bluuebunny/crossref_metadata_2025 huggingface dataset:
Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
Authors: Briot Karine , Portale Anthony A , Brandi Maria Luisa , Carpenter Thomas O , Cheong Hae Ii , Cohen-Solal Martine , Crowley Rachel K , Eastell Richard , Imanishi Yasuo , Ing Steven , Insogna Karl , Ito Nobuaki , Jan de Beur Suzanne , Javaid Muhammad K , Kamenicky Peter , Keen Richard , Kubota Takuo , Lachmann Robin H , Perwad Farzana , Pitukcheewanont Pisit , Ralston Stuart H , Takeuchi Yasuhiro , Tanaka Hiroyuki , Weber Thomas J , Yoo Han-Wook , Nixon Annabel , Nixon Mark , Sun Wei , Williams Angela , Imel Erik A
Published: September 2021

Objectives

To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks.

Methods

Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT).

Results

Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks.

Conclusions

Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function.

Trial registration number

NCT02526160.
COVID-19 and the cardiovascular system: insights into effects and treatments
Authors: Chammas Joey , Delaney Dylan , Chabaytah Naim , Abdulkarim Sarah , Schwertani Adel
Published: September 2021

Coronavirus disease 2019 (COVID-19), an acute and highly transmissible infectious disease, has reached a pandemic level since 11 March 2020 and continues to challenge the healthcare system worldwide. The pathogenesis of COVID-19 is a complex process involving mechanisms that suppress the host antiviral and innate immune response, while triggering marked activation of coagulation and hyperinflammation leading to cytokine storm in severe COVID-19. This review summarizes current evidence related to COVID-19-associated cardiovascular severe illness and mortality, which encompasses life-threatening clinical manifestations, including myocardial injury, fulminant myocarditis, cardiac arrhythmia, and ischemic stroke. The onset of hypercoagulable state is consistent with increased venous thromboembolism including deep vein thrombosis and pulmonary embolism. Thromboembolic manifestations include arterial thrombotic events such as stroke, myocardial infarction, and limb ischemia. Several treatment strategies have been investigated to mitigate COVID-19-associated cardiovascular clinical manifestations. The prevalence of thrombo-inflammatory syndrome and subsequent cardiovascular dysfunction prompted the implementation of antithrombotic therapy and strategies targeting major pro-inflammatory cytokines involved in COVID-19 cytokine storm. The development of new guidelines for effective treatment strategies requires concerted efforts to refine our understanding of the mechanisms underlying cardiovascular disease and large-scale clinical trials to reduce the burden of COVID-19 hospitalization and mortality.
Age-structure model for oncolytic virotherapy
Authors: Ding Chuying , Wang Zizi , Zhang Qian
Published: September 2021

A non-local delay differential system was developed by age-infected consideration to understand the interaction between tumor cells and oncolytic virus. The critical threshold value [Formula: see text] was obtained that dominates the dynamical behaviors of our model. By strongly [Formula: see text]-persistent and Comparison theorem, the global stability and uniformly strongly persistent were investigated. Our global sensitivity analyses indicate that [Formula: see text] is most sensitive to virus clearance rate [Formula: see text] while is least sensitive to viral life cycle [Formula: see text]. Finally, our model was used to fit with experimental data which indicates that viral life cycle [Formula: see text] plays a key role in data fitting. And the trained model shows perfect prediction in the testing data set with the coefficient of determination [Formula: see text].
About this title - Applications of Non-Pollen Palynomorphs: from Palaeoenvironmental Reconstructions to Biostratigraphy
Authors: Marret F. , O'Keefe J. , Osterloff P. , Pound M. , Shumilovskikh L.
Published: September 2021

This long-awaited book about non-pollen palynomorphs (NPPs) aims to cover gaps in our knowledge of these abundant but understudied palynological remains. NPPs, such as fungal spores, testate amoebae, dinoflagellate cysts, acritarchs and animal remains, are routinely recovered from palynological preparations of marine or terrestrial material, from Proterozoic to recent geological times. This book gives the reader a comprehensive overview of the different types of NPPs, with examples from diverse time periods and environments. It provides guidance on sample preparation to maximize the recovery of these NPPs, detailed information on their diversity and ecological affinity, clarification on the nomenclature and demonstrates their value as environmental indicators. This volume will become the reference guide for any student, academic or practitioner interested in everything else in their palynological preparations.
Using sensors to measure inbox stress
Authors: Akbar Fatema
Published: September 2021

