bluuebunny/crossref_metadata_2025 huggingface dataset:
Zishenwan Decreases Kidney Damage in Recurrent Urinary Tract Infection through the Inhibition of Toll‐Like Receptor 4 Signal
Authors: Liang Guoqiang , Tang Hua , Ni Daolei , Ren Yan , Zhang Chenxi , Zheng Wenyi , Song Yongliang , Shen Xiaofeng , Jin Weimin , Jiang Chunbo
Published: November 2018

Objectives. To investigate the mechanism of the protective effect of Zishenwan on pyelonephritis rats. Methods. In the rat model of pyelonephritis, protective effects of Zishenwan, the content of secretory immunoglobulin A (SIg A), and interleukins were detected by ELISA. The expressions of TLR4‐NFκB pathway were detected by Western blot in renal and urinary tract mucosa. The protective effect and influence on TLR4‐NFκB pathway of Zishenwan were studied. Results. Zishenwan protected rats from pyelonephritis which related to the increase of SIgA, the regulation of interleukins, and the inhibition of TLR4‐NFκB pathway. Serum containing Zishenwan can significantly decrease LPS‐induced expression of TLR4, MyD88, and NFκB in vitro. And the inhibition of TLR4 signal by Zishenwan related to the degradation of TRAF3 and TRAF6. Conclusions. Zishenwan protected rats from urinary tract infection by clearance of bacteria and decrease of tissue damage. 20S proteasomes mediated the degradation of TRAF3 which is important to the decrease of tissue damage from Zishenwan.
An Interval‐Valued Pythagorean Fuzzy Compromise Approach with Correlation‐Based Closeness Indices for Multiple‐Criteria Decision Analysis of Bridge Construction Methods
Authors: Chen Ting-Yu
Published: November 2018

The purpose of this paper is to develop a novel compromise approach using correlation‐based closeness indices for addressing multiple‐criteria decision analysis (MCDA) problems of bridge construction methods under complex uncertainty based on interval‐valued Pythagorean fuzzy (IVPF) sets. The assessment of bridge construction methods requires the consideration of multiple alternatives and conflicting tangible and intangible criteria in intricate and varied circumstances. The concept of IVPF sets is capable of handling imprecise and ambiguous information and managing complex uncertainty in real‐world applications. Inspired by useful ideas concerning information energies, correlations, and correlation coefficients, this paper constructs new concepts of correlation‐based closeness indices for IVPF characteristics and investigates their desirable properties. These indices can be utilized to achieve anchored judgments in decision‐making processes and to reflect a certain balance between connections with positive and negative ideal points of reference. Moreover, these indices can fully consider the amount of information associated with higher degrees of uncertainty and effectively fuse imprecise and ambiguous evaluative ratings to construct a meaningful comparison approach. By using the correlation‐based closeness index, this paper establishes effective algorithmic procedures of the proposed IVPF compromise approach for conducting multiple‐criteria evaluation tasks within IVPF environments. The proposed methodology is implemented in a practical problem of selecting a suitable bridge construction method to demonstrate its feasibility and applicability. The practicality and effectiveness of the proposed methodology are verified through a comparative analysis with well‐known compromise methods and other relevant nonstandard fuzzy models.
A Novel Fuzzy Model Predictive Control of a Gas Turbine in the Combined Cycle Unit
Authors: Hou Guolian , Gong Linjuan , Dai Xiaoyan , Wang Mengyi , Huang Congzhi
Published: November 2018

The complex characteristics of the gas turbine in a combined cycle unit have brought great difficulties in its control process. Meanwhile, the increasing emphasis on the efficiency, safety, and cleanliness of the power generation process also makes it significantly important to put forward advanced control strategies to satisfy the desired control demands of the gas turbine system. Therefore, aiming at higher control performance of the gas turbine in the gas‐steam combined cycle process, a novel fuzzy model predictive control (FMPC) strategy based on the fuzzy selection mechanism and simultaneous heat transfer search (SHTS) algorithm is presented in this paper. The objective function of rolling optimization in this novel FMPC consists of two parts which represent the state optimization and output optimization. In the weight coefficient selection of those two parts, the fuzzy selection mechanism is introduced to overcome the uncertainties existing in the system. Furthermore, on account of the rapidity of the control process, the SHTS algorithm is used to solve the optimization problem rather than the traditional quadratic programming method. The validity of the proposed method is confirmed through simulation experiments of the gas turbine in a combined power plant. The simulation results demonstrate the remarkable superiorities of the adopted algorithm with higher control precision and stronger disturbance rejection ability as well as less optimization time.
Morphological Modification and Analysis of ZnO Nanorods and Their Optical Properties and Polarization
Authors: Mufti Nandang , Maryam Siti , Fibriyanti Anggun A. , Kurniawan Robi , Fuad Abdulloh , Taufiq Ahmad , Sunaryono
Published: November 2018

