bluuebunny/crossref_metadata_2025 huggingface dataset:
Introducing a Thermo-Alkali-Stable, Metallic Ion-Tolerant Laccase Purified From White Rot Fungus Trametes hirsuta
Authors: Si Jing , Ma Hongfei , Cao Yongjia , Cui Baokai , Dai Yucheng
Published: May 2021

This study introduces a valuable laccase, designated ThLacc-S, purified from white rot fungus Trametes hirsuta. ThLacc-S is a monomeric protein in nature with a molecular weight of 57.0 kDa and can efficiently metabolize endocrine disrupting chemicals. The enzyme was successfully purified to homogeneity via three consecutive steps consisting of salt precipitation and column chromatography, resulting in a 20.76-fold increase in purity and 46.79% yield, with specific activity of 22.111 U/mg protein. ThLacc-S was deciphered as a novel member of the laccase family and is a rare metalloenzyme that contains cysteine, serine, histidine, and tyrosine residues in its catalytic site, and follows Michaelis-Menten kinetic behavior with a Km and a kcat/Km of 87.466 μM and 1.479 s–1μM–1, respectively. ThLacc-S exerted excellent thermo-alkali stability, since it was markedly active after a 2-h incubation at temperatures ranging from 20 to 70°C and retained more than 50% of its activity after incubation for 72 h in a broad pH range of 5.0–10.0. Enzymatic activities of ThLacc-S were enhanced and preserved when exposed to metallic ions, surfactants, and organic solvents, rendering this novel enzyme of interest as a green catalyst for versatile biotechnological and industrial applications that require these singularities of laccases, particularly biodegradation and bioremediation of environmental pollutants.
Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer
Authors: Liu Jingchao , Ma Hong , Meng Lingfeng , Liu Xiaodong , Lv Zhengtong , Zhang Yaoguang , Wang Jianye
Published: May 2021

Purpose: To identify whether ferroptosis-related genes play predictive roles in bladder cancer patients and to develop a ferroptosis-related gene signature to predict overall survival outcomes.

Materials and Methods: We downloaded the mRNA expression files and clinical data of 256 bladder samples (188 bladder tumour and 68 nontumour samples) from the GEO database and 430 bladder samples (411 bladder tumour and 19 nontumour samples) from the TCGA database. A multigene signature based on prognostic ferroptosis-related genes was constructed by least absolute shrinkage and selection operator Cox regression analysis in the GEO cohort. The TCGA cohort was used to validate the ferroptosis-related gene signature. Next, functional enrichment analysis, including both Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses, was performed to elucidate the mechanism underlying the signature. The ssGSEA scores of 16 immune cells and 13 immune-related pathway activities between the high-risk and low-risk groups were also analysed in our study.

Results: Thirty-three (67.3%) ferroptosis-related genes were differentially expressed between bladder tumour samples and nontumour samples in the GEO cohort. The intersection of prognostic ferroptosis-related genes and differentially expressed genes identified four prognostic targets, including ALOX5, FANCD2, HMGCR and FADS2. The least absolute shrinkage and selection operator Cox regression successfully built a 4-gene signature: risk score value = esum (each gene’s normalized expression * each gene’s coefficient). Univariate and multivariate Cox regression analyses were performed in both the GEO and TCGA cohorts to test the independent prognostic value of the 4-gene risk signature. Multivariate Cox regression analysis in the GEO cohort identified age (p < 0.001), grade (p = 0.129) and risk score (p = 0.016) as independent prognostic predictors for overall survival. Multivariate Cox regression analysis in the TCGA cohort also identified age (p = 0.002), stage (p < 0.001) and risk score (p = 0.006) as independent prognostic predictors for overall survival. The type II IFN response was determined to be significantly weakened in the high-risk group in both the GEO and TCGA cohorts.

Conclusion: We successfully built a ferroptosis-related gene signature of significant predictive value for bladder cancer. These results suggest a novel research direction for targeted therapy of bladder cancer in the future.
Predicting Brain Regions Related to Alzheimer's Disease Based on Global Feature
Authors: Wang Qi , Chen Siwei , Wang He , Chen Luzeng , Sun Yongan , Yan Guiying
Published: May 2021

Alzheimer's disease (AD) is a neurodegenerative disease that commonly affects the elderly; early diagnosis and timely treatment are very important to delay the course of the disease. In the past, most brain regions related to AD were identified based on imaging methods, and only some atrophic brain regions could be identified. In this work, the authors used mathematical models to identify the potential brain regions related to AD. In this study, 20 patients with AD and 13 healthy controls (non-AD) were recruited by the neurology outpatient department or the neurology ward of Peking University First Hospital from September 2017 to March 2019. First, diffusion tensor imaging (DTI) was used to construct the brain structural network. Next, the authors set a new local feature index 2hop-connectivity to measure the correlation between different regions. Compared with the traditional graph theory index, 2hop-connectivity exploits the higher-order information of the graph structure. And for this purpose, the authors proposed a novel algorithm called 2hopRWR to measure 2hop-connectivity. Then, a new index global feature score (GFS) based on a global feature was proposed by combing five local features, namely degree centrality, betweenness centrality, closeness centrality, the number of maximal cliques, and 2hop-connectivity, to judge which brain regions are related to AD. As a result, the top ten brain regions identified using the GFS scoring difference between the AD and the non-AD groups were associated to AD by literature verification. The results of the literature validation comparing GFS with the local features showed that GFS was superior to individual local features. Finally, the results of the canonical correlation analysis showed that the GFS was significantly correlated with the scores of the Mini-Mental State Examination (MMSE) scale and the Montreal Cognitive Assessment (MoCA) scale. Therefore, the authors believe the GFS can also be used as a new biomarker to assist in diagnosis and objective monitoring of disease progression. Besides, the method proposed in this paper can be used as a differential network analysis method for network analysis in other domains.
Machine Learning-Based Prediction of Brain Tissue Infarction in Patients With Acute Ischemic Stroke Treated With Theophylline as an Add-On to Thrombolytic Therapy: A Randomized Clinical Trial Subgroup Analysis
Authors: Modrau Boris , Winder Anthony , Hjort Niels , Johansen Martin Nygård , Andersen Grethe , Fiehler Jens , Vorum Henrik , Forkert Nils D.
Published: May 2021

