bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS10-08: Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting
Authors: Eriksson Mikael , Román Marta , Gräwingholt Axel , Heywang-Köbrunner Sylvia , Rossi Paolo , Hall Per 
Published: May 2024

Abstract
Background:
Image-derived AI risk models for breast cancer have shown high discriminatory performances compared with clinical risk models based on family history and lifestyle factors. However, little is known about their generalizability across different screening settings and clinical feasibility.
Purpose:
To investigate the predictive performance of a clinically used image-derived AI-based breast cancer risk model in multiple European screening populations.
Methods:
Four European mammographic screening populations in three countries screened between 2009-2020 for women aged 45-69 was used to perform a nested case-control study. In total, 739 women with incident breast cancers were included together with 7,812 controls matched to cases on year of study-entry. Mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) for risk assessment were extracted using AI from full-field digital mammograms. Breast cancer occurrence was assessed after two years of follow-up. Absolute risks of breast cancer were predicted using the risk model from negative mammograms at study-entry. Adjusted Area Under the receiver operating characteristic Curves (aAUC) estimated discriminatory performance and, adjusted risk-ratios estimated the stratification performance of women at high/general risk per the clinical guidelines.
Results:
The overall aAUC of the AI risk model was 0.72 (95%CI 0.70-0.75), range 0.71 (95%CI 0.67-0.75) to 0.74 (95%CI 0.69-0.78) for breast cancers developed in four screening populations. In the 4.6% of women classified at high risk using the NICE guidelines thresholds, cancers were more likely diagnosed after 2 years follow-up, risk-ratio (RR) 6.7 (95%CI 5.6-8.0), compared with the 71% of women classified at general risk by the model. Similar risk-ratios were observed across tertiles of mammographic density. In the high-risk group, 22% of the 2-year future cancers were diagnosed, and 29% of stage 2 and higher cancers, p&lt; 0.01.
Conclusions:
The AI risk model showed generalizable discriminatory performances across European populations and, captured ~30% of clinically relevant stage 2 and higher breast cancers in ~5% of high-risk women who were sent home with a negative mammogram. Similar results were seen in fatty and dense breasts. An image-derived AI model is feasible for personalized screening to improve screening outcomes.

Citation Format: Mikael Eriksson, Marta Román, Axel Gräwingholt, Sylvia Heywang-Köbrunner, Paolo Rossi, Per Hall. Validation of a clinical image-based AI-risk model for individualized breast cancer screening in a multi-national setting [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-08.
Abstract PS12-04: Inhibition of GPX4 enhances CDK4/6 inhibitor activity in breast cancer
Authors: Abreu Maria Teresa Herrera , Khalid Uzma , Ning Jian , Cutts Rosalind , Wilson Gemma , Lord Christopher , Swain Amanda , Turner Nicholas 
Published: May 2024

Abstract
Background:
Cyclin D-dependent kinases 4 and 6 (CDK4/6) inhibitors (CDK4/6i) including palbociclib, ribociclib and abemaciclib in combination with endocrine therapy are the standard of care for patients with estrogen receptor-positive (ER+). Despite the success of these treatments, cytostasis is frequently observed, and novel strategies that enhance efficacy are required to eradicate residual cancer in the clinic.
Methods:
In the search of an effective drug combinations to enhance the efficacy of CDK4/6 inhibitors in breast cancer, we performed a whole genome CRISPR-Cas9 suppressor screen in MCF-7, an ER+ model. We also carried out transcriptomics, proteomics, and functional molecular biology analysis of breast cancer models treated with palbociclib to identify resistant mechanisms.
Results:
The whole genome CRISPR-Cas9 screen revealed that multiple genes involved in oxidative stress and ferroptosis modulated palbociclib sensitivity, being GPX4 the top sensitizing hit. GPX4 is a key glutathione peroxidase that protects again ferroptosis by catalysing the reduction of phospholipid and cholesterol hydroperoxides. CRISPR-depletion or drug inhibition of GPX4 increased sensitivity to palbociclib in ER+ breast cancer models, and in addition sensitised triple negative breast cancer models to palbociclib. Moreover, GPX4 null xenografts were highly sensitive to palbociclib in vivo. Transcriptomics and proteomics analysis showed that palbociclib upregulate pathways involved in oxidative stress and lipid metabolism promoting a redox-lipid imbalance. Palbociclib induced lipid peroxidation leading to a ferroptosis vulnerable state with GPX4 preventing cell death. Polyunsaturated fatty acids (PUFAs) are highly susceptible of lipid peroxidation, and pathways that regulate their abundance in membrane phospholipids were explored. Interestedly, in ER+ breast cancer models, lipid peroxidation relied on a peroxisome AGPAT3-dependent pathway rather than the classical ACSL4 pathway.
Conclusion:
Our studies demonstrate that quiescence induced by palbociclib results in a ferroptosis-vulnerable state that could be exploited through combination with GPX4 inhibitors to enhance sensitivity to CDK4/6 inhibition in breast cancer.
Citation Format: Maria Teresa Herrera Abreu, Uzma Khalid, Jian Ning, Rosalind Cutts, Gemma Wilson, Christopher Lord, Amanda Swain, Nicholas Turner. Inhibition of GPX4 enhances CDK4/6 inhibitor activity in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS12-04.
Abstract SoA1-02: Engineered T cell therapies- what is the outlook for breast cancer?
Authors: Velez V. Hoyos 
Published: May 2024

