bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of TGFβ-induced Fibroblast to Myofibroblast Transition by Conditioned Medium From Human Rhinovirus-infected Airway Epithelial Cells is Mediated by Prostaglandin E2
Authors: Pham Diana , Kooi Cora , Proud David , Leigh Richard 
Published: February 2022

Abstract
Background
Airway remodeling, including increased deposition of extracellular matrix proteins, is a hallmark of asthma. Myofibroblasts, derived via fibroblast to myofibroblast transition (FMT), play an important role in this increased deposition of matrix proteins. Expression of transforming growth factor β1 (TGFβ1) is increased in asthmatic airways and is known to induce FMT, as assessed by increased expression of α-smooth muscle actin (α-SMA). Because human rhinovirus (HRV) infections of airway epithelial cells have been linked to the generation of mediators involved in airway remodeling, we tested the hypothesis that conditioned medium from HRV-infected human airway epithelial cells from healthy normal subjects would enhance FMT, either alone or in combination with TGFβ1.
Methods
FMT was assessed by measuring α-SMA expression in human airway fibroblasts, both by western blotting and by immunohistochemistry. Statistical analysis was performed using ANOVA and Holm-Sidak or Bonferonni post hoc tests.
Results
Our data showed that conditioned medium from HRV infected epithelial cells significantly inhibited TGFβ1-induced expression of α-SMA in fibroblasts when compared to conditioned medium from uninfected epithelial cells. Treatment of epithelial cells with the nonselective cyclooxygenase inhibitor, diclofenac, during HRV infection significantly reversed the inhibitory effects of conditioned medium on TGFβ1-induced expression of α-SMA. This led us to hypothesize that HRV-infected epithelial cells release PGE2 that acts on EP receptors to suppress TGFβ1-induced expression of α-SMA in fibroblasts. We confirmed that HRV-infection of airway epithelial cells upregulated PGE2 release, and that exposure of fibroblasts to PGE2 significantly inhibited TGFβ1-induced expression of α-SMA in fibroblasts. Finally, studies using selective agonists and antagonists demonstrated that PGE2 inhibited TGFβ1-induced expression of α-SMA in fibroblasts via effects at the EP2 receptor.
Conclusions
Thus, using cells derived from healthy normal subjects we demonstrate that HRV infection of airway epithelial cells induces release of PGE2 that acts on EP2 receptors on fibroblasts to suppress TGFβ1-induced FMT. Additional studies are needed to determine if a different pattern of response is seen using cells from asthmatic subjects to determine if the inhibitory role of PGE2 on FMT in normal cells helps prevent airway remodeling in normal subjects.
TRX1 mediates melatonin-induced osteogenic differentiation and the inhibition of osteoporosis
Authors: Teng Zhaowei , Yu Xiaochao , Zhang Shaoxiong , Sun Shuo , Zhao Dake , Jiang Lihong , Reiter Russel 
Published: February 2022

Abstract
Osteoporosis is a common systemic bone disorder characterized by bone loss and an increased risk of fracture. Melatonin has powerful antioxidant and anti-aging functions and has been proposed as a treatment for osteoporosis; however, the therapeutic effect of this agent needs further validation and the mechanisms remain to be explored. In this study, we observed that melatonin markedly stimulated osteogenic differentiation in vitro and alleviated osteoporosis symptoms in mice. After melatonin treatment, thioredoxin1 (TRX1) was upregulated under both in vivo and in vitro conditions, while its expression notably decreased in osteoporotic mice, thereby suggesting this gene possibly mediated the therapeutic effect of melatonin on osteoporosis. Moreover, the following overexpression or silencing of TRX1 proved its ability to induce osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Furthermore, osteogenic differentiation and osteoporosis after melatonin pretreatment was attenuated both in BMSCs and in mice with TRX1 knockdown. These findings confirm that TRX1 is potentially associated with the beneficial effects of melatonin and that the use of melatonin may reduce osteoporosis. Overall, melatonin treatment induced expression of TRX1, and the up-regulated gene enhanced osteogenic differentiation and eventually reduced bone loss in osteoporosis. The results indicate that TRX1 may be a target of osteoporosis therapy.
Exercise Before and After­ Cerebral Ischemia-Reperfusion Inhibits Inflammation and Reduces Apoptosis in the Hippocampus in Rats
Authors: Dehqanizadeh Behzad , Mohammadi Ziya Fallah , Mohammadi Mohammad Fallah 
Published: February 2022

