bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Impact of Simulation‐Based Learning on Student Satisfaction and Self‐Confidence in Critical Care Medicine
Authors: Ageel Mohammed 
Published: October 2024

Background: Simulation‐based learning (SBL) is increasingly used in medical education to prepare students for clinical practice. This study aimed to evaluate the satisfaction and self‐confidence of final‐year medical students after attending SBL in critical care medicine.Methods: A cross‐sectional study was conducted among 117 final‐year medical students at Jazan University, Saudi Arabia. Participants attended SBL sessions focusing on critical care skills and scenarios. Data were collected using a self‐administered questionnaire, which included demographic information and the Student Satisfaction and Self‐Confidence in Learning Scale. Statistical analyses included descriptive and inferential statistics.Results: The study population comprised 61.54% females and 38.46% males, with a majority aged 24 years. Students who rated their overall learning experience as “Good” showed significantly higher satisfaction (4.20 ± 0.77) and self‐confidence (4.20 ± 0.69) scores. The overall mean scores for satisfaction and self‐confidence were 3.71 ± 0.88 and 3.70 ± 0.87, respectively. A strong positive correlation (p < 0.001) was found between satisfaction and self‐confidence levels. The highest satisfaction and self‐confidence scores were associated with the variety of learning materials and the instructors’ helpfulness.Conclusion: The SBL intervention was effective in enhancing student satisfaction and self‐confidence in critical care medicine. The strong correlation between satisfaction and self‐confidence highlights the importance of well‐designed SBL programs in preparing medical students for clinical practice in critical care settings.
Abstract A016: Bitter taste receptor T2R5 regulates cell viability and apoptosis in head and neck squamous cell carcinoma
Authors: Sywanycz Sarah M , Hill Brianna L , Miller Zoey A , Lee Robert J , Carey Ryan M 
Published: October 2024

Abstract
Bitter taste receptors (T2Rs) are a large family of G-protein coupled receptors (GPCRs) first identified for their role in detecting bitter stimuli. T2Rs have been shown to be expressed in benign and malignant extra-oral tissue, including head and neck squamous cell carcinomas (HNSCC), a cancer with high morbidity and mortality. In HNSCC, certain T2Rs appear to regulate proliferation and apoptosis. Bitter taste receptor, T2R5, may pose a novel therapeutic target for HNSCC due to its higher relative expression in cancerous tissue compared to normal tissue and high specificity for agonists. 1,10-phenanthroline-5,6-dione (phenanthroline) is a high potency T2R5 agonist yet to be studied for potential anti-cancer effects. We hypothesized that phenanthroline will act on endogenously expressed T2R5 in HNSCC lines to stimulate a GPCR-mediated calcium response, decrease cell viability, and increase caspase 3/7-mediated apoptosis. We found that three HNSCC cell lines (SCC 47, RPMI 2650, FaDu) express T2R5 but to varying degrees measured by qPCR (n= 6). There was a significant dose-dependent calcium response to phenanthroline measured by calcium fluorescent indicator dye, Fluo- 4 AM, for all three cell lines. Calcium responses were significantly dampened with Gα protein inhibitors, YM254890 and FR900359, suggesting a GPCR mediated calcium response consistent with established T2R functionality. Treatment with phenanthroline showed a dose-dependent decrease on cell viability at 24 hours measured by crystal violet assay. Individual IC50 values from crystal violet were roughly inversely correlated to level of T2R5 expression. Stimulation with phenanthroline increased apoptosis measured by a caspase 3/7 activity dye (CellEvent) at 24 hours. Pretreatment with phenanthroline prior to treatment with cisplatin showed decreased overall cell viability compared to each treatment alone (p = 0.0062), which may suggest a role as a sensitizing agent. Comparison of HNSCC patients with high or low expression of T2R5 using The Cancer Genome Atlas showed greater long-term overall survival for the high versus low expression group (p= 0.04), possibly supporting T2R5’s role in cancer regulation. In summary, T2R5 and its high potency agonist phenanthroline may be important regulators of apoptosis in HNSCC warranting further exploration. Future direction will continue to explore the mechanisms and roles of T2R5 in HNSCC and potential sensitization effects when used in combination with other agents like cisplatin.
Citation Format: Sarah M Sywanycz, Brianna L Hill, Zoey A Miller, Robert J Lee, Ryan M Carey. Bitter taste receptor T2R5 regulates cell viability and apoptosis in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A016.
Abstract A029: Preferential ability of IL-7 versus IL-2 to restore effector T cell responses in the presence of regulatory T cells assessed using MR-MCTM assays in vitro
Authors: Welsh Emma , Li Zhi , Sallie Leila , Pegg Ashley , Chan Hujo , Cowley Jamie , Kaur Arshpreet , Harrison Neale , Smith David J , Bryant Mark , Brady Catherine A , Gordon John , Barnes Nicholas , Qureshi Omar 
Published: October 2024