Abstract
With the promising outcomes seen in hematological malignancies, engineered T-cell therapies, notably chimeric antigen receptor (CAR) therapies, have emerged as breakthroughs in the field of oncology. Yet, their prospect in treating breast cancer and other solid tumors remains a topic of intense investigation. This presentation aims to delve into the diverse engineered T-cell treatments, contextualizing their role in breast cancer. We explore the intrinsic therapeutic challenges these modalities face and the concerted efforts in the scientific community to overcome them. We will look at the current clinical trial landscape for CAR-T cell therapies in breast cancer, underscoring their potential in shaping breast cancer treatment in the years to come.
Citation Format: V. Hoyos Velez. Engineered T cell therapies- what is the outlook for breast cancer? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SoA1-02.
Abstract SoA2-01: Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity
Authors: Ruscetti M. 
Published: May 2024

Abstract
Cellular senescence is a stress-induced program following aberrant oncogene activation or administration of cancer therapies, including chemotherapeutic agents and CDK4/6 inhibitors commonly used for treating advanced breast cancers, that results in the proliferative arrest of damaged cells and induction of the senescence associated secretory phenotype (SASP). The SASP involves secretion of inflammatory cytokines and chemokines and upregulation of immunomodulatory cell surface molecules on senescent cells that can promote their clearance by the immune system and tumor resolution. However, if left unchecked, the chronic SASP can also lead to immune suppression and further tissue damage that drives tumor dissemination and metastasis. Here we will discuss our efforts to understand how the SASP can promote anti-tumor immunity and immunotherapy activity in some cancer contexts yet in others immune suppression and tumor promotion. Our findings in other solid tumor contexts demonstrate that the tissue microenvironment has a profound impact of the type of SASP program activated and SASP-mediated immune responses produced and suggest further therapeutic interventions to remodel the SASP for immune control of cancer. Moreover, our results in other hormone-driven cancers suggest that CDK inhibitor and chemotherapy regimens produce different SASPs and resulting effects on myeloid cell and lymphocyte phenotypes that could explain their varying effects on anti-tumor immunity and treatment outcomes. Collectively these findings have important implications for breast cancer treatment and pave the path for rationale combination therapies with senescence-inducing agents to achieve immune control in breast and other immunologically “cold” solid tumor malignancies that are generally unresponsive to current immunotherapy regimens.
Citation Format: M. Ruscetti. Cellular senescence: The senescence-associated secretory phenotype (SASP) and immunity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SoA2-01.
Abstract SS02-03: Cancer risk associated with exogenous hormone use in BRCA mutation carriers
Authors: Kotsopoulos J. 
Published: May 2024

Abstract
Women with a pathogenic vari ant (mutation hereafter) in the BRCA1 or BRCA2 gene face the highest known lifetime risks of developing breast cancer. Notably, incidence rates increase rapidly in early adulthood but remain high even after age 60. Thus, understanding how exogenous (anti)hormones impact these risks is important for the safe clinical management of high-risk women, especially following early surgical menopause. In this session, I will review the current data on the role of tamoxifen chemoprevention, as well as the impact of oral contraceptives, hormone replacement therapy and fertility medication on breast cancer risk. Where possible, I will also discuss associations with ovarian cancer, given that managing BRCA-cancer risks is a balancing act, and present findings by gene mutation. Gaps in the literature and opportunities for further research will also be described. Our goal should be to maximize survival while optimizing health following risk-reducing salpingo-oophorectomy.
Citation Format: J. Kotsopoulos. Cancer risk associated with exogenous hormone use in BRCA mutation carriers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SS02-03.
Abstract Wrk2-01: Organoid Models of Cancer and the Tumor Microenvironment
Authors: Kuo C. 
Published: May 2024

