang , Jung Nancy Y. , Atari Adel , Kesar Devishi , Rodriguez Diego J. , Rees Matthew A. , Ronan Melissa , Sellers William R. 
Published: June 2023

Abstract
The paradigm of cancer dependencies and targeted therapies has been nearly exclusively focused on inhibiting critical pathways or nodes in cancer. However, conditional activation of signaling pathways as a new source of selective cancer vulnerabilities has not been systematically characterized. In this study, we sought to systematically identify context-specific gene activation lethalities in cancer. We performed lineage-specific mutual-exclusivity (ME) analysis using 69,393 cancer patient genomes in cohorts of AACR-GENIE, TCGA, and Foundation One, across 12 cancer lineages, and identified ME mutation pairs within MAPK, PI3K and WNT pathways indicative of evolutionarily negative selection. To functionally test whether mutual exclusive genetic alterations likely create negative selection pressures in cancer, we developed a lentiviral method to achieve simultaneous ectopic ORF expression ~500 barcoded cancer cell lines for large-scale gain-of-function genetic perturbation. Using this technology, we systematically profiled the pan-cancer vulnerability landscape upon activating 10 key pathway nodes, revealing selective activation dependencies associated with specific biomarkers. We validated the anti-tumor effect of PI3K hyperactivation in PIK3CA/PTEN double-mutant endometrial cancer cell lines. Notably, we find that subsets of APC-mutant colorectal cancers retain active destruction complexes. Upon further depletion of APC or direct expression of β-catenin, the resulting WNT pathway hyperactivation impairs the viability of APC-mutant colorectal cancers in in vitro cell lines and organoids and in in vivo tumor models. Together, our study reveals a new class of conditional gene activation dependencies in cancer.
Citation Format: Liang Chang, Nancy Y. Jung, Adel Atari, Devishi Kesar, Diego J. Rodriguez, Matthew A. Rees, Melissa Ronan, William R. Sellers. Systematic profiling of conditional pathway activation as a new class of cancer dependency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1175.
Abstract 1266: MYC mediated HIF-2α modulates the altruistic stemness reprogramming in leukemia stem cells
Authors: Mitra Shirsajit , Pathak Lekhika , Saikia Partha Jyoti , Pal Bidisha , Das Bikul 
Published: June 2023

Abstract
Potential cell surface markers specifically enriching the leukemia stem cell (LSC) subfraction based on stemness genes expression have not yet been identified. Previously, we reported ABCG2, a drug efflux pump, enriches a subpopulation of cells exhibiting a very high level of stemness genes expression in ES cells. These ABCG2+ ES cells exhibited high HIF-2α, which in cooperation with MYC-regulated Nanog and Sox-2. ABCG2+ cells demonstrated highly cytoprotective altruistic behavior by secreting high levels of glutathione. In the present study, we evaluated whether ABCG2+ subfraction of human LSCs exhibits high level of stemness genes and altruistic behavior. We isolated the ABCG2+ cell subfraction from cervical lymph node and blood of human T-ALL(n=5) and CML(n=7) patients exhibiting high levels of stemness genes in addition to MYC and HIF-2α. We investigated the altruistic stemness phenotype of the ABCG2+ cells by studying the molecular signature of MYC binding to HIF-2α. siRNA HIF-2α treatment led to ABCG2+ cell loss of proliferative capacity and reduced GSH levels, suggesting reduction of cytoprotective altruistic behavior in vitro. Treatment of ABCG2+ cell harboring mice with FM19G11 led to marked loss in the secondary engraftment in NOD/SCID mice, indicating loss of ABCG2+ cell self-renewal capacity. We found siRNA MYC inhibition led to loss of HIF-2α expression, suggesting that MYC might be regulating HIF-2α mediated altruistic stemness program in the ABCG2+ cells. Overall, we found that ABCG2 can be a probable marker to enrich the LSC subfraction having high expression of stemness genes and altruistic stemness phenotype.
Citation Format: Shirsajit Mitra, Lekhika Pathak, Partha Jyoti Saikia, Bidisha Pal, Bikul Das. MYC mediated HIF-2α modulates the altruistic stemness reprogramming in leukemia stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1266.
Abstract 1477: TICRR is a prognosis biomarker associated with RNA epigenetic modification, DDR pathway, and RNA metabolism of lung adenocarcinoma
Authors: Zheng Xunbo , Guan Jun , Chen Chenteng , Han Li , Huang Hanxing 
Published: June 2023