We report on the effect of the morphological modification on optical properties and polarization of ZnO nanorods (NR). Here, the morphology and structure of the ZnO NR were modified by introducing different annealing temperatures. The increase of length and diameter and change in density of the ZnO NR were clearly observed by increasing the annealing temperature. We found that the samples show different oxygen vacancy (VO) and zinc interstitial (ZnI) concentrations. We suggest that the different concentrations of VO and ZnI are originated from morphological and structural modification. Our results reveal that optical absorption and polarization of ZnO NR could be enhanced by producing a high concentration of VO and ZnI. The modification of VO and ZnI promotes a decrease in the band gap and coexistence of high optical absorption and polarization in our ZnO NR. Our findings would give a broad insight into the morphological modification and characterization technique on ZnO NR. The high optical and polarization characteristics of ZnO NR are potential for developing the high-performance nanogenerator device for multitype energy harvesting.
An Approach to Data Reduction for Learning from Big Datasets: Integrating Stacking, Rotation, and Agent Population Learning Techniques
Authors: Czarnowski Ireneusz , Jędrzejowicz Piotr
Published: November 2018

In the paper, several data reduction techniques for machine learning from big datasets are discussed and evaluated. The discussed approach focuses on combining several techniques including stacking, rotation, and data reduction aimed at improving the performance of the machine classification. Stacking is seen as the technique allowing to take advantage of the multiple classification models. The rotation‐based techniques are used to increase the heterogeneity of the stacking ensembles. Data reduction makes it possible to classify instances belonging to big datasets. We propose to use an agent‐based population learning algorithm for data reduction in the feature and instance dimensions. For diversification of the classifier ensembles within the rotation also, alternatively, principal component analysis and independent component analysis are used. The research question addressed in the paper is formulated as follows: does the performance of a classifier using the reduced dataset be improved by integrating the data reduction mechanism with the rotation‐based technique and the stacking?
Manilkara zapota (L.) P. Royen Leaf Water Extract Induces Apoptosis in Human Hepatocellular Carcinoma (HepG2) Cells via ERK1/2/Akt1/JNK1 Signaling Pathways
Authors: Tan Bee Ling , Norhaizan Mohd Esa , Chan Lee Chin
Published: November 2018

Manilkara zapota (L.) P. Royen, called sapodilla, or locally known as ciku, belongs to the family Sapotaceae. We found that Manilkara zapota leaf water extract has cytotoxic effect against human hepatocellular carcinoma (HepG2) cell line in our earlier study. Therefore, this study aimed to explore the anticancer properties of Manilkara zapota leaf water extract in HepG2 cells. We also aimed to unravel yet undiscovered mechanisms and identified several expressed genes whose functions in cytotoxicity activity of Manilkara zapota leaf water extract in HepG2 cells have not been well‐studied. The apoptosis and intracellular reactive oxygen species (ROS) activities were analyzed using Annexin V‐propidium iodide staining and dichlorodihydrofluorescein diacetate, respectively, by NovoCyte Flow Cytometer. Bax and Bcl‐2 expression were assessed using Enzyme‐Linked Immunosorbent Assay. The associated molecular pathways were evaluated by quantitative real‐time PCR. Overall analyses revealed that Manilkara zapota leaf water extract can increase percentage of early apoptotic cells, induce the formation of ROS, upregulate c‐Jun N‐terminal kinase 1 (JNK1) and inducible nitric oxide synthase (iNOS), and reduce Akt1 and vascular endothelial growth factor A (VEGFA) transcriptional activities. Our data suggest that Manilkara zapota leaf water extract can suppress the growth of HepG2 cells via modulation of ERK1/2/Akt1/JNK1 transcriptional expression.
The Possible Pathophysiological Outcomes and Mechanisms of Tourniquet‐Induced Ischemia‐Reperfusion Injury during Total Knee Arthroplasty
Authors: Leurcharusmee Prangmalee , Sawaddiruk Passakorn , Punjasawadwong Yodying , Chattipakorn Nipon , Chattipakorn Siriporn C.
Published: November 2018

Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords “ischemia reperfusion injury,” “oxidative stress,” “tourniquet,” and “knee arthroplasty.” The search was limited to research articles published in the English language. Twenty‐eight clinical studies were included in this qualitative review. Skeletal muscle I/R reduces protein synthesis, increases protein degradation, and upregulates genes in cell stress pathways. The I/R of the lower extremity elevates local and systemic oxidative stress as well as inflammatory reactions and impairs renal function. Propofol reduces oxidative injury in this I/R model. Ischemic preconditioning (IPC) and vitamin C may prevent oxygen free radical production. However, a high dose of N‐acetylcysteine possibly induces kidney injury. In summary, TQ‐related I/R during TKA leads to muscle protein metabolism alteration, endothelial dysfunction, oxidative stress, inflammatory response, and renal function disturbance. Propofol, IPC, and vitamin C show protective effects on oxidative and inflammatory markers. However, a relationship between biochemical parameters and postoperative clinical outcomes has not been validated.
A New Dynamic Path Planning Approach for Unmanned Aerial Vehicles
Authors: Huang Chenxi , Lan Yisha , Liu Yuchen , Zhou Wen , Pei Hongbin , Yang Longzhi , Cheng Yongqiang , Hao Yongtao , Peng Yonghong
Published: November 2018

