bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAP Polypeptide Promotes Osteogenesis in Jaw Bone Defect Repair by Inhibiting Inflammatory Reactions
Authors: Guo Ke , Zhao Haoming , Chen Guokun , Zhang Ying , Wang Yu , Huo Liang , Sun Shoufu , Wei Wenjia 
Published: June 2022

Jaw defects are common in oral and maxillofacial diseases and require surgical repair in extreme cases. Given the limitations in availability and efficacy of autologous bone grafts or allografts, great effort has been made in finding suitable, biocompatible, and effective artificial bone materials. Considering the key role of inflammation in bone resorption, we sought to identify a polypeptide with anti-inflammatory and bone-promoting effects. Rat bone marrow-derived mesenchymal cells (BMSCs) were treated with lipopolysaccharide (LPS) to induce an inflammatory environment, and 1,538 differentially abundant polypeptides were identified using mass spectrometry. Based on mass spectrometry signal intensity, multiple of difference, and structural stability, PAP was screened out as the polypeptide with the lowest abundance in the inflammatory condition. PAP showed no cytotoxicity to BMSCs with increasing concentrations. PAP (10 μM) also increased alkaline phosphatase activity and mRNA expression of Ocn, Bmp2, and Runx2 in a concentration-dependent manner, which confirmed that it can promote osteogenic induction of rat BMSCs. Moreover, PAP reduced LPS-induced expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and reactive oxygen species and inhibited polarization of RAW 264.7 macrophages to the inflammatory type. Finally, a skull defect mouse model was established, and mice were injected with LPS and/or PAP. Micro-CT, histological analysis, and immunohistochemical staining showed that PAP significantly reduced the number of LPS-induced bone resorption pits and maintained bone integrity. Overall, the polypeptide PAP screened using LPS stimulation of BMSCs is not cytotoxic and can inhibit the inflammatory reaction process to promote osteogenesis. This study thus provides a basis for development of PAP as a new osteogenic material in the repair of jaw defects.
Bioprosthetic Valve Fracturing: In vitro Testing of Edwards PERIMOUNT Model P 2900
Authors: Ruge Hendrik , Alvarez-Covarrubias Hector A. , Deutsch Oliver , Alalawi Zahra , Vitanova Keti , Lange Rüdiger 
Published: June 2022

BackgroundBioprosthetic valve fracturing (BVF) results in low gradients following valve-in-valve transcatheter aortic valve replacement (ViV-TAVR). For the commonly used Edwards PERIMOUNT valve data from bench-testing are lacking to provide technical specifications for successful BVF during ViV-TAVR.MethodsUsing four Perimount 19- and 21-mm valves, in-vitro high-pressure balloon valvuloplasty with the True Dilatation Balloon Valvuloplasty Catheter and Atlas Gold PTA Dilatation Catheter was performed to analyze balloon-oversizing and pressure-thresholds to successfully achieve BVF.ResultsHigh-pressure balloons one millimeter larger than the labeled valve size and pressure rates of 20 atm (for Perimount 19-mm) and &gt; 22 atm (for Perimount 21-mm) were required to achieve BVF. Caliper measurements demonstrated 2.5 mm (Perimount 19-mm) and 1.5 mm (Perimount 21-mm) enlarged inner prosthetic diameters after BVF. The Atlas TM Gold PTA Dilatation Catheter achieved BVF with the Perimount 21-mm, whereas the True TM Dilatation Balloon Valvuloplasty Catheter failed in the Perimount 21-mm either for balloon-rupture or pinhole-defect.ConclusionBoth 19-mm and 21-mm Perimount P 2900 are amendable to BVF, thereby increasing the inner prosthetic diameter. High-pressure balloons 1 mm larger than the labeled valves are essential for this purpose, and the Atlas Gold PTA Dilatation Catheter alone should ensure success in the 21-mm prosthetics.
Combining Z-Score and Maternal Copy Number Variation Analysis Increases the Positive Rate and Accuracy in Non-Invasive Prenatal Testing
Authors: Chen Liheng , Wang Lihong , Hu Zhipeng , Tao Yilun , Song Wenxia , An Yu , Li Xiaoze 
Published: June 2022

