bluuebunny/crossref_metadata_2025 huggingface dataset:
Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
Authors: Wu Dacheng , Wu Keyan , Zhu Qingtian , Xiao Weiming , Shan Qing , Yan Zhigang , Wu Jian , Deng Bin , Xue Yan , Gong Weijuan , Lu Guotao , Ding Yanbing
Published: January 2018

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.
Zanthoxylum ailanthoides Suppresses Oleic Acid‐Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells
Authors: Kwon Eun-Bin , Kang Myung-Ji , Kim Soo-Yeon , Lee Yong-Moon , Lee Mi-Kyeong , Yuk Heung Joo , Ryu Hyung Won , Lee Su Ui , Oh Sei-Ryang , Moon Dong-Oh , Lee Hyun-Sun , Kim Mun-Ock
Published: January 2018

Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA‐M) could reduce oleic acid‐ (OA‐) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA‐M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA‐M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA‐M also inhibited OA‐induced production of reactive oxygen species (ROS) and TNF‐α, suggesting that ZA‐M possess the anti‐inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA‐M attenuates OA‐induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells.
Long-Term Effects of Environmental Lead Exposure on Blood Pressure and Plasma Soluble Cell Adhesion Molecules in Young Adults: A Follow-Up Study of a Prospective Cohort in Kosovo
Authors: Camaj Pashko R. , Graziano Joseph H. , Preteni Emine , Popovac Dusan , LoIacono Nancy , Balac Olgica , Factor-Litvak Pam
Published: January 2018

Background and Aims. Epidemiologic studies examining the relationship between environmental lead (Pb) exposure and blood pressure (BP) generally report small associations between blood lead concentration (BPb) and BP. However, these studies are predominantly cross-sectional. In addition, no epidemiologic studies evaluate associations between either current or past Pb exposure and serum levels of markers of systemic inflammation and endothelial dysfunction, including soluble vascular adhesion molecule (sVCAM-1) and soluble intercellular cell adhesion molecule (sICAM-1).We prospectively investigate these associations later in life.Methods. From our original prospective birth cohort study in Mitrovica (a mining town) and Prishtina (a control town), Kosovo, from 1985 to 1998, we located and assessed BPb and BP in 101 participants (mean age of 24.9 years old) in 2011.Results. We found highly statistically significant association between concurrent BPb and sVCAM-1 in men and a marginally significant association between concurrent PBb and sICAM.-1 in women. We did not find evidence of mediation.Conclusion. Current study results, along with previously reported findings on this cohort, provide evidence for the hypothesis that exposure to Pb leads to small increases in sBP and perhaps to increased circulating levels of sVCAM-1 and sICAM-1 later in life.
Self-Powered Wireless Sensor Network for Automated Corrosion Prediction of Steel Reinforcement
Authors: Su Dan , Xia Ye , Yuan Robert
Published: January 2018

Corrosion is one of the key issues that affect the service life and hinders wide application of steel reinforcement. Moreover, corrosion is a long-term process and not visible for embedded reinforcement. Thus, this research aims at developing a self-powered smart sensor system with integrated innovative prediction module for forecasting corrosion process of embedded steel reinforcement. Vibration-based energy harvester is used to harvest energy for continuous corrosion data collection. Spatial interpolation module was developed to interpolate corrosion data at unmonitored locations. Dynamic prediction module is used to predict the long-term corrosion based on collected data. Utilizing this new sensor network, the corrosion process can be automated predicted and appropriate mitigation actions will be recommended accordingly.
Determination and Application of Comprehensive Specific Frictional Resistance in Heating Engineering
Authors: Tian Yanan , Wang Haosen , Shi Yongjiang , Rong Jiayu , Ma Zhenhua , Xie Cong
Published: January 2018

In this study, we analyze the deficiencies of specific frictional resistance in heating engineering. Based on economic specific frictional resistance, we put forward the concept of comprehensive specific frictional resistance, which considers the multiple factors of technology, economy, regulation modes, pipe segment differences, and medium pressure. Then, we establish a mathematical model of a heating network across its lifespan in order to develop a method for determining the comprehensive specific frictional resistance. Relevant conclusions can be drawn from the results. As an application, we have planned the heating engineering for Yangyuan County in China, which demonstrates the feasibility and superiority of the method.
Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels
Authors: Ahring Kirsten K. , Lund Allan M. , Jensen Erik , Jensen Thomas G. , Brøndum-Nielsen Karen , Pedersen Michael , Bardow Allan , Holst Jens Juul , Rehfeld Jens F. , Møller Lisbeth B.
Published: January 2018