Background and Purpose: The theophylline in acute ischemic stroke trial investigated the neuroprotective effect of theophylline as an add-on to thrombolytic therapy in patients with acute ischemic stroke. The aim of this pre-planned subgroup analysis was to use predictive modeling to virtually test for differences in the follow-up lesion volumes.

Materials and Methods: A subgroup of 52 patients from the theophylline in acute ischemic stroke trial with multi-parametric MRI data acquired at baseline and at 24-h follow-up were analyzed. A machine learning model using voxel-by-voxel information from diffusion- and perfusion-weighted MRI and clinical parameters was used to predict the infarct volume for each individual patient and both treatment arms. After training of the two predictive models, two virtual lesion outcomes were available for each patient, one lesion predicted for theophylline treatment and one lesion predicted for placebo treatment.

Results: The mean predicted volume of follow-up lesions was 11.4 ml (standard deviation 18.7) for patients virtually treated with theophylline and 11.2 ml (standard deviation 17.3) for patients virtually treated with placebo (p = 0.86).

Conclusions: The predicted follow-up brain lesions for each patient were not significantly different for patients virtually treated with theophylline or placebo, as an add-on to thrombolytic therapy. Thus, this study confirmed the lack of neuroprotective effect of theophylline shown in the main clinical trial and is contrary to the results from preclinical stroke models.
Improvement in Midline Shift Is a Positive Prognostic Predictor for Malignant Middle Cerebral Artery Infarction Patients Undergoing Decompressive Craniectomy
Authors: Chen Xin , Hao Qiang , Yang Shu-Zhe , Wang Shuo , Zhao Yuan-Li , Zhang Dong , Ye Xun , Wang Hao
Published: May 2021

Objective: The aim of this retrospective study is to evaluate the risk factors of malignant middle cerebral artery infarction (MMCAI) patients and explore an applicable prognostic predictor for MMCAI patients undergoing decompressive craniectomy (DC).

Methods: Clinical data from the period 2012–2017 were retrospectively evaluated. Forty-three consecutive MMCAI patients undergoing DC were enrolled in this study. The 30-day mortality was assessed, and age, location, hypertension, pupil dilation, onset to operation duration, midline shift, and Glasgow Coma Scale (GCS) score were identified by univariate analysis and binary logistic regression.

Results: In this retrospective study for DC patients, the 30-day mortality was 44.2%. In the univariate analysis, advanced age (≥60 years), right hemispheric location, hypertension, pupil dilation, shorter onset to operation duration (<48 h), improved midline shift (t = 4.214, p < 0.01), and lower pre-operation GCS score were significant predictors of death within 30 days. In binary logistic regression analysis, age [odds ratio (OR) = 1.141, 95% CI 1.011–1.287], the improvement of the midline shift (OR = 0.764, 95% CI 0.59–0.988), and pupillary dilation (OR = 15.10, 95% CI 1.374–165.954) were independent influencing factors. For the receiver operating characteristic (ROC) analysis of the relationship between post-operation outcomes and midline shift improvement, the area under the curve (AUC) was 0.844, and the cutoff point of midline shift improvement was 0.83 cm.

Conclusion: Improved midline shift was a significant predictor of 30-day mortality. The improved midline shift of >0.83 cm indicated survival at 30 days.
Acupuncture May Decrease the Incidence of Post-stroke Dementia: A Taiwan Nationwide Retrospective Cohort Study
Authors: Chu Shao-Ang , Chen Te-Yuan , Chen Po-Yuan , Tzeng Wei-Jie , Liang Cheng-Loong , Lu Kang , Chen Han-Jung , Wu Cheng-Chun , Chen Jian-Han , Tsai Chin-Chuan , Wang Hao-Kuang
Published: May 2021

Background: Post-stroke dementia may affect up to one-third of stroke survivors. Acupuncture as a complementary treatment for stroke has been shown to be beneficial for subsequent post-stroke rehabilitation. The purpose of this retrospective cohort study was to investigate the potential effect of acupuncture to protect stroke patients from dementia.

