bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling liver cancer microenvironment: novel 3D culture system as a potential anti-cancer drug screening tool
Authors: Hrout Ala’a Al , Cervantes-Gracia Karla , Chahwan Richard , Amin Amr 
Published: November 2021

ABSTRACTThe tumor microenvironment and its contribution to tumorigenesis has been a focal highlight in recent years. A two-way communication between the tumor and the surrounding microenvironment sustains and contributes to the growth and metastasis of tumors. Progression and metastasis of hepatocellular carcinoma have been reported to be exceedingly influenced by diverse microenvironmental cues. In this study, we present a 3D-culture model of liver cancer to better mimic in vivo tumor settings. By creating novel 3D co-culture model that combines free-floating and scaffold based 3D-culture techniques of liver cancer cells and fibroblasts, we aimed to establish a simple albeit reproducible ex vivo cancer microenvironment model that captures tumor-stroma interactions. The model presented herein exhibited unique gene expression and protein expression profiles when compared to 2D and 3D mono-cultures of liver cancer cells. Our results showed that in vivo like conditions cannot be mimicked by simply growing cancer cells as spheroids, but by co-culturing them with 3D fibroblast with which they were able to cross-talk. This was evident by the upregulation of several pathways involved in HCC, and the increase in secreted factors by co-cultured cancer cells, many of which are also involved in tumor-stroma interactions. Compared to the conventional 2D culture, the proposed model exhibits an increase in the expression of genes associated with development, progression, and poor prognosis of HCC. Our results correlated with an aggressive outcome that better mirrors in vivo HCC, and therefore, a more reliable platform for molecular understanding of HCC and possibly better anti-cancer drug screening.
Trachymyrmex septentrionalis ant microbiome assembly is unique to individual colonies and castes
Authors: Green Emily A. , Klassen Jonathan L. 
Published: November 2021

ABSTRACTWithin social insect colonies, microbiomes often differ between castes due to their different functional roles, and between colony locations. Trachymyrmex septentrionalis fungus-growing ants form colonies throughout the eastern USA and Northern Mexico that include workers, female and male alates (unmated reproductive castes), larvae, and pupae. How T. septentrionalis microbiomes vary across this geographic range and between castes is unknown. Our sampling of individual ants from colonies across the Eastern USA revealed a conserved T. septentrionalis worker ant microbiome, and that worker ant microbiomes are more conserved within colonies than between them. A deeper sampling of individual ants from two colonies that included all available castes (pupae, larvae, workers, female and male alates), from both before and after adaptation to controlled laboratory conditions, revealed that ant microbiomes from each colony, caste, and rearing condition were typically conserved within but not between each sampling category. Tenericute bacterial symbionts were especially abundant in these ant microbiomes and varied widely in abundance between sampling categories. This study demonstrates how individual insect colonies primarily drive the composition of their microbiomes, and that these microbiomes are further modified by developmental differences between insect castes and the different environmental conditions experienced by each colony.IMPORTANCEThis study investigates microbiome assembly in the fungus-growing ant Trachymyrmex septentrionalis, showing how colony, caste, and lab adaptation influences the microbiome and revealing unique patterns of Mollicute symbiont abundance. We find that ant microbiomes differ strongly between colonies but less so within colonies. Microbiomes of different castes and following lab adaptation also differ in a colony-specific manner. This study advances understanding of the nature of individuality in social insect microbiomes, and cautions against the common practice of only sampling a limited number of populations to understand microbiome diversity and function.
Characteristics analysis of behavioural portfolio theory in the Markowitz portfolio theory framework
Authors: Mittal Saksham , Bhattacharya Sujoy , Mandal Satrajit 
Published: November 2021

