bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C056: The initiation and progression of pancreatic ductal adenocarcinoma through a p53 lens
Authors: Hanson Kathryn J. , Minor Allegra C. , Flowers Brittany M. , Kaiser Alyssa M. , Hughes Nicholas , Vogel Hannes , Cong Le , Attardi Laura D. 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of only 11%. Slated to be the 2nd most deadly cancer by 2026, pancreatic cancer survival rates have not improved substantially over the years. With a lack of early detection methods and a highly immunosuppressive tumor microenvironment (TME), PDAC tumors are highly resistant to treatment. Oncogenic mutations in KRAS are present in &gt;90% of cases and mutations in the tumor suppressor gene TP53 are present in ~72% of cases. However, why p53 mutations are so prevalent and how they enhance PDAC development is not well understood. To elucidate how exactly p53 loss promotes PDAC, we are using genetically engineered mouse models combined with single-cell and spatial transcriptomic technologies. In this mouse model, PDAC is driven from adult acinar cells with a tamoxifen-inducible Ptf1aCreER allele by oncogenic Kras (KrasG12D) along with either p53 wild type (p53wt) or p53 deficiency (p53flox). In this model, acinar cells can give rise to PDAC likely through a transdifferentiation process called acinar-to-ductal metaplasia (ADM), which leads to pancreatic intraepithelial neoplasias (PanINs) and then PDAC. The initial cell fate transition, ADM, can be activated by growth factors, inflammation, and injury. We have conducted single-cell and spatial transcriptomics to compare early stages of tumor development in the presence and absence of p53, and we will present our latest analyses. Providing insight into the early events of PDAC will lead to new approaches for improving clinical intervention in human PDAC.
Citation Format: Kathryn J. Hanson, Allegra C. Minor, Brittany M. Flowers, Alyssa M. Kaiser, Nicholas Hughes, Hannes Vogel, Le Cong, Laura D. Attardi. The initiation and progression of pancreatic ductal adenocarcinoma through a p53 lens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C056.
Abstract C079: Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new approach to treat pancreatic cancer
Authors: Sainz Bruno Jr , Alcalá Sonia , Villarino Lara , Ruíz-Cañas Laura , Couceiro José , Martínez-Calvo Miguel , Palencia-Campos Adrián , Navarro Diego , Cabezas-Sainz Pablo , Cordero-Barreal Alfonso , Rubiolo Juan A. , González-Páramos Cristina , Carrato Alfredo , Hermann Patrick C. , Sánchez Laura , Torrente Susana , Fernández-Moreno Miguel Ángel , Mascareñas José L. 
Published: January 2024

Abstract
Background and aims: Annual world-wide cancer-related fatalities remain high for pancreatic ductal adenocarcinoma (PDAC), largely due to the presence of “stem-like” tumor cells known as cancer stem cells (CSCs). Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic CSCs meet their energetic requirements; therefore, OXPHOS represents an Achille’s heel of these highly tumorigenic cells. Methods: The anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) was evaluated across primary PDAC cultures and 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. Results: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for PaCSCs that heavily depend on mitochondrial respiration. Conclusion Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover an unprecedented approach to fight PDAC based on targeting CSC OXPHOS.
Citation Format: Bruno Jr Sainz, Sonia Alcalá, Lara Villarino, Laura Ruíz-Cañas, José Couceiro, Miguel Martínez-Calvo, Adrián Palencia-Campos, Diego Navarro, Pablo Cabezas-Sainz, Alfonso Cordero-Barreal, Juan A. Rubiolo, Cristina González-Páramos, Alfredo Carrato, Patrick C. Hermann, Laura Sánchez, Susana Torrente, Miguel Ángel Fernández-Moreno, José L. Mascareñas. Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new approach to treat pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C079.
Abstract C082: Decoding the KRAS-dependent proteome through the ribosomal lens
Authors: Singh Kamini , Nguyen Trang Uyen , Pederson Eric Nels , Kumar Vinay , Yun Xiaoling , Ouyang Zhengqing 
Published: January 2024