Methods: We included 9,547 patients receiving ambulatory or hospital care for stroke and 9.547 non-stroke patients; patients were matched for sex, age, and Charlson Comorbidity Index. Each individual was traced for the subsequent development of dementia. Two thousand four hundred and forty-nine stroke patients received acupuncture treatment and 7,098 residue stroke patients without acupuncture treatment served as control groups. This is a 3-year follow-up cohorts study: the incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of post- stroke dementia in the Cox proportional hazard regression.

Results: During the 3-year follow-up, 1,403 patients with stroke (14.70%) and 427 patients without stroke (4.47%) developed dementia. The adjusted HRs of development of dementia among stroke patients were 3.64-times (range, 3.27–4.06), and the incidence of dementia was higher in male. Stroke patients receiving acupuncture treatment had a lower probability of dementia than those without acupuncture during the follow-up period, the adjusted HRs was 0.49 (95% CI, 0.42–0.58; p < 0.001).

Conclusions: The association between stroke and dementia existed in both sexes, more prominent in male. Patients with stroke receiving acupuncture treatments showed decreased risk of dementia. Care must be taken evaluating these results because this study was limited to lack of information regarding lifestyles, stroke severities, and acupuncture methods that were used in treatments.
Evaluation of Three Machine Learning Algorithms for the Automatic Classification of EMG Patterns in Gait Disorders
Authors: Fricke Christopher , Alizadeh Jalal , Zakhary Nahrin , Woost Timo B. , Bogdan Martin , Classen Joseph
Published: May 2021

Gait disorders are common in neurodegenerative diseases and distinguishing between seemingly similar kinematic patterns associated with different pathological entities is a challenge even for the experienced clinician. Ultimately, muscle activity underlies the generation of kinematic patterns. Therefore, one possible way to address this problem may be to differentiate gait disorders by analyzing intrinsic features of muscle activations patterns. Here, we examined whether it is possible to differentiate electromyography (EMG) gait patterns of healthy subjects and patients with different gait disorders using machine learning techniques. Nineteen healthy volunteers (9 male, 10 female, age 28.2 ± 6.2 years) and 18 patients with gait disorders (10 male, 8 female, age 66.2 ± 14.7 years) resulting from different neurological diseases walked down a hallway 10 times at a convenient pace while their muscle activity was recorded via surface EMG electrodes attached to 5 muscles of each leg (10 channels in total). Gait disorders were classified as predominantly hypokinetic (n = 12) or ataxic (n = 6) gait by two experienced raters based on video recordings. Three different classification methods (Convolutional Neural Network—CNN, Support Vector Machine—SVM, K-Nearest Neighbors—KNN) were used to automatically classify EMG patterns according to the underlying gait disorder and differentiate patients and healthy participants. Using a leave-one-out approach for training and evaluating the classifiers, the automatic classification of normal and abnormal EMG patterns during gait (2 classes: “healthy” and “patient”) was possible with a high degree of accuracy using CNN (accuracy 91.9%), but not SVM (accuracy 67.6%) or KNN (accuracy 48.7%). For classification of hypokinetic vs. ataxic vs. normal gait (3 classes) best results were again obtained for CNN (accuracy 83.8%) while SVM and KNN performed worse (accuracy SVM 51.4%, KNN 32.4%). These results suggest that machine learning methods are useful for distinguishing individuals with gait disorders from healthy controls and may help classification with respect to the underlying disorder even when classifiers are trained on comparably small cohorts. In our study, CNN achieved higher accuracy than SVM and KNN and may constitute a promising method for further investigation.
Microglia Stimulation by Protein Extract of Injured Rat Spinal Cord. A Novel In vitro Model for Studying Activated Microglia
Authors: Hernández Joaquim , Francos-Quijorna Isaac , Redondo-Castro Elena , López-Vales Rubén , Navarro Xavier
Published: May 2021

Research on microglia has established the differentiation between the so-called M1 and M2 phenotypes. However, new frameworks have been proposed attempting to discern between meaningful microglia profiles. We have set up an in vitro microglial activation model by adding an injured spinal cord (SCI) lysate to microglial cultures, obtained from postnatal rats, in order to mimic the environment of the spinal cord after injury. We found that under the presence of the SCI lysate microglial cells changed their phenotype, developing less ramified but longer processes, and proliferated. The SCI lysate also led to upregulation of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, downregulation of the anti-inflammatory cytokines IL-10 and IL-4, and a biphasic profile of iNOS. In addition, a latex beads phagocytosis assay revealed the SCI lysate stimulated the phagocytic capacity of microglia. Flow cytometry analysis indicated that microglial cells showed a pro-inflammatory profile in the presence of SCI lysate. Finally, characterization of the microglial activation in the spinal cord on day 7 after contusion injury, we showed that these cells have a pro-inflammatory phenotype. Overall, these results indicate that the use of SCI lysates could be a useful tool to skew microglia towards a closer phenotype to that observed after the spinal cord contusion injury than the use of LPS or IFNγ.
CircRNA-ceRNA Network Revealing the Potential Regulatory Roles of CircRNA in Alzheimer’s Disease Involved the cGMP-PKG Signal Pathway
Authors: Zhang Yuan , Qian Lili , Liu Yingying , Liu Ying , Yu Wanpeng , Zhao Yanfang
Published: May 2021

Background: Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease. The characteristic pathologies include extracellular senile plaques formed by β-amyloid protein deposition, neurofibrillary tangles formed by hyperphosphorylation of tau protein, and neuronal loss with glial cell hyperplasia. Circular RNAs (circRNAs) are rich in miRNA-binding sites (miRNA response elements, MREs), which serve as miRNA sponges or competitive endogenous RNAs (ceRNAs). Although several research groups have identified dysregulated circRNAs in the cerebral cortex of SAMP8 mice or APP/PS1 mice using deep RNA-seq analysis, we need to further explore circRNA expression patterns, targets, functions and the signaling pathways involved in the pathogenesis of AD and in particular the hippocampal circRNA expression profiles in AD.

