bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Neurovascular Signals in the Degraded Condylar Cartilage
Authors: Qin Wenpin , Zhang Zibin , Yan Jianfei , Han Xiaoxiao , Niu Li-Na , Jiao Kai 
Published: April 2022

Introduction: Degradation of the condylar cartilage during temporomandibular joint osteoarthritis (TMJ-OA) results in the infiltration of nerves, blood vessels and inflammatory cells from the subchondral bone into the cartilage. The interaction among innervation, angiogenesis and inflammation in the condylar cartilage of TMJ-OA remains largely unknown.Method: In the present study, microarray-based transcriptome analysis was used to detect, and quantitative real-time polymerase chain reaction was used to validate transcriptome changes in the condylar cartilage from a well-established rat TMJ-OA model. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein-protein interaction (PPI) analyses were conducted.Result: There were 1817 differentially expressed genes (DEGs, fold change ≥2, p &lt; 0.05) between TMJ-OA and control cartilages, with 553 up-regulated and 1,264 down-regulated genes. Among those genes, representative DEGs with known/suspected roles in innervation, angiogenesis and inflammation were further validated by enriched GO terms and KEGG pathways. The DEGs related to innervation were predominately enriched in the GO terms of neurogenesis, generation of neurons, and KEGG pathways of cholinergic synapse and neurotrophin signaling. Genes related to angiogenesis were enriched in GO terms of vasculature and blood vessel development, and KEGG pathways of hypoxia-inducible factor 1 (HIF-1) pathway and calcium signaling pathway. For inflammation, the DEGs were enriched in the GO terms of immune system process and immune response, and KEGG pathways of Toll-like receptor and transforming growth factor β (TGFβ) signaling. Analysis with PPI indicated that the aforementioned DEGs were highly-interacted. Several hub genes such as v-akt murine thymoma viral oncogene homolog 1 (Akt1), glycogen synthase kinase 3β (Gsk3b), fibroblast growth factor 2 (Fgf2) and nerve growth factor receptor (Ngfr) were validated.Conclusion: The present study demonstrated, for the first time, that intimate interactions exist among innervation, angiogenesis and inflammation in the condylar cartilage of TMJ-OA.
A Multicomponent Polymer-Metal-Enzyme System as Electrochemical Biosensor for H2O2 Detection
Authors: Tong Pengfei , Asif Muhammad , Ajmal Muhammad , Aziz Ayesha , Sun Yimin 
Published: April 2022

Herein, an Au nanoparticles-polydopamine-poly acrylic acid-graphene (Au NPs-PDA-PAA-graphene) multicomponent nanohybrid is fabricated by surface functionalization of graphene alongside extensive in-situ growth of Au nanoparticles. The as-obtained nanocomposite possesses good hydrophilicity, excellent biocompatibility and high biomolecules loading capacity, which acts as an ideal platform for enzyme modification. Considering this fact, Horseradish peroxidase is expressively immobilized upon Au NPs-PDA-PAA-graphene surface, in order to lay the foundations of a biosensor that is majorly based on enzymatic activity. The biosensor exhibits higher sensitivity towards the determination of H2O2 with linearity ranging from 0.1 μm upto 20 mm, and the limit of detection going down to 0.02 μm. Encouraged by its acceptable electrocatalytic performance, this multicomponent system can also be easily employed for carrying out the real-time tracking of H2O2 coming out of Macrophage cells. Therefore, this work designs an extraordinarily updated platform for biosensing related applications, and also presents a reliable platform for the direct detection of H2O2in vivo and in vitro, which show great potential in bioelectroanalytical chemistry, cellular biology, and pathophysiology.
Bimetallic Cobalt–Copper Nanoparticle-Decorated Hollow Carbon Nanofibers for Efficient CO2 Electroreduction
Authors: He Congyi , Wang Siyu , Jiang Xingxing , Hu Qi , Yang Hengpan , He Chuanxin 
Published: April 2022

