bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental Perception of the Social and Physical Environment Contributes to Gender Inequalities in Children’s Screen Time
Authors: Rodrigues Daniela , Nogueira Helena , Gama Augusta , Machado-Rodrigues Aristides M. , Silva Maria-Raquel G. , Rosado-Marques Vítor , Padez Cristina
Published: January 2022

Background: This cross-sectional study aimed to explore how parental perceptions of the social and physical environment of the neighborhood was associated with 3- to 10-year-old children’s use of traditional and modern screen devices. Methods: Participants were recruited under the scope of the project ObesInCrisis, conducted in 2016–2017 in the cities of Porto, Coimbra, and Lisbon (Portugal). Data from 6347 children aged 3–10 years were analyzed (3169 boys [49.9%]). A parental questionnaire was used to collect data on children’s screen time (dependent variable) and parents’ perceived social and physical environment (from the Environmental Module of the International Physical Activity Prevalence Study questionnaire; independent variable), parental education, and urbanization (used as covariates). Results: Neighborhood features were more correlated with girls’ screen time, than with boys’, particularly among younger children. Also, more social than physical characteristics of the neighborhood were positively associated with children’s use of television and mobile devices (ie, tablet and smartphone). Conclusions: Community-based approaches should improve the social environment and implement supervised after-school programs to encourage and support children to be outdoors and spend less time in sedentary pursuits.
Complaints about excessive use of police force in women’s neighborhoods and subsequent perinatal and cardiovascular health
Authors: Freedman Alexa A. , Papachristos Andrew V. , Smart Britney P. , Keenan-Devlin Lauren S. , Khan Sadiya S. , Borders Ann , Kershaw Kiarri N. , Miller Gregory E.
Published: January 2022

There are substantial, unexplained racial disparities in women’s health. Some of the most pronounced involve elevated rates of preterm delivery (PTD) and cardiovascular disease (CVD) among Black women. We hypothesized that stress associated with excessive use of force by police may contribute to these disparities. In two prospective cohorts derived from electronic health records (pregnancy cohort,
N
= 67,976; CVD cohort,
N
= 6773), we linked formal complaints of excessive police force in patients’ neighborhoods with health outcomes. Exposed Black women were 1.19 times as likely to experience PTD [95% confidence interval (CI): 1.04 to 1.35] and 1.42 times as likely to develop CVD (95% CI: 1.12 to 1.79), even after adjustment for neighborhood disadvantage and homicide. The excess risks of PTD were also observed in maternal fixed-effects analyses comparing births to the same woman. These findings suggest police violence may be an unrecognized contributor to health inequity for Black women.
Antiviral Activity and Resistance Profile of the Novel HIV-1 Non-Catalytic Site Integrase Inhibitor JTP-0157602
Authors: Ohata Yoshitsugu , Tomonaga Mitsunori , Watanabe Yasuo , Tomura Keiko , Kimura Koji , Akaki Tatsuo , Adachi Kaoru , Kodama Eiichi N. , Matsuzaki Yuji , Hayashi Hironori
Published: January 2022

Non-catalytic site integrase inhibitors (NCINIs) are allosteric HIV-1 integrase (IN) inhibitors that bind to the lens epithelium-derived growth factor (LEDGF)/p75 binding pocket of IN. NCINIs are expected to be a new class of anti-HIV-1 agents.
Identification of a Permissive Secondary Mutation That Restores the Enzymatic Activity of Oseltamivir Resistance Mutation H275Y
Authors: Jiang Li , Samant Neha , Liu Ping , Somasundaran Mohan , Jensen Jeffrey D. , Marasco Wayne A. , Kowalik Timothy F. , Schiffer Celia A. , Finberg Robert W. , Wang Jennifer P. , Bolon Daniel N. A.
Published: January 2022

The potential for influenza A virus (IAV) to cause pandemics makes understanding evolutionary mechanisms that impact drug resistance critical for developing surveillance and treatment strategies. Oseltamivir is the most widely used therapeutic strategy to treat IAV infections, but mutations in IAV can lead to drug resistance.
Rosin Soap Exhibits Virucidal Activity
Authors: Bell Stephen H. , Fairley Derek J. , Kettunen Hannele , Vuorenmaa Juhani , Orte Juha , Bamford Connor G. G. , McGrath John W.
Published: January 2022

Viruses remain a significant cause of human disease and death, most notably illustrated through the current coronavirus disease 2019 (COVID-19) pandemic. Control of virus infection continues to pose a significant global health challenge to the human population.
Supplemental Material: Ultrahigh-temperature granites and a curious thermal eye in the post-collisional South Bohemian batholith of the Variscan orogenic belt (Europe)
Authors: Finger Fritz , al. et
Published: January 2022

Zircon thermometry protocol and geochemical data.
Supplemental Material: U-Pb detrital zircon analysis of sedimentary rocks of the southeastern New England Avalon terrane in the U.S. Appalachians: Evidence for a separate crustal block
Authors: Kuiper Yvette D. , al. et
Published: January 2022

Table S1: LA-ICP-MS isotopic U-Pb and trace element concentration data and Table S2: CA-TIMS zircon U-Pb isotopic data for Seiland standard reference material
Supplemental Material: Cenozoic magmatism and plate tectonics in western North America: Have we got it wrong?
Authors: Glazner Allen
Published: January 2022

Animation of space-time patterns of magmatism in the western United States
Public support for policies to regulate flavoured tobacco and e-cigarette products in rural California
Authors: Payán Denise Diaz , Burke Nancy J , Persinger Jamie , Martinez Juliette , Jones Barker Lisa , Song Anna V
Published: January 2022

Introduction

Flavoured tobacco control policy exemptions and electronic cigarette products may contribute to increased youth access and tobacco use disparities.

