bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 881: Desmocollin-3 and tumor immune microenvironment: Bioinformatics evaluation
Authors: Dheeraj Arpit , Khamar Bakulesh M. , Shukla Chandreshwar P. , Jain Nayan K. , Modi Rajiv I. 
Published: April 2023

Abstract
Desmocollin-3 (DSC3) is a desmosomal adhesion molecule responsible for integrity and cell adhesion under normal physiological condition. Its expression is altered during carcinogenesis. DSC3 is a p53 responsive gene. Like other adhesion molecules, it is described to provide barrier for immune infiltration of tumor. To identify a specific immune gene signature related to DSC3, spearman correlation coefficient was determined for 207 immune related genes using Cbioportal in cancer having high and low level of DSC3 gene expression .We classified renal adenocarcinoma lung, hepatocellular carcinoma and renal cancer as DSC3low and squamous lung cancer, cervical cancer and head and Neck cancer as DSC3high based on DSC3 gene expression level. In DSC3high group, six genes were found to be correlated (Spearman correlation ≥ 0.3) with DSC3 expression (Table), while none of the 207 immune related genes were correlated with DSC3low expression. Of genes with positive correlation, CD44 is a marker for stem cell and is associated with resistance to chemotherapy while S100A12 and TOLLIP are associated with carcinogenesis and inflammation. Of immune genes with negative correlation, GATA6 is a tumor suppressive gene, IL-12A is responsible for T-cell-independent induction of IFNγ and CD63 is associated with survival as described in lung cancer. This findings suggests DSC3high expression may be associated with poor prognosis compared DSC3low . DSC3 expression is specific for squamous lung cancer and is used to differentiate it from adenocarcinoma lung. Squamous lung cancer is also known to have poor prognosis compared to adenocarcinoma of lung. We will be presenting full details about 207 selected genes and their correlation with DSC3 in our presentation.
Table: Spearman’s correlation of DSC3 with Immune genes DSC3 expression Immune genes with positive spearman’s correlation Immune genes with negative spearman’s correlation Cancer Median RSEM (N) CD44 S100A12 TOLLIP CD63 GATA6 IL12A LUSC 6208 (n=501) 0.4 0.3 0.4 -0.4 -0.3 -0.3 CESC 10086 (n=306) 0.6 0.6 0.6 -0.6 -0.4 -0.4 HNSC 15287(n=522) 0.3 0.3 0.3 -0.5 -0.3 -0.4 KIPAN 1.5 (n=720) &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 LIHC 2.0 (n=231) &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 LUAD 10 (n=496) &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3 &lt; 0.3
Citation Format: Arpit Dheeraj, Bakulesh M. Khamar, Chandreshwar P. Shukla, Nayan K. Jain, Rajiv I. Modi. Desmocollin-3 and tumor immune microenvironment: Bioinformatics evaluation [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 881.
Abstract 898: Generation and validation of anti-linker monoclonal antibodies for the detection of surface expressed scFv-based CARs
Authors: Singh Amrik , L'Heureux Sarah , Sinapius Ryan , Kvorjak Michael , Wade Emma , Lohmueller Jason , Fisher Jeremy , Prioli Reginaldo 
Published: April 2023