Bimetallic materials are one of the most promising catalysts for the electrochemical reduction of CO2, but there are still many challenges to be overcome on the route to industrialization. Herein, a series of carbon nanofiber-supported bimetallic cobalt–copper catalysts (CoxCuy/CFs) are designed and constructed through the electrospinning technique and a subsequent pyrolysis procedure. Small-sized Co–Cu nanoparticles are homogenously distributed on the porous carbon nanofibers, which can significantly improve the utilization rate of metal sites and greatly reduce the loading amount of metals. Moreover, different product distributions and catalytic performance can be obtained in CO2 reduction via adjusting the metal proportion of CoxCuy/CFs. Especially, Co3Cu/CFs can bring forth a 97% total faradaic efficiency (FE) of CO (68%) and HCOOH (29%) at –0.8 VRHE cathode potential in 0.5 M KHCO3 electrolyte. Furthermore, the hierarchical pores can firmly confine the small Co–Cu nanoparticles and keep them from easy agglomeration during electrolysis, eventually leading to 60 h of stability for Co3Cu/CFs in CO2 electroreduction. This study might provide a facile and economic method to fabricate efficient bimetallic catalysts for CO2 electroreduction and other electrocatalysis applications.
Evaluation of Stroke Risk in Patients With Atrial Fibrillation Using Morphological and Hemodynamic Characteristics
Authors: Wang Lingfeng , Wang Zidun , Fang Runxin , Li Zhi-Yong 
Published: April 2022

BackgroundIt is well known that the thrombus triggering stroke in patients with atrial fibrillation (AF) mainly comes from the left atrial appendage (LAA). This study aims to characterize the morphological and hemodynamic parameters and evaluate their differences between AF patients with and without a stroke history.MethodsCardiac CT images were obtained from AF patients with (n = 10) and without a history of stroke (n = 10). 3D models of the left atrium (LA) were reconstructed by processing the CT image, and the LA/LAA morphological parameters were measured. Computational fluid dynamics (CFD) simulations were performed to calculate the hemodynamic parameters in LA. The species-transport model and discrete phase model (DPM) were applied to analyze blood residual ratio and particle residual ratio, two qualitative parameters for thrombus formation and flow-out potential, respectively.ResultsThere were significant differences in LAA actual depth (p = 0.002), and direct length (p = 0.049) between the non-stroke and stroke groups. Significant differences were also found in certain hemodynamic parameters. The blood residual ratio in LAA was significantly smaller in the stroke group than in the non-stroke group (p &lt; 0.05). Moreover, the particle residual ratio within LAA was significantly smaller in the stroke groups than in the non-stroke group (p &lt; 0.05).ConclusionThere are significant differences in both morphological and hemodynamic parameters between AF patients with and without a stroke history. A high blood residual ratio in LAA confirms that thrombus is more likely to form in AF patients. A significantly smaller particle residual ratio in the stroke group may suggest the thrombus formed with LAA is more likely to flow out of LAA, leading to a higher risk of stroke. The proposed morphological and hemodynamic parameters may be additional risk factors that can be used to better risk stratify AF patients.
Association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Use With Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus Patients With Stabilized Acute Myocardial Infarction: A Propensity Score Matching Study
Authors: Chang Ting-Yung , Lu Chi-Ting , Huang Hsin-Lei , Chou Ruey-Hsing , Chang Chun-Chin , Liu Chung-Te , Huang Po-Hsun , Lin Shing-Jong 
Published: April 2022

