Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of Paeoniflorin on ANIT-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology

Background: Paeoniflorin (PF), the major active compound isolated from the roots of Paeonia lactiflora Pall. , has been used in the treatment of severe hepatic diseases for several decades and displays bright prospects in liver protective effect. However, its biological mechanism that regulates bile acid metabolism and cholestatic liver injury has not been fully elucidated. Our study aims to investigate the mechanism by which PF in the treatment of cholestatic liver injury using a comprehensive approach combining metabolomics and network pharmacological analysis. Methods: The hepatoprotective effect of PF against cholestasis liver injury, induced by α-naphthylisothiocyanate (ANIT), was evaluated in rats. The serum biochemical indices including ALT, AST, TBA, TBIL, ALP, ALB, and the pathological characteristics of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to explore the feces of rats with ANIT-induced cholestatic liver injury treated with PF and the potential biomarkers were screened by metabolomics. The targets for the regulation of potential biomarkers by PF were screened by network pharmacology, and then the relevant key targets were verified by immunohistochemical and western blotting methods. Results: PF significantly improved serum indexes and alleviated liver histological damage. Metabolomics analyses showed that the therapeutic effect of PF is mainly associated with the regulation of 13 metabolites involved in 16 metabolic pathways. The “PF-targets-metabolites” interaction network was constructed, and then five key targets including CDC25B, CYP2C9, MAOB, mTOR, and ABCB1 that regulated the potential biomarkers were obtained. The above five targets were further verified by immunohistochemistry and western blotting, and the results showed that PF significantly improved the expression of key proteins regulating these biomarkers. Conclusion: Our study provides direct evidence for the modulatory properties of PF treatment on ANIT-induced cholestatic liver injury using metabolomics and network pharmacology analyses. PF exhibits favorable pharmacological effect by regulating related signal pathways and key targets for biomarkers. Therefore, these findings may help better understand the complex mechanisms and provide a new and effective approach to the treatment of cholestatic liver injury.
An Immune-Associated Genomic Signature Effectively Predicts Pathologic Complete Response to Neoadjuvant Paclitaxel and Anthracycline-Based Chemotherapy in Breast Cancer

Breast cancer is now the leading cause of cancer morbidity and mortality among women worldwide. Paclitaxel and anthracycline-based neoadjuvant chemotherapy is widely used for the treatment of breast cancer, but its sensitivity remains difficult to predict for clinical use. In our study, a LASSO logistic regression method was applied to develop a genomic classifier for predicting pathologic complete response (pCR) to neoadjuvant chemotherapy in breast cancer. The predictive accuracy of the signature classifier was further evaluated using four other independent test sets. Also, functional enrichment analysis of genes in the signature was performed, and the correlations between the prediction score of the signature classifier and immune characteristics were explored. We found a 25-gene signature classifier through the modeling, which showed a strong ability to predict pCR to neoadjuvant chemotherapy in breast cancer. For T/FAC-based training and test sets, and a T/AC-based test set, the AUC of the signature classifier is 1.0, 0.9071, 0.9683, 0.9151, and 0.7350, respectively, indicating that it has good predictive ability for both T/FAC and T/AC schemes. The multivariate model showed that 25-gene signature was far superior to other clinical parameters as independent predictor. Functional enrichment analysis indicated that genes in the signature are mainly enriched in immune-related biological processes. The prediction score of the classifier was significantly positively correlated with the immune score. There were also significant differences in immune cell types between pCR and residual disease (RD) samples. Conclusively, we developed a 25-gene signature classifier that can effectively predict pCR to paclitaxel and anthracycline-based neoadjuvant chemotherapy in breast cancer. Our study also suggests that the immune ecosystem is actively involved in modulating clinical response to neoadjuvant chemotherapy and is beneficial to patient outcomes.
Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p<0.05, but lower concentrations of IL-10, p<0.001, IL-6, p<0.001 and brain-derived neurotrophic factors (BDNF) p<0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p<0.01, a significant decrease in the concentrations of anthranilic acid (AA) p<0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p<0.001, was found in this cohort. These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ), displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites. We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms.
Anger Experience and Anger Expression Through Drawing in Schizophrenia: An fNIRS Study