Introduction. Management of phenylketonuria (PKU) is achieved through low-phenylalanine (Phe) diet, supplemented with low-protein food and mixture of free-synthetic (FS) amino acid (AA). Casein glycomacropeptide (CGMP) is a natural peptide released in whey during cheese-making and does not contain Phe. Lacprodan® CGMP-20 used in this study contained a small amount of Phe due to minor presence of other proteins/peptides.Objective. The purpose of this study was to compare absorption of CGMP-20 to FSAA with the aim of evaluating short-term effects on plasma AAs as well as biomarkers related to food intake.Methods. This study included 8 patients, who had four visits and tested four drink mixtures (DM1–4), consisting of CGMP, FSAA, or a combination. Plasma blood samples were collected at baseline, 15, 30, 60, 120, and 240 minutes (min) after the meal. AA profiles and ghrelin were determined 6 times, while surrogate biomarkers were determined at baseline and 240 min. A visual analogue scale (VAS) was used for evaluation of taste and satiety.Results. The surrogate biomarker concentrations and VAS scores for satiety and taste were nonsignificant between the four DMs, and there were only few significant results for AA profiles (not Phe).Conclusion. CGMP and FSAA had the overall same nonsignificant short-term effect on biomarkers, including Phe. This combination of FSAA and CGMP is a suitable supplement for PKU patients.
A Rare Case of Retrogastric Abscess Occurring Six Months after N-Butyl-2-Cyanoacrylate Injection into Gastric Varices
Authors: Hussain Ikram , Kwek Andrew Eu Boon , Meyyur Aravamudan Veeraraghavan , Chong Chern Hao , Ang Tiing Leong
Published: January 2018

Background. Injection with N-butyl-2-cyanoacrylate is a proven and successful therapeutic modality for treatment of patients with bleeding gastric varices. However, a variety of complications have also been associated with its use. Here, we report a rare case of retrogastric abscess which occurred almost six months after this therapy. This abscess was attributed to the hampered microbial clearance caused by the venous obliterations from N-butyl-2-cyanoacrylate. The abscess was successfully treated with 3 months of antibiotics.
Binding Energies and Dissociation Temperatures of Heavy Quarkonia at Finite Temperature and Chemical Potential in theN-Dimensional Space
Authors: Abu-Shady M. , Abdel-Karim T. A. , Khokha E. M.
Published: January 2018

TheN-dimensional radial Schrödinger equation has been solved using the analytical exact iteration method (AEIM), in which the Cornell potential is generalized to finite temperature and chemical potential. The energy eigenvalues have been calculated in theN-dimensional space for any state. The present results have been applied for studying quarkonium properties such as charmonium and bottomonium masses at finite temperature and quark chemical potential. The binding energies and the mass spectra of heavy quarkonia are studied in theN-dimensional space. The dissociation temperatures for different states of heavy quarkonia are calculated in the three-dimensional space. The influence of dimensionality number (N) has been discussed on the dissociation temperatures. In addition, the energy eigenvalues are only valid for nonzero temperature at any value of quark chemical potential. A comparison is studied with other recent works. We conclude that the AEIM succeeds in predicting the heavy quarkonium at finite temperature and quark chemical potential in comparison with recent works.
Pediatric Trauma Boot Camp: A Simulation Curriculum and Pilot Study
Authors: Khobrani Ahmad , Patel Nirali H. , George Richard L. , McNinch Neil L. , Ahmed Rami A.
Published: January 2018

Trauma is a leading cause of morbidity and mortality in infants and children worldwide. Trauma education is one of the most commonly reported deficiencies in pediatric emergency medicine (PEM) training. In this study, we describe the creation of a pediatric trauma boot camp in which trainees’ basic knowledge, level of confidence, teamwork, and communication skills are assessed. The primary goal of this pilot study was to create a simulation-based pediatric trauma curriculum for PEM fellows and emergency medicine residents utilizing Kern’s curricular conceptual framework. This was a pilot, prospective, single cohort, exploratory, observational study utilizing survey methodology and a convenience sample. The curriculum consisted of a two-day experience that included confidence surveys, a cognitive multiple-choice questionnaire, and formative and summative simulation scenarios. At the conclusion of this intensive simulation-based trauma boot camp participants reported increased confidence and demonstrated significant improvement in the basic knowledge and performance of the management of pediatric trauma cases in a simulated environment.
Analysis of the Impact of Configuration of the Stabilisation System for Femoral Diaphyseal Fractures on the State of Stresses and Displacements
Authors: Słowiński Jakub J. , Kudłacik Konrad
Published: January 2018

Introduction. The treatment of femoral diaphyseal fractures by intramedullary nailing has become a common procedure in orthopaedic surgery. The purpose of this numerical simulation was to present how the changes in configuration of the stabilisation system can affect the stress and displacement state in the bone tissue and implanted device.Material and Methods. The numerical comparison of the stabilisation variants for the type 32-A2 femoral diaphyseal fracture (according to the AO classification) performed by using the Charfix2 (ChM®) anatomical nail locked in a number of chosen ways. The displacement and the stress distributions both in the bone and implant were obtained and analysed by computational simulation.Results. In all models, there was the same characteristic distribution, which shows there were minimal rotational movements of the bone around the anatomical axis. In all cases, stress concentrations were generated in the nail material in the area of the fracture gap.Conclusions. The obtained results indicate that there is a visible advantage to one-plane distal stabilisation in the reduction of stresses regardless of the type of proximal stabilisation. The results of calculations indicate that the use of proximal stabilisation with a neck screw reduces the possibility of damage to the implant.
The Form of Waiting Time Distributions of Continuous Time Random Walk in Dead-End Pores
Authors: Hou Yusong , Jiang Jianguo , Wu J.
Published: January 2018

