bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA13: Molecular and genomic mechanisms of estrogen signaling and gene regulation in breast cancer
Authors: Kraus W. Lee 
Published: February 2024

Abstract
Transcriptional enhancers function as nucleation sites for the assembly of transcription-regulating complexes across the genome, which act to drive cell type-specific patterns of gene expression. Although many features of active enhancers [e.g., H3K4me1, H3K27ac, enrichment of p300/CBP and Mediator, and production of enhancer RNAs (eRNAs)] have been defined by genomic assays, the roles of these features in estrogen receptor alpha (ERa) enhancer function are not well understood. We are interested in how the molecular underpinnings of ERa enhancer formation and activity control the gene expression programs that drive breast cancer phenotypes and responses to therapeutic agents. We have used a variety of molecular, biochemical, genomic, genetic, and computational approaches to determine the following aspects of ERa enhancers biology in hormone-responsive breast cancer cells: (1) where ERa enhancers are formed across the genome, (2) the kinetics of ERa enhancer formation and disassembly, (3) the influence of genetic variation on ERa enhancer function, (4) the role of the enhancer features noted above in ERa enhancer function, and (5) how protein complexes and small polypeptides serve as coregulators to drive ERa transcriptional activity. Our current focus has been on eRNAs, which are poorly characterized noncoding RNAs that are thought to regulate enhancer function and gene expression. We have identified a ~40 nucleotide functional eRNA regulatory motif (FERM) present in many estrogen-regulated eRNAs that promotes gene expression by increasing ERα recruitment and stimulating p300-catalyzed H3K27 acetylation. In addition, we have been examining how the dose of estrogen impacts the efficiency of enhancer assembly by ERα. Finally, we have been exploring the role of PARP1, a ubiquitous chromatin-associated regulator, and small polypeptides derived from “non-coding” RNAs, control ERa enhancer function. In all cases, we perform analyses to link enhancer function to gene expression outcomes and breast cancer biology. Collectively, our results demonstrate the biological and mechanistic roles of eRNAs in breast cancer. This work is supported by grants from the NIH/NIDDK (DK058110) and CPRIT (RP160319) to W.L.K.
Citation Format: W. Lee Kraus. Molecular and genomic mechanisms of estrogen signaling and gene regulation in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr IA13.
Abstract A025: Adaptive therapy: Leveraging evolutionary dynamics for colorectal cancer management in vivo
Authors: Richker Harley I. , Marquez-Alcaraz Gissel , Maley Carlo 
Published: February 2024

Abstract
Therapeutic resistance to chemotherapy is frequently the proximate cause of cancer treatment failure and, ultimately, patient mortality. Evolutionary therapies have been developed to address this problem and potentially reduce toxicities. The most successful strategy to date, adaptive therapy (AT), is designed to use chemosensitive cells to out-compete and suppress the chemoresistant cells. However, detailed observations to elucidate the mechanisms of AT's success are lacking. Typically, AT involves lowering the dose of the chemotherapy, thereby reducing toxicity and preserving the immune system. We are evaluating AT for the first time in colorectal cancer, using syngeneic orthotopic xenograft models. This project marks several firsts: 1) sensitive and resistant clones will be tracked longitudinally, 2) AT will be tested with a targeted therapy (MRTX1133), 3) AT will be tested in an immune competent model, 4) multiple drugs will be used for AT, and 5) extinction therapy will be tested in mice. We will employ genetic barcodes and differential luciferase tagging to track the tumor cell subpopulations longitudinally. Currently, we are conducting an in-vivo pilot experiment to validate our protocol, emphasizing tumor engraftment efficacy and tracking cell subpopulations. Additionally, we are investigating the potential of Lactobacillus acidophilus to inhibit tumor growth, augment chemotherapy, and bolster immune response in colorectal cancer.
Citation Format: Harley I. Richker, Gissel Marquez-Alcaraz, Carlo Maley. Adaptive therapy: Leveraging evolutionary dynamics for colorectal cancer management in vivo [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A025.
Abstract B041: Identification of m3C modification sites within mRNAs of pancreatic cancer cells by long-read direct RNA sequencing
Authors: Mitsutomi Shuhei , Sugawara Anzu , Takahashi Kenji , Mizukami Yusuke , Akimitsu Nobuyoshi , Taniue Kenzui 
Published: February 2024