BackgroundCoronary artery disease (CAD) is one of the leading causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), who are at a greater risk of acute myocardial infarction (AMI) and sudden cardiac death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular events and mortality in T2DM patients with a risk of cardiovascular disease. This study aimed to investigate the effect of SGLT2 inhibitor use on the adverse cardiovascular and renal outcomes in T2DM patients with AMI.MethodsA total of 1,268 patients admitted to the Coronary Care Unit due to AMI were retrospectively screened.Patients taking SGLT2 inhibitors before or during the index AMI hospitalization were assigned as group 1. Patients who never received SGLT2 inhibitors were assigned as group 2. Patients in groups 1 and 2 were matched in a 1:2 ratio, and 198 T2DM patients with stabilized AMI were retrospectively enrolled for the final analysis.ResultsWith a mean follow-up period of 23.5 ± 15.7 months, 3 (4.5%) patients in group 1 and 22 (16.7%) patients in group 2 experienced rehospitalization for acute coronary syndrome (ACS), while 1 (1.5%) patient in group 1 and 7 (5.3%) patients in group 2 suffered sudden cardiac death. The Kaplan–Meier curves demonstrated that the patients in group 1 had a lower risk of adverse cardiovascular outcomes. According to the multivariate analysis, the baseline estimated glomerular filtration rate (eGFR) (P = 0.008, 95% CI: 0.944–0.991) and the use of SGLT2 inhibitors (P = 0.039, 95% CI: 0.116–0.947) were both independent predictors of adverse cardiovascular outcomes. On the other hand, the use of SGLT2 inhibitors was not associated with adverse renal outcomes.ConclusionIn T2DM patients with stabilized AMI, the use of SGLT2 inhibitors was associated with a lower risk of adverse cardiovascular outcomes. In addition, the baseline renal function was also an independent predictor of adverse cardiovascular outcomes.
Low-Temperature Thermal Conductivity of the Two-Phase Superconductor CeRh2As2
Authors: Onishi Seita , Stockert Ulrike , Khim Seunghyun , Banda Jacintha , Brando Manuel , Hassinger Elena 
Published: April 2022

CeRh2As2is a rare unconventional superconductor (Tc= 0.26 K) characterized by two adjacent superconducting phases for a magnetic fieldH‖c-axis of the tetragonal crystal structure. Antiferromagnetic order, quadrupole-density-wave order (T0= 0.4 K) and the proximity of this material to a quantum-critical point have also been reported: The coexistence of these phenomena with superconductivity is currently under discussion. Here, we present thermal conductivity and electrical resistivity measurements on a single crystal of CeRh2As2between 60 mK and 200 K and in magnetic fields (H‖c) up to 8 T. Extrapolation of our normal-state data to zero temperature validates the Wiedemann-Franz law within the error bars. TheTdependence of the thermal conductivityκ(T) shows a pronounced drop belowTcwhich is also field dependent and thus interpreted as the signature of superconductivity. However, the large residual resistivity and the lack of sharp anomalies inκ(T) at the expected transition temperatures clearly indicate that samples of much higher purity are required to gain more information about the superconducting gap structure.
Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
Authors: Wang Nan , Wei Linfeng , Liu Die , Zhang Quyan , Xia Xiaobo , Ding Lexi , Xiong Siqi 
Published: April 2022

BackgroundDiabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in diabetic patients. The etiology of DR is complex, accumulated studies have shown that autophagy plays an important role in the pathogenesis of DR, but its specific mechanism needs to be further studied.MethodsThis study chose the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE146615 to carry on the research. Autophagy-related genes that were potentially differentially expressed in DR were screened by R software. Then, the differentially expressed autophagy-related genes were analyzed by correlation analysis, tissue-specific gene expression, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) network analysis. Finally, retinal pigment epithelial cell line (ARPE-19) incubated with high glucose (HG) was used to mimic the DR model, and the mRNA level of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in vitro.ResultsA total of 23 differentially expressed autophagy-related genes (9 up-regulated genes and 14 down-regulated genes) were identified by differential expression analysis. The analysis of tissue-specific gene expression showed that these differentially expressed autophagy-related genes were enriched in the retina. GO and KEGG enrichment analysis showed that differentially expressed autophagy-related genes were significantly enriched in autophagy-related pathways such as regulation of autophagy and macroautophagy. Then 10 hub genes were identified by PPI network analysis and construction of key modules. Finally, qRT-PCR confirmed that the expression of MAPK3 in the DR model was consistent with the results of bioinformatics analysis of mRNA chip.ConclusionThrough bioinformatics analysis, we identified 23 potential DR autophagy-related genes, among which the down-regulated expression of MAPK3 may affect the occurrence and development of DR by regulating autophagy. It provides a novel insight into the pathogenesis of DR.
Prenatal Exposure to a Climate-Related Disaster Results in Changes of the Placental Transcriptome and Infant Temperament
Authors: Buthmann Jessica , Huang Dennis , Casaccia Patrizia , O’Neill Sarah , Nomura Yoko , Liu Jia 
Published: April 2022

