bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the service‐related experiences and outcomes of caregivers involved in a system of care who experienced everyday discrimination
Authors: Champine Robey B. , Rozas Lisa Werkmeister , Schreier Alayna , Kaufman Joy S.
Published: October 2018

Individuals who report everyday experiences of discrimination are at heightened risk for adverse health outcomes and tend to report underutilization of health services. Systems of care (SOCs) have the potential to engage members of minority groups and to reduce health disparities. We examined the service‐related experiences of predominantly Latinx caregivers enrolled in a SOC for their children with severe psychological health needs. We used independent samples t‐tests and regression analyses to compare relations among service access, perceived service characteristics, and caregiver stress according to whether caregivers reported frequent or infrequent discrimination. The frequent discrimination group scored significantly higher on dimensions of stress and had greater dosage than the infrequent group. There were no differences in relations between service characteristics and outcomes by group. Findings indicated important differences in the service‐related experiences and outcomes of caregivers who reported frequent and infrequent discrimination. We discuss limitations and implications.
Protecting youth from gang membership: Individual and school‐level emotional competence
Authors: Lenzi Michela , Sharkey Jill D. , Wroblewski Allie , Furlong Michael J. , Santinello Massimo
Published: October 2018

The current study examined the association between adolescent emotional competence, operationalized and measured at both the individual and the school levels, and gang membership. The study involved a sample of 12,040 students (51.4% females; mean = 16.9 years) participating in the biennial state department of education coordinated California Healthy Kids Survey, which assesses a range of adolescent health‐related behaviors. Hierarchical linear modeling indicated that higher levels of individual emotional competence were associated with a lower likelihood of identifying as a gang member. Moreover, a stronger negative association between emotional competence and identifying as a gang member was found when emotional competence was operationalized at the school level. Implications include the role of schools in promoting emotional regulation, empathy, and behavioral regulation of their entire student body as part of an overall strategy to reduce individual student's attraction to gangs.
Retracted: In vivo and in vitro effects of microRNA‐221 on hepatocellular carcinoma development and progression through the JAK–STAT3 signaling pathway by targeting SOCS3
Authors: Huang Shan , Zhou Da , Li Yu‐Xuan , Ming Zhi‐Yong , Li Ke‐Zhi , Wu Guo‐Bin , Chen Chuang , Zhao Yin‐Nong
Published: October 2018

Hepatocellular carcinoma (HCC), as the third leading cancer‐caused deaths, prevails with high mortality, and affects more than half a million individuals per year worldwide. A former study revealed that microRNA‐221 (miR‐221) was involved in cell proliferation of liver cancer and HCC development. The current study aims to evaluate whether miR‐221 targeting SOCS3 affects HCC through JAK–STAT3 signaling pathway. A series of miR‐221 mimic, miR‐221 inhibitor, siRNA against SOCS3, and SOCS3 plasmids were introduced to SMMC7721 cells with the highest miR‐221 expression assessed. The expression of JAK–STAT3 signaling pathway–related genes and proteins was determined by Western blot analysis. Cell apoptosis, viability, migration, and invasion were evaluated by means of flow cytometry, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide, and transwell assays, respectively. HCC xenograft in nude mice was performed to measure HCC tumor growth. miR‐221 was found to be highly expressed but SOCS3 was poorly expressed in HCC tissues. miR‐221 expression was correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) of HCC, and SOCS3 expression was correlated with LNM, differentiation and TNM of HCC. SOCS3 is a target gene of miR‐221. MiR‐221 mimic or si‐SOCS3 exposure was found to induce cell viability, migration, and invasion, and reduce apoptosis. MiR‐221 inhibitor was observed to have inhibitory effects on HCC cell proliferation, migration, and invasion. Moreover, the expression of JAK–STAT3 signaling pathway was suppressed by miR‐221 inhibitor. Downregulated miR‐221 expression could promote its target gene SOCS3 to inhibit the proliferation, invasion and migration of HCC cells by repressing JAK–STAT3 signaling pathway.
ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection
Authors: Liu Yanyan , Zhu Jingyu , Ma Xiaoli , Han Shuyi , Xiao Dongjie , Jia Yanfei , Wang Yunshan
Published: October 2018

Gastric cancer (GC) is a lethal disease, and among its variety of etiological factors, Helicobacter pylori (H. pylori) infection is the strongest risk factor. However, the genetic and molecular mechanisms underlying H. pylori‐related GC need further elucidation. We investigated the competing endogenous RNA (ceRNA) network differences between H. pylori (+) and H. pylori (−) GC. The long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression data from 32 adjacent noncancerous samples and 18 H. pylori (+) and 141 H. pylori (−) stomach adenocarcinoma samples were downloaded from the TCGA database. After construction of lncRNA–miRNA–mRNA ceRNA networks of H. pylori (+) and H. pylori (−) GC, Panther and Kobas databases were used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, survival analysis was used to discover the key genes. In H. pylori (+) GC, we identified a total of 1,419 lncRNAs, 82 miRNAs, and 2,501 mRNAs with differentially expressed profiles. In H. pylori (−) GC, 2,225 lncRNAs, 130 miRNAs, and 3,146 mRNAs were differentially expressed. Furthermore, three unique pathways (cytokine–cytokine receptor interaction, HIF‐1 signaling pathway, and Wnt signaling pathway) were enriched in H. pylori (+) GC. According to the overall survival analysis, three lncRNAs (AP002478.1, LINC00111, and LINC00313) and two mRNAs (MYB and COL1A1) functioned as prognostic biomarkers for patients with H. pylori (+) GC. In conclusion, our study has identified the differences in ceRNA regulatory networks between H. pylori (+) and H. pylori (−) GC and provides a rich candidate reservoir for future studies.
Fibroblast growth factor‐2 inhibits CD40‐mediated periodontal inflammation
Authors: Fujihara Chiharu , Kanai Yu , Masumoto Risa , Kitagaki Jirouta , Matsumoto Masahiro , Yamada Satoru , Kajikawa Tetsuhiro , Murakami Shinya
Published: October 2018

