bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Key Signaling Pathways Associating miR‐204 and Common Retinopathies
Authors: Bereimipour Ahmad , Satarian Leila , Taleahmad Sara
Published: October 2021

MicroRNAs are a large group of small noncoding RNAs that work in multiple cellular pathways. miR‐204, as one of the key axes in the development, maintenance, and pathogenesis of the retina, plays several roles by modulating its target genes. This study was aimed at evaluating the target genes of miR‐204 involved in the development and progression of common retinopathies such as glaucoma, retinoblastoma, and age‐related macular degeneration. In this study, three datasets related to retinopathies (GSE50195, GSE27276, and GSE97508) were selected from Gene Expression Omnibus. miR‐204 target genes were isolated from TargeScan. The shares between retinopathy and miR‐204 target genes were then categorized. Using Enrichr and STRING, we highlighted the signaling pathways and the relationships between the proteins. SHC1 events in ERBB2, adherent junction’s interactions, NGF signaling via TRKA from the plasma membrane, IRF3‐mediated activation of type 1 IFN, pathways in upregulated genes and G0 and early G1, RORA‐activated gene expression, PERK‐regulated gene expression, adherent junction’s interactions, and CREB phosphorylation pathways in downregulated genes were identified in glaucoma, retinoblastoma, and age‐related macular degeneration. WEE1, SMC2, HMGB1, RRM2, and POLA1 proteins were also observed to be involved in the progression and invasion of retinoblastoma; SLC24A2 and DTX4 in age‐related macular degeneration; and EPHB6, EFNB3, and SHC1 in glaucoma. Continuous bioinformatics analysis has shown that miR‐204 has a significant presence and expression in retinal tissue, and approximately 293 genes are controlled and regulated by miR‐204 in this tissue; also, target genes of miR‐204 have the potential to develop various retinopathies; thus, a study of related target genes can provide appropriate treatment strategies in the future.
Influence of Different Antiepileptic Drugs on Blood Ammonia and Homocysteine Levels in Children with Epilepsy
Authors: Sun Meng , Zhou Ran , Wang Xin , Cheng Yaying
Published: October 2021

In this study, we performed a study on 106 children with epilepsy who were treated with sodium valproate (the VPA group, n = 37), oxcarbazepine (the OXC group, n = 34), or levetiracetam (the LEV group, n = 35). In addition, the clinical data of epileptic children who were newly diagnosed in the same period without antiepileptic drug (AED) treatment (the untreated group, n = 35) and normal children who received physical examination in our hospital (the healthy group, n = 35) were selected as controls. We analyzed the efficacy and safety of different AEDs, used blood ammonia and homocysteine levels as the observation indicators, and calculated the incidence of hyperammonemia (VAH) and hyperhomocysteinemia (HHcy) treated with different AEDs. And, based on the effect of epilepsy status on the cognitive function of patients, we also analyzed the effect of different AED treatments on children’s cognitive function. Our results show that sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels, so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.
Growth Scale Optimization of Discrete Innovation Population Systems with Multichoice Goal Programming
Authors: Zhai Su-Lan , Liu Ying , Wang Sheng-Yuan , Wu Xiao-Lan
Published: October 2021

How are limited resources efficiently allocated among different innovation populations? The performances of different innovation populations are quite different with either synergy or competition between them. If the innovation population is kept under an appropriate scale, full use can be made of the allocated resources. The maximization of the development and performance for a certain scale of innovation population is a typical multichoice development problem. Therefore, the scale optimization of the innovation population should be analyzed. According to the population dynamics, a resource constraint model for the growth of innovation population is developed, and the growth of innovation population under resource constraints is in equilibrium accordingly. With the help of a multichoice goal programming model, the scale optimization of innovation population performance can be obtained. The results of the resource constraint model and multichoice goal programming model are used to determine the optimal scale of the innovation population. From the panel data of the innovation population in Jiangsu Province from 2000 to 2017, we have found that R&D investment was the main innovation resource variable and that patent number was the main innovation output variable. Based on these data, the scale optimization of the innovation population under resource constraints can be calculated. The results of the study show that, in the observation period, the enterprise innovation population is often in the appropriate scale state. The scale development of enterprise innovation population is often more suitable for innovation ecosystem than that of scientific research institutions. According to these results, the government can provide appropriate guiding policies and incentives for different innovation populations. The innovative population can adjust its own development strategy and plan in time accordingly.
Study on the Catastrophic Evolution of Tianshan Road Slope under the Freeze-Thaw Cycles
Authors: Wang Luqi , Zhang Yibing , Guo Jian , Ou Qiang , Liu Songlin , Wang Lin
Published: October 2021