Abstract
Introduction: Chimeric Antigen Receptor (CAR)-T cell therapy is a highly innovative form of immunotherapy that has proven to be successful in the treatment of B cell malignancies and multiple myeloma. As this treatment modality continues to evolve toward the targeting of novel tumor antigens and engineering of cells with greater persistence, there is a need in multiple phases of the CAR-T development pipeline for highly specific detection reagents that can be leveraged to monitor the expression of CARs on the cell surface. Many commercially available CAR detection reagents, however, either lack specificity or are not versatile in their ability to detect CARs of differing antigen specificity. Here, we report on the generation and validation of rabbit monoclonal antibodies raised against two linker sequences that are commonly integrated into single-chain variable fragment (scFv)-based CARs. These antibodies serve as versatile detection reagents that can be used to interrogate the surface expression of CARs.
Methods: The monoclonal antibodies, E7O2V and E3U7Q, were generated by rabbits immunized with peptide sequences most commonly used to construct the linker region of scFv based CARs, Gly4Ser and Whitlow, respectively. E7O2V and E3U7Q were validated for specificity and versatility using flow cytometric analysis of non-transduced versus CAR-transduced cell lines and primary human T cells.
Results: Flow cytometric analysis of live Jurkat cells and primary human T cells transduced with CAR constructs revealed that E7O2V and E3U7Q could detect surface expressed CARs containing the appropriate linker sequence, independently of scFv specificity. No specific staining was observed on non-transduced cells.
Conclusions: In a flow cytometry assay, E7O2V and E3U7Q specifically detect surface expressed scFv-based CARs containing either a Gly4Ser linker or a Whitlow linker, respectively. Furthermore, these monoclonal antibodies are versatile in that they can also detect their respective linker sequence independently of scFv specificity. The potential exists to leverage these antibodies for CAR-T cell enrichment and for incorporation into multiparametric flow cytometry panels used to phenotype CAR-T cells during the discovery, manufacturing, and clinical phases of the development pipeline.
Citation Format: Amrik Singh, Sarah L'Heureux, Ryan Sinapius, Michael Kvorjak, Emma Wade, Jason Lohmueller, Jeremy Fisher, Reginaldo Prioli. Generation and validation of anti-linker monoclonal antibodies for the detection of surface expressed scFv-based CARs [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 898.
Abstract 9: Histological characterization of two genetically engineered mouse models of non-small cell lung cancer
Authors: Leon Nicole F. , Baliu-Rodriguez David , Murugesh Deepa K. , Sebastian Aimy , Loots Gabriela G. , Hum Nicholas R. 
Published: April 2023

Abstract
Non-small cell lung cancer (NSCLC) patients exhibit minimal symptoms until late-stage disease, resulting in approximately 80% of patients being diagnosed at advanced stages when the response to therapy is low. Effective pre-clinical models are needed to accurately reflect NSCLC disease progression and improve basic NSCLC research. This work characterizes two genetically engineered mouse models (GEMM) that reflect human NSCLC. These mouse lines utilize a cre recombinase system to induce the expression of two oncogenic mutations (KrasG12D, Trp53fl) in club cells or alveolar epithelial cells based on cell type-specific promoters (Scgb1a1, Sftpc), thereby inducing NSCLC in mice. Furthermore, these mice harbor tumor cell-specific transgenes (GFP, MetRS) for cancer tracking. The MetRS transgene allows tumor cells to incorporate azide-bearing methionine analogs (ANL) into newly synthesized proteins which can then be detected via fluorescent noncanonical amino acid tagging (FUNCAT). Cancer mutations were induced at 6 weeks of age and lung samples were collected for histological analysis at early, mid, and late time points. Histological analysis of the club cell model revealed that hyperplasias are most abundant at the early time point and develop into invasive carcinomas within the bronchioles and alveoli at later time points. Histological scoring of this model showed that tumor burden increased from 28% to 61% of the total lung area after 15 weeks. The alveolar cell model progressed rapidly and exhibited adenocarcinomas and squamous cell carcinomas throughout disease progression. Histological scoring of this model revealed that tumor burden rapidly increased from 55% to 89% of total lung area after 5 weeks. FUNCAT analysis demonstrated that the incorporation of ANL within tumor-bearing mice was cancer-cell-specific. These findings suggest that the GEMM models accurately represent human NSCLC based on their cellular profile, morphology, and localization within the lung. The results also confirm that the tumor cells, and not the normal cells/tissues, are able to incorporate ANL into their proteins via the MetRS transgene. These models have the potential to identify biomarkers of NSCLC progression to improve patient prognosis.
*This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-839507.
Citation Format: Nicole F. Leon, David Baliu-Rodriguez, Deepa K. Murugesh, Aimy Sebastian, Gabriela G. Loots, Nicholas R. Hum. Histological characterization of two genetically engineered mouse models of non-small cell lung 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 9.
Abstract 953: Development of a predictive biomarker signature for the highly potent SIK3 inhibitor OMX-0407
Authors: Maser Ilona-Petra , Lacher Sonja , Piras Vincent , Kracher Barbara , Zanziger Kai , Yule Murray , Loferer Hannes , Bissinger Stefan 
Published: April 2023