PurposeIn recent times, behavioural models for asset allocation have been getting more attention due to their probabilistic modelling for scenario consideration. Many investors are thinking about the trade-offs and benefits of using behavioural models over conventional mean-variance models. In this study, the authors compare asset allocations generated by the behavioural portfolio theory (BPT) developed by Shefrin and Statman (2000) against the Markowitz (1952) mean-variance theory (MVT).Design/methodology/approachThe data used have been culled from BRICS countries' major index constituents from 2009 to 2019. The authors consider a single period economy and generate future probable outcomes based on historical data in order to determine BPT optimal portfolios.FindingsThis study shows that a fair number of portfolios satisfy the first entry constraint of the BPT model. BPT optimal portfolio exhibits high risk and higher returns as compared to typical Markowitz optimal portfolio.Originality/valueThe BRICS countries' data were used because the dynamics of the emerging markets are significantly different from the developed markets, and many investors have been considering emerging markets as their new investment avenues.
Stable Isotopes and Halogen Geochemistry of the Huayuan Carbonate‐hosted Pb‐Zn Ore District, South China: Implications for the Salt Source of Ore‐forming Fluids
Authors: YANG Zhen , JIANG Mengjie , ZHAO Shaorui , DING Zhenju , HE Mouchun 
Published: November 2021

AbstractThe Huayuan Pb‐Zn ore district in China, located in western Hunan Province, is a giant carbonate‐hosted Pb‐Zn ore district. The source of ore‐forming brines in this ore district remains poorly constrained. Whether the highly saline brines are derived from evaporated seawater or dissolved evaporates continues to be intensely debated. Carbonate minerals associated with Pb‐Zn mineralization have δ13CV‐PDB and δ18OV‐SMOW values ranging from −5.55‰ to +1.35‰ (mean value of −0.69‰; n = 14) and +16.28‰ to +25.05‰ (mean value of +20.22‰; n = 14), respectively. This indicates that carbonate minerals are dominantly formed from dissolved ore‐hosted carbonate rocks. The δ34S values of sulfides range from +20.2‰ to +36.8‰, with an average value of +30.0‰ (n = 27). These results suggest that sulfur is predominantly derived from the thermochemical sulfate reduction of marine sulfate. The crush‐leach analyzed solute data of fluid inclusions in sphalerite show the ore‐forming fluids have Cl/Br molar ratios range from 118 to 384, and Na/Br molar ratios from 39 to 160 (n = 8). These Cl/Br ratios of hydrothermal fluid are much lower than those of seawater (657 to 564), but are consistent with bittern brines through early halite precipitation. We propose that ore‐forming fluids are mainly derived from evaporitic basin brines, which leached base metals from the basement and/or country rocks. The brine then migrated to the basin margins through clastic rocks of basement and then precipitated sulfides by thermochemical sulfate reduction.
Formation, contents, functions of exosomes and their potential in lung cancer diagnostics and therapeutics
Authors: Xia Zhenkun , Qing Bei , Wang Wei , Gu Linguo , Chen Hongzuo , Yuan Yunchang 
Published: November 2021

AbstractLung cancer is the leading cause of cancer‐related death worldwide due to diagnosis in the advanced stage and drug resistance in the subsequent treatments. Development of novel diagnostic and therapeutic methods is urged to improve the disease outcome. Exosomes are nano‐sized vehicles which transport different types of biomolecules intercellularly, including DNA, RNA and proteins, and are implicated in cross‐talk between cells and their surrounding microenvironment. Tumor‐derived exosomes (TEXs) have been revealed to strongly influence the tumor microenvironment, antitumor immunoregulatory activities, tumor progression and metastasis. Potential of TEXs as biomarkers for lung cancer diagnosis, prognosis and treatment prediction is supported by numerous studies. Moreover, exosomes have been proposed to be promising drug carriers. Here, we review the mechanisms of exosomal formation and uptake, the functions of exosomes in carcinogenesis, and potential clinical utility of exosomes as biomarkers, tumor vaccine and drug delivery vehicles in the diagnosis and therapeutics of lung cancer.
Novel small molecule inhibition of IKK/NF‐κB activation reduces markers of senescence and improves healthspan in mouse models of aging
Authors: Zhang Lei , Zhao Jing , Mu Xiaodong , McGowan Sara J. , Angelini Luise , O'Kelly Ryan D. , Yousefzadeh Matthew J. , Sakamoto Ayumi , Aversa Zaira , LeBrasseur Nathan K. , Suh Yousin , Huard Johnny , Kamenecka Theodore M. , Niedernhofer Laura J. , Robbins Paul D. 
Published: November 2021