Dynamic path planning is one of the key procedures for unmanned aerial vehicles (UAV) to successfully fulfill the diversified missions. In this paper, we propose a new algorithm for path planning based on ant colony optimization (ACO) and artificial potential field. In the proposed algorithm, both dynamic threats and static obstacles are taken into account to generate an artificial field representing the environment for collision free path planning. To enhance the path searching efficiency, a coordinate transformation is applied to move the origin of the map to the starting point of the path and in line with the source‐destination direction. Cost functions are established to represent the dynamically changing threats, and the cost value is considered as a scalar value of mobile threats which are vectors actually. In the process of searching for an optimal moving direction for UAV, the cost values of path, mobile threats, and total cost are optimized using ant optimization algorithm. The experimental results demonstrated the performance of the new proposed algorithm, which showed that a smoother planning path with the lowest cost for UAVs can be obtained through our algorithm.
Metabolic Volumetric Parameters in 11C-Choline PET/MR Are Superior PET Imaging Biomarkers for Primary High-Risk Prostate Cancer
Authors: Tseng Jing-Ren , Yang Lan-Yan , Lin Yu-Chun , Liu Chung-Yi , Pang See-Tong , Hong Ji-Hong , Yen Tzu-Chen , Wang Li-Jen
Published: November 2018

Purpose. Positron emission tomography/magnetic resonance imaging (PET/MRI) can facilitate the use of noninvasive imaging biomarkers in clinical prostate cancer staging. Although multiparametric MRI is a widely used technique, the clinical value of simultaneous PET imaging remains unclear. This study aimed at investigating this issue. Methods. Between January 2015 and December 2016, 31 high-risk prostate cancer patients underwent 11C-choline PET/MRI for staging purposes. Clinical characteristics and imaging parameters, including the standardized uptake value (SUV) and metabolic volumetric parameters from PET imaging; apparent diffusion coefficient (ADC) values from diffusion-weighted imaging; and volume transfer rate constant (Ktrans), reflux rate constant (Kep), and initial area under curve (iAUC) in 60 seconds from dynamic contrast-enhanced (DCE) MRI were analyzed. Results. 11C-Choline PET imaging parameters were significantly correlated with prostate-specific antigen (PSA) levels, and metabolic volumetric parameters, including metabolic tumor volume (MTV) and uptake volume product (UVP), showed significant correlations with other MRI parameters. In our cohort analysis, the PET/MRI parameters UVP/minimal ADC value (ADCmin) and kurtosis of Kep (Kepkur)/ADCmin were significant predictors for progression-free survival (PFS) (HR = 1.01, 95% CI: 1.00–1.02, p=0.031 and HR = 1.09, 95% CI: 1.02–1.16, p=0.009, respectively) in multivariate Cox regression analysis. High UVP/ADCmin and Kepkur/ADCmin values were significantly associated with shorter PFS. Conclusions. Metabolic volumetric parameters such as MTV and UVP can be routinely used as PET imaging biomarkers to add prognostic value and show better correlations in combination with MR imaging parameters in high-risk prostate cancer patients undergoing 11C-choline PET/MRI.
Chorea Hyperglycemia Basal Ganglia Syndrome in a 63-Year-Old Male
Authors: Sperling Michael , Bhowansingh Roshan
Published: November 2018

Chorea hyperglycemia basal ganglia syndrome (CHBG) is a rare condition that manifests within the setting of uncontrolled nonketotic diabetes mellitus. The objective of this case report is to present a patient found to have CHBG and provide a timeline in terms of his workup and subsequent treatment. We also present a commentary on the current understanding of the pathophysiology and treatment and how this was applied to our patient. The case involves a 63-year-old poorly controlled diabetic male who presented with a one-week history of uncontrolled choreiform movements of his left upper extremity. His initial glucose level was 339 mg/dl. HbA1C was 9.9%. CT scan of the head demonstrated an abnormal increased intensity within the right lenticular nucleus and right caudate head most likely due to microcalcifications/mineralization. MRI of the brain demonstrated nonspecific T1 and T2 hyperintense abnormalities in the same area about the right basal ganglia. These findings were consistent with the movement pattern he was displaying and with a diagnosis of CHBG. Gradual control of his blood sugar levels over 48 hours led to resolution of his choreiform symptoms. After better medication adherence as an outpatient, endocrinology follow-up 6 months after discharge found his HbA1C drop to a level of 7.1%. There was no recurrence of his symptoms. CHBG is a rare manifestation of poorly controlled diabetes but is the one that clinicians should be aware of. Early recognition and gradual treatment of elevated blood glucose levels appear to lead to total resolution of choreiform symptoms.
Pharmaceutical Induction of PGC‐1α Promotes Retinal Pigment Epithelial Cell Metabolism and Protects against Oxidative Damage
Authors: Satish Sangeeta , Philipose Hannah , Rosales Mariana Aparecida Brunini , Saint-Geniez Magali
Published: November 2018

