bluuebunny/crossref_metadata_2025 huggingface dataset:
Is cancer stage data missing completely at random? A report from a large population-based cohort of non-small cell lung cancer
Authors: Robinson Andrew G. , Nguyen Paul , Goldie Catherine L. , Jalink Matthew , Hanna Timothy P.
Published: April 2023

Introduction

Population-based datasets are often used to estimate changes in utilization or outcomes of novel therapies. Inclusion or exclusion of unstaged patients may impact on interpretation of these studies.

Methods

A large population-based dataset in Ontario, Canada of non-small cell lung cancer patients was examined to evaluate the characteristics and outcomes of unstaged patients compared to staged patients. Multivariable Poisson regression was used to evaluate differences in patient-level characteristics between groups. Kaplan-Meier estimates of survival and log-rank statistics were utilized.

Results

In our Ontario cohort of 51,152 patients with NSCLC, 11.2% (n=5,707) were unstaged, and there was evidence that stage data was not missing completely at random. Those without assigned stage were more likely than staged patients to be older (RR [95%CI]), (70-79 vs. 20-59: 1.51 [1.38-1.66]; 80+ vs. 20-59: 2.87 [2.62-3.15]), have a higher comorbidity index (Score 1-2 vs 0: 1.19 [1.12-1.27]; 3 vs. 0: 1.49 [1.38-1.60]), and have a lower socioeconomic class (4 vs. 1 (lowest): 0.91 [0.84-0.98]; 5 vs. 1 (lowest): 0.89 [0.83-0.97]). Overall survival of unstaged patients suggested a mixture of early and advanced stage, but with a large proportion that are probably stage IV patients with more rapid death than those with reported stage IV disease.

Conclusion

In this case study, evaluation of stage-specific health care utilization and outcomes for staged patients with stage IV disease at the population level may have a bias as a distinct subset of stage IV patients with rapid death are likely among those without a documented stage in administrative data.
Early detection of lung cancer in a real-world cohort via tumor-associated immune autoantibody and imaging combination
Authors: Liu Zhong , Zhang Feng , Jiang Jianwen , Zhao Chenzhao , Zhu Lu , Liu Chenbing , Li Nan , Qiu Lihong , Shen Chao , Sheng Di , Zeng Qiang
Published: April 2023

Background

Efficient early detection methods for lung cancer can significantly decrease patient mortality. One promising approach is the use of tumor-associated autoantibodies (TAABs) as a diagnostic tool. In this study, the researchers aimed to evaluate the potential of seven TAABs in detecting lung cancer within a population undergoing routine health examinations. The results of this study could provide valuable insights into the utility of TAABs for lung cancer screening and diagnosis.

Methods

In this study, the serum concentrations of specific antibodies were measured using enzyme-linked immunosorbent assay (ELISA) in a cohort of 15,430 subjects. The efficacy of both a 7-TAAB panel and LDCT for lung cancer detection were evaluated through receiver operating characteristic (ROC) analyses, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) being assessed and compared. These results could have significant implications for the development of improved screening methods for lung cancer.

Results

Over the 12-month observation period, 26 individuals were diagnosed with lung cancer. The 7-TAAB panel demonstrated promising sensitivity (61.5%) and a high degree of specificity (88.5%). The panel’s area under the receiver operating characteristic (ROC) curve was 0.8062, which was superior to that of any individual TAAB. In stage I patients, the sensitivity of the panel was 50%. In our cohort, there was no gender or age bias observed. This 7-TAAB panel showed a sensitivity of approximately 60% in detecting lung cancer, regardless of histological subtype or lesion size. Notably, ground-glass nodules had a higher diagnostic rate than solid nodules (83.3% vs. 36.4%, P = 0.021). The ROC analyses further revealed that the combination of LDCT with the 7-TAAB assay exhibited a significantly superior diagnostic efficacy than LDCT alone.

Conclusion

In the context of the study, it was demonstrated that the 7-TAAB panel showed improved detective efficacy of LDCT, thus serving as an effective aid for the detection of lung cancer in real-world scenarios.
Jinhong decoction protects sepsis-associated acute lung injury by reducing intestinal bacterial translocation and improving gut microbial homeostasis
Authors: Bao Kaifan , Wang Meiling , Liu Li , Zhang Dongya , Jin Cuiyuan , Zhang Junfeng , Shi Liyun
Published: April 2023

Background: Currently no specific treatments are available for sepsis and the associated syndromes including acute lung injury (ALI). Jinhong Decoction (JHD) is a traditional Chinese prescription, and it has been applied clinically as an efficient and safe treatment for sepsis, but the underlying mechanism remains unknown. The aim of the study was to explore the potential mechanisms of JHD ameliorating sepsis and concurrent ALI.

Methods: The cecum ligation puncture (CLP)- induced murine sepsis model was established for determining the efficacy of JHD protecting CLP and ALI. The role of gut microbiota involved in the efficacy of JHD was evaluated by 16S rRNA sequencing and fecal microbiota transplantation (FMT). Translocation of intestinal Escherichia coli (E. coli) to lungs after CLP was verified by qPCR and in vivo-imaging. Intestinal permeability was analyzed by detecting FITC-dextran leakness. Junction proteins were evaluated by Western blotting and immunofluorescence.