The maximum temperature difference of Tianshan Road can reach 77.4°C in a year. Under such complex mechanical environment, the mechanical properties of rock mass and structural planes will change significantly as the increase of freeze-thaw cycles (FTC). Consequently, the FTC has become a key factor in the instability and failure of rocky slopes along the Tianshan Road. In this paper, the progressive deformation of rocky slopes and sudden failure process after critical instability were studied through the FTC tests of rock mass and structural planes, discrete element method, and theoretical analysis. The results show that the structural planes and internal microcracks of the rock mass expand under the action of the FTC, causing a gradual decrease in the stability of the slope. The dynamic collapse of the rocky slope has a certain degree of randomness caused by the spatial distribution of structural planes and the interaction between the rock fragments. Due to the limitation of the slipping space and the tilt angle of the trailing edge of the slope, long-distance migration did not occur, and the in situ accumulation of the slope was obvious after failure. The analysis method in this paper can provide an important reference for guiding the catastrophe mechanism analysis and protection of engineering slopes in cold regions.
A Robust Approach to CCRM Interval Regression considering Interval Coincidence Degree
Authors: Yu Wang , Shilin Yan
Published: October 2021

Traditional CCRMs (Constrained Center-and-Range Methods) in solving the problem of interval regression could hardly make tradeoffs between the overall fitting accuracy and the coincidence degree between the observed and predicted intervals and could also hardly reduce the number of disjoint elements between the observed and predicted intervals, as well as raise the average ratio of all predicted intervals contained within their observed intervals. This paper constructed a nonlinear regression model based on center-and-range method, in which the maximization of coincidence degree for the sample with the worst coincidence degree between the observed and predicted interval was incorporated into the traditional CCRM model’s objective. This novel nonlinear programming model was proven to be a convex one that satisfied K-T condition. Monte Carlo simulation shows that the model is degenerated to the compared CCRM+ model as the objective only contains the minimization of the overall fitting accuracy for both center and range sample series. In this situation, it could obtain a better solution than the use of the compared CCRM model. In addition, when the proposed model only takes into account the maximization of coincidence degree for the sample with the worst coincidence degree between the observed and predicted interval, the model shows a better performance than the CCRM+ model in terms of the average ratio of all predicted intervals contained within their observed intervals, as well as the average number of forecasts with 0% accuracy.
Patients’ Perception of Morocco’s Medicine Pricing Reform and Determinants of Their Access to Health Care and Medicine
Authors: Cheikh Amine , Moutahir Meryem , Bennani Ismail , Attjioui Houda , Zerhouni Wadie , Bouatia Mustapha
Published: October 2021

Background. In 2014, the Ministry of Health of Morocco implemented a reform of medicine pricing that leads to lower prices. This reform has brought about a new method of pricing medicines and a reduction in the prices of more than 1,400 of the 5,000 medicines on the market. The objective of this study was to survey patients’ perceptions of the impact of the reform on medicine prices and affordability of health care, including medicine. Methods. Between September 2017 and September 2018, 360 patients that visited a community pharmacy in four selected areas of different socioeconomic levels were interviewed based on a questionnaire. Findings were studied through univariate and multivariate analyses. Results. Three hundred patients (83%) were included given their completed questionnaire. The majority (89%) of respondents considered medicine prices as a potential barrier to access to health care. Lower medicine prices following the reform were not perceived to have actually impacted respondents’ spending on health care. In some cases, care was delayed, in particular by lower‐income respondents and people without insurance and health coverage. Conclusion. The majority of patients participating in the study did not perceive the decrease in medicine prices as sufficient. In addition, the study findings pointed to the relevance of further determinants of access to medicines, such as health insurance coverage. Patients think that the generalized third‐party payment mode, which does not oblige patients to spend out of their pockets to have their treatment but rather their health insurance funds that will pay for them, provides optimal access to medicines.
A Two-Stage Robust Optimization Method Based on the Expected Scenario for Islanded Microgrid Energy Management
Authors: Duan Qing , Sheng Wanxing , Wang Haoqing , Zhao Caihong , Ma Chunyan
Published: October 2021

One of the main challenges in microgrid system energy management is dealing with uncertainties such as the power output from renewable energy sources. The classic two-stage robust optimization (C-TSRO) method was proposed to cope with these uncertainties. However, this method is oriented to the worst-case scenario and is therefore somewhat conservative. In this study, focusing on the energy management of a typical islanded microgrid and considering uncertainties such as the power output of renewable energy sources and the power demand of loads, an expected-scenario-oriented two-stage robust optimization (E-TSRO) method is proposed to alleviate the conservative tendency of the C-TSRO method because the E-TSRO method chooses to optimize the system cost according to the expected scenario instead, while ensuring the feasibility of the first-stage variables for all possible scenarios, including the worst case. According to the structural characteristics of the proposed model based on the E-TSRO method, a column-and-constraint generation (C & CG) algorithm is utilized to solve the proposed model. Finally, the effectiveness of the E-TSRO model and the solution algorithm are analysed and validated through a series of experiments, thus obtaining some important conclusions, i.e., the economic efficiency of system operation can be improved at about 6.7% in comparison with the C-TSRO results.
Study about Chinese Speech Synthesis Algorithm and Acoustic Model Based on Wireless Communication Network
Authors: Shi Liu , Li Moyan , Su Yawen , Chen Yi
Published: October 2021