Anomalous dispersion of solute in porous media can be explained by the power-law distribution of waiting time of solute particles. In this paper, we simulate the diffusion of nonreactive tracer in dead-end pores to explore the waiting time distributions. The distributions of waiting time in different dead-end pores show similar power-law decline at early time and transit to an exponential decline in the end. The transition time between these two decline modes increases with the lengths of dead-end pores. It is well known that power-law distributions of waiting time may lead to anomalous (non-Fickian) dispersion. Therefore, anomalous dispersion is highly dependent on the sizes of immobile zones. According to the power-law decline, we can directly get the power index from the structure of dead-end pores, which can be used to judge the anomalous degree of solute transport in advance.
Study of the Bullwhip Effect under Various Forecasting Methods in Electronics Supply Chain with Dual Retailers considering Market Share
Authors: Ma Junhai , Zhang Jing , Zhu Liqing
Published: January 2018

We establish in this paper a new two‐stage supply chain with one manufacturer and two retailers which have a fixed market share in the mature and stable market with specific reference to consumer electronics industry. This paper offers insights into how the three forecasting methods affect the bullwhip effect considering the market share under the ARMA(1,1) demand process and the order‐up‐to inventory policy. We also discuss the stability of the order with the theory of entropy. In particular, we derive the expressions of bullwhip effect measure under the MMSE, MA, and ES methods and compare them by numerical simulations. Results show that the MA is always better in contrast to the ES for reducing the bullwhip effect in our supply chain model. When moving average coefficient is lower than a certain value, the MMSE method is the best for reducing the bullwhip effect; otherwise, the MA method is the best. Moreover, the larger the market share of the retailer with a long lead time is, the greater the bullwhip effect is, no matter what the forecasting method is.
Prospective of68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation
Authors: Velikyan Irina
Published: January 2018

During the last decade, the utilization of68Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of68Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management.
PD2/PAF1 at the Crossroads of the Cancer Network
Authors: Karmakar Saswati , Dey Parama , Vaz Arokia P. , Bhaumik Sukesh R. , Ponnusamy Moorthy P. , Batra Surinder K.
Published: January 2018

Pancreatic differentiation 2 (PD2)/RNA polymerase II–associated factor 1 (PAF1) is the core subunit of the human PAF1 complex (PAF1C) that regulates the promoter-proximal pausing of RNA polymerase II as well as transcription elongation and mRNA processing and coordinates events in mRNA stability and quality control. As an integral part of its transcription-regulatory function, PD2/PAF1 plays a role in posttranslational histone covalent modifications as well as regulates expression of critical genes of the cell-cycle machinery. PD2/PAF1 alone, and as a part of PAF1C, provides distinct roles in the maintenance of self-renewal of embryonic stem cells and cancer stem cells, and in lineage differentiation. Thus, PD2/PAF1 malfunction or its altered abundance is likely to affect normal cellular functions, leading to disease states. Indeed, PD2/PAF1 is found to be upregulated in poorly differentiated pancreatic cancer cells and has the capacity for neoplastic transformation when ectopically expressed in mouse fibroblast cells. Likewise, PD2/PAF1 is upregulated in pancreatic and ovarian cancer stem cells. Here, we concisely describe multifaceted roles of PD2/PAF1 associated with oncogenic transformation and implicate PD2/PAF1 as an attractive target for therapeutic development to combat malignancy. Cancer Res; 78(2); 313–9. ©2018 AACR.
O-GlcNAcylation of the Tumor Suppressor FOXO3 Triggers Aberrant Cancer Cell Growth
Authors: Shin Heon , Cha Hyun-Jeong , Na Keun , Lee Min Jung , Cho Jin-Young , Kim Chae-Yeon , Kim Eun Kyung , Kang Chang Moo , Kim Hoguen , Paik Young-Ki
Published: January 2018

Posttranslational modifications of tumor suppressors can induce abnormal cell growth. Here, we identify site-specific O-GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven O-GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in O-GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth. Overexpression of either O-GlcNAcylated FOXO3 (FOX-OV) or a Ser-to-Ala mutant (S284A) in PANC-1 cells indicated that S284 O-GlcNAc acts as a critical block of the FOXO tumor suppressor and induces proliferation in PANC-1 cancer cells by stimulating the MDM2-p53-p21 axis. Furthermore, S284A mutant cells lacking S284 O-GlcNAc and FOX-OV cells exhibited opposing MDM2-p53-p21 axis expression patterns at both the mRNA and protein levels. Thus, our study provides evidence to support a role for S284 O-GlcNAc as a critical block of FOXO3 to induce subsequent cancer cell growth via abrogation of the p53 regulatory circuit.

