bluuebunny/crossref_metadata_2025 huggingface dataset:
Threshold Estimation Based on Local Minima for Nucleus and Cytoplasm Segmentation
Authors: Mayala Simeon , Haugsøen Jonas Bull
Published: November 2021

Background: Image segmentation is a process of partitioning the input image into its separate objects or regions. It is an essential step in image processing to segment the regions of interest (ROI) for further processing. We propose a method for segmenting neucleus and cytoplasm from the white blood cells (WBC).Methods: Initially, the method computes an initial value based on the minimum and maximum values of the input image. Then, a histogram of the input image is computed and then approximated to obtain function values. The method searches for the first local maximum and local minimum from the approximated function values. We approximate the required threshold from the first local minimum and the computed initial value based on defined conditions. The threshold is applied to the input image to binarize it and then perform post-processing to obtain the final segmented nucleus. We segment the whole WBC before segmenting the cytoplasm depending on the complexity of the objects in the image. For WBCs which are well separated from the RBCs, n thresholds are generated and then produce n thresholded images. Then, a standard Otsu method is used to binarize the average of the produced images. Morphological operations are applied on the binarized image and then use a single-pixel point from the segmented nucleus to segment the WBCs. For images in which RBCs touch the WBCs, we segment the whole WBC using SLIC and watershed methods. The cytoplasm is obtained by subtracting the segmented nucleus from the segmented WBC. Results: The method is tested on two different public data sets. Performance analysis is done and the results show that the proposed method segments well the nucleus and cytoplasm. Conclusion: We propose a method for nuclei and cytoplasm segmentation based on the local minima of the approximated function values from the histogram of image. The method has demonstrated its utility in segmenting nuclei, WBCs and cytoplasm and the results are reasonable.
A Novel Signature Derived from Metabolism-Related Genes GPT and SMS to Predict Prognosis of Laryngeal Squamous Cell Carcinoma
Authors: Shen Yujie , Huang Qiang , Zhang Yifan , Hsueh Chi-Yao , Zhou Liang
Published: November 2021

Background

A growing body of evidence has suggested the involvement of metabolism in the occurrence and development of tumors. But the link between metabolism and laryngeal squamous cell carcinoma (LSCC) has rarely been reported. This study seeks to understand and explain the role of metabolic biomarkers in predicting the prognosis of LSCC.
Methods

We identified the differentially expressed metabolism-related genes (MRGs) through RNA-seq data of TCGA (The Cancer Genome Atlas) and GSEA (Gene set enrichment analysis). After the screening of protein-protein interaction (PPI), hub MRGs were analyzed by least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic signature. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) was applied to verify the effectiveness of the prognostic signature in four cohorts (TCGA cohort, GSE27020 cohort, TCGA-sub1 cohort and TCGA-sub2 cohort). The expressions of the hub MRGs in cell lines and clinical samples were verified by quantitative reverse transcriptase PCR (qRT-PCR). The immunofluorescence staining of the tissue microarray (TMA) was carried out to further verify the reliability and validity of the prognostic signature. Cox regression analysis was then used to screen for independent prognostic factors of LSCC and a nomogram was constructed based on the results.
Results

Among the 180 differentially expressed MRGs, 14 prognostic MRGs were identified. A prognostic signature based on two MRGs (GPT and SMS) was then constructed and verified via internal and external validation cohorts. Compared to the adjacent normal tissues, SMS expression was higher while GPT expression was lower in LSCC tissues, indicating poorer outcomes. The risk score proved the prognostic signature as an independent risk factor for LSCC in both internal and external validation cohorts. A nomogram based on these results was developed for clinical application.
Conclusions

Differentially expressed MRGs were found and proven to be related to the prognosis of LSCC. We constructed a novel prognostic signature based on MRGs in LSCC for the first time and verified via different cohorts from both databases and clinical samples. A nomogram based on this prognostic signature was developed.
Hex Hox: De Novo Transcriptome Assembly and Embryonic Hox Gene Expression in the Burrowing Mayfly Hexagenia Limbata (Ephemeridae)
Authors: Gonzalez Christopher J , Hildebrandt Tobias R , O'Donnell Brigid C
Published: November 2021

Background: Hox genes are key regulators of appendage development in the insect body plan. The body plan of Mayfly (Ephemeroptera) nymphs differs due to the presence of evolutionarily significant abdominal appendages called gills. Despite mayflies’ basal phylogenetic position and novel morphology amongst insects, little is known of their developmental genetics. Here we present an annotated transcriptome for the mayfly Hexagenia limbata, with annotated sequences for putative Hox peptides and embryonic expression profiles for the Hox genes Antp and Ubx/abd-A. Results: Transcriptomic sequencing of early instar H. limbata nymphs yielded a high-quality assembly of 83,795 contigs, of which 22,975 were annotated against Folsomia candida, Nilaparvata lugens, Zootermopsis nevadensis and UniRef90 protein databases. Peptide annotations included eight of the ten canonical Hox genes (lab, pb, Dfd, Scr, Antp, Ubx, abd-A and Abd-B), most of which contained all functional domains and motifs conserved in insects. Expression patterns of Antp and Ubx/abd-A in H. limbata were visualized from early to late embryogenesis, and are also highly conserved with patterns reported for other non-holometabolous insects.Conclusions: We present evidence that both H. limbata Hox peptide sequences and embryonic expression patterns for Antp and Ubx/abd-A are extensively conserved with other insects. These findings suggest mayfly Antp and Ubx/abd-A play similar appendage promoting and repressing roles in the thorax and abdomen, respectively. The identified expression of Ubx and abd-A in early instar nymphs further suggests that mayfly gill development is not subject to Ubx or abd-A repression. Previous studies have shown that insect Ubx and abd-A repress appendages by inhibiting their distal structures, which can permit the development of proximal appendage types. In line with past morphology-based work, we propose that mayfly gills are proximal appendage structures, possibly homologous to the proximal appendage structures of crustaceans.
Identification of a Ferroptosis-related lncRNA Signature for Prognosis Prediction in Lung Squamous Cell Carcinoma
Authors: Cai Jiahao , Gu Jie , Ge Di , Xu Fengkai
Published: November 2021

