bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor cell-induced macrophage senescence plays a pivotal role in tumor initiation followed by stable growth in immunocompetent condition
Authors: Wada Haruka , Otsuka Ryo , Germeraad Wilfred T V , Murata Tomoki , Kondo Toru , Seino Ken-ichiro 
Published: November 2023

BackgroundThe cancer stem cell theory proposes that tumor formation in vivo is driven only by specific tumor-initiating cells having stemness; however, clinical trials conducted to test drugs that target the tumor stemness provided unsatisfactory results thus far. Recent studies showed clear involvement of immunity in tumors; however, the requirements of tumor-initiation followed by stable growth in immunocompetent individuals remain largely unknown.MethodsTo clarify this, we used two similarly induced glioblastoma lines, 8B and 9G. They were both established by overexpression of an oncogenic H-RasL61 in p53-deficient neural stem cells. In immunocompromised animals in an orthotopic transplantation model using 1000 cells, both show tumor-forming potential. On the other hand, although in immunocompetent animals, 8B shows similar tumor-forming potential but that of 9G’s are very poor. This suggests that 8B cells are tumor-initiating cells in immunocompetent animals. Therefore, we hypothesized that the differences in the interaction properties of 8B and 9G with immune cells could be used to identify the factors responsible for its tumor forming potential in immunocompetent animals and performed analysis.ResultsDifferent from 9G, 8B cells induced senescence-like state of macrophages around tumors. We investigated the senescence-inducing factor of macrophages by 8B cells and found that it was interleukin 6. Such senescence-like macrophages produced Arginase-1, an immunosuppressive molecule known to contribute to T-cell hyporesponsiveness. The senescence-like macrophages highly expressed CD38, a nicotinamide adenine dinucleotide (NAD) glycohydrolase associated with NAD shortage in senescent cells. The addition of nicotinamide mononucleotide (NMN), an NAD precursor, in vitro inhibited to the induction of macrophage senescence-like phenotype and inhibited Arginase-1 expression resulting in retaining T-cell function. Moreover, exogenous in vivo administration of NMN after tumor inoculation inhibited tumor-initiation followed by stable growth in the immunocompetent mouse tumor model.ConclusionsWe identified one of the requirements for tumor-initiating cells in immunocompetent animals. In addition, we have shown that tumor growth can be inhibited by externally administered NMN against macrophage senescence-like state that occurs in the very early stages of tumor-initiating cell development. This therapy targeting the immunosuppressive environment formed by macrophage senescence-like state is expected to be a novel promising cancer therapeutic strategy.
De novo variants inKCNJ3are associated with early-onset epilepsy
Authors: Li Juan , Mei Shiyue , Mao Xiao , Wan Lily , Wang Hua , Xiao Bo , Song Yanmin , Gu Weiyue , Liu Yan , Long Lili 
Published: November 2023

BackgroundKCNJ3encodes a subunit of G-protein-coupled inwardly rectifying potassium channels, which are important for cellular excitability and inhibitory neurotransmission. However, the genetic basis ofKCNJ3in epilepsy has not been determined. This study aimed to identify the pathogenicKCNJ3variants in patients with epilepsy.MethodsTrio exome sequencing was performed to determine potential variants of epilepsy. Individuals withKCNJ3variants were recruited for this study. Detailed clinical information and genetic data were obtained and systematically reviewed. Whole-cell patch-clamp recordings were performed to evaluate the functional consequences of the identified variants.ResultsTwo de novo missense variants (c.998T>C (p.Leu333Ser) and c.938G>A (p. Arg313Gln)) inKCNJ3were identified in two unrelated families with epilepsy. The variants were absent from the gnomAD database and were assumed to be damaging or probably damaging using multiple bioinformatics tools. They were both located in the C‐terminal domain. The amino acid residues were highly conserved among various species. Clinically, the seizures occurred at a young age and were under control after combined treatment. Electrophysiological analysis revealed that theKCNJ3Leu333Ser and Arg313Gln variants significantly compromised the current activities and exhibited loss-of-function (LOF) effects.ConclusionOur findings suggest that de novo LOF variants inKCNJ3are associated with early-onset epilepsy. Genetic testing ofKCNJ3in patients with epilepsy may serve as a strategy for precision medicine.
Causal effects of time-varying body size on selected autoimmune disorders: a life course Mendelian randomisation study
Authors: Freuer Dennis , Meisinger Christa 
Published: November 2023

