bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ1-TNFα regulated secretion of neutrophil chemokines is independent of epithelial-mesenchymal transitions in breast tumor cells
Authors: SenGupta Shuvasree , Cohen Erez , Serrenho Joseph , Ott Kaleb , Coulombe Pierre A. , Parent Carole A. 
Published: October 2024

ABSTRACTNeutrophils have tumor-promoting roles in breast cancer and are detected in higher numbers in aggressive breast tumors. How aggressive breast tumors recruit neutrophils remains undefined. Here, we investigated the roles of TGF-β1 and TNF-α in the regulation of neutrophil recruitment by breast cancer cells. TGF-β1 and TNF-α are pro-inflammatory factors upregulated in breast tumors and induce epithelial to mesenchymal transitions (EMT), a process linked to cancer cell aggressiveness. We report that, as expected, dual treatment with TGF-β1 and TNF-α induces EMT signatures in premalignant M2 cells, which are part of the MCF10A breast cancer progression model. Conditioned media (CM) harvested from M2 cells treated with TGF-β1/TNF-α gives rise to amplified neutrophil chemotaxis compared to CM from control M2 cells. This response correlates with higher levels of the neutrophil chemokines CXCL1, CXCL2, and CXCL8 and is significantly attenuated in the presence of a CXCL8-neutralizing antibody. Furthermore, we found that secretion of CXCL1 and CXCL8 from treated M2 cells depends on p38MAPK activity. By combining gene editing, immunological and biochemical approaches, we show that the regulation of neutrophil recruitment and EMT signatures are not mechanistically linked in treated M2 cells. Finally, analysis of publicly available cancer cell line transcriptomic databases revealed a significant correlation between CXCL8 and TGF-β1/TNF-α-regulated or effector genes in breast cancer. Together, our findings establish a novel role for the TGF-β1/TNF-α/p38 MAPK signaling axis in regulating neutrophil recruitment in breast cancer, independent of TGF-β1/TNF-α regulated EMT.
Novel Transgenic Humanized Alpha-1 Antitrypsin Deficiency Mouse Model on MurineSERPINA1Null Background
Authors: Oshins Regina , Aranyos Alek M. , Grey Skylar , Mohammad Naweed , Lu Yuanqing , Lascano Jorge E. , Flagg Tammy , Serban Karina , Brantly Mark , Khodayari Nazli 
Published: October 2024

ABSTRACTAlpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by accumulation of misfolded α-1 antitrypsin within hepatocytes. AATD patients are prone to develop liver disease that remains undiagnosed until the late stages of the disease. Due to challenges in manipulating the α-1 antitrypsin genes in mice, determining a true loss of function of α-1 antitrypsin in previous AATD mouse models has been challenging. Here, we report generation and liver characterization of a new humanized transgenic mouse model for AATD with a background of a CRISPR-Cas9 generatedSERPINA1-null mouse. Male and female transgenic mice for normal (Pi*M) and mutant (Pi*Z) variants of human α-1 antitrypsin at 4-6 months of age were subjected to this study. The accumulation of human α-1 antitrypsin in the hepatocytes and fibrotic features of the liver were monitored by performing an in vivo study. We demonstrate a strong liver phenotype satisfying clinically relevant manifestations of liver pathology associated with AATD, including hepatic accumulation of human α-1 antitrypsin globules, liver deposition of extracellular matrix proteins, hepatic ER stress, and liver fibrosis in Pi*Z mice, in addition to mild systemic inflammation. In addition to major phenotypic criteria of AATD-associated liver fibrosis, accompanying single-nucleus RNA-seq data demonstrate activation of pathways associated with liver metabolic changes, inflammation, and regeneration. Data from this study suggest our humanized transgenic AATD mouse model could provide a suitable model to study α-1 antitrypsin loss of function, replicate the pathophysiology of AATD associated liver disease, and evaluate therapeutic reagents against this disease.NEW & NOTEWORTHYWe have characterized a new humanized transgenic mouse model of α-1 antitrypsin deficiency with aSERPINA1-null background that shows strong manifestations of liver disease. Our data explores the altered phenotype of α-1 antitrypsin deficient hepatocytes and suggests a relationship between liver cell types during disease progression. This model may become a useful tool for investigating α-1 antitrypsin loss of function, pathogenic mechanisms, and for drug discovery aimed at both prevention and treatment of the disease.
Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation
Authors: Caldwell Allyson , Yang Liheng , Scheef Elizabeth A. , Kaur Amitinder , Coyne Carolyn B. 
Published: October 2024

