bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B030: Expression patterns of miR181a and miR30d in patients with breast cancer
Authors: Tavakolpournegari Alireza , Hashemi Mehrdad , Matinahmadi Arash , Moosavi Seyedeh Safoora , Bidooki Seyed Hesamoddin 
Published: June 2024

Abstract
Background: One of the important molecular pathways in breast cancer is the PTEN-PI3K-AKT pathway. Any change in the activity of the PTEN gene can alter the PI3K-AKT pathway. Moreover, there are subsets of genes and pathways their expression changes by post-transcriptional regulations. For instance, gene regulation alters by non-coding RNAs such as micro-RNAs as post-transcriptional regulators that prevent the expression of the target transcript. Therefore, it is essential to assess the related alterations in micro-RNA expression patterns to find out the possible causes of conversions in related transcripts and pathways such as the PTENPI3K-AKT pathway in breast cancer. Methods: To determine the expression level of miR-181a and miR-30d in 30 breast tumor samples and 30 adjacent normal samples, the RNA extraction, and cDNA synthesis was performed by RiboEx (GeneAll, Korea). Finally, the Real-Time PCR method was used for quantitative analysis of the expression levels of these miRNAs. all the experimental part of the project in done at Islamic Azad University in 2017. Results: After analyzing comparisons in the expression level of miR-181a and miR-30d in tumor and normal tissues, there was a significant increase in the expression level of miR-181a in tumor samples compared with normal samples. Moreover, the expression level of miR-30d in tumor samples reported a significant decrease in comparison with normal samples (P&lt;0.05). Conclusion: Upregulation of miR-181a may affect the transcription of the PTEN gene resulting in the cell progress to cancer. The Downregulation of miR-30d may also lead to cancer cell growth, due to a reduction in the affecting on the CREB gene transcript.
Citation Format: Alireza Tavakolpournegari, Mehrdad Hashemi, Arash Matinahmadi, Seyedeh Safoora Moosavi, Seyed Hesamoddin Bidooki. Expression patterns of miR181a and miR30d in patients with breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B030.
Abstract IA012: Generation and Mining of a Pediatric-focused Cancer Cell Line Atlas to Define Druggable Genetic Interactions in Childhood Malignancies
Authors: Firestein Ron 
Published: June 2024

Abstract
Pediatric solid and central nervous system tumors are the primary cause of cancer-related fatalities in children. Discovering novel targeted therapies requires utilizing pediatric cancer models that accurately mirror the patient's illness. However, the creation and evaluation of these models have significantly trailed adult cancer research, emphasizing the pressing demand for pediatric-centric cell line repositories. Here, we establish a centralized collection of over 450 childhood cancer cell lines. We subjected over 250 of these cell lines to comprehensive multi-omics analyses (including DNA sequencing, RNA sequencing, and DNA methylation analysis), while concurrently conducting pharmacological screenings and genetic CRISPR-Cas9 loss-of-function assays to unveil pediatric-specific treatment avenues and biomarkers. Machine learning approaches were then applied to uncover genotype-phenotype relationships and synthetic lethal interactions. Our endeavor sheds light on the specific vulnerabilities of pathways in molecularly characterized pediatric tumor subclasses and reveals clinically relevant therapeutic opportunities linked with biomarkers. We offer access to the cell line data and resources through an open-access portal.
Citation Format: Ron Firestein. Generation and Mining of a Pediatric-focused Cancer Cell Line Atlas to Define Druggable Genetic Interactions in Childhood Malignancies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA012.
Abstract IA015: Identifying and targeting synthetic lethalities of aneuploid (cancer) cells
Authors: Ben-David Uri 
Published: June 2024