Fibroblast growth factor‐2 (FGF‐2) stimulates periodontal regeneration by a broad spectrum of effects on periodontal ligament (PDL) cells, such as proliferation, migration, and production of extracellular matrix. A critical factor in the success of periodontal regeneration is the rapid resolution of inflammatory responses in the tissue. We explored an anti‐inflammatory effect of FGF‐2 during periodontal regeneration and healing. We found that FGF‐2 on mouse periodontal ligament cells (MPDL22) markedly downregulated CD40 expression, a key player of inflammation. In addition, FGF‐2 inhibited CD40 signaling by the non‐canonical nuclear factor‐kappa B2 (NFκB2) pathway, resulting in decreased production of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α), which have the potential to recruit immune cells to inflamed sites. Furthermore, in vivo treatment of FGF‐2 enhanced healing of skin wounds by counteracting the CD40‐mediated inflammation. These results reveal that FGF‐2 has an important function as a negative regulator of inflammation during periodontal regeneration and healing.
Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the NLRP3 inflammasomes
Authors: Shirasuna Koumei , Karasawa Tadayoshi , Takahashi Masafumi
Published: October 2018

Inflammasome mechanisms are involved as some of the pathways of sterile inflammation. Inflammasomes are large multiprotein complexes in the cytosol and are a key system for the production of the pivotal inflammatory cytokines, interleukin (IL)‐1β and IL‐18, and inflammatory cell death called pyroptosis. Although a number of inflammasomes have been described, the nucleotide‐binding oligomerization domain‐, leucine‐rich repeat‐, and pyrin domain‐containing 3 (NLRP3) is the most extensively investigated inflammasome. Exogenous pathogen‐associated molecular patterns released during infection and endogenous crystalline danger/damage‐associated molecular patterns (DAMPs) are well‐known activators of NLRP3 inflammasomes. In addition, nanoparticle‐associated molecular patterns (NAMPs), which are mediated by synthetic materials, including nanomaterials and nanoparticles, are proposed to be new danger signals of NLRP3 inflammasomes. Importantly, NAMP‐ and DAMP‐triggered inflammation, a defining characteristic in inflammatory diseases, is termed as sterile inflammation because it occurs in the absence of foreign pathogens. This review focuses on the role of inflammasomes in exogenous NAMP‐ and endogenous crystalline DAMP‐mediated sterile inflammation. Moreover, many regulatory mechanisms have been identified to attenuate NLRP3 inflammasomes. Therefore, we also summarize endogenous negative regulators of NLRP3 inflammasome activation, particularly induced by NAMPs or crystalline DAMPs.
Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR‐136/SH2B1 axis
Authors: Jin Canhui , Wang Aihong , Liu Linbo , Wang Gongping , Li Guangshuai
Published: October 2018

Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. Currently, an increasing evidence showed that circular RNAs (circRNAs) play important roles in tumor progression. However, the effects and underlying mechanisms of circRNAs in CRC progression remain unclear. In the present study, through circRNA high‐throughput sequencing and quantitative real‐time polymerase chain reaction, we identified that hsa_circ_0136666 was significantly overexpressed in CRC tissues and cell lines. High hsa_circ_0136666 expression was associated with poor overall survival of patients with CRC. In vitro function assays showed that hsa_circ_0136666 inhibition suppressed CRC cell proliferation, migration, invasion, and arrested CRC cells in the G0/G1 phase. Furthermore, we showed that hsa_circ_0136666 inhibition reduced CRC cell growth in vivo. Mechanistically, we revealed that hsa_circ_0136666 could increase SH2B1 expression via competitively binding miR‐136 in CRC cells. In addition, SH2B1 overexpression could reverse the effects of hsa_circ_0136666 inhibition on CRC cell progression. In conclusion, our data suggested that hsa_circ_0136666 could promote CRC cell progression via the miR‐136/SH2B1 axis, elucidating a novel approach to improve the effectiveness of CRC treatment.
Characterizing the multiple roles of FGF‐2 in SOD1G93A ALS mice in vivo and in vitro
Authors: Kefalakes Ekaterini , Böselt Sebastian , Sarikidi Anastasia , Ettcheto Miren , Bursch Franziska , Naujock Maximilian , Stanslowsky Nancy , Schmuck Martin , Barenys Marta , Wegner Florian , Grothe Claudia , Petri Susanne
Published: October 2018