Retinal pigment epithelium (RPE) dysfunction due to accumulation of reactive oxygen species and oxidative damage is a key event in the development of age‐related macular degeneration (AMD). Here, we examine the therapeutic potential of ZLN005, a selective PGC‐1α transcriptional regulator, in protecting RPE from cytotoxic oxidative damage. Gene expression analysis on ARPE‐19 cells treated with ZLN005 shows robust upregulation of PGC‐1α and its associated transcription factors, antioxidant enzymes, and mitochondrial genes. Energetic profiling shows that ZLN005 treatment enhances RPE mitochondrial function by increasing basal and maximal respiration rates, and spare respiratory capacity. In addition, ZLN005 robustly protects ARPE‐19 cells from cell death caused by H2O2, ox‐LDL, and NaIO3 without exhibiting any cytotoxicity under basal conditions. ZLN005 protection against H2O2‐mediated cell death was lost in PGC‐1α‐silenced cells. Our data indicates that ZLN005 efficiently protects RPE cells from oxidative damage through selective induction of PGC‐1α and its target antioxidant enzymes. ZLN005 may serve as a novel therapeutic agent for retinal diseases associated with RPE dystrophies.
A New Generalized Range Control Chart for the Weibull Distribution
Authors: Arif Osama H. , Aslam Muhammad
Published: November 2018

In this study, a generalized range control chart is designed for the Weibull distribution using generally weighted moving average statistics. The proposed chart is based on minimum generally weighted moving average statistic and maximum generally weighted moving average statistics. We utilize the inverse erf function to transform the Weibull data to normal data. The necessary measures are given to assess the performance of the proposed control chart. The comparison study shows that the proposed control chart outperforms the existing control charts based on exponentially weighted moving average statistic in terms of the average run length. A real example is given for applying the proposed chart in the industry.
Transcranial Direct Current Stimulation (tDCS) Paired with Occupation-Centered Bimanual Training in Children with Unilateral Cerebral Palsy: A Preliminary Study
Authors: Rich Tonya L. , Nemanich Samuel , Chen Mo , Friel Kathleen , Feyma Timothy , Krach Linda , Nawshin Tanjila , Meekins Gregg , Gillick Bernadette T.
Published: November 2018

Objective. We investigated the preliminary efficacy of cathodal transcranial direct current stimulation (tDCS) combined with bimanual training in children and young adults with unilateral cerebral palsy based on the principle of exaggerated interhemispheric inhibition (IHI). Methods. Eight participants with corticospinal tract (CST) connectivity from the lesioned hemisphere participated in an open-label study of 10 sessions of cathodal tDCS to the nonlesioned hemisphere (20 minutes) concurrently with bimanual, goal-directed training (120 minutes). We measured the frequency of adverse events and intervention efficacy with performance (bimanual—Assisting Hand Assessment (AHA)—and unimanual—Box and Blocks), self-report (Canadian Occupational Performance Measure (COPM), ABILHAND), and neurophysiologic (motor-evoked potential amplitude, cortical silent period (CSP) duration, and motor mapping) assessments. Results. All participants completed the study with no serious adverse events. Three of 8 participants showed gains on the AHA, and 4 of 8 participants showed gains in Box and Blocks (more affected hand). Nonlesioned CSP duration decreased in 6 of 6 participants with analyzable data. Cortical representation of the first dorsal interosseous expanded in the nonlesioned hemisphere in 4 of 6 participants and decreased in the lesioned hemisphere in 3 of 4 participants with analyzable data. Conclusions. While goal achievement was observed, objective measures of hand function showed inconsistent gains. Neurophysiologic data suggests nonlinear responses to cathodal stimulation of the nonlesioned hemisphere. Future studies examining the contributions of activity-dependent competition and cortical excitability imbalances are indicated.
A Combination CDK4/6 and IGF1R Inhibitor Strategy for Ewing Sarcoma
Authors: Guenther Lillian M. , Dharia Neekesh V. , Ross Linda , Conway Amy , Robichaud Amanda L. , Catlett Jerrel L. , Wechsler Caroline S. , Frank Elizabeth S. , Goodale Amy , Church Alanna J. , Tseng Yuen-Yi , Guha Rajarshi , McKnight Crystal G. , Janeway Katherine A. , Boehm Jesse S. , Mora Jaume , Davis Mindy I. , Alexe Gabriela , Piccioni Federica , Stegmaier Kimberly
Published: November 2018

Purpose:

Novel targeted therapeutics have transformed the care of subsets of patients with cancer. In pediatric malignancies, however, with simple tumor genomes and infrequent targetable mutations, there have been few new FDA-approved targeted drugs. The cyclin-dependent kinase (CDK)4/6 pathway recently emerged as a dependency in Ewing sarcoma. Given the heightened efficacy of this class with targeted drug combinations in other cancers, as well as the propensity of resistance to emerge with single agents, we aimed to identify genes mediating resistance to CDK4/6 inhibitors and biologically relevant combinations for use with CDK4/6 inhibitors in Ewing.

Experimental Design:

We performed a genome-scale open reading frame (ORF) screen in 2 Ewing cell lines sensitive to CDK4/6 inhibitors to identify genes conferring resistance. Concurrently, we established resistance to a CDK4/6 inhibitor in a Ewing cell line.