Abstract
Aneuploidy, an imbalanced number of chromosomes or chromosome arms, is a genetic hallmark of cancer cells, yet aneuploidy remains a biological enigma and a missed opportunity for cancer therapy. Aneuploid cells must cope with several types of cellular stresses, potentially creating synthetic lethalities that can be used to target aneuploid cancer cells. Here, I will describe our efforts to identify synthetic lethalities of the aneuploid state (in contrast to synthetic lethalities of specific recurrent aneuploidies. Specifically, I will focus on three recent unpublished studies, where we report that: (1) Aneuploid cells are preferentially sensitive to perturbation of the spindle assembly checkpoint (SAC) and its regulator KIF18A; the expression and activity of CDC20 determine the sensitivity to SAC inhibition. (2) Aneuploid cells depend on MAPK signaling for overcoming aneuploidy-induced DNA damage; targeting MAPK signaling can sensitize aneuploid cells to DNA damage inducing agents and to PARP inhibitors. (3) Aneuploid cells depend on RNA and protein degradation mechanisms to attenuate the cellular consequence of extra chromosomes; this renders aneuploid cells more sensitive to inhibition of nonsense-mediate decay, miRNA-mediated gene silencing, and the proteasome complex.
Citation Format: Uri Ben-David. Identifying and targeting synthetic lethalities of aneuploid (cancer) cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA015.
Integrating Clinical Phenotype With Multiomics Analyses of Human Cardiac Tissue Unveils Divergent Metabolic Remodeling in Genotype-Positive and Genotype-Negative Patients With Hypertrophic Cardiomyopathy
Authors: Nollet Edgar E. , Schuldt Maike , Sequeira Vasco , Binek Aleksandra , Pham Thang V. , Schoonvelde Stephan A.C. , Jansen Mark , Schomakers Bauke V. , van Weeghel Michel , Vaz Fred M. , Houtkooper Riekelt H. , Van Eyk Jennifer E. , Jimenez Connie R. , Michels Michelle , Bedi Kenneth C. , Margulies Kenneth B. , dos Remedios Cristobal G. , Kuster Diederik W.D. , van der Velden Jolanda 
Published: June 2024

BACKGROUND:
Hypertrophic cardiomyopathy (HCM) is caused by sarcomere gene mutations (genotype-positive HCM) in ≈50% of patients and occurs in the absence of mutations (genotype-negative HCM) in the other half of patients. We explored how alterations in the metabolomic and lipidomic landscape are involved in cardiac remodeling in both patient groups.

METHODS:
We performed proteomics, metabolomics, and lipidomics on myectomy samples (genotype-positive N=19; genotype-negative N=22; and genotype unknown N=6) from clinically well-phenotyped patients with HCM and on cardiac tissue samples from sex- and age-matched and body mass index–matched nonfailing donors (N=20). These data sets were integrated to comprehensively map changes in lipid-handling and energy metabolism pathways. By linking metabolomic and lipidomic data to variability in clinical data, we explored patient group–specific associations between cardiac and metabolic remodeling.

RESULTS:
HCM myectomy samples exhibited (1) increased glucose and glycogen metabolism, (2) downregulation of fatty acid oxidation, and (3) reduced ceramide formation and lipid storage. In genotype-negative patients, septal hypertrophy and diastolic dysfunction correlated with lowering of acylcarnitines, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines. In contrast, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines were positively associated with septal hypertrophy and diastolic impairment in genotype-positive patients.

CONCLUSIONS:
We provide novel insights into both general and genotype-specific metabolic changes in HCM. Distinct metabolic alterations underlie cardiac disease progression in genotype-negative and genotype-positive patients with HCM.
Chemogenetic inhibition of dopaminergic neurons reduces stimulus-induced dopamine release, thereby altering the hemodynamic response function in the prefrontal cortex
Authors: Helbing Cornelia , Brocka Marta , Arboit Alberto , Lippert Michael T. , Angenstein Frank 
Published: June 2024

Abstract
To investigate the effect of endogenously released dopamine on the stimulus-induced blood oxygen level–dependent (BOLD) responses, we used rats expressing inhibitory designer receptors exclusively activated by designer drugs (DREADDs) in neurons of the ventral tegmental area (VTA) and electrically stimulated the fimbria/fornix. This stimulation activates multiple components of the mesolimbic dopamine system, as demonstrated by the BOLD signal changes during functional magnetic resonance imaging (fMRI) and dopamine release in the nucleus accumbens (NAcc) as detected by in vivo fast-scan cyclic voltammetry. Activation of inhibitory DREADDs by clozapine N-oxide (CNO) significantly reduced stimulus-induced dopamine release and the BOLD response in the NAcc. In contrast, the concurrently induced BOLD response in the medial prefrontal cortex (mPFC) was not significantly reduced after CNO administration, but the hemodynamic response was shifted to the left. Specifically, the Granger causality test showed that the temporal relationship between the BOLD signal changes in the hippocampus and the mPFC, changed. Under control conditions (i.e., in the absence of CNO), the BOLD signal changes in the mPFC and NAcc clearly preceded the BOLD signal changes in the right hippocampus, whereas in the presence of CNO this was only the case for the BOLD signal changes in the NAcc. In the control rats, that is, the rats that received a control virus and thus did not express DREADDs in the VTA, this CNO-mediated effect was not present. Our results indicate that activation of the endogenous dopaminergic system has region-specific effects on the stimulus-induced BOLD responses, so there is no generally applicable fMRI parameter that clearly indicates increased activity of the dopaminergic system.
Evolution of modes of nutrient absorption in entomoparasitic nematodes of the order Tylenchida revealed by structural and phylogenetic analysis
Authors: Takahashi Ayumi , Fujimori Yuta , Kanzaki Natsumi , Shinya Ryoji , Ekino Taisuke 
Published: June 2024