Significance: These findings highlight a posttranslational mechanism for indirect abrogation of the p53 pathway, one that may occur with some frequency in human cancer cells. Cancer Res; 78(5); 1214–24. ©2018 AACR.
Genomic Correlates of Response to Everolimus in Aggressive Radioiodine-refractory Thyroid Cancer: A Phase II Study
Authors: Hanna Glenn J. , Busaidy Naifa L. , Chau Nicole G. , Wirth Lori J. , Barletta Justine A. , Calles Antonio , Haddad Robert I. , Kraft Stefan , Cabanillas Maria E. , Rabinowits Guilherme , O'Neill Anne , Limaye Sewanti A. , Alexander Erik K. , Moore Francis D. , Misiwkeiwicz Krystof , Thomas Tom , Nehs Matthew , Marqusee Ellen , Lee Stephanie L. , Jänne Pasi A. , Lorch Jochen H.
Published: January 2018

Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy of everolimus in aggressive, radioactive iodine–refractory (RAIR) thyroid cancer and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic thyroid cancer cohorts were included.

Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 to 2013 in patients with incurable RAIR thyroid cancer who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis.

Results: Thirty-three patients with differentiated thyroid cancer (DTC), 10 with medullary thyroid cancer (MTC), and 7 with anaplastic thyroid cancer (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3–18.5) with a 2-year PFS of 23.6% (95% CI, 10.5–39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8–85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months after study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt–mutated ATC subgroups appeared to benefit from everolimus. Treatment-related adverse events were as anticipated.

Conclusions: Everolimus has significant antitumor activity in thyroid cancer. While genomic profiling does not currently guide therapeutic selection in thyroid cancer patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. Clin Cancer Res; 24(7); 1546–53. ©2018 AACR.
Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance)
Authors: Magbanua Mark Jesus M. , Rugo Hope S. , Wolf Denise M. , Hauranieh Louai , Roy Ritu , Pendyala Praveen , Sosa Eduardo V. , Scott Janet H. , Lee Jin Sun , Pitcher Brandelyn , Hyslop Terry , Barry William T. , Isakoff Steven J. , Dickler Maura , van't Veer Laura , Park John W.
Published: January 2018

Purpose: We profiled circulating tumor cells (CTCs) to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC).

Methods: CTCs were isolated from 105 patients with MBC using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACS), 28 of whom had serial CTC analysis (74 samples, 2–5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes (n = 151) and genome-wide copy-number analysis by array comparative genomic hybridization (aCGH; n = 49).

Results: Combined transcriptional and genomic profiling showed that CTCs were 26% ESR1−ERBB2−, 48% ESR1+ERBB2−, and 27% ERBB2+. Serial testing showed that ERBB2 status was more stable over time compared with ESR1 and proliferation (MKI67) status. While cell-to-cell heterogeneity was observed at the single-cell level, with increasingly stable expression in larger pools, patient-specific CTC expression “fingerprints” were also observed. CTC copy-number profiles clustered into three groups based on the extent of genomic aberrations and the presence of large chromosomal imbalances. Comparative analysis showed discordance in ESR1/ER (27%) and ERBB2/HER2 (23%) status between CTCs and matched primary tumors. CTCs in 65% of the patients were considered to have low proliferation potential. Patients who harbored CTCs with high proliferation (MKI67) status had significantly reduced progression-free survival (P = 0.0011) and overall survival (P = 0.0095) compared with patients with low proliferative CTCs.

Conclusions: We demonstrate an approach for complete isolation of EPCAM-positive CTCs and downstream comprehensive transcriptional/genomic characterization to examine the biology and assess breast cancer biomarkers in these cells over time. Clin Cancer Res; 24(6); 1486–99. ©2018 AACR.
Keeping Tumors Out of the MAPK Fitness Zone
Authors: Stern David F.
Published: January 2018

Summary: Greatest fitness of tumor cell subclones in patients undergoing MAPK-targeting therapies requires just-right levels of MAPK pathway signaling. New therapeutic approaches induce tumor cell death by intensifying MAPK signaling induced by inhibitor withdrawal in combination with DNA damage, or prevent selection of resistant clones with a steep fitness barrier imposed by triple combination of BRAF, MEK, and ERK inhibitors. Cancer Discov; 8(1); 20–3. ©2018 AACR.

See related article by Hong et al., p. 74.
ABO Mistyping of cis-AB Blood Group by the Automated Microplate Technique
Authors: Chun Sejong , Ryu Mi Ra , Cha Seung-Yeon , Seo Ji-Young , Cho Duck
Published: January 2018