Results: JHD treatment remarkably increased survival rate of septic mice and alleviated sepsis-associated lung inflammation and injury. FMT suggested that the protective role for JHD was mediated through the regulation of gut microbiota. We further revealed that JHD administration partially restored the diversity and configuration of microbiome that was distorted by CLP operation. Of interest, the intestinal bacteria, E. coli particularly, was found to translocate into the lungs upon CLP via disrupting the intestinal mucosal barrier, leading to the inflammatory response and tissue damage in lungs. JHD impeded the migration and hence lung accumulation of intestinal E. coli, and thereby prevented severe ALI associated with sepsis. This effect is causatively related with the ability of JHD to restore intestinal barrier by up-regulating tight junctions.

Conclusion: Our study unveils a mechanism whereby the migration of gut bacteria leads to sepsis-associated ALI, and we demonstrate the potential of JHD as an effective strategy to block this bacterial migration for treating sepsis and the associated immunopathology in the distal organs.
Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling
Authors: Wilson Claire , Zi Min , Smith Matthew , Hussain Munir , D’Souza Alicia , Dobrzynski Halina , Boyett Mark R.
Published: April 2023

Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by studying changes in the whole nodal transcriptome. The mouse transverse aortic constriction model of pressure overload-induced heart failure was studied; functional changes were assessed using electrocardiography and echocardiography and the transcriptome of the AV node was quantified using RNAseq. Heart failure was associated with a significant increase in the PR interval, indicating a slowing of AV node conduction and AV node dysfunction, and significant changes in 3,077 transcripts (5.6% of the transcriptome). Many systems were affected: transcripts supporting AV node conduction were downregulated and there were changes in transcripts identified by GWAS as determinants of the PR interval. In addition, there was evidence of remodelling of the sarcomere, a shift from fatty acid to glucose metabolism, remodelling of the extracellular matrix, and remodelling of the transcription and translation machinery. There was evidence of the causes of this widespread remodelling of the AV node: evidence of dysregulation of multiple intracellular signalling pathways, dysregulation of 109 protein kinases and 148 transcription factors, and an immune response with a proliferation of neutrophils, monocytes, macrophages and B lymphocytes and a dysregulation of 40 cytokines. In conclusion, inflammation and a widespread transcriptional remodelling of the AV node underlies AV node dysfunction in heart failure.
Zanthoxylum bungeanum seed oil inhibits tumorigenesis of human melanoma A375 by regulating CDC25A/CyclinB1/CDK1 signaling pathways in vitro and in vivo
Authors: Wang Wanting , Pang Wenwen , Yan Suying , Zheng Xiaoli , Han Qiurong , Yao Yao , Jin Leixin , Zhang Chunze
Published: April 2023

Background:Zanthoxylum bungeanum seed oil (ZBSO) is extracted from the seeds of the traditional Chinese medicine Z. bungeanum Maxim, which has been shown to have anti-melanoma effects. However, the specific mechanisms are not illustrated adequately.

Aims: To further investigate the mechanism by which ZBSO inhibits melanoma and to provide scientific evidence to support ZBSO as a potential melanoma therapeutic candidate.

Methods: CCK-8 assays were used to detect the function of ZBSO on A375 cells. Based on transcriptomics analyses, Western blot analysis was applied to determine whether an association existed in ZBSO with the CDC25A/CyclinB1/CDK1 signaling pathway. In addition, RT-qPCR and immunohistochemistry analysis validated that ZBSO has the anti-melanoma effect in a nude mouse xenograft model of human melanoma. Then, 16S rRNA sequencing was used to detect the regulation of gut microbes.

Results: Cellular assays revealed that ZBSO could inhibit A375 cell viability by regulating the cell cycle pathway. Further studies presented that ZBSO could constrain CDC25A/CyclinB1/CDK1 signaling pathway in vitro and in vivo models of melanoma. ZBSO did not produce toxicity in mice, and significantly reduced tumor volume in xenotransplants of A375 cells. Genome analysis indicated that ZBSO successfully altered specific gut microbes.

Conclusion: ZBSO inhibited the growth of A375 cells by regulating CDC25A/cyclinB1/CDK1 signaling pathway both in vitro and in vivo, suggesting that ZBSO may be a novel potential therapeutic agent.
Antennal transcriptomic analysis of carboxylesterases and glutathione S-transferases associated with odorant degradation in the tea gray geometrid, Ectropis grisescens (Lepidoptera, Geometridae)
Authors: Zhang Fangmei , Chen Yijun , Zhao Xiaocen , Guo Shibao , Hong Feng , Zhi Yanan , Zhang Li , Zhou Zhou , Zhang Yunhui , Zhou Xuguo , Li Xiangrui
Published: April 2023

Introduction: Carboxylesterases (CXEs) and glutathione S-transferases (GSTs) can terminate olfactory signals during chemosensation by rapid degradation of odorants in the vicinity of receptors. The tea grey geometrid, Ectropis grisescens (Lepidoptera, Geometridae), one of the most devastating insect herbivores of tea plants in China, relies heavily on plant volatiles to locate the host plants as well as the oviposition sites. However, CXEs and GSTs involved in signal termination and odorant clearance in E. grisescens remains unknown.

Methods: In this study, identification and spatial expression profiles of CXEs and GSTs in this major tea pest were investigated by transcriptomics and qRT-PCR, respectively.