BackgroundBased on Barker’s hypothesis, some studies investigated the associations between birth weight and several disorders. Apart from issues with statistical power and well-known shortcomings of the observational study design, there are no studies accounting for changes in weight-related body size over the life course regarding rheumatoid arthritis, psoriasis, psoriatic arthritis and multiple sclerosis.MethodsUsing genetic information of up to 806 834 participants, this study investigated the associations between time-varying weight-related body size from birth to adulthood and the mentioned autoimmune diseases. Performing Mendelian randomisation (MR), the radial inverse-variance weighted approach was used iteratively in primary analyses. Robustness of the results was confirmed in several sensitivity analyses. Potential time-dependent mediation mechanisms were identified through network-clustering and assessed using multivariable MR.ResultsGenetically predicted birth weight (fetal effect) was positively associated with rheumatoid arthritis (OR 1.44; 95% CI 1.17 to 1.77; Padj=0.005) but not with psoriasis, psoriatic arthritis or multiple sclerosis. This association was found to be mediated by body mass index (BMI) in adulthood (OR 1.45; 95% CI 1.14 to 1.84; Padj=0.019) rather than childhood. The direct effect of birth weight attenuated (OR 1.19; 95% CI 0.88 to 1.62); Padj=1) after adjustment for time-varying BMI.ConclusionIncreased birth weight appears to be a risk factor for later manifestation of rheumatoid arthritis due to both fetal genetic components and high BMI persisting into adulthood. Approaches to prevent and minimise the risk of rheumatoid arthritis could include preventing obesity in adults with high birth weight.
Consumer preferences on quality of supermarket services in organized retailing: Structural equation modeling approach
Authors: Deepika D. E. Vijaya , Kannan N. 
Published: November 2023

Retailing in India has come a long way. The rapid development and advancement in technology and consumer needs have made the retail sector hold a pivotal role in our economy. Organized retailing has brought in more satisfied and convenient shopping practices among consumers. The major segments covered in organized or modern retailing include store-based and nonstore-based. The organized retail market has a lot of scope and opportunities due to value for money, changing consumer shopping patterns, rural market, enhanced middle-class consumers, growth and awareness of consumerism, technological impact, media and social media apprising and increased income ( Suresh , 2019 ). This study focuses on the supermarket segment of organized retailing, where the major daily groceries and monthly household needs of consumers are extensively delivered. Even though the major online grocery stores and applications have become a part of consumers’ lives, supermarkets and hypermarkets are enduring and growing due to the constant support offered by consumers of all categories. Despite the pandemic hindrances, the organized retailing sectors have registered strong growth and performance. This study aims to analyze consumer preferences for supermarkets and the reasons behind choosing supermarkets. The data were collected from 128 respondents who were shoppers of various supermarkets with reference to Chennai city. The data were collected through a self-administered survey using a structured questionnaire. The analysis of data was performed using descriptive statistics and SPSS AMOS. Structural equation modeling (SEM) was used in order to evaluate the association between variables used in the study.
Multi-element geochemical analyses on ultrafine soils in Western Australia – towards establishing abundance ranges in mineral exploration settings
Authors: Henne Anicia , Noble Ryan R. P. , Williams Morgan 
Published: November 2023

In this study, we present summary statistics for multi-element soil geochemistry across Western Australia based on over 74 000 soil samples using the UltraFine+
®
method that extracts and analyses the clay (<2