Background: The cis-AB phenotype, although rare, is the relatively most frequent of ABO subgroups in Koreans. To prevent ABO mistyping of cis-AB samples, our hospital has applied a combination of the manual tile method with automated devices. Herein, we report cases of ABO mistyping detected by the combination testing system. Methods: Cases that showed discrepant results by automated devices and the manual tile method were evaluated. These samples were also tested by the standard tube method. The automated devices used in this study were a QWALYS-3 and Galileo NEO. Exons 6 and 7 of the ABO gene were sequenced. Results: 13 cases that had the cis-AB allele showed results suggestive of the cis-AB subgroup by manual methods, but were interpreted as AB by either automated device. This happened in 87.5% of these cases by QWALYS-3 and 70.0% by Galileo NEO. Genotyping results showed that 12 cases were ABO*cis-AB01/ABO*O01 or ABO*cis-AB01/ABO*O02, and one case was ABO*cis-AB01/ ABO*A102. Conclusion: Cis-AB samples were mistyped as AB by the automated microplate technique in some cases. We suggest that the manual tile method can be a simple supplemental test for the detection of the cis-AB phenotype, especially in countries with relatively high cis-AB prevalence.
Serotonin Transporter Gene (SLC6A4) Polymorphism May Be Associated with Chinese Globus Pharyngeus and Its Antidepressant Effects
Authors: Liu Yao , Jia Lin , Jiang Shu-man , Chen Dong-yun , Song Jiang-shun , Xu Jian
Published: January 2018

Background: Although globus pharyngeus is not rare in clinical practice, little is known about its associated gene polymorphism. We investigated the association between the SLC6A4 polymorphism and globus pharyngeus and its response to treatment with antidepressants. Methods: A total of 84 patients were diagnosed with globus pharyngeus according to Rome III, and 160 healthy controls were genotyped for the SLC6A4 polymorphism using polymerase chain reaction amplification and agarose gel electrophoresis. All patients with globus were studied using high-resolution manometry pre-therapy. Globus patients were randomized into paroxetine or amitriptyline groups for a 6-week treatment and asked to complete the following pre- and post-therapy questionnaires: the Glasgow Edinburgh Throat Scale (GETS), the Pittsburgh Sleep Quality Index, and the Hamilton Rating Scale Anxiety/Depression. Treatment response was defined as a >50% reduction in the GETS scores. Results: A significant difference was observed in the globus S/S genotype with anxiety compared to that without anxiety (χ2 = 14.579, p = 0.006). The L/S genotype showed a significant difference between high upper esophageal sphincter pressure (>104 mm Hg) and non-high upper esophageal sphincter pressure patients (χ2 = 14.433, p = 0.006). A significant association between the S/S genotype and the response to antidepressant treatment was also observed, while patients with sleep disorders or depression showed no association. Conclusion: A significant association was observed between the S/S genotype of the SLC6A4 polymorphism and globus pharyngeus, suggesting that SLC6A4 is a potential candidate gene involved in the pathogenesis of globus pharyngeus.
Association of Soluble Interleukin-2 Receptor and C-Reactive Protein with the Efficacy of Bendamustine Salvage Treatment for Indolent Lymphomas and Mantle Cell Lymphoma
Authors: Kawaguchi Yukiko , Nakamaki Tsuyoshi , Abe Maasa , Baba Yuta , Murai So , Watanuki Megumi , Arai Nana , Fujiwara Shun , Kabasawa Nobuyuki , Tsukamoto Hiroyuki , Uto Yui , Ariizumi Hirotsugu , Yanagisawa Kouji , Hattori Norimichi , Harada Hiroshi , Saito Bungo
Published: January 2018

Bendamustine has demonstrated favourable efficacy in relapsed or refractory indolent lymphoma and mantle cell lymphoma. We retrospectively evaluated the pre-treatment clinical and laboratory factors and their correlation with the clinical outcome of these lymphomas. We analysed 53 patients who had been treated with bendamustine alone (n = 6) or rituximab plus bendamustine (n = 47). The overall response rate was 81.1%, with a complete response (CR) rate of 39.6%. The CR rate was significantly low in patients who had elevated levels of soluble interleukin-2 receptor (p = 0.024) and C-reactive protein (CRP; p = 0.004). The 1-year overall survival (OS) rate was 79.3%. An elevated CRP was associated with a short OS (p = 0.056). The present findings suggest that the lymphoma microenvironment and immune response were involved in the effects of bendamustine. These findings are also important in order to understand the pathophysiology of refractory lymphoma and to find effective strategies using bendamustine.
Efficacy of Reduced Dosage of Amoxicillin in an Eradication Therapy for Helicobacter pylori Infection in Patients on Hemodialysis: A Randomized Controlled Trial
Authors: Sahara Shu , Sugimoto Mitsushige , Ichikawa Hitomi , Kagami Takuma , Sakao Yukitoshi , Ohashi Naro , Horio Yoshiaki , Sugimoto Ken , Kato Akihiko , Furuta Takahisa , Yasuda Hideo
Published: January 2018