We have previously shown that knockout of fibroblast growth factor‐2 (FGF‐2) and potential compensatory effects of other growth factors result in amelioration of disease symptoms in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive neurological disorder leading to degeneration of cortical, brain stem, and spinal motor neurons followed by subsequent denervation and muscle wasting. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for approximately 20% of familial ALS cases and SOD1 mutant mice still are among the models best mimicking clinical and neuropathological characteristics of ALS. The aim of the present study was a thorough characterization of FGF‐2 and other growth factors and signaling effectors in vivo in the SOD1G93A mouse model. We observed tissue‐specific opposing gene regulation of FGF‐2 and overall dysregulation of other growth factors, which in the gastrocnemius muscle was associated with reduced downstream extracellular‐signal‐regulated kinases (ERK) and protein kinase B (AKT) activation. To further investigate whether the effects of FGF‐2 on motor neuron death are mediated by glial cells, astrocytes lacking FGF‐2 were cocultured together with mutant SOD1
G93A motor neurons. FGF‐2 had an impact on motor neuron maturation indicating that astrocytic FGF‐2 affects motor neurons at a developmental stage. Moreover, neuronal gene expression patterns showed FGF‐2‐ and SOD1
G93A‐dependent changes in ciliary neurotrophic factor, glial‐cell‐line‐derived neurotrophic factor, and ERK2, implying a potential involvement in ALS pathogenesis before the onset of clinical symptoms.
Hepcidin and iron regulatory proteins coordinately regulate ferroportin 1 expression in the brain of mice
Authors: Wang Lan , Liu Xiaopeng , You Lin‐Hao , Ci Yun‐Zhe , Chang Shiyang , Yu Peng , Gao Guofen , Chang Yan‐Zhong
Published: October 2018

Iron plays an essential role in various cellular metabolic processes of the body. Maintenance of cellular iron homeostasis is particularly important for keeping the normal functions of the cells. Ferroportin 1 (FPN1) is the currently only known iron exporter on the cell membrane. It has been indicated that the regulation of FPN1 in response to the alteration of iron level mainly involves two processes, posttranscriptional repression by iron regulatory proteins (IRPs) and posttranslational degradation by hepcidin, the major iron‐sensing hormone. However, whether there is any communication between the two types of regulations or which one plays dominant role has not been reported. In our study with IRP2−/− mice, we found that knockout of IRP2 increased FPN1 expression in the cerebral cortex of IRP2−/− mice, whereas the upregulation of FPN1 was more significant in IRP1/IRP2 dual knockdown fibroblasts. Interestingly, we found that the knockout of IRP2 severely affected the regulation effect of hepcidin on FPN1 in mouse brain. FPN1 level decreased dramatically in the brain of wild‐type mice injected with hepcidin, but it did not decrease much in IRP2 knockout mice. Further investigation disclosed that the compromised hepcidin–FPN1 regulation in IRP2−/− cells was directly dependent on the existence of iron‐responsive element (IRE) in FPN1 messenger RNA. These results indicate that IRPs and hepcidin coordinately regulate the FPN1 level in mice. This study will provide a more comprehensive understanding of the regulatory mechanisms of FPN1 expression.
Matrine is a novel inhibitor of the TMEM16A chloride channel with antilung adenocarcinoma effects
Authors: Guo Shuai , Chen Yafei , Pang Chunli , Wang Xuzhao , Shi Sai , Zhang Hailin , An Hailong , Zhan Yong
Published: October 2018

Calcium‐activated chloride channels (CaCCs) are ion channels with key roles in physiological processes. They are abnormally expressed in various cancers, including esophageal squamous cell cancer, head and neck squamous cell carcinoma, colorectal cancer, and gastrointestinal stromal tumors. The CaCC component TMEM16A/ANO1 was recently shown to be overexpressed in lung adenocarcinoma cells and may serve as a tumorigenic protein. In this study, we determined that matrine is a potent TMEM16A inhibitor that exerts anti‐lung adenocarcinoma effects. Patch clamp experiments showed that matrine inhibited TMEM16A current in a concentration‐dependent manner with an IC
50 of 27.94 ± 4.78 μM. Molecular simulation and site‐directed mutation experiments demonstrated that the matrine‐sensitive sites of the TMEM16A channel involve the amino acids Y355, F411, and F415. Results of cell viability and wound healing assays showed that matrine significantly inhibited the proliferation and migration of LA795 cells, which exhibit high TMEM16A expression. In contrast, matrine has only weak inhibitory effect on CCD‐19Lu and HeLa cells lacking TMEM16A expression. Matrine‐induced effects on the proliferation and migration of LA795 cells were abrogated upon shRNA‐mediated TMEM16A knockdown in LA795 cells. Finally, in vivo experiments demonstrated that matrine dramatically inhibited the growth of lung adenocarcinoma xenograft tumors in mice but did not affect mouse body weight. Collectively, these data indicate that matrine is an effective and safe TMEM16A inhibitor and that TMEM16A is the target of matrine anti‐lung adenocarcinoma activity. These findings provide new insight for the development of novel treatments for lung adenocarcinoma.
Combinatorial screening algorithm to engineer multiepitope subunit vaccine targeting human T‐lymphotropic virus‐1 infection
Authors: Pandey Rajan K. , Ojha Rupal , Chatterjee Nina , Upadhyay Nitesh , Mishra Amit , Prajapati Vijay K.
Published: October 2018