Email notifications are constantly calling for our attention, and the volume of emails is ever-increasing. A research group at the University of California, Irvine explores how managing the inbox affects stress for different working populations.
Sleep, health, productivity, and the double-edged sword of technology
Authors: Mattingly Stephen M.
Published: September 2021

While technology has traditionally impaired sleep, it also has the potential to enable and reframe sleep as a productivity and health booster.
Critical thinking of mobile sensing for health
Authors: Doryab Afsaneh
Published: September 2021

What you need to consider before collecting, processing, and analyzing mobile data for health applications.
A conversation with Tengyu Ma
Authors: Anjum Bushra
Published: September 2021

In this interview, Ubiquity's senior editor Dr. Bushra Anjum chats with Dr. Tengyu Ma, an assistant professor of Computer Science and Statistics at Stanford University. They discuss Dr. Ma's research that aims to bridge the gap between theory and practice in deep learning by developing novel mathematical tools to understand complex and mysterious deep learning systems.
Psychology Within and Without the State
Authors: Barrett H. Clark
Published: September 2021

Psychological research in small-scale societies is crucial for what it stands to tell us about human psychological diversity. However, people in these communities, typically Indigenous communities in the global South, have been underrepresented and sometimes misrepresented in psychological research. Here I discuss the promises and pitfalls of psychological research in these communities, reviewing why they have been of interest to social scientists and how cross-cultural comparisons have been used to test psychological hypotheses. I consider factors that may be undertheorized in our research, such as political and economic marginalization, and how these might influence our data and conclusions. I argue that more just and accurate representation of people from small-scale communities around the world will provide us with a fuller picture of human psychological similarity and diversity, and it will help us to better understand how this diversity is shaped by historical and social processes.
Quantum Cognition
Authors: Pothos Emmanuel M. , Busemeyer Jerome R.
Published: September 2021

Uncertainty is an intrinsic part of life; most events, affairs, and questions are uncertain. A key problem in behavioral sciences is how the mind copes with uncertain information. Quantum probability theory offers a set of principles for inference, which align well with intuition about psychological processes in certain cases: cases when it appears that inference is contextual, the mental state changes as a result of previous judgments, or there is interference between different possibilities. We motivate the use of quantum theory in cognition and its key characteristics. For each of these characteristics, we review relevant quantum cognitive models and empirical support. The scope of quantum cognitive models encompasses fallacies in decision-making (such as the conjunction fallacy or the disjunction effect), question order effects, conceptual combination, evidence accumulation, perception, over-/underdistribution effects in memory, and more. Quantum models often formalize psychological ideas previously expressed in heuristic terms, allow unified explanations of previously disparate findings, and have led to several surprising, novel predictions. We also cast a critical eye on quantum models and consider some of their shortcomings and issues regarding their further development.
Remote Inflammatory Preconditioning Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Intrinsic Apoptosis in Rats
Authors: Liu Yong , Xu Jiahang , Zhao Liang , Cheng Jing , Chen Baojun
Published: September 2021

Background. Acute lung injury (ALI) always leads to severe inflammation. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). Method. A total of 21 Sprague-Dawley rats were used for the animal experiments. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Animals were sacrificed 24 hours later. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. Results. In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Increasing of TNF-α, IL-1β, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. Conclusion. RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats.
A New Truncated Muth Generated Family of Distributions with Applications
Authors: Almarashi Abdullah M. , Jamal Farrukh , Chesneau Christophe , Elgarhy Mohammed
Published: September 2021

In recent years, the Muth distribution has been used for the construction of accurate statistical models, with applications in various applied fields. In this paper, we use a truncated‐composed scheme to create a new unit Muth distribution, from which we motivate a more general family of continuous distributions called the truncated Muth generated family. The key benefits of this family are its analytical simplicity, connections with the exponential generated family, and flexibility conferred on any parental distribution. In particular, it improves the capability of the functions of the parental distribution, enhancing their peak, asymmetry, tail, and flatness levels, among others. The characteristics of quantile and moment measures and functions of the truncated Muth generated family are described in detail. As a concrete example, a particular distribution that extends the Weibull distribution is highlighted. In an applied part, the parameters are calculated using the maximum likelihood procedure. We use a comprehensive simulation analysis to demonstrate the accuracy of the derived estimates. The revised Weibull model is then used to fit two real‐world datasets. The new model is shown to be more suited to these datasets than other competing models.
The Level and Significance of Circulating Angiotensin-III in Patients with Coronary Atherosclerosis
Authors: Yao Guoqing , Li Wenjing , Liu Wenzhao , Xing Jingbo , Zhang Cheng
Published: September 2021