Abstract
Our study addresses the gap in understanding the KRAS-specific translation landscape and functional proteome in cancer. We demonstrate that mutant KRAS drives distinct mechanisms of translational control to fuel cancer growth. By leveraging ribosome footprinting and advanced sequencing techniques, we investigate the impact of sotorasib, a targeted inhibitor of G12C mutant KRAS activity, on translation. Notably, KRAS (G12C) inhibition profoundly alters the translation of ribosomal proteins and translation elongation factors. Additionally, we reveal that KRAS inhibition resulted in ribosome stalling on a specific subset of mRNAs. Acute treatment with sotorasib hampers the translation of crucial oncogenic proteins, including MYC, as well as proteins involved in metabolism. These translational changes are facilitated by specific RNA motifs and RNA binding proteins that respond to KRAS activity. In essence, our study delineates the KRAS (G12C)-specific regulation of translation and elucidates the mechanism underlying KRAS (G12C)-mediated control over the cancer proteome.
Citation Format: Kamini Singh, Trang Uyen Nguyen, Eric Nels Pederson, Vinay Kumar, Xiaoling Yun, Zhengqing Ouyang. Decoding the KRAS-dependent proteome through the ribosomal lens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C082.
Sublimação, angústia e violência no cenário do sofrimento psíquico contemporâneo
Authors: Loffredo Ana Maria 
Published: January 2024

No cenário das expressões do sofrimento psíquico contemporâneo, os atos terroristas são recortados como veículos privilegiados da violência urbana, sendo examinados no campo de operação da sublimação, em sua relação com a angústia e com a pulsão de morte, no âmbito da sublimação da agressividade. Impõem-se uma peculiaridade essencial da ocorrência terrorista: seu estatuto de espetáculo, em seu atravessamento pela mídia, destacando-se sua repercussão eminentemente visual. Como a pulsão de saber é tributária de duas pulsões parciais, a pulsão escopofílica e a pulsão de dominação, a exposição recorrente ao fascínio de “ver” remete à capacidade de pensar, potencializando-se a operação de uma das vertentes do arcaico, mais facilmente reativada nessas circunstâncias.
Social Media, Fake News and Covid-19 Vaccine Hesitancy in Zimbabwe
Authors: Chiweshe Manase Kudzai , Dandah Gerald 
Published: January 2024

Abstract
This exploratory paper uses online ethnography to analyse how fake news on social media shaped perceptions and cognitions about Covid-19 vaccines in Zimbabwe. It explores the emergence of social media as an important space for instilling vaccine hesitancy in the context of Covid-19. The paper focuses on how memes, jokes, fake news stories and reports that were shared and consumed on platforms such as WhatsApp, Facebook, Twitter, and YouTube shaped the health-seeking behaviour of people in the context of Covid vaccines in Zimbabwe. The findings show that most people do not trust the government or health institutions. This distrust means they turn to unofficial online sources of information that fuel myths, conspiracies, rumours and gossip and cause fear, panic and vaccine hesitancy. Most citizens resorted to social media to update each other on the efficacy of vaccines and the pros and cons of getting inoculated, highlighting the scepticism surrounding Covid-19 vaccines in Zimbabwe.
Public Health and Political Governance
Authors: Ajiola Felix Oludare 
Published: January 2024

Abstract
In the light of the Covid-19 pandemic, its mutations, concealment by people and the resistance to vaccines against it, it is relevant to examine the outbreak of bubonic plague in colonial Lagos during the early twentieth century and the response by the British colonial authorities. The methodology applied to this study is historical, drawing information from medical, sanitary, land use and physical planning documents accessed from various archives as well as some secondary sources. It is clear that the colonial government’s housing and public health regulations, which allowed authorities to inspect people’s homes for cases of infectious disease, drove people to escape into the hinterland, increasing the spread of the plague. Consequently, the colonial authorities carried out a massive structural and physical reorganisation of towns and villages. They also embarked on large-scale land reclamation, decongested overcrowded houses and introduced sanitary measures to make the environment more habitable. This paper argues that through effective political governance structures the colonial government strategically eliminated the bubonic plague in Lagos.
Multinational Joint Task Force: Lessons for Comprehensive Regional Approaches to Cross-Border Conflict in Africa
Authors: Aniekwe Chika Charles , Brooks Katharine 
Published: January 2024