BACKGROUNDThe incidence of lung cancer ranks first among malignant tumors all over the world. Based on the histological features, lung cancer could be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), of which non-small cell lung cancer accounts for about 80%. NSCLC mainly includes lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and large cell lung cancer (LLC). Most of the patients were diagnosed at a late stage, which means the 5-year overall survival rate for patients was shallow. According to the situation, new biomarkers are needed to recognize patients at high risk, which would help give them appropriate treatment to improve their outcomes.Ferroptosis, an important iron-dependent cell death driven by oxidative phospholipid damage and characterized by lipid peroxidation, was recently found to play a novel role in several cancers. Existing research have identified many genes related to ferroptosis in tumor tissues. However, research on ferroptosis-genes-related long non-coding RNA (lncRNA) in lung cancer is still insufficient. METHODSWe acquired the statistics from the public database TCGA Lung Squamous Cell Carcinoma (LUSC). Then a multi-lncRNA signature was constructed to recognize patients at high risk based on differentially expressed ferroptosis-genes-related lncRNAs in lung squamous cell carcinoma. RESULTSWe finally identified eight differently expressed ferroptosis-genes-related lncRNAs are predictive of outcomes in LUSC patients. Kaplan-Meier analyses revealed that the high-risk-related lncRNAs signature has strong predictive power for poor LUSC prognosis (AUC=0.686). Our risk-predictive model was superordinate to the traditional predictive method based on clinicopathological characteristics (Stage, AUC=0.563). Gene set enrichment analysis (GSEA) revealed signaling pathways that ferroptosis-genes-related lncRNAs may participate in. Further study of immune function-related gene sets showed that parainflammation, APC co-stimulation, inflammation-promoting, T cell co-stimulation, Type I and type II INF response were significantly associated with risk-related lncRNAs signature. Immune checkpoint-related genes such as PDCD-1, CD70, CD28, and CD27, etc., also expressed differently between the two risk groups.CONCLUSIONThe specific differentially expressed ferroptosis-related lncRNAs have a strong predictive effect on the prognosis in patients with lung squamous cell carcinoma.
WITHDRAWN: Qihuzha Granule Alleviated Cyclophosphamide-induced Immune Deficiency in Mice via IL-6 Related Signaling Pathways
Authors: Zhong Ting , Feng Min , Su Minzhi , Wu Hongshan , Li Qing , Luo Fang , Wang Haibo , Li Linzhen , Fan yanhua
Published: November 2021

BackgroundQihuzha granule (QHZG) is a Chinese patent medicine, composed of 11 kinds of edible medicinal plants, which is used to treat dyspepsia and anorexia in children caused by spleen and stomach deficiency syndrome. However, its role and mechanism in immunosuppression induced by cyclophosphamide remained unclear. The purpose of this study is to investigate the effect of QHZG on immunosuppression induced by cyclophosphamide in mice and its possible mechanism.MethodsThe immunosuppression injury model was induced by intraperitoneal injection of cyclophosphamide (100 mg/kg); the mRNA level of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3) were tested by QPCR; related protein levels were detected by western blotting; hematoxylin-eosin (HE) staining was employed to observe the histological alterations; macrophages and neutrophils in the mouse spleen were examined by immunofluorescence analysis. ResultsQHZG significantly increased the spleen index and thymus index of mice with immunodeficiency induced by cyclophosphamide and up-regulated the mRNA expression of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3), which were decreased by cyclophosphamide treatment. The results of immunofluorescence staining and histological analysis showed that QHZG could also protect mice from immunosuppressive injury caused by cyclophosphamide via keeping structural integrity of spleen, and partially restoring the production levels of macrophages and monocytes in the spleen. Further studies indicated that QHZG could significantly counter the decline of phosphorylated protein levels of JAK2/SRC-STAT3 axes (P-JAK2, P-SRC and P-STAT3), and MAPK pathways (P-JNK, P-ERK and P-P38) induced by cyclophosphamide, suggesting that the protective effects of QHZG on immunosuppressive injury triggered by cyclophosphamide were involved in JAK2/SRC-STAT3 axes, and MAPK pathways. Meanwhile, we also found that QHZG could partially restore the vital phosphorylated proteins of PI3K/Akt/mTOR signaling pathway (P-Akt, P-mTOR), which were reduced by cyclophosphamide. The data implied that PI3K signaling pathway was also responsible for the protection of QHZG against the immunosuppression induced by cyclophosphamide in mice. ConclusionsOur study demonstrated that QHZG protected mice from cyclophosphamide-triggered immunosuppressive injury via IL-6 and its downstream signaling pathways including PI3K/Akt/mTOR signal pathway and JAK2-SRC/MAPK/STAT3 axes. These results suggested that QHZG might serve as a new drug for the treatment of the immunosuppression caused by cyclophosphamide therapy.
Specification of Interventions and Selection of Control in Acupuncture Randomized Controlled Trials: A Cross-Sectional Study
Authors: Liu Jiali , Li Ling , Luo Xiaochao , Qin Xuan , Zhao Ling , Zhao Jiping , Zhou Xu , Liu Yanmei , Deng Ke , Ma Yu , Zou Kang , Sun Xin
Published: November 2021