Objective: To evaluate positive rate and accuracy of non-invasive prenatal testing (NIPT) combining Z-score and maternal copy number variation (CNV) analysis. To assess the relationship between Z-score and positive predictive value (PPV).Methods: This prospective study included 61525 pregnancies to determine the correlation between Z-scores and PPV in NIPT, and 3184 pregnancies to perform maternal CNVs analysis. Positive results of NIPT were verified by prenatal diagnosis and/or following-up after birth. Z-score grouping, logistic regression analysis, receiver operating characteristic (ROC) curves, and S-curve trends were applied to correlation analysis of Z-scores and PPV. The maternal CNVs were classified according to the technical standard for the interpretation of ACMG. Through genetic counseling, fetal and maternal phenotypes and family histories were collected.Results: Of the 3184 pregnant women, 22 pregnancies were positive for outlier Z-scores, suggesting fetal aneuploidy. 12 out of 22 pregnancies were true positive (PPV = 54.5%). 17 pregnancies were found maternal pathogenic or likely pathogenic CNVs (&gt; 0.5 Mb) through maternal CNV analysis. Prenatal diagnosis revealed that 7 out of 11 fetuses carried the same CNVs as the mother. Considering the abnormal biochemical indicators during pregnancy and CNV-related clinical phenotypes after birth, two male fetuses without prenatal diagnosis were suspected to carry the maternally-derived CNVs. Further, we identified three CNV-related family histories with variable phenotypes. Statistical analysis of the 61525 pregnancies revealed that Z-scores of chromosomes 21 and 18 were significantly associated with PPV at 3 ≤ Z ≤ 40. Notably, three pregnancies with Z &gt; 40 were both maternal full aneuploidy. At Z &lt; -3, fetuses carried microdeletions instead of monosomies. Sex chromosome trisomy was significantly higher PPV than monosomy.Conclusion: The positive rate of the NIPT screening model combining Z-score and maternal CNV analysis increased from 6.91‰ (22/3184) to 12.25‰ (39/3184) and true positives increased from 12 to 21 pregnancies. We found that this method could improve the positive rate and accuracy of NIPT for aneuploidies and CNVs without increasing testing costs. It provides an early warning for the inheritance of pathogenic CNVs to the next generation.
Identification of Differentially Expressed Genes and miRNAs for Ulcerative Colitis Using Bioinformatics Analysis
Authors: Hu Weitao , Fang Taiyong , Chen Xiaoqing 
Published: June 2022

Introduction:Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine whose cause and underlying mechanisms are not fully understood. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in UC.Materials and methods:Three UC datasets (GSE179285, GSE75214, GSE48958) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and UC tissues were identified using the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using Metascape. Protein-protein interaction network (PPI) analysis and visualization using STRING and Cytoscape. Finally, the miRNA gene regulatory network was constructed by Cytoscape to predict potential microRNAs (miRNAs) associated with DEGs.Results:A total of 446 DEGs were identified, consisting of 309 upregulated genes and 137 downregulated genes. The enriched functions and pathways of the DEGs include extracellular matrix, regulation of cell adhesion, inflammatory response, response to cytokine, monocarboxylic acid metabolic process, response to toxic substance. The analysis of KEGG pathway indicates that the DEGs were significantly enriched in Complement and coagulation cascades, Amoebiasis, TNF signaling pathway, bile secretion, and Mineral absorption. Combining the results of the PPI network and CytoHubba, 9 hub genes including CXCL8, ICAM1, CXCR4, CD44, IL1B, MMP9, SPP1, TIMP1, and HIF1A were selected. Based on the DEG-miRNAs network construction, 7 miRNAs including miR-335-5p, mir-204-5p, miR-93-5p, miR106a-5p, miR-21-5p, miR-146a-5p, and miR-155-5p were identified as potential critical miRNAs.Conclusion:In summary, we identified DEGs that may be involved in the progression or occurrence of UC. A total of 446 DEGs,9 hub genes and 7 miRNAs were identified, which may be considered as biomarkers of UC. Further studies, however, are needed to elucidate the biological functions of these genes in UC.
Mechanism of COVID-19-Related Proteins in Spinal Tuberculosis: Immune Dysregulation
Authors: Chen Liyi , Liu Chong , Liang Tuo , Ye Zhen , Huang Shengsheng , Chen Jiarui , Sun Xuhua , Yi Ming , Zhou Chenxing , Jiang Jie , Chen Tianyou , Li Hao , Chen Wuhua , Guo Hao , Chen Wenkang , Yao Yuanlin , Liao Shian , Yu Chaojie , Wu Shaofeng , Fan Binguang , Gan Zhaoping , Zhan Xinli 
Published: June 2022