Methods: We used deep RNA sequencing to investigate circRNA-ceRNA network patterns in the hippocampus of APP/PS1 mice.

Results: In our study, 70 dysregulated circRNAs, 39 dysregulated miRNAs and 121 dysregulated mRNAs were identified between the APP/PS1 group and the wild-type group at 8 months in the hippocampus of the mice. Through correlation analysis, we identified 11 dysregulated circRNAs, 7 dysregulated miRNAs and 8 dysregulated mRNAs forming 16 relationships in the circRNA-miRNA-mRNA regulatory network. Gene ontology (GO) analysis indicated that the dysregulated circRNAs were most enriched in biological metabolic processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the dysregulation of circRNAs was enriched in the cGMP-PKG signaling pathway, cAMP signaling pathway, Hippo signaling pathway, platelet activation, long-term potentiation and axon guidance. In addition, our findings preliminarily verified that the novel_circ_0003012/mmu-miR-298-3p/Smoc2 signaling axis may regulate the pathophysiology of AD by affecting the cGMP-PKG signaling pathway.

Conclusions: These newly identified circRNAs in networks and signaling pathways reveal potential diagnostic or therapeutic targets for AD.
Emerging Role of Serum Glucocorticoid-Regulated Kinase 1 in Pathological Pain
Authors: Liu Baowen , Li Ningbo , He Zhigang , Zhang Xianwei , Duan Guangyou
Published: May 2021

Currently, the management of acute and chronic pain in clinical practice remains unsatisfactory due to the existence of limited effective treatments, and novel therapeutic strategies for pathological pain are urgently needed. In the past few decades, the role of serum and glucocorticoid-inducible kinase 1 (SGK1) in the development of pain and diurnal rhythms has been implicated in numerous studies. The expression levels of SGK1 mRNA and protein were found to be elevated in the spinal cord and brain in various pathological pain models. Blocking SGK1 significantly attenuated pain-like responses and the development of pathological pain. These studies provide strong evidence that SGK1 plays a role in the development of various types of pathological pain and that targeting SGK1 may be a novel therapeutic strategy for pain management. In this review article, we provide evidence from animal models for the potential role of SGK1 in the regulation of pathological pain caused by inflammation, nerve injury, psychiatric disorders, and chronic opioid exposure.
Organ-Specific Immune-Related Adverse Events for PD-1 Antibodies in Lung Cancer Treatment
Authors: Zheng Xiaohu , Wei Haiming
Published: May 2021

Anti-PD-1 therapy has revolutionized the clinical treatment of lung cancer. With the increasing number of lung cancer patients being treated, there is also an increase in the number of immune-related adverse events (irAEs) being reported. These irAEs involve multiple organs and systems, mainly manifest as inflammatory side effects, and are different from the adverse events observed with traditional lung cancer treatment. These effects are often mild and treatable and reversible; however, in a few cases the side effects can be severe and lead to termination of immunotherapy. Management involves glucocorticoid-based related immunomodulators, which should be carefully prescribed to balance the efficacy and side effects of the PD-1 antibody treatment. This review will describe the characteristics and mechanisms of irAEs in specific organs, and will serve as a guide to help optimize treatment plans and improve patient outcomes.
Beyond Conventional: The New Horizon of Targeted Therapy for the Treatment of Advanced Non Small Cell Lung Cancer
Authors: Tartarone Alfredo , Lapadula Vittoria , Di Micco Concetta , Rossi Gemma , Ottanelli Carlotta , Marini Andrea , Giorgione Roberta , Ferrari Katia , Catalano Martina , Voltolini Luca , Mini Enrico , Roviello Giandomenico
Published: May 2021

In the last few years the advent of targeted therapies against oncogenic drivers significantly improved the survival of non small cell lung cancer (NSCLC) patients with a favourable toxicity profile. Therefore, genetic testing, including at least EGFR mutations and ALK/ROS1 rearrangements, should be performed in all NSCLC patients (in particular with adenocarcinoma) who received a diagnosis of advanced disease. This review focuses on novel druggable oncogenic drivers, such as MET exon 14 mutations/MET amplification, RET fusions, BRAF V600E mutations, KRAS G12C mutations, NTRK rearrangements, and HER2 alterations.
The Role of Microtubules in Pancreatic Cancer: Therapeutic Progress
Authors: Albahde Mugahed Abdullah Hasan , Abdrakhimov Bulat , Li Guo-Qi , Zhou Xiaohu , Zhou Dongkai , Xu Hao , Qian Huixiao , Wang Weilin
Published: May 2021