AbstractConstitutive NF‐κB activation is associated with cellular senescence and stem cell dysfunction and rare variants in NF‐κB family members are enriched in centenarians. We recently identified a novel small molecule (SR12343) that inhibits IKK/NF‐κB activation by disrupting the association between IKKβ and NEMO. Here we investigated the therapeutic effects of SR12343 on senescence and aging in three different mouse models. SR12343 reduced senescence‐associated beta‐galactosidase (SA‐β‐gal) activity in oxidative stress‐induced senescent mouse embryonic fibroblasts as well as in etoposide‐induced senescent human IMR90 cells. Chronic administration of SR12343 to the Ercc1−/∆ and Zmpste24−/− mouse models of accelerated aging reduced markers of cellular senescence and SASP and improved multiple parameters of aging. SR12343 also reduced markers of senescence and increased muscle fiber size in 2‐year‐old WT mice. Taken together, these results demonstrate that IKK/NF‐κB signaling pathway represents a promising target for reducing markers of cellular senescence, extending healthspan and treating age‐related diseases.
University students' adherence and vaccination attitudes during the COVID‐19 pandemic: Focusing on costs and benefits
Authors: Kulcar Vanessa , Straganz Christoph , Kreh Alexander , Siller Heidi , File Norbert , Canazei Markus , Bork‐Hüffer Tabea , Juen Barbara 
Published: November 2021

AbstractNumerous measures were implemented to contain the COVID‐19 pandemic. Adhering to these measures as well as getting vaccinated is associated with subjective costs and benefits. Since young people like university students largely feel less vulnerable to the virus, other costs and benefits than health might be more decisive for them. This article combines the results of a qualitative and a quantitative longitudinal study conducted with university students mainly living in Tyrol, Austria. The studies focused on the second wave of infections of the COVID‐19 pandemic. Health concerns, altruistic concerns, worrying about the economic consequences of the measures and reactance played an important role for students in deciding what measures to follow and their vaccination attitudes. The effects were partially mediated by understanding the measures' necessity. Qualitative results enabled further insights into thought processes during these decisions and revealed additional aspects, such as concerns about mental health consequences. This research suggests that students make their decisions about adherence and vaccinations based on a variety of aspects that they weigh against each other. Understanding the individual assessments of costs and benefits is crucial to promote both adherence to the measures against the COVID‐19 pandemic and vaccination readiness.
Rapid morphological change in a small mammal species after habitat fragmentation over the past half‐century
Authors: Li Jiaqi , Dirzo Rodolfo , Wang Yanping , Zeng Di , Liu Juan , Ren Peng , Zhong Lei , Ding Ping 
Published: November 2021

AbstractAimTo compare the rapid shifts in body size of mainland and island populations of a native rodent and examine the mechanisms underlying these changes.LocationThousand Island Lake, China, which was created in 1959 when the Xin'anjiang Dam was constructed for generating hydroelectricity.TaxonThe Chinese white‐bellied rat,Niviventer confucianus.MethodsField surveys were conducted from 2015 to 2018 to collect data on body size of the rodents from a set of islands and nearby mainland sites. We constructed multiple linear models to examine the relationships between body size (length and mass) of rodents and biological variables (predators, competitors and food availability). We also conducted structural equation modelling (SEM) by constructing models via confirmatory path analysis.ResultsAll island populations ofN.confucianushad significantly larger body size (both body mass and body length) than their mainland counterparts. Moreover, populations on small and more isolated islands had larger body size than their relatives on big islands. The relative absence of predators (large‐bodied mammals, snakes and raptors) on islands was most strongly associated with shifts in the body size of rodents. The documented changes occurred after only a half‐century of fragmentation.Main conclusionsThe observed rapid body enlargement of rodents after habitat fragmentation is consistent with a release from predation pressure. SEM indicated that island area, rather than island isolation, had positive effects on the abundance of predators, interspecific competitors and food resources, which then had an indirect impact on body size of the rodents. In this study, we report a remarkably rapid case of mammal morphological shifts in a small mammal in response to habitat fragmentation. Given the omnipresence of dams and other anthropogenic disturbances, our findings suggest that a wave of rapid phenotypic shifts in terrestrial vertebrates is taking place in the Anthropocene.
Generalization of sustained neurophysiological effects of short‐term auditory 13‐Hz stimulation to neighbouring frequency representation in humans
Authors: Kleeva Daria F. , Rebreikina Anna B. , Soghoyan Gurgen A. , Kostanian Daria G. , Neklyudova Anastacia N. , Sysoeva Olga V. 
Published: November 2021