Methods

We assessed public support among California Central Valley residents for four policies to regulate flavoured tobacco products and e-cigarettes. The probability-based, multimode survey was conducted with English-speaking and Spanish-speaking registered voters (n=845) across 11 counties between 13 and 18 August 2020. Weighted logistic regression analyses measured odds of policy support, adjusting for predictor variables (attitudes and beliefs) and covariates.

Results

The weighted sample was 50% female and predominantly Latino (30%) or non-Hispanic white (46%); 26% had a high school education or less, and 22% an annual household income <US$30 000. Overall, 58% support a comprehensive flavoured tobacco product sales ban, and 59% support a flavoured e-cigarette product sales ban. In addition, 81% support limiting the amount of nicotine in e-cigarette pods, and 91% support mandating vaping health warning signs at local retailers. Flavour bans were more likely to be backed by women, seniors, Latinos, non-smokers and non-vapers. Participants who believe minors have more access to flavoured products had greater odds of supporting all policies. Those aware of the association between e-cigarettes and lung injury were more likely to support non-ban policies. Participants who believe e-cigarettes help to reduce tobacco use or e-cigarettes are relatively less addictive were less likely to support bans.

Discussion

Findings add to mounting evidence of support for policies to regulate flavoured tobacco and e-cigarette products. Results on attitudes and beliefs elucidate how these factors influence support.
High intramuscular triglyceride turnover rates and the link to insulin sensitivity: influence of obesity, type 2 diabetes and physical activity
Authors: Barrett J.S. , Whytock K.L. , Strauss J.A. , Wagenmakers A.J.M. , Shepherd S.O.
Published: January 2022

Large intramuscular triglyceride (IMTG) stores in sedentary, obese individuals have been linked to insulin resistance, yet well-trained athletes exhibit high IMTG levels whilst maintaining insulin sensitivity. Contrary to previous assumptions, it is now known that IMTG content per se does not result in insulin resistance. Rather, insulin resistance is caused, at least in part, by the presence of high concentrations of harmful lipid metabolites, such as diacylglycerols and ceramides in muscle. Several mechanistic differences between obese sedentary individuals and their highly trained counterparts have been identified, which determine the differential capacity for IMTG synthesis and breakdown in these populations. In this review, we first describe the most up-to-date mechanisms by which a low IMTG turnover rate (both breakdown and synthesis) leads to the accumulation of lipid metabolites and results in skeletal muscle insulin resistance. We then explore current and potential exercise and nutritional strategies that target IMTG turnover in sedentary obese individuals, to improve insulin sensitivity. Overall, improving IMTG turnover should be an important component of successful interventions that aim to prevent the development of insulin resistance in the ever-expanding sedentary, overweight and obese populations.

Novelty: A description of the most up-to-date mechanisms regulating turnover of the IMTG pool. An exploration of current and potential exercise/nutritional strategies to target and enhance IMTG turnover in obese individuals. Overall, highlights the importance of improving IMTG turnover to prevent the development of insulin resistance.
An improved car-following model considering the preceding vehicle’s velocity feedback and desired inter-vehicle distance
Authors: Kang Chengjun , Qian Yongsheng , Zeng Junwei , Wei Xuting
Published: January 2022

In this paper, an improved car-following model is raised by taking the preceding vehicle’s velocity feedback and desired inter-vehicle distance into account. The asymptotic and local stability criteria are obtained via control theory method to analyze the effect of the preceding vehicle’s velocity feedback and desired inter-vehicle distance on dynamic characteristics of traffic flow. In addition, numerical simulations are constructed on vehicle starting and traffic flow evolution processes, which show that the proposed car-following model can better present the characteristics of traffic flow. The preceding vehicle’s velocity feedback and desired inter-vehicle distance play a vital role on vehicle starting process and the stability of traffic flow.
Deep Learning-Based Image Geolocation for Travel Recommendation via Multi-Task Learning
Authors: Gu Fangfang , Jiang Keshen , Hu Xiaoyi , Yang Jie
Published: January 2022

Localizing images by visual information is a very challenging task in image-based travel recommendations. Travelers take a large number of pictures every day and share them on social networks (Facebook, Sina Weibo, Yelp, etc.). Many of these images are associated with the location where they are taken. But for images that do not associate with geographic location information, how to estimate where they are taken? With the rapid development of social media, the increasing number of shared geographic-labeled images brings an opportunity to address this problem. Using geographic-labeled images to estimate the location of unlabeled images is a popular approach. In this paper, we propose an image geographic location estimation model via multi-task learning (GLML). It combines the classification task and retrieval task to calculate the similarity between the query image and dataset images. Additionally, it fuses multi-global features through multiple global pooling techniques to enhance feature extraction. Each part of the proposed GLML model is flexible and extensible. Experiments on seven public datasets show the effectiveness of the proposed model.
GPU enabled Improved Reference Ideal Method (I-RIM) for Web Service Selection
Authors: Swetha N. G. , Karpagam G. R.
Published: January 2022