Results: As a result, we identified 28 CXEs and 16 GSTs from female and male antennal transcriptomes. Phylogenetic analyses clustered these candidates into several clades, among which antennal CXEs, mitochondrial and cytosolic CXEs, and delta group GSTs contained genes commonly associated with odorants degradation. Spatial expression profiles showed that most CXEs (26) were expressed in antennae. In comparison, putative GSTs exhibited a diverse expression pattern across different tissues, with one GST expressed specifically in the male antennae.

Disscussion: These combined results suggest that 12 CXEs (EgriCXE1, 2, 4, 6, 8, 18, 20-22, 24, 26, and 29) and 5 GSTs (EgriGST1 and EgriGST delta group) provide a major source of candidate genes for odorants degradation in E. grisescens.
Exploring the relationship between exposure to COVID-19 and donations during the COVID-19 pandemic: The mediating roles of emotions and risk perception
Authors: Bao Yun , Zhang Yan , Wang Junxiu
Published: April 2023

Objective

Public emergency events like the COVID-19 pandemic are special occasions that need immediate massive funding from public donations. Thus, understanding the determinants of donation behaviors under public emergencies is important for both researchers and practitioners. This study investigated the effect of personal and local exposure to incidences of COVID-19 on donation behaviors. Specifically, we examined the mediating effects of risk perception and emotions on the relationship between exposure to COVID-19 and donation behaviors.

Methods

The data were from a survey distributed in China between March 20 and 30th, 2020. Participants’ donation choice at the end of the survey was used to measure their donation behaviors. Participants’ emotions, risk perception, and personal exposure were assessed in the questionnaire. Local exposure was the 30-day confirmed cases obtained from the National Health Commission of the People’s Republic of China. A total of 8,720 participants (Mean age = 28.91, 43.6% females) completed the online survey.

Results

Based on the results from the mediation analysis, we found that people with stronger positive and negative emotions, higher risk perception, and more personal exposure to COVID-19 were more likely to donate. Furthermore, the effects of both personal and local exposure on donations are mediated by risk perception and negative emotion. Both higher personal and local exposure led to stronger negative emotions and higher risk perception, which in turn led to more donation behaviors.

Discussion

This study extends our knowledge of donation behaviors during public emergencies. Our results suggest that policymakers and charity organizations should elicit stronger emotions and risk perception by exposing the severity of the disaster in advertisements to promote donations.
Perceived financial burden is indirectly linked to sexual well-being via quality of life among couples seeking medically assisted reproduction
Authors: Allsop David B. , Péloquin Katherine , Saxey Matthew T. , Rossi Meghan A. , Rosen Natalie O.
Published: April 2023

Introduction

Medically assisted reproduction is a difficult treatment process for couples both financially and sexually. Yet, these two domains have not been examined together among couples seeking treatment, leaving couples and practitioners without guidance on how to address these domains together.

Methods

In line with Couples and Finance Theory, we tested the hypothesis that perceived financial burden and couple income would predict quality of life during medically assisted reproduction, which would then predict four domains of sexual well-being (i.e., sexual satisfaction, desire, distress, and frequency). We also examined if the results differed by treatment status—that is, between partners who were receiving treatment and those who were not. Cross-sectional data from 120 couples who had undergone medically assisted reproduction in the past six months were analyzed via structural equation modeling through an actor-partner interdependence mediation model.

Results

An individual’s greater perceived financial burden predicted their own lower quality of life during medically assisted reproduction, which in turn predicted their lower sexual satisfaction, desire and distress, as well as their partner’s lower sexual satisfaction. Household income did not indirectly predict any sexual well-being domains, and results regarding treatment status were inconclusive.

Discussion

Clinicians can discuss with couples how perceived financial strain of medically assisted reproduction affects their quality of life and what ramifications that may have for their sexual well-being.
Reshaping the Curriculum for Academy in Factory in Malaysia
Authors: Jamaludin Khairul Azhar , Ealangov Suganti , Saleh Siti Nur Haslinda Md , Zabidi Nor’Aqilah Ahmad , Alias Norlidah , Yasin Mohd Hanafi Mohd , Alias Bity Salwana
Published: April 2023

Academy in Factory (AiF) was recently introduced in Malaysia to cater to the talent development and education attainment for a future-ready workforce. Though ideally expected to be an effective initiative, a lack of a strong curriculum framework hinders its implementation. To date the literature on AiF is very limited. It was found that its vague definition and characteristics, non-harmonised interaction between industry and academia, and non-existing curriculum framework are among contributing factors to its ineffective implementation. Thus, this study is aimed at reshaping a curriculum framework that is responsive to its aims and objectives. Building upon an extensive review of literature on AiF, industry-based curriculum, employability and human capital development, and best practices in the international context, the proposed framework is hoped to serve as a reference to improve its current practice.
Validation of online mindfulness-enhanced course for stress reduction in teachers
Authors: Ye Qun , Huang Ying , Ge Xingcheng , Song Xiaolan
Published: April 2023

Background

Mindfulness-based interventions have gained popularity as a means of reducing stress and increasing resilience among the preclinical population. The present study aimed to investigate the effects of an online mindfulness-enhanced course on stress reduction in teachers, especially since online learning and teaching have been frequently applied to respond to emergencies such as COVID-19-relevant school suspension.

