bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Improved Deep Learning Model: S-TextBLCNN for Traditional Chinese Medicine Formula Classification
Authors: Cheng Ning , Chen Yue , Gao Wanqing , Liu Jiajun , Huang Qunfu , Yan Cheng , Huang Xindi , Ding Changsong 
Published: December 2021

Purpose: This study proposes an S-TextBLCNN model for the efficacy of traditional Chinese medicine (TCM) formula classification. This model uses deep learning to analyze the relationship between herb efficacy and formula efficacy, which is helpful in further exploring the internal rules of formula combination.Methods: First, for the TCM herbs extracted from Chinese Pharmacopoeia, natural language processing (NLP) is used to learn and realize the quantitative expression of different TCM herbs. Three features of herb name, herb properties, and herb efficacy are selected to encode herbs and to construct formula-vector and herb-vector. Then, based on 2,664 formulae for stroke collected in TCM literature and 19 formula efficacy categories extracted from Yifang Jijie, an improved deep learning model TextBLCNN consists of a bidirectional long short-term memory (Bi-LSTM) neural network and a convolutional neural network (CNN) is proposed. Based on 19 formula efficacy categories, binary classifiers are established to classify the TCM formulae. Finally, aiming at the imbalance problem of formula data, the over-sampling method SMOTE is used to solve it and the S-TextBLCNN model is proposed.Results: The formula-vector composed of herb efficacy has the best effect on the classification model, so it can be inferred that there is a strong relationship between herb efficacy and formula efficacy. The TextBLCNN model has an accuracy of 0.858 and an F1-score of 0.762, both higher than the logistic regression (acc = 0.561, F1-score = 0.567), SVM (acc = 0.703, F1-score = 0.591), LSTM (acc = 0.723, F1-score = 0.621), and TextCNN (acc = 0.745, F1-score = 0.644) models. In addition, the over-sampling method SMOTE is used in our model to tackle data imbalance, and the F1-score is greatly improved by an average of 47.1% in 19 models.Conclusion: The combination of formula feature representation and the S-TextBLCNN model improve the accuracy in formula efficacy classification. It provides a new research idea for the study of TCM formula compatibility.
Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy
Authors: Li Xueyan , Zhong Jiahui , Deng Xue , Guo Xuan , Lu Yantong , Lin Juze , Huang Xuhui , Wang Changjun 
Published: December 2021

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are activated under pathological conditions, such as cancer, or mature myeloid cells that are converted immune-suppressive cells via tumor-derived exosomes, and potently support the tumor processes at different levels. Currently, multiple studies have demonstrated that MDSCs induce immune checkpoint blockade (ICB) therapy resistance through their contribution to the immunosuppressive network in the tumor microenvironment. In addition, non-immunosuppressive mechanisms of MDSCs such as promotion of angiogenesis and induction of cancer stem cells also exert a powerful role in tumor progression. Thus, MDSCs are potential therapeutic targets to enhance the antitumor efficacy of ICB therapy in cases of multiple cancers. This review focuses on the tumor-promoting mechanism of MDSCs and provides an overview of current strategies that target MDSCs with the objective of enhancing the antitumor efficacy of ICB therapy.
Gateway Reflex and Mechanotransduction
Authors: Matsuyama Shiina , Tanaka Yuki , Hasebe Rie , Hojyo Shintaro , Murakami Masaaki 
Published: December 2021

SummaryThe gateway reflex explains how autoreactive CD4+ T cells cause inflammation in tissues that have blood-barriers, such as the central nervous system and retina. It depends on neural activations in response to specific external stimuli, such as gravity, pain, stress, and light, which lead to the secretion of noradrenaline at specific vessels in the tissues. Noradrenaline activates NFkB at these vessels, followed by an increase of chemokine expression as well as a reduction of tight junction molecules to accumulate autoreactive CD4+ T cells, which breach blood-barriers. Transient receptor potential vanilloid 1 (TRPV1) molecules on sensory neurons are critical for the gateway reflex, indicating the importance of mechano-sensing. In this review, we overview the gateway reflex with a special interest in mechanosensory transduction (mechanotransduction).
Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases Identified That TNC Is a Novel Biomarker for Keloid
Authors: Xie Jiaheng , Chen Liang , Cao Yuan , Wu Dan , Xiong Wenwen , Zhang Kai , Shi Jingping , Wang Ming 
Published: December 2021