Abstract
Using the iOTarg genetic screening platform, salt-inducible kinase 3 (SIK3), a serine/threonine kinase of the AMP-activated protein kinase (AMPK) family was recently identified as a novel cell signaling modulator in cancer biology. OMX-0407, an orally available, single-digit nanomolar inhibitor of SIK3 was shown to inhibit tumor growth in a distinct panel of tumor models in vitro as well as in vivo by decreasing downstream pro-survival signaling of SIK3, enhancing caspase-mediated apoptosis and repolarizing the tumor microenvironment by decreasing regulatory T cells.
In a comprehensive viability screening, more than 200 murine and human cancer cell lines and patient derived tumor models of different indications were used to identify a distinct subset of cancers highly sensitive towards OMX-0407. Representative for these tumors, OMX-0407 demonstrated dose-dependent anti-tumor efficacy in the renal cell carcinoma model RENCA, the squamous non-small cell lung cancer model (sqNSCLC) KLN205 and the murine colorectal tumor model MC38. With significantly prolonged overall survival of more than 60% tumor growth inhibition in all tumor models, OMX-0407 demonstrated equivalent or superior efficacy compared to anti-PD-1 monotherapy. In addition, OMX-0407 enhances the therapeutic potential of the standard of care chemotherapy in a broad range of human cancer cells and murine tumor models of sqNSCLC.
Using comprehensive transcriptomics and proteomics analyses the selective activity profile of OMX-0407 on individual cancer cell lines and PDX models was used to identify and validate a predictive biomarker signature. With this gene signature, 84% of the selected cancer cells lines are correctly classified and would benefit from OMX-0407 therapy. The predictive biomarker will be evaluated in the clinical Phase I trial of OMX-0407 scheduled to start enrollment shortly.
In summary, OMX-0407, a first-in-class oral SIK3 inhibitor, demonstrates potent monotherapy efficacy in tumor indications with high unmet medical need equal or superior to anti-PD-1 checkpoint blockade. By screening sensitive and non-sensitive tumor cell lines and PDX models, we identified a response-prediction biomarker signature. In upcoming clinical studies, this predictive biomarker signature will be evaluated for it’s potential to enrich for patients highly responsive to OMX-0407 therapy.
Citation Format: Ilona-Petra Maser, Sonja Lacher, Vincent Piras, Barbara Kracher, Kai Zanziger, Murray Yule, Hannes Loferer, Stefan Bissinger. Development of a predictive biomarker signature for the highly potent SIK3 inhibitor OMX-0407 [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 953.
Abstract 969: Non-invasive detection of plasma proteins in immune checkpoint inhibitor-treated patients with advanced non-small cell lung cancer
Authors: Stensgaard Simone , Thomsen Astrid , Dissing Julie G. , Helstrup Sofie , Meldgaard Peter , Sorensen Boe S. 
Published: April 2023