Background: An optimum Helicobacter pylori-eradication regimen for hemodialysis patients is yet to be established because of different pharmacokinetics of amoxicillin involved between hemodialysis patients and healthy subjects. We investigated to establish appropriate doses of amoxicillin for H. pylori infection eradication in hemodialysis patients. Methods: Of 409 hemodialysis patients screened for H. pylori infection, 37 H. pylori-positive patients were randomized to different 1-week eradication regimens: esomeprazole 20 mg twice a day (b.i.d.) and clarithromycin 200 mg b.i.d., plus amoxicillin at either 750 mg b.i.d. (group A; conventional) or 250 mg b.i.d. (group B; experimental). Sixty-three patients with normal renal function received the conventional regimen (group C). Successful eradication was confirmed by urea breath testing. Results: Eradication rates of group B (reduced amoxicillin-regimen) were 84.2% in intention-to-treat analysis and 88.9% in per-protocol analysis, which were similar with group A (77.8 and 77.8%) and group C (74.6 and 81.0%). However, the incidence of adverse events in group A was significantly higher than that in group C (22.2 vs. 5.1%, p = 0.027). Conclusions: In H. pylori-positive hemodialysis patients, amoxicillin at 250 mg b.i.d. may be an appropriate scheme for eradication with equivalent effects to the conventional therapy and safety effects for adverse events.
Vonoprazan is Superior to Rabeprazole for Healing Endoscopic Submucosal Dissection: Induced Ulcers
Authors: Yamasaki Akira , Yoshio Toshiyuki , Muramatsu Yusuke , Horiuchi Yusuke , Ishiyama Akiyoshi , Hirasawa Toshiaki , Tsuchida Tomohiro , Sasaki Yutaka , Fujisaki Junko
Published: January 2018

Background and Aims: Endoscopic submucosal dissection (ESD) is a well-established minimally invasive treatment for early gastric cancer. To heal ESD-induced ulcers, we commonly prescribe proton pump inhibitors (PPIs). Vonoprazan is our new choice, which is reported to have a stronger and longer acid inhibitory effect than existing PPIs. Here, we aimed to evaluate the efficacy of vonoprazan for healing ESD-induced ulcers compared with rabeprazole. Methods: We reviewed 190 patients who underwent ESD before and after we switched the acid secretion inhibitor from rabeprazole to vonoprazan. We evaluated scarring and reduction rates at 4 weeks after ESD. Results: Scarring rates were not different between vonoprazan and rabeprazole (31.7 vs. 18.9%; p = 0.07). However, for ulcers ≤35 mm, vonoprazan was superior to rabeprazole (42.2 vs. 19.2%; p < 0.05). Reduction rates were superior for vonoprazan compared with rabeprazole (93.0 vs. 90.4%; p < 0.05). In multivariate analysis, vonoprazan was superior to rabeprazole for ulcer scarring (OR 2.21; p < 0.05), and ulcer location in the lower-third of the stomach had higher risk of incomplete scarring (OR 0.37; p < 0.05). Conclusion: Vonoprazan was superior to rabeprazole for healing ESD-induced ulcers.
Space and Time in the Obsessive-Compulsive Phenomenon
Authors: Doerr-Zegers Otto
Published: January 2018

Following the tradition of researchers of the phenomenological-anthropological school such as Straus, von Gebsattel, Tellenbach, and Blankenburg, the author attempts to approach the obsessive-compulsive disorder from a phenomenological perspective. This means setting aside any previous ideas about the phenomenon in question, including genetic, neurobiological, and clinical-statistical considerations. He takes as his starting point a clinically typical case he studied and treated with psychoanalytically oriented psychotherapy for many years. After delving briefly into the interesting psychodynamic connections between the patient's symptoms and life story, he proceeds to analyze the obsessive world itself from a spatial and temporal point of view. Regarding the former, he points out that the features associated with human spatiality, according to Heidegger, the tendency to diminish distance and concede space, are specifically altered in the obsessive phenomenon. With respect to temporality, the author demonstrates the circularity and sterility of obsessive time (unlike that of creativity, which evolves in linear time) and the fact that the rites involved do not represent a victory over the rule of the clock, as religious rites do, but rather a deep submission to chronological time.
Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis
Authors: Gao Yana , Yu Hai , Liu Yunhui , Liu Xiaobai , Zheng Jian , Ma Jun , Gong Wei , Chen Jiajia , Zhao Lini , Tian Yu , Xue Yixue
Published: January 2018

Background/Aims: Vasculogenic mimicry (VM) has been reported to be a novel glioma neovascularization process. Anti-VM therapy provides new insight into glioma clinical management. In this study, we revealed the role of the long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) in malignant glioma behaviors and VM formation. Methods: Quantitative real-time PCR was performed to determine the expression levels of HOXA-AS2 in glioma samples and glioblastoma cell lines. CD34-periodic acid-Schiff dual-staining was performed to assess VM in glioma samples. CCK-8, transwell, and Matrigel tube formation assays were performed to measure the effects of HOXA-AS2 knockdown on cell viability, migration, invasion, and VM tube formation, respectively. RNA immunoprecipitation, dual-luciferase reporter and Western blot assays were performed to explore the molecular mechanisms underlying the functions of HOXS-AS2 in glioblastoma cells. A nude mouse xenograft model was used to investigate the role of HOXA-AS2 in xenograft glioma growth and VM density. Student’s t-tests, one-way ANOVAs followed by Bonferroni posthoc tests, and chi-square tests were used for the statistical analyses. Results: HOXA-AS2 was upregulated in glioma samples and cell lines and was positively correlated with VM. HOXA-AS2 knockdown attenuated cell viability, migration, invasion, and VM formation in glioma cells and inhibited the expression of vascular endothelial-cadherin (VE-cadherin), as well as the expression and activity of matrix metalloproteinase matrix metalloproteinase (MMP)-2 and MMP-9. miR-373 was downregulated in glioma samples and cell lines and suppressed malignancy in glioblastoma cells. HOXA-AS2 bound to miR-373 and negatively regulated its expression. Epidermal growth factor receptor (EGFR), a target of miR-373, increased the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9, via activating phosphatidylinositol 3-kinase/serine/threonine kinase pathways. HOXA-AS2 knockdown combined with miR-373 overexpression yielded optimal tumor suppressive effects and the lowest VM density in vivo. Conclusion: HOXA-AS2 knockdown inhibited malignant glioma behaviors and VM formation via the miR-373/EGFR axis.
Cardiac Endothelial Cell Transcriptome
Authors: Lother Achim , Bergemann Stella , Deng Lisa , Moser Martin , Bode Christoph , Hein Lutz
Published: January 2018