Pancreatic cancer has an extremely low prognosis, which is attributable to its high aggressiveness, invasiveness, late diagnosis, and lack of effective therapies. Among all the drugs joining the fight against this type of cancer, microtubule-targeting agents are considered to be the most promising. They inhibit cancer cells although through different mechanisms such as blocking cell division, apoptosis induction, etc. Hereby, we review the functions of microtubule cytoskeletal proteins in tumor cells and comprehensively examine the effects of microtubule-targeting agents on pancreatic carcinoma.
The Global, Regional, and National Burden and Trends of Breast Cancer From 1990 to 2019: Results From the Global Burden of Disease Study 2019
Authors: Xu Shangbo , Liu Yiyuan , Zhang Taofeng , Zheng Jiehua , Lin Weixun , Cai Jiehui , Zou Juan , Chen Yaokun , Xie Yanna , Chen Yexi , Li Zhiyang
Published: May 2021

Background

The burden of breast cancer has been increasing globally. The epidemiology burden and trends need to be updated. This study aimed to update the burden and trends of breast cancer incidences, deaths, and disability-adjusted life-years (DALYs) from 1990 to 2019, using the Global Burden of Disease 2019 study.

Methods

The data of incidences, deaths, DALYs, and age-standardized rates were extracted. Estimated annual percentage changes were used to quantify the trends of age-standardized rates. Besides, the population attributable fractions of the risk factors of breast cancer were also estimated.

Results

Globally, the incidences of breast cancer increased to 2,002,354 in 2019. High social-development index (SDI) quintiles had the highest incidence cases with a declining trend in age-standardized incidence rate. In 2019, the global deaths and DALYs of breast cancer increased to 700,660 and 20,625,313, respectively. From 1990 to 2019, the age-standardized mortality rates and age-standardized DALY rates declined globally, especially in high and high-middle SDI quintiles. Besides, the trends varied from different regions and countries. The proportion of the patients in the 70+ years age group increased globally. Deaths of breast cancer attributable to high fasting plasma glucose and high body mass index increased globally, and high fasting plasma glucose was the greatest contributor to the global breast cancer deaths.

Conclusion

The burden of breast cancer in higher SDI quintiles had gone down while the burden was still on the rise in lower SDI quintiles. It is necessary to appeal to the public to decrease the exposure of the risk factors.
Pediatric Pulmonary Function Testing in COVID-19 Pandemic and Beyond. A Position Statement From the Hellenic Pediatric Respiratory Society
Authors: Fouzas Sotirios , Gidaris Dimos , Karantaglis Nikolaos , Opsimos Harry , Alexopoulos Emmanouil I. , Douros Konstantinos , Kirvassilis Fotios , Paraskakis Emmanouil , Anthracopoulos Michael B. , Marangos Markos , Tsanakas Ioannis ,   the Hellenic Pediatric Respiratory Society
Published: May 2021

As the COVID-19 pandemic is still evolving, guidelines on pulmonary function testing that may dynamically adapt to sudden epidemiologic changes are required. This paper presents the recommendations of the Hellenic Pediatric Respiratory Society (HPRS) on pulmonary function testing in children and adolescents during the COVID-19 era. Following an extensive review of the relevant literature, we recommend that pulmonary function tests should be carried out after careful evaluation of the epidemiologic load, structured clinical screening of all candidates, and application of special protective measures to minimize the risk of viral cross infection. These principles have been integrated into a dynamic action plan that may readily adapt to the phase of the pandemic.
Acid Suppression Use Among Infants in One Tertiary Children's Hospital in China, 2015–2018: A Retrospective Observational Study
Authors: Zhou Yue , Xu Lina , Wushouer Haishaerjiang , Yu Aichen , Xu Ziyue , Chen Chaoyang , Cui Yimin , Lu Qinghong , Guan Xiaodong , Shi Luwen
Published: May 2021

Clinical guidelines emphasized that physicians should be cautious when prescribing acid suppressions to infants. Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are not approved for use in infants aged below 2 years in China. We investigated H2RA/PPI use in infants aged below 2 years hospitalized between 1st January 2015 and 31st December 2018 in a Chinese tertiary children's hospital. Our study observed that H2RAs/PPIs were frequently prescribed with a prevalence of 4.4% (7,158/162,192). The frequency of PPI use was over two-fold than that of H2RA use (71.9%, 5,148/7,158; 28.1%, 2,011/7,158). H2RAs/PPIs were commonly used to treat infants without digestive system diseases (57.5%, 4,118/7,158). Further studies are urgently needed to evaluate the effectiveness and safety of H2RAs/PPIs in infants.
Bicyclol Regulates Hepatic Gluconeogenesis in Rats with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease by Inhibiting Inflammation
Authors: Li Hongxue , Xu Qian , Xu Chengye , Hu Yuxin , Yu Xingyang , Zhao Kangqi , Li Mingqing , Li Meng , Xu Junfang , Kuang Hongyu
Published: May 2021