μ

m) fraction of a soil sample. This method is a critical advancement for the detection of mobile element signatures for soil geochemical mineral exploration surveys in cover. However, existing estimates of background metal abundances acquired with other methods and on different sample media do not readily provide context for these analyses, as recovery from the fine fraction differs to that of whole-sample analysis. We therefore present herein the geochemical results for 52 elements, including precious, base and critical metals, as well as commonly associated pathfinder elements for Western Australian samples analysed during several research projects by the Commonwealth Scientific and Industrial Research Organisation (CSIRO). This dataset is separated by tectonic unit into the Eastern Goldfields Superterrane and the Youanmi Terrane in the Yilgarn Craton, the Pilbara Craton and Sylvania Inlier, the Gascoyne, Lamboo and Aileron Provinces, and the Bryah and Earaheedy Basins to provide exploration-relevant context in these areas. We discuss some of the general trends observed for 12 of these elements, as well as some considerations for the use of these data in comparison to other geochemical soil surveys and with regards to mineral exploration settings. The samples presented in this study are not evenly distributed across Western Australia and limited information is available to correlate whether lithology at depth is mineralized or barren. However, in the absence of other systematic datasets using the <2

μ

m-size fraction, these data present a suitable first-pass resource of element abundance ranges in areas of mineral exploration interest using the UltraFine+
®
method in some of the mineral-endowed areas of Western Australia.

Supplementary material:
Supplementary data A, UltraFine+
®
Soil Sampling Guide; B, UltraFine+
®
analyses results for available samples in Western Australia; C, Summary statistics of UltraFine+
®
analyses by simplified tectonic units; Supplementary Figure 1, Comparison of elemental mean values and uncertainties for ultrafine reference materials QC 320 and QC 422; Supplementary Figure 2, Violin plots of Ni, Cd, Mg and Au by simplified tectonic unit; Supplementary Figure 3, Location of soil samples in the Eastern Goldfields Superterrane analysed via UltraFine+
®
, and those collected as part of the NGSA and GSWA regolith programme; Supplementary Figure 4, Comparison of W, Al, Mg and Ca results from UltraFine+
®
, NGSA and GSWA analyses in the Eastern Goldfields Superterrane are available at
https://doi.org/10.6084/m9.figshare.c.6919933
CircMMP2(6,7) Cooperates with β-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis
Authors: Xu Yingru , Li Xincheng , Zhang Shuxia , Tang Miaoling , Yu Ruyuan , Liao Xinyi , Li Ziwen , Li Man , Chen Suwen , Qian Wanying , Song Libing , Ke Zunfu , Li Jun 
Published: November 2023

Abstract

The bone is the most common site of distant metastasis of breast cancer, which leads to serious skeletal complications and mortality. Understanding the mechanisms underlying breast cancer bone metastasis would provide potential strategies for the prevention and treatment of breast cancer bone metastasis. In this study, we identified a circular RNA that we named circMMP2(6,7) that was significantly upregulated in bone metastatic breast cancer tissues and correlated with breast cancer–bone metastasis. Upregulation of circMMP2(6,7) dramatically enhanced the metastatic capability of breast cancer cells to the bone via inducing bone metastatic niche formation by disrupting bone homeostasis. Mechanistically, circMMP2(6,7) specifically bound to the promoters of bone-remodeling factors calcium-binding protein S100A4 and carbohydrate-binding protein LGALS3 and formed a complex with β-catenin and arginine methyltransferase PRMT5, eliciting histone H3R2me1/H3R2me2s-induced transcriptional activation. Treatment with GSK591, a selective PRMT5 inhibitor, effectively inhibited circMMP2(6,7)/β-catenin/PRMT5 complex–induced breast cancer bone metastasis. These findings reveal a role for circMMP2(6,7) in bone homeostasis disruption and shed light on the mechanisms driving breast cancer bone metastasis.