Objective. Angiotensin-III (Ang-III) is the downstream product of angiotensin-II (Ang-II) metabolized by aminopeptidase A (APA). At present, the research of Ang-III mainly concentrates on hypertension and the central renin-angiotensin system (RAS). However, few studies have focused on the relationship between Ang-III and coronary atherosclerosis (CAS). Methods and Results. Plasma Ang-III and APA levels were measured by the enzyme-linked immunosorbent assay (ELISA) in 44 normal subjects and 84 patients confirmed as having CAS by coronary angiography. Circulating Ang-III levels were significantly lower in patients with CAS than in normal controls ([Formula: see text]). APA levels were slightly lower in the CAS group ([Formula: see text]). According to the severity of atherosclerosis, CAS patients were divided into two groups. Compared with the controls, the APA and Ang-III levels were lower in the high scoring group and APA decreased significantly. Conclusions. Circulating Ang-III levels were reduced in patients with CAS, and the possible reason may be related to the decrease in the APA level.
A Review of Evolutionary Trends in Cloud Computing and Applications to the Healthcare Ecosystem
Authors: Molo Mbasa Joaquim , Badejo Joke A. , Adetiba Emmanuel , Nzanzu Vingi Patrick , Noma-Osaghae Etinosa , Oguntosin Victoria , Baraka Mushage Olivier , Takenga Claude , Suraju Sadeeq , Adebiyi Ezekiel F.
Published: September 2021

Cloud computing is a technology that allows dynamic and flexible computing capability and storage through on-demand delivery and pay-as-you-go services over the Internet. This technology has brought significant advances in the Information Technology (IT) domain. In the last few years, the evolution of cloud computing has led to the development of new technologies such as cloud federation, edge computing, and fog computing. However, with the development of Internet of Things (IoT), several challenges have emerged with these new technologies. Therefore, this paper discusses each of the emerging cloud-based technologies, as well as their architectures, opportunities, and challenges. We present how cloud computing evolved from one paradigm to another through the interplay of benefits such as improvement in computational resources through the combination of the strengths of various Cloud Service Providers (CSPs), decrease in latency, improvement in bandwidth, and so on. Furthermore, the paper highlights the application of different cloud paradigms in the healthcare ecosystem.
Crosstalk between Heart Failure and Cognitive Impairment via hsa‐miR‐933/RELB/CCL21 Pathway
Authors: Feng Wenxiao , Yang Jie , Song Wenchao , Xue Yitao
Published: September 2021

Background. The association between heart failure (HF) and cognitive impairment has received increasing attention from scholars and researchers in recent years. However, no systematic studies have been carried out yet focused on the crosstalk between heart failure and cognitive impairment via miRNAs. Methods. GSE104150, GSE53473, GSE120584, and GSE116250 with RNA‐seq data and clinical data were downloaded from the GSE database. All data were statistically analysed using R software to detect DE‐miRNAs and DE‐mRNAs associated with both HF and cognitive impairment. Protein‐protein interaction (PPI) networks were mapped, and a logistic regression model for cognitive impairment prediction was developed. Furthermore, the TTRUST database and miRWalk were used to map miRNA‐transcription factor (TF) and messenger RNA (mRNA) regulatory pathways. Finally, core TFs were enriched for analysis. Results. Differentially enriched DE‐miRNAs and DE‐mRNAs both present in HF and cognitive impairment were determined. A logistic regression model established based on DE‐miRNAs was validated to have a strong performance in cognitive impairment prediction. The core miRNA‐TF‐mRNA pathway was formed by mapping the PPI networks associated with the two diseases. Further GSEA was performed with V‐rel reticuloendotheliosis viral oncogene homolog B (RELB) as the core TF, and the retinol metabolism and gap junction pathways were analysed. Conclusions. This study was the first attempt to predict the crosstalk and examine underlying mechanisms between HF and cognitive impairment applying bioinformatics. The findings suggested a potential hsa‐miR‐933/RELB/CCL21 regulatory axis correlated with HF and neurological disorders (or cognitive impairment), according to PPI networks.
Method for Determining Critical Slip Surface of Cohesive Soil Slope Based on the Principle of Simple Penetration Test
Authors: Zhang Aiqing , Li Jinyun , Zhang Youheng
Published: September 2021

