bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthotopic injection of an established syngeneic mouse oral cancer cell line (MOC1) induces a robust draining lymph node response
Authors: Kansal Vikash , Kinney Brendan L.C. , Schmitt Nicole C. 
Published: January 2024

ABSTRACTBackgroundPreclinical models are invaluable for studies on the pathogenesis and treatment of head and neck cancer. In recent years, there has been growing interest in the use of orthotopic syngeneic models, wherein head and neck cancer cell lines are injected into the oral cavity of immunocompetent mice. However, few such orthotopic models have been described in detail. In this brief report, we describe techniques for injection of mouse oral cancer 1 (MOC1) cells into the buccal mucosa and illustrate the tumor growth pattern, lymph node response, and changes in the tumor immune microenvironment over time.MethodsMOC1 cells were injected into the buccal mucosa of C57BL6 mice. Animals were sacrificed at 7, 14, 21, or 27 days. Tumors and lymph nodes were harvested and analyzed for immune cell subsets by flow cytometry.ResultsAll inoculated mice developed palpable buccal tumors by day 7 and required euthanasia for tumor burden and/or weight loss by day 27. Lymph node mapping showed that these tumors reliably drain to a submandibular lymph node, which enlarges considerably over time. As in MOC1 tumors in the flank, the proportion of intratumoral CD8+ T cells decreased over time, while neutrophilic myeloid cells increased dramatically. However, the pattern and time course of immune changes in the TME were slightly different in the orthotopic buccal model.ConclusionsWhen used orthotopically in the buccal mucosa, the MOC1 model induces a robust lymph node response and distinct pattern of immune cell infiltration, with peak immune infiltration by day 14.
Potent Estrogen Receptor β Agonists with Inhibitory ActivityIn Vitro, Fail to Suppress Xenografts of Endocrine-Resistant Cyclin-dependent Kinase 4/6 inhibitor-Resistant Breast Cancer Cells
Authors: Marcho Lynn M. , Coss Christopher C. , Xu Menglin , Datta Jharna , Manouchehri Jasmine M. , Cherian Mathew A. 
Published: January 2024

ABSTRACTObjectiveSeventy percent of newly diagnosed breast cancers are estrogen receptor-α positive and HER2/neu negative [1]. First-line treatments incorporate endocrine therapy and cyclin-dependent kinase 4/6 inhibitors [2]. However, therapy resistance occurs in most patients [3-5]. Hence, there is an urgent need for effective second-line treatments. We previously showed that the potent estrogen receptor-β agonists, OSU-ERb-12 and LY500307, synergized with the selective estrogen receptor modulator, tamoxifen, in vitro. Furthermore, we showed that these compounds inhibited endocrine-resistant and cyclin-dependent kinase 4/6-inhibitor-resistant estrogen receptor α-positive cell lines in vitro [6]. Here, we used fulvestrant- and abemaciclib-resistant T47D-derived cell line xenografts to determine the efficacy of the combination of OSU-ERb-12 and LY500307 with tamoxifen in vivo.ResultsDespite efficacy in vitro, treatments failed to reduce xenograft tumor volumes. Hence, we conclude that this treatment strategy lacks direct cancer cell-intrinsic cytotoxic efficacy in vivo.
Compositional pretraining improves computational efficiency and matches animal behavior on complex tasks
Authors: Hocker David , Constantinople Christine M. , Savin Cristina 
Published: January 2024

1AbstractRecurrent neural networks (RNN) are ubiquitously used in neuroscience to capture both neural dynamics and behaviors of living systems. However, when it comes to complex cognitive tasks, training RNNs with traditional methods can prove difficult and fall short of capturing crucial aspects of animal behavior. Here we propose a principled approach for identifying and incorporating compositional tasks as part of RNN training. Taking as target a temporal wagering task previously studied in rats, we design a pretraining curriculum of simpler cognitive tasks that reflect relevant sub-computations. We show that this pretraining substantially improves learning efficacy and is critical for RNNs to adopt similar strategies as rats, including long-timescale inference of latent states, which conventional pretraining approaches fail to capture. Mechanistically, our pretraining supports the development of slow dynamical systems features needed for implementing both inference and value-based decision making. Overall, our approach is an important step for endowing RNNs with relevant inductive biases, which is important when modeling complex behaviors that rely on multiple cognitive computations.
The role of m6A methyltransferase WTAP in inflammatory response of atherosclerosis through NF-κB/NLRP3 mediated pyroptosis
Authors: Hu Bing , He Mei , Sha Yanhua , Guo Fengxia 
Published: January 2024