Background: Specification of interventions and selection of control are two methodological determinants for a successful acupuncture trial. However, it is not fully understood about the current practice of these two determinants. We thus conduced a cross-sectional study to examine specification of interventions and selection of control among current acupuncture randomized controlled trials (RCTs). Methods: We searched PubMed for acupuncture RCTs published in the core clinical journals and complementary and alternative medicine (CAM) journals from January 2010 to December 2019 (10 years), and included RCTs that assessed treatment effects of acupuncture versus any type of control. Teams of methods-trained investigators who had experiences in acupuncture trials independently screened reports for eligibility and collected data, using a prespecified standardized questionnaire. We used network meta-analyses to investigate whether treatment effect was differential in patients with chronic pain when using sham acupuncture as a control versus using waiting-list or no treatment.Results: Of 319 eligible RCTs, most well specified style of acupuncture (86.8%), acupoint prescription (96.2%), type of needle stimulation (90.3%) and needle retention time (85.6%). However, other acupuncture details were less specified, including achievement of response sought (65.5%) and needle manipulation (50.5%), specification of number of needle insertions (21.9%), angle and direction of insertion (31.3%), patients posture (32.3%) and co-interventions (22.9%). Sham acupuncture (41.4%) was the most frequently used control, followed by waiting-list or no treatment (32.9%). There was no differential treatment effect when using sham acupuncture versus waiting-list/no treatment as a control (SMD = -0.15, 95% CI -0.91 to 0.62).Conclusions: Over a decade of research practice, important gaps remained in the specification of acupuncture interventions, including specification of response sought, needle manipulation, and co-interventions. While sham acupuncture was largely used, waiting-list or no treatment may also be used as an appropriate control.
Dietary Ellagic Acid Ameliorated Clostridium Perfringens-Induced Subclinical Necrotizing Enteritis In Broilers Via Regulating Inflammation Signaling Pathways And Cecal Microbiota to Inhibit Intestinal Barrier Damage
Authors: Tang Yu , Zhang Xinyue , Wang Yanan , Guo Yongpeng , Zhu Peiqi , Li Guiguan , Zhang Jianyun , Ma Qiugang , Zhao Lihong
Published: November 2021

Background: Subclinical necrotizing enteritis (SNE) is a common intestinal disease caused by Clostridium perfringens in broilers, which cause chronic intestinal damage, affect the digestion and absorption of nutrients, and reduce production performance. Ellagic acid (EA) has been reported to have antioxidant and anti-inflammatory properties in many aspects. This study was conducted to evaluate the effect and mechanism of EA in relieving subclinical necrotizing enteritis in broilers induced by C. perfringens. Results: C. perfringens challenge decreased body weight (BW), average daily gain (ADG); jejunal villi height/crypt depth (V/C); the activity of catalase (CAT), and the mRNA expression of zonula occludens 1 (ZO-1) in jejunum mucosa of broilers. While it increased feed conversion ratios (FCR); jejunal crypt depth (CD); activities of myeloperoxidase (MPO) and diamine oxidase (DAO), as well as concentrations of interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) in serum; activities of inducible nitric oxide synthase (iNOs) and lysozyme (LZM), the concentration of malondialdehyde (MDA), and the mRNA expression of claudin-2, TNF-α, IL-1β, TLR4, TLR2, NF-κB, JAK3, STAT6 and iNOs in jejunum mucosa of broilers. Dietary EA supplement relieved these adverse effects, and heightened jejunal villi height (VH); the concentration of D-xylose in plasma; activities of superoxide dismutase (SOD), and the mRNA expression of occludin in jejunum mucosa of broilers. The alpha diversity of cecal microbiota exhibited dietary EA supplement increased observed species and Shannon index. C. perfringens challenge increased the relative abundance of Firmicutes and decreased the relative abundance of Desulfobacterota. Similarly, EA increased relative abundance of Firmicutes. LEfSe analysis showed that C. perfringens challenge harmed the cecal microbiota of broiler chickens, dietary EA supplementation led to a small beneficial effect, while the simultaneous effect of them seems to stimulate the immune function of broilers and made broilers possess a better cecal microbiota. Conclusions: Dietary EA ameliorated C. perfringens-induced SNE in broilers via regulating jejunal inflammation signaling pathways TLR/NF-κB and JAK3/STAT6, relieving jejunal oxidative stress, and balancing cecal microbiota to inhibit intestinal barrier damage, prevent systemic inflammatory response, and improve nutrient absorption capacity, finally protect and enhance growth performance of broilers.
Multi-Omics Analysis Identifies the Heterogeneity and Prognosis in Bladder Cancer
Authors: Ma Wenchao , Li Cheng , Liu Yuchao , Zhang Wentao , Guo Yadong , Yang Fuhan , Zhang Junfeng , Wang Hong , Jia Weihua , Yao Xudong , Xiao Jun , Yan Yang
Published: November 2021