Web services are globally utilized by clients to accomplish the required functionality over the web. As a result of its popularity and flexibility in usage, thousands of functionally similar web services are available over the network. Hence, it becomes necessary to select the optimal web service to satisfy the clients’ need. Various methodologies like machine learning, genetic algorithm, bio-inspired techniques, multi-criteria decision making (MCDM) methods and many others aid in the process of selecting the best web service from thousands of alternatives. This paper aims in proposing a relatively new MCDM approach to solve the selection issue and thereby proposes a novel framework incorporating the proposed MCDM method to aid in the process of service selection. Reference ideal method (RIM) is a state-of-the-art MCDM technique to select the optimal web service based on user inputs. In spite of its popularity, this method is found to have multiple pitfalls which make the selection process less effective. This paper proposes a novel MCDM methodology named improved RIM (I-RIM) to overcome the existing pitfalls in RIM. The paper also proposes a novel framework which combines the power of graphics processing unit (GPU) and I-RIM to enhance the efficiency of the selection process. The proposed I-RIM when parallelized using GPU is found to outperform the parallelized MCDM techniques taken for study. The results also imply that the I-RIM is more consistent and stable towards the ranking process. It is also evident that the proposed framework which incorporates I-RIM outperforms RIM in terms of execution time, mean reciprocal rank and Spearman’s correlation coefficient which makes the framework more stable and reliable, thus, making it suitable for real-time web service selection.
The sulfur isotopic consequence of seawater sulfate distillation preserved in the Neoproterozoic Sete Lagoas post-glacial carbonate, eastern Brazil
Authors: Okubo Juliana , Kaufman Alan J. , Warren Lucas V. , Evans Michael N. , Marroquín Selva , Varni Michael A. , Misi Aroldo , Bahniuk Anelize M. , Xiao Shuhai
Published: January 2022

Since the report of tubular structures interpreted as
Cloudina
from the Neoproterozoic Sete Lagoas Formation (SLF) in the Bambuí basin of eastern Brazil, this stratigraphic unit has become a focus of numerous geochemical, palaeomagnetic, geochronological and sequence stratigraphic studies. Geochemical data from the SLF have been used to infer palaeoenvironmental conditions in the Bambuí basin and to study the
13
C enrichment reported in this and overlying units. To further address depositional environments of the SLF, we present high-resolution

δ

13
C and

δ

34
S data from the SLF in the Januária and Sete Lagoas regions. We report the presence of superheavy pyrite with

δ

34
S value greater than carbonate-associated sulfate (CAS) and observe a decrease in CAS abundance coupled with a

δ

34
S change from
c.
+20 to near +50‰. These data are interpreted as evidence for distillation of sulfate through CAS and pyrite removal from the epeiric Bambuí basin. These changes are qualitatively consistent with quantitative simulations of isotopic distillation over a period of
c.
10 myr of a seawater sulfate reservoir comparable with modern concentration. Considering that Neoproterozoic seawater sulfate concentrations were probably much lower than in modern oceans, the distillation time interval was probably much shorter than 10 myr.

Supplementary material
: MATLAB/Octave code to replicate Figs 11, 12 and 13 is available at
https://doi.org/10.6084/m9.figshare.c.5845089

Thematic collection:
This article is part of the Sulfur in the Earth system collection available at:
https://www.lyellcollection.org/cc/sulfur-in-the-earth-system
Acellular human amniotic fluid protects the ischemic-reperfused rat myocardium
Authors: Lee Young Sook , Javan Hadi , Reems Jo-Anna , Li Ling , Lusty Jessica , Schaaf Christine I. , Pierce Jan , Phillips John D. , Selzman Craig H.
Published: January 2022

Rather than targeting a single pathway implicated in myocardial reperfusion injury, cell-free human amniotic fluid—a naturally derived cocktail composed of thousands of proteins involved with innate immunity and anti-inflammation—markedly reduces injury and preserves cardiac function in a model of rodent myocardial ischemia-reperfusion. With its ubiquitous availability as well as its anti-inflammatory and nonimmunogenic properties, human cell-free amniotic fluid offers potential for use as a cardioprotective adjunct.
Evaluation and Analysis of High Quality Economic Development Indicators by the Analytic Hierarchy Process Model
Authors: Wang Guoqiang
Published: January 2022

The extensive and unsustainable economic development has seriously hindered the friendly development of the economy. The economy pays more attention to the quality and quality of development and needs a way to evaluate economic development objectively. The study puts forward four first-level indicators and 12 second-level indicators for high-quality economic development, which can be evaluated from the essence of economic development. The initial stage is to construct the model structure, with high-quality economic development as the higher level and economic structure and green development as the middle levels of the analytic hierarchy process (AHP); to construct the matrix and introduce secondary indicators; to calculate the maximum eigenvalue; and to analyze and evaluate. In the example, the economic development quality of a region is evaluated, and the corresponding quality membership degree is higher, which belongs to the better development quality. The hierarchical development model proposed in this paper can better evaluate the lack of development power due to the imbalance of economic development and environmental factors and fundamentally realize the fair and just evaluation of the process of economic development.
Development of Assessment Tool to Measure Children’s Knowledge on Dengue Prevention Activities in Malaysia
Authors: Siti Nur Farhana H. , Noorlaile J. , Manimaran K. , Kamarul Zaman S. , Normawati A. , Panting Albeny Joslyn
Published: January 2022