Chinese speech synthesis refers to the technology that machines transform human speech signals into corresponding texts or commands through recognition and understanding. This paper combines the classic VAD and GSM VAD1 algorithm simulations, improves on the above two algorithms to recognize and collect speech, and analyzes their Chinese proficiency by amplifying the signal through a filter, in order to study the adulthood of Zhengzhou University in Southeast Asian students (mother tongues are Indonesian and Thai) as the research objects, to explore the relationship between the Chinese phonetic proficiency and the acquisition motivation of Southeast Asian students. This article combines algorithm and language disciplines. According to the results of Praat and SPSS: 55‐80 points account for 70%, 55 points below 20% and 80 points above 10%, we find that intrinsic motivation plays a role in CSL acquisition, a vital role. Intrinsic motivation can help mature learners from Southeast Asia to acquire Chinese better and better. The earlier you learn Chinese, the higher your motivation, and the easier it is to set your Chinese learning goals. The greater the enthusiasm for learning Chinese, the better the Chinese scores (such as HSK test scores and Chinese phonetic test scores). Therefore, the Chinese proficiency of international students has a great relationship with their interest in Chinese language, that is, the greater the interest in Chinese, the stronger their motivation to learn, and the Chinese proficiency will be very good.
Synthesis of Isatin Derivatives Using Silver Nanoparticles as Green Catalyst: Study of Molecular Docking Interactions in SARS-CoV-2 3c-Like Protease and Determination of Cytotoxic Activities of the Compounds
Authors: Packialakshmi Ponnusamy , Gobinath Perumal , Vijayakumar Kaliappillai , Ali Daoud , Alarifi Saud , Ravindran Balasubramani , PitchaiSangan  , Surendrakumar Radhakrishnan
Published: October 2021

The coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As isatin-containing compounds exhibit several remarkable biological activities, isatin derivatives were prepared to combat the global pandemic caused by SARS-CoV-2 that is gripping the world. Herein, the synthesis of novel isatin derivatives has been reported. The cytotoxic activities of the compounds were determined using cancer cell (MCF-7) and normal cell (MCF-10A and MRC-5) lines. In silico molecular docking experiments were conducted using AutoDock Vina. We have successfully predicted the binding energies and the number of hydrogen bonds present. We have also identified the residues involved in hydrogen bond formation. The target compounds were synthesized using Schiff base following cyclization and Knoevenagel condensation reactions. We have focused on the recyclable synthesis of silver nanoparticles (AgNPs) using the extracts obtained from Dipteryx odorata. The extracts were used to reduce silver ions for the production of AgNPs. The synthesized nanoparticles exhibited excellent catalytic activities during the synthesis of isatin derivatives in ethanol. The formation of the target isatin derivatives has been confirmed using the Fourier transform-infrared (FT-IR), proton nuclear magnetic resonance (1H NMR) spectroscopy, 13C NMR spectroscopy, mass spectrometry, and elemental analysis techniques. Compound 3e was found to be the most active compound when tested against the MCF-7 cancer cell line (IC50=20.5 μM). The activity was comparable to the activities of standard doxorubicin and other compounds. In silico molecular docking experiments were conducted to study the spike protein in SARS-CoV-2 (PDB ID: 6LU7). Compound 3c exhibited high binding ability (−9.4 kcal/mol). The inhibition ability was studied using hydroxychloroquine as a standard. Results from docking studies revealed that the inhibition ability of compound 3c was higher than the inhibition abilities exhibited by other compounds. The synthesized compound 3e is a potential antiviral drug that can be used for treating the COVID-19 disease.
Real-Time Modeling of Regional Tropospheric Delay Based on Multicore Support Vector Machine
Authors: Yang Xu , Jiang Xinyuan , Jiang Chuang , Xu Lei
Published: October 2021

Real-time modeling of regional troposphere has attracted considerable research attention in the current GNSS field, and its modeling products play an important role in global navigation satellite system (GNSS) real-time precise positioning and real-time inversion of atmospheric water vapor. Multicore support vector machine (MS) based on genetic optimization algorithm, single-core support vector machine (SVM), four-parameter method (FP), neural network method (BP), and root mean square fusion method (SUM) are used for real-time and final zenith tropospheric delay (ZTD) modeling of Hong Kong CORS network in this study. Real-time ZTD modeling experiment results for five consecutive days showed that the average deviation (bias) and root mean square (RMS) of FP, BP, SVM, and SUM reduced by 48.25%, 54.46%, 41.82%, and 51.82% and 43.16%, 48.46%, 30.09%, and 33.86%, respectively, compared with MS. The final ZTD modeling experiment results showed that the bias and RMS of FP, BP, SVM, and SUM reduced by 3.80%, 49.78%, 25.71%, and 49.35% and 43.16%, 48.46%, 30.09%, and 33.86%, respectively, compared with MS. Accuracy of the five methods generally reaches millimeter level in most of the time periods. MS demonstrates higher precision and stability in the modeling of stations with an elevation at the average level of the survey area and higher elevation than that of other models. MS, SVM, and SUM exhibit higher precision and stability in the modeling of the station with an elevation at the average level of the survey area than FP. Meanwhile, real-time modeling error distribution of the five methods is significantly better than the final modeling. Standard deviation and average real-time modeling improved by 43.19% and 24.04%, respectively.
Evolution of Pore Characteristics for Bentonite Modified by an Ionic Soil Stabilizer during Hydration Processes
Authors: Huang Wei , Feng Zili , Fu Huanran , Xiang Wei
Published: October 2021

