bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B007: Investigation of the mechanism of PADI2 regulation by the FBXW7 tumor suppressor
Authors: Kafle Chandra Mani , Bell Daphne W. 
Published: March 2024

Abstract
Serous endometrial cancer (SEC) is an aggressive form of cancer that frequently exhibits recurrent somatic mutations in FBXW7 at residues 465, 479, and 505. FBXW7 is a tumor suppressor and is part of a Skp1-Cullin-F-box containing (SCF) complex that targets various proteins, including certain oncoproteins, for ubiquitin-mediated proteasomal degradation. FBXW7 interacts with Cdc4 phosphodegron (CPD) motif(s) within substrate proteins. We previously reported upregulation of peptidyl arginine deiminase 2 (PADI2), a potentially druggable protein, in FBXW7-mutant SEC cell lines compared to the isogenic FBXW7-wildtype cells. The purpose of this study is to investigate the mechanism by which FBXW7 regulates PADI2 levels. We searched for the CPD motif in the PADI2 protein sequence. We used co-immunoprecipitation and immunoblotting to study FBXW7-PADI2 interactions after transiently transfecting HEK293 cells with constructs expressing MYC-tagged FBXW7 and/or HA-tagged PADI2, in the presence or absence of bortezomib. We identified three putative CPD motifs in PADI2, leading us to hypothesize that wildtype FBXW7 binds PADI2 and thus targets PADI2 for degradation via a proteasome-dependent mechanism. Our experimental data show that FBXW7 interacts with PADI2, in the presence of bortezomib, a proteasome inhibitor, in transiently transfected HEK293 cells. Additionally, we have shown that mutation of the putative CPD motifs of PADI2 abrogates the PADI2-FBXW7 interaction. Our findings implicate PADI2 as a novel substrate of the FBXW7 tumor suppressor.
Citation Format: Chandra Mani Kafle, Daphne W. Bell. Investigation of the mechanism of PADI2 regulation by the FBXW7 tumor suppressor [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B007.
Abstract B016: Novel curcumin analogues as therapies for endometrial cancer with TP53 mutations
Authors: Leslie Kimberly K. , Goss Alex , Padilla Jamie , Smith Lane E. 
Published: March 2024

Abstract
The protein p53 is designated as the guardian of the genome because it is the principal tumor suppressor and functions to surveil the genome, enforce cell cycle checkpoints, and trigger apoptosis when genomic instability is beyond repair. Mutations in TP53 are found in &gt;50% of human tumors and in 25% of the deadliest endometrial malignancies. Yet, few studies have targeted the mutant protein to restore its wild type (WT) tumor suppressor functions. Curcumin, a turmeric derivative, has been shown to help return WT function to mutant p53. However, curcumin is not bioavailable to most of the body because of its water insolubility, hydrophobic nature and rapid metabolization. Our laboratory is testing novel, more bioavailable analogs of curcumin including HO-3867 and AKT-100. In these studies, we tested these agents in preclinical models of serous endometrial cancer to assess their effects on cell growth and p53-dependent signaling. We used CyQUANT cell proliferation assay to identify IC50 values for HO-3867 and AKT-100 in ECC-1 and KLE endometrial cancer cell lines. We performed RNA sequencing to elucidate mechanisms of action and verified p53 expression changes via Western blotting. IC50 values ranged from 100 nanomolar (AKT-100) to low micromolar (HO-3867). RNA sequencing data revealed the re-enforcement of cell cycle checkpoints including the upregulation of CDKN1A (p21) and GADD45 (Gadd45). Proliferative signaling downstream of ATM, an important protein kinase stimulating cell growth, was downregulated by both agents. Western blotting confirmed the classic negative feedback loop of p53, where total p53 levels decreased after drug treatment. Taken together, our findings show that AKT-100 and HO-3867 are able to restore WT tumor suppressor function in otherwise oncogenic mutant p53 by reducing cell replication and promoting apoptosis. Thus, curcumin analogues such as AKT-100 and HO-3867 show promise in the treatment of a subset of endometrial tumors expressing mutant p53 by returning WT p53 functionality, and future studies will move to in vivo analyses of curcumin analogue function.
Citation Format: Kimberly K. Leslie, Alex Goss, Jamie Padilla, Lane E. Smith. Novel curcumin analogues as therapies for endometrial cancer with TP53 mutations [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B016.
Abstract IA021: Novel genomic features of POLE-mutant tumors: the utility for tumor classification and identification of new driver alleles
Authors: Ostroverkhova Daria , Tyryshkin Kathryn , Beach Annette K. , Moore Elizabeth A. , Masoudi-Sobhanzadeh Yosef , Barbari Stephanie R. , Rogozin Igor B , Shaitan Konstantin V , Panchenko Anna R , Shcherbakova Polina V. 
Published: March 2024