PurposeThe purpose of this article was to investigate the mechanism of immune dysregulation of COVID-19-related proteins in spinal tuberculosis (STB).MethodsClinical data were collected to construct a nomogram model. C-index, calibration curve, ROC curve, and DCA curve were used to assess the predictive ability and accuracy of the model. Additionally, 10 intervertebral disc samples were collected for protein identification. Bioinformatics was used to analyze differentially expressed proteins (DEPs), including immune cells analysis, Gene Ontology (GO) and KEGG pathway enrichment analysis, and protein-protein interaction networks (PPI).ResultsThe nomogram predicted risk of STB ranging from 0.01 to 0.994. The C-index and AUC in the training set were 0.872 and 0.862, respectively. The results in the external validation set were consistent with the training set. Immune cells scores indicated that B cells naive in STB tissues were significantly lower than non-TB spinal tissues. Hub proteins were calculated by Degree, Closeness, and MCC methods. The main KEGG pathway included Coronavirus disease-COVID-19. There were 9 key proteins in the intersection of COVID-19-related proteins and hub proteins. There was a negative correlation between B cells naive and RPL19. COVID-19-related proteins were associated with immune genes.ConclusionLymphocytes were predictive factors for the diagnosis of STB. Immune cells showed low expression in STB. Nine COVID-19-related proteins were involved in STB mechanisms. These nine key proteins may suppress the immune mechanism of STB by regulating the expression of immune genes.
Identification and Isolation of Type II NKT Cell Subsets in Human Blood and Liver
Authors: Yang Zhou Jordi , Werner Jens M. , Glehr Gunther , Geissler Edward K. , Hutchinson James A. , Kronenberg Katharina 
Published: June 2022

BackgroundSteatotic livers are more prone to rejection, but are often transplanted owing to the shortage of available organs. Type II NKT (T2NKT) cells are liver-resident lymphocytes that react to lipids presented by CD1d. The role of T2NKT cells in rejection of fatty liver transplants is unclear, partly because of a lack of T2NKT cell markers and their very low frequency in blood. Here, we quantify human T2NKT cells in blood and liver tissue by flow cytometry and provide a strategy for their enrichment and expansion.MethodsHuman T2NKT cells were identified as CD3+ CD56+ CD161+ TCR-γᵹ- TCRVα7.2- and TCRVα24- cells. T2NKT cells were enriched from blood by sequential positive selection using CD56 and CD3 microbeads. These were subsequently FACS-sorted to purity then expanded in vitro for 3 weeks using anti-CD3/CD28 beads and TGF-β1.ResultsThe frequency of human T2NKT cells in blood was very low (0.8 ± 0.4% of CD3+ T cells) but they were a more abundant population in liver (6.3 ± 0.9%). Enriched T2NKT cells expressed the transcription factor PLZF. A novel subset of FoxP3+ T2NKT cells was discovered in blood and liver tissue. T2NKT cells were expanded in culture by 15- to 28-fold over 3 weeks, during which time they maintained expression of all identifying markers, including PLZF and FoxP3.ConclusionsOur work defines new strategies for identifying and isolating T2NKT cells from human blood and liver tissue. We showed that this rare population can be expanded in vitro in order to obtain experimentally amenable cell numbers. Further, we identified a novel T2NKT cell subset that stably expresses FoxP3, which might play a role in regulating innate-like lymphocyte responses in steatotic liver transplants.
Growth Performance, Immune Response, Antioxidative Status, and Antiparasitic and Antibacterial Capacity of the Nile Tilapia (Oreochromis niloticus) After Dietary Supplementation With Bottle Gourd (Lagenaria siceraria, Molina) Seed Powder
Authors: Radwan Mahmoud , Abbas Mahmoud Mahrous M. , Mohammadein Amaal , Al Malki Jamila S. , Elraey Said M. A. , Magdy Mohammad 
Published: June 2022