In order to propose a new method for determining the critical slip surface of the cohesive soil slope, the relational expression between the number of simple penetration and slope bearing capacity is established on the basis of studying the principle of the simple penetration test with reference to the research result concerning the number of standard penetration and bearing capacity of foundation soil. The measuring points are arranged at the slope of a certain road slope according to the actual conditions, to measure the number of simple penetration, calculate the slope bearing capacity at different depths with the relational expression, draw the curve of slope bearing capacity changing with the depth, search the points of abrupt change in slope bearing capacity to get the arc curve of abrupt change points, and then determine the critical slip surface of slope. The test results are compared with the results calculated by the finite element method (FEM) and theoretical method, to verify the feasibility and rationality of the simple penetration method. The research results show that the simple penetration method is applicable to and capable of quick and accurate determination of critical slip surface of the cohesive soil slope, thus providing a new method for analyzing the slope stability of cohesive soil.
Gasotransmitters: Potential Therapeutic Molecules of Fibrotic Diseases
Authors: Chen Yingqing , Yuan Shuo , Cao Yuying , Kong Guangyao , Jiang Feng , Li You , Wang Qi , Tang Minli , Zhang Qinggao , Wang Qianqian , Liu Liping
Published: September 2021

Fibrosis is defined as the pathological progress of excessive extracellular matrix (ECM), such as collagen, fibronectin, and elastin deposition, as the regenerative capacity of cells cannot satisfy the dynamic repair of chronic damage. The well‐known features of tissue fibrosis are characterized as the presence of excessive activated and proliferated fibroblasts and the differentiation of fibroblasts into myofibroblasts, and epithelial cells undergo the epithelial‐mesenchymal transition (EMT) to expand the number of fibroblasts and myofibroblasts thereby driving fibrogenesis. In terms of mechanism, during the process of fibrosis, the activations of the TGF‐β signaling pathway, oxidative stress, cellular senescence, and inflammatory response play crucial roles in the activation and proliferation of fibroblasts to generate ECM. The deaths due to severe fibrosis account for almost half of the total deaths from various diseases, and few treatment strategies are available for the prevention of fibrosis as yet. Recently, numerous studies demonstrated that three well‐defined bioactive gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), generally exhibited anti‐inflammatory, antioxidative, antiapoptotic, and antiproliferative properties. Besides these effects, a number of studies have reported that low‐dose exogenous and endogenous gasotransmitters can delay and interfere with the occurrence and development of fibrotic diseases, including myocardial fibrosis, idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, diabetic diaphragm fibrosis, and peritoneal fibrosis. Furthermore, in animal and clinical experiments, the inhalation of low‐dose exogenous gas and intraperitoneal injection of gaseous donors, such as SNAP, CINOD, CORM, SAC, and NaHS, showed a significant therapeutic effect on the inhibition of fibrosis through modulating the TGF‐β signaling pathway, attenuating oxidative stress and inflammatory response, and delaying the cellular senescence, while promoting the process of autophagy. In this review, we first demonstrate and summarize the therapeutic effects of gasotransmitters on diverse fibrotic diseases and highlight their molecular mechanisms in the process and development of fibrosis.
Complex q‐Rung Orthopair Fuzzy N‐Soft Sets: A New Model with Applications
Authors: Akram Muhammad , Wasim Faiza , Al-Kenani Ahmad N.
Published: September 2021

This research article expands the formal representation of human thinking to a most generalized hybrid theory, namely, complex q‐rung orthopair fuzzy N‐soft set. It is able to capture a great deal of graded imprecision and vagueness, which so often appear together in human interpretations. This model renders a parameterized mathematical tool for the ranking‐based fuzzy modeling of two‐dimensional paradoxical data. To that purpose, the proposed theory integrates complex q‐rung orthopair fuzzy sets with the parametric structure of N‐soft sets. The framework that arises captures information beyond the confined space of complex intuitionistic fuzzy N‐soft sets and complex Pythagorean fuzzy N‐soft sets, with the assistance of a parameter q. We establish the basic set‐theoretical operations of this model and prove some of its fundamental properties. The Einstein and other elementary algebraic operations on complex q‐rung orthopair fuzzy N‐soft values shall be introduced to broaden the mathematical toolbox of this field. Its relationships with contemporary approaches shall demonstrate its outstanding flexibility. Moreover, we establish two competent multicriteria decision‐making algorithms that capture the nuances of periodical inconsistent data. Their feasibility shall be demonstrated with an explicit application to the selection of optimum aerospace technology required for the economic development of the Mexican space agency. A comparative analysis of both strategies with the prevailing techniques substantiates their rationality. In addition, we illustrate this comparative study with an explicative bar chart that shows the compatibility of their outcomes. Finally, we examine the functionality of the proposed model and compare it with alternative theories.
Visual Object Tracking with Online Updating for Car Sharing Services
Authors: Zhu Zhou , Zhao Haifeng , Hui Fang , Zhang Yan
Published: September 2021