Summary
Adult female entomoparasitic nematodes of the order Tylenchida have degenerate digestive organs and body surfaces that lack cuticles and are covered with microvilli. These morphologic features indicate that tylenchids absorb nutrients via the integument. A previous study hypothesised that the nutrient intake of entomoparasitic tylenchids evolved from oral to transdermal in a step-by-step manner, and this evolutionary process is reflected in the development of the integument ultrastructure of these species. However, the evolution of the nutrient absorption of entomoparasitic tylenchids remains unclear. This evolution has not been phylogenetically examined because of a lack of information on the integument structure associated with phylogenetic relationships. In the present study, we examined the integument ultrastructure and molecular sequence of four entomoparasitic tylenchids: Bradynema sp., Contortylenchus sp., C. genitalicola and Deladenus sp. The body surface of Bradynema sp. was covered with microvilli, suggesting that Bradynema sp. absorbs nutrients via the integument. By contrast, the body surfaces of Contortylenchus sp., C. genitalicola and Deladenus sp. were covered with a thin cuticle-like layer and well-developed epidermis without microvilli, suggesting that these species absorb nutrients only partially via the integument. We also classified the nutrient absorption mode based on the integument ultrastructure and molecular phylogenetic analysis of entomoparasitic tylenchids in previous studies. Our maximum parsimony analysis supported the step-by-step evolution hypothesised in the previous study. However, the parsimony analysis also generated new evolutionary processes in which atavism and/or saltation occur instead of stepwise evolution.
Ricoeur, ideology critique, and genetic phenomenology
Authors: Hui Ka-yu 
Published: June 2024

Abstract
This paper elucidates Ricoeur’s use of genetic phenomenology in his analysis of ideology and utopia, and how genetic phenomenology contributes to ideology critique. I argue that Ricoeur’s analysis, examined through the lens of genetic phenomenology, unveils the genesis of the experience of ideology. I propose a model of ideology critique emphasizing the liberation of individuals from ideological delusion without proclaiming an ideology-free position. Additionally, I explore the strategic use of utopian imagination to incite liberating experiences. In conclusion, I underscore the role of social identity constitution as an implicit counterforce to ideology critique.
Avenues for Engagement? Testing the Democratic Nature of Library Book Challenge Processes
Authors: Callahan Pamela Catherine , Miller Joel D. 
Published: June 2024

Background or Context: Public school library book challenges have garnered ample media attention in recent years as many school districts and advocacy organizations have reported record numbers of book challenges. Book challenges are not a new phenomenon, historically speaking, but they have often illuminated values clashes in communities and raise questions about the rights and freedoms of public school students. Judicial rulings and school district policies that address book challenges could provide insights for many members of school communities (including, but not limited to, school board members, students, parents, and teachers) as they experience challenges, but these aspects of the legal record and their influence on responses to book challenges remains underexamined in scholarship. Purpose, Objective, Research Question, or Focus of Study: The 1982 Supreme Court case Island Trees School District v. Pico remains the lasting judicial precedent for interpreting public school students’ First Amendment rights as they interact with school library books. We examine the extent to which school district book challenge policies align with court precedent set in Pico (1982) and the implications for students’ rights and democratic participation during book challenges. Research Design: Drawing on elements of the law and society framework as well as political analysis categories, this study uses qualitative methods to illuminate specific elements of district policies that govern book challenges. Specifically, we examine 29 policies in school districts that experienced a publicly reported book challenge between 2017 and 2021 to understand relationships between school district book challenge policies and the Pico (1982) precedent. Conclusions or Recommendations: Our findings reveal ample space between judicial rulings and school district policies we examine. In fact, we find a broader array of relevant actors in book challenge processes than conceived by the courts and raise implications for students’ constitutional rights and protections related to who policies indicate may or must be involved in these processes, the settings in which book challenge decisions are made, and the limited roles for public involvement during school library book challenges.
Quorum sensing gene lasR promotes phage vB_Pae_PLY infection in Pseudomonas aeruginosa
Authors: Liu Yan , Yao Zhuocheng , Mao Zhenzhi , Tang Miran , Chen Huanchang , Qian Changrui , Zeng Weiliang , Zhou Tieli , Wu Qing 
Published: June 2024

Abstract
Background
Quorum sensing (QS) is a cell density-based intercellular communication system that controls virulence gene expression and biofilm formation. In Pseudomonas aeruginosa (P. aeruginosa), the LasR system sits at the top of the QS hierarchy and coordinates the expression of a series of important traits. However, the role of lasR in phage infection remains unclear. This study aims to investigate the role of lasR QS in phage infection.