AbstractA fuller understanding of the effects of auditory tetanization in humans would inform better language and sensory learning paradigms; however, there are still unanswered questions. Here, we probe sustained changes in the event‐related potentials (ERPs) to 1020‐ and 980‐Hz tones following a rapid presentation of 1020‐Hz tone (every 75 ms, 13.3 Hz, tetanization). Consistent with some previous studies, we revealed the increase in the P2 ERP component after tetanization. Contrary to some other studies, we did not observe the expected N1 increase after tetanization even in the identical experimental sequence. We detected a significant N1 decrease after tetanization. Expanding previous research, we showed that P2 increase and N1 decrease are not specific to the stimulus type (tetanized 1020 Hz and non‐tetanized 980 Hz), suggesting the generalizability of tetanization effect to the not‐stimulated auditory tones, at least to those of the neighbouring frequency. The ERPs' tetanization effects were observed for at least 30 min—the most prolonged interval examined, consistent with the duration of long‐term potentiation, LTP. In addition, the tetanization effects were detectable in the blocks where the participants watched muted videos, an experimental setting that can be easily used in children and other challenging groups. Thus, auditory 13‐Hz stimulation affects brain processing of tones including those of neighbouring frequencies.
Sitagliptin's renoprotective effect in a diabetic nephropathy model in rats: The potential role of PI3K/AKT pathway
Authors: Mohamed Reham Hussein , Sedky Amina Ahmed , Hamam Ghada Galal , Elkhateb Lobna , Kamar Sherif A. , Adel Seham , Tawfik Sherin Shafik 
Published: November 2021

AbstractManagement of diabetic nephropathy (DN) is far from satisfactory. There is a rising role of the involvement of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) pathway in the pathogenesis of DN. This study aimed at investigating the renoprotective effects of PI3K/AKT pathway via sitagliptin in a rat model of DN. Thirty‐two male Wistar rats were divided into four groups (eight rats each): (I) control, (II) sitagliptin, (III) DN, and (IV) DN + sitagliptin. Fasting blood glucose (FBG), kidney index, and kidney function tests in both blood and urine were measured. The levels of superoxide dismutase (SOD), tumor necrosis factor‐alpha (TNF‐α), and transforming growth factor‐beta (TGF‐β) and gene expressions of PI3K, pPI3K, AKT, and pAKT in renal tissue were detected. Renal histopathological and immunohistochemical studies were evaluated. DN + sitagliptin group showed significant decrease in FBG and kidney index, improvement in kidney function tests, and a decrease in levels of TNF‐α and TGF‐β in renal tissues compared with DN group. This was associated with significant increase in SOD and gene expressions of PI3K and AKT and their phosphorylated active forms in renal tissue in DN + sitagliptin group compared with DN group. Moreover, DN + sitagliptin group showed apparent decrease in amount of collagen fibers and expression of alpha‐smooth muscle actin (α‐SMA) compared with DN group. This work shows that sitagliptin improved renal functions and histopathological changes, impeded inflammation, and oxidative stress and upregulated PI3K/AKT pathway which highlights its renoprotective effects in a rat model of DN.
Land as a Global Commons?
Authors: Blomfield Megan 
Published: November 2021

ABSTRACTLand is becoming increasingly scarce relative to the demands of the global economy; a problem significantly exacerbated by climate change. In response, some have suggested that land should be conceptualised as a global commons. This framing might seem like an appealing way to promote sustainable and equitable land use. However, it is a poor fit for the worldʼs land because global commons are generally understood as resources located beyond state borders. I argue that land can be seen to fit the definition of a global commons, if viewed in a particular way; namely, as a biogeochemical resource system that sequesters carbon emissions. The question then arises whether land should be conceptualised as a global commons. I consider this question by reference to three contemporary problems of land justice (land grabbing, forced displacement, and unfairness in land‐based climate mitigation); arguing that the global‐commons framing will not be conducive to understanding or responding to these problems. I leave the question of how the global community should conceptualise land in the context of climate change open, claiming that any answer must include the voices and perspectives of those whose livelihoods and identities are closely connected to the land.
The impact of augmented reality on cognitive load and performance: A systematic review
Authors: Buchner Josef , Buntins Katja , Kerres Michael 
Published: November 2021