Abstract
Alterations in the exonuclease domain of POLE drive the development of ultramutated endometrial tumors with better prognosis. A hallmark of these tumors is the accumulation of G&gt;T mutations in AGA sequences; however, understanding of their genomic features beyond the trinucleotide motifs is limited. We applied a novel computational framework to the whole-exome sequencing data of 524 endometrial tumors reported by The Cancer Genome Atlas network to analyze the extended DNA sequence context of ultramutation. We found that the presence of POLE driver alleles is associated with an increased frequency of G&gt;T mutations in polypurine tracts. Sequences containing three consecutive purines, including the classic AGA context, are only moderately mutable, but the mutability increased abruptly as the tract length reached six or more purines. Moreover, mutations showed a strong preference for certain positions within the tracts, creating a characteristic quantifiable pattern. Using this signature, we developed a machine learning classifier to identify tumors with hitherto unknown POLE drivers and validated two new drivers, POLE-E978G and POLE-S461L, by functional assays in yeast. Unlike previously known pathogenic variants, the E978G substitution affects the DNA polymerase rather than exonuclease domain of POLE. We further show that the extended genomic signature of POLE ultramutation is shared by tumors with POLD1 drivers. These findings uncover new mechanisms of ultramutation and highlight the limitations of the current focus on POLE exonuclease domain variants when stratifying patients.
Citation Format: Daria Ostroverkhova, Kathryn Tyryshkin, Annette K. Beach, Elizabeth A. Moore, Yosef Masoudi-Sobhanzadeh, Stephanie R. Barbari, Igor B Rogozin, Konstantin V Shaitan, Anna R Panchenko, Polina V. Shcherbakova. Novel genomic features of POLE-mutant tumors: the utility for tumor classification and identification of new driver alleles [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA021.
Abstract PR005: Patients with endometrial cancer and benign gynecologic conditions exhibit unique vaginal and rectal microbiomes
Authors: Jimenez Nicole R. , Herman Chloe , Laniewski Pawel , Cope Emily K. , Mourad Jamal , Mahnert Nichole , Chase Dana M. , Caporaso J. G. , Herbst-Kralovetz Melissa M. 
Published: March 2024