In this paper, we address the problem of online updating of visual object tracker for car sharing services. The key idea is to adjust the updating rate adaptively according to the tracking performance of the current frame. Instead of setting a fixed weight for all the frames in the updating of the object model, we assign the current frame a larger weight if its corresponding tracking result is relatively accurate and unbroken and a smaller weight on the contrary. To implement it, the current estimated bounding box’s intersection over union (IOU) is calculated by an IOU predictor which is trained offline on a large number of image pairs and used as a guidance to adjust the updating weights online. Finally, we imbed the proposed model update strategy in a lightweight baseline tracker. Experiment results on both traffic and nontraffic datasets verify that though the error of predicted IOU is inevitable, the proposed method can still improve the accuracy of object tracking compared with the baseline object tracker.
Effect of Microwave Roasting and Extraction Solvents on the Bioactive Properties of Coffee Beans
Authors: Mohammad Salamatullah Ahmad , Hayat Khizar , Mabood Husain Fohad , Asif Ahmed Mohammed , Arzoo Shaista , Mohammed Alghunaymi Abdullah , Alzahrani Abdulhakeem , Alyahya Heba Kahlil , Al-Badr Nawal , Bourhia Mohammed
Published: September 2021

Coffee is an intricate mixture of thousands of chemical compounds that are accountable for its flavor and aroma. Roasting is a key step in the processing of coffee beans. This study assessed the effect of microwave roasting (MW) and extraction solvents (ES) on the total polyphenol content, total flavonoid content, and antioxidant activity of coffee beans. The untreated and microwave-roasted (MR) coffee beans showed a total polyphenol content of 40.40 and 35.15 mg GAE/gm DW, respectively, when methanol was used as the solvent for extraction. Similarly, for the untreated coffee beans, the methanol extracted coffee had a significantly (

p
<
0.05

) higher total flavonoid content (39.34 mg CE/g DW) as compared to ethanol (34.82 mg CE/g DW). The obtained IC50 for the untreated and microwave-roasted samples as extracted by methanol were 4.13 and 5.68 mg/mL, respectively, while the IC50 values of untreated and microwave-roasted samples extracted by ethanol were 4.59 and 6.24 mg/mL, respectively. Untreated coffee beans exhibited a higher reducing power (1.237) than that of the microwave-roasted ones (0.839) when extracted with methanol. Chlorogenic acid was the major (2.31–2.68%) phenolic compound found in all the coffee samples whether it was untreated or microwave-roasted. Vanillin demonstrated the lowest (0.118–0.166%) phenolic compound found in the coffee bean samples. These results might be helpful for obtaining the maximum health benefits from coffee.
Endogenous Estrogen Influences Predator Odor-Induced Impairment of Cognitive and Social Behaviors in Aromatase Gene Deficiency Mice
Authors: Gao Yaner , Ma Lei , Gao Feng , Sun Zuoli , Zhang Zhengrong , Li Yuhong , Li Rena
Published: September 2021

Epidemiological studies have suggested that traumatic stress increases vulnerability to various mental disorders, such as dementia and psychiatric disorders. While women are more vulnerable than men to depression and anxiety, it is unclear whether endogenous estrogens are responsible for the underlying sex-specific mechanisms. In this study, the aromatase gene heterozygous (Ar+/-) mice were used as an endogenous estrogen deficiency model and age- and sex-matched wild type mice (WT) as controls to study the predator odor 2,3,5-trimethyl-3-thiazoline- (TMT-) induced short- and long-term cognitive and social behavior impairments. In addition, the changes in brain regional neurotransmitters and their associations with TMT-induced changes in behaviors were further investigated in these animals. Our results showed TMT induced immediate fear response in both Ar+/- and WT mice regardless of sexes. TMT induced an acute impairment of novel object recognition memory and long-term social behavior impairment in WT mice, particularly in females, while Ar+/- mice showed impaired novel object recognition in both sexes and TMT-elevated social behaviors, particularly in males. TMT failed to induce changes in the prepulse inhibition (PPI) test in both groups. TMT resulted in a slight increase of DOPAC/DA ratio in the cortex and a significant elevation of this ratio in the striatum of WT mice. In addition, the ratio of HIAA/5-HT was significantly elevated in the cortex of TMT-treated WT mice, which was not found in TMT-treated Ar+/- mice. Taken together, our results indicate that TMT exposure can cause cognitive and social behavior impairments as well as change catecholamine metabolism in WT mice, and endogenous estrogen deficiency might desensitize the behavioral and neurochemical responses to TMT in Ar+/- mice.
Network Pharmacology‐Based Identification of Potential Targets of Lonicerae japonicae Flos Acting on Anti‐Inflammatory Effects
Authors: Guo Xiaoying , Yu Xiao , Zheng Bingqing , Zhang Longfei , Zhang Fang , Zhang Yongqing , Li Jia , Pu Gaobin , Zhang Lijun , Wu Haifeng
Published: September 2021