An ionic soil stabilizer (ISS) is used to reinforce clay soils because the ISS can regulate the hydration processes and microstructures of clays. To evaluate the regulation of ISS, natural bentonite was modified by ISS at different concentrations in this research. Water vapour adsorption and X-ray diffraction (XRD) were carried out to interpret the hydration mechanism of bentonite. Meanwhile, an associated analysis between hydration pore structures and hydration mechanisms was implemented through variation of pore characteristic tests at different relative humidities (RHs) to distinguish multiscale pore adsorption of water during the corresponding hydration process. In addition, the pore characteristics were studied via XRD, nitrogen adsorption, and mercury injection tests. Finally, the origins that adsorbed water and pore structures changed by adding ISS were discussed. The results showed that for calcium bentonite, the cations hydrated first in the range of [Formula: see text], accompanied by the expansion of micropores. Then, adsorption occurred on the basal surface of the crystal layer in the range of [Formula: see text], with water mainly adsorbed into the mesopores. With further hydration when [Formula: see text], diffused double layer (DDL) water ceaselessly entered the macropores. Both adsorbed water and multiscale pore size decreased when ISS was added to bentonite. The origins of the reduction were the regulation of ISS to exchangeable cations and the basal surface of the crystal layer.
[Retracted] Small Target Detection Algorithm Based on Transfer Learning and Deep Separable Network
Authors: Wang Peng , Wang Haiyan , Li Xiaoyan , Zhang Lingling , Di Ruohai , Lv Zhigang
Published: October 2021

With the development of deep learning, target detection from vision sensor has achieved high accuracy and efficiency. However, small target detection remains a challenge due to inadequate use of semantic information and detailed texture information of underlying features. To solve the above problems, this paper proposes a small target detection algorithm based on Mask R‐CNN model which integrates transfer learning and deep separable network. Firstly, the feature pyramid fusion structure is introduced to enhance the learning effect of low‐level and high‐level features, especially to strengthen the information channel of low‐level feature and meanwhile optimize the feature information of small target. Secondly, the ELU function is used as the activation function to solve the problem that the original activation function disappears in the negative half axis gradient. Finally, a new loss function F‐Softmax combined with Focal Loss was adopted to solve the imbalance of positive and negative sample proportions. In this paper, self‐made data set is used to carry out experiments, and the experimental results show that the proposed algorithm makes the detection accuracy of small targets reach 66.5%.
Gene Expression Characteristics of Liver Tissue Reveal the Underlying Pathogenesis of Hepatocellular Carcinoma
Authors: Guo Congfang , Guo Xiang , Rong Yudong , Guo Yirui , Zhang Li
Published: October 2021

Background. Hepatocellular carcinoma (HCC) is high‐mortality primary liver cancer and the most common malignant tumor in the world. This study is based on a hepatocellular carcinoma‐related dysfunction module designed to explore the dysregulation of genes in liver cancer tissue. Methods. By downloading the relevant data on the GEO database, we performed a differential analysis of healthy liver tissue and liver cancer tissues as well as healthy liver tissue and hepatocellular carcinoma tissue and then obtained two sets of differential genes and combined them. We performed a cointerpretation analysis of these differential genes and constructed related functional disorder modules. A hypergeometric test was performed to calculate the potential regulatory effects of multiple factors on the module, and a series of ncRNA and TF regulators were identified. We obtained a total of 4479 differentially expressed genes in hepatocellular carcinoma, and these genes were clustered into ten hepatocellular carcinoma‐related functional interpretation disorder modules. Results. Enrichment analysis revealed that these modular genes are mainly involved in signal transduction including cell cycle, TGF‐beta signal transduction, and p53 signal transduction. Depending on the predictive analysis of multidimensional regulators, 323 ncRNAs and 52 TF‐mediated hepatocellular carcinoma‐related dysregulation modules were found to regulate disease progression. Conclusions. Based on a series of investigations, it was found that miR‐30b‐5p may participate in the peroxisome signal transduction by downregulating ABCD3‐mediated module 1, thereby promoting the development and progression of hepatocellular carcinoma. Our research results not only provide a theoretical basis for biologists to study hepatocellular carcinoma further but also offer new methods and new ideas for the personalized care and treatment of hepatocellular carcinoma.
In Silico Analysis of the Gene Expression Patterns between Aldosterone-Producing Adenoma and Nonfunctional Adrenocortical Adenoma
Authors: Dai Yongfa , Li Jing , Wen Hong , Liu Jie , Li Jianling
Published: October 2021