Differences in emotion experience and emotion expression between patients with schizophrenia and the healthy population have long been the focus of research and clinical attention. However, few empirical studies have addressed this topic using art-making as a tool of emotion expression. This study explores the differences in brain mechanism during the process of expressing anger between patients with schizophrenia and healthy participants using pictographic psychological techniques. We used functional near-infrared spectroscopy to fully detect changes in frontal cortex activity among participants in two groups—schizophrenia and healthy—during the process of experiencing and expressing anger. The results showed that there were no differences in the experience of anger between the two groups. In the process of anger expression, the dorsolateral prefrontal cortex, frontal pole, and other regions showed significant negative activation among patients with schizophrenia, which was significantly different from that of the healthy group. There were significant differences between patients with schizophrenia and the healthy group in the drawing features, drawing contents, and the ability to describe the contents of their drawings. Moreover, the effect size of the latter was greater than those of the former two. In terms of emotion expression, the drawing data and brain activation data were significantly correlated in each group; however, the correlation patterns differed between groups.
Review and Hypothesis: A Potential Common Link Between Glial Cells, Calcium Changes, Modulation of Synaptic Transmission, Spreading Depression, Migraine, and Epilepsy—H+

There is significant evidence to support the notion that glial cells can modulate the strength of synaptic connections between nerve cells, and it has further been suggested that alterations in intracellular calcium are likely to play a key role in this process. However, the molecular mechanism(s) by which glial cells modulate neuronal signaling remains contentiously debated. Recent experiments have suggested that alterations in extracellular H+ efflux initiated by extracellular ATP may play a key role in the modulation of synaptic strength by radial glial cells in the retina and astrocytes throughout the brain. ATP-elicited alterations in H+ flux from radial glial cells were first detected from Müller cells enzymatically dissociated from the retina of tiger salamander using self-referencing H+-selective microelectrodes. The ATP-elicited alteration in H+ efflux was further found to be highly evolutionarily conserved, extending to Müller cells isolated from species as diverse as lamprey, skate, rat, mouse, monkey and human. More recently, self-referencing H+-selective electrodes have been used to detect ATP-elicited alterations in H+ efflux around individual mammalian astrocytes from the cortex and hippocampus. Tied to increases in intracellular calcium, these ATP-induced extracellular acidifications are well-positioned to be key mediators of synaptic modulation. In this article, we examine the evidence supporting H+ as a key modulator of neurotransmission, review data showing that extracellular ATP elicits an increase in H+ efflux from glial cells, and describe the potential signal transduction pathways involved in glial cell—mediated H+ efflux. We then examine the potential role that extracellular H+ released by glia might play in regulating synaptic transmission within the vertebrate retina, and then expand the focus to discuss potential roles in spreading depression, migraine, epilepsy, and alterations in brain rhythms, and suggest that alterations in extracellular H+ may be a unifying feature linking these disparate phenomena.
A Novel CpG Methylation Risk Indicator for Predicting Prognosis in Bladder Cancer

Purpose Bladder cancer (BLCA) is one of the most common cancers worldwide. In a large proportion of BLCA patients, disease recurs and/or progress after resection, which remains a major clinical issue in BLCA management. Therefore, it is vital to identify prognostic biomarkers for treatment stratification. We investigated the efficiency of CpG methylation for the potential to be a prognostic biomarker for patients with BLCA. Patients and Methods Overall, 357 BLCA patients from The Cancer Genome Atlas (TCGA) were randomly separated into the training and internal validation cohorts. Least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) were used to select candidate CpGs and build the methylation risk score model, which was validated for its prognostic value in the validation cohort by Kaplan–Meier analysis. Hazard curves were generated to reveal the risk nodes throughout the follow-up. Gene Set Enrichment Analysis (GSEA) was used to reveal the potential biological pathways associated with the methylation model. Quantitative real-time polymerase chain reaction (PCR) and western blotting were performed to verify the expression level of the methylated genes. Results After incorporating the CpGs obtained by the two algorithms, CpG methylation of eight genes corresponding to TNFAIP8L3, KRTDAP, APC, ZC3H3, COL9A2, SLCO4A1, POU3F3, and ADARB2 were prominent candidate predictors in establishing a methylation risk score for BLCA (MRSB), which was used to divide the patients into high- and low-risk progression groups (p < 0.001). The effectiveness of the MRSB was validated in the internal cohort (p < 0.001). In the MRSB high-risk group, the hazard curve exhibited an initial wide, high peak within 10 months after treatment, whereas some gentle peaks around 2 years were noted. Furthermore, a nomogram comprising MRSB, age, sex, and tumor clinical stage was developed to predict the individual progression risk, and it performed well. Survival analysis implicated the effectiveness of MRSB, which remains significant in all the subgroup analysis based on the clinical features. A functional analysis of MRSB and the corresponding genes revealed potential pathways affecting tumor progression. Validation of quantitative real-time PCR and western blotting revealed that TNFAIP8L3 was upregulated in the BLCA tissues. Conclusion We developed the MRSB, an eight-gene-based methylation signature, which has great potential to be used to predict the post-surgery progression risk of BLCA.
Utilizing Heart Rate Variability for Coaching Athletes During and After Viral Infection: A Case Report in an Elite Endurance Athlete

