bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory markers in children with obstructive sleep apnea syndrome
Authors: Wang Yingge , Chen Ying , Lin Wei , Huang Min , Xu Yuanteng , Chen Guohao 
Published: April 2023

ObjectiveTo evaluate serum inflammatory markers of YKL-40, Interleukin-6 (IL-6), Interleukin-8(IL-8), Interleukin-10(IL-10), TNF-α(tumor necrosis factor-α), and CRP (C-reactive protein) in children with and without OSAS.MethodsThe ELISA technique has been used to identify the concentration of inflammatory markers such as YKL-40, IL-6, IL-8, IL-10, TNF-α, and CRP in the serum of 83 children with OSAS and 83 children without OSAS.ResultsSerum levels of YKL-40, IL-6, IL-8, and IL-10 were found to be increased in children with OSAS. YKL-40 was found to be positively correlated with IL-6 and IL-8, and negatively correlated with IL-10. At the same time,YKL-40 was also found to be positively correlated with OAHI and LoSpO2% in OSAS group. IL-8 was positively correlated with OAHI whereas IL-10 was positively correlated with LoSpO2.ConclusionChildren with OSAS are in a systemic inflammatory state. YKL-40 together with IL-8 may act as serum inflammatory markers and provide an indication for the diagnosis of children with OSAS.
A Chinese family with cat eye syndrome and abnormality of eye movement: First case report
Authors: Lu Yang , Shen Liping , Zheng Yue , Zhang Haichen , Liu Yanbo , Qi Ming , Huang Shangzhi , Shen Bo 
Published: April 2023

BackgroundCat eye syndrome (CES) is a rare disease with a wide spectrum of phenotypic variability that is observed in 1:150,000 newborns. CES is characterized clinically by the combination of iris coloboma, anal atresia, and preauricular tags and/or pits. Many eye malformations have been reported to be associated with CES, such as iris and chorioretinal coloboma. However, an abnormality of eye movement has not been previously reported.Case presentationWe report on a Chinese family carrying a 22q11.1-q11.21 duplication of 1.7Mb tetrasomy (chr22:16,500,000–18,200,000, hg38) in two generations. Based on the proband and her father’s clinical manifestations, including ophthalmological examination, cytogenetic analysis, FISH, CNV-seq, and WES, the diagnosis of CES with an abnormality of eye movement was made.ConclusionOur findings broadened the symptom spectrum of CES syndrome and laid the foundation for pathogenesis, diagnostic targets, and drug research on the abnormality of eye movement, and were helpful for early diagnosis and intervention of CES.
Utility of fetal cardiovascular magnetic resonance imaging in assessing the fetuses with complete vascular ring
Authors: Zhang Xia , Zhu Ming , Dong Su-Zhen 
Published: April 2023

ObjectiveThis study aimed to report our experience in qualitative and quantitative evaluation of fetal complete vascular ring (CVR) using fetal cardiovascular magnetic resonance imaging (MRI) to improve prenatal diagnosis and make early postnatal management possible.MethodsA retrospective case-control study was performed on cases of CVR diagnosed using fetal cardiovascular MRI, and confirmed by postnatal imaging diagnosis. Associated abnormalities were recorded. The diameters of aortic arch isthmus (AoI) and ductus arteriosus (DA), and tracheal diameters in fetuses with tracheal compression were measured and compared with those of the control group.ResultsAll fetal CVR cases in this study included right aortic arch (RAA) with aberrant left subclavian artery (ALSA) and left DA (n = 93), double aortic arch (DAA) (n = 29), RAA with mirror-image branching and retroesophageal left ductus arteriosus (RLDA) (n = 8). Compared with the control group, the diameters of AoI in fetuses with DAA were decreased (p &lt; 0.001), and the diameters of DA in fetuses with RAA with ALSA and left DA were increased (p &lt; 0.001). The diameters of AoI and DA were positively correlated with gestational age (GA) in the normal control group (both p &lt; 0.001); The diameters of AoI and DA were also positively correlated with GA in RAA with ALSA and left DA subgroup (both p &lt; 0.001) and RAA with mirror-image branching and RLDA subgroup (AoI: p = 0.003; DA: p = 0.002); The diameters of DA were positively associated with GA in DAA subgroup (p &lt; 0.001), however, there was no linear tendency between the diameters of AoI and GA in the DAA subgroup (p = 0.074). There were CVR fetuses with associated intracardiac malformation (n = 13), especially ventricular septal defect rather than complex heart disease, and extracardiac malformation (n = 14). Sixteen fetuses were shown the airway compression whose tracheal diameters were smaller than the normal (p &lt; 0.001).ConclusionsThe altered diameters of AoI and DA can be detected and measured in CVR fetuses using fetal cardiovascular MRI. Fetal CVR can occur alone or with intracardiac and extracardiac malformation. Fetal CVR can be associated with prenatal airway compression.
Use of physiological based pharmacokinetic modeling for cross-species prediction of pharmacokinetic and tissue distribution profiles of a novel niclosamide prodrug
Authors: Yang Mengbi , Wang Amy Q. , Padilha Elias C. , Shah Pranav , Hagen Natalie R. , Ryu China , Shamim Khalida , Huang Wenwei , Xu Xin 
Published: April 2023