Abstract
Background: Cerebral ischemic/reperfusion (I/R) causes severe damage. The purpose of this study was to evaluate the effect of exercise before or/and after I/R on inflammation and apoptosis in the CA1 region of hippocampus in rats. Methods: Male Wistar rats were assigned to six groups (sham, exercise, ischemia, exercise+ischemia, ischemia+exercise, exercise+ischemia+exercise). Rats in the exercise groups received progressive treadmill training for 8 weeks, 5 days a week prior or/and after ischemic stroke. Ischemia was induced by occlusion of both common carotid arteries for 45 min. Cell apoptosis were detected by TUNEL staining. Caspase-3, NF-kB and TNF-α were determined by immunohistochemistry, and motor function was evaluated by ladder test.Results: The cerebral ischemia caused neuronal loss through apoptosis in the hippocampus and reduced sensorimotor functions in lesion animals. The results of TUNEL and immunohistochemistry methods showed that rats in exercise+ischemia+exercise group had more significant decrease in the number of apoptotic cells and inhibited the expression of caspase-3, NF-κB and TNF-α compared to other groups (p < .05). Also, the results of Ladder test at the end of the eighth week showed significant improvements compared to 2 and 24 hours (p < .05). Conclusion: This study showed that performing treadmill exercise, whether as a preconditioning or following cerebral ischemic event, could promote neuronal and motor recovery. However, such a protocol imposes more significant effect if conducted both pre and early after ischemia compared to each one alone.
Adaptive Responsivity: A Youth-Driven Model for Thriving in Foster Care
Authors: Shdaimah Corey , Zhao Lucy 
Published: February 2022

Abstract
With notable and growing exceptions, there is a dearth of research on mechanisms by which youth in foster care build resilience and achieve positive outcomes. We report on data from an interview study with young adults exiting or recently exited foster care in Maryland (N=15) designed to understand what facilitates their engagement with courts. Our findings indicate that despite challenges of “being in foster care”, youth found ways to pursue their goals and make their voices heard through developing stable relationships with supportive adults (including judges, caseworkers, or lawyers) and demanding that child welfare professionals “speak to me not at me.” Youth indicated that their needs, capabilities, and goals changed as they matured and as their circumstances changed. Such changes helped them find their voices but also created tensions within their child-welfare system interactions. This led us to develop the theory of adaptive responsivity, according to which child welfare stakeholders should respond appropriately to developmental and circumstantial changes to help child-welfare involved youth face difficult circumstances and thrive. Such responses include providing developmentally and situationally appropriate information and decision-making power to youth in their own cases as well as opportunities to weigh in on systems change.
Cytotoxic T cells specific for alpha-myosin drive immunotherapy related myocarditis
Authors: Balko Justin , Axelrod Margaret , Meijers Wouter , Screever Elles , Carroll Mary Grace , Sun Xiaopeng , Tannous Elie , Qin Juan , Zhang Yueli , Sugiura Ayaka , Wright Jordan , Wei Spencer , Opalenik Susan , Toren Abigail , Rathmell Jeffrey , Ferrell P , Phillips Elizabeth , Mallal Simon , Johnson Douglas , Allison James , Moslehi Javid 
Published: February 2022

Abstract
Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to immune checkpoint inhibitor (ICI) utility in anti-cancer therapy1. The pathogenesis of ICI-myocarditis is poorly understood. Pdcd1-/-Ctla4+/- mice recapitulate clinicopathologic features of ICI-myocarditis, including myocardial T cell infiltration2. Single cell RNA/T cell receptor (TCR) sequencing on the cardiac immune infiltrate of Pdcd1-/-Ctla4+/- mice identified activated, clonal CD8+ T cells as the dominant cell population. Treatment with anti-CD8, but not anti-CD4, depleting antibodies rescued survival of Pdcd1-/-Ctla4+/- mice. Adoptive transfer of immune cells from mice with myocarditis induced fatal myocarditis in recipients which required CD8+ T cells. Alpha-myosin, a cardiac specific protein absent from the thymus3,4, was identified as the cognate antigen source for three MHC-I restricted TCRs derived from mice with fulminant myocarditis. Peripheral blood T cells from two patients with ICI-myocarditis were expanded by alpha-myosin peptides, and these alpha-myosin expanded T cells shared TCR clonotypes with diseased heart and skeletal muscles, indicating that alpha-myosin may be a clinically important autoantigen in ICI-myocarditis. These studies underscore the critical role for cytotoxic CD8+ T cells, are the first to identify a candidate autoantigen in ICI-myocarditis and yield new insights into ICI toxicity pathogenesis.
Understanding Homeowner Proactive Actions for Managing Wildfire Risks
Authors: Lee Ji Yun , Ma Fangjiao , Li Yue 
Published: February 2022