Background

The multi-omics integrated analysis can help researchers understand the biological behavior of bladder cancer(BCa) in a more systematic and comprehensive manner, and further provide new clues for finding valuable tumor markers and therapeutic targets.
Methods

In this study, we applied the DNA methylation data to construct a prognosis classifier and stratified the BCa patients into high- and low-risk subtype. The differences of transcriptome, single nucleotide variants and copy number variations between two subgroups were explored for finding the changes of molecular mechanism.
Results

With 18 pairs DNA methylation samples, ten differentially methylated positions(DMPs) were identified and applied to evaluate the risk score of each sample. Kaplan-Meier survival analysis displayed that BCa patients with high risk had a poor prognosis than the lower(p<0.0001). In transcriptome analysis, many immune related pathways and biological process changed between high- and low-risk patients. The results also displayed that naive B cells, plasma cells, CD8+ T cells and T cell regulatory(Tregs) infiltrated less in high-risk patients and these patients were less sensitive to immunotherapy and chemotherapy. As for single nucleotide variants, we found that TP53, CDKN1A, STAG2 and other genes were more frequently mutated in high-risk BCa patients. Only copy number variation in high-risk patients were displayed for the limitation of TCGA data.
Conclusions

The high- and low-risk patients identified by DNA methylation data of bladder cancer were significant different in survival. The comprehensive comparison of multi-omics data between subgroups can help clinicians find the heterogeneity of tumor biological behavior and contribute to precision treatment in bladder cancer.
Affibody Molecule for Positron Emission Tomography Imaging of Human Epidermal Growth Factor Receptor: Validation in Mouse Models and Human Cancer Tissues
Authors: Chen Weizhi , Miao Shuang , Sun Yao , Liu Yang , Wang Chunhe , Liu Xiang , Cheng Zhen , Sun Xilin
Published: November 2021

Background: Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) expression status over time post challenges for the design of strategies for effective anti-EGFR monoclonal antibodies in the treatment of non-small-cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for real-time and comprehensive tumor EGFR profiling especially in lung cancer precision medicine trials. Radionuclide imaging of EGFR expression in tumors may screen patients for EGFR-targeting therapies and predict response or resistance to certain treatments.Methods: EGFR-specific Affibody molecule (ZEGFR:1907) was radiolabeled with 68Ga. The radioligands were characterized in vitro and in mice bearing subcutaneous tumors with varying levels of EGFR expression: HCC827 (EGFR overexpression), H1975 (moderate-high), A549 (moderate), H358 (low), and H520 (negative). In vivo tumor targeting activity using PET imaging and biodistribution were conducted in tumor-bearing nude mice. Autoradiography, western blot, immunofluorescence, and immunohistochemistry were performed in human tumor samples. Statistical analyses were performed using GraphPad Prism 7.0. One-way or two-way analysis of variance (ANOVA) followed by the Bonferroni’s multiple comparisons test was used. Statistical significance was set at P < 0.05.Results: 68Ga-NOTA-ZEGFR:1907 showed higher uptake in high EGFR-expressing cells (HCC827, H1975) when compared to cells with moderate to low EGFR (A549, H358) or without EGFR (H520). Radionuclide imaging showed probe accumulation was preferential in EGFR-expressing tumors, particularly in HCC827, H1975 xenografts. A549 and H358 xenografts were mildly and indistinctly visualized. EGFR-negative H520 xenografts were barely visible at any time-point. Biodistribution showed a significantly higher accumulation in HCC827 tumors when compared to H520 tumors (3.20 ± 0.10 %ID/g vs. 0.81 ± 0.08 %ID/g at 2h, P< 0.05). Specific binding to EGFR could be competitively blocked by excess un-radiolabeled affibody molecules in cell uptake, PET imaging and biodistribution assays. Autoradiography showed the regions with high radiotracer uptake partly overlapped with the area of positive EGFR immunofluorescence and immunohistochemistry. Finally, the overall accumulation of autoradiography was positively correlated with immunohistochemistry score.Conclusion: Affibody-based radiotracer 68Ga-NOTA-ZEGFR:1907 is suitable for identification of EGFR expression, showing great potential for further applications and clinical translation.
The Unvirtuous Cycle of Discrimination Affecting People with Hepatitis B
Authors: Freeland Catherine , Mendola Lindsay , Cheng Vivian , Cohen Chari , Wallace Jack
Published: November 2021