BackgroundThe pathophysiology of keloid formation is not yet understood, so the identification of biomarkers for kelod can be one step towards designing new targeting therapies which will improve outcomes for patients with keloids or at risk of developing keloids.MethodsIn this study, we performed single-cell RNA sequencing analysis, weighted co-expression network analysis, and differential expression analysis of keloids based on public databases. And 3 RNA sequencing data from keloid patients in our center were used for validation. Besides, we performed QRT-PCR on keloid tissue and adjacent normal tissues from 16 patients for further verification.ResultsWe identified the sensitive biomarker of keloid: Tenascin-C (TNC). Then, Pseudotime analysis found that the expression level of TNC decreased first, then stabilized and finally increased with fibroblast differentiation, suggesting that TNC may play an potential role in fibroblast differentiation. In addition, there were differences in the infiltration level of macrophages M0 between the TNC-high group and the TNC-low group. Macrophages M0 had a higher infiltration level in low TNC- group (P&lt;0.05).ConclusionOur results can provide a new idea for the diagnosis and treatment of keloid.
Identification of Diagnostic Markers Correlated With HIV+ Immune Non-response Based on Bioinformatics Analysis
Authors: Bai Ruojing , Li Zhen , Hou Yuying , Lv Shiyun , Wang Ran , Hua Wei , Wu Hao , Dai Lili 
Published: December 2021

Background: HIV-infected immunological non-responders (INRs) are characterized by their inability to reconstitute CD4+ T cell pools after antiretroviral therapy. The risk of non-AIDS-related diseases in INRs is increased, and the outcome and prognosis of INRs are inferior to that of immunological responders (IRs). However, few markers can be used to define INRs precisely. In this study, we aim to identify further potential diagnostic markers associated with INRs through bioinformatic analyses of public datasets.Methods: This study retrieved the microarray data sets of GSE106792 and GSE77939 from the Gene Expression Omnibus (GEO) database. After merging two microarray data and adjusting the batch effect, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) resource and Kyoto Encyclopedia of Genes and Genomes (KEGG) resource were conducted to analyze the biological process and functional enrichment. We performed receiver operating characteristic (ROC) curves to filtrate potential diagnostic markers for INRs. Gene Set Enrichment Analysis (GSEA) was conducted to perform the pathway enrichment analysis of individual genes. Single sample GSEA (ssGSEA) was performed to assess scores of immune cells within INRs and IRs. The correlations between the diagnostic markers and differential immune cells were examined by conducting Spearman’s rank correlation analysis. Subsequently, miRNA-mRNA-TF interaction networks in accordance with the potential diagnostic markers were built with Cytoscape. We finally verified the mRNA expression of the diagnostic markers in clinical samples of INRs and IRs by performing RT-qPCR.Results: We identified 52 DEGs in the samples of peripheral blood mononuclear cells (PBMC) between INRs and IRs. A few inflammatory and immune-related pathways, including chronic inflammatory response, T cell receptor signaling pathway, were enriched. FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1 were considered as potential diagnostic markers. ssGSEA results showed that the IRs had significantly higher enrichment scores of seven immune cells compared with IRs. The miRNA-mRNA-TF network was constructed with 97 miRNAs, 6 diagnostic markers, and 26 TFs, which implied a possible regulatory relationship.Conclusion: The six potential crucial genes, FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1, may be associated with clinical diagnosis in INRs. Our study provided new insights into diagnostic and therapeutic targets.
A Systematic Review and Recommendations Around Frameworks for Evaluating Scientific Validity in Nutritional Genomics
Authors: Keathley Justine , Garneau Véronique , Zavala-Mora Daniela , Heister Robyn R. , Gauthier Ellie , Morin-Bernier Josiane , Green Robert , Vohl Marie-Claude 
Published: December 2021