Maternal stress during pregnancy exerts long-term effects on the mental well-being of the offspring. However, the long-term effect of prenatal exposure on the offspring’s mental status is only partially understood. The placenta plays a vital role in connecting the maternal side to the fetus, thereby serving as an important interface between maternal exposure and fetal development. Here, we profiled the placental transcriptome of women who were pregnant during a hurricane (Superstorm Sandy), which struck New York City in 2012. The offspring were followed longitudinally and their temperament was assessed during the first 6–12 months of age. The data identified a significant correlation between a Superstorm Sandy stress factor score and infant temperament. Further, analysis of the placental transcriptomes identified an enrichment of functional pathways related to inflammation, extracellular matrix integrity and sensory perception in the specimen from those infants with “Slow-to-Warm-up” temperament during the first year of life. Together, these findings provide initial evidence that maternal exposure to climate-related disasters results in altered placental transcriptome, which may be related to long-term emotional and behavioral consequences in children.
A Machine Learning Model Based on PET/CT Radiomics and Clinical Characteristics Predicts Tumor Immune Profiles in Non-Small Cell Lung Cancer: A Retrospective Multicohort Study
Authors: Tong Haipeng , Sun Jinju , Fang Jingqin , Zhang Mi , Liu Huan , Xia Renxiang , Zhou Weicheng , Liu Kaijun , Chen Xiao 
Published: April 2022

BackgroundThe tumor immune microenvironment (TIME) phenotypes have been reported to mainly impact the efficacy of immunotherapy. Given the increasing use of immunotherapy in cancers, knowing an individual’s TIME phenotypes could be helpful in screening patients who are more likely to respond to immunotherapy. Our study intended to establish, validate, and apply a machine learning model to predict TIME profiles in non-small cell lung cancer (NSCLC) by using 18F-FDG PET/CT radiomics and clinical characteristics.MethodsThe RNA-seq data of 1145 NSCLC patients from The Cancer Genome Atlas (TCGA) cohort were analyzed. Then, 221 NSCLC patients from Daping Hospital (DPH) cohort received18F-FDG PET/CT scans before treatment and CD8 expression of the tumor samples were tested. The Artificial Intelligence Kit software was used to extract radiomic features of PET/CT images and develop a radiomics signature. The models were established by radiomics, clinical features, and radiomics-clinical combination, respectively, the performance of which was calculated by receiver operating curves (ROCs) and compared by DeLong test. Moreover, based on radiomics score (Rad-score) and clinical features, a nomogram was established. Finally, we applied the combined model to evaluate TIME phenotypes of NSCLC patients in The Cancer Imaging Archive (TCIA) cohort (n = 39).ResultsTCGA data showed CD8 expression could represent the TIME profiles in NSCLC. In DPH cohort, PET/CT radiomics model outperformed CT model (AUC: 0.907 vs. 0.861, P = 0.0314) to predict CD8 expression. Further, PET/CT radiomics-clinical combined model (AUC = 0.932) outperformed PET/CT radiomics model (AUC = 0.907, P = 0.0326) or clinical model (AUC = 0.868, P = 0.0036) to predict CD8 expression. In the TCIA cohort, the predicted CD8-high group had significantly higher immune scores and more activated immune pathways than the predicted CD8-low group (P = 0.0421).ConclusionOur study indicates that 18F-FDG PET/CT radiomics-clinical combined model could be a clinically practical method to non-invasively detect the tumor immune status in NSCLCs.
pcMSC Modulates Immune Dysregulation in Patients With COVID-19-Induced Refractory Acute Lung Injury
Authors: Chen Mei-Chuan , Lai Kevin Shu-Leung , Chien Ko-Ling , Teng Sing Teck , Lin Yuh-Rong , Chao Wei , Lee Meng-Jung , Wei Po-Li , Huang Yen-Hua , Kuo Han-Pin , Weng Chih-Ming , Chou Chun-Liang 
Published: April 2022

