bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B097: Image analysis-guided spatial transcriptomics improves recognition of biological features important for outcome in high grade serous carcinoma
Authors: Laury Anna R. , Zheng Shuyu , Aho Niina , Fallegger Robin , Hänninen Satu M. , Rodriguez Julio Saez , Tanevski Jovan , Youssef Omar , Tang Jing , Carpén Olli 
Published: March 2024

Abstract
High-grade serous ovarian carcinoma (HGSC) is characterized by late presentation, frequent recurrence, and treatment resistance. Our understanding of this disease is limited, partly due to considerable tumor heterogeneity, which is reflected in the variable tumor morphology. Beyond the diagnosis itself, no particular histologic features have proven sensitive or specific enough for use in clinical practice. Image analysis based deep learning models are now able to extract new information from standard H&E pathology slides, though biological interpretation of the regions detected by artificial intelligence (AI) remains a challenge. In this work, we interrogate the molecular features of tissue regions identified as being highly associated with patient outcome by a deep-learning based AI classification model. We determined the spatial transcriptomic profiles of these regions in 16 patients and compared them to the profiles of background tumor regions not selected by the AI model. We used multiple methods to characterize the regions types, including: differential gene expression, UMAP distances, machine learning-based outcome prediction, pathway enrichment, and spatial organization analyses. We find that regions identified by the AI-based model are significantly different from background tumor regions, and that their transcriptomic profiles are more predictive of patient outcome. We determine the differential signaling pathways and validate a representative transcript using RNA in-situ hybridization. We show that AI-detected regions in poor prognosis tumors have upregulated JUN expression, and are characterized by tumor cell subpopulations with a stress-associated transcriptomic signature. In contrast, spatial pattern analyses show that AI-detected regions in tumors with better outcome are typified by macrophage and plasma cell depleted DNA repair-signature tumor cell subpopulations. The synergy of spatial transcriptomic and image analysis data in our study offers a promising strategy to enhance clinical translation by establishing a more interpretable AI model.
Citation Format: Anna R. Laury, Shuyu Zheng, Niina Aho, Robin Fallegger, Satu M. Hänninen, Julio Saez Rodriguez, Jovan Tanevski, Omar Youssef, Jing Tang, Olli Carpén. Image analysis-guided spatial transcriptomics improves recognition of biological features important for outcome in high grade serous carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B097.
Abstract B107: Elucidating the influence of long-chain fatty acids on ovarian cancer progression
Authors: Ogura Jumpei , Yamanoi Koji , Taki Mana , Murakami Ryusuke , Yamaguchi Ken , Hamanishi Junzo , Mandai Masaki 
Published: March 2024

Abstract
Objective: High-fat diets have been associated with cancer progression. Yet, studies indicate that the effects can differ based on the type of fat involved, such as saturated versus unsaturated fatty acids. Uncovering the role of fatty acids may help guide nutrition and provide dietary therapy for cancer patients. In this study, we investigated the effect of common long-chain fatty acids, stearic acid (SA) and oleic acid (OA), on ovarian cancer (OC). Methods: We evaluated the cytotoxicity of SA and the effects of OA using IC50, a 72-hour proliferation assay, flow cytometry, and western blot. The concentration of fatty acids within the tumor was measured using liquid chromatography-mass spectrometry (LC/MS). CAY10566 was used to inhibit SCD1, the enzyme that converts SA to OA. In vivo, tumor growth was analyzed in human OC cell lines and patient-derived xenografts (PDX) using a mouse model fed with a normal diet (ND), an SA-rich diet, or an OA-rich diet combined with CAY10566. The SA-rich diet, which we specially created, had a stearic acid concentration of 33%. Results: SA displayed prominent cytotoxicity compared to other fatty acids. SA dose-dependently increased unfolded protein response (UPR) marker expression. Adding 1μM CAY10566 increased intracellular SA, decreased OA, and reduced IC50 to 20μM (p&lt;0.05). CAY10566 significantly enhanced the cytotoxicity of SA, but the addition of exogenous OA canceled the increase in cell toxicity and UPR marker expression induced by SA (p&lt;0.05). In vivo, tumor growth of OC cell lines and PDXs was significantly suppressed in the SA-rich with CAY10566 group compared to the ND group (p&lt;0.05), while this suppression was nullified in the OA-rich with CAY10566 group. As confirmed by LC/MS, the stearic acid concentration significantly increased in the SA-rich group. Immunohistochemistry demonstrated that CHOP, gH2AX, and caspase-3 expression significantly increased in the SA-rich with CAY10566 group and dramatically decreased in the OA-rich with CAY10566 group (p&lt;0.01). Conclusion: An ectopic supply of SA inhibits OC growth via UPR, while OA counteracts this effect. Creating a Stearate-rich/Oleate-limited environment through diet might affect tumor growth in vivo. Dietary content may greatly contribute to altering function in cancer.
Citation Format: Jumpei Ogura, Koji Yamanoi, Mana Taki, Ryusuke Murakami, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai. Elucidating the influence of long-chain fatty acids on ovarian cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B107.
Abstract IA010: Latest developments in targeting the DNA damage response in the clinic
Authors: Yap Timothy A. 
Published: March 2024