AbstractBackgroundPyroptosis is a new form of pro-inflammatory programmed cell death that has been linked to the development of atherosclerosis (AS). However, its exact mechanisms are not known. N6-methyladenosine (m6A) methylation is the commonest and most abundant epigenetic modification of eukaryotic mRNAs. m6A methylation modulates pathological and physiological processes involved in cardiovascular diseases. However, the exact mechanism by which it regulates inflammation in AS is unclear.MethodsIn this study, the level of m6A and WTAP in CHD was explored. To determine the effect of WTAP on the release of pyrolysis-related proteins and pro-inflammatory cytokines, the expression of WTAP in lipopolysaccharide (LPS)-treated endothelial cells was silenced. Pyroptosis-related proteins and pro-inflammatory cytokines were quantified in the presence of NLRP3 shRNA (shNLRP3) and NF-kB shRNA (shNF-kB(p50)). The interaction of NF-kB and NLRP3 was examined through immunoprecipitation (CO-IP), immunofluorescence (IF) and GST-pull down assays.ResultIt was observed that lipopolysaccharide (LPS) induced Nod-like receptor protein 3 (NLRP3)-mediated pyroptosis and inflammation, both of which were abolished through the knockdown of WTAP. Interestingly, our results indicated that WTAP enhanced the function of nuclear factor κB (NF-κB) p50 (an NF-κB subunit) and that p50 could interact with NLRP3 in endothelial cells.ConclusionIn conclusion, these results suggested that WTAP in the formation of pyroptosis and inflammation in endothelial cells exposed to LPS stress by activating the NF-κB/NLRP3 signaling pathway. These findings demonstrate the mechanism of WTAP regulation during the progression of AS.
A germline heterozygousPOLQnonsense mutation causes hereditary colorectal cancer
Authors: Xu Ning , Zhang Deng-Feng , Yang Kexin , Fan Yu , Huang Fengchang , Ren Junyu , Bi Rui , Li Yu , Ye Maosen , Xu Min , Zhou Yongchun , Li Wenhui , Shi Xiaoxiao , Wei Yubo , Zhang Chao , Yao Yong-Gang , Li Wen-Liang 
Published: January 2024

AbstractThe causal genes for a large proportion of hereditary colorectal adenomas and early-onset colorectal cancer (CRC) remain to be identified. Here, we identified a germline heterozygous stop-gain mutation p.Arg1953X (rs150312701) of thePOLQ(DNA Polymerase Theta) gene, which is co-segregated with disease status, by whole-exome sequencing of twelve hereditary CRC pedigrees. The mutation was validated in an independent pedigree, resulting in ten p.Arg1953X carriers from two CRC families. Mechanically, the heterozygous nonsense mutation led to compensated overexpression of the mRNA with wild-typePOLQallele under DNA damage stress, resulting in hyperactivation of the error-prone theta mediated end-joining (TMEJ) DNA repair pathway, which enables the survival of mutation-enriched cells. Concordantly, tumor tissues from p.Arg1953X mutation carriers showed microsatellite instability and hypermutation, and were resistant to radiotherapy. We found that an FDA-approved antibiotic Novobiocin inhibits thePOLQ-mediated TMEJ pathway, eliminates the p.Arg1953X mutation-related resistance to DNA damage, finally benefits tumor radiotherapy. Collectively, we defined a POLQ-mutated CRC type and suggested for a mutation-based potential target therapeutic strategy.
Association of “Metabolic Dysfunction-Associated Steatotic Pancreas Disease” (MASPD) with Insulin Resistance
Authors: de Oliveira Andrade Luís Jesuino , Matos de Oliveira Gabriela Correia , Vinhaes Bittencourt Alcina Maria , Peixoto Nascimento Guilherme , Magno Baptista Gustavo , Peixoto Silva Catharina , Matos de Oliveira Luís 
Published: January 2024