Primary aldosteronism is the most common form of secondary hypertension, and aldosteronoma makes up a significant proportion of primary aldosteronism cases. Aldosteronoma is also called aldosterone-producing adenoma (APA). Although there have been many studies about APA, the pathogenesis of this disease is not yet fully understood. In this study, we aimed to find out the difference of gene expression patterns between APA and nonfunctional adrenocortical adenoma (NFAA) using a weighted gene coexpression network (WGCNA) and differentially expressed gene (DEG) analysis; only the genes that meet the corresponding standards of both methods were defined as real hub genes and then used for further analysis. Twenty-nine real hub genes were found out, most of which were enriched in the phospholipid metabolic process. WISP2, S100A10, SSTR5-AS1, SLC29A1, APOC1, and SLITRK4 are six real hub genes with the same gene expression pattern between the combined and validation datasets, three of which indirectly or directly participate in lipid metabolism including WISP2, S100A10, and APOC1. According to the gene expression pattern of DEGs, we speculated five candidate drugs with potential therapeutic value for APA, one of which is cycloheximide, an inhibitor for phospholipid biosynthesis. All the evidence suggests that phospholipid metabolism may be an important pathophysiological mechanism for APA. Our study provides a new perspective regarding the pathophysiological mechanism of APA and offers some small molecules that may possibly be effective drugs against APA.
The Promotion Mechanism of Frozen Stagnant Water on the Sliding in the Loess Landslide Zone of Heifangtai
Authors: Zhang Mingli , Li Guang , Wang Dekai , Ye Weilin , Zhou Zhixiong , Ma Zhao , Xia Kai
Published: October 2021

Freeze-thaw cycles can significantly change the hydrologic and thermal state of slopes in cold regions and affect their stability. Landslides occur continuously in the slip area of seasonally frozen soil area during the freezing period. The freeze-thaw action and the difference in the characteristics of the underlying surface of the slope are important factors inducing landslides. Taking Heifangtai slope in Gansu Province as an example, the freezing-thawing characteristics of the slope surfaces under different underlying surface conditions were analyzed by field monitoring. A thermohydromechanical coupling model was established to reconstruct the frozen stagnant water process of the Heifangtai landslide zone, and the impact of freeze-thaw action on the loess landslide zone was studied. The results show that differences in the underlying surface led to different freezing-thawing characteristics between the unsaturated area and the groundwater overflow zone. During the freezing period, the soil freezing depth was greater, and the freezing duration was longer in the unsaturated area. The frozen stagnant water effect of the Heifangtai loess landslide zone is obvious. The maximum difference in the groundwater level between February and August could reach nearly 1 m. Meanwhile, the frozen stagnant water process of the Heifangtai landslide zone has a slip-promoting action on the slope. The factor of safety declined during the freezing period and increased during the thawing period. It reached a minimum of 1.42 in February.
Experimental Study on Reducing the Heat of Curing Reaction of Polyurethane Polymer Grouting Material
Authors: Zhang Bei , Wang Baolin , Zhong Yanhui , Wang Shuangjie , Li Xiaolong , Wang Lei
Published: October 2021

Polyurethane polymer grouting material has been effectively applied and promoted in the repair of road damages in nonfrozen areas. However, this material undergoes an exothermic reaction in the curing stage, which can cause a thermal disturbance in the frozen soil subgrade. To minimize the influence of the thermal disturbance of the polyurethane polymer grouting material in the repair of the frozen soil subgrade, an experiment was conducted to reduce the heat of the curing reaction under the influence of different proportions of a foaming agent, high-boiling point solvent, catalyst, and prepolymer. According to these test results, a proportioning scheme for the low exothermic polymer grouting material was formulated. The results indicated that the curing reaction temperature threshold of the polyurethane polymer grouting material was negatively related to the proportion of physical foaming agent (HCFC-141b) and high-boiling point solvent and positively related to the proportion of water weight. In the three stages of rapid temperature rise, slow temperature rise, and constant temperature, the rate of the temperature rise of the low exothermic polymer grouting material was lower than that of the common polymer, and the curing temperature threshold was 30.34% lower at a value of 101°C. At a density of 80 kg/m3, the compressive strength and tensile strength of the low heat release polymer grouting material were lower than those of the common polymer grouting material, thereby ensuring the excellent performance of polyurethane foam and providing a theoretical reference for the rapid repair of frozen soil roadbed diseases.
Development of Rapid and Visual Nucleic Acid Detection Methods towards Four Serotypes of Human Adenovirus Species B Based on RPA‐LF Test
Authors: Qi Yong , Li Wei , Li Xiaoling , Shen Wanpeng , Zhang Jinhai , Li Jiameng , Lv Ruichen , Lu Nianhong , Zong Liqiang , Zhuang Susu , Gui Qiyuan , Zhou Dongming , Li Jing , Xu Yingjia , Shen Hongbing , Li Yuexi
Published: October 2021