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. These alterations promote the clonal evolution of cancer cells via the accumulation of driver aberrations, including gene copy-number changes, rearrangements, and mutations; however, these same defects also create vulnerabilities that are relatively specific to cancer cells, which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The discovery that BRCA-mutant cancer cells are exquisitely sensitive to inhibition of poly(ADP-ribose) polymerase has ushered in a new era of research on biomarker-driven synthetic lethal treatment strategies for different cancers. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATM, ATR, CHK1 and CHK2, DNA-PK, POLQ, USP1 and WEE1. Efforts to optimize these therapies are ongoing across a range of cancers, involving the development of predictive biomarker assays of responsiveness (beyond BRCA mutations), assessment of the mechanisms underlying intrinsic and acquired resistance, and evaluation of rational, tolerable combinations with standard-of-care treatments (such as chemotherapeutics and radiation), novel molecularly targeted agents and immune-checkpoint inhibitors.
Citation Format: Timothy A. Yap. Latest developments in targeting the DNA damage response in the clinic [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr IA010.
Abstract IA015: Is salpingectomy as effective as bilateral salpingo-oophorectomy in preventing ovarian, fallopian tube, and peritoneal cancer? Let’s prove it!
Authors: Pennington Kathryn P. 
Published: March 2024

Abstract
Since ovarian cancer screening does not reduce ovarian cancer mortality, the main focus to reduce ovarian cancer mortality is prevention. For individuals at increased risk of ovarian carcinoma, risk-reducing bilateral salpingo-oophorectomy (RRSO) is highly effective, but uptake at the recommended age is suboptimal, likely due to concerns about premature menopause. Mounting evidence suggests that many “ovarian” cancers originate in the fallopian tube, making bilateral salpingectomy with delayed oophorectomy an attractive, but as of yet, unproven option for risk-reduction in those who decline RRSO. This talk will review the scientific evidence supporting a tubal origin of ovarian cancer, preliminary data supporting the safety and possible efficacy of salpingectomy and will discuss two prospective clinical trials powered to test the hypothesis that bilateral salpingectomy with delayed oophorectomy is non-inferior to RRSO to reduce the incidence of ovarian, fallopian tube, and peritoneal cancer among mutation carriers at high risk of ovarian cancer.
Citation Format: Kathryn P. Pennington. Is salpingectomy as effective as bilateral salpingo-oophorectomy in preventing ovarian, fallopian tube, and peritoneal cancer? Let’s prove it! [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr IA015.
Abstract PR-008: Follicular fluid aids in cell adhesion, spreading and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells
Authors: Salvi Amrita , Li Wenping , Cologna Stephanie M. , Pavone Mary Ellen , Duncan Francesca E. , Burdette Joanna E. 
Published: March 2024