Background An estimated 296 million individuals live with chronic hepatitis B worldwide, most have not been diagnosed and remain at risk of liver disease and cancer. People with hepatitis B often face discrimination that denies them employment or education opportunities, results in unfair treatment at work or in school, limits their ability to emigrate to certain countries, and in some cases prohibits them from serving in the military. Discrimination specific to hepatitis B has not been widely documented within the literature. This study aims to investigate and describe hepatitis B related discrimination, document discrimination occurring around the globe, and provide initial recommendations for addressing discrimination using key informant interviews.MethodsPurposive and snowball sampling were used to identify potential key informants for qualitative interview. Key informants identified as community health leaders, public health scientists, doctors, and researchers, many of whom were also living with hepatitis B. Using a semi-structured guide, participants were asked to describe their experience and any challenges for people living with hepatitis B including marginalization and its’ consequences. A codebook was used to guide the organization of data for analysis, and all transcripts N=17 were double coded. Results The overarching themes identified from interviews demonstrate explicit experiences with discrimination of those directly affected, the psychological responses, and the negative health outcomes associated with the unvirtuous cycle of discrimination. All key informants reported on the substantial quality of life implications and often poorer health outcomes resulting from hepatitis B discrimination. Participants also identified the significant impact of hepatitis B discrimination occurring within a range of education-based services across several countries as well as military exclusion or removal if individuals are found to have hepatitis B. ConclusionOur data demonstrate that hepatitis B discrimination has a significant impact. Discrimination can occur in a cyclic nature at various points in life from education, to seeking employment, to marriage, to restrictions on entry, travel and stay in other countries. Hepatitis B discrimination impacts mental and physical health of those experiencing it and limits overall wellbeing, quality of life, can lead to poor health outcomes and avoidance of testing and management.
Optical Coherence Tomography Angiography in Herpetic Leucoma
Authors: Almeida Inês , Dias Libânia , Jesus Jeniffer , Fonseca Inês , Matias Maria João , Pedro João Carlos
Published: November 2021

Background: Herpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. This study instends to investigate the potential of Optical Coherence Tomography Angiography (OCTA) device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology. Methods: A Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and Optical Coherence Tomography Angiography (OCT) with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6x6 mm in a depth of 800 μm. Results: Patients included had a mean age 53.267±21.542 (years±SD). The mean total vessel area was 50.907±3.435%. VD was higher in the nasal quadrant (51.156±4.276) but there were no significant differences between the three analyzed areas (p=0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings. Conclusions: OCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection.
Based on Network Pharmacology to Explore the Mechanisms of Radix Astragali Combined with Prepared Radix Rehmanniain for Treating Osteoporosis
Authors: Kang Wenqian , Liu Chunyu , Tang Yu , Geng Zhixin , Zhang Jiahao , Li Min , Gao Feng , Ou Li , Wei Peifeng
Published: November 2021

Background: With the improvement of people's living standards, the aging population in China has gradually increased, and the treatment of osteoporosis (OP) has become a major problem afflicting the medical field. Radix Astragali(RA) and Prepared Radix Rehmannia(PRR) are commonly used Chinese herbal medicines. The combination of them can achieve a synergistic effect in the treatment of osteoporosis. However, its mechanism of action remains uncertain.Objective: This study aims to investigate the possible molecular mechanism of RA combined with PRR in the treatment of OP using an integrated strategy of network pharmacology and experimental validation.Methods: The active ingredients of RA combined with PRR were searched and screened by TCMSP database, and the targets of active ingredients were predicted and supplemented by TCMSP and SwissTargetPrediction databases. The target genes related to OP diseases were searched in GeneCards and OMIM comprehensive databases. The intersection targets of drugs and diseases were imported into String database to obtain the interaction information of intersection target genes. Cytoscape3.7.1 software was used to construct the protein interaction network diagram and "drug component-target-disease" network diagram. Then DAVID database was used for GO gene enrichment analysis and KEGG metabolic pathway analysis. Finally, in vivo experiments were also performed to validate the findings of network pharmacology.Results: A total of 98 active components of RA combined with PRR were finally retrieved and integrated into the TCMSP database, 1700 target genes related to OP were obtained through the disease database, 149 gene targets were obtained by taking the intersection of disease genes, and drug targets, 122 core targets and 514 interaction relationships were obtained after protein interaction network and topology analysis. GO analysis and KEGG pathway enrichment analysis showed that RA combined with PRR intervention for OP mainly through multiple pathways such as PI3K-Akt, MAPK, TNF, Rap1, and Toll-like receptors. In addition, in vivo experiments confirmed that RA combined with PRR could significantly increase bone mineral density, reduce bone spacing, improve bone tissue structure, and improve osteoporosis in ovariectomized rats.Conclusion: In this study, the network pharmacological approach was used to reveal the potential targets and key signal pathways of RA combined with PRR in treating osteoporosis. This study was also verified by animal experiments, which provided a reliable basis for clinical application.
Multidrug-Resistant Klebsiella Pneumoniae: A Retrospective Study in Manaus, Brazil
Authors: Nakamura-Silva Rafael , Cerdeira Louise , Oliveira-Silva Mariana , Costa Karen Regina Carim da , Sano Elder , Fuga Bruna , Moura Quézia , Esposito Fernanda , Lincopan Nilton , Wyres Kelly , Pitondo-Silva André
Published: November 2021