Abstract
Within the tumour microenvironment, regulatory T cells diminish anti-tumour responses by inhibiting effector T cell activation. Immunotherapies that enhance the effector T cell response may also enhance Treg activity, limiting the overall action of the therapy. It is therefore important to consider the ‘net-effect’ of immune activation in systems containing both cell types. To better understand responder T cell activation in a relevant cellular environment, we have investigated human effector T cell activation in the presence of regulatory T cells in vitro exploiting multiple readouts from multi-cell type suppression assays (MR-MCTM suppression assay). These assays have been performed in the absence or presence of IL-2 (hypothesised to boost both effector and regulatory T cell responses), and the absence or presence of IL-7 (hypothesised to skew towards effector T cell responses), to assess potential for biased activation of effector T cells over regulatory T cells. For certain activation markers, e.g. CD25 and CD71, the ability to restore effector T cell expression in the presence of regulatory T cells was greater for IL-7 compared to IL-2. We have also investigated the impact of these two cytokines on a range of early and later activation readouts of the responder T cell populations to add granularity to overall impact. Interestingly and in contrast to IL-7, IL-2 evoked greater increases in activation marker expression by regulatory T cells, indicating enhanced regulatory T cell function may contribute to the differential impact of these cytokines upon the responder T cell response. These results demonstrate how potential immunotherapies may differentially impact effector and regulatory T cell populations and highlight the considerable utility of investigating potential immunotherapies (e.g. checkpoint inhibitors) in MR-MCTM assays to better understand impact upon the overall balance of immune activation.
Citation Format: Emma Welsh, Zhi Li, Leila Sallie, Ashley Pegg, Hujo Chan, Jamie Cowley, Arshpreet Kaur, Neale Harrison, David J Smith, Mark Bryant, Catherine A Brady, John Gordon, Nicholas Barnes, Omar Qureshi. Preferential ability of IL-7 versus IL-2 to restore effector T cell responses in the presence of regulatory T cells assessed using MR-MCTM assays in vitro [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A029.
Abstract A043: Costimulation by type 1 dendritic cells facilitates the differentiation of non-exhausted anti-tumor T cells
Authors: Duong Ellen , Banta Karl , Nutsch Katie , Wu Thomas , Chiang Eugene , Mellman Ira 
Published: October 2024