Significance:
Upregulation of bone-remodeling factors S100A4 and LGALS3 mediated by a circMMP2(6,7)/β-catenin/PRMT5 complex generates a niche that supports breast cancer bone metastasis, identifying PRMT5 as a promising target for treating metastasis.
RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion
Authors: Zhuang Qiuyu , Dai Zhiguo , Xu Xuechun , Bai Shaoyi , Zhang Yindan , Zheng Youshi , Xing Xiaohua , Hu En , Wang Yingchao , Guo Wuhua , Zhao Bixing , Zeng Yongyi , Liu Xiaolong 
Published: November 2023

Abstract

Immunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and antitumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2′-O-methyltransferase, in HCC by suppressing antitumor immune responses. FTSJ3 was upregulated in hepatocellular carcinoma, and high FTSJ3 expression correlated with reduced patient survival. Deletion of FTSJ3 blocked HCC growth and induced robust antitumor immune responses. Mechanistically, FTSJ3 suppressed double-stranded RNA (dsRNA)–induced IFNβ signaling in a 2′-O-methyltransferase manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued the in vivo tumor growth defect caused by FTSJ3 deficiency, indicating that FTSJ3 deletion suppresses tumor growth by activating the RNA sensor–mediated type I IFN pathway. Furthermore, FTSJ3 deletion significantly enhanced the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade. The combination of FTSJ3 deficiency and anti–PD-1 antibody treatment effectively eradicated tumors and increased the survival time. In conclusion, this study reveals an epigenetic mechanism of tumor immune evasion and, importantly, suggests FTSJ3-targeting therapies as potential approach to overcome immunotherapy resistance in patients with HCC.

Significance:
Hepatocellular carcinoma cells use 2′-O-methylation catalyzed by FTSJ3 for immune evasion by suppressing abnormal dsRNA-mediated type I IFN responses, providing a potential target to activate antitumor immunity and enhance immunotherapy efficacy.
Gated recurrent unit decision model for device argumentation in ambient assisted living
Authors: Kumar G. S. Madhan , Prakash S. P. Shiva , Krinkin Kirill 
Published: November 2023

The increasing elderly population worldwide is facing a variety of social, physical, and cognitive issues, such as walking problems, falls, and difficulties in performing daily activities. To support elderly people, continuous monitoring and supervision are needed. Due to the busy modern lifestyle of caretakers, taking care of elderly people is difficult. As a result, many elderly people prefer to live independently at home without any assistance. To help such people, an ambient assisted living (AAL) environment is provided that monitors and evaluates the daily activities of elderly individuals. An AAL environment has heterogeneous devices that interact, and exchange information of the activities performed by the users. The devices can be involve in an argumentation about the occurrence of an activity thus leading to generate conflicts. To address this issue, the paper proposes a gated recurrent unit (GRU) learning techniques to facilitate decision-making for device argumentation during activity occurrences. The proposed model is used to initially classify user activities and each sensor value status. Then a novel method is used to identify argumentation among devices for activity occurrences in the classified user activities. Later, the GRU decision making model is used to resolve the argumentation and to identify the target activity that occurred. The result of the proposed model is compared with other existing techniques. The proposed model outperformed the other existing methods with an accuracy of 85.45%, precision of 72.32%, recall of 65.83%, and F1-Score of 60.22%.
Cooperative Response to Endocardial Notch Reveals Interaction With Hippo Pathway
Authors: Luna-Zurita Luis , Flores-Garza Brenda Giselle , Grivas Dimitrios , Siguero-Álvarez Marcos , de la Pompa José Luis 
Published: November 2023

BACKGROUND:
The endocardium is a crucial signaling center for cardiac valve development and maturation. Genetic analysis has identified several human endocardial genes whose inactivation leads to bicuspid aortic valve formation and calcific aortic valve disease, but knowledge is very limited about the role played in valve development and disease by noncoding endocardial regulatory regions and upstream factors.