Klebsiella pneumoniae is an opportunistic pathogen that can cause several infections, mainly in hospitalised or immunocompromised individuals. The spread of K. pneumoniae emerging virulent and multidrug-resistant clones is a worldwide concern and its identification is crucial to control these strains especially in hospitals. This article reports data related to multi-resistant K. pneumoniae strains, isolated from inpatients in the city of Manaus, Brazil, harbouring virulence and antimicrobial resistance genes, including high-risk international clones belonging to clonal group (CG) 258. Twenty-one strains isolated from different patients admitted to four hospitals in the city of Manaus, located in the state of Amazonas, Northern Brazil (Amazon Rainforest region) were evaluated. The majority of strains (61.9 % n = 13) were classified as multidrug-resistant (MDR), and five strains (23.8 %) as extensively drug-resistant (XDR). Several virulence and antimicrobial resistance genes were found among the strains and eight strains (38.1 %) presented the hypermucoviscous phenotype. MLST analysis demonstrated a great diversity of STs among the strains, totaling 12 different STs (ST11, ST23, ST198, ST277, ST307, ST340, ST378, ST462, ST502, ST3991, ST3993 and ST5209). Four of these (ST11, ST23, ST307 and ST340) belong to CG258.
Skin Autofluorescence Profile in Tunisian Subjects with and Without Metabolic Disorders
Authors: Khochtali Ines , Bouida Wahid , Boubaker Hamdi , Nouira Semir , Kerkeni Mohsen
Published: November 2021

Background: The AGE Reader, as a clinical tool for non invasive assessment, measures the accumulation of advanced glycation end products (AGEs) in skin tissues shown as skin autofluorescence (SAF). AGEs Accumulation has been implicated in several diseases. There is no data about SAF profile in Tunisian population, this study aimed to assess firstly SAF profile in subjects with and without metabolic disorders and secondly to examine the association between SAF and various clinical parameters.Methods: In a cross-sectional study, we included 220 participants between 19 and 86 years of age who were subdivided in two groups: a healthy group (n=93) and patients group with metabolic disorders (n=127) contains three subgroups as following: diabetic patients (n=32), hypertensive patients (n=54) and patients with both diabetes and hypertension (n=41). Skin AGEs accumulation was measured by AGE Reader and clinical data was obtained.Results: SAF was significantly higher in patients group compared to healthy group [2.40 AU (2.10-2.60) vs. 2.00 AU (1.70-2.10) respectively; P <0.001]. Diabetic patients and hypertensive patients showed an increased level of SAF. The highest of SAF was observed in patient with both coexistence of diabetes, hypertension and dyslipidemia. SAF was associated with age, gender, BMI, duration of diabetes, HbA1c, triglyceride and obesity. Multivariate analysis showed that age and duration of diabetes were independent determinant of SAF. The ROC analysis indicated that an SAF > 2.25 AU was optimal cut-off point to predict the presence of metabolic disorders (P <0.001). Conclusion: SAF was increased in patients with diabetes and/or with hypertension and dyslipidemia. AGE Reader device is a rapid and helpful tool in clinical practice for evaluating and screening metabolic disorders in undiagnosed subjects.
Effect of Impurities on a Two-Dimensional Dodecagonal Quasicrystal
Authors: Fuwa Masahiro , Sato Masahide
Published: November 2021

Langevin dynamics simulations are performed to examine how impurities affect two-dimensional dodecagonal quasicrystals. We assumed that the interaction potential between two particles is the Lennard-Jones-Gauss potential if at least one of these particles is a matrix particle and that the interaction potential between two impurities is the Lennard-Jones potential. Matrix particles and impurities impinge with constant rates on the substrate created by a part of a dodecagonal quasicrystal consisting of square and triangular tiles. The dependences of the twelve-fold rotational order and the number of shield-like tiles on the impurity density are examined after sufficient solid layers are grown. While the change in the twelve-fold rotational symmetry is small, the number of shield-like tiles in the solid increases greatly with increasing impurity density.
The Involvement of CXCL17-GPR35 in Gastric Cancer Initiation and Development
Authors: Li Yi-zhi , Liu Ao-ran , Liu Song-yi , Yan Li-rong , Yuan Yuan , Xu Qian
Published: November 2021

Background: C-X-C motif chemokine 17 (CXCL17), a newly identified chemokine, and its possible receptor, G-protein coupled receptor 35 (GPR35) were potential proteins involved in carcinogenesis; nevertheless, their involvement in gastric cancer (GC) initiation and development, which we aimed to evaluated in this study, remains undefined.Methods and materials: CXCL17 and GPR35 expressions in normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissues was determined by immunohistochemistry. Their possible roles were analyzed by the Cancer Genome Atlas (TCGA) data mining and western blot.Results: Either CXCL17 or GPR35 showed a strongest expression in GC-IM among the four types of tissues: CXCL17: GC-IM vs. AG-IM (P < 0.001), GC-IM vs. GC (P < 0.001); GPR35: GC-IM vs. AG-IM (P < 0.001), GC-IM vs. GC (P < 0.01). Their expressions were positively correlated in GC tissues (Spearman r = 0.2933, P < 0.001). CXCL17 expression was negatively correlated with the depth of tumor invasion (P = 0.015) and tumor maximum diameter (P = 0.003). Higher CXCL17 expression independently predicted for better survival in GC patients. TCGA analysis suggested CXCL17 expression was positively correlated with the transcriptional level of gastric mucosal maturation indicators TFF1, TFF2, PGC and MUC5AC, but negatively with the dedifferentiation indicators CDX1 and SFRP family members. Protein-protein interaction (PPI) revealed the potential connection of GPR35-CXCL17-CCL20. Overexpressing CXCL17 in HGC27 cell line downregulated SFRP2 and CDX1, but upregulated CCL20 expression.Conclusion: CXCL17 and GPR35 may play a vital role in GC initiation and development, especially in the IM to GC process. A higher CXCL17 expression independently predicted for better survival in GC patients, with a possible role in maintaining gastric mucosa maturation.
Enzyme-catalyzed Synthesis of Novel Solid–liquid Phase Change Energy Storage Materials Based on Levulinic Acid and 1,4 butanediol
Authors: Zhai Siyu , Zhang Lihe , Zhao Xi , Wang Qian , Yan Yin , Li Cui , Xu Zhang
Published: November 2021