Abstract
Introduction: Immunotherapy has altered the therapeutic landscape for patients with advanced non-small cell lung cancer (NSCLC). The immune checkpoint inhibitor pembrolizumab targets the PD-1 signaling axis and has produced durable clinical response, but the efficacy is dependent on the anti-tumor activity of the immune system. We aimed to identify plasma proteins that could be used to identify patients who will respond to treatment with pembrolizumab.
Methods: Plasma samples were collected from 42 patients with advanced NSCLC before start of treatment with pembrolizumab and after 1 and 2 cycles of treatment. The plasma samples were analyzed using the Olink Proximity Extension Assay with an immuno-oncology panel detecting the expression level of 92 circulating plasma proteins. To evaluate the association between plasma protein expression and progression-free survival (PFS) the patients were stratified into two subgroups based on the median PFS (median=220 days).
Results: The patient subgroup with long PFS had significantly higher levels of Fas Ligand (FasL) and Inducible T Cell Costimulator Ligand (ICOSLG) before the start of treatment than patients with short PFS (p=0.0021 and p=0.0230 for FasL and ICOSLG). FasL remained significantly higher for patients with long PFS after 1 and 2 cycles of treatment (p=0.0170 and p=0.0190, respectively). Kaplan-Meier analysis of baseline ICOSLG and FasL expression showed longer PFS and overall survival (OS) for patients with high ICOSLG expression (p=0.0489 and p=0.0223 for PFS and OS) and for patients with high FasL expression (p=0.0064 and p=0.0069 for PFS and OS). An association was found between ICOSLG and FasL expression at baseline (R2=0.1403, p=0.0145), however the two proteins showed different dynamics during treatment, with FasL expression increasing during the early weeks of treatment, while little to no change is observed in ICOSLG expression. Combining the baseline expression of the two proteins identified a patient group with either a high expression of FasL or ICOSLG, or both, that had superior PFS (p=0.044) and OS (p=0.0017).
Conclusion: These findings suggest that the expression of FasL and ICOSLG at baseline may help identify patients who will respond to treatment with pembrolizumab.
Citation Format: Simone Stensgaard, Astrid Thomsen, Julie G. Dissing, Sofie Helstrup, Peter Meldgaard, Boe S. Sorensen. Non-invasive detection of plasma proteins in immune checkpoint inhibitor-treated patients with advanced non-small cell lung 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 969.
Abstract SY32-03: Overcoming PARP inhibitor resistance through rational combinations in the clinic
Authors: Yap Timothy A. 
Published: April 2023

Abstract
Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of key mediators of DNA repair and replication beyond PARP, such as ATR and WEE1. Dr Yap will cover the latest advances in biomarker-driven synthetic lethal combination treatment strategies for different cancers. He will discuss efforts to optimize combination therapies that are ongoing across a range of cancers, involving the development of predictive biomarkers of response, assessment of the mechanisms underlying resistance, and the evaluation of rational, tolerable combinations with novel molecularly targeted agents, immune-checkpoint inhibitors and antibody drug conjugates.
Citation Format: Timothy A. Yap. Overcoming PARP inhibitor resistance through rational combinations in the clinic. [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 SY32-03.
The Mentoring and Monitoring Practices of Schools District Supervisors
Authors: Caayaman Teresita A. 
Published: April 2023

Mentoring and Monitoring are crucial skills of Schools District Supervisors in doing their roles and functions as mandated in Republic Act 9155. However, it has been observed that formal mentoring and monitoring were not yet fully implemented in the Department of Education, Bohol Division, specifically to the Secondary School Principals. On this ground, this study was conducted to assess the mentoring and monitoring practices of Schools District Supervisors in terms of Instructional Leadership and in terms of Curricula Supervision. The study utilized data triangulation in qualitative research to examine three sources of data from the two groups of respondents who were the twenty Full-fledged Schools District Supervisors and twenty-eight Full-fledged Secondary School Principals in the three Congressional Districts in Bohol. Both respondents were conducted an open-ended interview with the same questions while on the documentary data, data from the Schools District Supervisors of their trainings attended were included. The results showed that the mentoring and the monitoring practice of Schools District Supervisors in terms of Instructional Leadership was communicating verbally, while there were no practices revealed for the following: mentoring and monitoring practices of Schools District Supervisors in terms of Curricula Supervision. mentoring and monitoring practices of Schools District Supervisors which are effectively implemented to the Secondary School Principals in terms of Instructional Leadership and in terms of Curricula Supervision, mentoring and monitoring practices of Schools District Supervisors how they are effectively implemented to the Secondary School Principals in terms of Instructional Leadership and in terms of Curricula Supervision These results imply the need to intensify the mentoring and monitoring practices of Schools District Supervisors by creating a policy on it.
Accounting Learning Gaps of K-12 Accountancy, Business, and Management (ABM) Graduates: Basis for Remediation Program for BSA Accountancy Program of Sorsogon State University (SorSu)
Authors: Bongalonta Michael B. , Bongalonta Michelle M. 
Published: April 2023

