bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B012: The effect of a novel therapy on DNA methylation in Ewing Sarcoma
Authors: Isenhart Emily , Gupta Ajay , Ohm Joyce 
Published: February 2025

Abstract
Ewing sarcoma (EwS) is a rare and aggressive disease affecting the bone and soft tissue of children and young adults. A FET::ETS fusion protein, typically EWSR1-FLI1 is pathognomonic for this disease. EwS is genomically quiet with widespread dysregulation driven by aberrant fusion activity leading to elevated endogenous levels of replication stress and epigenetic drift. While five-year survival rates are moderate for localized primary disease (∼70%), metastasized, relapsed, and refractory disease have much lower rates of survival (15-35%) and are associated with increased epigenetic heterogeneity. Treatment options are currently limited to systemic therapies which have not seen major advancement since the development of interval compression of chemotherapy and often lead to secondary complications for these patients. Our lab has identified a novel combination of replication stress response inhibitors (RSRi), DDK (DDKi) and WEE1 (WEE1i), which sensitize EwS cells to their own elevated levels of replication stress by removing repair strategies and forcing mitotic catastrophe and apoptosis. In one in vivo study, cell line derived xenografts in NSG mice were treated with DDKi (simurosertib) and WEE1i (adavosertib) in the following design: 1) vehicle control (n=5), 2) Irinotecan + Temozolomide (n=9), 3) Irinotecan (full dose) + DDKi + WEE1i (n=7), 4) Irinotecan (half dose) + DDKi + WEE1i (n=9), for a total of 30 samples. We have shown that this RSRi combination is able to effectively limit tumor growth over time even in the context of decreased chemotherapeutic dose. As increased replication stress can cause epigenetic drift, changes in methylation associated with treatment condition were investigated by reduced representation bisulfite sequencing. Differential methylation analysis was performed on individual CpG sites, CpG structures (islands, shores) and transcriptional elements (promoters, enhancers, transcription start sites). In this context, key pathways were found to be differentially methylated between treatment conditions, including those involved in cell signaling, motility, metabolism, and neuronal processes. Overall, this targeted therapy presents a promising therapeutic option for this pediatric patient population.
Citation Format: Emily Isenhart, Ajay Gupta, Joyce Ohm. The effect of a novel therapy on DNA methylation in Ewing Sarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B012.
Abstract B014: MCED - DNA methylation-based liquid biopsy for early detection of HPV-related cancers
Authors: Nedjai Belinda 
Published: February 2025

Abstract
Human papillomavirus (HPV)-related cancers, particularly cervical cancer, as well as other malignancies such as oropharyngeal, anal, and penile cancers, represent significant global health concerns. While HPV infections are common and usually transient, persistent infection with high-risk HPV types (such as HPV-16 and HPV-18) can lead to the development of cancer through a multi-step process that involves the integration of viral DNA into the host genome, leading to disruptions in cellular processes like DNA repair, apoptosis, and cell cycle regulation. In recent years, there has been growing interest in the use of methylation biomarkers as a tool for early detection and prognostication in HPV-related cancers. Methylation, the addition of a methyl group to DNA, is a key epigenetic modification that can influence gene expression without altering the DNA sequence itself. In the context of cancer, abnormal methylation patterns often serve as early indicators of disease, long before the emergence of genetic mutations or overt clinical symptoms. We have developed a DNA methylation biomarkers S5 classifier able to detect high grade cervical precancer lesions and cancer with high accuracy ranging from 93% for CIN3 to 100% for cancer. Here will demonstrate that the same classifier could detect anal, oropharyngeal and vulvar cancer. Results: Over the past 10 years we have extensicely validated this biomarker on cervical collected sanples urine and vagival samples and self-collected samples. We will share the results we ontained for the esrly dtection of cervical cancer, oropharungeal cancer anal cancer and multizonal cancer.This multicancer test could have range of application for gynaecologic cancers and also male cancers.
Citation Format: Belinda Nedjai. MCED - DNA methylation-based liquid biopsy for early detection of HPV-related cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B014.
Abstract B022: TEDEdb: Transposable element differential expression database
Authors: Calendo Gennaro H , Chaunzwa Morgan , Dehzangi Iman , Madzo Jozef , Issa Jean-Pierre 
Published: February 2025