Background: Viral diseases have different individual progressions and can lead to considerable risks/long-term consequences. Therefore, it is not suitable to give general recommendations on a time off from training for athletes. This case report aims to investigate the relevance of detecting heart rate (HR) and HR variability (HRV) during an orthostatic test (OT) to monitor the progression and recovery process during and after a viral disease in an elite endurance athlete. Methods: A 30-year-old elite marathon runner contracted a viral infection (upper respiratory tract infection) 4 weeks after a marathon race. RR intervals in HR time series in supine and standing positions were monitored daily in the morning. Analyzed parameters included HR, the time-domain HRV parameter root mean square of successive difference (RMSSD), peak HR (HRpeak) in a standing position, and the time to HR peak (tHRpeak). Results: During the 6-day viral infection period, HR increased significantly by an average of 11 bpm in the supine position and by 22 bpm in the standing position. In addition, the RMSSD decreased from 20.8 to 4.2 ms, the HRpeak decreased by 13 bpm, and the tHRpeak increased by 18 s in the standing position significantly. There were no significant changes in the pre-viral infection RMSSD values in the supine position. The viral infection led to a significant change in HR and HRV parameters. The cardiac autonomic system reacted more sensitively in the standing position compared to the supine position after a viral infection in the present case study. Conclusion: These data have provided supportive rationale as to why the OT with a change from supine to standing body position and the detection of different indicators based on HR and a vagal driven time-domain HRV parameter (RMSSD) is likely to be useful to detect viral diseases early on when implemented in daily routine. Given the case study nature of the findings, future research has to be conducted to investigate whether the use of the OT might be able to offer an innovative, non-invasive, and time-efficient possibility to detect and evaluate the health status of (elite endurance) athletes.
Rotation Variance in Graph Convolutional Networks

Convolution filters in deep convolutional networks display rotation variant behavior. While learned invariant behavior can be partially achieved, this paper shows that current methods of utilizing rotation variant features can be improved by proposing a grid-based graph convolutional network. By performing spectral graph convolutions on features extracted from subareas of images, we are able to take advantage of the geometric nature of relational machine learning in graph neural networks to be able to overcome rotation variant features to perform object localization. We demonstrate that Grid-GCN heavily outperforms existing models on rotated images, and through a set of ablation studies, we show how the performance of Grid-GCN implies that there exist more performant methods to utilize fundamentally rotation variant features and we conclude that the inherit nature of spectral graph convolutions is able to learn invariant behavior.
Smartphone-Based Color Measurement of Tooth Shade Guide in Clinical Lighting Conditions

Caries is a common disease of hard tissues of teeth which results in dental cavities, which are usually replaced by dental fillings. Matching the color of a dental filling is usually a subjective assessment. In this study, we conducted a color analysis of GC Gradia Direct shade guide in the lighting conditions of the dental office. Color measurement was performed using Color Grab mobile app and the results were acquired as values of RGB (red, green, blue) and HSV (hue, saturation, color value) values. The results indicate the possibility of identifying each shade of tooth by the most prominent changes in RGB and/or HSV components.
Semi-automated Algorithm for Complex Test Data Generation for Interface-based Regression Testing of Software Components

This paper describes in detail the Complex Object Generation (COG) algorithm, which is a semi-automated algorithm for the generation of instances of classes (i.e., objects) with a complex inner structure for Java and similar languages designed for black-box testing (i.e., without available source code). The algorithm was developed and tested as a stand-alone algorithm and can be used as such (e.g., during unit testing). However, we plan to use it to generate the parameter values of generated method invocations, which is a vital part of our interface-based regression testing of software components.
The Dynamics of Horizontal Economic Inequality in Countries Affected by Ethnic Conflict