AbstractThroughout evolution, the placenta has diversified in both structure and cellular composition while maintaining its fundamental function. Trophoblasts are fetal-derived cells responsible for nourishing and protecting the developing fetus and are a universal component of all placentas. While primate placentas exhibit many shared morphological features, species-specific differences in gene expression remain largely unexplored, primarily due to the lack of suitablein vitromodels. To address this gap, we developed organoids from rhesus macaque placentas, including trophoblast and maternal-derived decidua types, and compared them with organoids derived from human placentas. We performed comparative single-cell RNA sequencing to delineate shared and distinct transcriptional signatures between rhesus macaque and human trophoblasts. We further defined the differentiation trajectories leading to the multinucleated syncytiotrophoblast, highlighting both shared and unique transcriptional signatures between rhesus macaque and human placentas. This work establishes novelin vitromodels of the non-human primate placenta and characterizes distinct trophoblast gene profiles in rhesus macaques and humans, providing insights into interspecies variations in placental biology.
Reconstructing signaling history of single cells with imaging-based molecular recording
Authors: Hao Kai , Barrett Mykel , Samadi Zainalabedin , Zarezadeh Amirhossein , McGrath Yuka , Askary Amjad 
Published: October 2024

AbstractThe intensity and duration of biological signals encode information that allows a few pathways to regulate a wide array of cellular behaviors. Despite the central importance of signaling in biomedical research, our ability to quantify it in individual cells over time remains limited. Here, we introduce INSCRIBE, an approach for reconstructing signaling history in single cells using endpoint fluorescence images. By regulating a CRISPR base editor, INSCRIBE generates mutations in genomic target sequences, at a rate proportional to signaling activity. The number of edits is then recovered through a novel ratiometric readout strategy, from images of two fluorescence channels. We engineered human cell lines for recording WNT and BMP pathway activity, and demonstrated that INSCRIBE faithfully recovers both the intensity and duration of signaling. Further, we used INSCRIBE to study the variability of cellular response to WNT and BMP stimulation, and test whether the magnitude of response is a stable, heritable trait. We found a persistent memory in the BMP pathway. Progeny of cells with higher BMP response levels are likely to respond more strongly to a second BMP stimulation, up to 3 weeks later. Together, our results establish a scalable platform for genetic recording andin situreadout of signaling history in single cells, advancing quantitative analysis of cell-cell communication during development and disease.
Design of a biomolecular adaptive controller to restore sustained periodic behavior
Authors: Bisso Frank Britto , Dey Subham , Stan Guy-Bart , Cuba Samaniego Christian 
Published: October 2024

AbstractPeriodic behavior is a widespread biological phenomenon occurring across various spatiotemporal scales, where upstream stimuli are encoded into dynamic intracellular signals such as oscillations, varying in duration, amplitude, and frequency. Disruptions to this periodicity can lead to a range of pathologies, for which we propose an adaptive feedback controller with an Incoherent Feedforward Loop (IFFL)-like topology, based on chemical reactions, designed to restore sustained oscillations in systems that have lost their periodicity. By approximating the controller’s dynamics, we defined the design requirements for the first implementation of a biomolecular adaptive controller and tested its applicability for destabilizing the steady–state behavior of a self-inhibiting gene. Numerical simulations illustrate the adaptive behavior of the controller and its ability to tune both the amplitude and the period of the resulting oscillations.
How could you think that? Supervisor misattribution leads to reduced subsequent employee organizational citizenship behavior
Authors: Mcilveene Timothy R. , Davis Maggie , White Sonia 
Published: October 2024