ABSTRACTIntroduction“Metabolic Dysfunction-Associated Steatotic Pancreas Disease” (MASPD) is not yet a term or condition described in the medical literature. The MASPD is a relatively new and emerging condition that has garnered significant attention in the field of metabolic disorders.Objectiveto investigate the association between MASPD and IR and explore the potential mechanisms that may contribute to this relationship.Materials and MethodsThis cross-sectional study involved 157 participants diagnosed with MASPD based on ultrasonography criteria. Baseline demographic data were collected, including age, gender, and body mass index. Serum levels of fasting glucose, insulin, lipid profile (including total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), glycated hemoglobin and insulin were measured using standardized laboratory techniques. Abdominal ultrasonography was performed on all participants using convex transducer (frequency range, 3,5 MHz) by experienced radiologist blinded to the clinical data. The association between MASPD and IR was assessed using logistic regression analysis, adjusting for potential confounders. Statistical significance was set at a p-value of less than 0.05.ResultsThe logistic regression analysis was performed to verify whether IR was a risk factor for MASPD. After adjusting for gender and age, the results demonstrate a significant correlation between MDASPD and markers of IR. TyG index: OR (95% IC) 5.72 (1.90 – 16.00),P0.021, and HOMA –IR: OR (95% IC) 6.20 (2.1 – 22.00)P0.037.ConclusionThis study presents the first description of MDASPD and its association with IR indices. Our findings demonstrate a significant correlation between MDASPD and markers of IR. These results suggest that MDASPD may contribute to the development of insulin resistance and further highlight the importance of pancreatic health in metabolic disorders.
Mitigating reactive oxygen species production and increasing gel porosity improves lymphocyte motility and fibroblast spreading in photocrosslinked gelatin-thiol hydrogels
Authors: Ozulumba Tochukwu , Zatorski Jonathan M. , Arneja Abhinav , Hammel Jennifer H. , Braciale Thomas J. , Luckey Chance J. , Munson Jennifer M. , Pompano Rebecca R. 
Published: January 2024

ABSTRACTOn-chip 3D culture systems that incorporate immune cells such as lymphocytes and stromal cells are needed to model immune organs in engineered systems such as organs-on-chip. Photocrosslinking is a useful tool for creating such immune-competent hydrogel cultures with spatial cell organization. However, loss of viability and motility in photocrosslinked gels can limit its utility, especially when working with fragile primary cells. We hypothesized that optimizing photoexposure-induced ROS production, hydrogel porosity or a combination of both factors was necessary to sustain cell viability and motility during culture in photocrosslinked gelatin-thiol (GelSH) hydrogels. Jurkat T cells, primary human CD4+ T cells and human lymphatic fibroblasts were selected as representative lymphoid immune cells to test this hypothesis. Direct exposure of these cells to 385 nm light and LAP photoinitiator dramatically increased ROS levels. Pretreatment with an antioxidant, ascorbic acid (AA), protected the cells from light + LAP-induced ROS and was non-toxic at optimized doses. Furthermore, scanning electron microscopy showed that native GelSH hydrogels had limited porosity, and that adding collagen to GelSH precursor before crosslinking markedly increased gel porosity. Next, we tested the impact of AA pretreatment and increasing gel porosity, alone or in combination, on cell viability and function in 3D GelSH hydrogel cultures. Increasing gel porosity, rather than AA pretreatment, was more critical for rescuing viability of Jurkat T cells and spreading of human lymphatic fibroblasts in GelSH-based gels, but both factors improved the motility of primary human CD4+ T cells. Increased porosity enabled formation of spatially organized co-cultures of primary human CD4+ T cells and human lymphatic fibroblasts in photo-crosslinked gels in a multi-lane microfluidic chip, towards modeling the lymphoid organ microenvironment. Some optimization is still needed to improve homogeneity between regions on the chip. These findings will enable researchers utilizing photocrosslinking methods to develop immunocompetent 3D culture models that support viability and function of sensitive lymphoid cells.
Cell-free expression with a quartz crystal microbalance enables rapid, dynamic, and label-free characterization of membrane-interacting proteins
Authors: Khakimzhan Aset , Izri Ziane , Thompson Seth , Dmytrenko Oleg , Fischer Patrick , Beisel Chase , Noireaux Vincent 
Published: January 2024