Abstract
Chemical modification is a precise and effective way to control the biogenesis, stability, and function of biological molecules, such as nucleic acids, proteins, and lipids. More than 170 different types of modifications have been discovered in coding and non-coding RNAs, constituting a diverse RNA modification landscape, called epitranscriptome. RNA modifications were mediated by three types of proteins: writers, erasers, and readers. Recently, RNA modification machinery has been dysregulated in several types of cancers and may be promising targets for cancer therapy. 3-methylcytidine (m3C), which is catalyzed by METTL2A, 2B, 6, and 8, is found at position 32 of cytoplasmic tRNAs in organisms ranging from yeast to humans, however, their functions and regulatory machinery in mRNA and non-coding RNA has not been clarified because there were no effective anti- m3C antibodies. Here we discovered that the expression of m3C writers was higher in pancreatic tumors than in noncancerous tissues. We further found that METTL2A expression is associated with a poor prognosis in pancreatic cancer patients. We also showed that METTL2A depletion led to a reduction in the growth of AsPC1 cells. We next attempted to identify the m3C sites in cellular transcripts regulated by METTL2A in AsPC1 cells using long-read direct RNA sequencing. We corrected the transcriptome using ESPRESSO and searched for the RNA modifications using Nanocompore. We then found that METTL2A targets the NYCYN motif in mRNAs and mitochondrial rRNAs. Moreover, we found that transcripts with METTL2A-mediated m3C modification were upregulated in AsPC-1 cells knocked down by METTL2A. Our study provides evidence for METTL2A-mediated down-regulation of target mRNAs via m3C modification in the survival of pancreatic tumor cells.
Citation Format: Shuhei Mitsutomi, Anzu Sugawara, Kenji Takahashi, Yusuke Mizukami, Nobuyoshi Akimitsu, Kenzui Taniue. Identification of m3C modification sites within mRNAs of pancreatic cancer cells by long-read direct RNA sequencing [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B041.
Abstract IA006: Leveraging the extreme selection induced by therapeutic bottlenecks to subvert resistance via identifying evolutionarily-informed targets for orthogonal immunotherapy
Authors: Fisk J. Nic , Politi Katerina , Gettinger Scott , Townsend Jeffrey P 
Published: February 2024

Abstract
Evolutionary dynamics underlie carcinogenesis, with tumor cells constantly adapting, resulting in cell populations that outgrow their non-tumor cell neighbors, evade treatment, and ultimately lead to death. Well-designed therapies to treating cancer induce immense and specific selection. The heterogenous cancer cell population either goes extinct or continues to evolve during and in response to the therapeutically induced bottleneck, leading to a subsequent selective sweep and newfound prominence of cells exhibiting the resistance phenotype. However, this bottleneck period provides a unique opportunity wherein the diversity of cells constituting the tumor is predictably reduced. Here, we introduce a framework to quantify the selection upon variants before, during, and after the therapeutic bottleneck, facilitating richer understanding of the mechanisms by which therapeutic resistance is acquired. We additionally couple measures of selection intensity with the prediction of neoantigens in a cohort of patients to identify potential orthogonal targets for immunotherapy. The result is a schema for leveraging predictability induced by the primary therapeutic bottleneck to drive the remnant tumor cell population to extinction. Finally, we demonstrate the utility of this schema in mutant EGFR lung adenocarcinoma.
Citation Format: J. Nic Fisk, Katerina Politi, Scott Gettinger, Jeffrey P Townsend. Leveraging the extreme selection induced by therapeutic bottlenecks to subvert resistance via identifying evolutionarily-informed targets for orthogonal immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr IA006.
Abstract IA013: Using genetic ancestry in genomics of tumor evolution
Authors: Davis Melissa B. 
Published: February 2024