Abstract
Both cell-intrinsic and microenvironmental influences vitally govern tumor progression. Mutational, chromosomal and epigenetic alterations represent the former, while the latter is influenced by diverse stromal populations including fibroblasts, vasculature and immune cells. In vitro organoid culture provides an experimentally tractable platform for cancer research that is applicable to cell-autonomous and tumor microenvironmental studies. The first part of this lecture will describe our work using organoid culture to functionally validate tumor cell-intrinsic genomic alterations. Notably, cancer research has traditionally lacked in vitro methods where tumors can be holistically cultured in a non-reconstitutive manner that co-preserves neoplastic cells together with endogenous stromal components. Thus, the second part of this lecture will describe advances in 3D tumor organoid culture that allow growth of cancer cells in a manner that preserves their native interaction with diverse tumor-infiltrating immune cells and allows analysis of immune checkpoint inhibition.
Citation Format: C. Kuo. Organoid Models of Cancer and the Tumor Microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Wrk2-01.
Abstract Wrk2-02: Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability
Authors: Laughney A. 
Published: May 2024

Abstract
Multicellular programs underly emergent phenotypes in health and disease. Yet, deciphering the functional effects of interactions amongst cell types remains a major challenge. Cells typically send messages to their microenvironment by emitting ligands, which bind to complimentary receptors on the surfaced of target cells; then triggering a change in the behavior of the target cell. Complimentary ligand-receptor-pairs are well annotated and methods have been developed to infer cell-cell interactions from single cell expression data based on their mutual expression. However, these methods do not assess the effect of ligand-receptor-mediated interactions on the microenvironment. Thus, we developed ContactTracing – a fundamentally new, systems level approach that exploits inter- and intra-sample variability to infer ligand effects on gene expression in target (receptor-expressing) cells without prior knowledge of downstream signaling (Nature, 2023). Foundational work towards benchmarking and validation of this method was performed in isogenic breast cancer models distinguished by tumor cell-intrinsic rates of chromosome missegregation (a cellular process called chromosomal instability, or CIN). Through this, we identified tumor ligands emanating from an endoplasmic reticulum (ER)-stress response as potential mediators of immune suppression in chromosomally unstable tumors. Indeed, CIN-induced chronic STING activation led to rapid interferon-selective desensitization and a switch to ER-stress-dependent transcription. Moreover, inhibition of chronic STING - or key mediators of its unfolded protein response to ER-stress - suppressed metastasis in syngeneic models of melanoma, breast and colorectal cancer; validating this innovative methodology and identifying a targetable mediator of cancer metastasis.
Citation Format: A. Laughney. Modelling the effects of cell-cell interactions in the tumor microenvironment from single cell variability [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Wrk2-02.
Examining the Impact of the COVID-19 Pandemic on Student Employability Skills - an Employer’s Perspective
Authors: Gibson van Mil Lorraine , De-Pascale Egizia , Burns Emma , Scott Fraser J. , Walker Sarah E. 
Published: May 2024

Like most university learners, students in the Department of Pure and Applied Chemistry at the University of Strathclyde, experienced hybrid learning environments from March 2020 transitioning into hybrid approaches for the full academic year 21/22. As students who were in the early years of their programme at this time, and experienced a shift from traditional education practices are soon to graduate, a short research project was undertaken to better understand the perception of employers on the impact of remote and hybrid learning on current, and future, graduate skills, and competencies. Several employers in the chemical industries were surveyed to rate changes in their perception of, and importance of, key graduate skills and competencies after the pandemic. In general, it was shown that the employers responding to this survey did not show concern about the level of personal, professional, and higher-level cognitive skills developed by students working in remote/hybrid environments during the pandemic. A gap in practical skills was acknowledged as indicated by employers’ viewing students as being less skilled in this area, however the skills gap was not thought to be important with regards to employability. Additionally, employers indicated an increased importance on a student’s ability to develop and demonstrate basic personal and professional skills including communication, collaboration, interpersonal/networking, autonomy, self-management, and resilience. The research suggests programme leaders creating or modifying curricula should place attention on the development of these skills and competencies to ensure students are self-led to successfully transition into the workplace.
The Effectiveness of Local Culture-Based Human Values in Efforts to Strengthen Pancasila Student Profiles in Elementary Schools
Authors: Astawaa Dewa Nyoman Wija , Handayani Ni Nyoman Lisna , Meylani Vita 
Published: May 2024

Introduction: Human values, including Truth, Virtue, Peace, Compassion, and Non-Violence, should be ingrained and educated in pupils from a young age to enhance their character in accordance with a nation's standards. The degradation of human values can be attributed to the growing prevalence of individualist views that are in line with contemporary societal norms. It is imperative to enhance and cultivate human values that are rooted in indigenous knowledge and are congruent with the characteristics of Pancasila students. The objective of this study is to conduct a detailed analysis of various methodologies employed in the integration of human values into the development of Pancasila student profiles. Method: A qualitative research design and descriptive approach are employed in this study. The study was carried out in a State Elementary School located in the West Selemadeg District of Tabanan Regency. The data was acquired by extensive observations of kids' learning activities and learning environments, as well as through focus group discussions (FGD) involving school principals, instructors, and parents. Results: The qualitative analysis of the data revealed that the inclusion of human values derived from the local culture is a pertinent pedagogical approach within the independent learning curriculum. Conclusions: The efficacy of this strategy in enhancing the holistic development of Pancasila pupils has been well-documented.
IL-1β Inhibition Partially Negates the Beneficial Effects of Diet-Induced Atherosclerosis Regression in Mice
Authors: Karnewar Santosh , Karnewar Vaishnavi , Deaton Rebecca A. , Shankman Laura S. , Benavente Ernest D. , Williams Corey M. , Bradley Xenia , Alencar Gabriel F. , Bulut Gamze B. , Kirmani Sara , Baylis Richard A. , Zunder Eli R. , den Ruijter Hester M. , Pasterkamp Gerard , Owens Gary K. 
Published: May 2024