Dengue is one of the public health concerns in developing and developed countries. Since the main control measure for dengue is health prevention and control activities, especially among children, it is essential to assess children’s knowledge on dengue prevention activities in preventing the disease. This study aimed to develop an assessment tool (CAB-IHBR-Dengue-C-01) attempting to measure children’s knowledge of dengue prevention activities in Malaysia. Twelve (12) pictorials with descriptions were developed to capture children’s understanding of the correct method of dengue prevention activities. Cronbach’ alpha test was used to assess the internal consistency of the items, and the test and retest reliability method was used to measure the consistency of the questionnaire. For test-retest reliability analysis, tests were conducted twice, with an interval of two (2) weeks from the first test. In total, 58 respondents comprising of Malay, Chinese, and Indian aged between 7 and 12 years old were included in this study. The results showed the intraclass correlation coefficient (ICC) score was 0.640; with moderate reliability; meanwhile, Cronbach’s alpha score was 0.606. In conclusion, CAB-IHBR-Dengue-C-01 (Cognitive Affective Behaviour-Institute for Health Behavioural Research-Dengue-Children-Version 01) is reliable to be used.
Construction and Validation of a Newly Prognostic Signature for CRISPR-Cas9-Based Cancer Dependency Map Genes in Breast Cancer
Authors: Yan Xin , You Sai-Nan , Chen Yan , Qian Ke
Published: January 2022

Cancer Dependency Map (CDM) genes comprise an extensive series of genome-scale RNAi-based loss-of-function tests; hence, it served as a method based on the CRISPR-Cas9 technique that could assist scientists in investigating potential gene functions. These CDM genes have a role in tumor cell survival and proliferation, suggesting that they may be used as new therapeutic targets for some malignant tumors. So far, there have been less research on the involvement of CDM genes in breast cancer, and only a tiny percentage of CDM genes have been studied. In this study, information of patients with breast cancer was extracted from The Cancer Genome Atlas (TCGA), from which differentially expressed CDM genes in breast cancer were determined. A variety of bioinformatics techniques were used to assess the functions and prognostic relevance of these confirmed CDM genes. In all, 290 CDM genes were found differentially expressed. Six CDM genes (SRF, RAD51, PMF1, EXOSC3, EXOC1, and TSEN54) were found to be associated with the prognosis of breast cancer samples. Based on the expression of the identified CDM genes and their coefficients, a prognosis model was constructed for prediction, according to which patients with breast cancer were separated into two risk groups. Those with high risk had substantially poorer overall survival (OS) than patients in the other risk group in the TCGA training set, TCGA testing set, and an external cohort from Gene Expression Omnibus (GEO) database. The area under the receiver operating characteristic (ROC) curve for this prognostic signature was, respectively, 0.717 and 0.635 for TCGA training and testing sets, demonstrating its reliability in predicting the prognosis of patients with breast cancer. We next created a nomogram using the six CDM genes discovered to create a therapeutically useful model. The Human Protein Atlas database was used to acquire all immunohistochemistry staining images of the discovered CDM genes. The proportions of tumor-infiltrating immune cells, as well as the expression levels of checkpoint genes, varied substantially between the two risk groups, according to the analyses of immune response. In conclusion, the findings of this research may aid in the understanding of the prognostic value and biological roles of CDM genes in breast cancer.
User Recruitment Algorithm for Maximizing Quality under Limited Budget in Mobile Crowdsensing
Authors: Jiang Weijin , Chen Pingping , Zhang Wanqing , Sun Yongxia , Junpeng Chen , Wen Qing
Published: January 2022

In the mobile crowdsensing task assignment, under the premise that the data platform does not know the user’s perceived quality or cost value, how to establish a suitable user recruitment mechanism is the critical issue that this article needs to solve. It is necessary to learn the user’s perceived quality in the execution p. It also needs to try its best to ensure the efficiency and profit maximization of the mobile group intelligence perception platform. Therefore, this paper proposes a mobile crowdsensing user recruitment algorithm based on Combinatorial Multiarmed Bandit (CMAB) to solve the recruitment problem with known and unknown user costs. Firstly, the user recruitment process is modeled as a combined multiarm bandit model. Each rocker arm represents the selection of different users, and the income obtained represents the user’s perceived quality. Secondly, it proposes the upper confidence bound (UCB) algorithm, which updates the user’s perceptual quality according to the completion of the task. This algorithm sorts the users’ perceived quality values from high to low, then selects the most significant ratio of perceived quality to recruitment costs under the budget condition, assigns tasks, and updates their perceived quality. Finally, this paper introduces the regret value to measure the efficiency of the user recruitment algorithm and conducts many experimental simulations based on real data sets to verify the feasibility and effectiveness of the algorithm. The experimental results show that the recruitment algorithm with known user cost is close to the optimal algorithm, and the recruitment algorithm with unknown user cost is more than 75% of the optimal algorithm result, and the gap tends to decrease as the budget cost increases, compared with other comparisons. The algorithm is 25% higher, which proves that the proposed algorithm has good learning ability and can independently select high‐quality users to realize task assignments.
Rumor Detection with Bidirectional Graph Attention Networks
Authors: Yang Xiaohui , Ma Hailong , Wang Miao
Published: January 2022