Objectives. Human adenoviruses (HAdV) are classified as 7 HAdV species, and some serotypes in species B like HAdV 3, HAdV 7, HAdV 21, and HAdV 55 caused severe symptoms, even fatalities. Patients may be misdiagnosed and inadequately treated without reliable and practical methods for HAdV serotyping. Developing rapid, sensitive, and specific diagnostic methods for HAdV is critical. Methods. Detection methods were established based on a recombinase polymerase amplification (RPA) assay and lateral flow (LF) test. Specific target sequence was screened, targeting which, primers and probes were designed, synthesized, and screened for establishing assay with high amplification efficiency. Primer or probe concentrations and amplification time were optimized. Detection limit, sensitivity, and specificity were evaluated. Results and Conclusions. Simple, sensitive, and specific RPA‐LF methods for detection of four serotypes of HAdV together or separately were established, which had detection limits of 10 to 280 copies/reaction comparable to real‐time PCR without recognizing other pathogens. The sensitivity and specificity were >92% and >98%, respectively, evaluated by limited clinical samples. The detection can be completed in 25 min without requirement of any instrument except a constant temperature equipment, showing superior detection performance and promising for a wide use in the field and resource‐limited area.
Oral Health Knowledge, Attitude, and Practices among School Teachers in Chitwan District, Nepal
Authors: Singh Harender , Chaudhary Sanjeeb , Gupta Abhishek , Bhatta Anusha
Published: October 2021

Background. Oral health is dependent on the knowledge and awareness of the individuals. Teachers as individuals influence the children in every aspect including oral health maintenance. The objective of this study was to assess the oral health knowledge, attitude, practices, and oral health status among school teachers in Chitwan District, Nepal. Materials and Methods. A cross-sectional study was conducted on 550 school teachers of private and government schools in Chitwan District, to assess the knowledge, attitude, practices, and oral health status. Descriptive analysis was done and data were analyzed using chi-square. A five-point Likert Scale was applied to compute knowledge, attitude, and practices of the school teachers. Results. Most of the school teachers had good knowledge about periodontal diseases in comparison to dental caries. Private school (20.7% : 57) teachers had higher good oral health knowledge as compared to government school teachers (9.8% : 27). An almost equal percentage of private and government teachers (73.5% : 202 and 74.2% : 204, respectively) were found with fair knowledge about oral health. Males had a higher percentage for good oral health knowledge as compared to females. Conclusion. There is an incredible need to improve oral health knowledge and attitude among school teachers concerning different problems of the oral cavity and the avoidance of dental diseases. These enhancements can be applied through regular training of teachers by oral health seminars, materials, and other such types of methods.
Density of CD3+ and CD8+ Cells in the Microenvironment of Colorectal Cancer according to Prediagnostic Physical Activity
Authors: Renman David , Gylling Björn , Vidman Linda , Bodén Stina , Strigård Karin , Palmqvist Richard , Harlid Sophia , Gunnarsson Ulf , van Guelpen Bethany
Published: October 2021

Background:

Physical activity is associated not only with a decreased risk of developing colorectal cancer but also with improved survival. One putative mechanism is the infiltration of immune cells in the tumor microenvironment. Experimental findings suggest that physical activity may mobilize immune cells to the tumor. We hypothesized that higher levels of physical activity prior to colorectal cancer diagnosis are associated with higher densities of tumor-infiltrating T-lymphocytes in colorectal cancer patients.

Methods:

The study setting was a northern Swedish population-based cohort, including 109,792 participants with prospectively collected health- and lifestyle-related data. For 592 participants who later developed colorectal cancer, archival tumor tissue samples were used to assess the density of CD3+ and CD8+ cytotoxic T cells by IHC. Odds ratios for associations between self-reported, prediagnostic recreational physical activity and immune cell infiltration were estimated by ordinal logistic regression.

Results:

Recreational physical activity >3 times per week was associated with a higher density of CD8+ T cells in the tumor front and center compared with participants reporting no recreational physical activity. Odds ratios were 2.77 (95% CI, 1.21–6.35) and 2.85 (95% CI, 1.28–6.33) for the tumor front and center, respectively, after adjustment for sex, age at diagnosis, and tumor stage. The risk estimates were consistent after additional adjustment for several potential confounders. For CD3, no clear associations were found.

Conclusions:

Physical activity may promote the infiltration of CD8+ immune cells in the tumor microenvironment of colorectal cancer.

Impact:

The study provides some evidence on how physical activity may alter the prognosis in colorectal cancer.
Advances in Understanding Early-Onset Colorectal Cancer
Authors: Hayes Richard B.
Published: October 2021

Since the 1990s, the incidence of early-onset colorectal cancer (at <50 years of age) in the US has increased by more than 50%; similar increases have also been observed internationally. These increases are found particularly among individuals born during and after the 1960s, raising the possibility that the increased rates of early-onset colorectal cancer are attributable to changes in risk-factor patterns throughout successive generations. The reasons for these alarming epidemiologic patterns for early-onset colorectal cancer worldwide are only recently being investigated and major gaps in our knowledge remain. In the current issue of this journal, Arif and colleagues differentiated characteristics and outcomes of early-onset colorectal cancer in patients with the predisposing conditions of inflammatory bowel disease or hereditary genetic syndromes, compared with patients who have sporadic disease. Also, in this issue, Schumacher and colleagues investigated risk factors for early-onset colorectal adenocarcinoma in a nested case-control study among Kaiser Permanente Southern California (KPSC) health plan members. The research presented on characteristics and outcomes points to the importance of sporadic disease in the rise of early-onset colorectal cancer, while the research presented on risk factors points to the importance of obesity as a potential explanatory factor for this rise.