Objective—

Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome.

Approach and Results—

We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors. We found an overrepresentation of corresponding transcription factor binding motifs within the promotor region of EC-enriched genes, suggesting that they control the EC transcriptome. Cardiac ECs exhibit a distinct gene expression profile when compared with renal, cerebral, or pulmonary ECs. For example, we found the
Meox2
/
Tcf15, Fabp4
, and
Cd36
signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis.

Conclusions—

The results from this study provide a comprehensive resource of gene expression and transcriptional control in cardiac ECs. The cardiac EC transcriptome exhibits distinct differences in gene expression compared with other cardiac cell types and ECs from other organs. We identified new candidate genes that have not been investigated in ECs yet as promising targets for future evaluation.
Endogenous LINE-1 (Long Interspersed Nuclear Element-1) Reverse Transcriptase Activity in Platelets Controls Translational Events Through RNA–DNA Hybrids
Authors: Schwertz Hansjörg , Rowley Jesse W. , Schumann Gerald G. , Thorack Ulrike , Campbell Robert A. , Manne Bhanu Kanth , Zimmerman Guy A. , Weyrich Andrew S. , Rondina Matthew T.
Published: January 2018

Objective—

One source of endogenous reverse transcriptase (eRT) activity in nucleated cells is the LINE-1/L1 (long interspersed nuclear element-1), a non-LTR retrotransposon that is implicated in the regulation of gene expression. Nevertheless, the presence and function of eRT activity and LINE-1 in human platelets, an anucleate cell, has not previously been determined.

Approach and Results—

We demonstrate that human and murine platelets possess robust eRT activity and identify the source as being LINE-1 ribonucleoprotein particles. Inhibition of eRT in vitro in isolated platelets from healthy individuals or in people with HIV treated with RT inhibitors enhanced global protein synthesis and platelet activation. If HIV patients were treated with reverse transcriptase inhibitor, we found that platelets from these patients had increased basal activation. We next discovered that eRT activity in platelets controlled the generation of RNA–DNA hybrids, which serve as translational repressors. Inhibition of platelet eRT lifted this RNA–DNA hybrid-induced translational block and was sufficient to increase protein expression of target RNAs identified by RNA–DNA hybrid immunoprecipitation.

Conclusions—

Thus, we provide the first evidence that platelets possess L1-encoded eRT activity. We also demonstrate that platelet eRT activity regulates platelet hyperreactivity and thrombosis and controls RNA–DNA hybrid formation and identify that RNA–DNA hybrids function as a novel translational control mechanism in human platelets.
(Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis
Authors: Ren Liwei , Sun Yuan , Lu Hong , Ye Dien , Han Lijuan , Wang Na , Daugherty Alan , Li Furong , Wang Miaomiao , Su Fengting , Tao Wenjun , Sun Jie , Zelcer Noam , Mullick Adam E. , Danser A.H. Jan , Jiang Yizhou , He Yongcheng , Ruan Xiongzhong , Lu Xifeng
Published: January 2018

Rationale:

An elevated level of plasma LDL (low-density lipoprotein) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDLR (LDL receptor) and SORT1 (sortilin-1), independently of the renin–angiotensin system.

Objectives:

To investigate the physiological role of (P)RR in lipid metabolism in vivo.

Methods and Results:

We used N-acetylgalactosamine modified antisense oligonucleotides to specifically inhibit hepatic (P)RR expression in C57BL/6 mice and studied the consequences this has on lipid metabolism. In line with our earlier report, hepatic (P)RR silencing increased plasma LDL-C (LDL cholesterol). Unexpectedly, this also resulted in markedly reduced plasma triglycerides in a SORT1-independent manner in C57BL/6 mice fed a normal- or high-fat diet. In LDLR-deficient mice, hepatic (P)RR inhibition reduced both plasma cholesterol and triglycerides, in a diet-independent manner. Mechanistically, we found that (P)RR inhibition decreased protein abundance of ACC (acetyl-CoA carboxylase) and PDH (pyruvate dehydrogenase). This alteration reprograms hepatic metabolism, leading to reduced lipid synthesis and increased fatty acid oxidation. As a result, hepatic (P)RR inhibition attenuated diet-induced obesity and hepatosteatosis.