Methods

The study consisted of two phases. Phase 1 aimed to explore the relationship between teachers' perceived stress and mindfulness traits. In total of 6,252 teachers completed assessments of stress symptoms using the Chinese Perceived Stress Scale (CPSS) and occupational stress sources, as well as mindfulness using the Five Factor Mindfulness Questionnaire (FFMQ). Phase 2 aimed to examine the effectiveness of the online mindfulness-enhanced course. In total of 132 teachers were randomly assigned to either receive a 3-week online mindfulness course specifically designed for stress reduction and emotion regulation (N = 66) or a matched active control group (N = 66) and their pre-training and post-training self-reported states (e.g., perceived stress, mindfulness level, practice time) were measured.

Results

The detection rate of Health Risk Stress (≥26 scores) was as high as 61.72%, and a negative association between the score of FFMQ and perceived stress level was found. Importantly, compared to the control group, the mindfulness training group showed a significant decrease in perceived stress and negative emotion, as well as an increase in understanding of the core mechanisms of mindfulness after training. Additionally, individual improvement in FFMQ scores was predicted by practice time.

Conclusions

The study showed a high percentage of teachers experiencing stress, and the data supported the reliability and validity of the brief online mindfulness-enhanced course designed to reduce stress and regulate emotion for frontline teachers.
ARMA model development and analysis for global temperature uncertainty
Authors: Hasan Mahmud , Wathodkar Gauree , Muia Mathias
Published: April 2023

Temperature uncertainty models for land and sea surfaces can be developed based on statistical methods. In this paper, we developed a novel time-series temperature uncertainty model, which is the autoregressive moving average (ARMA) (1,1) model. The model was developed for an observed annual mean temperature anomaly X(t), which is a combination of a true (latent) global anomaly Y(t) for a year (t) and normal variable w(t). The uncertainty is taken as the variance of w(t), which was divided into land surface temperature (LST) uncertainty, sea surface temperature (SST) uncertainty, and the corresponding source of uncertainty. The ARMA model was analyzed and compared with autoregressive (AR) and autoregressive integrated moving average (ARIMA) for the data obtained from the NASA Goddard Institute for Space Studies Surface Temperature (GISTEMP) Analysis. The statistical analysis of the autocorrelation function (ACF), partial autocorrelation function (PACF), normal quantile–quantile (normal Q-Q) plot, density of the residuals, and variance of normal variable w(t) shows that ARMA (1,1) fits better than AR (1) and ARIMA (1, d, 1) for d = 1, 2.
COVID-19 Mass Vaccination Campaign: An International Comparison of Qatar With GCC Nations and Other Global Groups
Authors: Abdullahi Yasmin Ali Morad
Published: April 2023

Objectives: Mass vaccination has been a key component in the effort to control the COVID-19 pandemic. Different countries have formulated their mass vaccination campaigns in different ways and with different priorities, with varying results. This study focuses on the case of Qatar in comparison with regional neighbors in the Gulf Cooperation Community (GCC) and with global benchmarks (G7 and OECD nations) in terms of the deployment of its mass vaccination program.

Methods: Data on national vaccine administration and policy were obtained from Our World in Data and the Oxford COVID-19 Government Response Tracker for the period of 25 November 2020, when public vaccination first began to be implemented within the GCC, and June 2021, when Qatar’s mass vaccination campaign concluded. Factors compared cross-nationally included the total number of vaccine doses administered, doses administered per 100 population, the time taken to reach certain vaccination thresholds (5, 10, 25, 50, and 100 doses per 100 population), and policy regarding administration to specific priority groups. Cumulative vaccination rates were also compared graphically by date.

Results: A descriptive comparison of vaccination rates illustrated that there were similar aggregate patterns among the GCC, G7, and OECD groups of countries, and that there was a great deal of heterogeneity in the patterns of vaccination between countries within each of these groups. The mass vaccination program in Qatar outpaced the aggregate GCC, G7, and OECD groups.

Conclusion: There were large between-country differences in the speed of mass vaccination progress which did not appear to be directly explained by national wealth. It is suggested that administrative and program management factors could account for some of these differences.
A Novel Fault-Tolerant Air Traffic Management Methodology Using Autoencoder and P2P Blockchain Consensus Protocol
Authors: Hashemi Seyed Mohammad , Hashemi Seyed Ali , Botez Ruxandra Mihaela , Ghazi Georges
Published: April 2023

This paper presents a methodology for designing a highly reliable Air Traffic Management and Control (ATMC) methodology using Neural Networks and Peer-to-Peer (P2P) blockchain. A novel data-driven algorithm was designed for Aircraft Trajectory Prediction (ATP) based on an Autoencoder architecture. The Autoencoder was considered in this study due to its excellent fault-tolerant ability when the input data provided by the GPS is deficient. After conflict detection, P2P blockchain was used for securely decentralized decision-making. A meta-controller composed of this Autoencoder, and P2P blockchain performed the ATMC task very well. A comprehensive database of trajectories constructed using our UAS-S4 Ehécatl was used for algorithms validation. The accuracy of the ATP was evaluated for a variety of data failures, and the high-performance index confirmed the excellent efficiency of the autoencoder. Aircraft were considered in several local encounter scenarios, and their trajectories were securely managed and controlled using our in-house Smart Contract software developed on the Ethereum platform. The Sharding approach improved the P2P blockchain performance in terms of computational complexity and processing time in real-time operations. Therefore, the probability of conflicts among aircraft in a swarm environment was significantly reduced using our new methodology and algorithm.
Fermentation Profile, Nutritional Quality and Microbial Populations of Melon Plant Biomass Silage Ensiled with Corn Bran
Authors: Nascimento Romilda Rodrigues do , Edvan Ricardo Loiola , Nascimento Keuven dos Santos , Alves Barros Dhiéssica Morgana , Rocha Arturene Marques , Dias e Silva Tairon Pannunzio , Santos Edson Mauro , Miranda Rafael de Souza , Biagiotti Daniel , Araújo Marcos Jácome de
Published: April 2023