In order to extract the relevant features of rumors effectively, this paper proposes a novel rumor detection model with bidirectional graph attention network on the basis of constructing a directed graph, named P-BiGAT. Firstly, this model builds the propagation tree and diffusion tree through the tweet comment and reposting relationship. Secondly, the improved graph attention network (GAT) is used to extract the propagation feature and the diffusion feature through two different directions, and the multihead attention mechanism is used to extract the semantic information of the source tweet. Finally, the propagation feature, diffusion feature, and semantic information representation of the source tweet are connected together through a fully connected layer, and the mapping function is used to determine the authenticity of the information. In addition, this paper also proposes a new node update method and applies it to the model in order to select neighbor node information effectively. Specifically, it can select the neighbor information node with larger weight to update the node according to the weight of the neighbor node. The results of the experiment show that the model is better than the baseline method of comparison in accuracy, precision, recall, and F1 measure on the public datasets.
Forest Ecological Diversity Change Prediction Discrete Dynamic Model
Authors: Li Jingxia , Zhou Aijun , Liao Yongfeng , Zhao Zixin , Mao Xiaoli , Zhang Shuoxin
Published: January 2022

Forest ecosystem is the most important terrestrial ecosystem type of species diversity in the world. The protection and sustainable use of forest ecological diversity is of great significance to forest protection and sustainable management. In order to maintain biodiversity, the traditional concept of forest resources management must be changed. In recent years, the mining and application of big data have become the frontier content of international ecological diversity and macroecology research. By establishing the discrete dynamic model of forest ecological diversity change, this study finds a method that can keep the number of trees stable in a short time and ensure the sustainable development of forest resources. This article studies and constructs the forest information system and constructs an open‐source WebGIS (network geographic information system) scheme for the field of spatial information and supporting OGC (occupationally generated content). At the same time, the grey theory GM (1,1) model is used to predict the development trend of forest resources in China. The results show that under the promotion of policies and research projects, China’s forestry development has realized the double growth of forest area and volume, and the forest coverage rate has reached a new level.
Estimation of Hydraulic Properties in Permeable Pavement Subjected to Clogging Simulation
Authors: Lu Guoyang , He Zijian , Liu Pengfei , He Zhihao , Li Gaoyang , Jiang Hao , Oeser Markus
Published: January 2022

Permeable pavements are often affected by pore clogging, which leads to their functional failure and reduced service life. However, the clogging mechanism and its impact on the permeability and complex pore microstructures in pervious pavement remain unclear. The aim of current study is to quantify the clogging behavior in pervious pavement materials and carry out investigations on the development of pore characteristics and permeability. Novel polyurethane‐bound pervious mixture (PUPM) was adopted for comparative study in present research with conventional Porous Asphalt (PA). The Aachen Polishing Machine (APM) was selected to perfectly serve as a simulator for clogging process of pavement in the actual service condition. The permeability and pore microstructure of the pervious pavement material were then characterized by using the self‐developed permeameter and X‐ray Computed Tomography (CT) scanning, respectively. The development of pore characteristics in terms of clogging was experimentally illustrated. Based on the pore characteristics, the flow behavior of PUPM subjected to different clogging periods was predicted based on the developed non‐Darcy flow model. The developed experiments and analysis can further strengthen the understanding of the clogging mechanism within the porous pavement material. The results can also serve for the optimization of the pervious pavement design in the engineering application.
Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis
Authors: Yao Xueming , Wang Qiuyi , Chen Changming , Zeng Ping , Hou Lei , Zhou Jing , Huang Ying , Ma Wukai
Published: January 2022

Rheumatoid arthritis (RA) represents the consequence of an immune response of the body’s immune system attacking healthy cells. This chronic inflammatory disorder has complicated pathogenesis. Traditional Chinese medicine (TCM) is well recognized as an effective therapy in treating RA and has been widely applied for centuries. Wu-Teng-Gao (WTG) is used as a representative natural herb formula in RA treatment in China, while its mechanisms are to be fully clarified. The present study attempted to explore mechanisms of WTG on RA treatment in a network pharmacological approach and verified using experiments in vitro. Following the establishment of a rat model of collagen-induced arthritis (CIA), WTG was applied externally on the metapedes of rats. HE staining was subsequently performed to visualize the pathological changes of synovium and bone. Simultaneously, flow cytometry was conducted to detect the cell ratio of T helper 17 (Th17) and Regulatory T cells (Treg) in splenic lymphocytes. Additionally, ELISA, qRT-PCR, and Western blot assays were adopted to determine expressions of RA-related factors in joints and serum. Results of network pharmacological analysis suggested that Th17 cell differentiation might serve as a potential signaling pathway of WTG therapy for RA. Animal experiments demonstrated that WTG ameliorated the articular inflammation and effectively inhibited the destruction of articular cartilage, and decreased Th17 and Treg cell ratios in CIA rats. Furthermore, WTG also greatly suppressed relevant levels of inflammatory cytokines (IL-17, TNF-α, IL-1, and IL-6) and RNAKL, whereas it elevated expressions of anti-inflammatory cytokines IL-10 and TGF-β. Our results confirmed that WTG might improve the imbalance of Th17/Treg cells in CIA animals through differentiation regulation, thus alleviating joint inflammation and bone destruction.
A Bipolar Output Active-Switched-Inductor Converter for Bipolar DC Microgrid
Authors: Guo Yingjun , Sun Hexu
Published: January 2022