See related articles by Arif et al., p. 1785 and by Schumacher et al., p. 1792
Traumatic Refractory Ventricular Fibrillation Successfully Treated with Intra-Arrest Esmolol
Authors: Raymond Kevin , Wheeler Emily , Shank Mark
Published: October 2021

Here, we describe a case of refractory ventricular fibrillation (RVF) in an undifferentiated trauma patient that responded to intra-arrest esmolol. To our knowledge, this is the first case of RVF in an undifferentiated trauma patient that responded to intra-arrest esmolol. This case continues to support the growing evidence for use of esmolol as a treatment of refractory fibrillation and should be considered even in undifferentiated traumatic arrest patients prior to the cessation of resuscitation efforts.
3D-Printed Template-Guided 125I Seed Brachytherapy: A Salvage Approach for Locoregional Refractory Recurrence of Papillary Thyroid Cancer
Authors: Gao Zhen , Zhang Hongtao , Zhang Lijuan , Yu Huimin , Di Xuemin , Wang Zeyang , Liu Zezhou , Sui Aixia , Wang Juan , Shi Gaofeng
Published: October 2021

Background: Papillary thyroid carcinoma (PTC) is typically treated with surgical resection, even in recurrent cases. However, some cases of recurrent PTC are refractory to the conventionally used locoregional radiotherapy and resection methods. 125I seed permanent brachytherapy has emerged as a promising alternative for such PTCs, but no effective brachytherapy protocol has been reported for tumors with a huge volume, liquefaction, necrosis, and skin invasion. Case Presentation: A 47-year-old man presented with recurrence 8 years after 2 thyroidectomy procedures for PTC and recurrent PTC. The tumor measured 6 × 7 × 8 cm3 and exhibited liquefaction, necrosis, and skin invasion. The patient was treated at our hospital from December 2017 to November 2018. He received one round of 125I seed temporary brachytherapy and 4 rounds of 125I seed permanent implantation. The activity of the seeds was 0.3–3.0 mCi, and the total dose delivered to the tumor was 145 Gy. The recurrent tumor was successfully removed by 125I seed brachytherapy guided with a 3D-printed template and ultrasound and CT scanning. The refractory tumor healed uneventfully after 125I seed brachytherapy without recurrence over the 25-month follow-up. Conclusions: To the best of our knowledge, this is the first reported case of a large thyroid carcinoma that was effectively treated by 3D-printed template-guided 125I seed brachytherapy.
Metabolic Long-Term Monitoring of Transcorneal Electrical Stimulation in Retinitis Pigmentosa
Authors: Meral Nesrin , Zabek Olga , Camenzind Zuche Hanna , Müller Ursula , Prétot Dominique , Rickmann Annekatrin , Scholl Hendrik P.N. , della Volpe Waizel Maria
Published: October 2021

Introduction: Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyze oxygen saturation in retinal vessels and has shown promising short-term results as a therapy monitoring tool for TES. The aim of our study was to measure the long-term effects of TES on RO parameters over a period of 3 years (3Y). Methods: A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0–1.5 optic-disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V SO2) were measured and their difference (A-V SO2) was calculated. In addition, we recorded the diameters in the main arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were employed for statistical analysis using SPSS®. Results: After 3Y of TES treatment both the mean A-SO2 (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V SO2 (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A-V SO2, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D-A and D-V (p > 0.05). Conclusion: Our long-term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow-up study and to confirm this trend reflecting a possible benefit of TES for RP.
Importance of the Activation Sequence of the His or Right Bundle for Diagnosis of Complex Tachycardia Circuits
Authors: Viswanathan Mohan N. , Julie He Beixin , Sung Raphael , Hoffmayer Kurt S. , Badhwar Nitish , Lee Adam , Goldberger Jeffrey J. , Hsia Henry H. , Jackman Warren M. , Scheinman Melvin M.
Published: October 2021