BACKGROUND:
Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions is the global leading cause of death. The most common and effective means to reduce these major adverse cardiovascular events, including myocardial infarction and stroke, is aggressive lipid lowering via a combination of drugs and dietary modifications. However, we know little regarding the effects of reducing dietary lipids on the composition and stability of advanced atherosclerotic lesions, the mechanisms that regulate these processes, and what therapeutic approaches might augment the benefits of lipid lowering.

METHODS:

Smooth muscle cell lineage-tracing

Apoe
−/−

mice were fed a high-cholesterol Western diet for 18 weeks and then a zero-cholesterol standard laboratory diet for 12 weeks before treating them with an IL (interleukin)-1β or control antibody for 8 weeks. We assessed lesion size and remodeling indices, as well as the cellular composition of aortic and brachiocephalic artery lesions, indices of plaque stability, overall plaque burden, and phenotypic transitions of smooth muscle cell and other lesion cells by smooth muscle cell lineage tracing combined with single-cell RNA sequencing, cytometry by time-of-flight, and immunostaining plus high-resolution confocal microscopic z-stack analysis.

RESULTS:

Lipid lowering by switching

Apoe
−/−

mice from a Western diet to a standard laboratory diet reduced LDL cholesterol levels by 70% and resulted in multiple beneficial effects including reduced overall aortic plaque burden, as well as reduced intraplaque hemorrhage and necrotic core area. However, contrary to expectations, IL-1β antibody treatment after diet-induced reductions in lipids resulted in multiple detrimental changes including increased plaque burden and brachiocephalic artery lesion size, as well as increasedintraplaque hemorrhage, necrotic core area, and senescence as compared with IgG control antibody–treated mice. Furthermore, IL-1β antibody treatment upregulated neutrophil degranulation pathways but downregulated smooth muscle cell extracellular matrix pathways likely important for the protective fibrous cap.

CONCLUSIONS:
Taken together, IL-1β appears to be required for the maintenance of standard laboratory diet–induced reductions in plaque burden and increases in multiple indices of plaque stability.
The Thai Discourse Treebank: Annotating and Classifying Thai Discourse Connectives
Authors: Prasertsom Ponrawee , Jaroonpol Apiwat , Rutherford Attapol T. 
Published: May 2024

Abstract
Discourse analysis is a highly applicable area of natural language processing. In English and other languages, resources for discourse-based tasks are widely available. Thai, however, has hitherto lacked such resources. We present the Thai Discourse Treebank, the first, large Thai corpus annotated in the style of the Penn Discourse Treebank. The resulting corpus has over 10,000 sentences and 18,000 instances of connectives in 33 different relations. We release the corpus alongside our list of 148 potentially polysemous discourse connectives with a total of 340 form-sense pairs and their classification criteria to facilitate future research. We also develop models for connective identification and classification tasks. Our best models achieve an F1 of 0.96 in the identification task and 0.46 on the sense classification task. Our results serve as benchmarks for future models for Thai discourse tasks.
To the knowledge of the subgenus Phrator Semenov, 1922 of the genus Omophron Latreille, 1802 (Coleoptera: Carabidae)
Authors: ANICHTCHENKO ALEXANDER , VALAINIS ULDIS 
Published: May 2024

The species of the subgenus Phrator Semenov, 1922 are reviewed, with six species now recognized. One species is downgraded to subspecies: O. multiguttatum depressum Klug, 1853 stat. nov. Some new synonymies are proposed Omophron variegatum boiteli Alluaud, 1935 syn. n. = Omophron variegatum sardoum Reitter, 1907 syn. n. = Omophron variegatum seurati Alluaud, 1935 syn. n. = Omophron (Phrator) variegatum Olivier, 1812; Omophron (Phrator) ethiopiensis Valainis, 2016 syn. nov. = O. multiguttatum (s.str) Chaudoir, 1850; and Omophron (Phrator) alluaudi Dupuis, 1913 syn. n. = O. vittulatum Fairmaire, 1894. The variability of all the treated species is discussed. A key to the species, together with new distributional data, maps of distribution, illustrations of the habitus and of the most important features are provided.