With the rapid development of society, all kinds of non-renewable energy resources are constantly developed and utilized, energy storage is one of the best ways to solve the energy shortage. In this study , levulinic acid (LA) and 1,4 butanediol (BDO) were used to synthesize a novel polyol ester (LABDO) by biological and chemical methods. The biological method exhibited excellent performance in the synthesis process, where 87.5% of LABDO yield under optimal conditions, while the chemical method had more byproducts and higher energy consumption. Finally, the thermal properties of the obtained phase change materials (PCMs) were evaluated. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the melting temperature of LABDO was 50.51°C, the latent heat of melting was 156.1J/g, and the pyrolysis temperature was 150-160°C. Compared with traditional paraffin wax, the prepared PCMs have suitable phase transition temperature, higher latent heat of melting and better thermal stability. The thermal conductivity can be increased to 0.34W·m-1· k-1 by adding expanded graphite. In summary, LABDO can be used as low temperature phase change energy storage materials.
Comparative transcriptomics identifies the transcription factors BRANCHED1 and TCP4, as well as the microRNA miR166 as candidate genes involved in the evolutionary transition from dehiscent to indehiscent fruits in Lepidium
Authors: Gramzow Lydia , Klupsch Katharina , Pozo Noé Fernández , Hölzer Martin , Marz Manja , Rensing Stefan A. , Theißen Günter
Published: November 2021

Background: Fruits are the seed-bearing structures of flowering plants and are highly diverse in terms of morphology, texture and maturation. Dehiscent fruits split open upon maturation to discharge their seeds while indehiscent fruits are dispersed as a whole. Indehiscent fruits evolved from dehiscent fruits several times independently in the crucifer family (Brassicaceae). The fruits of Lepidium appelianum, for example, are indehiscent while the fruits of the closely related L. campestre are dehiscent. Here, we investigate the molecular and genetic mechanisms underlying the evolutionary transition from dehiscent to indehiscent fruits using these two Lepidium species as model system.Results: We have sequenced the transcriptomes and small RNAs of floral buds, flowers and fruits of L. appelianum and L. campestre and analyzed differentially expressed genes (DEGs) and differently differentially expressed genes (DDEGs). DEGs are genes that show significantly different transcript levels in the same structures (buds, flowers and fruits) in different species, or in different structures in the same species. DDEGs are genes for which the change in expression level between two structures is significantly different in one species than in the other. Comparing the two species, the highest number of DEGs was found in flowers, followed by fruits and floral buds while the highest number of DDEGs was found in fruits versus flowers followed by flowers versus floral buds. Several gene ontology terms related to cell wall synthesis and degradation were overrepresented in different sets of DEGs highlighting the importance of these processes for fruit opening. Furthermore, the fruit valve identity genes FRUITFUL and YABBY3 were among the DEGs identified. Finally, the microRNA miR166 as well as the TCP transcription factors BRANCHED1 (BRC1) and TCP FAMILY TRANSCRIPTION FACTOR 4 (TCP4) were found to be DDEGs.Conclusions: Our study reveals differences in gene expression between dehiscent and indehiscent fruits and uncovers miR166, BRC1 and TCP4 as possible causes for the evolutionary transition from dehiscent to indehiscent fruits in Lepidium.
Resonant Frequency of Circular Sectorial Microstrip Antenna Printed On Double-Layered Anisotropic Substrates
Authors: FRIHA Souad , Bedra Sami , CHEBBARA Fouad , BEDRA Randa , BENKOUDA Siham
Published: November 2021

In this work, modal characteristics have been rigorously studied which germinate an improved, accurate, and efficient computer-aided design (CAD) formulation to estimate the resonant frequency of sectorial circular microstrip antennas printed on anisotropic suspended and composite substrates. The obtained results demonstrated that the resonant frequencies of the sectorial circular microstrip patch on suspended and composite substrates can be adjusted to obtain the maximum operating frequency of the antenna. The computed results show a fairly good agreement with measured results. Such theoretical validation and results may prove to be more useful for design engineers and further investigation.
Movement Patterns and Habitat use of Adult Giant Trevally (Caranx Ignobilis) in the South China Sea
Authors: Chiang Wei‐Chuan , Lin Shian-Jhong , Soong Ker-Yea , Liao Te-Yu , Chen Yu-Yun , Ho Yuan-Hsing , Tseng Chen-Te , Musyl Michael K.
Published: November 2021