Human T‐lymphotropic virus (HTLV), the first human retrovirus has been discovered which is known to cause the age‐old assassinating disease HTLV‐1 associated myelopathy. Cancer caused by this virus is adult T cell leukemia/lymphoma which targets 10–20 million throughout the world. The effect of this virus extends to the fact that it causes chronic disease to the spinal cord resulting in loss of sensation and further causes blood cancer. So, to overcome the complications, we designed a subunit vaccine by the assimilation of B‐cell, cytotoxic T‐lymphocyte , and helper T‐lymphocyte epitopes. The epitopes were joined together along with adjuvant and linkers and a vaccine was fabricated which was further subjected to 3D modeling. The physiochemical properties, allergenicity, and antigenicity were evaluated. Molecular docking and dynamics were performed with the obtained 3D model against toll like receptor (TLR‐3) immune receptor. Lastly, in silico cloning was performed to ensure the expression of the designed vaccine in pET28a(+) expression vector. The future prospects of the study entailed the in vitro and in vivo experimental analysis for evaluating the immune response of the designed vaccine construct.
Emerging roles of noncoding RNAs in multiple myeloma: A review
Authors: Yang Qian , Shen Xianjuan , Su Zhangyao , Ju Shaoqing
Published: October 2018

Multiple myeloma (MM) is a hematologic malignancy characterized by unrestricted secretion of monoclonal immunoglobulin and uncontrolled plasma cell proliferation. Extra‐medullary infiltration and drug resistance are two major obstacles in the treatment of MM. To solve these problems, it is necessary to elucidate the underlying pathological mechanisms and find new therapeutic targets. Noncoding RNAs (ncRNAs), which were once considered “transcriptional noise,” have been recognized as crucial regulators in the process of tumorigenesis including MM. Increasing evidence has shown that ncRNAs participate in MM pathogenesis via a series of complex cellular or extracellular processes. This review article summarizes examples of ncRNAs involved in myelosis and discusses their potential as biomarkers and therapeutic targets in the diagnosis and treatment of myelosis.
Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT‐mediated PF
Authors: Qu Jiao , Zhang Zhihui , Zhang Panpan , Zheng Cheng , Zhou Wencheng , Cui Wenhui , Xu Liang , Gao Jian
Published: October 2018

Epithelial–mesenchymal transition (EMT) is considered to be the key event in the formation of pulmonary fibrosis (PF). High‐mobility group box 1 (HMGB1) is a novel mediator of EMT. Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a critical transcription factor for protecting against PF. However, it is unknown the relationship between Nrf2 and HMGB1 in EMT‐mediated PF. Bleomycin (BLM)‐induced PF in Nrf2‐knockout (Nrf2−/−) and wild‐type (WT) mice and transforming growth factor β1 (TGF‐β1)‐induced EMT in rat type II alveolar epithelial cell line (RLE‐6TN) and human alveolar epithelial cell line (A549) were established to observe the relationship among Nrf2, HMGB1, and EMT by western blot and immunohistochemistry. BLM‐induced EMT was more severe and the expression of HMGB1 was more increased in Nrf2
−/− mice compared with WT mice. In vitro, Nrf2 activation attenuated TGF‐β1‐induced EMT and ROS production accompanied by the downregulation of HMGB1. In contrast, silencing Nrf2 enhanced TGF‐β1‐induced EMT and ROS production along with increased the protein expression and the release of HMGB1. Moreover, HMGB1 activation aggravated TGF‐β1‐induced EMT and HMGB1 deficiency alleviated TGF‐β1‐induced EMT. Furthermore, HMGB1 silence attenuated the protective effect of Nrf2 on EMT. These findings suggest downregulation of HMGB1, which is required for the protective role of Nrf2 in EMT‐mediated PF and provide an important therapeutic target for PF.
Potential biomarkers for heart failure
Authors: Wang Che , Yang Honghui , Gao Chuanyu
Published: October 2018

In this study, we identified candidate biomarkers for heart failure (HF). The gene expression profile GSE57338, containing 117 ischemic cardiomyopathic HF and 136 control samples, was downloaded and analyzed using various bioinformatics approaches. In total, 376 differentially expressed genes (DEGs) were identified, and four modules were explored in protein–protein interaction networks. DEGs (including ankyrin repeat and SOCS box‐containing 14 [ASB14]) in the modules were mainly categorized by the function. Several relationships including interferon regulatory factor 1 (IRF1)‐C‐C motif chemokine ligand 5 (CCL5) were revealed in the transcription factor microRNA target gene regulatory network. Gene–drug analysis revealed 11 DEGs (such as the cluster of differentiation 163 [CD163]) for the target drugs. Data verification analysis identified 118 overlapping DEGs including ASB14, CD163, and CCL5. ASB14 may be involved in HF progression via protein ubiquitination and CCL5 may be involved in HF via the IRF1‐CCL5 interaction. Genes including CD163 are potential biomarkers for HF.
Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism
Authors: Gong Xiaoyuan , Li Gaoming , Huang Yang , Fu Zhenlan , Song Xiongbo , Chen Cheng , Yang Liu
Published: October 2018