Abstract
The burgeoning field of genomic science, particularly in the context of cancer research, has undergone a transformative shift with the incorporation of genetic ancestry in understanding tumor evolution. The work of Melissa B. Davis highlights this paradigm shift, revealing how biases within genomic data, primarily due to the underrepresentation of diverse ethnic groups, have historically influenced our understanding of cancer disparities. Davis's research emphasizes the critical importance of including diverse ethnic groups in genomic studies, not merely as a token inclusion but as a rigorous scientific necessity. Her research demonstrates that by integrating genetic ancestry into the study of tumor biology, we can gain a more comprehensive understanding of cancer's evolution and behavior. This approach is instrumental in identifying unique genetic markers and pathways influenced by ancestry, which may contribute to differences in cancer incidence, progression, and treatment response among different populations. Davis's work thus represents a significant stride towards personalized medicine, where treatment strategies can be tailored not just to the individual's genetic makeup but also to their ancestral background. This shift in focus towards a more inclusive genomic science has the potential to bridge the gap in cancer care disparities. By acknowledging and addressing these disparities, research spearheaded by scientists like Davis paves the way for more equitable healthcare outcomes. The inclusion of genetic ancestry in the study of tumor evolution is more than a scientific advancement; it's a step towards justice and equity in healthcare, ensuring that all groups benefit equally from the advancements in cancer research and treatment.
Citation Format: Melissa B. Davis. Using genetic ancestry in genomics of tumor evolution [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr IA013.
Abstract PR016: Topology of the tumor microenvironment: Integrating imaging, modeling, and topological data analysis
Authors: Barker-Clarke Rowan , Gray Jason M. , Scott Jacob G. 
Published: February 2024

Abstract
Cancer evolution involves multiple stochastic processes across many scales. In addition to genomic and transcriptomic changes, hallmarks of cancer within solid tumors include the malignant co-evolution of the tumor microenvironment. Although the evaluation of tissue architecture plays a key role in pathologist staging, the automated extraction of additional structural features remains far from translation to the clinic. However, one particularly effective novel methodology for extracting patterns from these clinical images is topological data analysis(TDA). TDA is a field that studies the shape of data and its connectedness using concepts from geometric and algebraic topology. Recent work using topological data analysis has allowed the extraction of image features. Such features have been associated with clinical outcomes in both the analysis of H&E images in prostate cancer and CT images in lung cancer. We set out to question how the topological features of tissues, including tumor and stromal composition, evolve during treatment and between original sites and metastasis. To analyze this we use a combination of tissue sections, imaging, and cell-automata models and persistent homology and cubical persistence techniques from TDA. We apply certain topological methods for the first time to tissue images (H&E) and to the output of spatial simulations. We focus specifically on analyzing the evolution of topological features in ovarian and lung cancer and compare our features to 2D and 3D simulations (HAL) with varying game theoretical interactions as well as comparing features across tissues from matched primary and metastatic sites. We find that several topological features are conserved between primary and metastatic sites and some feature evolution is replicated in simulation.
Citation Format: Rowan Barker-Clarke, Jason M. Gray, Jacob G. Scott. Topology of the tumor microenvironment: Integrating imaging, modeling, and topological data analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr PR016.
Overcoming Clinical Resistance to EZH2 Inhibition Using Rational Epigenetic Combination Therapy
Authors: Kazansky Yaniv , Cameron Daniel , Mueller Helen S. , Demarest Phillip , Zaffaroni Nadia , Arrighetti Noemi , Zuco Valentina , Kuwahara Yasumichi , Somwar Romel , Ladanyi Marc , Qu Rui , de Stanchina Elisa , Dela Cruz Filemon S. , Kung Andrew L. , Gounder Mrinal M. , Kentsis Alex 
Published: February 2024