Abstract
Endometrial cancer (EC) rates are increasing in the United States, with 66,200 women diagnosed this year. The microbiome may be a key target for understanding EC etiology and progression and hold vital information for prevention strategies. With the largest cross-sectional cohort to date, a rich set of patient-related meta-data, and samples from multiple mucosal sites, we explored the gut-vagina axis in EC compared to benign gynecologic conditions. Vaginal and rectal swabs were collected from 192 patients diagnosed with benign conditions (n=108), hyperplasia (n= 18), and EC (n= 66). 16S rRNA amplicon sequencing was conducted on DNA samples, and data analysis was performed with QIIME 2 and R software. The clinical and demographic analysis identified risk factors associated with EC, such as BMI and menopausal status, that differed between disease groups. Global microbial analyses identified a distinct microbial composition between benign and EC, as well as higher diversity in rectal samples and lower diversity in vaginal samples in benign patients compared to cancer patients. Differential abundance analysis, even after adjustment for known risk factors, revealed unique microbial features such as depletion of Lactobacillus and increase of Anaerococcus, Porphyromonas, and Peptoniphilus in vaginal samples when EC is compared to benign conditions. While Rectal samples indicated a depletion of Peptoniphilus and Prevotella and an increase in Buttiaxella in EC compared to benign conditions. Additionally, community networks were different between cancer patients compared to benign, where taxa in Peptoniphilaceae had the most microbial network connections in EC compared to benign conditions. Notably, putative metabolic pathway analysis identified dysregulation of amino acid metabolism, complex carbohydrate metabolism, and hormone metabolism between cancer patients and benign, which provide key insight into the potential pathophysiological mechanisms employed by the microbiome in EC. This study provides key findings on unique singular and community microbial signatures that may directly affect EC development and be important targets for prevention.
Citation Format: Nicole R. Jimenez, Chloe Herman, Pawel Laniewski, Emily K. Cope, Jamal Mourad, Nichole Mahnert, Dana M. Chase, J. G. Caporaso, Melissa M. Herbst-Kralovetz. Patients with endometrial cancer and benign gynecologic conditions exhibit unique vaginal and rectal microbiomes [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr PR005.
Genetic Testing in Brugada Syndrome: A 30-Year Experience
Authors: Pannone Luigi , Bisignani Antonio , Osei Randy , Gauthey Anaïs , Sorgente Antonio , Monaco Cinzia , Della Rocca Domenico Giovanni , Del Monte Alvise , Strazdas Antanas , Mojica Joerelle , Al Housari Maysam , Miraglia Vincenzo , Mouram Sahar , Vetta Giampaolo , Paparella Gaetano , Ramak Robbert , Overeinder Ingrid , Bala Gezim , Almorad Alexandre , Ströker Erwin , Pappaert Gudrun , Sieira Juan , de Ravel Thomy , La Meir Mark , Sarkozy Andrea , Brugada Pedro , Chierchia Gian Battista , Van Dooren Sonia , de Asmundis Carlo 
Published: March 2024

BACKGROUND:
A pathogenic/likely pathogenic variant can be found in 20% to 25% of patients with Brugada syndrome (BrS) and a pathogenic/likely pathogenic variant in SCN5A is associated with a worse prognosis. The aim of this study is to define the diagnostic yield of a large gene panel with American College of Medical Genetics and Genomics variant classification and to assess prognosis of SCN5A and non-SCN5A variants.

METHODS:

All patients with BrS, were prospectively enrolled in the Universitair Ziekenhuis Brussel registry between 1992 and 2022. Inclusion criteria for the study were (1) BrS diagnosis; (2) genetic analysis performed with a large gene panel; (3) classification of variants following American College of Medical Genetics and Genomics guidelines. Patients with a pathogenic/likely pathogenic variant in SCN5A were defined as SCN5A
+
. Patients with a reported variant in a
non-SCN5A
gene or with no reported variants were defined as patients with SCN5A
−
. All variants were classified as missense or predicted loss of function.

RESULTS:

A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A
+
and 396 patients (79.2%) were SCN5A
−
. A
non-SCN5A
gene variant was found in 75 patients (15.0%), of whom, 58 patients (77.3%) had a missense variant and 17 patients (22.7%) had a predicted loss of function variant. At a follow-up of 84.0 months, 48 patients (9.6%) experienced a ventricular arrhythmia (VA). Patients without any variant had higher VA-free survival, compared with carriers of a predicted loss of function variant in

SCN5A
+

or
non-SCN5A
genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in

SCN5A
+

or
non-SCN5A
genes. At Cox analysis, SCN5A
+
or non-SCN5A predicted loss of function variant was an independent predictor of VA.

CONCLUSIONS:

In a large BrS cohort, the yield for SCN5A
+
is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.
Text Attribute Control via Closed-Loop Disentanglement
Authors: Sha Lei , Lukasiewicz Thomas 
Published: March 2024