Introduction: Niclosamide (Nc) is an FDA-approved anthelmintic drug that was recently identified in a drug repurposing screening to possess antiviral activity against SARS-CoV-2. However, due to the low solubility and permeability of Nc, its in vivo efficacy was limited by its poor oral absorption.Method: The current study evaluated a novel prodrug of Nc (PDN; NCATS-SM4705) in improving in vivo exposure of Nc and predicted pharmacokinetic profiles of PDN and Nc across different species. ADME properties of the prodrug were determined in humans, hamsters, and mice, while the pharmacokinetics (PK) of PDN were obtained in mice and hamsters. Concentrations of PDN and Nc in plasma and tissue homogenates were measured by UPLC-MS/MS. A physiologically based pharmacokinetic (PBPK) model was developed based on physicochemical properties, pharmacokinetic and tissue distribution data in mice, validated by the PK profiles in hamsters and applied to predict pharmacokinetic profiles in humans.Results: Following intravenous and oral administration of PDN in mice, the total plasma clearance (CLp) and volume of distribution at steady-state (Vdss) were 0.061–0.063 L/h and 0.28–0.31 L, respectively. PDN was converted to Nc in both liver and blood, improving the systemic exposure of Nc in mice and hamsters after oral administration. The PBPK model developed for PDN and in vivo formed Nc could adequately simulate plasma and tissue concentration-time profiles in mice and plasma profiles in hamsters. The predicted human CLp/F and Vdss/F after an oral dose were 2.1 L/h/kg and 15 L/kg for the prodrug respectively. The predicted Nc concentrations in human plasma and lung suggest that a TID dose of 300 mg PDN would provide Nc lung concentrations at 8- to 60-fold higher than in vitro IC50 against SARS-CoV-2 reported in cell assays.Conclusion: In conclusion, the novel prodrug PDN can be efficiently converted to Nc in vivo and improves the systemic exposure of Nc in mice after oral administration. The developed PBPK model adequately depicts the mouse and hamster pharmacokinetic and tissue distribution profiles and highlights its potential application in the prediction of human pharmacokinetic profiles.
Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma
Authors: Zhu Yi-Pan , Deng Hui-Ting , Wang Xiuyu , Rahat Michal A. , Sun Shupeng , Zhang Qiang-Zhe 
Published: April 2023