AbstractBackgroundPrevious studies on augmented reality‐enriched learning and training indicated conflicting results regarding the cognitive load involved: some authors report that AR can reduce cognitive load, others have shown that AR is perceived as cognitively demanding and can lead to poorer performance.ObjectivesThe aim of this study is to systematically analyse previous research on AR and cognitive load, including performance, and thus to be able to contribute to answering the question of the impact of AR on cognitive load when used in learning environments.MethodsThis study applied the systematic review method. A total of 58 studies were identified and analysed using rigorously defined inclusion and exclusion criteria. The results are now reported as a synthesis.Results and ConclusionsCompared to other technologies, AR seems to be less cognitively demanding and also leads to higher performance. However, these results are based on media comparison studies that have been criticized for years. The spatial AR type is better compared to see‐through AR. However, the latter can be improved by visual cues and the addition of learning activities, such as value‐added studies have revealed.Major takeawaysThe essential findings of this study are that the technology used, for example, AR glasses, can unnecessarily increase cognitive load and that still many studies focus on the comparison of AR with more traditional media. Less studies applied alternative research designs, for example, value‐added comparisons. However, such designs are better suited to investigate design principles for AR‐enriched learning environments, which can then in turn reduce cognitive load as well as positively affect performance.
Rad50 promotes ovarian cancer progression through NF‐κB activation
Authors: Li Yinuo , Wang Shourong , Li Peng , Li Yingwei , Liu Yao , Fang Haiya , Zhang Xiyu , Liu Zhaojian , Kong Beihua 
Published: November 2021

AbstractRad50 is a component of MRN (Mre11‐Rad50‐Nbs1), which participates in DNA double‐strand break repair and DNA‐damage checkpoint activation. Here, we sought to investigate the clinical and functional significance of Rad50 in high‐grade serous ovarian cancer (HGSOC). We found that Rad50 was frequently upregulated in HGSOCs and enhanced Rad50 expression inversely correlated with patient survival. In addition, ectopic expression of Rad50 promoted proliferation/invasion and induced EMT of ovarian cancer cells, whereas knockdown of Rad50 led to decreased aggressive behaviors. Mechanistic investigations revealed that Rad50 induced aggressiveness in HGSOC via activation of NF‐κB signaling pathway. Moreover, we identified CARD9 as an interacting protein of Rad50 in ovarian cancer cells and the activation of NF‐κB pathway by Rad50 is CARD9 dependent. Our findings provide evidence that Rad50 exhibits oncogenic property via NF‐κB activation in HGSOC.
Going home for tea and medals: How members of the flood risk management authorities in England construct flooding and flood risk management
Authors: Mehring Phiala , Geoghegan Hilary , Cloke Hannah L. , Clark Joanna M. 
Published: November 2021

AbstractThe construction of flooding and flood risk management are complex and there is potential for dissonance between individual and institutional understanding and experience of both. In this article, we start by investigating how flooding is managed and the change in paradigm from flood defence to more adaptive approaches, which embed resilience into flood risk management. Using analysis of semi‐structured interviews with members of the flood authorities in England, we explore how flood management authorities construct ‘flooding’ and establish that it is often defined by in‐the‐moment impacts. Whilst these in‐the‐moment impacts are understood to be devastating, there is less appreciation of long‐term human impacts of living at risk of flooding. We uncover how the construction of ‘flood risk management’ by the flood authorities is complicated by factors, such as the construction of resilience, availability of funding, technical expertise and responsibility fragmentation that the Floods and Water Management Act (2010) has created. We conclude that the differing constructions of flooding and flood risk management between flood management authorities in England hinder how flooding is managed. Therefore, we propose that a more nuanced understanding of flooding and flood risk management is essential for effective partnership working between flood risk management authorities and communities.