Hepatic gluconeogenesis plays an important role in maintaining the body’s glucose metabolism homeostasis. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases, when combined with type 2 diabetes mellitus (T2DM), it can cause severe glucose metabolism disorders. Studies have confirmed that chronic liver inflammatory lesions are the basis of T2DM combined with NAFLD (T2DM–NAFLD), inhibiting liver inflammation can improve glucose metabolism disorders. It is essential to explore safe and effective drugs to inhibit liver inflammation to improve the body’s glucose metabolism disorders. Bicyclol is a biphenyl derivative that has anti-oxidative and anti-inflammatory properties. In the present study, the hepatoprotective effects and underlying mechanisms of bicyclol in T2DM–NAFLD were investigated, and T2DM–NAFLD with/without bicyclol treatment models were established. The results revealed that bicyclol alleviated fasting blood glucose, serum transaminase levels, insulin resistance, hepatic adipogenesis, lipid accumulation and markedly reduced T2DM–NAFLD rat histological alterations of livers. Not only that, bicyclol markedly attenuated T2DM–NAFLD induced production of inflammation factors (IL-1β and TNF-α). Moreover, bicyclol suppressed the expression of insulin/gluconeogenesis signaling pathway (Akt, PGC-1α and PEPCK). These findings suggested that bicyclol might be a potentially effective drug for the treatment of T2DM–NAFLD and other metabolic disorders.
Genistein From Fructus sophorae Protects Mice From Radiation-Induced Intestinal Injury
Authors: Zhang Jieyu , Pang Zhijun , Zhang Yuting , Liu Jiaxin , Wang Zhaowei , Xu Chuanyang , He Lei , Li Weina , Zhang Kuo , Zhang Wangqian , Wang Shuning , Zhang Cun , Hao Qiang , Zhang Yingqi , Li Meng , Li Zhengmin
Published: May 2021

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in high-dose ionizing radiation-induced acute damage. Genistein has shown bioactivity in alleviating radiation damage and is currently synthesized by chemosynthetic methods. Due to concerns about chemical residues and high costs, the clinical application of genistein is still a major challenge. In this study, we aimed to establish an efficient method for the extraction of genistein from Fructus sophorae. The effects of extracted genistein (FSGen) on preventing intestinal injury from radiation were further investigated in this study. C57/BL mice were exposed to 7.5 Gy whole body irradiation with and without FSGen treatments. Histological analysis demonstrated significant structural and functional restitution of the intestine and bone marrow in FSGen-pretreated cohorts after irradiation. Through mRNA expression, protein expression, and small interfering RNA analyses, we demonstrated that FSGen protects IEC-6 cells against radiation damage by upregulating the Rassf1a and Ercc1 genes to effectively attenuate DNA irradiation damage. Together, our data established an effective method to extract genistein from the Fructus sophorae plant with high purity, and validated the beneficial roles of the FSGen in protecting the radiation damage. These results promise the future applications of Fructus sophorae extracted genistein in the protection of radiation related damages.
Molecular Action of Hydroxytyrosol in Attenuation of Intimal Hyperplasia: A Scoping Review
Authors: Vijakumaran Ubashini , Yazid Muhammad Dain , Hj Idrus Ruszymah Bt , Abdul Rahman Mohd Ramzisham , Sulaiman Nadiah
Published: May 2021

Objective: Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation.

Methods: A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria.

Results: Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1β, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model.

Conclusions: Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.
Preclinical Investigation of Alpinetin in the Treatment of Cancer-Induced Cachexia via Activating PPARγ
Authors: Zhang Yujie , Zhang Yuxin , Li Yichen , Zhang Li , Yu Shiying
Published: May 2021

The ongoing loss of skeletal muscle is a central event of cancer cachexia, and its consequences include adverse effects on patient’s quality of life and survival. Alpinetin (Alp), a natural plant-derived flavonoid obtained from Alpinia katsumadai Hayata, has been reported to possess potent anti-inflammatory and antitumor activities. This study aimed to explore the therapeutic effect and underlying mechanism of Alp in the prevention of cancer cachexia. We found that Alp (25–100 μM) dose-dependently attenuated Lewis lung carcinoma–conditioned medium-induced C2C12 myotube atrophy and reduced expression of the E3 ligases Atrogin-1 and MuRF1. Moreover, Alp administration markedly improved vital features of cancer cachexia in vivo with visible reduction of the loss of tumor-free body weight and wasting of multiple tissues, including skeletal muscle, epididymal fat, and decreased expression of Atrogin-1 and MuRF1 in cachectic muscle. Alp suppressed the elevated spleen weight and serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Further, Alp treatment remained protective against cancer cachexia in the advanced stage of tumor growth. Molecular docking results suggested that Alp was docked into the active site of PPARγ with the docking score of –7.6 kcal/mol, forming a hydrogen bond interaction with PPARγ protein amino acid residue HIS449 with a bond length of 3.3 Å. Mechanism analysis revealed that Alp activated PPARγ, resulting in the downregulated phosphorylation of NF-κB and STAT3 in vitro and in vivo. PPARγ inhibition induced by GW9662 notably attenuated the improvement of Alp on the above cachexia phenomenon, indicating that PPARγ activation mediated the therapeutic effect of Alp. These findings suggested that Alp might be a potential therapeutic candidate against cancer cachexia.
Identification and Characterization of Two Transmembrane Proteins Required for Virulence of Ustilago maydis
Authors: Weiland Paul , Altegoer Florian
Published: May 2021