Background: T cell exhaustion (TEX) heterogeneity leads to unfavorable immunotherapeutic responses in patients with cancer. Classification of TEX molecular phenotypes is pivotal to overcoming TEX and improving immunotherapies in the clinical setting. Cuproptosis is a novel form of programmed cell death associated with tumor progression. However, the relation between cuproptosis-related genes (CuRGs) and the different TEX phenotypes has not been investigated in lung adenocarcinoma (LUAD).Methods: Unsupervised hierarchical clustering and principal component analysis (PCA) algorithm were performed to determine CuRGs-related molecular subtypes and scores for patients with LUAD. The tumor immune microenvironment (TIME) landscape in these molecular subtypes and scores was estimated using ESTIMATE and ssGSEA algorithms. Furthermore, TEX characteristics and phenotypes were evaluated in distinct molecular subtypes and scores through GSVA and Spearman correlation analysis. Finally, TIDE scores, immunophenoscore, pRRophetic, GSE78220, and IMvigor210 datasets were employed to appraise the distinguishing capacity of CuRGscore in immunotherapy and pharmacotherapy effectiveness.Results: We identified three CuRGclusters, three geneClusters, and CuRGscore based on 1012 LUAD transcriptional profiles from five datasets. Compared with other molecular subtypes, CuRGcluster B, geneCluster C, and low-CuRGscore group with good prognosis presented fewer TEX characteristics, including immunosuppressive cells infiltration and TEX-associated gene signatures, signal pathways, checkpoint genes, transcription and inflammatory factors. These molecular subtypes were also responsive in distinguishing TEX phenotype in the terminal, GZMK+, and OXPHOS- TEX subtypes, but not the TCF7+ TEX subtype. Notably, copper importer and exporter, SLC31A1 and ATP7B, were remarkably associated with four TEX phenotypes and nine checkpoint genes such as PDCD1, CTLA4, HAVCR2, TIGIT, LAG3, IDO1, SIGLEC7, CD274, PDCD1LG2, indicating that cuproptosis was involved in the development of TEX and immunosuppressive environment in patients with LUAD. Moreover, CuRGscore was significantly related to the TIDE score, immunophenoscore, and terminal TEX score (Spearman R = 0.62, p &lt; 0.001) to effectively predict immunotherapy and drug sensitivity in both training and external validation cohorts.Conclusion: Our study demonstrated the extensive effect of cuproptosis on TEX. CuRGs-related molecular subtypes and scores could illuminate the heterogeneity of TEX phenotype as reliable tools in predicting prognosis and directing more effective immunotherapeutic and chemotherapeutic strategies for patients with LUAD.
A study on the influence of product environmental information transparency on online consumers’ purchasing behavior of green agricultural products
Authors: Fu Shaoling , Ma Ruili , He Guangyao , Chen Zhiyi , Liu Hua 
Published: April 2023

IntroductionIn 2020, the outbreak of COVID-19 has forced consumers to shift their consumption patterns online. However, the problem of online fraud in green agricultural products seriously undermines consumer trust and is detrimental to the sustainable consumption of green agricultural products. Therefore, it is particularly important to enhance consumers’ trust in online sellers. This study aims to investigate how the product environmental information transparency(soil information transparency and water information transparency) affects online consumers’ purchasing behavior of green agricultural products.MethodsThis study constructs a theoretical framework of “product environmental information transparency - online consumer trust - online purchase behavior”.We conducted an online randomized questionnaire to collect data from a sample of 512 consumers who had experience buying green agricultural products online fitted a structural equation model (SEM).ResultsThe results show that (1) the two dimensions of product environmental information transparency have different effects on different dimensions of online consumer trust. Among them, soil information transparency has a significant positive effect on competence trust, while it does not have a significant positive effect on benevolence trust. Water information transparency has a significant positive effect on both dimensions of online consumer trust, (2) online consumer trust has a significant positive effect on online consumer purchase behavior, and (3) competence trust has a significant positive effect on benevolence trust.DiscussionOur study shows that consumer trust in merchants is significantly enhanced by increasing the transparency of environmental information about green agricultural products. different dimensions of environmental information transparency have different effects on different dimensions of online consumer trust. Product information transparency is proposed as a tool for producers to use in the online marketing of green agricultural products. Consumers’ access to information can be improved through online public disclosure of environmental quality indicators in the production process of green agricultural products, and ultimately enhance online consumption of green agricultural products.
Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction
Authors: Feng Yu , Shen Jing , He Jin , Lu Minyan 
Published: April 2023

BackgroundSchizophrenia (SC) is one of the most common psychiatric diseases. Its potential pathogenic genes and effective treatment methods are still unclear. Cell senescence has been confirmed in mental diseases. A link exists between cellular senescence and immunity, and immune-related problems affect suicide rates in individuals suffering from schizophrenia. Therefore, the aims of this study were to identify candidate genes based on cell senescence that can affect the diagnosis and treatment of schizophrenia.MethodsTwo data sets of schizophrenia were provided by the Gene Expression Omnibus (GEO) database, one was taken as training and the other as a validation group. The genes related to cell senescence were obtained from the CellAge database. DEGs were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). The function enrichment analysis was conducted, followed by machine learning-based identification for least absolute shrinking and selection operators (LASSO) regression. Random Forest were used to identify candidate immune-related central genes and establish artificial neural networks for verification of the candidate genes. The receiver operating characteristic curve (ROC curve) was used for the diagnosis of schizophrenia. Immune cell infiltrates were constructed to study immune cell dysregulation in schizophrenia, and relevant drugs with candidate genes were collected from the DrugBank database.ResultsThirteen co-expression modules were screened for schizophrenia, of which 124 were the most relevant genes.There were 23 intersected genes of schizophrenia (including DEGs and the cellular senescence-related genes), and through machine learning six candidate genes were finally screened out. The diagnostic value was evaluated using the ROC curve data. Based on these results it was confirmed that these candidate genes have high diagnostic value.Two drugs related to candidate genes, Fostamatinib and Ritodine, were collected from the DrugBanks database.ConclusionSix potential candidate genes (SFN, KDM5B, MYLK, IRF3, IRF7, and ID1) had been identified, all of which had diagnostic significance. Fostamatinib might be a drug choice for patients with schizophrenia to develop immune thrombocytopenic purpura (ITP) after treatment, providing effective evidence for the pathogenesis and drug treatment of schizophrenia.
Clozapine prescription rates in Southeast Europe: A cross-sectional study
Authors: Russo Manuela , Ignjatovic-Ristic Dragana , Cohen Dan , Arenliu Aliriza , Bajraktarov Stojan , Dzubur Kulenovic Alma , Injac Stevovic Lidija , Maric Nadja , Novotni Antoni , Jovanovic Nikolina 
Published: April 2023