Background and ObjectivesThe novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been well reported, particularly, in patients associated with moderate to severe acute respiratory distress syndrome (ARDS).MethodsOn Days 0 and 4, an intravenous infusion of 2 × 107 placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) were administered to five severe COVID-19 patients refractory to current standard therapies. Peripheral blood inflammatory markers and immune profiles were determined by multi-parameter flow cytometry and studied at Days 0, 4, and 8. Clinical outcomes were also observed.ResultsNone of the pc-MSC treated patients experienced 28-day mortality compared with the control group and showed a significant improvement in the PaO2/FiO2 ratio, Murray’s lung injury scores, reduction in serum ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. The cytokine profiles also showed a reduction in IL-1β, IFN-γ, IL-2, and IL-6, and an increase in IL-13 and IL-5 type 2 cytokines within 7 days of therapy. Lymphopenia was also significantly improved after 7 days of treatment. Immune cell profiles showed an increase in the proportions of CD4+ T cells (namely, CD4+ naïve T cells and CD4+ memory T cell subtypes), Treg cells, CD19+ B cells (namely, CD19+ naïve B cells, CD27+ switched B cell subtypes) and dendritic cells, and a significant decrease in the proportion of CD14+ monocytes (namely, CD16- classical and CD16+ non-classical subtypes), and plasma/plasmablast cells. No adverse effects were seen at the serial follow-up visits for 2 months after initial therapy.Conclusionpc-MSCs therapy suppressed hyper-inflammatory states of the innate immune response to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoting CD4+ T cells and CD19+ B cells toward adaptive immune responses in severely critically ill COVID-19 patients with moderate to severe ARDS, especially those who were refractory to current standard care and immunosuppressive therapies.
Tumor Microenvironment Characterization for Assessment of Recurrence and Survival Outcome in Gastric Cancer to Predict Chemotherapy and Immunotherapy Response
Authors: Chen Yan , Sun Zepang , Wan Li , Chen Hongzhuan , Xi Tieju , Jiang Yuming 
Published: April 2022

BackgroundThe tumor microenvironment (TME) is crucial for tumor recurrence, prognosis, and therapeutic responses. We comprehensively investigated the TME characterization associated with relapse and survival outcomes of gastric cancer (GC) to predict chemotherapy and immunotherapy response.MethodsA total of 2,456 GC patients with complete gene-expression data and clinical annotations from twelve cohorts were included. The TME characteristics were evaluated using three proposed computational algorithms. We then developed a TME-classifier, a TME-cluster, and a TME-based risk score for the assessment of tumor recurrence and prognosis in patients with GC to predict chemotherapy and immunotherapy response.ResultsPatients with tumor recurrence presented with inactive immunogenicity, namely, high infiltration of tumor-associated stromal cells, low infiltration of tumor-associated immunoactivated lymphocytes, high stromal score, and low immune score. The TME-classifier of 4 subtypes with distinct clinicopathology, genomic, and molecular characteristics was significantly associated with tumor recurrence (P = 0.002), disease-free survival (DFS, P &lt;0.001), and overall survival (OS, P &lt;0.001) adjusted by confounding variables in 1,193 stage I–III GC patients who underwent potential radical surgery. The TME cluster and TME-based risk score can also predict DFS (P &lt;0.001) and OS (P &lt;0.001). More importantly, we found that patients in the TMEclassifier-A, TMEclassifier-C, and TMEclassifier-D groups benefited from adjuvant chemotherapy, and patients in the TMEclassifier-B group without chemotherapy benefit responded best to pembrolizumab treatment (PD-1 inhibitor), followed by patients in the TMEclassifier-A, while patients in the C and D groups of the TMEclassifier responded poorly to immunotherapy.ConclusionWe determined that TME characterization is significantly associated with tumor recurrence and prognosis. The TME-classifier we proposed can guide individualized chemotherapy and immunotherapy decision-making.