Background: There is a significant lack of consistency used to determine the scientific validity of nutrigenetic research. The aims of this study were to examine existing frameworks used for determining scientific validity in nutrition and/or genetics and to determine which framework would be most appropriate to evaluate scientific validity in nutrigenetics in the future.Methods: A systematic review (PROSPERO registration: CRD42021261948) was conducted up until July 2021 using Medline, Embase, and Web of Science, with articles screened in duplicate. Gray literature searches were also conducted (June-July 2021), and reference lists of two relevant review articles were screened. Included articles provided the complete methods for a framework that has been used to evaluate scientific validity in nutrition and/or genetics. Articles were excluded if they provided a framework for evaluating health services/systems more broadly. Citing articles of the included articles were then screened in Google Scholar to determine if the framework had been used in nutrition or genetics, or both; frameworks that had not were excluded. Summary tables were piloted in duplicate and revised accordingly prior to synthesizing all included articles. Frameworks were critically appraised for their applicability to nutrigenetic scientific validity assessment using a predetermined categorization matrix, which included key factors deemed important by an expert panel for assessing scientific validity in nutrigenetics.Results: Upon screening 3,931 articles, a total of 49 articles representing 41 total frameworks, were included in the final analysis (19 used in genetics, 9 used in nutrition, and 13 used in both). Factors deemed important for evaluating nutrigenetic evidence related to study design and quality, generalizability, directness, consistency, precision, confounding, effect size, biological plausibility, publication/funding bias, allele and nutrient dose-response, and summary levels of evidence. Frameworks varied in the components of their scientific validity assessment, with most assessing study quality. Consideration of biological plausibility was more common in frameworks used in genetics. Dose-response effects were rarely considered. Two included frameworks incorporated all but one predetermined key factor important for nutrigenetic scientific validity assessment.Discussion/Conclusions: A single existing framework was highlighted as optimal for the rigorous evaluation of scientific validity in nutritional genomics, and minor modifications are proposed to strengthen it further.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261948, PROSPERO [CRD42021261948].
Importance of Normalization of Carbohydrate Antigen 19-9 in Patients With Intrahepatic Cholangiocarcinoma
Authors: Li Hui , Feng Yuan , Liu Chang , Li Jiawang , Li Jiaxin , Wu Hong , Wang Genshu , Li Dewei 
Published: December 2021

BackgroundAlthough carbohydrate antigen 19-9 (CA19-9) is an established prognostic marker for intrahepatic cholangiocarcinoma (ICC) patients, the significance of elevated preoperative CA19-9 that normalized after resection remains unknown. This study aimed to investigate whether elevated preoperative CA19-9 that normalized after curative resection had an impact on prognosis among patients with ICC.MethodsPatients who underwent curative resection for stage I to III ICC between 2009 and 2018 were identified. Patients were categorized into three cohorts: normal preoperative CA19-9, elevated preoperative CA19-9 but normalized postoperative CA19-9, and persistently elevated postoperative CA19-9. Overall survival (OS), recurrence-free survival (RFS), and hazard function curves over time were analyzed.ResultsA total of 511 patients (247 [48.3%] male; median age, 58 years) were included. Patients with elevated preoperative CA19-9 (n = 378) were associated with worse RFS and OS than those with normal preoperative CA19-9 (n = 152) (both p &lt; 0.001). Patients with persistently elevated postoperative CA19-9 (n = 254) were correlated with lower RFS and OS than the combined cohorts with normal postoperative CA19-9 (n = 257) (both p &lt; 0.001). The hazard function curves revealed that the risk of recurrence and mortality peaked earlier and higher in the elevated postoperative CA19-9 group than the other 2 groups. Multivariate analyses identified persistently elevated, rather than normalized, postoperative CA19-9 as an independent risk factor for shorter RFS and OS in ICC.ConclusionsElevated preoperative serum CA19-9 that normalizes after curative resection is not an indicator of poor prognosis in ICC. Patients with persistently elevated postoperative CA19-9 are at increased risk of recurrence and death.
Intravenous Metoclopramide to Improve the Success Rate of Blind Bedside Post-pyloric Placement of Feeding Tube in Critically Ill Children: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Ketsuwan Sirima , Tanpowpong Pornthep , Ruangwattanapaisarn Nichanan , Phaopant Supatra , Suppalarkbunlue Nattanicha , Kooanantkul Chula , Anantasit Nattachai , Vaewpanich Jarin 
Published: December 2021