IntroductionInternational reports indicate that clozapine is under prescribed. Yet, this has not been explored in Southeast European (SEE) countries. This cross-sectional study investigates clozapine prescription rates in a sample of 401 outpatients with psychosis from Bosnia and Herzegovina, Kosovo by United Nations resolution, North Macedonia, Montenegro and Serbia.MethodsDescriptive analysis was used to explore clozapine prescription rates; daily antipsychotic dosage was calculated and converted into olanzapine equivalents. Patients receiving clozapine were compared to those not receiving clozapine; next those that were on clozapine monotherapy were compared to those who were on clozapine polytherapy regime.ResultsIt was showed that clozapine was prescribed to 37.7% of patients (with cross-country variation: from 25% in North Macedonia to 43.8% in Montenegro), with average dose of 130.7 mg/daily. The majority of patients on clozapine (70.5%) were prescribed at least one more antipsychotic (the most frequent combination was with haloperidol).DiscussionOur findings suggested that clozapine prescription rate in SEE outpatients is higher than in Western Europe. The average dose is significantly below the optimal therapeutic dosage recommended by clinical guidelines, and clozapine polytherapy is common. This might indicate that clozapine is prescribed mainly for its sedative effect rather than antipsychotic. We hope that this finding will be taken up by relevant stakeholders to address this non-evidence-based practice.
Electrophysiological evidence for the characteristics of implicit self-schema and other-schema in patients with major depressive disorder: An event-related potential study
Authors: Yao Jia-yu , Zheng Zi-wei , Zhang Yi , Su Shan-shan , Wang Yuan , Tao Jing , Peng Yi-hua , Wu Yan-ru , Jiang Wen-hui , Qiu Jian-yin 
Published: April 2023

BackgroundThe significance of implicit self-schema and other-schema in major depressive disorder (MDD) is highlighted by both cognitive theory and attachment theory. The purpose of the current study was to investigate the behavioral and event-related potential (ERP) characteristics of implicit schemas in MDD patients.MethodsThe current study recruited 40 patients with MDD and 33 healthy controls (HCs). The participants were screened for mental disorders using the Mini-International Neuropsychiatric Interview. Hamilton Depression Rating Scale-17 and Hamilton Anxiety Rating Scale-14 were employed to assess the clinical symptoms. Extrinsic Affective Simon Task (EAST) was conducted to measure the characteristics of implicit schemas. Meanwhile, reaction time and electroencephalogram data were recorded.ResultsBehavioral indexes showed that HCs responded faster to positive self and positive others than negative self (t = −3.304, p = 0.002, Cohen’s d = 0.575) and negative others (t = −3.155, p = 0.003, Cohen’s d = 0.549), respectively. However, MDD did not show this pattern (p &gt; 0.05). The difference in other-EAST effect between HCs and MDD was significant (t = 2.937, p = 0.004, Cohen’s d = 0.691). The ERP indicators of self-schema showed that under the condition of positive self, the mean amplitude of LPP in MDD was significantly smaller than that in HCs (t = −2.180, p = 0.034, Cohen’s d = 0.902). The ERP indexes of other-schema showed that HCs had a larger absolute value of N200 peak amplitude for negative others (t = 2.950, p = 0.005, Cohen’s d = 0.584) and a larger P300 peak amplitude for positive others (t = 2.185, p = 0.033, Cohen’s d = 0.433). The above patterns were not shown in MDD (p &gt; 0.05). The comparison between groups found that under the condition of negative others, the absolute value of N200 peak amplitude in HCs was larger than that in MDD (t = 2.833, p = 0.006, Cohen’s d = 1.404); under the condition of positive others, the P300 peak amplitude (t = −2.906, p = 0.005, Cohen’s d = 1.602) and LPP amplitude (t = −2.367, p = 0.022, Cohen’s d = 1.100) in MDD were smaller than that in HCs.ConclusionPatients with MDD lack positive self-schema and positive other-schema. Implicit other-schema might be related to abnormalities in both the early automatic processing stage and the late elaborate processing stage, while the implicit self-schema might be related only to the abnormality in the late elaborate processing stage.
Investigation of treatment satisfaction and health-related quality of life after add-on to metformin-based therapy in patients with type 2 diabetes
Authors: Chang Yu-Wen , Shen Feng-Chin , Chen Chung-Yu 
Published: April 2023