Abstract
The recent proliferation of cross-border conflicts in Africa has led to the establishment of multiple Ad Hoc Security Initiatives (asi s) on the continent. However, the effectiveness of these initiatives has varied considerably. As such, there is now increased academic and policy interest in the Multinational Joint Task Force (mnjtf), which has seen substantial operational success over the course of its mandate. This paper seeks to contribute to the debate on the strengths and weaknesses of the mnjtf model and the effectiveness of the Force in the Lake Chad region through an exploration of the mnjtf from an internal perspective. The authors of this paper have both worked closely with the mnjtf in recent years and the paper is based upon interviews with current and former mnjtf personnel, staff of the Lake Chad Basin Commission (which oversees the mnjtf) as well as donor and UN partners. In exploring this internal perspective, the article undertakes an in-depth examination of the mnjtf, including the relationship between the headquarters and the sectors, and assesses the impact the mnjtf has had upon the Troop Contributing Countries (tcc s). It identifies areas where the mnjtf has become a regional hub of best practice, challenges that have compromised its effectiveness, and the impact of military diplomacy on the security of the region. Finally, it concludes by drawing lessons from this experience for other conflicts requiring a comprehensive regional and international response.
The Representation of Women in African-Led Peace Support Operations
Authors: Olaitan Zainab Monisola 
Published: January 2024

Abstract
The discourse on the evolving nature of African-led peace support operations (pso) is not complete without asking how gender-inclusive they are. Women have historically been underrepresented within the peace and security space. While several interventions have been made to ensure that pso s on the continent become better, the same cannot be said for gender inclusion. This article examines the participation of women in African-led pso s. It draws on Rwanda as a case study to contextualize the discourse on how gender inclusive African police and troops contributing countries (p/tcc s) are. The analysis finds that efforts at improving pso s on the African continent have not translated into increased representation of women. In particular, African p/tcc s are yet to ensure a considerable number of women in their deployments. The article recommends that there needs to be concerted effort by African p/tcc s and other regional organizations to ensure gender-inclusivity in African-led pso s.
Uncovering the Genomic Regions Associated with Yield Maintenance in Rice Under Drought Stress Using an Integrated Meta-Analysis Approach
Authors: Daryani Parisa , Amirbakhtiar Nazanin , Soorni Jahad , Loni Fatemeh , Darzi Ramandi Hadi , Shobbar Zahra-Sadat 
Published: January 2024

AbstractThe complex trait of yield is controlled by several quantitative trait loci (QTLs). Given the global water deficit issue, the development of rice varieties suitable for non-flooded cultivation holds significant importance in breeding programs. The powerful approach of Meta-QTL (MQTL) analysis can be used for the genetic dissection of complicated quantitative traits. In the current study, a comprehensive MQTL analysis was conducted to identify consistent QTL regions associated with drought tolerance and yield-related traits under water deficit conditions in rice. In total, 1087 QTLs from 134 rice populations, published between 2000 to 2021, were utilized in the analysis. Distinct MQTL analysis of the relevant traits resulted in the identification of 213 stable MQTLs. The confidence interval (CI) for the detected MQTLs was between 0.12 and 19.7 cM. The average CI of the identified MQTLs (4.68 cM) was 2.74 times narrower compared to the average CI of the initial QTLs. Interestingly, 63 MQTLs coincided with SNP peak positions detected by genome-wide association studies for yield and drought tolerance-associated traits under water deficit conditions in rice. Considering the genes located both in the QTL-overview peaks and the SNP peak positions, 19 novel candidate genes were introduced, which are associated with drought response index, plant height, panicle number, biomass, and grain yield. Moreover, an inclusive MQTL analysis was performed on all the traits to obtain “Breeding MQTLs”. This analysis resulted in the identification of 96 MQTLs with a CI ranging from 0.01 to 9.0 cM. The mean CI of the obtained MQTLs (2.33 cM) was 4.66 times less than the mean CI of the original QTLs. Thirteen MQTLs fulfilling the criteria of having more than 10 initial QTLs, CI < 1 cM, and an average phenotypic variance explained greater than 10%, were designated as “Breeding MQTLs”. These findings hold promise for assisting breeders in enhancing rice yield under drought stress conditions.
Genome-scale metabolic network model and phenome of solvent-tolerant Pseudomonas putida S12
Authors: Han Sol , Kim Dohyeon , Kim Youngshin , Yoon Sung Ho 
Published: January 2024