In this review, we emphasize the unique value of recording the activation sequence of the His bundle or right bundle branch (RB) for diagnoses of various supraventricular and fascicular tachycardias. A close analysis of the His to RB (H-RB) activation sequence can help differentiate various forms of supraventricular tachycardias, namely atrioventricular nodal reentry tachycardia from concealed nodofascicular tachycardia, a common clinical dilemma. Furthermore, bundle branch reentry tachycardia and fascicular tachycardias often are included in the differential diagnosis of supraventricular tachycardia with aberrancy, and the use of this technique can help the operator make the distinction between supraventricular tachycardias and these other forms of ventricular tachycardias using the His-Purkinje system. We show that this technique is enhanced by the use of multipolar catheters placed to span the proximal His to RB position to record the activation sequence between proximal His potential to the distal RB potential. This allows the operator to fully analyze the activation sequence in sinus rhythm as compared to that during tachycardia and may help target ablation of these arrhythmias. We argue that 3 patterns of H-RB activation are commonly identified—the anterograde H-RB pattern, the retrograde H-RB (right bundle to His bundle) pattern, and the chevron H-RB pattern (simultaneous proximal His and proximal RB activation)—and specific arrhythmias tend to be associated with specific H-RB activation sequences. We show that being able to record and categorize this H-RB relationship can be instrumental to the operator, along with standard pacing maneuvers, to make an arrhythmia diagnosis in complex tachycardia circuits. We highlight the importance of H-RB activation patterns in these complex tachycardias by means of case illustrations from our groups as well as from prior reports.
Genome-Wide Association Study of Peripheral Artery Disease
Authors: van Zuydam Natalie R. , Stiby Alexander , Abdalla Moustafa , Austin Erin , Dahlström Emma H. , McLachlan Stela , Vlachopoulou Efthymia , Ahlqvist Emma , Di Liao Chen , Sandholm Niina , Forsblom Carol , Mahajan Anubha , Robertson Neil R. , Rayner N. William , Lindholm Eero , Sinisalo Juha , Perola Markus , Kallio Milla , Weiss Emily , Price Jackie , Paterson Andrew , Klein Barbara , Salomaa Veikko , Palmer Colin N.A. , Groop Per-Henrik , Groop Leif , McCarthy Mark I. , de Andrade Mariza , Morris Andrew P. , Hopewell Jemma C. , Colhoun Helen M. , Kullo Iftikhar J. , Grétarsdóttir Sólveig , Þorleifsson Guðmar , þorsteinsdóttir Unnur , Stefansson Kari , Mark Michael , Kanninen Timo , Thorand Barbara , Remuzzi Giuseppe , Dunger David , Shore Angela , Smith Ulf , Ylä-Herttuala Seppo , Cobelli Claudio , Bellazzi Riccardo , Ferrannini Ele , Patrono Carlo , Nuutila Pirjo , McKeague Paul , Steckel-Hamann Birgit , Gan Li-ming , Nogoceke Everson , Tortoli Piero , Jablonka Bernd , Brosnan Mary-Julia
Published: October 2021

Background:

Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status.

Methods:

We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status.

Results:

We identified 5 genome-wide significant (
P

association

≤5×10
−8
) associations with PAD in 449 548 (N
cases
=12 086) individuals of European ancestry near
LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit
) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the
CCSER1 (coiled-coil serine rich protein 1
) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32–1.74],
P

diabetes

=2.5×10
−9
,
P

interactionwithdiabetes

=5.3×10
−7
). Furthermore, in smokers, rs12910984 at the
CHRNA3
locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11–1.19],
P

smokers

=9.3×10
−10
,
P

interactionwithsmoking

=3.9×10
−5
).

Conclusions:

Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.
Truncating Variants in
OBSCN
Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy
Authors: Wu Guixin , Liu Jie , Liu Minghao , Huang Qiya , Ruan Jieyun , Zhang Channa , Wang Dong , Sun Xiaolu , Jiang Wen , Kang Lianming , Wang Jizheng , Song Lei
Published: October 2021

Background:

The presence of variants in
OBSCN
was identified to be linked to hypertrophic cardiomyopathy (HCM), but whether
OBSCN
truncating variants were associated with HCM remained unknown.

Methods:

Whole-exome sequencing was performed in 986 patients with HCM and 761 non-HCM controls to search for
OBSCN
truncating variants, and the result was tested in a replication cohort consisting of 529 patients with HCM and 307 controls. The association of the
OBSCN
truncating variants with baseline characteristics and prognosis of patients with HCM were ascertained.

Results:

There were 28 qualifying truncating variants in the
OBSCN
gene detected in 26 (2.6%) patients with HCM and 6 (0.8%) controls. The
OBSCN
truncating variants were more prevalent in patients with HCM than controls (odds ratio, 3.4,
P
=0.004). This association was confirmed in the replication cohort (odds ratio, 3.8,
P
=0.024). The combined effects of the two cohorts estimated the odds ratio to be 3.58 (
P
<0.001). Patients with or without
OBSCN
truncating variants shared similar demographic and echocardiographic variables at baseline. During 3.3±2.4 years (4795 patient-years) follow-up, the patients with
OBSCN
truncating variants were more likely to experience cardiovascular death (adjusted hazard ratio, 3.1 [95% CI, 1.40–6.70],
P
=0.005) and all-cause death (adjusted hazard ratio, 2.63 [95% CI, 1.21–5.71],
P
=0.015).

Conclusions:

Our data indicated that
OBSCN
truncating variants contributed to the disease-onset of HCM, and increased the risk of malignant events in patients with HCM.