Lonicerae japonicae flos (LJF) is widely used for the treatment of inflammation‐related diseases in traditional Chinese medicine (TCM). To clarify the anti‐inflammatory mechanism of LJF, 29 compounds with high content in LJF were selected for network pharmacology. Then, a comprehensive network pharmacology strategy was implemented, which involved compound‐inflammation‐target construction, protein‐protein interaction (PPI) network analysis, and enrichment analysis. Finally, molecular docking and in vitro experiments were performed to verify the anti‐inflammatory activity and targets of the key compound. As a result, 279 inflammation‐associated proteins were identified, which are mainly involved in the AGE/RAGE signaling pathway in diabetic complications, the HIF‐1 signaling pathway, the PI3K‐AKT signaling pathway, and EGFR tyrosine kinase inhibitor resistance. A total of 12 compounds were linked to more than 35 targets, including apigenin, kaempferol, quercetin, luteolin, and ferulic acid. The results of molecular docking showed that AKT has the most binding activity, exhibiting certain binding activity with 10 compounds, including vanillic acid, protocatechuic acid, secologanic acid, quercetin, and luteolin; the results of qRT‐PCR and WB confirmed that two key compounds, secologanic acid and luteolin, could significantly decrease the secretion of TNF‐α and the AKT expression of RAW264.7 murine macrophages stimulated by LPS (lipopolysaccharide). These results demonstrate that the comprehensive strategy can serve as a universal method to illustrate the anti‐inflammatory mechanisms of traditional Chinese medicine by identifying the pathways or targets.
From Centralized Protection to Distributed Edge Collaboration: A Location Difference-Based Privacy-Preserving Framework for Mobile Crowdsensing
Authors: Shao Zihao , Wang Huiqiang , Zou Yifan , Gao Zihan , Lv Hongwu
Published: September 2021

Mobile Crowdsensing (MCS) has evolved into an effective and valuable paradigm to engage mobile users to sense and collect urban-scale information. However, users risk their location privacy while reporting data with actual sensing locations. Existing works of location privacy-preserving are primarily based on single-region location information, which rely on a trusted and centralized sensing platform and ignore the impact of regional differences on user privacy-preserving demands. To tackle this issue, we propose a Location Difference-Based Privacy-Preserving Framework (LDPF), leveraging the powerful edge servers deployed between users and the sensing platform to hide and manage users according to regional user characteristics. More specifically, for popular regions, based on the edge servers and the k-anonymity algorithm, we propose a Coordinate Transformation and Bit Commitment (CTBC) privacy-preserving method that effectively guarantees the privacy of location data without relying on a trusted sensing platform. For remote regions, based on a more realistic distance calculation mode, we design a Paillier Encryption Data Coding (PDC) privacy-preserving method that realizes the secure computation for users’ location and prevents malicious users from deceiving. The theoretical analysis and simulation results demonstrate the security and efficiency of the proposed framework in location difference-based privacy-preserving.
UGT1A Gene Family Members Serve as Potential Targets and Prognostic Biomarkers for Pancreatic Cancer
Authors: Feng Lei , Wang Yi , Qin Jiasheng , Fu Yu , Guo Zeyi , Zhang Jianmin , He Guolin , Jiang Zesheng , Xu Xiaoping , Zhou Chenjie , Gao Yi
Published: September 2021

Background. Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. Methods. Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan‐Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. Results. The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine‐cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor‐infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. Conclusions. These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.
Lactobacillus plantarum and Lactobacillus brevis Alleviate Intestinal Inflammation and Microbial Disorder Induced by ETEC in a Murine Model
Authors: Han Xuebing , Ding Sujuan , Ma Yong , Fang Jun , Jiang Hongmei , Li Yi , Liu Gang
Published: September 2021