Objective: Impaired gastric emptying is a common cause of delayed feeding in critically ill children. Post-pyloric feeding may help improve feeding intolerance and nutritional status and, hence, contribute to a better outcome. However, post-pyloric feeding tube insertion is usually delayed due to a technical difficulty. Therefore, prokinetic agents have been used to facilitate blind bedside post-pyloric feeding tube insertion. Metoclopramide is a potent prokinetic agent that has also been used to improve motility in adults and children admitted to intensive care units. The objective of this study was to determine the efficacy of intravenous metoclopramide in promoting the success rate of blind bedside post-pyloric feeding tube placement in critically ill children.Design: The design of this study is randomized, double blind, placebo controlled.Setting: The setting of the study is a single-center pediatric intensive care unit.Patients: Children aged 1 month−18 years admitted to the pediatric intensive care unit with severe illness or feeding intolerance were enrolled in this study.Intervention: Patients were randomly selected to receive intravenous metoclopramide or 0.9% normal saline solution (the placebo) prior to the tube insertion. The study outcome was the success rate of post-pyloric feeding tube placement confirmed by an abdominal radiography 6–8 h after the insertion.Measurements and Main Results: We found that patients receiving metoclopramide had a higher success rate (37/42, 88%) of post-pyloric feeding tube placement than the placebo (28/40, 70%) (p = 0.04). Patients who received sedative drug or narcotic agent showed a tendency of higher success rate (p = 0.08).Conclusion: Intravenous metoclopramide improves the success rate of blind bedside post-pyloric placement of feeding tube in critically ill children.Trial Registration: Thai Clinical Trial Registry TCTR20190821002. Registered 15th August 2019.
Skin Sympathetic Nerve Activity and the Short-Term QT Interval Variability in Patients With Electrical Storm
Authors: Chen Songwen , Meng Guannan , Doytchinova Anisiia , Wong Johnson , Straka Susan , Lacy Julie , Li Xiaochun , Chen Peng-Sheng , Everett IV Thomas H. 
Published: December 2021

Background: Skin sympathetic nerve activity (SKNA) and QT interval variability are known to be associated with ventricular arrhythmias. However, the relationship between the two remains unclear.Objective: The aim was to test the hypothesis that SKNA bursts are associated with greater short-term variability of the QT interval (STVQT) in patients with electrical storm (ES) or coronary heart disease without arrhythmias (CHD) than in healthy volunteers (HV).Methods: We simultaneously recorded the ECG and SKNA during sinus rhythm in patients with ES (N = 10) and CHD (N = 8) and during cold-water pressor test in HV (N = 12). The QT and QTc intervals were manually marked and calculated within the ECG. The STVQT was calculated and compared to episodes of SKNA burst and non-bursting activity.Results: The SKNA burst threshold for ES and HV was 1.06 ± 1.07 and 1.88 ± 1.09 μV, respectively (p = 0.011). During SKNA baseline and burst, the QT/QTc intervals and STVQT for ES and CHD were significantly higher than those of the HV. In all subjects, SKNA bursts were associated with an increased STVQT (from 6.43 ± 2.99 to 9.40 ± 5.12 ms, p = 0.002 for ES; from 9.48 ± 4.40 to 12.8 ± 5.26 ms, p = 0.016 for CHD; and from 3.81 ± 0.73 to 4.49 ± 1.24 ms, p = 0.016 for HV). The magnitude of increased STVQT in ES (3.33 ± 3.06 ms) and CHD (3.34 ± 2.34 ms) was both higher than that of the HV (0.68 ± 0.84 ms, p = 0.047 and p = 0.020).Conclusion: Compared to non-bursting activity, SKNA bursts were associated with a larger increase in the QTc interval and STVQT in patients with heart disease than in HV.
The Effects of Institution-Driven Entrepreneurial Education in Chinese Universities: A Qualitative Comparative Analysis Approach
Authors: Liu Rongzhi , Huo Yuxin , He Jing , Zuo Dun , Qiu Zhiqiang , Zhao Jun 
Published: December 2021