Ca2+ has been recognized as a key molecule for chondrocytes, however, the role and mechanism of spontaneous [Ca
2+]
i signaling in cartilaginous extracellular matrix (ECM) metabolism regulation are unclear. Here we found that spontaneous Ca
2+ signal of in‐situ porcine chondrocytes was [Ca
2+]
o dependent, and mediated by [Ca
2+]
i store release. T‐type voltage‐dependent calcium channel (T‐VDCC) mediated [Ca
2+]
o influx was associated with decreased cell viability and expression levels of ECM deposition genes. Further analysis revealed that chondrocytes expressed both inositol 1,4,5‐trisphosphate receptor (InsP3R) and Orai isoforms. Inhibition of endoplasmic reticulum (ER) Ca
2+ release and store‐operated calcium entry significantly abolished spontaneous [Ca
2+]
i signaling of in‐situ chondrocytes. Moreover, blocking ER Ca
2+ release with InsP3R inhibitors significantly upregulated ECM degradation enzymes production, and was accompanied by decreased proteoglycan and collagen type II intensity. Taken together, our data provided evidence that spontaneous [Ca
2+]
i signaling of in‐situ porcine chondrocytes was tightly regulated by [Ca
2+]
o influx, InsP3Rs mediated [Ca
2+]
i store release, and Orais mediated calcium release‐activated calcium channels activation. Both T‐VDCC mediated [Ca
2+]
o influx and InsP3Rs mediated ER Ca
2+ release were found crucial to cartilaginous ECM metabolism through distinct regulatory mechanisms.
Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane‐induced lupus mice model
Authors: Khorasani Sahar , Mahmoudi Mahmoud , Kalantari Mahmoud Reza , Lavi Arab Fahimeh , Esmaeili Seyed‐Alireza , Mardani Fatemeh , Tabasi Nafiseh , Rastin Maryam
Published: October 2018

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane‐induced lupus mice model. Fifty‐four female BALB/c mice (3–5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE‐induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble‐stranded DNA (anti‐dsDNA), antiribonucleoprotein (anti‐RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL‐6), IL‐10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti‐dsDNA, and anti‐RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti‐dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL‐6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE‐induced mice.
Targeting phosphoinositide‐3‐kinase pathway in biliary tract cancers: A remedial route?
Authors: Kaavya Jayaramayya , Mahalaxmi Iyer , Devi Subramaniam Mohana , Santhy K. S. , Balachandar Vellingiri
Published: October 2018

Biliary tract cancers (BTC) are aggressive tumours with a low survival rate. At the advent of the genomic era, various genetic mutations in cell signalling pathways have been incriminated in carcinogenesis. Genomic analysis studies have connected main components of the phosphoinositide‐3‐kinase (PI3K) signalling pathway to BTC. PI3K pathway playing a central role in cell signalling and being deregulated in various tumours has been studied as a target for chemotherapy. Novel compounds have also been identified in preclinical trials that specifically target the PI3K pathway in BTCs, but these studies have not accelerated to clinical use. These novel compounds can be examined in upcoming studies to validate them as potential therapeutic agents, as further research is required to combat the growing need for adjuvant chemotherapy to successfully battle this tumour type. Furthermore, these molecules could also be used along with gemcitabine, cisplatin and 5‐fluorouracil to improve sensitivity of the tumour tissue to chemotherapy. This review focuses on the basics of PI3K signalling, genetic alterations of this pathway in BTCs and current advancement in targeting this pathway in BTCs. It emphasizes the need for gene‐based drug screening in BTC. It may reveal various novel targets and drugs for amelioration of survival in patients with BTC and serve as a stepping stone for further research.
Altered expression patterns of circular RNAs between implantation sites and interimplantation sites in early pregnant mice
Authors: Zhang Shuang , Ding Yubin , He Junlin , Zhang Juanjuan , Liu Xueqing , Chen Xuemei , Su Yan , Wang Yingxiong , Gao Rufei
Published: October 2018

Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have been found to play important roles in regulating gene expression and participate in several biological processes. However, their specific roles in embryo implantation remain unclear. This study aims to investigate the roles of circRNAs in embryo implantation. In the current study, we screened the expression profiles of circRNAs between implantation sites and interimplantation sites in the endometrial tissue of early pregnant mice on Day 5 using microarray assay. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) of four dysregulated circRNAs was performed to validate the microarray results. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and circRNA–microRNA (miRNA)–messenger RNA (mRNA) negative correlation network analyses were performed. The microarray results showed 101 upregulated and 75 downregulated circRNAs (fold change [FC] ≥ 1.5 and p value < 0.05) at implantation sites compared with interimplantation sites. Four randomly selected circRNAs were successfully verified by qRT‐PCR. The GO and KEGG analyses revealed some meaningful terms. Moreover, based on circRNAs microarray data and the miRNA and mRNA high‐throughput data previously published by our groups, differently expressed circRNAs, miRNAs, and mRNAs were performed to conjoint analysis. Then circRNA–miRNA–mRNA negative correlation networks were constructed and 21 downregulated circRNAs, 14 upregulated miRNAs, and 79 downregulated mRNAs were involved in the networks. The findings of this study may provide a novel perspective on circRNAs and lay a foundation for future research into the potential roles of circRNAs in embryo implantation.
Modeling of gas pipeline in order to implement a leakage detection system using artificial neural networks based on instrumentation
Authors: Rahmati Mohsen
Published: October 2018