Abstract
Background
Pseudomonas putida S12 is a gram-negative bacterium renowned for its high tolerance to organic solvents and metabolic versatility, making it attractive for various applications, including bioremediation and the production of aromatic compounds, bioplastics, biofuels, and value-added compounds. However, a metabolic model of S12 has yet to be developed.

Results
In this study, we present a comprehensive and highly curated genome-scale metabolic network model of S12 (iSH1474), containing 1,474 genes, 1,436 unique metabolites, and 2,938 metabolic reactions. The model was constructed by leveraging existing metabolic models and conducting comparative analyses of genomes and phenomes. Approximately 2,000 different phenotypes were measured for S12 and its closely related KT2440 strain under various nutritional and environmental conditions. These phenotypic data, combined with the reported experimental data, were used to refine and validate the reconstruction. Model predictions quantitatively agreed well with in vivo flux measurements and the batch cultivation of S12, which demonstrated that iSH1474 accurately represents the metabolic capabilities of S12. Furthermore, the model was simulated to investigate the maximum theoretical metabolic capacity of S12 growing on toxic organic solvents.

Conclusions
iSH1474 represents a significant advancement in our understanding of the cellular metabolism of P. putida S12. The combined results of metabolic simulation and comparative genome and phenome analyses identified the genetic and metabolic determinants of the characteristic phenotypes of S12. This study could accelerate the development of this versatile organism as an efficient cell factory for various biotechnological applications.
Genome-wide characterization of COMT family and regulatory role of CsCOMT19 in melatonin synthesis in Camellia sinensis
Authors: Pham Thanh Huyen , Tian Xingyu , Zhao Huimin , Li Tong , Lu Litang 
Published: January 2024

Abstract
Background
Caffeic acid O-methyltransferase (COMT) is a key enzyme that regulates melatonin synthesis and is involved in regulating the growth, development, and response to abiotic stress in plants. Tea plant is a popular beverage consumed worldwide, has been used for centuries for its medicinal properties, including its ability to reduce inflammation, improve digestion, and boost immune function. By analyzing genetic variation within the COMT family, while helping tea plants resist adversity, it is also possible to gain a deeper understanding of how different tea varieties produce and metabolize catechins, then be used to develop new tea cultivars with desired flavor profiles and health benefits.

Results
In this study, a total of 25 CsCOMT genes were identified based on the high-quality tea (Camellia sinensis) plant genome database. Phylogenetic tree analysis of CsCOMTs with COMTs from other species showed that COMTs divided into four subfamilies (Class I, II, III, IV), and CsCOMTs was distributed in Class I, Class II, Class III. CsCOMTs not only undergoes large-scale gene recombination in pairs internally in tea plant, but also shares 2 and 7 collinear genes with Arabidopsis thaliana and poplar (Populus trichocarpa), respectively. The promoter region of CsCOMTs was found to be rich in cis-acting elements associated with plant growth and stress response. By analyzing the previously transcriptome data, it was found that some members of CsCOMT family exhibited significant tissue-specific expression and differential expression under different stress treatments. Subsequently, we selected six CsCOMTs to further validated their expression levels in different tissues organ using qRT-PCR. In addition, we silenced the CsCOMT19 through virus-induced gene silencing (VIGS) method and found that CsCOMT19 positively regulates the synthesis of melatonin in tea plant.