The purpose of this research is to explore the positive effects of Lactobacillus plantarum and Lactobacillus brevis on the tissue damage and microbial community in mice challenged by Enterotoxigenic Escherichia coli (ETEC). Twenty‐four mice were divided into four groups randomly: the CON group, ETEC group, LP‐ETEC group and LB‐ETEC group. Our results demonstrated that, compared with the ETEC group, the LP‐ETEC and LB‐ETEC groups experienced less weight loss and morphological damage of the jejunum. We measured proinflammatory factors of colonic tissue and found that L. plantarum and L. brevis inhibited the expression of proinflammatory factors such as IL‐β, TNF‐α, and IL‐6 and promoted that of the tight junction protein such as claudin‐1, occludin, and ZO‐1. Additionally, L. plantarum and L. brevis altered the impact of ETEC on the intestinal microbial community of mice, significantly increased the abundance of probiotics such as Lactobacillus, and reduced that of pathogenic bacteria such as Proteobacteria, Clostridia, Epsilonproteobacteria, and Helicobacter. Therefore, we believe that L. plantarum and L. brevis can stabilize the intestinal microbiota and inhibit the growth of pathogenic bacteria, thus protecting mice from the gut inflammation induced by ETEC.
Adsorption Performance of La(III) and Y(III) on Orange Peel: Impact of Experimental Variables, Isotherms, and Kinetics
Authors: Liu Li , Rao Yunzhang , Tian Changshun , Huang Tao , Lu Jiacheng , Zhang Meidao , Han Min
Published: September 2021

To alleviate the environmental problem associated with rare earth wastewater, this research applied waste orange peel (OP) for the adsorption of La(III) and Y(III) from aqueous solution. The adsorption properties of orange peel are characterized using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), and the participation of hydroxyl and other oxygen-containing groups that promote the physical-chemical interaction is verified. Batch adsorption results suggest that orange peel possesses a satisfactory adsorption performance for La(III) and Y(III). The optimal adsorption conditions were obtained at pH of 6, temperature of 40°C, appropriate dosage of 2 g/L and 3 g/L, contact time of 30 min, and initial ion concentration of 32 mg/L. Under the same condition, adsorption performance of La(III) is better than that of Y(III). The experimental data is well fitted by the Langmuir isotherm model with [Formula: see text] and the minimum standard error values. Equilibrium results show that Langmuir monolayer adsorption capacity of La(III) and Y(III) onto orange peel is up to 37.61 and 31.10 mg/g. The fitting results of kinetics prove that the adsorption process of La(III) and Y(III) follows the pseudosecond-order model. Thus, natural orange peel as a recyclable biosorbent has potential economic and applicative benefits to remove La(III) and Y(III) from aqueous solutions.
Restoration of Citropsis articulata, a Species at Risk from Medicinal Overharvesting in a Ugandan Rainforest Reserve
Authors: Olupot William
Published: September 2021

Citropsis articulata, the African cherry orange, is considered to be threatened in Ugandan forests as a result of its purported aphrodisiac properties. This study, part of an ongoing effort to address restoration needs of Mabira Central Forest Reserve in Uganda, demonstrates the feasibility of restoring depleted C. articulata populations using seedlings transplanted from nursery-grown seeds. Phenology of 20 Mabira forest plants was monitored with the aim of collecting seeds. One hundred and fifty-six ripe fruits were collected, and 233 of the extracted seeds were planted in pots in a nursery during January–March 2019. During November-December 2019, seedlings were planted near the sites from which fruits were collected. Seed germination success rate was 89%, and fifteen months after transplanting, in situ survival was 100%. These results suggest that depleted C. articulata populations may be restored in situ using nursery-grown seeds.
Machine Learning Classification Techniques for Detecting the Impact of Human Resources Outcomes on Commercial Banks Performance
Authors: Atiku Sulaiman O. , Obagbuwa Ibidun C.
Published: September 2021