Abstract
Wildfires have become increasing threats to residents, built environments, and ecosystems in the United States. Individual responsibility plays a significant role in reducing structure-level ignitability, and in turn, overall community vulnerability. Moreover, homeowners insurance can serve as the second line of defense by allowing homeowners to avoid substantial financial burden from repair/reconstruction costs induced by wildfire. To understand homeowner decisions on wildfire-related proactive actions and the effects of such decisions on the housing recovery, this study conducted an online survey of homeowners living in high to extreme risk of wildfire in the Western United States and collected data related to two types of proactive actions, i.e., individual-level risk reduction actions and homeowners insurance. First, a regression model for each proactive action was estimated to identify key characteristics of homeowners and house/property that had the greatest impact on these actions. The results indicated that homeowner age and household income were the two common factors affecting their decisions about home hardening and insurance policies, while the only statistically significant factor in homeowner decisions about defensible space was satisfaction with the surrounding environment. Moreover, the effects of each proactive action on the housing recovery process were evaluated. The results showed that home hardening was a more effective action in reducing wildfire damage to a house than defensible space was, which was consistent with homeowner perception. The survey results also indicated that homeowners with insurance were less likely to experience post-wildfire financial hardship, and subsequently were more likely to repair their damaged houses.
An Innovative Training Program for Community Health Workers to Support Engagement of Racial and Ethnic Minorities in Genomics Research and Clinical Programs: a Protocol for the Development of the PREFER (PaRtnEring to build understanding oF gEnomics Responsibly) Training Program
Authors: Allen Caitlin G. 
Published: February 2022

Abstract
Community health workers (CHWs) are trusted members of communities who have well-established relationships with individuals and families, especially among underserved populations. Prior research highlights interest among CHWs in learning about complex topics related to genetics, especially as public awareness is being raised about hereditary conditions. However, to date, there have been limited efforts to train CHWs on these topics of systematically involve this workforce in research related to genetics and genomics applications. To overcome this gap in training opportunities, we will develop a training specifically designed for CHWs to build competencies in genomics, hereditary conditions, and precision health approaches. The PREFER (PaRtnEring to build understanding oF gEnomics Responsibly) training will follow a Delphi process to gather expert feedback and use social cognitive theory and adult learning theory to guide the course content. In this protocol, we outline the planned approach for the development of the PREFER training program components, evaluation outcomes, and delivery plans.
Cross-platform validation of a mouse blood gene signature for quantitative reconstruction of radiation dose
Authors: Ghandhi Shanaz A. , Shuryak Igor , Ponnaiya Brian , Wu Xuefeng , Garty Guy , Morton Shad R. , Kaur Salan P. , Amundson Sally A. 
Published: February 2022

Abstract
In the search for biological markers after a large-scale exposure of the human population to radiation, gene expression is a sensitive endpoint easily translatable to in-field high throughput applications. Primarily, the ex-vivo irradiated healthy human blood model has been used to generate available gene expression datasets. This model has limitations i.e., lack of signaling from other irradiated tissues and deterioration of blood cells cultures over time. In vivo models are needed; therefore, we present our novel approach to define a gene signature in mouse blood cells that quantitatively correlates with radiation dose (at 1 Gy/min). Starting with available microarray datasets, we selected 30 radiation-responsive genes and performed cross-validation/training-testing data splits to downselect 16 radiation-responsive genes. We then tested these genes in an independent cohort of irradiated adult C57BL/6 mice (50:50 both sexes) and measured mRNA by quantitative RT-PCR in whole blood at 24h. Dose reconstruction using net Signal (difference between geometric means of top 3 positively correlated and top 4 negatively correlated genes with dose), was highly improved over the microarrays, with a root mean square error of ±1.04 Gy in male and female mice combined. There were no significant sex-specific differences in mRNA or cell counts after irradiation.
Breast Cancer Cell Secretome Analysis to Decipher miRNA Tumor Biology and Discover Potential Biomarkers
Authors: Feser Riley , Opperman Reid , Nault Braydon , Maiti Sujit , Chen Vincent , Majumder Mousumi 
Published: February 2022