PurposeFrom a social cognitive perspective, the current study examines how the relationship between the employee and the organization changes following supervisor motive misattribution of organizational citizenship behavior (OCB).Design/methodology/approachThe current study utilizes an experimental vignette methodology (EVM), linear regression and Hayes' (2017) Process Version 4 macro in SPSS to examine the relationships between supervisor misattribution of employee OCB, personality and individual differences and future organizational citizenship behavior intentions.FindingsResults indicate that supervisor misattribution of employee OCB, specifically when the act is attributed to impression management, will reduce the intention to engage in future OCBs. Results also indicate that this negative relationship is enhanced when subordinates are high in openness.Research limitations/implicationsThis study extends social exchange theory by demonstrating how the misattribution of motivation to perform OCBs creates a negative social exchange and discourages future organizational citizenship behavior from the employee. The current research demonstrates the importance of supervisors understanding employees' motivations for engaging in (OCB). If an employee engages in OCB based on intrinsic motivation, such as a desire to help others, and their motivation is attributed to external motivation, such as impression management, the employee may feel misunderstood and believe their values and motivations are incorrectly perceived, leading to reduced OCB.Originality/valueThe current research is examined using EVM. By immersing participants in realistic hypothetical scenarios, experimental vignette methodology allows researchers to explore the intricacies of decision-making across unique scenarios, unraveling both the “why” and the “what next” behind decision-making.
Investigating the influence of perceived humanization of service encounters on value creation of chatbot-assisted services
Authors: Khan Md Irfanuzzaman , Fatima Johra Kayeser , Bahmannia Somayeh , Chatrath Sarvjeet Kaur , Dale Naomi F. , Johns Raechel 
Published: October 2024

PurposeWhile prior research has examined customer acceptance of humanized chatbots, the mechanisms through which they influence customer value creation remain unclear. This study aims to investigate the emerging concept of Perceived Humanization (PH), examining how hedonic motivation, social influence and anthropomorphism influence value creation through the serial mediation of PH and trust. The moderating roles of rapport and social presence are also explored.Design/methodology/approachBased on data from an online survey involving 257 respondents, this study employs Partial Least Squares Structural Equation Modeling utilizing SmartPLS3 software.FindingsHedonic motivation leads to value creation via two routes: PH and affective trust; and PH and cognitive trust. Social influence and anthropomorphism also positively impact value creation through similar pathways. Rapport moderates the impact of social influence on PH, while social presence moderates the relationship between PH and both affective and cognitive trust. A cross-cultural analysis of China, India and New Zealand highlights varying cultural dimensions influencing PH and its effects on value creation.Practical implicationsFor practitioners in the tourism industry, the findings highlight the strategic importance of enhancing PH in chatbot interactions. By understanding and optimizing these elements, businesses can significantly improve their customer value-creation process.Originality/valueThis study contributes to the service marketing literature by generating a comprehensive framework for the comprehension and application of PH. Its cross-cultural perspective provides rich insights, offering valuable information for service marketers aiming to thrive in the dynamic and competitive tourism industry.
Evaluation of real estate investment performance of insurance companies by NHF Act in curbing housing deficit in Nigeria
Authors: Inuwa Mohammed Danlami , Said Rosli 
Published: October 2024