The banking industry is a market with great competition and dynamism where organizational performance becomes paramount. Different indicators can be used to measure organizational performance and sustain competitive advantage in a global marketplace. The execution of the performance indicators is usually achieved through human resources, which stand as the core element in sustaining the organization in the highly competitive marketplace. It becomes essential to effectively manage human resources strategically and align its strategies with organizational strategies. We adopted a survey research design using a quantitative approach, distributing a structured questionnaire to 305 respondents utilizing efficient sampling techniques. The prediction of bank performance is very crucial since bad performance can result in serious problems for the bank and society, such as bankruptcy and negative influence on the country’s economy. Most researchers in the past adopted traditional statistics to build prediction models; however, due to the efficiency of machine learning algorithms, a lot of researchers now apply various machine learning algorithms to various fields, including performance prediction systems. In this study, eight different machine learning algorithms were employed to build performance models to predict the prospective performance of commercial banks in Nigeria based on human resources outcomes (employee skills, attitude, and behavior) through the Python software tool with machine learning libraries and packages. The results of the analysis clearly show that human resources outcomes are crucial in achieving organizational performance, and the models built from the eight machine learning classifier algorithms in this study predict the bank performance as superior with the accuracies of 74–81%. The feature importance was computed with the package in Scikit-learn to show comparative importance or contribution of each feature in the prediction, and employee attitude is rated far more than other features. Nigeria’s bank industry should focus more on employee attitude so that the performance can be improved to outstanding class from the current superior class.
Integrated Analysis of lncRNA-Associated ceRNA Network Identifies Two lncRNA Signatures as a Prognostic Biomarker in Gastric Cancer
Authors: Zhang Shuyan , Li Shanshan , Guo Jian-Lin , Li Ningyi , Zhang Cai-Ning , Liu Jie
Published: September 2021

Background. Gastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction. Methods. The lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs. Results. Differentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells. Conclusions. The authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.
Loading Behavior and Soil-Structure Interaction for a Floating Stone Column under Rigid Foundation: A DEM Study
Authors: Liu Feng , Guo Panpan , Hu Haibo , Zhu Chengwei , Gong Xiaonan
Published: September 2021

This paper investigates the loading behavior and soil-structure interaction associated with a floating stone column under rigid foundation by using the discrete element method (DEM). The aggregates and soft soil are simulated by particles with different sizes. The rigid foundation is simulated by two loading plates at the same position with the same velocity. The stress distributions and microscopic interaction between the column and soft soil are investigated. The vertical stress of the column increases with settlement and decreases with the depth. The position of the column with large radial stress also has large deformation, which decreases from top to bottom. The vertical and radial stresses of the soft soil increase with settlement, and the radial stress shows high value in the upper part of soft soil. The stress concentration ratio is obtained by two loading plates, which decreases from 2.5 to 1.55 during loading. The interaction between column and soft soil shows that the column does not penetrate into the underlying stratum but drags the surrounding soil down.
EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody–Drug Conjugate HER3–DXd
Authors: Haikala Heidi M. , Lopez Timothy , Köhler Jens , Eser Pinar O. , Xu Man , Zeng Qing , Teceno Tyler J. , Ngo Kenneth , Zhao Yutong , Ivanova Elena V. , Bertram Arrien A. , Leeper Brittaney A. , Chambers Emily S. , Adeni Anika E. , Taus Luke J. , Kuraguchi Mari , Kirschmeier Paul T. , Yu Channing , Shiose Yoshinobu , Kamai Yasuki , Qiu Yang , Paweletz Cloud P. , Gokhale Prafulla C. , Jänne Pasi A.
Published: September 2021

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for EGFR-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of the ERBB family that functions by dimerizing with other ERBB family members (EGFR and HER2) and is frequently overexpressed in EGFR-mutant NSCLC. Although EGFR TKI resistance mechanisms do not lead to alterations in HER3, we hypothesized that targeting HER3 might improve efficacy of EGFR TKI. HER3–DXd is an antibody–drug conjugate (ADC) comprised of HER3-targeting antibody linked to a topoisomerase I inhibitor currently in clinical development. In this study, we evaluated the efficacy of HER3–DXd across a series of EGFR inhibitor–resistant, patient-derived xenografts and observed it to be broadly effective in HER3-expressing cancers. We further developed a preclinical strategy to enhance the efficacy of HER3–DXd through osimertinib pretreatment, which increased membrane expression of HER3 and led to enhanced internalization and efficacy of HER3–DXd. The combination of osimertinib and HER3–DXd may be an effective treatment approach and should be evaluated in future clinical trials in EGFR-mutant NSCLC patients.

Significance:

EGFR inhibition leads to increased HER3 membrane expression and promotes HER3–DXd ADC internalization and efficacy, supporting the clinical development of the EGFR inhibitor/HER3–DXd combination in EGFR-mutant lung cancer.

See related commentary by Lim et al., p. 18