Abstract
MicroRNA (miRNA/miR) miR526b and miR655 overexpressed tumor cell free secretions promote breast cancer phenotypes in the tumor microenvironment (TME). However, the mechanisms of miRNA regulating TME have never been investigated. With mass spectrometry analysis of MCF7-miRNA-overexpressed versus miRNA-low MCF7-Mock tumor cell secretomes we identified 34 novel secretory proteins coded by eight genes YWHAB, TXNDC12, MYL6B, SFN, FN1, PSMB6, PRDX4, and PEA15 differentially regulated. We performed bioinformatic analysis and used systems biology approaches to identify these markers’ role in breast cancer. Gene ontology analysis showed that the top functions are related to apoptosis, oxidative stress, membrane transport, and motility, supporting miRNA-induced phenotypes. In breast tumors these secretory markers expression is high and a strong positive correlation exists between upregulated markers’ mRNA expressions with miRNA cluster expression in luminal A breast tumors. Gene expression of secretome markers are higher in tumor tissues compared to normal samples, and immunohistochemistry data supported gene expression data. Moreover, both up and downregulated marker expressions are associated with breast cancer patient survival. miRNA regulates these marker protein expressions by targeting transcription factors of these genes. Premature miRNA (pri-miR526b and pri-miR655) are established breast cancer blood biomarkers. Here we report novel secretory markers upregulated by miR526b and miR655 (YWHAB, MYL6B, PSMB6, and PEA15) are significantly upregulated in breast cancer patients’ plasma, and are potential breast cancer biomarkers.
The Zariski topology on the graded second spectrum of a graded module
Authors: Salam Saif , Al-Zoubi Khaldoun 
Published: February 2022

Abstract
Let R be a G-graded ring and M be a G-graded R-module. The graded second spectrum of M, denoted by SpecssG(M), is the set of all graded second submodules of M. In this paper, we define a topology on SpecssG(M) which is analogous to that for SpecG(R), and investigate several topological properties of this topology.
The Cell-Free mMIMO Network based on IRSs: Mathematical Analysis and Performance Evaluation
Authors: Shalaby Mohamed Saeid , Lamie Mina Wagih , Shokair Mona Mohamed Sabry 
Published: February 2022

Abstract
The massive multiple input multiple output mMIMO technology can improve the cellular system performance especially the cell edge users. Thanks to the large number of implemented antennas at both transmitters and receivers, the mMIMO technology is qualified to satisfy the requirements of the 5G networks and beyond. The Cell-Free network, wherein large spatially distributed antennas are implemented, can improve the performance of shadowed users and indoor ones. In this paper, there is a trial to improve the cell-Free mMIMO network performance by implementation of Intelligent Reflecting Surfaces IRSs. The Cell-Free mMIMO network based on IRSs is mathematically analyzed and simulated. The signals to interference plus noise ratio SINR as well as spectral efficiency SE are derived in closed form formula. It can be concluded that implementation of IRSs in Cell-Free mMIMO networks can increase the SE and EE performance for all cooperation levels.
Assessment and prediction of shoreline change using multi-temporal satellite data and geostatistics: A case study on the eastern coast of India
Authors: Basheer Ahammed K. K. , Pandey Arvind Chandra 
Published: February 2022