Abstract
Ovarian cancer is the 5th leading cause of cancer related death in women with a low 5-year survival rate. Ovarian cancer is rarely detected early, and likely arises from the fimbriated end of the fallopian tube epithelium (FTE). There is a correlation between ovarian cancer and ovulation whereby ovulation suppression through use of oral contraception or pregnancy reduces the risk of ovarian cancer. Despite the association of ovarian cancer with ovulation, due to the lack of early detection methods, the disease typically presents as late stage, metastatic cancer in post-menopausal women who are no longer ovulating. The goal of this study was to understand how ovulation and the process of aging interact to provide a permissive environment for ovarian cancer initiation and progression in the FTE. The process of ovulation releases follicular fluid and induces the DNA damage response pathway in the FTE, but the role of aging on FTE exposure to follicular fluid has not been tested. De-identified follicular fluid samples were collected from 14 women (7 reproductively young (29-35 years) and 7 reproductively aged (40-44 years)) undergoing ART (Assisted Reproductive Technology) through the Northwestern University Reproductive Tissue Library (NU-RTL). We found that follicular fluid caused DNA damage and lipid oxidation in an age-dependent manner and cell proliferation in a dose-dependent manner in FTE cells. Interestingly, follicular fluid disrupted FTE spheroid formation and instead stimulated attachment and growth on ultra-low attachment plates. Follicular fluid when coated on the surface of the ultra-low plates enhanced FTE cell adhesion, spreading and proliferation. Proteomics analysis of the follicular fluid identified vitronectin, a glycoprotein as the factor responsible for FTE cell attachment and spreading. Overall, this study demonstrated that aging contributed to lipid oxidation and DNA damage of FTE cells and identified vitronectin in the follicular fluid as a protein factor that facilitates FTE cells to detach from 3D spheroids and spread on low attachment surfaces.
Citation Format: Amrita Salvi, Wenping Li, Stephanie M. Cologna, Mary Ellen Pavone, Francesca E. Duncan, Joanna E. Burdette. Follicular fluid aids in cell adhesion, spreading and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr PR-008.
Abstract P17: Epigenomic fingerprinting of limited primary immune cells using automated CUT&RUN
Authors: Weinzapfel Ellen N. , Maier Keith E. , Marunde Matthew R. , Kumary Vishnu U. Sunitha , Windham Carolina P. Lin , Maryanski Danielle N , Albertorio-Saez Liz , Ahimovic Dughan J. , Bale Michael J. , Lee Juliana J. , Venters Bryan J. , Keogh Michael-Christopher ,   Immunological Genome Consortium
Published: March 2024

Abstract
Chromatin structure drives gene expression programs during immune cell development and in cancer, making it central to the advancement of precision medicine. Indeed, the study of chromatin regulation has provided valuable insight on effector cell differentiation and function, anti-tumor immune responses, and therapeutic resistance. Epigenomic features – such as histone post-translational modifications (PTMs) and chromatin-associated proteins – mark distinct genomic compartments (e.g., promoters, enhancers) and regulate chromatin function/gene expression. Mapping the genomic distribution of these may uncover new biomarkers or drug targets and provides a rich context for exploring immunology. Despite widespread interest, integration of epigenomics in large-scale immunotherapy and/or drug research has been hampered by the poor sensitivity, high background, and low throughput of traditional chromatin mapping technologies, most notably ChIP-seq. Instead, efforts to characterize chromatin dynamics have focused on DNA methylation (bisulfite-seq) or chromatin accessibility (ATAC-seq). However, these assays provide an incomplete view of the chromatin landscape, limiting their ability to define cell differentiation pathways or derive mechanistic insight into disease etiology. Here, we present autoCUT&RUN, a high-throughput assay for rapid, ultra-sensitive profiling of epigenomic features from FACS-isolated primary cells or tissues. This workflow generates reliable profiles from ~10,000 cells per reaction, and is supported by a rigorous optimization strategy, high-quality antibodies, and quantitative spike-in controls. As part of a multi-site collaboration with the Immunological Genome Consortium, we used our autoCUT&RUN platform to build a comprehensive epigenomic database of primary mouse immune cells - composed of &gt;1,500 epigenomic profiles from &gt;100 different FACS-isolated immune cell types. These studies set the stage to leverage high-throughput epigenomics in immunotherapy and precision medicine applications.
Citation Format: Ellen N. Weinzapfel, Keith E. Maier, Matthew R. Marunde, Vishnu U. Sunitha Kumary, Carolina P. Lin Windham, Danielle N Maryanski, Liz Albertorio-Saez, Dughan J. Ahimovic, Michael J. Bale, Juliana J. Lee, Bryan J. Venters, Michael-Christopher Keogh, Immunological Genome Consortium. Epigenomic fingerprinting of limited primary immune cells using automated CUT&RUN [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P17.
Abstract P31: Graph-Based Deep Learning for Predicting Synergy in Multi-Drug Treatments for Leukemia
Authors: Marrapu Archishma 
Published: March 2024