Abstract
T cell exhaustion, a differentiation state defined by reduced proliferative capacity, impaired effector function, and the upregulation of inhibitory checkpoint receptors, is pervasive in chronic diseases like cancer. While therapeutic antibodies targeting these inhibitory receptors can sustain T cell function, recent studies have underscored the importance of positive costimulation in limiting the development of the exhausted phenotype, a role canonically attributed to dendritic cells (DC). However, the functions of DC in the tumor microenvironment to support immunotherapy responses remain poorly characterized. We recently established that type 1 conventional DC (cDC1) are required for the therapeutic efficacy of TIGIT and PD-L1 combination blockade, thus providing a system to investigate the mechanisms by which intratumoral cDC1 can support T cell responses during immunotherapy. Following combination blockade, cDC1 exhibited an enhanced maturation and migratory phenotype, highly expressing both CD28 ligands (CD80 and CD86) and the CD226 ligand (PVR). Concurrently, therapy-responsive cytotoxic T cells in the tumor co-expressed both CD28 and CD226 receptors but strongly upregulated only CD226 expression, indicating increased costimulatory signaling through this specific pathway. Indeed, cDC1-specific PVR deletion or CD226 blockade both impaired therapeutic responses, causing T cells in the tumor to maintain features of exhaustion despite their expansion. Our work thus far highlights a critical role for intratumoral cDC1-mediated costimulation in preventing T cells from entering the exhaustion pathway. These findings further underscore the necessity of stimulatory cDC1 in tumors for successful immunotherapy responses.
Citation Format: Ellen Duong, Karl Banta, Katie Nutsch, Thomas Wu, Eugene Chiang, Ira Mellman. Costimulation by type 1 dendritic cells facilitates the differentiation of non-exhausted anti-tumor T cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A043.
Abstract A044: Meta-analysis of adoptive natural killer cell transfer immunotherapy against solid cancers in human patients
Authors: Jou Eric , Ho Jamie SY 
Published: October 2024

Abstract
Purpose: Recent studies revealed innate lymphoid cells (ILCs) to play critical roles in tumor pathogenesis across multiple preclinical cancer models, however their potential therapeutic efficacy in human cancer patients remain largely unclear. Natural killer (NK) cells, the founding members of group 1 ILCs, exhibit potent anti-tumor cytotoxic activities and NK cell adoptive transfer may serve as a promising immunotherapeutic strategy against solid cancers in patients, however to date this has not been conclusively demonstrated. Methods: A prospectively registered systematic review and meta-analysis (registration ID: CRD42024523774) was conducted assessing the safety and efficacy of NK cell-based adoptive transfer immunotherapies in patients with solid cancers. Major databases including Medline, Embase and Scopus were searched, and all controlled clinical trials utilising NK cell adoptive transfer in patients with solid cancers were included. Results: Of the 4597 articles screened, 44 clinical trials that utilise NK cell-based adoptive transfer therapies in patients with solid cancers were identified, of which 15 were controlled clinical trials and were included in the study. Combined meta-analysis of patients with advanced neuroblastoma, pancreatic, renal, liver, brain, colorectal and lung cancers treated with adoptive NK cell transfer together with standard treatment revealed a 44% and 67% increase in overall clinical response rate (RR=1.44; 95% CI 1.18-1.75, I2=0%, P&lt;0.0001) and complete response rate (RR=1.67, 95% CI 1.02-2.74, I2=0%, P=0.04) respectively, compared to standard treatment alone. Strikingly, the addition of adoptive NK cell transfer immunotherapy reduced the disease progression rate by 53% (RR=0.47, 95% CI 0.34-0.66, I2=0%, P&lt;0.0001), improved progression-free survival by an average of 2.87 months (95% CI=0.58-5.15, I2=0%, P=0.01), and was not associated with increased haematological or systemic adverse effects such as anaemia (P=0.30) and fever (P=0.13). Conclusions: The present study is the first meta-analysis to demonstrate that the addition of adoptive NK cell transfer immunotherapy to existing standard treatment is safe and efficacious in improving clinical response rate and prolonging survival in patients with solid cancers.
Citation Format: Eric Jou, Jamie SY Ho. Meta-analysis of adoptive natural killer cell transfer immunotherapy against solid cancers in human patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A044.
Abstract A054: Recruiting innate immune cells universally: Development of a novel universal innate cell engager for cancer-immunotherapy
Authors: Hutter-Karakoc Idil , Surowka Marlena , Darowski Diana , Klaus Christina , Koller Claudia Ferrara , Hofer Thomas , Freimoser-Grundschober Anne , Mössner Ekkehard , Leclair Stephane , Umana Pablo , Munz Christian , Amann Maria , Klein Christian 
Published: October 2024