Abstract
Climate change and rising sea level is transforming global coastlines as corroborated by significant changes in the position of shoreline witnessed through coastal erosion or accretion. Andhra Pradesh has the second longest (972 km) coastline in India. The present study analyzed shoreline change and its future prediction by employing satellite-derived data and geographic information system. End point rate (EPR) and linear regression rate (LRR) statistical tools in the Digital Shoreline Analysis System (DSAS) were used to estimate historical shoreline change rate between 1973 and 2015. Erosion and accretion of the coastline were delineated from Landsat satellite images for 1973, 1980, 1990, 2000, 2010, and 2015; subsequently, shoreline is predicted for short-term (2025) and long-term (2050) periods. The study showcased that the river mouths of Krishna and Godavari experienced higher rate of change in shoreline position influenced by the deltaic environment and fluvial processes. LRR model prediction depicts the average rate of shoreline change during 2015–2025 will be −4.64 m, while between 2015 and 2050 it will increase to −16.25 m. The study observed that the error between predicted and actual shoreline is higher in the river mouth and deltaic plains. Predicted shoreline position will provide baseline information for adaptation strategies and policy framework for coastal management.
Startup and initial operation of an MLE-MABR treating municipal wastewater
Authors: Silveira Isabel Telles , Cadee Keith , Bagg Wayne 
Published: February 2022

Abstract
A 630 m3/d pilot plant was installed at Subiaco WRRF to determine design and operational parameters of a hybrid Modified Ludzack-Ettinger – Membrane Aerated Biofilm Reactor (MLE-MABR) configuration. Two commercial ZeeLung MABR cassettes were installed in series in the anoxic zone and the pilot was fed with primary effluent (averaging COD 601 mg/L, TKN 68.5 mg/L and 17–29 °C). A nitrifying biofilm was developed within 3 weeks and the nitrous oxide (N2O) gas emissions from the MABR exhaust gas proved to be a reliable parameter to assess biofilm development. Both MABRs achieved the average nitrification rate (NR) of 3.7 gNH4-N/m2.d when air flow was 8.6 and 11.2 Nm3/h to MABR1 and MABR2 respectively, which reached a maximum oxygen transfer rate of 17.4 gO2/m2.d. Biofilm thickness was controlled via air scouring and intermittent coarse bubble mixing (90 s on/90 s off). This paper discusses the startup strategy, minimum requirements for process monitoring, impact of different air flow conditions, ORP and mixing patterns on performance efficiency over a 22-week period.
Human Factors and Technological Characteristics Influencing the Interaction of Medical Professionals With Artificial Intelligence–Enabled Clinical Decision Support Systems: Literature Review
Authors: Knop Michael , Weber Sebastian , Mueller Marius , Niehaves Bjoern 
Published: February 2022

Background
The digitization and automation of diagnostics and treatments promise to alter the quality of health care and improve patient outcomes, whereas the undersupply of medical personnel, high workload on medical professionals, and medical case complexity increase. Clinical decision support systems (CDSSs) have been proven to help medical professionals in their everyday work through their ability to process vast amounts of patient information. However, comprehensive adoption is partially disrupted by specific technological and personal characteristics. With the rise of artificial intelligence (AI), CDSSs have become an adaptive technology with human-like capabilities and are able to learn and change their characteristics over time. However, research has not reflected on the characteristics and factors essential for effective collaboration between human actors and AI-enabled CDSSs.

Objective
Our study aims to summarize the factors influencing effective collaboration between medical professionals and AI-enabled CDSSs. These factors are essential for medical professionals, management, and technology designers to reflect on the adoption, implementation, and development of an AI-enabled CDSS.

Methods
We conducted a literature review including 3 different meta-databases, screening over 1000 articles and including 101 articles for full-text assessment. Of the 101 articles, 7 (6.9%) met our inclusion criteria and were analyzed for our synthesis.

Results
We identified the technological characteristics and human factors that appear to have an essential effect on the collaboration of medical professionals and AI-enabled CDSSs in accordance with our research objective, namely, training data quality, performance, explainability, adaptability, medical expertise, technological expertise, personality, cognitive biases, and trust. Comparing our results with those from research on non-AI CDSSs, some characteristics and factors retain their importance, whereas others gain or lose relevance owing to the uniqueness of human-AI interactions. However, only a few (1/7, 14%) studies have mentioned the theoretical foundations and patient outcomes related to AI-enabled CDSSs.

Conclusions
Our study provides a comprehensive overview of the relevant characteristics and factors that influence the interaction and collaboration between medical professionals and AI-enabled CDSSs. Rather limited theoretical foundations currently hinder the possibility of creating adequate concepts and models to explain and predict the interrelations between these characteristics and factors. For an appropriate evaluation of the human-AI collaboration, patient outcomes and the role of patients in the decision-making process should be considered.