METHODS:
We manipulated Notch signaling in mouse embryonic endocardial cells by short-term and long-term coculture with OP9 stromal cells expressing Notch ligands and inhibition of Notch activity. We examined the transcriptional profile and chromatin accessibility landscape for each condition, integrated transcriptomic, transcription factor occupancy, chromatin accessibility, and proteomic datasets. We generated in vitro and in vivo models with CRISPR-Cas9-edited deletions of various noncoding regulatory elements and validated their regulatory potential.

RESULTS:
We identified primary and secondary transcriptional responses to Notch ligands in the mouse embryonic endocardium, and a NOTCH-dependent transcriptional signature in valve development and disease. By defining the changes in the chromatin accessibility landscape and integrating with the landscape in developing mouse endocardium and adult human valves, we identify potential noncoding regulatory elements, validated selected candidates, propose interacting cofactors, and define the timeframe of their regulatory activity. Additionally, we found cooperative transcriptional repression with Hippo pathway by inhibiting nuclear Yap (Yes-associated protein) activity in the endocardium during cardiac valve development.

CONCLUSIONS:

Sequential Notch-dependent transcriptional regulation in the embryonic endocardium involves multiple factors. Notch activates certain noncoding elements through these factors and simultaneously suppresses elements that could hinder cardiac valve development and homeostasis. Biorxviv:
https://www.biorxiv.org/content/10.1101/2023.03.23.533882v1.full
.
Prey size preference in the tokay gecko (Gekko gecko)
Authors: Probst Anja , Ringler Eva , Szabo Birgit 
Published: November 2023

Abstract
The optimal foraging theory posits that animals aim to maximize energy intake while minimizing predation and handling costs during foraging. Most observed animal behaviour supports this theory, but occasional deviations provide insights into the ecological factors that shape foraging decisions. We tested prey-size preference using a two-choice test between different prey sizes in tokay geckos. We expected geckos to prefer larger prey and decision latencies to be longer when discrimination was more difficult and when small prey was offered. Geckos preferred larger prey when the size difference was large, although decision latency remained consistent. This aligns with prior research on sit-and-wait predators. Together with previous findings showing freezing behaviour after prey capture in tokay geckos, our findings suggest a strong influence of predator avoidance on foraging decisions opening up a new avenue for future research investigating the link between decision making and predator avoidance in tokay geckos.
Religious Approaches to Constitutionalism: Empirical Scholarship and Exceptionalism
Authors: Powell Russell 
Published: November 2023

Abstract
Nearly half of all countries have official religions or give preference to specific religious traditions. Most countries with an official religion are majority Muslim; however, most of those with a preference for particular religious traditions are majority Christian. This paper considers empirical data related to constitutional references to specific religions as a framework for a discussion of the comparative constitutional histories of Turkey and the Republic of Ireland. Both moved from systems that preferred their majority religions to ostensive neutrality. This analysis reinforces the importance of religion in law and policy regardless of cultural context and constitutional choices. Constitutional drafters have established a number of approaches to the treatment of religion, including freedom of religion, establishment of religion, separation of religion and state, neutrality, official religion, conformity, repugnancy, and sources of law/legislation. Although these linguistic choices are significant, they may not result in consistent practices across jurisdictions.
Colloquium 5 Aristotle’s Rejection of Mathematized Metaphysics
Authors: Katz Emily 
Published: November 2023

Abstract
According to Aristotle, those who seek mathematical principles of sensible things are looking in entirely the wrong place. But despite his strong opposition to mathematized metaphysics, Aristotle does not outright reject mathematical explanation of the natural world. In fact, he argues that mathematics does explain certain sensible phenomena, that the natural world has many mathematical patterns and features, and that this is often not mere coincidence. That he devotes two books of his Metaphysics to shoring up the boundary between mathematics and metaphysics indicates that this issue is crucially important to him. Yet it receives little systematic scholarly discussion. I take up the issue by examining Aristotle’s treatment of the sensible phenomena that have mathematical explanations. This examination shows that—and why—on his view, mathematics explains many things about the natural world, but not the most fundamental things.