bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal priority and threshold assignment for fixed-priority preemption threshold scheduling
Authors: Hatvani Leo , Afshar Sara , Bril Reinder J.
Published: March 2018

Fixed-priority preemption-threshold scheduling (FPTS) is a generalization of fixed-priority preemptive scheduling (FPPS) and fixed-priority non-preemptive scheduling (FPNS). Since FPPS and FPNS are incomparable in terms of potential schedulability, FPTS has the advantage that it can schedule any task set schedulable by FPPS or FPNS and some that are not schedulable by either. FPTS is based on the idea that each task is assigned a priority and a preemption threshold. While tasks are admitted into the system according to their priorities, they can only be preempted by tasks that have priority higher than the preemption threshold.

This paper presents a new optimal priority and preemption threshold assignment (OPTA) algorithm for FPTS which in general outperforms the existing algorithms in terms of the size of the explored state-space and the total number of worst case response time calculations performed. The algorithm is based on back-tracking, i.e. it traverses the space of potential priorities and preemption thresholds, while pruning infeasible paths, and returns the first assignment deemed schedulable.

We present the evaluation results where we compare the complexity of the new algorithm with the existing one. We show that the new algorithm significantly reduces the time needed to find a solution. Through a comparative evaluation, we show the improvements that can be achieved in terms of schedulability ratio by our OPTA compared to a deadline monotonic priority assignment.
Mixed-Effects Modeling of Neurofeedback Self-Regulation Performance: Moderators for Learning in Children with ADHD
Authors: Zuberer Agnieszka , Minder Franziska , Brandeis Daniel , Drechsler Renate
Published: March 2018

Introduction. Neurofeedback (NF) has gained increasing popularity as a training method for children and adults with attention deficit hyperactivity disorder (ADHD). However, it is unclear to what extent children learn to regulate their brain activity and in what way NF learning may be affected by subject- and treatment-related factors. Methods. In total, 48 subjects with ADHD (age 8.5–16.5 years; 16 subjects on methylphenidate (MPH)) underwent 15 double training sessions of NF in either a clinical or a school setting. Four mixed-effects models were employed to analyze learning: training within-sessions, across-sessions, with continuous feedback, and with transfer in which performance feedback is delayed. Results. Age and MPH affected the NF performance in all models. Cross-session learning in the feedback condition was mainly moderated by age and MPH, whereas NF learning in the transfer condition was mainly boosted by MPH. Apart from IQ and task types, other subject-related or treatment-related effects were unrelated to NF learning. Conclusion. This first study analyzing moderators of NF learning in ADHD with a mixed-effects modeling approach shows that NF performance is moderated differentially by effects of age and MPH depending on the training task and time window. Future studies may benefit from using this approach to analyze NF learning and NF specificity. The trial name Neurofeedback and Computerized Cognitive Training in Different Settings for Children and Adolescents With ADHD is registered with NCT02358941.
Meta-Analysis of the Association between Vitamin D Receptor Polymorphisms and the Risk of Autoimmune Thyroid Disease
Authors: Gao Xue-Ren , Yu Yong-Guo
Published: March 2018

The association between vitamin D receptor (VDR) polymorphisms (rs731236, rs1544410, rs2228570, and rs7975232) and the risk of autoimmune thyroid disease (AITD) had been investigated in previous studies. However, the results of these studies remained controversial. Thus, a meta-analysis was performed to derive a more precise conclusion. All related articles were systematically searched by PubMed, Embase, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. The overall results indicated thatVDRrs731236 and rs2228570 polymorphisms were significantly associated with a reduced risk of AITD. However, a stratification analysis based on clinical types showed thatVDRrs731236 and rs2228570 polymorphisms were associated only with a reduced risk of HT. A stratification analysis by ethnicity showed thatVDRrs731236 polymorphism was significantly associated with a reduced risk of AITD in Asian and African populations.VDRrs2228570 polymorphism was associated with a reduced risk of AITD in Asian populations.VDRrs1544410 polymorphism was associated with a reduced risk of AITD in European and African populations, but with an increased risk of AITD in Asian populations.VDRrs7975232 polymorphism was significantly associated with an increased risk of AITD in African populations. In conclusion, the present study suggested thatVDRrs731236, rs1544410, rs2228570, and rs7975232 polymorphisms were significantly associated with AITD risk. However, more well-designed studies should be performed to verify the current results.
Biosimilars Have Arrived: Rituximab
Authors: Greenwald Maria , Tesser John , Sewell K. Lea
Published: March 2018