Medicinal plants are a potential safe source of bioactive compounds. Fish diet supplemented with the medicinal plant bottle gourd (Lagenaria siceraria) seed powder was evaluated in this study for the potential effect on growth performance, antioxidative status, immunological response, and resistance to infectious pathogens in the Nile tilapia (Oreochromis niloticus). Nile tilapia fingerlings with mean weight ( ± SD)= (25.64 ± 0.17 g), were fed four L. siceraria seed supplemented diets (LSSD) at 0.0, 1, 2, and 3% for 60 days. Specimens were then challenged with the bacterium Aeromonas hydrophila for 10 days. Also, three different concentrations (2.5, 5, and 10 ml/L) of Lagenaria siceraria ethanolic extract (LSEE) were tested for their antibacterial and antiparasitic efficacy on four selected bacterial and one parasitic species. All parameters’ values generally improved with elevating the content of the L. siceraria seed powder in the diet. Dietary administration of LSSD-3% enabled significant (P &lt; 0.05) higher growth performance, and feed utilization efficiency. It reduced the mortality induced by A. hydrophila infection, increased crude protein content in the fish body and exhibited the highest in vitro antibacterial and antiparasitic efficiency. RBCs, WBCs, Hb, PCV, MCV, MCH, and total serum protein values in pre- and post-challenge groups were significantly higher (P &lt; 0.05) in the LSSD-3% group. While MCHC, ALT, AST and glucose levels were significantly lower (P &lt; 0.05) than those of the other groups. Lysozyme and antioxidant enzyme activities in pre- and post-challenge groups were also higher (P &lt; 0.05) in the LSSD-3% group compared to the other groups. LSEE provided good efficacy against Gram-negative bacterial strains, mild efficacy against Gram-positive bacterial strains, and an antagonistic effect on the parasite Cichlidogyrus Tilapiae. The 10 ml/L concentration was the most effective against the pathogens followed by the 5 ml/L concentration and then 2.5 ml/L. Our findings suggest the feasibility of supplementation of Nile tilapia (O. niloticus) diet with L. siceraria seed powder by 3% to improve the growth performance, immunity, and vital parameters.
A Prospective Study to Evaluate the Impact of Golimumab Therapy on Work Productivity and Activity, and Quality of Life in Patients With Rheumatoid Arthritis, Psoriasis Arthritis and Axial Spondyloarthritis in a Real Life Setting in AUSTRIA. The GO-ACTIVE Study
Authors: Dejaco Christian , Mueller Thomas , Zamani Omid , Kurtz Ulrike , Egger Stefan , Resch-Passini Johannes , Totzauer Anna , Yazdani-Biuki Babak , Schwingenschloegl Thomas , Peichl Peter , Kraus Angelika , Naerr Gerhard W. 
Published: June 2022

ObjectiveTo analyze real-world evidence on work productivity and daily activity impairment (WPAI) and health-related quality of life (HRQoL) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients treated with golimumab in Austria.MethodsThis was a prospective, non-interventional, multi-center study conducted in RA, PsA and axSpA patients initiating golimumab between April 2016 and May 2020 in 40 centers in Austria. WPAI, HRQoL (RAQoL, ankylosing spondylitis (AS)QoL and PsAQoL) questionnaires and disease activity (Clinical Disease Activity Index, CDAI, in RA and PsA; Bath Ankylosing Spondylitis Disease Activity Index, BASDAI, in axSpA) were assessed at baseline and months 3, 6, 12, 18, and 24. Association between WPAI and disease activity was tested using linear regression.ResultsWe enrolled 233 patients (RA, n = 95; axSpA, n = 69; PsA, n = 69), 110 patients were followed up to month 24. Mean age was 50.2 ± 14.2 years; 64% were female. Disease activity decreased from baseline to month 24 (RA: CDAI −24.3 ± 13.5; axSpA: BASDAI −4.4 ± 2.1, and PsA: CDAI −21.7 ± 8.5, p &lt; 0.0001, each). Total work productivity impairment (TWPI), activity impairment and presenteeism subscores continuously decreased throughout month 24 in all indications: RA (−58.3 ± 23%, −62.6 ± 23.8% and −61.7 ± 23.3%, respectively as compared to baseline; p &lt; 0.0001, each), axSpA (−34.4 ± 38.3%, p = 0.0117; −60.9 ± 25.9%, and −43.8 ± 26.6%, respectively, p ≤ 0.0001 both) and PsA (−35.8 ± 43.7%, p = 0.0186; −52.3 ± 25.4%, p &lt; 0.0001; and −43.3 ± 33.5%, p = 0.0007, respectively). Absenteeism scores decreased only in RA patients (−9.2 ± 24.9%, p = 0.0234). HRQoL improved between baseline and month 24 (RAQoL: −12.6 ± 7.5; ASQoL: −8.0 ± 4.3; PsAQoL; −8.3 ± 6.4, p &lt; 0.0001, each). TWPI, presenteeism and activity impairment strongly associated with disease activity throughout the study.ConclusionsThis real-world study confirms the benefit of golimumab on work productivity/daily activity impairment in Austrian RA, PsA, and axSpA patients.
The Prognostic Model and Drug Sensitivity of LKB1-Mutant Lung Adenocarcinoma Based on Immune Landscape
Authors: Wang Guanghui , Zheng Haotian , Zhao Xiaogang , Wang Yadong , Zeng Yukai , Du Jiajun 
Published: June 2022