This study was conducted to identify the accounting learning gaps of K-12 ABM graduates enrolled in the Sorsogon State University (SorSU) BS in Accountancy program in the Academic Year 2021-2022. This study used mixed design to quantitatively determine the accounting learning gaps of K-12 ABM Graduates explore those issues concerning the causes of accounting learning gaps encountered by the respondents.
Results revealed that student-respondents were found to have weakness or very little accounting knowledge and skills were attributed to some factors such Limited Accounting Background and Proper Preparation, Lack of Calculation Skills, Non-integration of Accounting Lessons into Real-Life Context, Limited Physical and Human Resources are Available for the Implementation of the Accountancy, Business and Management (ABM) Track under the K-12 System and Students Study Habits and Approaches. The Proposed Accounting crash Corse was deemed necessary to address the identified learning gaps of ABM Graduates.
Playing Games to Earn Money: The Conceptual Framework of Interaction between Gender, Learning Styles, Problematic Gaming Behavior and Success-Economic Gain Motivation of Playing Games
Authors: Torralba Edwin M. 
Published: April 2023

This study identified the constructs of problematic gaming behavior that significantly impact the success-economic gain motivation of gamers. Furthermore, this study explored the role of gender, number of games played, and learning styles in problematic gaming behavior and the success-economic gain motivation of gamers using an online survey (N = 136). This study identified escape from adverse moods and preoccupation as the significant determinants of success-economic gain motivation of gamers. Escape from bad moods and preoccupation mediates the relationship between gamers' gender, number of games played, and success-economic gain motivation. Regression analysis reveals that active-reflective and sequential-global learning styles moderate the relationship between escapism, preoccupation, and success-economic gain motivation of gamers. The results suggest that the combination of active-global learning style and reflective-sequential learning style has the highest impact on the success-economic gain motivation of gamers. The results led to two conceptual frameworks that show how gender, learning styles, problematic gaming behavior, and success-economic gain motivation all play a role in game play.
Effectiveness of “How to Write a Sentence” as Instructional Material to Improve the Writing Skills of Grade 6 Pupils
Authors: Apolonio John Noah B. 
Published: April 2023

As students’ progress in their studies, they must learn a variety of important skills. Among these is writing, which is undeniably one of the most important skills that every student must develop. However, writing has always been a major challenge for students learning English, particularly in elementary schools and for second language learners. This study determined the effectiveness of the instructional material "How to Write a Sentence" as an intervention to improve the writing skills and academic performance in English of Grade 6 students at a public elementary school in the Philippines. The one-group pretest-posttest design of the quasi-experimental research design was used in this study. A 50-item pretest and posttest were used to assess the participants' academic performance before and after the intervention was implemented. The mean, standard deviation, and paired-samples t-test were used to interpret the data. Results revealed that the use of the instructional material "How to Write a Sentence" was found to be an effective intervention in improving the writing skills and academic performance in English of Grade 6 students at a public elementary school in the Philippines. It is recommended that administrators should encourage teachers to collaborate in order to further enhance or improve the intervention material or to create other contextualized and localized learning materials suited to diverse learner types.