PurposeThe purpose of this study is to evaluate the real estate investment performance portfolio decision-making of the insurance firms by the National Housing Fund (NHF) Act in reducing the housing deficit in Nigeria. The insurance companies' gross premium, real estate investment and return on investment trends for the period 2014–2019 were evaluated, to determine the extent of their investment in real estate in Nigeria, this ought to have reduced the shortfall in housing.Design/methodology/approachBoth primary and secondary sources were used. Cronbach’s alpha was used for testing the reliability. The Friedman mean rank with Chi-square was used for different types of real estate investment properties and for reasons for investing in real estate by insurance companies in Nigeria. The test for normality was conducted using the Shapiro–Wilk and Spearman correlation for the significance. The percentage and the data envelopment analysis frontier model were used for measuring performance and efficiency.FindingsThe results showed that the majority of real estate investments made by insurance companies were in commercial and land buying and reselling and that their performance was below average. However, their motivation for investing is not toward the NHF Act but rather for diversification and increasing their capital.Originality/valueTo the best of the authors’ knowledge, this is one of the first studies in Nigeria that looked at how well insurance firms have performed investing in real estate as required by the NHF Act. However, the new Act, the National Housing Fund (Establishment) Act of 2018 which was put on hold due to flaws, affected data availability beyond 2019.
Pollination‐related plant traits under environmental changes: Seasonal and daily mismatches produce temporal constraints
Authors: Leclerc Mathieu A. J. , Gibernau Marc , Pincebourde Sylvain 
Published: October 2024

Abstract

Pollination is a key tenet of ecosystem sustainability and food security, but it is threatened by climate change. While many studies investigated the response of plant‐pollination traits to temperature, few attempted multifactorial and integrative approaches with multiple floral traits.

We determined which plant‐pollination traits were disrupted by environmental changes and the consequence for plant fitness. We focused on the thermogenic plant, Arum italicum, which relies on floral scent and heat production to attract its pollinators with a deceptive strategy. In a field mesocosm, we measured the response of floral phenology, thermogenesis traits, scent and plant fitness to experimental changes in shade level, water supply and soil temperature. In the laboratory, we exposed plants to extreme heat to determine the thermoregulation ability at high temperatures.

Plant fitness decreased dramatically in response to soil warming and the level of shade. While both factors caused a lower number of inflorescences, soil warming was mostly responsible for the crash in number of fruits.

The plant traits related to thermogenesis and scent were relatively resilient to the environmental changes in the mesocosm and were unlikely to produce the observed decrease in plant fitness. First, environmental changes only weakly modified the scent composition. Second, the appendix regulated its maximal temperature almost perfectly, while stamen regulated imperfectly. In the laboratory experiment, the appendix maintained a thermal gradient supposedly to improve scent emission while stamen became cooler than ambient air, possibly preventing the pollinators from overheating within the floral chamber.

By contrast, the phenology of flowering was drastically modified. Flowers appeared earlier in the season in response to soil warming (by 39 days) or absence of shade (by 19 days). At the daily scale, flowering hour did not change across the season resulting in plants flowering before sunset late in the season and before the pollinator activity window (mostly nocturnal). The strong shift observed in the flowering period may induce a temporal mismatch with this pollinator both early and late in the season when the insects may not be active so early in the spring and during daytime, respectively, thereby altering plant fitness.

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A simple model of internal and external balance for resource‐rich developing countries
Authors: Davies M. H. , Schröder M. 
Published: October 2024

AbstractWe present a simple model of internal and external balance that incorporates key features of resource‐rich developing countries (RRDCs). The main result is that ‘government take’—the ratio of fiscal resource revenue to resource output—is a key determinant of the equilibrium real exchange rate (ERER) in these countries. Examining the case of Papua New Guinea, which has grappled with foreign exchange restrictions since 2015, we find that about half of the RER overvaluation estimated at 26% in 2019 would disappear if the current low level of government take was to be lifted to its long‐term average. The analysis has two key takeaways for RRDCs. First, changes in the government take require adjustments to the RER and fiscal policy to maintain internal and external balance. Second, economic adjustments to falls in the take are difficult; therefore, policies seeking to stabilise the take over time to promote macroeconomic stability are recommended.
Nutrient content and ultra‐performance liquid chromatography tandem mass spectrometry metabolomic comparative analysis of Lithocarpus corneus and Lithocarpus pachylepis
Authors: Deng Jinqing , Yin Xiufang , Shen Hongjian , Liu Biting , Ye Jiarong , Hu Yufan , Li Junren , Liao Boyong 
Published: October 2024