Abstract
Novel antibody-engineering approaches have enabled the development of targeted innate cell engagers which redirect innate immune cells to eliminate cancer or suppressive immune cells. These antibodies function through binding to surface antigens on target cells and engaging activating receptors on innate immune cells such as natural killer cells and macrophages. Although early innate cell engagers have shown promise in controlling various cancer types, several major challenges remain in the clinics, including high tumor heterogeneity, low tumor immunogenicity, and reduced efficacy in solid tumors. Here, we present a universal innate cell engager as part of a novel adaptor-based antibody platform. Our universal innate cell engager utilizes a two-step approach combining the power of an adaptor and an effector antibody. First, an Fc-silenced adaptor antibody comprising P329G LALA mutations is used to target the desired antigen in the tumor microenvironment. Then, as an effector antibody, a universal innate cell engager directed against the P329G mutation on the adaptor antibody is used. Innate immune cells are recruited by the universal innate cell engager through its active Fc, leading to antibody-dependent cellular cytotoxicity against the target cells. To maximize innate cell activation, the Fc portion of the universal innate cell engager can be glycoengineered for enhanced FcgRIII affinity.In vitro and in vivo assays showed that our universal innate cell engager is inducing innate immune cell activation and innate immune cell-mediated target cell killing when combined with different antigen-targeted adaptor antibodies. Ultimately, this approach may enable off-the-shelf personalization via combination of universal effector cell engagers and selected adaptor antibodies specific to the patient’s tumor profile.
Citation Format: Idil Hutter-Karakoc, Marlena Surowka, Diana Darowski, Christina Klaus, Claudia Ferrara Koller, Thomas Hofer, Anne Freimoser-Grundschober, Ekkehard Mössner, Stephane Leclair, Pablo Umana, Christian Munz, Maria Amann, Christian Klein. Recruiting innate immune cells universally: Development of a novel universal innate cell engager for cancer-immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A054.
Abstract B017: Chronic stress signaling in disseminated tumor cells promotes immune evasion in breast cancer metastasis
Authors: Cassandras Monica , Huang Yu , Codinachs Ia , Sanchez Xavier , Chuong Jeffrey , Getzler Adam , Flores Pilar Baldominos , Agudo Judith 
Published: October 2024

Abstract
Breast cancer is one of the most lethal diseases for women, with metastasis accounting for over 90% of mortalities. Metastasis occurs when disseminated tumor cells (DTCs) escape detection and killing by surveilling cytotoxic immune cells. The mechanisms of DTC immune evasion are currently not well understood, and this represents a crucial barrier to developing effective therapies to prevent metastatic disease. In the Agudo Lab, we investigate how DTCs evade immune surveillance by utilizing our JEDI CD8+ T cells, which recognize the Green Fluorescent Protein (GFP) to target tumor cells for killing. We used JEDI T cells in combination with a model of breast cancer dissemination in which the cancer cells express GFP. By profiling the GFP+ DTCs that successfully survive JEDI immune attack, we unexpectedly discovered that chronic stress hormone (glucocorticoid) signaling is a top driver of immune evasion in lung DTCs and micro-metastases. Further analysis revealed that activation of the glucocorticoid receptor (GR) promotes an immune evasive state in DTCs that is independent of the suppressive effect of glucocorticoids on immune cells. Indeed, elevated GR activation signatures in patients with primary breast cancer correlates with worse survival. We determined that GR signaling in disseminated breast cancer cells in the lung directly blocks cytotoxic lymphocyte killing by both CD8+ T cells and NK cells, which increases metastatic burden. Mechanistically, DTCs harness stress hormones to repress the death receptor FAS and acquire an overall anti- apoptotic phenotype in order to protect themselves from immune clearance. We determined that pharmacologic antagonism of GR by Mifepristone treatment synergizes with anti-PD1 immunotherapy to reduce metastasis by promoting cytotoxic killing of DTCs and early micro-metastases. Exploiting the mechanisms by which tumor-intrinsic GR signaling prevents immune responses represents promising new avenues for limiting metastasis, and opens the door for new combinatorial treatments with current immunotherapy regimens.
Citation Format: Monica Cassandras, Yu Huang, Ia Codinachs, Xavier Sanchez, Jeffrey Chuong, Adam Getzler, Pilar Baldominos Flores, Judith Agudo. Chronic stress signaling in disseminated tumor cells promotes immune evasion in breast cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B017.
Abstract B026: Modulation of signalling cross-talk between pJNK and pAKT generates optimal apoptotic response
Authors: Tikader Baishakhi , Biswas Sharmila , Kar Sandip , Viswanathan Ganesh A. 
Published: October 2024