This paper presents the first application of pop-up satellite archival tags (PSATs) to giant trevally (Caranx ignobilis) in a "no-take" marine protected area (MPA) comprising in a major reef system in the South China Sea (Dongsha Attol National Park). In order to determine appropriate management strategies in an around the MPA and to delimit stock boundaries to help restore populations, fundamental ecological information is required on movement patterns, habitat preferences and home range. In total 10 giant trevally were tagged from May 2016 to September 2018. Eight tags reported and remained affixed from 17 to 243 days and linear displacements ranged from 26 to 826 km from deployment to pop-up locations. Fish were mainly confined to the mixed-layer but occasionally made deeper descents (~50 -60 m) during nighttime and the distributions of time spent at depth (~0 - 67 m) and temperature (21.5 - 35.4°C) were significantly different between daytime and nighttime but the transitions were not pronounced. Most probable tracks calculated from a state-space Kalman filter suggested site-fidelity and/or cyclic N-S dispersal patterns possibly related to spawning or foraging as about half of the pop-up locations were within ~100 km of the tagging location. Given these findings and implications, it is possible that giant trevally may need to be managed at small spatial scales to preserve genetic diversity. Additional tagging studies, however, using genetic data and conventional tags to maximize cost-benefit and augmented with a sub-set of PSATs, will be required to test this hypothesis at a higher level of statistical power.
LncRNA PVT1 Regulates Biological Function of Osteoarthritis Cells by Regulating miR-497/AKT3 Axis
Authors: Chen Peng , Zhang Ying
Published: November 2021

Objective

There is growing evidence that lncRNA plays a role in the progression of many diseases, including osteoarthritis (OA). However, the role of lncRNA PVT1 in OA is still unclear. Thus, the present study aims to explore the function of PVT1 in the OA process, and analyze the possible mechanisms thereof.
Methods

PVT1 expression in articular cartilage tissue of OA patients and non-OA patients was evaluated. PVT1, miR-497 and AKT3 in IL-1β induced chondrocytes were knocked down or elevated to determine the proliferation and apoptosis of treated chondrocytes. And the changes of AKT3 and extracellular matrix (ECM) related factors (aggrecan, collagen Type II and MMP-9) were detected.
Results

PVT1 was elevated in OA cartilage tissue and chondrocytes induced by IL-1. Cell proliferation ability was enhanced while apoptosis rate was declined after PVT1 knock down and miR-497 elevation. In addition, aggrecan and collagen Type II levels reduced in IL-1β induced chondrocytes, while MMP-9 level elevated. Dual luciferase reporter confirmed that PVT1 and AKT3 interacted with miR-497, respectively. Rescue experiments revealed that increasing AKT3 or knocking down miR-497 could reverse the impacts of knocking down PVT1 on IL-1β-induced chondrocytes.
Conclusion

PVT1 is up-regulated in OA, and knock down PVT1 can decrease the effects of IL-1βon proliferation, apoptosis, and ECM degradation of chondrocyte through regulating miR-497/AKT3 axis.
Synthesis and characterization of Ni2C: An efficient electrocatalyst towards hydrogen evolution reaction
Authors: Vilvanathan Sathish , Gunasekaran Roshini
Published: November 2021

Ni2C electrocatalyst were synthesized and characterized for the Hydrogen Evolution Reaction (HER) electrolyzer. One step hydrothermal technique is used to synthesize Ni2C sample. Platinum based electro catalyst materials are initial and best electro catalyst for Hydrogen Evolution Reaction (HER). Ni2C (Nickel Carbide electro catalyst) was examined by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD). Electrochemical characterization like cyclic voltammetry (CV), Tafel polarization and electrochemical impedance spectroscopy (EIS) studies is employed to explore the elctrocatalytic behavior of Ni2C material for HER. FTIR study confirms the presence of Ni2C electrocatalyst by the presence of metal peaks and various functional groups. The isomeric nature and purity of synthesized material were explored by powder X-ray diffraction studies. Cyclic voltammetry technique was performed in 0.5 M H2SO4 solution to attain the polarization curve of Ni2C electrocatalyst for HER.
Music intervention affects the quality of life on Alzheimer’s disease: a meta-analysis
Authors: Yu Xin
Published: November 2021

BackgroundMusic intervention has been found to be beneficial for neurological diseases, especially in slowing down the progression of clinical symptom in patients. However, it remains unclear to what extend can music intervention may affect patients with Alzheimer’s disease (AD). Questions remain on whether music intervention can improve the quality of life (QOL) of AD patients, who are usually with poor QOL owning to the burden of disease.MethodsA search that compared the effectiveness of music intervention to improve the QOL of AD patients were carried out. PubMed, Cochrane library clinical trial database, and WANFANG database were searched to collect data from randomized controlled trials (RCTs). Two independent researchers extracted data from the selected eligible articles by using collection form and RevMan5.3 statistical software and applied for the meta-analysis.ResultsWe included six RCTs in our meta-analysis. The results showed that compared to the control group, music intervention can significantly increase the score of the QOL-AD scale (MD=5.10, 95%CI: 2.95-7.24, P<0.001) and The World Health Organization QOL Rating Scale Short Form score (MD=5.76, 95%CI: 1.59-9.92, P=0.007). ConclusionsResults suggested that music intervention could improve the QOL for the elderly patients with AD. Our findings indicated that music intervention might be considered as a non-pharmaceutical therapy for patients with AD in the future.
Selecting a Green, Agile and Industry 4.0 Supplier With the Fuzzy-Swara-Bwm Integrated Method
Authors: Tas Mehmet Ali , Akcan Serap
Published: November 2021

The authors have requested that this preprint be removed from Research Square.