In this paper, by using of gas flow pattern, a novel neural network‐based fault detection method is presented to detect the leakage in the gas pipeline. The pipe is divided into four segments, and each segment is modeled by using input/output pressure of the gas flow. For this purpose, the acquired practical data from the real life gas pipeline are gathered and utilized for training a neural network to model the process. Some of the data are used for training set to adjust the neural network weights, and others are used to evaluate the performance of the neural network‐based fault detection system. Gathered practical data from a real life pipeline made sure that the proposed method is prominent and applicable for practical implementations. The model was verified with the data obtained from the test in the actual pipeline and compared with leakage mode.
On contributions by wind‐induced mixing and eddy pumping to interannual chlorophyll variability during different ENSO phases in the northern South China Sea
Authors: Xiu Peng , Dai Minhan , Chai Fei , Zhou Kuanbo , Zeng Lili , Du Chuanjun
Published: October 2018

The chlorophyll in the northern South China Sea (NSCS) shows strong interannual variability between different phases of the El Niño‐Southern Oscillation (ENSO), primarily due to the influence from Kuroshio intrusion. Chlorophyll observations also reveal that significant year‐to‐year variation remains in the same ENSO phase, but its controlling mechanism is unknown. In this study, we examined driving mechanisms for such regional ecosystem variability on a year‐to‐year timescale. Using observational data and modeling results, we found that both cyclonic eddies (CEs) and wind‐induced mixing affect phytoplankton variability, but the former is the dominant factor regulating the interannual variability of chlorophyll during La Niña years, while the latter becomes the dominant one during El Niño years. The underlying mechanisms leading to the contrast in biological responses are attributable to changes in background nutricline depth and mixed‐layer depth (MLD) during different ENSO phases. During La Niña, both thermocline and nutricline are deepened in the NSCS. Thus, wind mixing is less effective in non‐eddy areas due to the deepened nutricline, while the CE‐induced subsurface nutrient anomaly associated with increased MLD is able to control the interannual variability of chlorophyll. During El Niño, wind‐induced mixing is more effective than CEs because the surface wind can influence a larger area.
Comparative genomics of the Komagataeibacter strains—Efficient bionanocellulose producers
Authors: Ryngajłło Małgorzata , Kubiak Katarzyna , Jędrzejczak‐Krzepkowska Marzena , Jacek Paulina , Bielecki Stanisław
Published: October 2018

Komagataeibacter species are well‐recognized bionanocellulose (BNC) producers. This bacterial genus, formerly assigned to Gluconacetobacter, is known for its phenotypic diversity manifested by strain‐dependent carbon source preference, BNC production rate, pellicle structure, and strain stability. Here, we performed a comparative study of nineteen Komagataeibacter genomes, three of which were newly contributed in this work. We defined the core genome of the genus, clarified phylogenetic relationships among strains, and provided genetic evidence for the distinction between the two major clades, the K. xylinus and the K. hansenii. We found genomic traits, which likely contribute to the phenotypic diversity between the Komagataeibacter strains. These features include genome flexibility, carbohydrate uptake and regulation of its metabolism, exopolysaccharides synthesis, and the c‐di‐GMP signaling network. In addition, this work provides a comprehensive functional annotation of carbohydrate metabolism pathways, such as those related to glucose, glycerol, acetan, levan, and cellulose. Findings of this multi‐genomic study expand understanding of the genetic variation within the Komagataeibacter genus and facilitate exploiting of its full potential for bionanocellulose production at the industrial scale.
The role of the hypoxia‐Nrp‐1 axis in the activation of M2‐like tumor‐associated macrophages in the tumor microenvironment of cervical cancer
Authors: Chen Xiao‐Jing , Wu Sha , Yan Rui‐Ming , Fan Liang‐Sheng , Yu Lan , Zhang Yan‐Mei , Wei Wen‐Fei , Zhou Chen‐Fei , Wu Xiang‐Guang , Zhong Mei , Yu Yan‐Hong , Liang Li , Wang Wei
Published: October 2018