A bipolar DC microgrid shows good performance since it improves the efficiency and system’s reliability. To transmit power to the load, several DC-DC converters are required by the conventional bipolar DC microgrid, which results into large weight, volume, and high cost. To integrate bipolar DC microgrid with the photovoltaic (PV) module, a novel bipolar output converter is proposed in this paper. This converter possesses very simple circuit configuration and can achieve a high step-up voltage gain by adopting active-switched-inductor (ASL) network; meanwhile, bipolar output voltage is between positive line (P), negative line (N), and common ground (O), which can offer three voltage classes (Vdc, +0.5 Vdc and -0.5 Vdc). To verify the precision of the analysis of the proposed converter, a prototype has been designed and experiments are performed in the lab.
The Permeability Alternation of Shale Fractures due to Sc-CO2 Soaking: Implications for Sc-CO2 Fracturing and Deep CO2 Sequestration in Shale Reservoirs
Authors: Lu Zhaohui , Jia Yunzhong , Zhou Jiankun , He Pei , Li Menglai , Song Zhengyang , Cai Xin
Published: January 2022

The shale fracture permeability is critical in determining gas production and deep CO2 sequestration performance. Moreover, how shale fracture permeability evolves after interactions with supercritical carbon dioxide (Sc-CO2) should be understood to constrain the shale reservoir permeability and evaluate the long-term sealing ability of shale formations. In this research, we conducted soaking experiments with shale fractures and Sc-CO2 at various times and then measured the shale fracture permeability and hydraulic aperture evolution under different stress states. Additionally, we quantify the chemical compositions, pore characteristics, fracture surface roughness alternation through X-ray diffraction, nuclear magnetic resonance, scanning electron microscope, and optical profilometry techniques. Our results indicate that soaking with Sc-CO2 will dramatically increase the shale fracture permeability and aperture due to the calcite and dolomite dissolution. This free-face dissolution process will remove the mineral particles in the fracture surface, resulting in larger pores, peaks, and valleys in the fracture surfaces. This process may last for seven days, and after that, chemical reactions may terminate, and the rock-Sc-CO2 system turns stable. Our results explain how Sc-CO2 alters the shale fracture permeability through the chemical dissolution of specific minerals from a microscale analysis.
Shear Strengthening of RC Beams with FRP Composites: Database of FE Simulations and Analysis of Studied Parameters
Authors: Abbasi Amirali , Chaallal Omar , El-Saikaly Georges
Published: January 2022

The use of externally bonded fiber-reinforced polymer (EB-FRP) composites for shear strengthening of reinforced concrete (RC) beams presents many challenges given the complex phenomena that come into play. Premature bond failure, the behavior of the interface layer between FRP composites and the concrete substrate, the complex and brittle nature of shear cracks, and the adverse interaction between internal steel stirrups and EB-FRP are some of these phenomena. Compared to experimental investigations, the finite element (FE) technique provides an accurate, cost-effective, and less time-consuming tool, enabling practicing engineers to perform efficient, accurate nonlinear and dynamic analysis as well as parametric studies on RC beams strengthened with EB-FRP. Since 1996, many numerical studies have been carried out on the response of RC beams strengthened using FRP. However, only a few have been related to RC beams strengthened in shear using EB-FRP composites. In addition, the analytical models that have been reported so far have failed to address and encompass all the factors affecting the contribution of EB-FRP to shear resistance because they have mostly been based on experimental studies with limited scopes. The aim of this paper is to build an extensive database of all the studies using finite element analysis (FEA) carried out on RC beams strengthened in shear with EB-FRP composites and to evaluate their strengths and weaknesses through various studied parameters.
Application of Multilevel Gray Model in Tourism Economic Performance Evaluation
Authors: Xu Bo , Gao Biao , Nimer Abukhalifeh Alaa , Zhang Songting , Wu Yichao , Jiang Naiyuan
Published: January 2022

The tourism industry is contributing to the rise in the national economy because of its outstanding advantages in increasing employment and winning regional economic vitality. But, there is no study to systematically evaluate the performance of China’s tourism economy. Therefore, this paper adopts a multilevel gray model and scientifically constructs a tourism economic performance evaluation index system. It is found that China’s tourism economic performance has the advantages of excellent development infrastructure conditions and abundant tourism resources but still has deficiencies in the aspects of social environment support, international market demand, and tourism environment support. The sustainable development potential of China’s tourism industry needs to be strengthened in three aspects in the future, namely, strengthening the government’s macroguidance, expanding the tourism high‐quality talent pool, and enhancing the construction of tourism infrastructure and service facilities.
Targeting Squalene Epoxidase Interrupts Homologous Recombination via the ER Stress Response and Promotes Radiotherapy Efficacy
Authors: Hong Zhipeng , Liu Tao , Wan Lingfeng , Fa Pengyan , Kumar Pankaj , Cao Yanan , Prasad Chandra Bhushan , Qiu Zhaojun , Liu Joseph , Wang Hongbing , Li Zaibo , Wang Qi-En , Guo Peixuan , Guo Deliang , Yilmaz Ayse S. , Lu Lanchun , Papandreou Ioanna , Jacob Naduparambil K. , Yan Chunhong , Zhang Xiaoli , She Qing-Bai , Ma Zhefu , Zhang Junran
Published: January 2022