Abstract
Background: TOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been identified as a prognostic biomarker in papillary renal cell carcinoma (PRCC). Nevertheless, there are few studies on the comprehensive analysis between mRNA expression of TICRR and lung adenocarcinoma (LUAD).
Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the mRNA expression between tumor and normal tissues, survival prognosis, and clinicopathology characters. The GO, KEGG, and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR with immune cell infiltration, RNA epigenetic modification, DDR pathway, and RNA metabolism of LUAD were further explored using TCGA and GEO database.
Results: TICRR was confirmed significantly upregulated in several cancers, like LUAD, Lung squamous cell carcinoma (LUSC), Uterine Corpus Endometrial Carcinoma (UCEC), except for Prostate adenocarcinoma (PRAD), Thyroid carcinoma (THCA), which was downregulated in tumor tissues. Cox analysis indicated the overexpression of TICRR was related to poor survival in several cancers. The KEGG enrichment showed TICRR expression positively related to cell cycle, homologous recombination, mismatch repair, DNA replication, and cysteine metabolism in LUAD. Pathway enrichment showed a close relationship with spliceosome, oxidative phosphorylation, and ubiquitin-mediated proteolysis. Immune infiltration analysis revealed TICRR expression was negatively correlated with B cell expression, immune score, stromal score, and immunostimulators like IL2 (P&lt;0.001), and positively correlated with neutrophil cell expression, immune inhibitors like PD-L1 and CTLA4. Interestingly, high mRNA expression of TICRR correlates with DDR pathway signature (37 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Single-cell analysis of six LUAD samples showed that TICRR was significantly enriched in macrophage and T cells.
Conclusions: TICRR has been identified to be a prognosis biomarker in LUAD, which is involved in immune activation, pathway transportation, RNA modification, and tumor energy metabolism. TICRR can be used as a promising therapeutic target and prognosis indicator for LUAD.
Citation Format: Xunbo Zheng, Jun Guan, Chenteng Chen, Li Han, Hanxing Huang. TICRR is a prognosis biomarker associated with RNA epigenetic modification, DDR pathway, and RNA metabolism of lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1477.
Abstract 1583: Bcl-6 as a potential therapeutic target for bladder cancer
Authors: Furuya Hideki , Murakami Kaoru , Kim Nari , Rosser Charles J. 
Published: June 2023

Abstract
Introduction and Objectives: B-cell lymphoma 6 (Bcl-6) is known to be a nuclear protein and a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. Previously, we reported on the increased angiogenic potential of human prostate cancer cells that overexpressed the Bcl-2. Comparative genomic profiling of the endothelial cells treated with/without conditioned media from Bcl-2-overexpressing human prostate cancer cells revealed approximately 250 differentially expressed genes. Interestingly, bioinformatics analysis identified Bcl-6 as one of several secreted proteins on the list. In this study, we first confirmed that Bcl-6 exists in liquid biopsy, and secondly evaluate the effect of Bcl-6 neutralization on angiogenesis and tumor growth in in vitro and in vivo models.
Methods: We first analyzed Bcl-6 levels in serum and urine by ELISA. Then we tested the effect of Bcl-6 antibody for the following: ability to inhibit in vitro and in vivo angiogenesis, ability to inhibit cellular proliferation, and tumor growth in cell line-derived xenograft model.
Results: First, we found that Bcl-6 exists in urine and serum. Interestingly, Bcl-6 level was significantly higher in cancer patients than healthy subjects. Next, we identified the effective clone tube formation assay. Then we further tested the effect of the antibody and exogenous Bcl-6 on cell proliferation, tube formation, and tube disruption in HUVEC. The exogenous Bcl-6 did not enhance cell proliferation of HUVEC. On the other hand, the Bcl-6 antibody significantly inhibited tube formation in HUVEC, but not tube disruption. Subsequently, we performed Matrigel plug assay to evaluate the effect on angiogenesis in vivo. The CD31 positive cells in Matrigel plug were significantly reduced by the Bcl-6 antibody treatment. To evaluate the effect on tumor growth, we first performed the cell proliferation assay to evaluate the effect on tumor growth in vitro. The Bcl-6 antibody significantly inhibited the cell proliferation of T24 and UM-UC-3 cell lines highly expressing Bcl-6. Finally, we tested the effect of the Bcl-6 antibody on tumor growth in an animal model. Intratumoral injection of Bcl-6 antibody (15 μg/tumor, twice weekly) significantly inhibited the tumor growth.
Conclusions: This is the first time to identify that Bcl-6 may be a secreted protein and found that neutralization of Bcl-6 by antibody inhibits angiogenesis and tumor growth in both in vitro and in vivo. The results suggest that neutralizing Bcl-6 by antibody could be a promising therapeutic agent in bladder cancer.
Citation Format: Hideki Furuya, Kaoru Murakami, Nari Kim, Charles J. Rosser. Bcl-6 as a potential therapeutic target for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1583.
Abstract 1589: Characterization of polyaminohydroxamic acids and polyaminobenzamides as inhibitors of HDAC10
Authors: Stewart Tracy Murray , Foley Jackson R. , Woster Patrick M. , Casero Robert A. 
Published: June 2023