Abstract

Epigenetic dependencies have become evident in many cancers. On the basis of antagonism between BAF/SWI-SNF and PRC2 in SMARCB1-deficient sarcomas, we recently completed the clinical trial of the EZH2 inhibitor tazemetostat. However, the principles of tumor response to epigenetic therapy in general, and tazemetostat in particular, remain unknown. Using functional genomics and diverse experimental models, we define molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors. We found distinct acquired mutations that converge on the RB1/E2F axis and decouple EZH2-dependent differentiation and cell-cycle control. This allows tumor cells to escape tazemetostat-induced G1 arrest, suggests a general mechanism for effective therapy, and provides prospective biomarkers for therapy stratification, including PRICKLE1. On the basis of this, we develop a combination strategy to circumvent tazemetostat resistance using bypass targeting of AURKB. This offers a paradigm for rational epigenetic combination therapy suitable for translation to clinical trials for epithelioid sarcomas, rhabdoid tumors, and other epigenetically dysregulated cancers.

Significance:
Genomic studies of patient epithelioid sarcomas and rhabdoid tumors identify mutations converging on a common pathway for response to EZH2 inhibition. Resistance mutations decouple drug-induced differentiation from cell-cycle control. We identify an epigenetic combination strategy to overcome resistance and improve durability of response, supporting its investigation in clinical trials.
See related commentary by Paolini and Souroullas, p. 903.
This article is featured in Selected Articles from This Issue, p. 897
Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti–PD-1 Therapy
Authors: Szóstak Natalia , Handschuh Luiza , Samelak-Czajka Anna , Tomela Katarzyna , Pietrzak Bernadeta , Schmidt Marcin , Galus Łukasz , Mackiewicz Jacek , Mackiewicz Andrzej , Kozlowski Piotr , Philips Anna 
Published: February 2024

Abstract
Recent research indicates that gut microbiota may be vital in the advancement of melanoma. In this study, we found that melanoma patients exhibited a distinct gut mycobiota structure compared with healthy participants. Candida albicans, Candida dubliniensis, and Neurospora crassa were more abundant in samples from patients with melanoma, whereas Saccharomyces cerevisiae and Debaryomyces hansenii were less abundant. During anti–PD-1 treatment, the relative amount of Malassezia restricta and C. albicans increased. A higher level of Saccharomyces paradoxus was associated with a positive response to anti–PD-1 treatment, whereas a higher level of Tetrapisispora blattae was associated with a lack of clinical benefits. High levels of M. restricta and C. albicans, elevated serum lactate dehydrogenase, and being overweight were linked to increased risk of melanoma progression and poorer response to anti–PD-1 treatment. Thus, this study has revealed melanoma-associated mycobiome dysbiosis, characterized by altered fungal composition and fungi species associated with a higher risk of melanoma progression, identifying a role for the gut mycobiome in melanoma progression.
Nudge: Empurrando para longe o gerenciamento de resultados
Authors: Moreira Caritsa Scartaty , Sousa Rossana Guerra de , Martins Orleans Silva , Aguiar Andson Braga de 
Published: February 2024

This research aimed to verify the effects of using nudges in reduction of earnings management. The study was classified as a between-subjects experiment. The sample consisted of 40 accountants. Descriptive statistics, Analysis of Variance, Structural Equation Model, and mean tests were used for data analysis and interpretation. The results revealed three main findings, as support for the developed hypotheses. First, the level of earnings management by accounting professionals is lower in the presence of nudges than in their absence; second, the level of earnings management by accounting professionals is lower in the presence of an injunctive nudge issued by the leader than in its absence; and third, there is no difference in the level of earnings management by accounting professionals when the descriptive nudge is issued by the leader, compared to the absence of it.
Preeclampsia Associated Differences in the Placenta, Fetal Brain, and Maternal Heart Can Be Demonstrated Antenatally: An Observational Cohort Study Using MRI
Authors: Hall Megan , de Marvao Antonio , Schweitzer Ronny , Cromb Daniel , Colford Kathleen , Jandu Priya , O’Regan Declan P , Ho Alison , Price Anthony , Chappell Lucy C. , Rutherford Mary A. , Story Lisa , Lamata Pablo , Hutter Jana 
Published: February 2024

BACKGROUND:
Preeclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multiorgan approach to magnetic resonance imaging (MRI) investigation of preeclampsia, with the acquisition of maternal cardiac, placental, and fetal brain anatomic and functional imaging.