Abstract
Epigenetic therapies that induce global DNA hypomethylation activate transcriptionally repressed transposable elements (TEs). The activation of a class of TEs known as human endogenous retroviruses (HERVs) can trigger an innate antiviral response in cells called “viral mimicry”. Viral mimicry induced by aberrantly expressed HERVs stimulates interferon signaling genes resulting in an adaptive immune response that can ultimately lead to immunogenic cell death. This heightened immune activity can enhance the efficacy of immune checkpoint inhibitor therapies. Identifying cancers that are susceptible to a viral mimicry response or treatment regimens that induce aberrant transcription of TEs has not yet been fully explored. Recent computational tools enable the measurement of TE signal from short-read RNA-seq data and several large-scale reprocessing pipelines have uniformly processed RNA-seq data of cancer cell lines treated with epigenetic and cytotoxic drugs. However, these large-scale pipelines omit the quantification of TEs. To address this gap and fully utilize publicly available data, we have developed a computational pipeline and database of TE expression for more than 7,000 samples from 220 cancer cell lines treated with over 700 cytotoxic and epigenetic drugs, yielding over 2,100 differential expression experiments. To illustrate the usefulness of this database, we ranked drugs by %TE activation and found that the top three targets were DNMT (Decitabine), CDK9 (MC180295), and Topoisomerase II (Doxorubicin). We enable the exploration of this dataset by implementing several meta-analysis methods and visualizations made available as an interactive web application. This database and web application can serve as a valuable resource for the cancer and epigenetics community by enabling hypothesis generation and providing insights into how specific drugs may induce TE expression.
Citation Format: Gennaro H Calendo, Morgan Chaunzwa, Iman Dehzangi, Jozef Madzo, Jean-Pierre Issa. TEDEdb: Transposable element differential expression database [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B022.
Abstract B023: Harnessing the dual therapeutic approach of CRISPR/CAS9 and CAR-T cell technologies in KRAS mutated solid tumors
Authors: Kadir SDanish 
Published: February 2025

Abstract
Kirsten Rat Sarcoma Virus mutation and its complications have been a major concern. Limitations to drawing its accurate configuration, its complications; mutates and thermodynamic properties, have limited their effectiveness as a molecular diagnostic tool. To counteract these challenges, over the years a different set of sophisticated Immunotherapeutic approaches have been adopted such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), Caspase Protein System (CAS), and Chimeric Antigen Receptor-T cell (CAR-T). Some of them have already managed approval of the Food and Drug Administration. One of the primary goals of CRISPR/CAS technology is to correct mutations within the genetic sequence, thereby potentially repairing defective genes like KRAS. Meanwhile, CAR-T immunotherapies capitalise on genetically modified T cells. In comparison to traditional therapies, immunotherapies can offer greater safety and precision. However, their efficacy is still questionable while treating solid tumours. Here authors have covered the various key targets such as p53, p21, WNT, and RAS, their success stories over the years and have proposed the importance of targets like KRAS oncogene to manage a better output. KRAS is a RAS family oncoprotein responsible for the development of 85% of different cancers. The missense mutations at the various KRAS hotspots can lead to the development of lung and Pancreatic Cancers. Some of the most recently conducted revolutionary studies synthesize CAR-NK, CAR-M, and CRISPR-Cas9/3/10/Novel CAS systems, as well as their prospective molecular combination to target the KRAS. The purpose of this study is to provide a present status of these therapies, limitations, clinical trials, and a proposal to sketch a combinatorial impact via the PRISMA model for 62 different manuscripts (2001-2024). This format aligns and organizes everything in Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, providing a clear and systematic infographic that represents the process, including stages of selection, screening, and documentation.
Citation Format: SDanish Kadir. Harnessing the dual therapeutic approach of CRISPR/CAS9 and CAR-T cell technologies in KRAS mutated solid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B023.
Abstract B025: Inducible mouse models of cancer driver mutations as a powerful tool for in vivo and epigenetic studies of colorectal cancer
Authors: Kalkat Manpreet , Hinoue Toshinori , Kang Liang , Laird Peter W. , Olesnavich Mary 
Published: February 2025

Abstract
Human colorectal cancer (CRC) most often arises as a result of spontaneous genetic driver mutations such as APC, BRAF, KRAS, SMAD4, and TP53. These are among the most common drivers of CRC and are thought to contribute directly to cancer initiation and growth. CRC tumors harboring BRAFV600E mutation exhibit a CpG Island Methylator Phenotype (CIMP). Other drivers are also more weakly associated with distinct DNA methylation profiles. It is not clear whether these DNA methylation profiles are a result of differences in the cells-of-origin for these cancers, with pre-existing methylation patterns or whether there is selective pressure for various DNA methylation alterations that cooperate with each driver. To address this question, we have modeled this in mice by inducing colon tumors in a controlled cell population at the same age, with either BRAFF-V600E, KRASLSLG12D, Smad4, or Trp53 drivers in combination with Apc heterozygosity. We have profiled DNA methylation in tumors arising in these mice to determine the interaction between different driver mutations and the tumor methylome. Using a multiple linear regression model, we have identified DNA methylation alterations that are shared across all tumor samples, as well as changes that are specific to each of the different genetic drivers. The DNA methylation profiles accurately recapitulate well-established findings, including high levels of hypermethylation in KRASLSLG12D and BRAF F-V600E tumors reminiscent of CpG Island Methylator Phenotype (CIMP), universal tumor hypermethylation at binding sites for transcription factors involved in intestinal epithelial differentiation, and hypomethylation at AP1 complex component binding sites. Driver-specific histology findings broadly align with those observed in human cancers, such as sessile serrated morphology in BRAFF-V600E mutated tumors. The tumor models with different driver mutations also show variation in hypermethylation of polycomb repressive complex target sites and replicative history. We are using the differences in the DNA methylation profiles between the driver tumor models in conjunction with RNA-seq analysis and conservation of the alterations in human CRC to identify epigenetic events cooperative with the drivers and functionally relevant to tumorigenesis.
Citation Format: Manpreet Kalkat, Toshinori Hinoue, Liang Kang, Peter W. Laird, Mary Olesnavich. Inducible mouse models of cancer driver mutations as a powerful tool for in vivo and epigenetic studies of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B025.
Abstract IA007: DNA methylation in cancer: From knowledge to applications
Authors: Esteller Manel 
Published: February 2025