Abstract
Elevated polyamine levels are essential for continual proliferation of cancer cells. Cytosolic histone deacetylase-10 (HDAC10) specifically deacetylates the modified polyamine N8-acetylspermidine (N8-AcSpd), of which extracellular sources can be abundant, particularly in the colonic lumen. We previously demonstrated that exogenously supplied N8-AcSpd can support tumor cell growth through HDAC10-mediated deacetylation into spermidine, which is then redistributed within the polyamine interconversion pathway to maintain homeostasis.In the current study, we investigate the utility of polyamine-based hydroxamic acids (PAHAs) and benzamides (PABAs) as pharmacological inhibitors of HDAC10-mediated polyamine deacetylation. Incorporation of the polyamine moiety enables these compounds to enter the cell selectively through the polyamine transport system, which is upregulated in cancer cells. A total of 42 compounds, including 21 PAHAs and 21 PABAs, were screened for HDAC10 inhibition using a cell-based growth assay in which polyamine-depleted, growth-arrested cells are exposed to N8-AcSpd: in the presence of HDAC10 activity, this polyamine is deacetylated and proliferation is restored. Several compounds in our screen inhibited HDAC10 activity in this assay, as indicated by a lack of growth rescue, and were selected for further analysis in which treatment was expanded over a range of doses, thereby allowing a dose-dependent evaluation and comparison of sensitivity. HPLC-based analysis of cell lysates functionally confirmed that deacetylation of N8-AcSpd into spermidine was inhibited by the test compounds. Finally, specificity of the selected PAHAs and PABAs for HDAC10 was evaluated by immunoblotting for increased acetylation of the substrates of related HDACs, including histones H3 and H4, and alpha-tubulin. These studies provide a basis for future drug design strategies targeting the polyamine deacetylase activity of HDAC10 as an antitumor strategy, which may be particularly important in the context of polyamine-blocking therapies.
Citation Format: Tracy Murray Stewart, Jackson R. Foley, Patrick M. Woster, Robert A. Casero. Characterization of polyaminohydroxamic acids and polyaminobenzamides as inhibitors of HDAC10 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1589.
Abstract 169: Leveraging space to advance terrestrial cancer research
Authors: Pham Jessica , Ladel Luisa , Wu Christina , Jamieson Catriona 
Published: June 2023

Abstract
The International Space Station (ISS) offers a unique macroenvironment to study biology. The effects of microgravity in low earth orbit (LEO) can be leveraged to study pre-cancer and cancer transformation in an accelerated timeframe. Thus, we launched two cancer cell types into space as a proof of concept and to establish an innovative model for studying cancer. The two cell types are TF1a, an erythroleukemia cell line, and Caco-2, a colon cancer cell line that was cultured as organoids. These studies were performed in collaboration with Axiom Space and were launched as part of the Ax-1 mission on April 8, 2022. To study these tumor organoids in space, cells were transduced with two lentiviral reporters, ADAR1 NanoLuciferase reporter, an A-to-I editing reporter, and Fucci2BL, a cell-cycle transit reporter. Fluorescent imaging at days 5 and 6 of the mission, courtesy of KEyence Research MIcroscope Testbed (KERMIT), allowed us to receive and assess the development of these tumor models in real-time. Caco-2 organoids in flight grew 3-5 times bigger than their ground counterparts. Preliminary whole genome sequencing (WGS) analysis showed that telomere length is shortened in flight samples compared to asynchronous ground control samples. In summary, research done in LEO has the capacity to strengthen terrestrial research. As we follow-up with these studies as part of the Ax-2 mission in May of 2023, we hope to gain more insight into the pathogenesis of cancer and develop strategies to mitigate cancer progression.
Citation Format: Jessica Pham, Luisa Ladel, Christina Wu, Catriona Jamieson. Leveraging space to advance terrestrial cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 169.