Conclusion
These results will contribute to the understanding the functions of CsCOMT gene family and provide valuable information for further research on the role of CsCOMT genes in regulating tea plant growth, development, and response to abiotic stress.
Molecular evolution analysis of MYB5 in Brassicaceae with specific focus on seed coat color of Brassica napus
Authors: Dai Guoqiang , Liu Yi , Shen Wenjie , Zhu Bo , Chen Lunlin , Chen Daozong , Tan Chen 
Published: January 2024

Abstract
Background
MYB transcription factors are splay a vital role in plant biology, with previous research highlighting the significant impact of the R2R3-MYB-like transcription factor MYB5 on seed mucilage biosynthesis, trichome branching, and seed coat development. However, there is a dearth of studies investigating its role in the regulation of proanthocyanidin (PA) biosynthesis.

Results
In this study, a total of 51 MYB5 homologous genes were identified across 31 species belonging to the Brassicaceae family, with particular emphasis on Brassica napus for subsequent investigation. Through phylogenetic analysis, these genes were categorized into four distinct subclasses. Protein sequence similarity and identity analysis demonstrated a high degree of conservation of MYB5 among species within the Brassicaceae family. Additionally, the examination of selection pressure revealed that MYB5 predominantly underwent purifying selection during its evolutionary history, as indicated by the Ka/Ks values of all MYB5 homologous gene pairs being less than one. Notably, we observed a higher rate of non-synonymous mutations in orthologous genes compared to paralogous genes, and the Ka/Ks value displayed a stronger correlation with Ka. In B. napus, an examination of expression patterns in five tissues revealed that MYB5 exhibited particularly high expression in the black seed coat. The findings from the WGCNA demonstrated a robust correlation between MYB5 and BAN(ANR) associated with PA biosynthesis in the black seed coat, providing further evidence of their close association and co-expression. Furthermore, the results obtained from of the analysis of protein interaction networks offer supplementary support for the proposition that MYB5 possesses the capability to interact with transcriptional regulatory proteins, specifically TT8 and TT2, alongside catalytic enzymes implicated in the synthesis of PAs, thereby making a contribution to the biosynthesis of PAs. These findings imply a plausible and significant correlation between the nuique expression pattern of MYB5 and the pigmentation of rapeseed coats. Nevertheless, additional research endeavors are imperative to authenticate and substantiate these findings.

Conclusions
This study offers valuable insights into the genetic evolution of Brassicaceae plants, thereby serving as a significant reference for the genetic enhancement of Brassicaceae seed coat color.
Relationship between serum soluble suppression of tumorigenicity (ST) 2 and global longitudinal strain in early onset preeclampsia
Authors: Prameswari Hawani Sasmaya , Effendi Cut Azlina , Khalid Achmad Fitrah , Irianti Setyorini , Fatati Ita , Akbar Mohammad Rizki 
Published: January 2024

Abstract
Background
Preeclampsia is one of the leading causes of death in childbearing women worldwide. Hemodynamic changes in preeclampsia can trigger cardiac remodeling as indicated by increase of soluble-ST2 (sST2). Global longitudinal strain were able to detect systolic dysfunction better than the ejection fraction. This study aims to evaluate the correlation between serum levels of sST2 towards GLS in patients with early-onset preeclampsia.

Methods
This is a cross-sectional observational study with correlation analysis. Subjects were patients with severe preeclampsia with gestational age before 34 weeks at Dr. Hasan Sadikin Central General Hospital Bandung and Bandung Kiwari Regional General Hospital from June to August 2022. Examination of sST2 was carried out through blood samples using the ELISA method. sST2 was measured using Presage ST2 Assay reagent. GLS examination was carried out using speckle tracking technique with EchoPAC. Correlation analysis was conducted using the Pearson test if normally distributed, otherwise Spearman’s correlation was conducted. Correlation analysis was followed by linear regression.

Results
A total of 30 patients met the inclusion criteria. The mean age was 30.83 ± 7.09, with 17 (56.7%) multiparous patients. The median sST2 was 145.75 ng/mL, and the median GLS was − 17.4%. Spearman correlation analysis showed that there was a significant positive correlation with moderate strength between sST2 and GLS (r = 0.583; p < 0.002). Linear regression showed that every 1 ng/ml increase in sST2 would give an increase in GLS of 0.014%.

Conclusion
There is a significant correlation between sST2 and GLS in patients with early onset severe preeclampsia.