Abstract
For the last thirty years an increasing amount of evidence has shown the relevance of epigenetics in cell biology and tissue physiology, being DNA methylation aberrations in cancer the flag-ship for the recognition of its disturbance in human diseases. From the candidate gene approaches, new powerful technologies such as comprehensive DNA methylation microarrays and whole genome bisulfite sequencing has recently emerged that have reinforced the notion of epigenetic disruption in the crossroad of many sickness. From the poster-boy case of MGMT hypermethylation in the prediction of alkylating drug response to the personalized treatment of leukemia with small molecules targeted to fusion proteins involving histone modifiers, the field has walked a long path. The current talk will focus in the epigenetic profiling, basically at the level of DNA methylation and histone modifications, that is starting to provide clinical value in the diagnosis, prognosis and prediction of response to drug therapies. For cancer, we have already a wide view of the undergoing DNA methylation events that expand beyond classical promoter CpG islands of tumor suppressor genes and we have a growing list of mutated chromatin remodeler genes that contributes to the tumorigenesis process. It is time to apply this knowledge in practical clinical situations like the diagnosis of cancers of unknown primary, the screening of malignancies in high-risk populations or a biomarker selection of the patients that should receive treatment with anticancer drugs, including immunotherapy. Beyond cancer, DNA methylation is starting to be recognized as playing a major role in infectious diseases, and in this regard, the present lecture will also address the epigenomic component of COVID-19. Most important, Epigenomics can be added to Genomics, Transcriptomics and Proteomics plus Bioinformatics to create a Multomics view of human diseases.
Citation Format: Manel Esteller. DNA methylation in cancer: From knowledge to applications [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA007
Frick’s Defense of the Procreation Asymmetry
Authors: Bykvist Krister , Campbell Tim 
Published: February 2025

Abstract
The Procreation Asymmetry, in strongest form, states (roughly) that while we have no reason to create happy people, we do have reason not to create unhappy people. Despite its popularity among non-utilitarian philosophers, it has been surprisingly difficult to give an adequate theoretical defense of this asymmetry. However, in a recent paper, Johann Frick attempts to provide a unified account of the asymmetry that avoids the problems with previous attempts. One of Frick’s novel claims is that a certain wide-scope conditional reasons principle, together with two plausible inference rules, serves to capture both conjuncts of the asymmetry. We argue that while Frick’s account is more plausible than previous accounts, it can explain the asymmetry only by appealing to a unexplained further asymmetry that in effect reaffirms the asymmetry, and that the wide-scope conditional reasons principle does not help to provide a satisfactory explanation of the asymmetry.
Febvre’s Climate of Sciences. When Human Geography Met Intellectual History (Tome 146, 7e Série, n° 1-2, (2025))
Authors: Brian Éric 
Published: February 2025

Abstract
Although Lucien Febvre left exemplary works of economic and social history and of intellectual and religious history, to dissociate these two aspects of his work would be to overlook his most important methodological contribution in this second area: the concept of the “climate of science” or the “climate” of intellectual activity. In order to reconstruct its development from the 1920s to the 1940s, it is important to show how Febvre constructed a synthesis of proposals formulated by the philosopher Henri Berr, the psychologist Henri Wallon and the physicist Paul Langevin. He was opposed to Ratzel’s deterministic approach to human geography and he considered that all innovative human activities were the result of probabilities of options within a spectrum of possibilities that it was then up to the historian to reconstruct.
A study on energy dissipation of aramid composite reinforced with a new shear thickening gel (n-STG)/PVA polymer matrix
Authors: Zarrin Nasim , Abbasi Marjan , Sadighi Mojtaba , Goodarz Mostafa 
Published: February 2025