AbstractIntegral and interacting membrane proteins (IIMPs) constitute a vast family of biomolecules that perform essential functions in all forms of life. However, characterizing their interactions with lipid bilayers remains limited due to challenges in purifying and reconstituting IIMPsin vitroor labeling IIMPs without disrupting their functionin vivo. Here, we report TXTL-QCMD to dynamically characterize interactions between diverse IIMPs and membranes without protein purification or labeling. As part of TXTL-QCMD, IIMPs are synthesized using cell-free transcription-translation (TXTL), and their interactions with supported lipid bilayers are measured using a quartz crystal microbalance with dissipation (QCMD). TXTL-QCMD reconstitutes known IIMP-membrane dependencies, including specific association with prokaryotic or eukaryotic membranes or oscillating interactions by theE. coliMin system. Applying TXTL-QCMD to the recently discovered Zorya anti-phage system unamenable to labeling, we discovered that ZorA and ZorB integrate together within the lipids found at the poles of bacteria while ZorE diffuses freely on the non-pole membrane. These efforts establish the potential of TXTL-QCMD to broadly characterize the large diversity of IIMPs.
A method to identify high consensus predictions of single-cell metabolic flux
Authors: Amiss Michael , Lum Julian J. , Jabbari Hosna 
Published: January 2024

AbstractAltered metabolism is a key contributor to pathology in numerous disease states, including cancer. These changes can occur within certain pathological cells, or within a population of cells. Two recently developed single-cell flux prediction tools, Single-cell Flux Estimation Analysis (“scFEA”) and Compass, have shown success in predicting cellular metabolism using readily available transcriptome data. By adapting the outputs of these tools, we sought to determine if they can work in concert to identify higher confidence consensus flux predictions. We created a set of reaction modules for the two systems. By testing multiple function composites with sets of modularized Compass outputs, we identified a method that showed the highest global similarity to the outputs of scFEA. Our analysis showed broad biological areas of agreement between the results of the two systems when applied to single-cell data arising from both pathological and healthy samples, with pathological samples increasing system consensus. Consensus testing on matched transcriptome and metabolomics data suggested that agreement between the two systems could indicate at least a minimal degree of coherence between both systems and direct metabolite measurements. Overall, we demonstrated that automated Comparisons between the outputs of Compass and scFEA are possible, applicable to data arising from pathological samples, and that such a consensus approach can reveal strongly correlated predictions between these two systems.Author summaryStudying the metabolism of individual cells allows us to understand the mechanisms behind a myriad of diseases. However, single-cell metabolism cannot readily be measured. Computational tools exist to predict metabolism, but validating their outputs requires metabolic measurements. To address this circular shortcoming, we created a method to automatically adapt and compare the outputs of two popular systems used to predict single-cell metabolism from genetic data. In other fields, using predictive methods in an ensemble has provided superior accuracy, and we speculated that the same may hold true for computational predictions of single-cell metabolism. Our work demonstrated that these two systems can be used together to find agreement on a broad range of metabolic processes related to disease. Further, our results, although early, suggest that system agreement may indicate genuine shifts in the underlying biology of a cell population. Owing to the methodologies used by the two systems, such changes could be studied at both a broad or granular level. As our comparison tools provide rapid readouts of such system agreement, they could potentially be used as part of an exploratory pipeline to aid in identification of candidate metabolic mechanisms as drug targets.
Sustainability drivers and national culture in buyer-supplier environmental practices: an institutional perspective
Authors: Ahmadi-Gh Zahra , Bello-Pintado Alejandro , Bortolotti Thomas , Boscari Stefania 
Published: January 2024

Purpose
This study aims to explore how sustainability drivers interact with national culture to explain the adoption of buyer–supplier environmental sustainability practices.

Design/methodology/approach
Drawing on Institutional Theory, this study proposes three sets of hypotheses focused on the role of key cultural dimensions: uncertainty avoidance, power distance and institutional collectivism. It uses a sample of 284 manufacturing plants across three industries and 14 countries to test these hypotheses, using regression analysis.

Findings
Findings suggest that national culture matters in the adoption of buyer–supplier environmental practices; however, its effect is contingent upon the particular combination of cultural dimensions and drivers analyzed.