Currently, there is no use for melon plant biomass in agriculture and animal feeding. Using this biomass as silage provides a more sustainable production system. Thus, the objective of this study was to evaluate the silage produced with different mixtures of melon plant biomass and ground corn. The experimental design was completely randomized in a factorial scheme (5 × 2) with five replications. The treatments consisted of five mixtures of melon plant biomass between the plant (branch + leaf) and the fruit (melon scrapings) in amounts of 0% fruit, 5% fruit, 10% fruit, 20% fruit, and 100% fruit on an as-fed basis and ground corn in amounts of 0% and 5% AF of the ensiled biomass. The greatest dry matter contents were found in silages with corn and 0 and 5% fruit, which were 225.6 g/kg and 235.2 g/kg, respectively. The highest concentrations of acetic acid were found in the silages with 0% fruit without corn and 20% fruit with ground corn and were 10.96 and 10.00 g/kg DM, respectively. The use of melon fruit biomass with 0%, 5%, and 100% fruit is the most suitable for silage making, and adding ground corn improves silage quality parameters.
Targeting IgE and Th2-Cytokines in Allergy: Brief Updates on Monoclonal Antibodies and Antibody Gene Therapy
Authors: Ezechukwu Henry C. , Adegboye Oyelola A. , Okunowo Wahab O. , Emeto Theophilus I.
Published: April 2023

The search for an effective treatment of allergic conditions is an ongoing global health challenge due to the high prevalence of allergies. Epinephrine and glucocorticosteroids remain the oldest and most widely used treatment regimen for allergy, and these medications are for short relief. In extreme allergy manifestations, the current treatment options aim to use monoclonal antibody (mAb) to target pathological pathways of inflammation involving mast cells, eosinophils, and basophils. These cells have the propensity to induce an allergic-inflammatory response. Studies have shown that they are responsible for several allergic diseases, such as allergic asthma, atopic dermatitis, rhinitis, and conjunctivitis. Studies evaluating monoclonal antibodies against serum IgE (Omalizumab), Th-2 cytokines, such as IL-4, IL-13 (dupilumab), and IL-5 suggest an attenuation of allergic symptoms and improvement in patients’ overall well-being. However, several factors such as cost of production (i.e., antibody purification), host immunogenicity, safety, and efficacy have hindered the availability of purified mAb in developing countries. Gene therapy is a promising tool for treating allergy, and emerging studies have suggested that antibody gene therapy may be the future for treating extreme cases of allergy manifestations. This paper describes the use of purified monoclonal antibodies for treating severe allergic responses and the associated limitations. It explores the prospects of antibody gene therapy for modulating allergy episodes.
New Insights into the Variation and Admixture of the Cave-Dwelling Spider Trogloneta yunnanensis in South China Karst
Authors: Liu Shiliang , Zhou Chuang , Lin Yucheng
Published: April 2023

Subterranean karst caves can contain unexpected biodiversity, but few studies related to spider population genetics have been conducted in the karst area of Southern China. In this study, we investigated the population genetic structure of Trogloneta yunnanensis (Song & Zhu, 1994) based on 73 spider samples from six underground populations in South China Karst. Population genetic structure analysis showed a clear divergence (FST > 0.9 and Nm < 0.05) among populations according to mitochondrial genes. The phylogenetic gene tree constructed by BI and ML methods recovered six geographic clades. Divergence time estimation indicated that the divergence of these six populations can be traced back to the late Pleistocene. We supposed that the geographic isolation led to the extreme population structure. According to this study and previous studies about troglobites living in this region, the subterranean habitats of the Yunnan-Guizhou Plateau may contain many organisms with similar genetic structures. The subterranean biodiversity in the karst area of Southern China needs to be re-evaluated and protected.
Identification of Potential miRNA-mRNA Regulatory Network Associated with Regulating Immunity and Metabolism in Pigs Induced by ASFV Infection
Authors: Pang Zhongbao , Chen Shiyu , Cui Shuai , Zhai Wenzhu , Huang Ying , Gao Xintao , Wang Yang , Jiang Fei , Guo Xiaoyu , Hao Yuxin , Li Wencai , Wang Lei , Zhu Hongfei , Wu Jiajun , Jia Hong
Published: April 2023