Results:

The ORF screen revealed IGF1R as a gene whose overexpression promoted drug escape. We also found elevated levels of phospho-IGF1R in our resistant Ewing cell line, supporting the relevance of IGF1R signaling to acquired resistance. In a small-molecule screen, an IGF1R inhibitor scored as synergistic with CDK4/6 inhibitor treatment. The combination of CDK4/6 inhibitors and IGF1R inhibitors was synergistic in vitro and active in mouse models. Mechanistically, this combination more profoundly repressed cell cycle and PI3K/mTOR signaling than either single drug perturbation.

Conclusions:

Taken together, these results suggest that IGF1R inhibitors activation is an escape mechanism to CDK4/6 inhibitors in Ewing sarcoma and that dual targeting of CDK4/6 inhibitors and IGF1R inhibitors provides a candidate synergistic combination for clinical application in this disease.
Targeting an Autocrine Regulatory Loop in Cancer Stem-like Cells Impairs the Progression and Chemotherapy Resistance of Bladder Cancer
Authors: Wang Kai-Jian , Wang Chao , Dai Li-He , Yang Jun , Huang Hai , Ma Xiao-Jing , Zhou Zhe , Yang Ze-Yu , Xu Wei-Dong , Hua Mei-Mian , Lu Xin , Zeng Shu-Xiong , Wang Hui-Qing , Zhang Zhen-Sheng , Cheng Yan-Qiong , Liu Dan , Tian Qin-Qin , Sun Ying-Hao , Xu Chuan-Liang
Published: November 2018

Purpose:

Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer.

Experimental Design:

The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6− bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in bladder cancer.

Results:

Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6− cells, OV6+ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ bladder cancer CSCs in an orthotopic bladder cancer model.

Conclusions:

OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.
A Combined Nomogram Model to Preoperatively Predict Histologic Grade in Pancreatic Neuroendocrine Tumors
Authors: Liang Wenjie , Yang Pengfei , Huang Rui , Xu Lei , Wang Jiawei , Liu Weihai , Zhang Lele , Wan Dalong , Huang Qiang , Lu Yao , Kuang Yu , Niu Tianye
Published: November 2018

Purpose:

The purpose of this study is to develop and validate a nomogram model combing radiomics features and clinical characteristics to preoperatively differentiate grade 1 and grade 2/3 tumors in patients with pancreatic neuroendocrine tumors (pNET).

Experimental Design: A total of 137 patients who underwent contrast-enhanced CT from two hospitals were included in this study. The patients from the second hospital (n = 51) were selected as an independent validation set. The arterial phase in contrast-enhanced CT was selected for radiomics feature extraction. The Mann–Whitney U test and least absolute shrinkage and selection operator regression were applied for feature selection and radiomics signature construction. A combined nomogram model was developed by incorporating the radiomics signature with clinical factors. The association between the nomogram model and the Ki-67 index and rate of nuclear mitosis were also investigated respectively. The utility of the proposed model was evaluated using the ROC, area under ROC curve (AUC), calibration curve, and decision curve analysis (DCA). The Kaplan–Meier (KM) analysis was used for survival analysis.

Results:

An eight-feature–combined radiomics signature was constructed as a tumor grade predictor. The nomogram model combining the radiomics signature with clinical stage showed the best performance (training set: AUC = 0.907; validation set: AUC = 0.891). The calibration curve and DCA demonstrated the clinical usefulness of the proposed nomogram. A significant correlation was observed between the developed nomogram and Ki-67 index and rate of nuclear mitosis, respectively. The KM analysis showed a significant difference between the survival of predicted grade 1 and grade 2/3 groups (P = 0.002).

Conclusions:

The combined nomogram model developed could be useful in differentiating grade 1 and grade 2/3 tumor in patients with pNETs.
Robot-Assisted Reconstruction in Head and Neck Surgical Oncology: The Evolving Role of the Reconstructive Microsurgeon
Authors: Chalmers Richard , Schlabe Juergen , Yeung Elizabeth , Kerawala Cyrus , Cascarini Luke , Paleri Vinidh
Published: November 2018

Transoral robotic surgery (TORS) is gaining more widespread use among head and neck surgical procedures. As experience grows with this technique, so do the indications of when and in which patients it can be used. Already established in the treatment of small oral cavity tumours, it is expanding into larger multi-site resections and resections, such as through-and-through-into-the-neck defects, that will require reconstruction. With robot-assisted surgery advancing, so robot-assisted reconstruction (RAR) is evolving. In this paper, we discuss the evolving role of reconstruction in post-TORS defects as well as the role of RAR in today’s practice.
Secreted Frizzled Related Protein 2 Modulates Epithelial–Mesenchymal Transition and Stemness via Wnt/β-Catenin Signaling in Choriocarcinoma
Authors: Zeng Xianling , Zhang Yafei , Xu Huiqiu , Zhang Taohong , Xue Yan , An Ruifang
Published: November 2018