Over 50% of all patients with cancer are treated with radiotherapy. However, radiotherapy is often insufficient as a monotherapy and requires a nontoxic radiosensitizer. Squalene epoxidase (SQLE) controls cholesterol biosynthesis by converting squalene to 2,3-oxidosqualene. Given that SQLE is frequently overexpressed in human cancer, this study investigated the importance of SQLE in breast cancer and non–small cell lung cancer (NSCLC), two cancers often treated with radiotherapy. SQLE-positive IHC staining was observed in 68% of breast cancer and 56% of NSCLC specimens versus 15% and 25% in normal breast and lung tissue, respectively. Importantly, SQLE expression was an independent predictor of poor prognosis, and pharmacologic inhibition of SQLE enhanced breast and lung cancer cell radiosensitivity. In addition, SQLE inhibition enhanced sensitivity to PARP inhibition. Inhibition of SQLE interrupted homologous recombination by suppressing ataxia-telangiectasia mutated (ATM) activity via the translational upregulation of wild-type p53-induced phosphatase (WIP1), regardless of the p53 status. SQLE inhibition and subsequent squalene accumulation promoted this upregulation by triggering the endoplasmic reticulum (ER) stress response. Collectively, these results identify a novel tumor-specific radiosensitizer by revealing unrecognized cross-talk between squalene metabolites, ER stress, and the DNA damage response. Although SQLE inhibitors have been used as antifungal agents in the clinic, they have not yet been used as antitumor agents. Repurposing existing SQLE-inhibiting drugs may provide new cancer treatments.

Significance:

Squalene epoxidase inhibitors are novel tumor-specific radiosensitizers that promote ER stress and suppress homologous recombination, providing a new potential therapeutic approach to enhance radiotherapy efficacy.
Differential Kinase Activity Across Prostate Tumor Compartments Defines Sensitivity to Target Inhibition
Authors: Karabacak Nezihi Murat , Zheng Yu , Dubash Taronish D. , Burr Risa , Micalizzi Douglas S. , Wittner Ben S. , Lin Maoxuan , Wiley Devon F. , Comaills Valentine , Emmons Erin , Niederhoffer Kira L. , Ho Uyen , Ukleja Jacob , Che Dante , Stowe Hannah , Nieman Linda T. , Haas Wilhelm , Stott Shannon L. , Lawrence Michael S. , Ting David T. , Miyamoto David T. , Haber Daniel A. , Toner Mehmet , Maheswaran Shyamala
Published: January 2022

Cancer therapy often results in heterogeneous responses in different metastatic lesions in the same patient. Inter- and intratumor heterogeneity in signaling within various tumor compartments and its impact on therapy are not well characterized due to the limited sensitivity of single-cell proteomic approaches. To overcome this barrier, we applied single-cell mass cytometry with a customized 26-antibody panel to PTEN-deleted orthotopic prostate cancer xenograft models to measure the evolution of kinase activities in different tumor compartments during metastasis or drug treatment. Compared with primary tumors and circulating tumor cells (CTC), bone metastases, but not lung and liver metastases, exhibited elevated PI3K/mTOR signaling and overexpressed receptor tyrosine kinases (RTK) including c-MET protein. Suppression of c-MET impaired tumor growth in the bone. Intratumoral heterogeneity within tumor compartments also arose from highly proliferative EpCAM-high epithelial cells with increased PI3K and mTOR kinase activities coexisting with poorly proliferating EpCAM-low mesenchymal populations with reduced kinase activities; these findings were recapitulated in epithelial and mesenchymal CTC populations in patients with metastatic prostate and breast cancer. Increased kinase activity in EpCAM-high cells rendered them more sensitive to PI3K/mTOR inhibition, and drug-resistant EpCAM-low populations with reduced kinase activity emerged over time. Taken together, single-cell proteomics indicate that microenvironment- and cell state–dependent activation of kinase networks create heterogeneity and differential drug sensitivity among and within tumor populations across different sites, defining a new paradigm of drug responses to kinase inhibitors.

Significance:

Single-cell mass cytometry analyses provide insights into the differences in kinase activities across tumor compartments and cell states, which contribute to heterogeneous responses to targeted therapies.
Characterization of Epigenomic Alterations in HPV16+ Head and Neck Squamous Cell Carcinomas
Authors: Berglund Anders , Muenyi Clarisse , Siegel Erin M. , Ajidahun Abidemi , Eschrich Steven A. , Wong Denise , Hendrick Leah E. , Putney Ryan M. , Kim Sungjune , Hayes D. Neil , Shibata David
Published: January 2022

Background:

Epigenetic changes associated with human papillomavirus (HPV)–driven tumors have been described; however, HPV type–specific alterations are less well understood. We sought to compare HPV16-specific methylation changes with those in virus-unassociated head and neck squamous cell carcinomas (HNSCC).