A biosimilar is a biologic product that is highly similar to a licensed biologic (“originator”) such that there are no clinically meaningful differences in safety, purity, or potency between the biosimilar and the originator. As patent protection and data exclusivity for the biologic rituximab expire, several potential biosimilars to rituximab are in development, which could soon lead to the availability of numerous rituximab biosimilars. Biosimilars are evaluated using thorough and rigorous analyses of the potential biosimilar versus the originator biological to confirm similar structure, function, and clinical efficacy as well as safety. Approval of a biosimilar is based upon the totality of the evidence demonstrating similarity to the originator. An understanding of the process of the interchangeable designation of a biosimilar is important in the context of patient outcomes. We conducted an analysis of the properties and benefits of rituximab in the treatment of inflammatory diseases, the development and approval of biosimilars, and the potential benefits of rituximab biosimilars. PubMed and ClinicalTrials.gov databases were searched for “biosimilar” and “rituximab” and regulatory and pharmaceutical company web pages were screened regarding biosimilars in development and specific guidelines developed for the approval of biosimilars. The results indicate that, at present, six rituximab biosimilar candidates are undergoing comparative clinical development, and two were recently approved in the European Union. Our analysis indicates rituximab biosimilars are expected to have a continuing role in treating inflammatory conditions such as rheumatoid arthritis.
Experimental Study on Parameters Affecting the Runout Range of Rockfall
Authors: Hu Jie , Li Shucai , Shi Shaoshuai , Li Liping , Zhang Qian , Liu Hongliang , He Peng
Published: March 2018

This paper presents the law of rockfall runout range and the effect on lateral dispersion caused by different parameters. A creative combined model test bench was developed as the test site, the slope, and blocks were artificial using similar materials that can meet the strength required in the experiment. As to the analysis of rockfall runout range, a series of experiments were carried out, and the shape, weight, and release heights of blocks were varied to clarify the effect of 3 factors. The motion trajectory of block was recorded based on a high‐speed camera and a defined coordinate system. In addition, the final longitudinal and lateral runout distances of block were also measured. Furthermore, an extended laboratory investigation was conducted, consisting of 160 tests with cubical blocks, and an empirical model was proposed from the test results that estimates the lateral dispersion W/L of cubical blocks with different mass and release height. For the design of practical mitigation measures, the research results in this paper may provide a useful reference.
A Modified Walker Model Dealing with Mean Stress Effect in Fatigue Life Prediction for Aeroengine Disks
Authors: Lu Shan , Su Yunlai , Yang Mao , Li Yan
Published: March 2018

Mean stress effect plays an important role in fatigue life prediction, and it is discovered that maximum stress has nonnegligible influence on mean stress effect. Therefore, a modified Walker model is proposed to account for mean stress effect on fatigue life of aeroengine disks, which contains the influence of stress ratio and maximum stress on mean stress effect. Eight sets of fatigue data for standard smooth bars from six kinds of materials commonly used in aeroengine disks as well as two sets of experimental data from simulated specimens of turbine disks were employed to investigate the prediction capability of the proposed model against other candidate mean stress relationships. It is found that Goodman model generates most conservative results, while Morrow model overestimates fatigue life for most cases. SWT model yields similar results to Walker model but with less accuracy. The results of the modified Walker model turn out to be superior to those of any other candidate models for all cases examined, especially for large mean stress ones. Thus, the modified Walker model can be an effective method to predict fatigue lives of aeroengine disks influenced by mean stresses.
NADH Oxidation onto Different Carbon-Based Sensors: Effect of Structure and Surface-Oxygenated Groups
Authors: Blandón-Naranjo Lucas , Hoyos-Arbeláez Jorge , Vázquez Mario V. , Della Pelle Flavio , Compagnone Dario
Published: March 2018