Background/Aims: Choriocarcinoma (CC) is a highly aggressive gestational trophoblastic neoplasia; however, the underlying molecular mechanisms of its invasiveness and metastasis remain poorly understood. Human secreted frizzled-related protein 2 (SFRP2) could function as a tumor promoter or suppressor in different tumors, yet the role it plays in CC’s invasion and metastasis is thoroughly unclear. The current study was aimed to explore the function and underlying mechanism of SFRP2 in CC. Methods: The expression of SFRP2 in CC tissues was examined via immunohistochemistry. The methylation level and expression of SFRP2 in CC cell lines, JEG-3 and JAR were examined via bisulfite sequencing PCR (BSP), western blotting and quantitative RT-PCR. The biological role of increasing expressed SFRP2 through its promoter demethylation with 5-Aza-2’-deoxycytidine (5-Aza) was examined by a series of in vitro functional studies. Furthermore, lentivirus transfection technology was adopted to investigate the biological roles of SFRP2 knockdown in JEG-3 and JAR cells in vitro and in vivo. Moreover, its downstream signaling pathway was investigated. Results: SFRP2 was downregulated in CC tissues, and its expression was inversely related to its promoter hypermethylation frequency in JEG-3 and JAR cells. Increased SFRP2 through its promoter demethylation inhibited cell migration, invasion and colony formation in JEG-3 and JAR cells, whereas decreased SFRP2 reversed the epithelial-mesenchymal transition (EMT) process and stemness in JEG-3 and JAR cells both in vitro and vivo. Mechanistically, SFRP2 regulated the EMT and stemness of CC cell lines via canonical Wnt/β-catenin signaling, validated by the usage of a Wnt activator and inhibitor. Conclusion: The current study indicates that downregulated SFRP2 has potent tumor-promotive effects in CC through the modulation of cancer stemness and the EMT phenotype via activation of Wnt/β-catenin signaling in vitro and in vivo.
Analysis of HCV Isolates Among the Li Ethnic in Hainan Island of South China Reveals Their HCV-6 Unique Evolution and a New Subtype
Authors: Wu Tao , Xing Zengbo , Yuan Manqiong , Ge Jun , Yuan Guosheng , Liang Kaijian , Wu Biao , Xiao Furong , Li Chunhua , Zhou Yuanping , Lin Feng , Lu Ling
Published: November 2018

Background/Aims: Hainan Island has been inhabited by the “Li” aboriginal minority for centuries where the HCV genotype distribution patterns maybe remarkably different from other parts of China. We aimed to provide a better understanding of the infection with HCV genotype 6 among “Li” aboriginals on Hainan Island. Methods: Firstly, using RT-PCR and DNA sequencing to determined 517 partial HCV Core-E1(115 from Li Ethnic, 402 from Han Ethnic) and 8 full-length genomes from Li ethnic in Hainan Island successfully, and then using the phylogenetic tree to determine the HCV genotype distribution and analyze the evolution of them. Results: Phylogenetic tree analysis showed that the distribution pattern of HCV genotypes among the Han and Li ethnic population exhibits significant diferences: 6a was the most prevalent subtype in Han ethnic of Hainan Island followed by 1b, 3b, 2a, 3a, and 1a. All genomes from Li ethnic were classified into genotype 6, while 84 out of 115 (73%) could not be classified. Nine sequences (HN1350 et al.) from Li ethnic might be assigned to a new subtype 6xh as their p-distances ranged from 5.9∼9.7%. Furthermore, we sequenced and characterized full-length genomes for eight HCV-6 isolates which were all from Li ethnic in Hainan Island. Among these isolates, the HN1350 was classified as a new subtype: 6xh. Conclusion: Overall, we firstly defined a new subtype of genotype 6xh through partial and new full length genome. And we found a unique distribution pattern of HCV 6 in the Li tribe, which might provide a better way to understand the genetic diversity of HCV-6 and to investigate the phylogeny of HCV strains from Li tribe.
Plasma Galectin-9 Concentrations in Normal and Diseased Condition
Authors: Niki Toshiro , Fujita Koji , Rosen Hugo , Hirashima Mitsuomi , Masaki Tsutomu , Hattori Toshio , Hoshino Katsuaki
Published: November 2018