Smut fungi comprise a large group of biotrophic phytopathogens infecting important crops such as wheat and corn. Through the secretion of effector proteins, the fungus actively suppresses plant immune reactions and modulates its host’s metabolism. Consequently, how soluble effector proteins contribute to virulence is already characterized in a range of phytopathogens. However, membrane-associated virulence factors have been much less studied to date. Here, we investigated six transmembrane (TM) proteins that show elevated gene expression during biotrophic development of the maize pathogen Ustilago maydis. We show that two of the six proteins, named Vmp1 and Vmp2 (virulence-associated membrane protein), are essential for the full virulence of U. maydis. The deletion of the corresponding genes leads to a substantial attenuation in the virulence of U. maydis. Furthermore, both are conserved in various related smuts and contain no domains of known function. Our biochemical analysis clearly shows that Vmp1 and Vmp2 are membrane-associated proteins, potentially localizing to the U. maydis plasma membrane. Mass photometry and light scattering suggest that Vmp1 mainly occurs as a monomer, while Vmp2 is dimeric. Notably, the large and partially unstructured C-terminal domain of Vmp2 is crucial for virulence while not contributing to dimerization. Taken together, we here provide an initial characterization of two membrane proteins as virulence factors of U. maydis.
The Influence of Personality Traits on School Bullying: A Moderated Mediation Model
Authors: Zhang Yun , Li Zuoshan , Tan Yalan , Zhang Xi , Zhao Qingyu , Chen Xin
Published: May 2021

We recruited 1,631 middle and high school students to explore the relationship between personality traits and school bullying, and the moderated and mediating roles of self-concept and loneliness on this relationship. Results showed that (1) neuroticism had a significant positive predictive effect on being bullied, extroversion had a significant negative predictive effect on being bullied, and agreeableness had a significant negative predictive effect on bullying/being bullied; (2) loneliness played a mediating role between neuroticism and bullied behaviors, extroversion and bullying behaviors, and agreeableness and bullying/bullied behaviors; (3) self-concept played a moderating role on the mediation pathway of loneliness on neuroticism, extraversion, agreeableness and bullying behaviors. Therefore, to reduce the frequency of school bullying among adolescents, we should not only reduce their levels of loneliness but also improve their levels of self-concept.
Development and Validation of the Win-Win Scale
Authors: Zhang Shan , Zang Xinlei , Zhang Feng
Published: May 2021

Accumulating evidence has shown that win-win is necessary for both individuals and the society. This research, including two studies, aimed to develop and validate a measurement of the win-win scale. In the first study, we screened the items by item analysis and extracted common factors using exploratory factor analysis (EFA), thus determining a total of 25 items in the initial scale consisted of five dimensions including integrity, advancement, altruism, harmoniousness, and coordination. In the second study, we used first- and second-order confirmatory factor analysis (CFA) to test the scale’s construct validity. The results indicated a good fit between the five-factor model and the data. Based on our results, we have formed a win-win scale by keeping 16 items from the original project pool.
Exploring Implicit and Explicit Attitudes of Employees’ Authentic Organizational Loyalty
Authors: Hong Ji-Woong , Hong Ah Jeong , Kim Sang Rak
Published: May 2021

The purpose of this study was to develop the OL-IAT (Organizational Loyalty – Implicit Association Test), an IAT tool that measures implicit attitudes toward organizational loyalty, and to verify its predictive validity. In total, 15 respondents were randomly selected from among the employees of P Company. The respondents were then asked open questions about the image they held of the target company. Based on their responses, a list of words was compiled for use on the OL-IAT. Evaluation categories, either like-dislike or positive-negative, were developed for this test based on the approach-avoidance words proposed by Ostafin and Palfai (2006). The OL-IAT was then administered to 127 employees of Company P, and self-reporting measures were also devised to measure explicit attitudes. A survey of whether the implicit attitude toward organizational loyalty was consistent with the explicit attitude showed that there was no significant correlation, and the attitude inconsistency was evident in the responses. When differences in rank were accounted for, organizational loyalty attitudes were consistent at the manager level, and organizational participation attitudes were consistent at the manager and general staff levels. This study will aid in the development of effective measures of organizational loyalty and accelerate interventions to increase it, which in turn will positively impact long-term organizational growth.
Cognition and Pain: A Review
Authors: Khera Tanvi , Rangasamy Valluvan
Published: May 2021

Cognition is defined as the brain’s ability to acquire, process, store, and retrieve information. Pain has been described as an unpleasant sensory or emotional experience, and for experiencing pain consciously, cognitive processing becomes imperative. Moreover, evaluation of pain strongly depends on cognition as it requires learning and recall of previous experiences. There could be a possible close link between neural systems involved in cognition and pain processing, and studies have reported an association between pain and cognitive impairment. In this narrative review, we explore the available evidence that has investigated cognitive changes associated with pain. We also examine the anatomical, biochemical, and molecular association of pain and neuro-cognition. Additionally, we focus on the cognitive impairment caused by analgesic medications. There is a need to improve our understanding of pathophysiology and cognitive impairment mechanisms associated with chronic pain and its treatment. This area provides a diverse opportunity for grounding future research, aiding institution of timely interventions to prevent chronic pain and associated cognitive decline, ultimately improving patient care.
Tracing the Single and Combined Contributions of Home-Grown Supply and Health Literacy on Fruit and Vegetable Consumption: An Empirical Exploration in Rural India
Authors: Wu Yun-Hsuan , Moore Spencer , McRae Cameron , Dubé Laurette
Published: May 2021