METHODS:
An observational study was performed recruiting 3 groups of pregnant women: those with preeclampsia, chronic hypertension, or no medical complications. All women underwent a cardiac MRI, and pregnant women underwent a placental-fetal MRI. Cardiac analysis for structural, morphological, and flow data were undertaken; placenta and fetal brain volumetric and T2* (which describes relative tissue oxygenation) data were obtained. All results were corrected for gestational age. A nonpregnant cohort was identified for inclusion in the statistical shape analysis.

RESULTS:
Seventy-eight MRIs were obtained during pregnancy. Cardiac MRI analysis demonstrated higher left ventricular mass in preeclampsia with 3-dimensional modeling revealing additional specific characteristics of eccentricity and outflow track remodeling. Pregnancies affected by preeclampsia demonstrated lower placental and fetal brain T2*. Within the preeclampsia group, 23% placental T2* results were consistent with controls, these were the only cases with normal placental histopathology. Fetal brain T2* results were consistent with normal controls in 31% of cases.

CONCLUSIONS:
We present the first holistic assessment of the immediate implications of preeclampsia on maternal heart, placenta, and fetal brain. As well as having potential clinical implications for the risk stratification and management of women with preeclampsia, this gives an insight into the disease mechanism.
Literary Imitation in Three Poems Attributed to Tahirih Qurrat al-ʿAyn
Authors: Shayani Sahba 
Published: February 2024

Abstract
Throughout both modern and contemporary periods of Iranian poetry, the figure of Tahirih Qurrat al-ʿAyn as a poet has been largely ignored, while some focus has been placed upon her historical roles. Although a large part of this active disregard for her poetry has undoubtedly stemmed from politico-religious intolerance, it has also partially resulted from a lack of detailed information and primary sources. This article advances our understanding of Tahirih the poet by comparing three of the most famous poems attributed to her – “Ay ʿāshiqān, ay ʿāshiqān shud āshikārā wajh-i ḥaqq,” “Ay bi sar-i zulf-i tu sawdā-yi man,” and “Jadhabāt shawqik uljimat bi-salāsil al-ghamm wa-l-balā” – all of which are “literary imitations” (istiqbāl), with the original pieces composed by Rumi, Hātif, and Jāmī, respectively. By comparing Tahirih’s poems with the previous pieces, we gain access to the subtleties and nuances that inform us about the poetic persona of this historical figure.
The genus Dedalopterus Sabatinelli & Pontuale, 1998 (Scarabaeidae: Melolonthinae: Leucopholini) in Laos and Vietnam, with description of a new species
Authors: PHAM PHU VAN , AHRENS DIRK , SABATINELLI GUIDO 
Published: February 2024

The genus Dedalopterus Sabatinelli & Pontuale, 1998 from Laos and Vietnam is reviewed: three species are present of which Dedalopterus lexuanhuei Pham, Ahrens & Sabatinelli, new species from Central Vietnam (Ngoc Linh Mts., Annamite Range) is here described. Dedalopterus malyszi Bunalski, 2001 is present in North Vietnam (Lao Cai, Hoang Lien Son Range), and Dedalopterus pulchellus Sabatinelli & Pontuale, 1998 (= D. bezdekorum Zídek & Krajčík, 2007, new synonymy) is known from Northeast Laos (Mt. Xiangkhouang and Mt. Phou Pan). Additional records, an updated checklist, and an identification key of the genus Dedalopterus are provided. All species treated are abundantly illustrated.