Background/Aims: Galectin-9 is a soluble immune modulator with versatile functions, including a role as an immune checkpoint molecule. Therefore, the amount of galectin-9 in the blood may reflect an individual’s immunological balance. Many studies have conducted galectin-9 measurements; however, the reported galectin-9 concentration in the blood varies greatly, even within healthy controls. This study investigates the variation between the reported and actual concentrations of galectin-9. Methods: A GalPharma ELISA and an R&D Systems ELISA kit were directly compared using the same set of plasma and a series of recombinant galectins, including degraded galectin-9. Furthermore, galectin-9 in plasma was concentrated using anti-galectin-9 antibody-conjugated beads, and subjected to western blotting to estimate the quantity and integrity of galectin-9 and assess the consistency of ELISA measurements. Results: The R&D Systems’ ELISA indicated a 50-fold higher median concentration of plasma galectin-9 than that indicated by the GalPharma ELISA. This variation is due to aberrantly enhanced reactivity of the R&D Systems’ ELISA to degraded galectin-9 present in small quantities in the plasma. The GalPharma ELISA could detect only intact galectin-9 and its results correlated well with the plasma galectin-9 level obtained by western blotting. Conclusion: ELISA kits from R&D Systems reacts aberrantly higher against degraded galectin-9 than the intact galectin-9. Therefore, the existence of a small amount of degraded galectin-9 in a test sample hinders the quantification. As galectin-9 is a fragile protein, this is a serious concern when using this kit. Based on quantifications from the GalPharma ELISA, the median (25th-75th percentiles) galectin-9 concentration in healthy subjects in the current study cohort was calculated as 110 pg/mL (67 -154 pg/mL).
A Six-LncRNA Expression Signature Associated with Prognosis of Colorectal Cancer Patients
Authors: Zhao Jian , Xu Jian , Shang An-quan , Zhang Rui
Published: November 2018

Background/Aims: Colorectal cancer (CRC) is one of the most common malignant tumor with high migration and invasion capacity. Long non-coding RNAs (lncRNAs) have been identified to influence multiple cancers progression through competitively binding microRNAs (miRNAs). In this study, we proposed to develop a lncRNA-based signature for CRC survival outcomes. Methods: LncRNA expression profiles of CRC patients were extracted from the Gene Expression Omnibus (GEO) data sets GSE38832 (training set) and GSE29621 (testing set) . Associations between lncRNA expression and CRC disease free survival (DFS) were evaluated through univariate Cox regression analysis, and prognosis signature constructed by combination of weighted lncRNA expression values were obtained through multivariate Cox regression analysis. Robustness of the prognosis signature was evaluated through receiver operating characteristics analysis in the testing set. Results: A weighted prognosis signature of six lncRNAs, including LINC01583, LINC00276, LUNAR1, DKFZp434J0226, SFTA1P and OGFOD3, was yielded from multivariate Cox regression analysis. Samples with significantly different DFS dislayed distinct signatures, indicating considerable predictory accuracy of this expression signature. Conclusion: Robustness of the prognosis signature was evaluated in the testing set through Kaplan-Meier and receiver operating characteristics (ROC) analysis. Furthermore, functional enrichment analysis of lncRNAs suggested significant enrichment of cancer related pathways. Our results revealed the promise of lncRNAs as prognostic biomarkers.
GOLM1 Stimulation of Glutamine Metabolism Promotes Osteoporosis via Inhibiting Osteogenic Differentiation of BMSCs
Authors: Shen Guangsi , Zhang Hong , Jia Peng , Li Guangfei , Wang Xiao , Zhou Xiaozhong , Xu Youjia
Published: November 2018

Background/Aims: Bone marrow mesenchymal stem cells (BMSCs) play an essential role in osteoporosis. However, the molecular mechanisms and the involvement of glutamine metabolism in osteogenic BMSCs differentiation and osteoporosis remain largely unclear. In this study, we investigated the role of Golgi membrane protein 1 (GOLM1) and glutamine metabolism in BMSCs differentiation and osteoporosis. Methods: Osteogenic differentiation-inducing media (Odi) was used to induce the osteogenic differentiation of BMSCs. The mRNA expression of GOLM1, ALP, Runx2, Osx, BSP and OCN was determined by qRT-PCR assay. Western blot assay was used to analyze GOLM1, p-mTOR, mTOR, p-S6 and S6 abundance in GOLM1 silencing and over-expressed BMSCs. Glutamine uptake, intracellular glutamine, glutamate and α-KG level was detected using indicated Kits. GOLM1 antibody, glutamine metabolism inhibitors EGCG and BPTES were used to treat ovariectomy (OVX)-induced osteoporosis. Bone mineral density and bone volume relative to tissue volume (%) were analyzed by micro-CT. Serum was collected from osteoporosis patients and healthy participants and subjected to GOLM1 determination using ELISA Kit. Results: GOLM1 expression and glutamine metabolism were suppressed by Odi. GOLM1 blockage or inhibition of glutamine metabolism promoted the osteogenic differentiation of BMSCs induced by Odi. GOLM1 activated glutamine metabolism depending on the mTOR signaling pathway. In vivo, GOLM1 antibody or combination of glutamine inhibitor EGCG and BPTES rescued the osteoporosis in an OVX-operated mouse model. Serum GOLM1 level was increased in the patients of osteoporosis compared with healthy people. Conclusion: GOLM1 stimulates glutamine metabolism to suppress the osteogenic differentiation of BMSCs and to promote osteoporosis. Therefore, GOLM1 activation of glutamine metabolism is a potential target for osteoporosis.
Targeting Thioredoxin System with an Organosulfur Compound, Diallyl Trisulfide (DATS), Attenuates Progression and Metastasis of Triple-Negative Breast Cancer (TNBC)
Authors: Liu Yuping , Zhao Yang , Wei Zhonghong , Tao Li , Sheng Xiaobo , Wang Siliang , Chen Jiao , Ruan Junshan , Liu Zhaoguo , Cao Yuzhu , Shan Yunlong , Wang Aiyun , Chen Wenxing , Lu Yin
Published: November 2018