AbstractChina possesses abundant species resources in genus Lithocarpus Blume, commonly known as “acorns.” These nuts are traditional foods in China, holding significant potential for local specialty food and rural economic development. To explore their edible value, we compared the nutritional components and metabolites between the fruits of Lithocarpus corneus (YD) and Lithocarpus pachylepis (HL), which are cultivated widely in south of China. Non‐targeted metabolomics analysis of YD and HL was performed using ultra‐performance liquid chromatography tandem mass spectrometry technology. A total of eight classes of differential metabolites (DAMs) were detected: alkaloids, amino acids and peptides, carbohydrates, fatty acids, polyketides, shikimates and phenylpropanoids, terpenoids, and other metabolites. In the positive ion mode, 225 DAMs were identified, whereas in the negative ion mode, 116 DAMs were identified. KEGG pathway enrichment analysis showed that the differentially abundant metabolites were generally enriched in three pathways: aminoacyl‐tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and ABC transporters. The nutritional content of YD has higher moisture, fructose, and total flavonoid levels, but lower starch, protein, fat, glucose, sucrose, and total sugar content than HL. Additionally, YD contains more Ca, K, P, and Fe, but less Mg and Zn compared to HL. Analyses indicate that YD is nutrient‐rich and beneficial, making it suitable for further development. Two species of Lithocarpus contain nandrolone, suggesting a new direction for specialty food development. The unique chemical composition and rich nutritional content of Lithocarpus fruits provide a theoretical basis for their development and application as food resources.Practical ApplicationL. corneus and L. pachylepis are traditional Chinese nuts, rich in starch, minerals, and flavonoids, making them suitable for consumption or use as food constituents. Their fruits contain various unique natural chemical compounds, indicating high application value and development potential.
Predictors of emergency medical transport refusal following opioid overdose in Washington, DC
Authors: Turley Ben , Zamore Kenan , Holman Robert P. 
Published: October 2024

AbstractBackground and AimsPatient initiated transport refusal during Emergency Medical Service (EMS) opioid overdose encounters has become an endemic problem. This study aimed to quantify circumstantial and environmental factors which predict refusal of further care.DesignIn this cross‐sectional analysis, a case definition for opioid overdose was applied retrospectively to EMS encounters. Selected cases had sociodemographic and situational/incident variables extracted using patient information and free text searches of case narratives. 50 unique binary variables were used to build a logistic model.SettingPrehospital EMS overdose encounters in Washington, DC, USA, from July 2017 to July 2023.ParticipantsOf EMS encounters in the study timeframe, 14 587 cases were selected as opioid overdoses.MeasurementsPredicted probability for covariates was the outcome variable. Model performance was assessed using Stratified K‐Fold Cross‐Validation and scored with positive predictive value, sensitivity and F1. Prediction accuracy and McFadden's pseudo‐R squared are also determined.FindingsThe model achieved a predictive accuracy of 78% with a high positive predictive value (0.83) and moderate sensitivity (0.68). Bystander type influenced the refusal outcome, with decreased refusal probability associated with family (nondescript) (−28%) and parents (−16%), while presence of a girlfriend increased it (+28%). Negative situational factors like noted physical trauma (−62%), poor weather (−14%) and lack of housing (−14%) decreased refusal probability. Characteristics of the emergency response team, like a prior crew member encounter (+20%) or crew experience <1 year (−36%), had a variable association with transport.ConclusionsRefusal of emergency transport for opioid overdose cases in Washington, DC, USA, has expanded by 43.8% since 2017. Several social, environmental and systematic factors can predict this refusal. Logistic regression models can be used to quantify broad categories of behavior in surveillance medical research.