African swine fever (ASF) is a devastating infectious disease in domestic pigs caused by African swine fever virus (ASFV) with a mortality rate of about 100%. However, the understanding of the interaction between ASFV and host is still not clear. In this study, the expression differences and functional analysis of microRNA (miRNA) in porcine peripheral blood lymphocytes of ASFV infected pigs and healthy pigs were compared based on Illumina high-throughput sequencing, then the GO and KEGG signal pathways were analyzed. The miRNA related to immunity and inflammation were screened, and the regulatory network of miRNA-mRNA was drawn. A total of 70 differentially expressed miRNAs were found (p ≤ 0.05). Of these, 45 were upregulated and 25 were downregulated in ASFV-infected pigs vs. healthy pigs. A total of 8179 mRNA genes targeted by these 70 differentially expressed miRNA were predicted, of which 1447 mRNA genes were targeted by ssc-miR-2320-5p. Five differentially expressed miRNA were validated by RT-qPCR, which were consistent with the RNA-Seq results. The GO analysis revealed that a total of 30 gene functions were significantly enriched, including 7 molecular functions (MF), 13 cellular components (CC), and 10 biological processes (BP). The KEGG enrichment analysis revealed that the differentially expressed genes were significantly enriched in pathways related to immunity, inflammation, and various metabolic processes, in which a total of two downregulated miRNAs after infection and eight upregulated miRNAs related to immunity and inflammation were screened in ASFV-infected pigs vs. healthy pigs. The network of miRNA-mRNA showed that the mRNA target genes were strongly regulated by ssc-miR-214, ssc-miR-199b-3p, and ssc-miR-199a-3p. The mRNA target genes were enriched into the MAPK signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, and IL-17 signaling pathway by using a KEGG enrichment analysis. Therefore, ASFV could regulate immunity and metabolism-related pathways in infected pigs by inducing differential expression of miRNAs. These results provided a new basis for further elucidating the interactions between ASFV and the host as well as the immunity regulation mechanisms of ASFV, which will be conducive to better controlling ASF.
Correlating Air Pollution Concentrations and Vehicular Emissions in an Italian Roadway Tunnel by Means of Low Cost Sensors
Authors: De Vito Saverio , Del Giudice Antonio , D’Elia Gerardo , Esposito Elena , Fattoruso Grazia , Ferlito Sergio , Formisano Fabrizio , Loffredo Giuseppe , Massera Ettore , Bellucci Patrizia , Ciarallo Francesca , Di Francia Girolamo
Published: April 2023

There is an increasing scientific interest in studying vehicular traffic pollution in road tunnels. This is due both to the interest in evaluating the effect that the different polluting gases can have on the driving style of motorists and also to the hypothesis that tunnels could be considered as closed systems in which the vehicular traffic–pollution correlation is easier to study because it is more easily separated from other effects. In this work, a system of low-cost IoT sensor nodes for the detection of carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matters (PM1, PM2.5, PM10), relative humidity (RH) and temperature (T) has been installed in an Italian tunnel, where vehicular traffic has been measured and classified for type of vehicles. The results of the measurement campaign, which lasted 3 months, from April to June 2022, allowed us to state that road tunnels actually behave like closed and isolated systems in which pollution may be directly correlated to the traffic volume and type. Furthermore, data show that quite high values of the major pollutants are observable in the tunnel in comparison to the external environment. As such, IoT sensor nodes may contribute to a distributed measuring approach on the road tunnel system mechanics assessment including, as an example, the operational impacts of forced ventilation.
Revisiting the Role of NAG across the Continuum of Kidney Disease
Authors: Novak Ruder , Salai Grgur , Hrkac Stela , Vojtusek Ivana Kovacevic , Grgurevic Lovorka
Published: April 2023

Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs). Due to its large molecular weight, plasma-soluble NAG cannot pass the glomerular filtration barrier; thus, increased urinary concentration of NAG (uNAG) may suggest injury to the proximal tubule. As the PTECs are the workhorses of the kidney that perform much of the filtration and reabsorption, they are a common starting point in acute and chronic kidney disease. NAG has previously been researched, and it is widely used as a valuable biomarker in both acute and chronic kidney disease, as well as in patients suffering from diabetes mellitus, heart failure, and other chronic diseases leading to kidney failure. Here, we present an overview of the research pertaining to uNAG’s biomarker potential across the spectrum of kidney disease, with an additional emphasis on environmental nephrotoxic substance exposure. In spite of a large body of evidence strongly suggesting connections between uNAG levels and multiple kidney pathologies, focused clinical validation tests and knowledge on underlining molecular mechanisms are largely lacking.
An Assessment of the Pathological Classification and Postoperative Outcome of Focal Cortical Dysplasia by Simultaneous Hybrid PET/MRI
Authors: Wang Ning , Wang Lingjie , Yu Yixing , Li Guangzheng , Cao Changhao , Xu Rui , Jiang Bin , Bi Yongfeng , Xie Minjia , Hu Chunhong , Gao Wei , Zhu Mo
Published: April 2023