Methods
The P. aeruginosa phage was isolated from sewage, and its biological characteristics and whole genome were analyzed. The adsorption receptor was identified via a phage adsorption assay. Following lasR gene knockout, the adsorption rate and bactericidal activity of phage were analyzed. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to explore how lasR promoting phage infection.

Results
The lytic phage vB_Pae_PLY was isolated and lipopolysaccharide (LPS) was identified as its adsorption receptor. The adsorption rate and bactericidal activity of vB_Pae_PLY were reduced after lasR knockout. RT-qPCR results showed that the expression of galU, a key gene involved in LPS synthesis, was down-regulated, and several genes related to type IV pili (T4P) were also down-regulated in the lasR mutant PaΔlasR.

Conclusions
The study showed that QS lasR may promote phage vB_Pae_PLY infection by involving in the synthesis of LPS and T4P. This study provides an example of QS in promoting phage infection and deepens the understanding of phage-bacteria interactions.
Determinants of mortality in hypertensive patients admitted with COVID-19: a single-centre retrospective study at a tertiary hospital in South Africa
Authors: Ikram Ahmed Sameer , Pillay Somasundram 
Published: June 2024

Abstract
Background
The Coronavirus Disease 2019 (COVID-19) pandemic has significantly impacted global health, with successive outbreaks leading to substantial morbidity and mortality. Hypertension, a leading cause of cardiovascular disease globally, has been identified as a critical comorbidity in patients with severe COVID-19, exacerbating the risk of adverse outcomes. This study aimed to elucidate the impact of hypertension on COVID-19 outcomes within the South African context.

Methods
A retrospective analysis was conducted at King Edward VIII Hospital, KwaZulu-Natal, South Africa, encompassing patients aged 13 years and above admitted with laboratory-confirmed SARS-CoV-2 infection between June 2020 and December 2021. The study investigated the association between hypertension and COVID-19 outcomes, analysing demographic, clinical, and laboratory data. Statistical analysis involved univariate and multivariate logistic regression to identify predictors of mortality among the hypertensive cohort.

Results
The study included 420 participants—encompassing 205 with hypertension. Hypertensive patients demonstrated significantly greater requirements for oxygen and steroid therapy (p < 0.001), as well as higher mortality rates (44.88%, p < 0.001)) compared to their non-hypertensive counterparts. Key findings demonstrated that a lower oxygen saturation (adjusted odds ratio (aOR) 0.934, p = 0.006), higher pulse pressure (aOR 1.046, p = 0.021), elevated CRP (aOR 1.007, p = 0.004) and the necessity for mechanical ventilation (aOR 5.165, p = 0.004) were independent risk factors for mortality in hypertensive COVID-19 patients. Notably, the study highlighted the pronounced impact of hypertension-mediated organ damage (HMOD) on patient outcomes, with ischemic heart disease being significantly associated with increased mortality (aOR 8.712, p = 0.033).

Conclusion
Hypertension significantly exacerbates the severity and mortality risk of COVID-19 in the South African setting, underscoring the need for early identification and targeted management of hypertensive patients. This study contributes to the understanding of the interplay between hypertension and COVID-19 outcomes, emphasising the importance of considering comorbidities in the management and treatment strategies for COVID-19. Enhanced pandemic preparedness and healthcare resource allocation are crucial to mitigate the compounded risk presented by these concurrent health crises.
Prenatal diagnosis of a severe form of frontonasal dysplasia with severe limb anomalies, hydrocephaly, a hypoplastic corpus callosum, and a ventricular septal defect using 3D ultrasound: a case report and literature review
Authors: Guo Cuixia , Zhang Tiejuan , Ma Ying , Yue Song , Sun Lijuan 
Published: June 2024

Abstract
Background
Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years.

Case presentation
A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND.

Conclusion
The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.
Pathomics and single-cell analysis of papillary thyroid carcinoma reveal the pro-metastatic influence of cancer-associated fibroblasts
Authors: Wang Yixian , Li Xin , Gang Qingwei , Huang Yinde , Liu Mingyu , Zhang Han , Shen Shikai , Qi Yao , Zhang Jian 
Published: June 2024

Abstract
Background
Papillary thyroid carcinoma (PTC) is globally prevalent and associated with an increased risk of lymph node metastasis (LNM). The role of cancer-associated fibroblasts (CAFs) in PTC remains unclear.

Methods
We collected postoperative pathological hematoxylin–eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1.

Results
A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells.

Conclusion
This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.