This paper examines the dynamics of horizontal inequality in countries that have experienced ethnic conflict. This contrasts with previous studies which have focused on the effect of inequality on conflict. Understanding how conflict affects inequality serves to shed light on reasons behind conflict recurrence and slow economic development. The complex relationship between inequality and conflict is analyzed using both quantitative information, i.e., Demographic and Health Surveys (DHS) data from 36 countries for the time 1986-2018, and qualitative information, i.e., six country case studies. The focus throughout is POLICY BRIEF The Dynamics of Horizontal Economic Inequality in Countries Affected by Ethnic Conflict Michel Armel Ndayikeza August 2021 / No.759 2 Policy Brief No.759 on conflicts in which a rebel group claimed to fight the government on behalf of an ethnic group. The study also compares different inequality indicators suggested by the literature and provides arguments for why some of them should be preferred to others. Overall, the analysis shows that ethnic conflicts generally raise ethnic inequality. Furthermore, the way a conflict ends does not entirely determine the dynamics of horizontal inequality thereafter. The country case studies suggest that for a country to witness declining horizontal inequality following an ethnic conflict, these three conditions are important: (1) a swift victory of the rebel group; (2) financial resources to redistribute; and (3) a firm determination by the winner to redistribute. However, these conditions do not guarantee inequality decline. Therefore, the study suggests that it is important for policy makers to emphasize horizontal inequality reduction in the post-conflict period irrespective of how the conflict ended to avoid conflict recurrence.
COPD_A_272711 147..158

1Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2The Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 3Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 4School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China; 5State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China
On-line solid phase microextraction derivatization for the sensitive determination of multi-oxygenated volatile compounds in air

Abstract. Multi-oxygenated volatile organic compounds are important markers of air pollution and precursors of ozone and secondary aerosols in both polluted and remote environments. Herein, their accurate determination was enhanced. The approach was based on an automated system for active sampling and on-fibre derivatization coupled with the gas chromatography–mass spectrometry (GC–MS) technique. The method capability was determined for different compound families, such as aldehydes, ketones, α-dicarbonyls, hydroxy-aldehydes, hydroxy-ketones, and carboxylic acids. A good accuracy (<7 %) was demonstrated from the results compared to Fourier-transform infrared spectroscopy (FTIR). Limits of detection (LODs) of 6–100 pptV were achieved with a time resolution lower than 20 min. The developed method was successfully applied to the determination of multi-oxygenated compounds in air samples collected during an intercomparison campaign (EUROCHAMP-2020 project). Also, its capability and accuracy for atmospheric monitoring was demonstrated in an isoprene ozonolysis experiment. Both were carried out in the high-volume outdoor atmospheric simulation chambers (EUPHORE, 200 m3). In summary, our developed technique offers near-real-time monitoring with direct sampling, which is an advantage in terms of handling and labour time for a proper quantification of trace levels of atmospheric multi-oxygenated compounds.
OPTH_A_311706 2317..2325

1Riverwoods Eye Center, Provo, UT, USA; 2Dean McGee Eye Institute, University of Oklahoma, Oklahoma City, OK, USA; 3Excel Eye Center, Saratoga Springs, UT, USA Purpose: To describe surgical technique and report short-term visual outcomes after suturefixation of a single-piece eyelet-toric (SET) intraocular lens (IOL) for treatment of concurrent aphakia and astigmatism. Design: Retrospective, noncomparative, and non-consecutive case series. Methods: This was a case series of eleven eyes who underwent successful SET. Eligible eyes had loss of capsular support or aphakia with a minimum of symmetric corneal astigmatism 1.75 diopters (D). Outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), magnitude of residual refractive cylinder, and complications resulting from the SET procedure. Results: Preoperative UDVA and CDVA in logMAR scale were 1.46 and 0.45, respectively. Mean preoperative keratometric and refractive cylinder were 3.67 D and 2.52D, respectively. Postoperative UDVA and CDVA were 0.51 and 0.27, respectively, three months after surgery (POM3). Residual refractive cylinder at POM3 was 0.93 D. Conclusion: SET technique reduced refractive cylinder and improved UDVA and CDVA. SET may be adapted by surgeons using a readily available IOL and familiar scleral-fixation maneuvers.
Corruption and Firm Export Performance in Fragile Economies: Evidence from Zimbabwe

In this paper, we examine the relationship between corruption and firm export performance in Zimbabwe. Using a new panel data set of manufacturing and service firms from World Bank Enterprise survey and a methodology that relies on within-firm variation, we show that corruption increases the probability of exporting indirectly through intermediaries and decreases the probability of exporting directly. This result highlight that corruption is a cost to the economy in the absence of intermediaries. In addition, it highlights the importance of strong institutions that reduce corruption for business dynamism and economic growth. Corruption and Firm Export pErFormanCE in FragilE EConomiEs: EvidEnCE From ZimbabwE 1