BackgroundThe complexity of oral antidiabetic drug (OAD) regimens affects the quality of life (QOL) and treatment satisfaction. However, data on the QOL of patients with type 2 diabetes mellitus (T2DM) receiving metformin-based OAD treatment in Asia are limited. Therefore, this study aimed to evaluate the QOL and treatment satisfaction and explore the influencing factors and their correlations among patients with T2DM receiving metformin-based OADs.MethodsThis was a cross-sectional study conducted at the Outpatient Department of Metabolism and Endocrinology at a medical center in Taiwan. Data were collected using the Audit of Diabetes-Dependent Quality of Life (ADDQoL) and the Chinese version of the Satisfaction with Oral Anti-Diabetic Agent Scale (C-SOADAS) questionnaires from patients with T2DM using metformin. The outcomes were analyzed by group and stratified based on the use of two, three, and more than three OADs. The level of agreement between the questionnaires was analyzed using Spearman’s rank correlation coefficient.ResultsA total of 153 patients with T2DM using metformin were included in this study. The average weighted impact score in the ADDQoL was −2.11, with no significant differences between the three groups. The C-SOADAS score showed a significant difference between the groups using two, three, and more than three OADs (21.42 [1.98] vs. 20.43 [2.09] vs. 19.00 [2.24], p &lt; 0.0001). The ADDQoL and C-SOADAS scores showed low correlations between patients’ QOL and treatment satisfaction. However, the impact of diabetes on specific aspects of life was negatively correlated with the total C-SOADAS scores.ConclusionIn Taiwan, a significantly greater effect on QOL was observed among patients with fewer OAD classes and higher treatment satisfaction. This study provides local evidence from self-reporting outcomes of patients with T2DM. Further studies focusing on different populations and treatment regimens for QOL are needed.
The accuracy of international and national fetal growth charts in detecting small-for-gestational-age infants using the Lambda-Mu-Sigma method
Authors: Saw Shier Nee , Lim Mei Cee , Liew Chuan Nyen , Ahmad Kamar Azanna , Sulaiman Sofiah , Saaid Rahmah , Loo Chu Kiong 
Published: April 2023

ObjectiveTo construct a national fetal growth chart using retrospective data and compared its diagnostic accuracy in predicting SGA at birth with existing international growth charts.MethodThis is a retrospective study where datasets from May 2011 to Apr 2020 were extracted to construct the fetal growth chart using the Lambda-Mu-Sigma method. SGA is defined as birth weight &lt;10th centile. The local growth chart's diagnostic accuracy in detecting SGA at birth was evaluated using datasets from May 2020 to Apr 2021 and was compared with the WHO, Hadlock, and INTERGROWTH-21st charts. Balanced accuracy, sensitivity, and specificity were reported.ResultsA total of 68,897 scans were collected and five biometric growth charts were constructed. Our national growth chart achieved an accuracy of 69% and a sensitivity of 42% in identifying SGA at birth. The WHO chart showed similar diagnostic performance as our national growth chart, followed by the Hadlock (67% accuracy and 38% sensitivity) and INTERGROWTH-21st (57% accuracy and 19% sensitivity). The specificities for all charts were 95–96%. All growth charts showed higher accuracy in the third trimester, with an improvement of 8–16%, as compared to that in the second trimester.ConclusionUsing the Hadlock and INTERGROWTH-21st chart in the Malaysian population may results in misdiagnose of SGA. Our population local chart has slightly higher accuracy in predicting preterm SGA in the second trimester which can enable earlier intervention for babies who are detected as SGA. All growth charts' diagnostic accuracies were poor in the second trimester, suggesting the need of improvising alternative techniques for early detection of SGA to improve fetus outcomes.