Purpose: This study aims to explore the effects of entrepreneurship education by examining the influences of the curriculum system, teaching team, design of practical programs, and the institutional systems on universities’ entrepreneurial education performance.Design/Methodology/Approach: This paper employs a case-based approach—Qualitative Comparative Analysis (QCA). Data were collected from 12 universities that were typical cases in the implementation of entrepreneurial education. The four dimensions of entrepreneurship education are applied as conditional indicators. fsQCA3.0 software is used to analyze the necessary conditions and condition combination of the truth table.Findings: There are three sets of condition combinations of the intermediate solution that results in a high level of entrepreneurial education performance: (1) when the credit ratio of entrepreneurship courses is higher and there are more practical platform platforms, even if the entrepreneurship education system and mechanism is less mature, the level of entrepreneurial education performance is high; (2) with a higher credit ratio of entrepreneurship courses, higher quality of teaching teams, and higher standard of practical platforms, the level of entrepreneurial education performance is high; (3) with a higher level of credit ratio of entrepreneurship courses and more practical platforms, as well as mature entrepreneurship education system and mechanism, even if the quality of the teaching team is lower, the level of entrepreneurial education performance is satisfied.Research Limitations/Implications: The dimensions of entrepreneurship education can be expanded; additionally, given that there are many other factors affecting entrepreneurial performance, it is necessary to identify and integrate other possible factors on an ongoing basis.Practical Implications: This study offers practical implications for universities and policy makers that can promote the transformation of theoretical knowledge into practice in the field of entrepreneurship in colleges and universities.Social Implications: This study is one of the first to empirically examine the effect of institutional-driven entrepreneurship education in developing countries. The enhancement of entrepreneurship education can benefit the development of individuals and schools, and even has a potential impact on the progress of the country and society as a whole.Originality/Value: This study emphasizes the significance of viewing the entrepreneurial education as a multi-dimensional concept by targeting different kinds of players. Furthermore, it employs a case-based approach to identify configurations of the antecedent attributes of the curriculum system, teaching team, design of practical programs, and the institutional systems, and their influence on universities’ entrepreneurial education performance.
The Impact of Maternal Anxiety on Early Child Development During the COVID-19 Pandemic
Authors: Jeličić Ljiljana , Sovilj Mirjana , Bogavac Ivana , Drobnjak And̄ela , Gouni Olga , Kazmierczak Maria , Subotić Miško 
Published: December 2021

Background: Maternal prenatal anxiety is among important public health issues as it may affect child development. However, there are not enough studies to examine the impact of a mother's anxiety on the child's early development, especially up to 1 year.Objective: The present prospective cohort study aimed to examine whether maternal trait anxiety, perceived social support, and COVID-19 related fear impacted speech-language, sensory-motor, and socio-emotional development in 12 months old Serbian infants during the COVID-19 pandemic.Methods: This follow-up study included 142 pregnant women (Time 1) and their children at 12 months (Time 2). Antenatal maternal anxiety and children's development were examined. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI). Child speech-language, sensory-motor, and socio-emotional development were assessed using the developmental scale in the form of an online questionnaire that examined the early psychophysiological child development. Information on socioeconomic factors, child and maternal demographics, clinical factors, and perceived fear of COVID-19 viral infection were collected. Multivariable General Linear Model analysis was conducted, adjusted for demographic, clinical, and coronavirus prenatal experiences, maternal prenatal anxiety levels, perceived social support, speech-language, motor skills, and cognitive and socio-emotional development at the infants' age of 12 months.Results: The study revealed the influence of the COVID-19 pandemic on maternal trait anxiety. The association between selected independent factors and infants' development was found in a demographically unified sample except for employment and the number of children. There was a correlation between all observed developmental functions. Univariate General Linear model statistical analysis indicated that linear models with selected independent factors and covariates could account for 30.9% (Cognition) up to 40.6% (Speech-language) of variability in developmental functions. It turned out that two-way and three-way interactions had a dominant role on models, and STAI-T Level and COVID-19 related fear were present in all interaction terms.Conclusion: Our findings reveal important determinants of child developmental outcomes and underline the impact of maternal anxiety on early child development. These findings lay the groundwork for the following interdisciplinary research on pregnancy and child development to facilitate and achieve positive developmental outcomes and maternal mental health.