Background/Aims: Metastasis is the leading cause resulting in high mortality in triple negative breast cancer (TNBC) patients. Cancer cells are skilled at utilizing thioredoxin (Trx) system as an efficient antioxidant system to counteract oxidative damage, facilitating the occurrence of metastasis. Here, we identified an organosulfur compound named DATS isolated from garlic, that inhibits the expression of Trx-1 and the enzyme activity of Trx reductase in breast cancer cells. Methods: Tissue microarray of breast cancer patients and immunohistochemical method were used to analyze the role of Trx-1 in breast cancer metastasis. Spotaneous metastasis model and experimental metastasis model combined with HE staining, immunohistochemistry were used to verify in vivo anti-metastatic effect of DATS as well as its regulation on thioredoxin. Western blot, immunofluorescence, redox state assessment and detection of enzyme activity were employed to determine the effect of DATS on thioredoxin system. Trx-1 siRNA interference was used to investigate the conclusive evidence that Trx-1 was the target of DATS. Results: In agreement with reduced Trx-1 nuclear translocation from cytoplasm by DATS, the production of reduced form of Trx-1 was dramatically decreased. Furthermore, in vivo, DATS administration was observed to significantly suppress spontaneous and experimental metastasis in nude mice. Delivery of DATS also resulted in decreased expression of Trx-1 as the direct target, as well as expression of NF-κB and MMP2/9 in primary tumor and lung tissue. Notably, the effects of DATS on the expression of downstream metastasis-associated genes were mediated by Trx-1, as demonstrated by the combination use of DATS and Trx-1 siRNA. Conclusion: Collectively, this present study indicates that targeting Trx system with DATS may provide a promising strategy for treating metastasis of TNBC.
Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury
Authors: Martin-Jiménez Cynthia , Gaitán-Vaca Diana Milena , Areiza Natalia , Echeverria Valentina , Ashraf Ghulam Md , González Janneth , Sahebkar Amirhossein , Garcia-Segura Luis Miguel , Barreto George E.
Published: November 2018

Traumatic brain injury (TBI) is a serious public health problem. It may result in severe neurological disabilities and in a variety of cellular metabolic alterations for which available therapeutic strategies are limited. In the last decade, the use of estrogenic compounds, which activate protective mechanisms in astrocytes, has been explored as a potential experimental therapeutic approach. Previous works have suggested estradiol (E2) as a neuroprotective hormone that acts in the brain by binding to estrogen receptors (ERs). Several steroidal and nonsteroidal estrogenic compounds can imitate the effects of estradiol on ERs. These include hormonal estrogens, phytoestrogens and synthetic estrogens, such as selective ER modulators or tibolone. Current evidence of the role of astrocytes in mediating protective actions of estrogenic compounds after TBI is reviewed in this paper. We conclude that the use of estrogenic compounds to modulate astrocytic properties is a promising therapeutic approach for the treatment of TBI.
Potential New Approaches in Predicting Adverse Cardiac Events One Month after Major Vascular Surgery
Authors: Golubovic Mladjan , Peric Velimir , Stanojevic Dragana , Lazarevic Milan , Jovanovic Nenad  , Ilic Nenad , Djordjevic Miodrag , Kostic Tomslav , Milic Dragan
Published: November 2018

Objective: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. Subjects and Methods: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. Results: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. Conclusion: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.
Crestal Bone Loss Around Submerged and Non-Submerged Dental Implants in Individuals with Type-2 Diabetes Mellitus: A 7-Year Prospective Clinical Study
Authors: Al Zahrani Saeed , Al Mutairi Abdullah A.
Published: November 2018

Objective: In establishing an evidence-based rationale for the optimal use of implant therapy in patients with type 2 diabetes mellitus (T2DM), it is essential to first understand the impact of glycemic control on early healing and the success of dental implants. The objective of this study was to evaluate crestal bone loss (CBL) and stability around submerged and non-submerged dental implants in Saudi patients with well- and poorly controlled T2DM. Subject and Methods: Thirty-five patients with well-controlled T2DM (24 males and 11 females) and 32 poorly controlled T2DM patients (19 males and 13 females) were included. CBL was measured on digital radiographs; resonance frequency analysis (RFA) measurements were made for each implant at the time of fixture placement and at 3 months in both the groups. A p value less than 0.05 was considered statistically significant. Results: A total of 124 dental implants were placed. Mean RFA values between baseline and 3 months in poorly controlled T2DM patients was statistically significant (p = 0.048). CBL at first year (p = 0.047), second year (p = 0.041), third year (p = 0.046), and seventh year (p = 0.035) was significantly worse in poorly controlled T2DM. CBL around non-submerged dental implants showed statistically significant differences at all time-intervals (p < 0.05). Conclusion: Poorly controlled T2DM patients present worse peri-implant bone outcomes as compared to patients with well-controlled T2DM. We suggest that the predictability of successful dental implant therapy outcomes depends on the maintenance of optimal haemoglobin A1c levels.