Background: Lung cancer is the most common cause of cancer-related deaths worldwide. LKB1-mutant lung adenocarcinoma (LUAD) is a unique subtype of this deadly cancer. LKB1 mutations cause functional changes in a variety of cell processes, including immune functions, that affect prognosis. To date, the potential role of immunity in the prognosis of LKB1-mutant LUAD is not well understood.Methods: We systematically analyzed immune-related genes in LUAD samples from The Cancer Genome Atlas (TCGA) database. ESTIMATE and CIBERSORT algorithms were used to explore the immune microenvironment. A prognostic risk model was constructed, and prognostic, immune function, drug sensitivity, and model specificity analyses were performed to identify the effectiveness of the model.Results: Our results showed that LKB1 mutations suppressed immune function in LUAD. A three-gene signature was constructed to stratify patients into two risk groups. The risk score was an independent predictor for overall survival (OS) in multivariate Cox regression analyses [hazard ratio (HR) &gt; 1, p = 0.002]. Receiver operating characteristic (ROC) curve analyses confirmed that the risk score has better performance than clinicopathological characteristics. Functional analysis revealed that the immune status was different between the risk groups. ZM.447439 was an appropriate treatment for the high-risk group of patients. This risk model is only suitable for LKB1-mutant tumors; it performed poorly in LUAD patients with wild-type LKB1.Conclusion: Our findings indicate the potential role of immunity in LKB1-mutant LUAD, providing novel insights into prognosis and guiding effective immunotherapy.
Soluble Insulin Receptor Levels in Plasma, Exosomes, and Urine and Its Association With HIV-Associated Neurocognitive Disorders
Authors: Cantres-Rosario Yisel M. , Wojna Valerie , Ruiz Rafael , Diaz Bexaida , Matos Miriam , Rodriguez-Benitez Rosa J. , Rodriguez Elaine , Skolasky Richard L. , Gerena Yamil 
Published: June 2022

BackgroundHIV-associated neurocognitive disorders (HAND) are one of the HIV-associated comorbidities affecting 20–50% of the people with HIV (PWH) infection. We found that the soluble insulin receptor (sIR) levels in plasma and cerebrospinal fluid (CSF) were significantly higher in HIV-infected women. The mechanism of sIR release into the plasma remains unknown, but the detection of the sIR in exosomes may uncover novel mechanisms of sIR secretion from HIV-infected cells and its contribution to HIV disease progression and HAND development. Quantification of sIR in urine may represent a less invasive and more accessible diagnostic tool. Our objective was to quantify sIR levels in plasma, plasma-derived exosomes, and urine, and evaluate their association with HAND and renal function.MethodsWe measured full-length sIR in the plasma and urine of 38 controls and 76 HIV-infected women by ELISA, and sIR, HIV-1 Tat, and reactive oxygen species (ROS) in exosomes by flow cytometry.ResultsPlasma and exosomes with sIR were significantly higher in HIV-infected women when compared with controls and HAND. Exosomal sIR positively correlated with exosomal ROS and exosomal HIV-1 Tat in HIV-infected women. Exosomal ROS was significantly higher in HIV-infected women with more symptomatic cognitive impairment. Plasma-derived exosomes exhibited significantly higher levels of astrocyte (GFAP) and neuronal (L1CAM) markers in HIV-infected women, confirming the presence of circulating CNS-derived exosomes in the blood of HIV-infected women. Urine sIR positively correlated with eGFR in controls, but not in HIV-infected women, regardless there was no significant difference in renal function as determined by the estimated glomerular filtration rate (eGFR, p = 0.762). In HIV-infected women, higher plasma sIR correlated with lower urine sIR that could suggest sIR retention in blood or decreased renal filtration.DiscussionHigher plasma sIR levels and their correlation with ROS in plasma-derived exosomes with HAND suggest a combined role of metabolic disturbances, oxidative stress, exosome release, and cognitive decline. Communication between CNS and periphery is compromised in PWH, thus plasma-derived exosomes may shed light on disrupted cellular mechanisms in the brain of PWH. High plasma and low urine sIR levels could suggest sIR retention in blood or decreased renal filtration.