Conclusions:

Collectively, our study suggests that (P)RR plays a key role in energy homeostasis and regulation of plasma lipids by integrating hepatic glucose and lipid metabolism.
The (Dis)empowering Effects of Transparency Beyond Information Disclosure: The Extractive Industries Transparency Initiative in Myanmar
Authors: Vijge Marjanneke J.
Published: January 2018

This article provides theoretical and empirical insights into the effects of transparency on civil society empowerment by analyzing the Extractive Industries Transparency Initiative (EITI) in Myanmar. It identifies three processes through which the EITI (dis)empowers civil society: constituting, using, and debating transparency. Whereas most transparency literature focuses on the effects of information disclosure—( using transparency)–the empowering effects of constituting and debating transparency are, for the EITI in Myanmar, much greater. While civil society organizations (CSOs) hardly use the EITI report as it lacks actionable information, the EITI has given CSOs a previously unimaginable role through their involvement in designing and implementing the EITI—i.e., in constituting transparency—and in EITI-related awareness-raising activities and debates, or debating transparency. Though in unequal ways, the processes of constituting and debating transparency empower CSOs to request, collect, and use more actionable information than through the EITI alone. This article argues that transparency initiatives could benefit from focusing attention on not only what information to disclose but also through which processes.
A new endemic Impatiens species on Mount Gorongosa (Mozambique) demonstrates the conservation importance of montane areas in Africa
Authors: JANSSENS STEVEN B. , BALLINGS PETRA , MERTENS ARNE , DESSEIN STEVEN
Published: January 2018

A new Impatiens species from Mozambique, Impatiens wuerstenii, is described and illustrated. The material used for the description was initially mistaken for the morphologically similar Impatiens species I. psychadelphoides, a known endemic from Mozambique. However, a combined molecular – morphological study demonstrates that the populations found on Mount Gorongosa do not belong to I. psychadelphoides but are a species on their own. Phylogenetic analyses based on chloroplast and nuclear gene markers demonstrate that I. wuerstenii is sister to the floral morphologically distinct I. salpinx, and that I. psychadelphoides and I. cecilii are sister to that lineage. The presence of a new endemic species on Mount Gorongosa indicates the importance of this mountain area on the overall biodiversity of the region and emphasizes the need for a more thorough conservation and biological exploration of the mountain.
A new species of Tabernaemontana (Apocynaceae; Rauvolfioideae: Tabernaemontaneae) from Mexico
Authors: ALVARADO-CÁRDENAS LEONARDO O. , SANTILLÁN VINISA SAYNES
Published: January 2018

A new species of Tabernaemontana from south-eastern Mexico is described and illustrated. Tabernaemontana riverae is separated from all known species of the genus by its long elliptic–lanceolate sepals and infundibuliform corolla. The new species is endemic to Mexico and only observed in the states of Oaxaca, Tabasco, and Veracruz. With this addition, Tabernaemontana is represented in Mexico by 15 species, six of them endemic. These numbers highlight Mexico as a diversity center for the genus. We propose a conservation status for the new species and provide a key to the Mesoamerican species of Tabernaemontana with leaf-like sepals.
A new species of Sonerila (Melastomataceae: Sonerileae) from southern Western Ghats, India
Authors: RESMI S. , MANUDEV K.M. , PRAMOD C. , NAMPY SANTHOSH
Published: January 2018

Sonerila lateritica, a tuberous species of Melastomataceae is described in connection with a taxonomic revision of Sonerila in India. The new species is morphologically close to S. anaimudica but differs by its tuberous root stocks, quadrangular stems, opposite-decussate leaves, many-flowered cymes and mucronate petals. Description, illustration, taxonomic notes and photoplates are provided.
WRF Model Simulations of the Influence of the Athabasca Oil Sands Development on Convective Storms
Authors: Brown Daniel , Reuter Gerhard
Published: January 2018

The Athabasca oil sands development has created a land surface disturbance of almost 900 km2 in northeastern Alberta. Both through industrial processes and the removal of boreal forest vegetation, this surface disturbance impacts meteorology in the vicinity by releasing waste heat, raising the surface temperature, and lowering the surface humidity. To investigate the effects of the Athabasca oil sands development on thunderstorm intensity, initiation time, and duration, the Weather Research and Forecasting (WRF) Model was employed to simulate the effect of the surface disturbance on atmospheric conditions on 10 case study days. The results suggested the oil sands surface disturbance was not associated with substantial increases in thunderstorm intensity on any of the case study days. On two case study days, however, the WRF Model simulations differed substantially from the observed meteorological conditions and only approached the observations when the oil sands surface disturbance was included in the model simulation. Including the oil sands surface disturbance in the model simulations resulted in thunderstorm initiation about 2 h earlier and increased thunderstorm duration. Data from commercial aircraft showed that the 850–500-mb temperature difference was greater than 30°C (very unstable) only on these 2 days. Such cases are sufficiently rare that they are not expected to affect the overall thunderstorm climatology. Still, in these very unstable cases, the oil sands development appears to have a significant effect on thunderstorm initiation time and duration.