Abstract
Leukemia, a cancer impacting blood-forming tissues such as bone marrow and the lymphatic system, presents in various forms, affecting children and adults differently. The therapeutic approach is complex and depends on the specific leukemia type. Effective management is crucial as it disrupts normal blood cell production, increasing infection susceptibility. Treatments like chemotherapy can further weaken immunity. Thus, a patient’s healthcare plan should focus on comfort, reducing chemotherapy side effects, protecting veins, addressing complications, and offering educational and emotional support. One of the greatest challenges we face in cancer research and treatment is the ability of cancer to adapt, evolve, and become drug-resistant. We expect that the future of cancer treatment will be in combining therapies to overcome resistance – but we need to get much better at predicting which drug combinations will work best for individual patients. Recent studies showed that a combination of two drugs keeps patients with chronic lymphocytic leukemia disease-free and alive longer than the current standard of care, according to the Stanford University School of Medicine and multiple other institutions. This article proposes studies on the combined use of drugs for treating leukemia. Employing a mix of medicines might decrease the chances of tumor resistance. Starting multiple drugs concurrently allows for immediate application during disease onset, avoiding delays. Initial chemotherapy uses a drug combination to eliminate maximum leukemia cells and restore normal blood counts. Afterward, intensification chemotherapy targets any residual, undetectable leukemia cells in the blood or bone marrow. To recommend a drug combination to treat/manage Leukemia, we have employed a Graph Neural Network to pass information between these trending drugs and genes that act as potential targets for Leukemia.
Citation Format: Archishma Marrapu. Graph-Based Deep Learning for Predicting Synergy in Multi-Drug Treatments for Leukemia [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P31.
Effects of Surface Turbulence Flux Parameterizations on the MJO: The Role of Ocean Surface Waves
Authors: Ikuyajolu Olawale James , Van Roekel Luke , Brus Steven R. , Thomas Erin E. , Deng Yi , Benedict James J. 
Published: March 2024

Abstract
This study investigates the sensitivity of the Madden–Julian oscillation (MJO) to changes to the bulk flux parameterization and the role of ocean surface waves in air–sea coupling using a fully coupled ocean–atmosphere–wave model. The atmospheric and ocean model components of the Energy Exascale Earth System Model (E3SM) are coupled to a spectral wave model, WAVEWATCH III (WW3). Two experiments with wind speed–dependent bulk algorithms (NCAR and COARE3.0a) and one experiment with wave-state-dependent flux (COR3.0a-WAV) were conducted. We modify COARE3.0a to include surface roughness calculated within WW3 and also account for the buffering effect of waves on the relative difference between air-side and ocean-side momentum flux. Differences in surface fluxes, primarily caused by discrepancies in drag coefficients, result in significant differences in MJO’s properties. While COARE3.0a has better convection–circulation coupling than NCAR, it exhibits anomalous MJO convection east of the date line. The wave-state-dependent flux (COR3.0-WAV) improves the MJO representation over the default COARE3.0 algorithm. Strong easterlies over the Pacific Ocean in COARE3.0a enhance the latent heat flux (LHFLX). This is responsible for the anomalous MJO propagation after the date line. In COR3.0a-WAV, waves reduce the anomalous easterlies, leading to a decrease in LHFLX and MJO dissipation after the date line. These findings highlight the role of surface fluxes in MJO simulation fidelity. Most importantly, we show that the proper treatment of wave-induced effects in bulk flux parameterization improves the simulation of coupled climate variability.
Labor Intensification and Value Production
Authors: Rieu Dong-Min 
Published: March 2024