Abstract
Changing an attribute of a text without changing the content usually requires first disentangling the text into irrelevant attributes and content representations. After that, in the inference phase, the representation of one attribute is tuned to a different value, expecting that the corresponding attribute of the text can also be changed accordingly. The usual way of disentanglement is to add some constraints on the latent space of an encoder-decoder architecture, including adversarial-based constraints and mutual-information-based constraints. However, previous semi-supervised processes of attribute change are usually not enough to guarantee the success of attribute change and content preservation. In this paper, we propose a novel approach to achieve a robust control of attributes while enhancing content preservation. In this approach, we use a semi-supervised contrastive learning method to encourage the disentanglement of attributes in latent spaces. Differently from previous works, we re-disentangle the reconstructed sentence and compare the re-disentangled latent space with the original latent space, which makes a closed-loop disentanglement process. This also helps content preservation. In addition, the contrastive learning method is also able to replace the role of minimizing mutual information and adversarial training in the disentanglement process, which alleviates the computation cost. We conducted experiments on three text datasets, including the Yelp Service review dataset, the Amazon Product review dataset, and the GoEmotions dataset. The experimental results show the effectiveness of our model.
Colonialism and Islamic Reform
Authors: Shlala Elizabeth H. 
Published: March 2024

Abstract
This essay engages a broad geographic, demographic, and chronological scope on the topic of colonialism and Islamic reform to avoid the reinforcement of colonial era inventions and gender(ed) myths across education, the law, enslavement, hierarchies of gender, and Islamic reform. This essay argues that understanding women and gender in various colonial contexts is an important avenue for recovering the restorative work that women have done to reject colonial ideologies throughout history. Reflecting upon scholarship situated at the intersection of modern Islamic thought and feminism, new possibilities emerge to reframe the meaning of justice and freedom in this historiography and beyond.
Corruption and Religion in Europe and Beyond
Authors: Berti Carlo 
Published: March 2024

Abstract
The concept of corruption is historically linked to religion, but research on the relationship between religion and corruption is scarce, coming mainly from the fields of economics and statistics, and partially from anthropology and cultural studies. This article aims to offer a critical review of the relevant international literature on religion, religiosity, and corruption, ranging from large, quantitative comparative studies to more focused and in-depth qualitative case studies. It critically reviews the main results and identifies knowledge gaps that could be addressed by future research. Moreover, it discusses the importance of further research in the European area in light of some features of religion and corruption in Europe, as well as recent changes in the religious panorama of the continent.
Indigenous Peoples’ Rights in International Investment: An Ongoing Compartmentalization
Authors: Boirin-Fargues Zoé 
Published: March 2024

Abstract
International investment law and arbitration have been in the spotlight due to their historical disconnection with issues related to human rights and the environment. Currently, we are witnessing a growing attention to the relationship between Indigenous peoples’ rights and the field of international law. This article presents the results of systematic research on the references to Indigenous peoples that have been made in international investment instruments and arbitration. It identifies key issues and ways to move forward in order to build a more inclusive yet consistent international investment law.
A Painful Divorce: Law vs Digital Technologies
Authors: Grumbach Stéphane , Zeno-Zencovich Vincenzo 
Published: March 2024

Abstract
In this article we wish to point out – using the metaphor of a marital crisis – some of the reasons behind the growing conflict between digital technologies and the law.
We identify various causes:

a)Over the last years there has been a radical change in roles: once one looked at the law for solutions, now they are searched in digital technologies, seen as very efficient instruments of governance.
b)Legal instruments are inadequate to cope with a phenomenon in constant evolution, and whose economic and socio-political weight is immense.
c)Digital actors have become the most effective law makers, with rules not only prescriptive but directly executable.

Our conclusions are that:

a)The digital has changed international relations. We see “digital empires” and “digital colonies”: the EU has gradually fallen in the latter category.
b)The EU approach, expressed by thousands of normative provisions, is ineffective and will be counter-productive in respect of its objectives.
c)It would be preferable to adopt a “general principles” model able to govern not only the present issues but also the changes expected in the next years.
A Cinematic Calling Card: Preludio 11 and Cuban-gdr Cultural Dialogue
Authors: Story Isabel 
Published: March 2024