In this article, a new shear thickening gel (n-STG)/Polyvinyl alcohol (PVA) polymer matrix-reinforced interlayers of Kevlar fabrics are used. Rheology and dynamic mechanical analysis (DMTA) tests were used to characterize the shear-thickening properties of n-STG. SEM images showed that the fabric’s surface was fully covered with n-STG after the STG treatment. Two layers of Kevlar fabrics with an area density of 600 g/m2 (total = 1200 g/m2) are compared to the six levels of the Kevlar fabrics with an area density of 200 g/m2. The puncture resistance of n-STG/Kevlar 200 composite is the highest. The pull-out test was performed to investigate the inter-yarn friction. In low-velocity impact test, n-STG/Kevlar absorbs about 90.0% of the impact energies. The energy-balance model very well matches the experimental results. Finally, the performance of the samples was examined in response to changing the impact energy, weight of n-STG, and number of layers.
Impact of psychedelics on craving in addiction: A systematic review
Authors: Chapron Sophie-Athéna , Bonazzi Guilhem , Di Lodovico Laura , de Ternay Julia , Landmann Camille , Nourredine Mikail , Salvo Francesco , Sessa Ben , Das Ravi , Rolland Benjamin , Garcia-Romeu Albert , Auriacombe Marc 
Published: February 2025

Background: In the context of the need to increase treatment options for substance use disorders, recent research has evaluated the therapeutic potential of psychedelics. However, there is an incomplete understanding of psychedelics’ effects on craving, a core symptom of addictive disorders and a predictor of substance use and relapse. Aims: To determine if the use of psychedelics is associated with changes in craving in humans. Methods: A systematic review of the literature, using PubMed, PsycInfo, and Scopus databases up to May 2023. We included all studies assessing any substance craving levels after psychedelic use (protocol registration number CRD42021242856). Results: Thirty-eight published articles were included, corresponding to 31 studies and 2639 participants, pertaining either to alcohol, opioid, cocaine, or tobacco use disorders. Twelve of the 31 included studies reported a significant decrease in craving scores following psychedelic use. All but two studies had methodological issues, leading to moderate to high risk of bias scores. Conclusions: Some psychedelics may show promising anti-craving effects, yet the diversity and high risk of bias of extant studies indicate that these results are to be considered with caution. Further well-controlled and larger-scale trials should be encouraged.
A Quantitative Fatty Infiltration Evaluation of the Supraspinatus Muscle: Enhanced Clinical Relevance and Improved Diagnostic Value on Predicting Retear Compared With the Goutallier Classification
Authors: Xie Jianhao , Zhou Meng , Guo Zhe , Zhu Yiming , Jiang Chunyan 
Published: February 2025

Background: Preoperative assessment of fatty degeneration is important for managing rotator cuff tears. The Goutallier classification is semiquantitative and observer dependent. Discrepancies among surgeons can be prominent. A quantitative method may improve accuracy and reliability in evaluating the exact percentage of fatty infiltration (Fat%). Hypothesis/Purpose: This study aimed to investigate the correlation between the new quantitative method and the Goutallier classification in assessing fatty infiltration (FI) of the supraspinatus muscle and to explore the use of this method in predicting retear after rotator cuff repair. It was hypothesized that the new method would significantly correlate with the Goutallier classification and be more sensitive to retear. Study Design: Cohort study (diagnosis); Level of evidence; 3. Methods: This study included 105 patients who underwent arthroscopic rotator cuff repair for large to massive tears. All patients underwent routine preoperative and 1-year postoperative magnetic resonance imaging and were divided into 2 groups according to tendon healing. Preoperative quantitative Fat% of the supraspinatus muscle was evaluated based on the signal intensity (SI) of the T1-weighted sequence. The Fat% was calculated using the following equation: SIsupraspinatus = SIfat× Fat% + SImuscle× (1 – Fat%). The correlation between the Fat% and the Goutallier grade was determined. Univariate and multivariate analyses were performed to identify the independent risk factors for retear. Results: The mean preoperative Fat% of the supraspinatus muscle was 23.77 ± 15.96. A significant correlation was found between the Fat% and the Goutallier grade of the supraspinatus muscle ( R = 0.655; P < .001). The overall retear rate was 21.9%; however, functional status significantly improved regardless of cuff healing. Multivariate analysis identified the Fat% ( P = .005) and the modified Patte classification ( P = .003) as independent risk factors of retear. The receiver operating characteristic curves showed that the cutoff value of Fat% for predicting retear was 33.2%. Fat% >33.2% possessed superior diagnostic accuracy (79.0%), Youden index (0.513), and positive and negative predictive values (51.6% and 90.5%, respectively) compared with the Goutallier grades. Conclusion: Although the quantitative method for assessing Fat% of the supraspinatus muscle significantly correlated with the Goutallier classification, the quantitative method is more clinically relevant to retear. Fat% of the supraspinatus muscle >33.2% possessed higher diagnostic value than the Goutallier grades in predicting retear.