Objectives: The purpose of this research was to investigate whether MRI and Simultaneous Hybrid PET/MRI images were consistent in the histological classification of patients with focal cortical dysplasia. Additionally, this research aimed to evaluate the postoperative outcomes with the MRI and Simultaneous Hybrid PET/MRI images of focal cortical dysplasia. Methods: A total of 69 cases in this research were evaluated preoperatively for drug-resistant seizures, and then surgical resection procedures of the epileptogenic foci were performed. The postoperative result was histopathologically confirmed as focal cortical dysplasia, and patients then underwent PET and MRI imaging within one month of the seizure. In this study, head MRI was performed using a 3.0 T magnetic resonance scanner (Philips) to obtain 3D T1WI images. The Siemens Biograph 16 scanner was used for a routine scanning of the head to obtain PET images. BrainLAB’s iPlan software was used to fuse 3D T1 images with PET images to obtain PET/MRI images. Results: Focal cortical dysplasia was divided into three types according to ILAE: three patients were classified as type I, twenty-five patients as type II, and forty-one patients as type III. Patients age of onset under 18 and age of operation over 18 had a longer duration (p = 0.036, p = 0.021). MRI had a high lesion detection sensitivity of type III focal cortical dysplasia (p = 0.003). Simultaneous Hybrid PET/MRI showed high sensitivity in detecting type II and III focal cortical dysplasia lesions (p = 0.037). The lesions in Simultaneous Hybrid PET/MRI-positive focal cortical dysplasia patients were mostly located in the temporal and multilobar (p = 0.005, 0.040). Conclusion: Simultaneous Hybrid PET/MRI has a high accuracy in detecting the classification of focal cortical dysplasia. The results of this study indicate that patients with focal cortical dysplasia with positive Simultaneous Hybrid PET/MRI have better postoperative prognoses.
Barriers to Energy Efficiency: Low-Income Households in Australia
Authors: Azimi Samaneh , Hon Carol K. H. , Tyvimaa Tanja , Skitmore Martin
Published: April 2023

Low-income housing plays an important, but frequently overlooked, role in energy use reduction. Barriers persist for low-income households to participate in energy efficiency programs and adopt efficient lifestyles. However, there has been only limited research into energy efficiency barriers faced by low-income households. Existing energy research studies primarily focus on homeowners whose demographic and socio-economic profiles are likely to be very different from low-income households or renters—limiting the applicability of previous findings to low-income households. This study aims to identify and evaluate the importance of the energy efficiency barriers faced by low-income households. A questionnaire survey was conducted with 212 low-income households in Australia. After randomly dividing the data into calibration and validation samples, an exploratory factor analysis (EFA) of the calibration sample identifies four energy efficiency barrier factors of financial, decision-making, information, and split incentives. These four factors are then validated by confirmatory factor analysis (CFA) of the validation sample in terms of goodness-of-fit, reliability, and validity to confirm financial as the most highly rated energy efficiency barrier. This research contributes to bridging the knowledge gap of the energy efficiency barriers of low-income households and providing a validated CFA model as a tool for assessment. The results provide a better understanding of the barriers involved and research evidence to facilitate the formulation of policies to overcome them.
Effects of Using High-Strength Reinforcement in the Seismic Performance of a Tall RC Shear Wall Building
Authors: Puentes Juan , Parra Pablo F. , Magna-Verdugo Carolina E. , Cendoya Patricio , Avudaiappan Siva
Published: April 2023

Chile’s reinforced concrete (RC) design is based on ACI 318-08, where high-strength reinforcement is not allowed in seismic force-resistant members. In 2019, new requirements adopted by ACI 318 permitted the incorporation of high-strength reinforcement in walls. This study compared the seismic performance of two Chilean 20-story residential buildings on soft soil, one designed with traditional Grade 60 and the other with high-strength Grade 80 reinforcement. The performance was assessed in terms of the probability of exceeding the ASCE 41 limit states during a 50-year lifecycle. Analyses showed that both buildings had similar seismic performance. However, the reduction in reinforcement in the Grade 80 building was close to 18%. It is concluded that using high-strength reinforcement in a typical wall building implies a significant reduction in the reinforcement used without affecting the seismic performance.
EBV and Lymphomagenesis
Authors: Sausen Daniel G. , Basith Ayeman , Muqeemuddin Syed
Published: April 2023

The clinical significance of Epstein–Barr virus (EBV) cannot be understated. Not only does it infect approximately 90% of the world’s population, but it is also associated with numerous pathologies. Diseases linked to this virus include hematologic malignancies such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Burkitt lymphoma, primary CNS lymphoma, and NK/T-cell lymphoma, epithelial malignancies such as nasopharyngeal carcinoma and gastric cancer, autoimmune diseases such as multiple sclerosis, Graves’ disease, and lupus. While treatment for these disease states is ever evolving, much work remains to more fully elucidate the relationship between EBV, its associated disease states, and their treatments. This paper begins with an overview of EBV latency and latency-associated proteins. It will then review EBV’s contributions to select hematologic malignancies with a focus on the contribution of latent proteins as well as their associated management.
Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways
Authors: Southekal Siddesh , Shakyawar Sushil Kumar , Bajpai Prachi , Elkholy Amr , Manne Upender , Mishra Nitish Kumar , Guda Chittibabu
Published: April 2023

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. Results revealed the enrichment of molecular pathways including Wnt signaling, Calcium signaling, and PI3K-Akt signaling in the OS tumors. Survival analyses showed that the expression levels of several genes such as RAMP1, CRIP1, CORT, CHST13, and DDX60L, miRNAs and lncRNAs were associated with survival of OS patients. Molecular subtyping using Cluster-Of-Clusters Analysis (COCA) for mRNA, lncRNA, and miRNA expression; DNA methylation; and mutation data from the TARGET dataset revealed two distinct molecular subtypes, each with a distinctive gene expression profile. Between the two subtypes, three upregulated genes, POP4, HEY1, CERKL, and seven downregulated genes, CEACAM1, ABLIM1, LTBP2, ISLR, LRRC32, PTPRF, and GPX3, associated with OS metastasis were found to be differentially regulated. Thus, the molecular subtyping results provide a strong basis for classification of OS patients that could be used to develop better prognostic treatment strategies.
Microvasculature Features Derived from Hybrid EPI MRI in Non-Enhancing Adult-Type Diffuse Glioma Subtypes
Authors: Arzanforoosh Fatemeh , van der Voort Sebastian R. , Incekara Fatih , Vincent Arnaud , Van den Bent Martin , Kros Johan M. , Smits Marion , Warnert Esther A. H.
Published: April 2023