Abstract
Preludio 11 is a little discussed Cuban-gdr co-production from the early 1960s that was part of a glut of cinematic collaborations between Cuba and predominantly socialist European partners as a means of skills exchange and relationship-building. However, the film and the fact of the organization of the collaboration can offer valuable insight into the dynamics within the international socialist camp and both Cuba and the gdr’s focus on national projection on the international stage. Through examination of the communication between collaborators – principally between the Cuban and East German cinematic institutes and internal gdr communication – on the film, this article sheds light on the political and symbolic value of Cuba to the gdr and vice versa. It also shows how those relations were in constant flux as the project developed and the two countries battled with their commitment to cultural expression and development and shifting political priorities.
DAWN: Dashboard for Agricultural Water Use and Nutrient Management—A Predictive Decision Support System to Improve Crop Production in a Changing Climate
Authors: Liang Xin-Zhong , Gower Drew , Kennedy Jennifer A. , Kenney Melissa , Maddox Michael C. , Gerst Michael , Balboa Guillermo , Becker Talon , Cai Ximing , Elmore Roger , Gao Wei , He Yufeng , Liang Kang , Lotton Shane , Malayil Leena , Matthews Megan L. , Meadow Alison M. , Neale Christopher M. U. , Newman Greg , Sapkota Amy Rebecca , Shin Sanghoon , Straube Jonathan , Sun Chao , Wu You , Yang Yun , Zhang Xuesong 
Published: March 2024

Abstract
Climate change presents huge challenges to the already-complex decisions faced by U.S. agricultural producers, as seasonal weather patterns increasingly deviate from historical tendencies. Under USDA funding, a transdisciplinary team of researchers, extension experts, educators, and stakeholders is developing a climate decision support Dashboard for Agricultural Water use and Nutrient management (DAWN) to provide Corn Belt farmers with better predictive information. DAWN’s goal is to provide credible, usable information to support decisions by creating infrastructure to make subseasonal-to-seasonal forecasts accessible. DAWN uses an integrated approach to 1) engage stakeholders to coproduce a decision support and information delivery system; 2) build a coupled modeling system to represent and transfer holistic systems knowledge into effective tools; 3) produce reliable forecasts to help stakeholders optimize crop productivity and environmental quality; and 4) integrate research and extension into experiential, transdisciplinary education. This article presents DAWN’s framework for integrating climate–agriculture research, extension, and education to bridge science and service. We also present key challenges to the creation and delivery of decision support, specifically in infrastructure development, coproduction and trust building with stakeholders, product design, effective communication, and moving tools toward use.
Regulation of endogenous hormone and miRNA in leaves of alfalfa (Medicago sativa L.) seedlings under drought stress by endogenous nitric oxide
Authors: Ruan Qian , Bai Xiaoming , Wang Yizhen , Zhang Xiaofang , Wang Baoqiang , Zhao Ying , Zhu Xiaolin , Wei Xiaohong 
Published: March 2024

Abstract
Background
Alfalfa (Medicago sativa. L) is one of the best leguminous herbage in China and even in the world, with high nutritional and ecological value. However, one of the drawbacks of alfalfa is its sensitivity to dry conditions, which is a global agricultural problem. The objective of this study was to investigate the regulatory effects of endogenous nitric oxide (NO) on endogenous hormones and related miRNAs in alfalfa seedling leaves under drought stress. The effects of endogenous NO on endogenous hormones such as ABA, GA3, SA, and IAA in alfalfa leaves under drought stress were studied. In addition, high-throughput sequencing technology was used to identify drought-related miRNAs and endogenous NO-responsive miRNAs in alfalfa seedling leaves under drought stress.

Result
By measuring the contents of four endogenous hormones in alfalfa leaves, it was found that endogenous NO could regulate plant growth and stress resistance by inducing the metabolism levels of IAA, ABA, GA3, and SA in alfalfa, especially ABA and SA in alfalfa. In addition, small RNA sequencing technology and bioinformatics methods were used to analyze endogenous NO-responsive miRNAs under drought stress. It was found that most miRNAs were enriched in biological pathways and molecular functions related to hormones (ABA, ETH, and JA), phenylpropane metabolism, and plant stress tolerance.

Conclusion
In this study, the analysis of endogenous hormone signals and miRNAs in alfalfa leaves under PEG and PEG + cPTIO conditions provided an important basis for endogenous NO to improve the drought resistance of alfalfa at the physiological and molecular levels. It has important scientific value and practical significance for endogenous NO to improve plant drought resistance.