To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor‐associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 polarization of macrophages. Immunofluorescence, western blot and qRT‐PCR were performed to detect the expression of neuropilin‐1 (Nrp‐1) and carbonic anhydrase IX (CAIX). An intermittent hypobaric hypoxia (IH) animal model was established to evaluate the role of hypoxia in activating M2‐like TAMs in vivo. We also used immunohistochemistry to analyze the association between CAIX, CD163+ macrophages and Nrp‐1 in a series of 72 human cervical cancer specimens. We found that the hypoxic cervical TME educated the recruited macrophages to transform into the M2 phenotype. Nrp‐1 expression was significantly increased in hypoxia‐primed cervical cancer cells. Blocking Nrp‐1 expression prevented hypoxic cells from recruiting and polarizing macrophages towards the M2 phenotype. Hypoxia exposure significantly increased the expression of Nrp‐1 as well as the infiltration of macrophages in vivo. Consistently, immunochemical staining in serial tissue sections of cervical cancer revealed upregulated levels of Nrp‐1 in CAIX‐positive hypoxic regions along with a concurrent significant elevation of M2 macrophages. Nrp‐1 and M2‐like TAMs were related to the malignant properties of cervical cancer, such as the FIGO stage and lymph node metastasis. Nrp‐1 plays critical roles in hypoxic TME‐induced activation and pro‐tumoral effects of TAMs in cervical cancer. Interfering with Nrp‐1 may be a potential therapeutic strategy in treating cervical cancer.
A new kind of nonlocal symmetry for the μ‐Camassa‐Holm equation with linear dispersion
Authors: Shi Zhenhua , Du Jingjing
Published: October 2018

The μ‐Camassa‐Holm equation with linear dispersion is a completely integrable model. In this paper, it is shown that this equation has quadratic pseudo‐potentials that allow us to construct pseudo‐potential–type nonlocal symmetries. As an application, we obtain its recursion operator by using this kind of nonlocal symmetry, and we construct a Darboux transformation for the μ‐Camassa‐Holm equation.
Site‐specific alert criteria to detect patient‐related errors with 3D EPID transit dosimetry
Authors: Olaciregui‐Ruiz Igor , Rozendaal Roel , Mijnheer Ben , Mans Anton
Published: October 2018

Purpose

To assess the sensitivity of various EPID dosimetry alert indicators to patient‐related variations and to determine alert threshold values that ensure excellent error detectability.

Methods

Our virtual dose reconstruction method uses in air EPID measurements to calculate virtual 3D dose distributions within a CT data set. Patient errors are introduced by transforming the plan‐CT into an error‐CT data set. Virtual patient dose distributions reconstructed using the plan‐CT and the error‐CT data set are compared to the planned dose distributions by γ(3%/3 mm) and DVH analysis using seven indicators: ΔDISOC, γ‐mean, near γ‐max, γ‐pass rate, ΔPTVD2, ΔPTVD50, and ΔPTVD98. Translation and rotation patient setup errors and uniform contour changes are studied for 104 VMAT plans of 4 treatment sites. Lung expansions and contractions to simulate changes in lung density are considered for 26 IMRT lung plans. A ROC curve is generated for each combination of error and indicator. For each ROC curve, the AUC value and the optimal alert threshold value of the indicator are determined.

Results

AUC values for γ‐indicators and ΔPTVD2 are consistently higher than for ΔDISOC and ΔPTVD98. For VMAT plans, error detectability to patient position shifts is worse for pelvic treatments and best for head‐and‐neck and brain plans. Excellent detectability is observed for 5 mm translations in head‐and‐neck plans (AUC = 0.94) and for 4° rotations in brain plans (AUC = 0.89). All sites but prostate show good‐to‐excellent detectability (AUC > 0.8) for 10 mm translations and 8° rotations and excellent detectability (AUC > 0.9) for ±6 mm patient contour changes. For head‐and‐neck, excellent detectability is obtained with γ‐mean and γ‐pass rate threshold values of around 0.63 and 83%, respectively. For brain and rectum, these threshold values are 0.53 and 90%, respectively. In IMRT lung plans, expansions of 3 mm and contractions of 6 mm are detected (AUC > 0.8).

Conclusions

By combining virtual dose reconstructions with synthetic patient data, we developed a framework to assess the sensitivity of our 3D EPID transit dosimetry method to patient‐related variations. The detectability of each introduced error is specific to the treatment site and indicator used. Optimal alert criteria can be determined to ensure excellent detectability for each combination of error type and indicator. The alert threshold values and the magnitude of the error that can be detected are site‐specific. In situations where the minimum error that can be detected is larger than the clinically desirable action level, EPID transit dosimetry must be used in combination with IGRT procedures to ensure correct patient positioning and early detection of anatomy variations.
Whole‐heart coronary MR angiography using a 3D cones phyllotaxis trajectory
Authors: Malavé Mario O. , Baron Corey A. , Addy Nii Okai , Cheng Joseph Y. , Yang Phillip C. , Hu Bob S. , Nishimura Dwight G.
Published: October 2018

Purpose

To develop a 3D cones steady‐state free precession sequence with improved robustness to respiratory motion while mitigating eddy current artifacts for free‐breathing whole‐heart coronary magnetic resonance angiography.

Method

The proposed sequence collects cone interleaves using a phyllotaxis pattern, which allows for more distributed k‐space sampling for each heartbeat compared to a typical sequential collection pattern. A Fibonacci number of segments is chosen to minimize eddy current effects with the trade‐off of an increased number of acquisition heartbeats. For verification, phyllotaxis‐cones is compared to sequential‐cones through simulations, phantom studies, and in vivo coronary scans with 8 subjects using 2D image‐based navigators for retrospective motion correction.

Results

Simulated point spread functions and moving phantom results show less coherent motion artifacts for phyllotaxis‐cones compared to sequential‐cones. Assessment of the right and left coronary arteries using reader scores and the image edge profile acutance vessel sharpness metric indicate superior image quality and sharpness for phyllotaxis‐cones.