This article serves as a commentary on Basu, Haas, and Moraitis’s (BHM’s) analysis of labor intensification. While endorsing the ramifications of BHM’s differentiation between labor’s capacity to process inputs into output per unit of time and labor’s capacity to create value per unit of time, I augment the discourse by introducing two supplementary considerations. First, it is erroneous to directly extrapolate the outcomes of the one-sector model to those of the n-sector model. Second, the impact of labor intensification can be scrutinized through an alternative lens by relaxing the ceteris paribus assumption. JEL Classification: B14, B51, C02
A parametric study on the effect of ring damper on wheel damping
Authors: Zhong Shuoqiao , Wu Kun , Sheng Xiaozhen 
Published: March 2024

Ring dampers have been widely applied to control vibration of, and noise from, train wheels due to the simple structure, negligible impact on operational safety and potential in vibration and noise reduction. Yet, parameters affecting the vibro-acoustic performance of a ring-damped wheel are not adequately studied. In this paper, the apparent modal damping ratios of a ring-damped wheel are studied numerically using a finite element model allowing for frictional nonlinearity. Studied parameters include the impact force used to excite the wheel, the preload in the ring, the friction coefficient of the interface between the ring and the wheel, and the number of rings installed. Several findings can be drawn from the study. Installation of one or two rings to the wheel does not change the resonance frequencies (they are also termed the modal frequencies of the ring-damped wheel) but reduces the resonance responses by generating extra damping to the modes. The ring is more effective for radial excitation than for axial excitation. At most modal frequencies, damping with double rings is higher than with a single ring. Although there are few modal frequencies at which the modal damping ratios are reduced by installing the second ring, the average damping ratio with two rings is much higher, by a factor of 2.37 for axial excitation and 1.73 for radial excitation, than that with a single ring. The apparent damping of the ring-damped wheel increases with the level of the impact force, especially for radial excitation. There is an optimal combination of the preload in the ring and the frictional coefficient with which damping induced by the ring is the highest. Besides, the average damping ratios of the modes above 2000 Hz are proposed to be an indicator of the effectiveness of the performance of a ring-damped wheel in noise reduction.
Ixabepilone related angiographically silent macular edema
Authors: Köksaldı Seher , Kayabaşı Mustafa , Emre Sinan , Saatci Ali Osman 
Published: March 2024

Introduction We present a single-eyed case with a previous diagnosis of breast cancer who had intraretinal cystoid changes associated with the systemic administration of ixabepilone in her only seeing eye. To our best knowledge, this is the first reported case describing this phenomenon related to the ixabepilone administration. Case Description A 54-year-old woman with a history of breast cancer was examined due to visual deterioration in her only good left eye. The patient had undergone cataract surgery and lens implantation in her right eye following a childhood accident, but subsequently had developed a refractory glaucoma and lost her right vision. Six cycles of 40 mg/m2 systemic ixabepilone (3-hly intravenous infusion once every 3 weeks) had been administered within the past six months. Her visual decline started two weeks following the last treatment session. She was offered intravitreal anti-vascular endothelial growth factor injection elsewhere. Fluorescein angiogram showed no dye leakage whereas spectral-domain optical coherence tomography demonstrated parafoveal intraretinal cystoid changes. En-face optical coherence tomography revealed petaloid type roundish hyporeflective areas at the level of superficial and deep vascular plexus. Ixabepilone-associated cystoid maculopathy was suspected as she received only ixabepilone for the chemotherapy in the last six months. We thus recommended her not to continue ixabepilone therapy. Ten weeks after the ixabepilone cessation, intraretinal cystoid changes had resolved completely. Conclusion Angiographically silent intraretinal cystoid changes may develop in association with the use of ixabepilone. Referral to an ophthalmologist should be considered for the patients experiencing visual complaints as ixabepilone cessation may lead to visual improvement and avoid unnecessary treatment.