Abstract
Tumor necrosis factor alpha (TNFα) is a well-known modulator of apoptosis by maintaining a balance between proliferation and cell-death in normal cells. Cancer cells often evade apoptotic response following TNFα stimulation by altering signaling cross- talks. Thus, varying the extent of signaling cross-talk could enable optimal TNFα mediated apoptotic dynamics. Herein, we use an experimental data-driven mathematical modeling to quantitate the extent of synergistic signaling cross-talk between the intracellular entities phosphorylated JNK (pJNK) and phosphorylated AKT (pAKT) that orchestrate the phenotypic apoptosis level by modulating the activated Caspase3 dynamics. Our study reveals that this modulation is orchestrated by the distinct dynamic nature of the synergism at early and late phases. We show that this synergism in signal flow is governed by branches originating from either TNFα receptor and NFκB, which facilitates signaling through survival pathways. We demonstrate that the experimentally quantified apoptosis levels semi-quantitatively correlates with the model simulated Caspase3 transients. Interestingly, perturbing pJNK and pAKT transient dynamics fine-tunes this accumulated Caspase3 guided apoptotic response. Thus, our study offers useful insights for identifying potential targeted therapies for optimal apoptotic response.
Citation Format: Baishakhi Tikader, Sharmila Biswas, Sandip Kar, Ganesh A. Viswanathan. Modulation of signalling cross-talk between pJNK and pAKT generates optimal apoptotic response [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B026.
Abstract B035: Enhanced tumor infiltration and functionality of anti-GPC3 CAR-T cells in hepatocellular carcinoma through locoregional administration
Authors: Wang Jue , Feng Bo 
Published: October 2024

Abstract
Despite the rapid development of anti-cancer immunotherapy, the prognosis of hepatocellular carcinoma (HCC) patients is far from satisfactory. GPC3 CAR-T cell therapy has shown varied patient response. One of the potential reasons of low response rates is due to the limited CAR-T cell infiltration. Therefore, locoregional GPC3 CAR-T therapy has been a promising option, with a hope of increasing the treatment efficacy. In this study, the therapeutic efficacy and underlying mechanisms of locoregional GPC3 CAR-T cell delivery were explored using orthotopic mouse HCC xenografts. CAR-T cell injection was performed locoregionally (through portal vein) and systemically (through tail vein). Compared to the systemic treatment, locoregional CAR-T therapy could better control the tumour growth, and was associated with improved liver function. In addition, increased percentage of tumour infiltrating CAR-T cells was observed in the locoregional therapy group, with those CAR-T cells gaining increased cytotoxicity, chemotaxis and less exhaustion phenotype. Furthermore, portal vein injection also exhibited a better tumour inhibition ability over tail vein injection on a metastatic model which simultaneously bore both orthotopic and extrahepatic tumour lesions. In the current study, we have demonstrated that locoregional administration of CAR-T cells is associated with increased tumour infiltration and better therapeutic efficacy. Moreover, our results provide insights that locoregional CAR-T therapy could also be employed to the late-stage patients with distant metastasis.
Citation Format: Jue Wang, Bo Feng. Enhanced tumor infiltration and functionality of anti-GPC3 CAR-T cells in hepatocellular carcinoma through locoregional administration [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B035.