Originality/value
This study enhances the understanding of the drivers behind buyer–supplier environmental practices by offering a novel examination of their interaction with national culture. This helps explain the heterogeneity in environmental sustainability adoption across countries.
Identification of novel antecedents towards generating positive electronic word of mouth: evidence from the hospitality and tourism industry
Authors: Khan Mehmood , Ajmal Mian M. , Jan Amin , Rahman Haseeb Ur , Zahid Muhammad 
Published: January 2024

Purpose
Literature shows that the antecedents of eWoM have received limited attention and the present scales used for measuring eWoM in the hospitality and tourism industry are outdated. Therefore, this study aims to construct a new scale for the generation of positive eWoM in the hospitality and tourism industry.

Design/methodology/approach
This study developed a novel scale on eWoM based on the four dimensions of the unified theory of acceptance and use of technology.

Findings
The exploratory and confirmatory factor analysis confirms the factorial structure of the new scale. The exploratory factor analysis shows that “performance expectancy” has the highest impact on the constitution of positive eWoM with 8 items, followed by “social influence” and “facilitation condition” with 5 items each. The factor “effort expectancy” is found to have the lowest impact on the constitution of positive eWoM in the hospitality and tourism industry with 3 items. The confirmatory factor analysis in terms of the construct reliability, average variance extracted and maximum shared variance tests confirmed the model validity of the new scale.

Originality/value
This study ensures measuring eWoM with the latest norms that will assist in prudent policy formulation. These results insights into policymakers from the hospitality and tourism industry for the generation of positive eWoM towards their business which will help them achieve better customer loyalty.
Romanian transnational families: insights from a qualitative study on care workers
Authors: Salaris Luisa , Tedesco Nicola 
Published: January 2024

Purpose
An increasing number of international immigrant workers enter the EU labour market to fill the gap in many key economic sectors. Labour migration often implies a process of family adaptation and, in some cases, a breakdown in the community structure and networks. This study aims to provide insights into the dynamics of transnational families, focusing on changes in the redefinition of roles within family members and children care arrangements.

Design/methodology/approach
The study was based on the analysis of 12 biographical interviews conducted using semi-structured interviews between November 2018 and December 2019 among Romanian women who worked as caregivers in families in an Italian metropolitan city and the surrounding urban area.

Findings
Despite the economic dimension being essential, psychological well-being increasingly burdens workers’ migratory experience and that of their family members. Findings suggest including employers and children among the actively involved actors of the family decision-making process; working and contractual conditions as factors that significantly impact the opportunities and capability of workers to provide and receive care, mainly if the latter are employed in the informal market.

Originality/value
The study makes it possible to highlight that the dynamics in decision-making processes in transnational families change in the different phases of the migration project and involve numerous actors. These processes are not always rational and are strongly influenced by the labour market structure in which migrants are employed.
The role of psychological contract in enhancing safety climate and safety behavior in the construction industry
Authors: M.G. Soundarya Priya , K.S. Anandh , Rajendran Sathyanarayanan , Sen Krishna Nirmalya 
Published: January 2024

Purpose
This study aims to explore the “psychological contract of safety” (PCS), a key factor in the safety climate (SC), which relies on the behavioral safety actions of workers at construction sites. While numerous factors have been identified in various sectors across different countries, there is a consensus among researchers that there is a dearth of common assessment factors specifically for the Indian construction industry (ICI). Therefore, this study undertakes a systematic review of existing literature to identify the factors that determine PCS in construction and to ascertain the relative importance index (RII) of these variables and their interrelationships using structural equation modelling (SEM).

Design/methodology/approach
A structured survey was conducted among 420 professionals in the ICI to collect data. This data was then analyzed using descriptive and inferential statistical methods to derive results.

Findings
The findings of the study indicate that PCS factors have a significant impact on the construction industry (CI). The inferential analysis ranks “Safety System” as the top factor with the highest RII value. The chi-square results highlight two key SC factors that enhance and regulate an organization’s safety performance. The SEM results reveal that SC factors contribute to the improvement of PCS and influence worker safety behavior.

Originality/value
The outcomes of this study will be beneficial for stakeholders aiming to improve safety at construction sites and enhance safety performance by fulfilling the mutual safety obligations of employers and employees and by improving safety norms, procedures and policy-making. This paper also provides a theoretical framework for scholars to reassess the results in various contexts.