Methods:

Within The Cancer Genome Atlas, 59 HPV16+ HNSCC, 238 nonviral HNSCC (no detectable HPV or other viruses), and 50 normal head and neck tissues were evaluated. Significant differentially methylated regions (DMR) were selected, and key associated genes were identified. Partial least squares models were generated to predict HPV16 status in additional independent samples.

Results:

HPV infection in HNSCC is associated with type-specific methylomic profiles. Multiple significant DMRs were identified between HPV16+, nonviral, and normal samples. The most significant differentially methylated genes, SYCP2, MSX2, HLTF, PITX2, and GRAMD4, demonstrated HPV16-associated methylation patterns with corresponding alterations in gene expression. Phylogenetically related HPV types (alpha-9 species; HPV31, HPV33, and HPV35) demonstrated a similar methylation profile to that of HPV16 but differed from those seen in other types, such as HPV18 and 45 (alpha-7).

Conclusions:

HNSCC linked to HPV16 and types from the same alpha species are associated with a distinct methylation profile. This HPV16-associated methylation pattern is also detected in cervical cancer and testicular germ cell tumors. We present insights into both shared and unique methylation alterations associated with HPV16+ tumors and may have implications for understanding the clinical behavior of HPV-associated HNSCC.

Impact:

HPV type–specific methylomic changes may contribute to understanding biologic mechanisms underlying differences in clinical behavior among different HPV+ and HPV− HNSCC.
Reproductive Factors Do Not Influence Survival with Ovarian Cancer
Authors: Phung Minh Tung , Alimujiang Aliya , Berchuck Andrew , Anton-Culver Hoda , Schildkraut Joellen M. , Bandera Elisa V. , Chang-Claude Jenny , Chase Anne , Doherty Jennifer Anne , Grout Bronwyn , Goodman Marc T. , Hanley Gillian E. , Lee Alice W. , McKinnon Deurloo Cindy , Menon Usha , Modugno Francesmary , Pharoah Paul D.P. , Pike Malcolm C. , Richardson Jean , Risch Harvey A. , Sieh Weiva , Terry Kathryn L. , Webb Penelope M. , Wentzensen Nicolas , Wu Anna H. , Pearce Celeste Leigh
Published: January 2022

Background:

Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small sample sizes.

Methods:

Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype.

Results:

During the mean follow-up of 6.34 years (SD = 4.80), 6,418 patients passed away (57.4%). There was no evidence of associations between the reproductive factors and survival among patients with ovarian cancer overall or by histotype.

Conclusions:

This study found no association between reproductive factors and survival after an ovarian cancer diagnosis.

Impact:

Reproductive factors are well-established risk factors for ovarian cancer, but they are not associated with survival after a diagnosis of ovarian cancer.
Radioimmunotherapy Targeting Delta-like Ligand 3 in Small Cell Lung Cancer Exhibits Antitumor Efficacy with Low Toxicity
Authors: Tully Kathryn M. , Tendler Salomon , Carter Lukas M. , Sharma Sai Kiran , Samuels Zachary V. , Mandleywala Komal , Korsen Joshua A. , Delos Reyes Avelyn Mae , Piersigilli Alessandra , Travis William D. , Sen Triparna , Pillarsetty Nagavarakishore , Poirier John T. , Rudin Charles M. , Lewis Jason S.
Published: January 2022

Purpose:

Small cell lung cancer (SCLC) is an exceptionally lethal form of lung cancer with limited treatment options. Delta-like ligand 3 (DLL3) is an attractive therapeutic target as surface expression is almost exclusive to tumor cells.

Experimental Design:

We radiolabeled the anti-DLL3 mAb SC16 with the therapeutic radioisotope, Lutetium-177. [177Lu]Lu-DTPA-CHX-A”-SC16 binds to DLL3 on SCLC cells and delivers targeted radiotherapy while minimizing radiation to healthy tissue.

Results:

[177Lu]Lu-DTPA-CHX-A”-SC16 demonstrated high tumor uptake with DLL3-target specificity in tumor xenografts. Dosimetry analyses of biodistribution studies suggested that the blood and liver were most at risk for toxicity from treatment with high doses of [177Lu]Lu-DTPA-CHX-A”-SC16. In the radioresistant NCI-H82 model, survival studies showed that 500 μCi and 750 μCi doses of [177Lu]Lu-DTPA-CHX-A”-SC16 led to prolonged survival over controls, and 3 of the 8 mice that received high doses of [177Lu]Lu-DTPA-CHX-A”-SC16 had pathologically confirmed complete responses (CR). In the patient-derived xenograft model Lu149, all doses of [177Lu]Lu-DTPA-CHX-A”-SC16 markedly prolonged survival. At the 250 μCi and 500 μCi doses, 5 of 10 and 7 of 9 mice demonstrated pathologically confirmed CRs, respectively. Four of 10 mice that received 750 μCi of [177Lu]Lu-DTPA-CHX-A”-SC16 demonstrated petechiae severe enough to warrant euthanasia, but the remaining 6 mice demonstrated pathologically confirmed CRs. IHC on residual tissues from partial responses confirmed retained DLL3 expression. Hematologic toxicity was dose-dependent and transient, with full recovery within 4 weeks. Hepatotoxicity was not observed.

Conclusions:

Together, the compelling antitumor efficacy, pathologic CRs, and mild and transient toxicity profile demonstrate strong potential for clinical translation of [177Lu]Lu-DTPA-CHX-A”-SC16.