In this study, we used the vessel size imaging (VSI) MRI technique to characterize the microvasculature features of three subtypes of adult-type diffuse glioma lacking enhancement. Thirty-eight patients with confirmed non-enhancing glioma were categorized into three subtypes: Oligo (IDH-mut&1p/19q-codeleted), Astro (IDH-mut), and GBM (IDH-wt). The VSI technique provided quantitative maps of cerebral blood volume (CBV), microvasculature (µCBV), and vessel size for each patient. Additionally, tissue samples of 21 patients were histopathologically analyzed, and microvasculature features were quantified. Both MRI- and histology-derived features were compared across the three glioma subtypes with ANOVA or Kruskal–Wallis tests. Group averages of CBV, μCBV, and vessel size were significantly different between the three glioma subtypes (p < 0.01). Astro (IDH-mut) had a significantly lower CBV and µCBV compared to Oligo (IDH-mut&1p/19q-codeleted) (p = 0.004 and p = 0.001, respectively), and a higher average vessel size compared to GBM (IDH-wt) (p = 0.01). The histopathological analysis showed that GBM (IDH-wt) possessed vessels with more irregular shapes than the two other subtypes (p < 0.05). VSI provides a good insight into the microvasculature characteristics of the three adult-type glioma subtypes even when lacking enhancement. Further investigations into the specificity of VSI to differentiate glioma subtypes are thus warranted.
Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype
Authors: Nisticò Nancy , Aloisio Annamaria , Lupia Antonio , Zimbo Anna Maria , Mimmi Selena , Maisano Domenico , Russo Rossella , Marino Fabiola , Scalise Mariangela , Chiarella Emanuela , Mancuso Teresa , Fiume Giuseppe , Omodei Daniela , Zannetti Antonella , Salvatore Giuliana , Quinto Ileana , Iaccino Enrico
Published: April 2023

Triple-negative breast cancer (TNBC) is an aggressive malignancy characterized by the lack of expression of estrogen and progesterone receptors and amplification of human epidermal growth factor receptor 2 (HER2). Being the Epidermal Growth Factor Receptor (EGFR) highly expressed in mesenchymal TNBC and correlated with aggressive growth behavior, it represents an ideal target for anticancer drugs. Here, we have applied the phage display for selecting two highly specific peptide ligands for targeting the EGFR overexpressed in MDA-MB-231 cells, a human TNBC cell line. Molecular docking predicted the peptide-binding affinities and sites in the extracellular domain of EGFR. The binding of the FITC-conjugated peptides to human and murine TNBC cells was validated by flow cytometry. Confocal microscopy confirmed the peptide binding specificity to EGFR-positive MDA-MB-231 tumor xenograft tissues and their co-localization with the membrane EGFR. Further, the peptide stimulation did not affect the cell cycle of TNBC cells, which is of interest for their utility for tumor targeting. Our data indicate that these novel peptides are highly specific ligands for the EGFR overexpressed in TNBC cells, and thus they could be used in conjugation with nanoparticles for tumor-targeted delivery of anticancer drugs.
Photobiomodulation at 660 nm Stimulates In Vitro Diabetic Wound Healing via the Ras/MAPK Pathway
Authors: Kasowanjete Patricia , Abrahamse Heidi , Houreld Nicolette N.
Published: April 2023

Diabetic foot ulcers (DFUs) are open chronic wounds that affect diabetic patients due to hyperglycaemia. DFUs are known for their poor response to treatment and frequently require amputation, which may result in premature death. The present study evaluated the effect of photobiomodulation (PBM) at 660 nm on wound healing via activation of Ras/MAPK signalling in diabetic wounded cells in vitro. This study used four human skin fibroblast cell (WS1) models, namely normal (N), wounded (W), diabetic (D), and diabetic wounded (DW). Cells were irradiated at 660 nm with 5 J/cm2. Non-irradiated cells (0 J/cm2) served as controls. Cells were incubated for 24 and 48 h post-irradiation, and the effect of PBM on cellular morphology and migration rate, viability, and proliferation was assessed. Basic fibroblast growth factor (bFGF), its phosphorylated (activated) receptor FGFR, and phosphorylated target proteins (Ras, MEK1/2 and MAPK) were determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting; nuclear translocation of p-MAPK was determined by immunofluorescence. PBM resulted in an increase in bFGF and a subsequent increase in FGFR activation. There was also an increase in downstream proteins, p-Ras, p-MEK1/2 and p-MAPK. PBM at 660 nm led to increased viability, proliferation, and migration as a result of increased bFGF and subsequent activation of the Ras/MAPK signalling pathway. Therefore, this study can conclude that PBM at 660 nm stimulates in vitro diabetic wound healing via the bFGF-activated Ras/MAPK pathway.