Conclusion

Phyllotaxis 3D cones results in improved qualitative image scores and coronary vessel sharpness for free‐breathing whole‐heart coronary magnetic resonance angiography compared to standard sequential ordering when using a steady‐state free precession sequence.
Segmented radial cardiac MRI during arrhythmia using retrospective electrocardiogram and respiratory gating
Authors: Chava Raghuram , Assis Fabrizio , Herzka Daniel , Kolandaivelu Aravindan
Published: October 2018

Purpose

To improve segmented cardiac MRI image quality during arrhythmia.

Methods

 Electrocardiogram (ECG) and respiratory waveforms were recorded during imaging. Imaging readouts were retrospectively classified into heartbeat‐types based on the RR interval of the current and preceding beats, QRS morphology, and respiratory phase. Image data were sorted by these classifiers to generate separate cine images of different heartbeat‐types during sinus rhythm and arrhythmia. A simulation study evaluated the efficiency of K‐space sampling over a range of heart rhythms, heart rates, and respiratory rates. In vivo imaging was performed in volunteers with sinus rhythm, swine with arrhythmia simulated by pacing, and a human subject with spontaneous premature beats.

Results

 K‐space sampling uniformity and image quality incrementally improve with additional occurrences of the desired normal sinus or arrhythmia heartbeat‐type. To approach the image quality of breath‐hold imaging, sufficiently restrictive gating parameters are required. Compared with real‐time imaging, retrospective gated images had reduced noise and improved sharpness while maintaining desired cine temporal resolution. Variations of cardiac function between arrhythmia heartbeats could be observed in arrhythmia imaging cases that are not captured by conventional segmented imaging.

Conclusion

Retrospective ECG and respiratory gating permits imaging of various heartbeats during arrhythmia with fewer resolution restrictions compared to real‐time imaging. For a fixed imaging time, imaging quality depends on frequency of the imaged heartbeat‐type. Imaging additional heartbeats permits incremental improvement in image quality.
A parallel time integrator for solving the linearized shallow water equations on the rotating sphere
Authors: Schreiber Martin , Loft Richard
Published: October 2018

With the stagnation of processor core performance, further reductions in the time to solution for geophysical fluid problems are becoming increasingly difficult with standard time integrators. Parallel‐in‐time exposes and exploits additional parallelism in the time dimension, which is inherently sequential in traditional methods. The rational approximation of exponential integrators (REXI) method allows taking arbitrarily long time steps based on a sum over a number of decoupled complex PDEs that can be solved independently massively parallel. Hence, REXI is assumed to be well suited for modern massively parallel super computers, which are currently trending. To date, the study and development of the REXI approach have been limited to linearized problems on the periodic two‐dimensional plane. This work extends the REXI time stepping method to the linear shallow‐water equations on the rotating sphere, thus moving the method one step closer to solving fully nonlinear fluid problems of geophysical interest on the sphere. The rotating sphere poses particular challenges for finding an efficient solver due to the zonal dependence of the Coriolis term. Here, we present an efficient REXI solver based on spherical harmonics, showing the results of a geostrophic balance test, a comparison with alternative time stepping methods, an analysis of dispersion relations indicating superior properties of REXI, and finally, a performance comparison on the Cheyenne supercomputer. Our results indicate that REXI not only can take larger time steps but also can be used to gain higher accuracy and significantly reduced time to solution compared with currently existing time stepping methods.
Inverse optimal control for unmanned aerial helicopters with disturbances
Authors: Ma Haoxiang , Chen Mou , Wu Qingxian
Published: October 2018

This paper proposes an optimal control method of an unmanned aerial helicopter (UAH) with unknown disturbances. Solving the Hamilton‐Jacobi‐Bellman (HJB) equation is considered as the common approach to design an optimal controller under a meaningful cost function when facing the nonlinear optimal control problem. However, the HJB equation is hard to solve even for a simple problem. The inverse optimal control method that avoids the difficulties of solving the HJB equation has been adopted. In this inverse optimal control approach, a stabilizing optimal control law and a particular cost function that are obtained by a control Lyapunov function are required. An integrator backstepping method is used in designing the optimal control law of the UAH. Furthermore, a disturbance‐observer–based control (DOBC) approach has been adopted in the optimal control law for dealing with the unknown disturbances of the UAH system. Simulation results have been given to certify the stability of the nonlinear UAH system and the validity of this developed control method.
Plasma treatment of polymer powders – from laboratory research to industrial application
Authors: Arpagaus Cordin , Oberbossel Gina , Rudolf von Rohr Philipp
Published: October 2018

This review provides a comprehensive overview of scientific research on plasma treatment of polymer powders over the last 40 years. The current state of the art is described with special focus on basic research in the laboratory and commercially available technologies in industrial applications. Different reactor systems with low‐pressure and atmospheric pressure plasma are presented. Then, numerous application examples of plasma‐treated polymer powders are presented together with a brief overview of the experimental test results. Furthermore, the effects of the process parameters on the final properties of the polymer powders are discussed. Attempts are made to determine similarity parameters and correlations between the generated surface functionalities. Finally, some suggestions for future research are given.