Low fruit and vegetable consumption (FVC) remains a global health challenge. Fostering subsistence agriculture through the production and home-grown consumption (HGC) of fruits and vegetables are seen as potential strategies for improving overall FVC, in particular, for developing countries like India. In addition, educational strategies targeting FVC health literacy are also used. Little evidence has documented a connection between these two strategies. We examine the single and combined influence of HGC and health literacy with regard to benefits from fruits and vegetable consumption. Data were collected from 427 rural households in the state of Odisha, India. Three outcomes were examined: FVC, as well as fruit and vegetables separately. Linear and Poisson regression were used to examine the association among home-grown consumption (HGC), FVC health literacy, and the FVC outcomes. Findings show that HGC, but not FVC health literacy, was directly associated with FVC (β = 0.65, SE = 0.10, p = 0.008) and vegetable consumption (β = 0.57, SE = 0.11, p = 0.02). However, both HGC (β = 0.58, SE = 0.05, p < 0.01) and FVC health literacy (β = −0.07, SE = 0.02, p = 0.001) were associated with fruit consumption. In addition, HGC effect is concentrated among participants who reported low FVC health literacy, especially on overall FVC and vegetables alone. Results are discussed in relation to the beneficial role played by HGC in those particularly vulnerable households who perceived little FVC health literacy. Our results provide insights on novel improved FVC consumption across all population segments. Future research should explore the complex interplay between agricultural policies and educational programs in the design of interventions promoting fruit and vegetable production and consumption.
Gaussian Process Autoregression for Joint Angle Prediction Based on sEMG Signals
Authors: Liang Jie , Shi Zhengyi , Zhu Feifei , Chen Wenxin , Chen Xin , Li Yurong
Published: May 2021

There is uncertainty in the neuromusculoskeletal system, and deterministic models cannot describe this significant presence of uncertainty, affecting the accuracy of model predictions. In this paper, a knee joint angle prediction model based on surface electromyography (sEMG) signals is proposed. To address the instability of EMG signals and the uncertainty of the neuromusculoskeletal system, a non-parametric probabilistic model is developed using a Gaussian process model combined with the physiological properties of muscle activation. Since the neuromusculoskeletal system is a dynamic system, the Gaussian process model is further combined with a non-linear autoregressive with eXogenous inputs (NARX) model to create a Gaussian process autoregression model. In this paper, the normalized root mean square error (NRMSE) and the correlation coefficient (CC) are compared between the joint angle prediction results of the Gaussian process autoregressive model prediction and the actual joint angle under three test scenarios: speed-dependent, multi-speed and speed-independent. The mean of NRMSE and the mean of CC for all test scenarios in the healthy subjects dataset and the hemiplegic patients dataset outperform the results of the Gaussian process model, with significant differences (p < 0.05 and p < 0.05, p < 0.05 and p < 0.05). From the perspective of uncertainty, a non-parametric probabilistic model for joint angle prediction is established by using Gaussian process autoregressive model to achieve accurate prediction of human movement.
Calibration of the DSCOVR EPIC Visible and NIR Channels using Multiple LEO Radiometers
Authors: Geogdzhayev Igor V. , Marshak Alexander , Alexandrov Mikhail
Published: May 2021

The first five years of operation of the Deep Space Climate Observatory (DSCOVR) Earth Polychromatic Imaging Camera (EPIC) at the Lagrange one point have produced results that uniquely complement the data from currently operating low orbit Earth-observing instruments. In this paper we describe an updated unified approach to EPIC calibration. In this approach, calibration coefficients and their trends were obtained by comparing EPIC observations to the measurements from polar orbiting radiometers. In this study L1B reflectances from Moderate Resolution Imaging Spectroradiometer (MODIS) onboard the Aqua and Terra satellites, Multi-angle Imaging Spectroradiometer (MISR) onboard Terra and Visible Infrared Imaging Radiometer (VIIRS) onboard the Suomi National Polar-orbiting Partnership (Suomi NPP) spacecraft were used to infer calibration coefficients for four EPIC visible and near-infrared channels: 443 nm, 551 nm, 680 nm, and 780 nm. EPIC Version three measurements made between June 2015 and August 2020 were used for comparison. The calibration procedure identifies the most homogeneous low Earth orbit radiometer scenes matching scattering angles that are temporarily and spatially collocated with EPIC observations. These scenes are used to determine reflectance to count (R/C) ratios in spectrally analogous channels. Seasonal average R/C ratios were analyzed to obtain EPIC calibration gains and trends. The trends for the full dataset period are not statistically significant except in the 443 nm channel. No significant changes in calibration were found after the instrument’s exit from safe hold in March 2020. The R/C ratios were also used to determine the differences in EPIC gains resulting from separate calibrations: against MODIS Aqua or Terra, as well as against forward or aftward MISR cameras. Statistical tests indicate that the differences between the two datasets are not significant except in the 780 nm channels where Aqua-derived coefficients may be around 2% lower compared to Terra. The dependence of EPIC calibration gains on the instrument scattering angle and on DSCOVR-Earth distance were investigated. Lastly, model Low Earth Orbit (LEO) reflectances calculated to match the EPIC viewing geometry were employed to study how EPIC calibration coefficients depend on EPIC-LEO viewing geometry differences. The effect of LEO and EPIC angular mismatch on calibration was shown to be small.