Different carbon-based materials have been compared for the development of NADH sensors: glassy carbon electrodes (GCE), multiwalled carbon nanotubes (MWCNT), and carbon black (CB). The GCE and MWCNT has been subjected to oxidative pretreatment to study the influence of oxidative groups for NADH oxidation. The materials had been characterized by FT-IR to identify the surface composition. The response of bare (GC) and GC/modified electrodes toward potassium ferricyanide have been employed to obtain information about the electroactive area and electron transfer rate. Studies of NAD+/NADH redox behavior showed that MWCNT and GCE exhibit high degree of passivation while CB shows no fouling effects. Catalytic effect of surface-oxygenated groups was also proved for GCE and MWCNT, and both, O-GCE and O-MWCNT, exhibited a lower oxidation overpotential compared to the respective untreated materials. Chronoamperometric quantification showed a linear dependence between 2–18 μmol·L−1 and a detection limits of 6.2 μmol·L−1 (GCE), 5.4 μmol·L−1 (O-GCE), 3.2 μmol·L−1 (GCE/CB), 9.6 μmol·L−1 (GCE/MWCNT), and 4.9 μmol·L−1 (GCE/O-MWCNT) were obtained. The analytical performances suggest that a careful choice of the material for NADH sensing is necessary depending on the sensor application.
Hydraulic Conductivity Variation of Coarse‐Fine Soil Mixture upon Mixing Ratio
Authors: Chung Choong-Ki , Kim Joon-Hyoun , Kim Joonyoung , Kim Taesik
Published: March 2018

This paper presents the theoretical and experimental investigations of the hydraulic conductivity variation of the soil mixture that contains two distinct particle size distributions, coarse and fine soils. A new model for the hydraulic conductivity is introduced that focuses on the relationship between the coarse‐fine soil mixing ratio and the hydraulic conductivity of the mixture. For the model verification, permeability tests were conducted. The glass beads and quality‐controlled standard sand and soils obtained from fields were used for the specimen. The experiment results showed that the hydraulic conductivity of the soil mixture strongly depends on the mixing ratio. As the amount of the coarse soil contained in the fine soil increased, the hydraulic conductivity of the mixture decreased from that for the fine soil until the critical mixing ratio. This ratio is defined as the fine soils perfectly fill the voids between the coarse soils without remains. When the ratio is greater than the critical mixing ratio, the hydraulic conductivity is drastically increased with the mixing ratio up to that of the coarse soil. The comparison between the computed values and the test results shows that the introduced model successfully describes the measurements.
TLR4-NF-κB Signal Involved in Depressive-Like Behaviors and Cytokine Expression of Frontal Cortex and Hippocampus in Stressed C57BL/6 and ob/ob Mice
Authors: Wang Yihe , Xu Jingjing , Liu Yuan , Li Ziyang , Li Xiaohong
Published: March 2018

Studies found that elevated levels of cytokines such as interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α (TNF-α) are closely associated with the pathogenesis of depression. Obesity providing a low-grade inflammation state was proposed to be implicated in susceptibility to depression in obesity. However, the alterations of cytokines and the TLR4-NF-κB signal in the brain of normal-weight and obese mice under stress have not been fully elucidated. This study used chronic unpredictable mild stress (CUMS) to induce a depressive-like behavior in an animal model and examine depressive-like behaviors, memory changes, and serum corticosterone levels, as well as the expressions of cytokines and NF-κB in the frontal cortex and hippocampus. We aimed to observe the role of neuroinflammation in susceptibility to depression in obesity under CUMS. In addition, we investigated the protective effect of inhibiting the TLR4-NF-κB signal. Our results demonstrated that CUMS induced depressive-like behavior and spatial memory damage, higher level of serum corticosterone, and overexpression of cytokines and NF-κB in the frontal cortex and hippocampus in both C57BL/6 and ob/ob mice. ob/ob mice displayed serious behavioral disorder and higher levels of IL-1β, IL-6, TNF-α, and NF-κB. Our results concluded that a hyperactive TLR4-NF-κB signal and higher level of cytokines are involved in susceptibility to depression in stressed obese mice.
Quality and Operations Management in Food Supply Chains: A Literature Review
Authors: He Yong , Huang Hongfu , Li Dong , Shi Chunming , Wu Sarah J.
Published: March 2018

We present a literature review on quality and operations management problems in food supply chains. In food industry, the quality of the food products declines over time and should be addressed in the supply chain operations management. Managing food supply chains with operations management methods not only generates economic benefit, but also contributes to environmental and social benefits. The literature on this topic has been burgeoning in the past few years. Since 2005, more than 100 articles have been published on this topic in major operations research and management science journals. In this literature review, we concentrate on the quantitative models in this research field and classify the related articles into four categories, that is, storage problems, distribution problems, marketing problems, and food traceability and safety problems. We hope that this review serves as a reference for interested researchers and a starting point for those who wish to explore it further.
Bactericidal and Cytotoxic Activities of Polyphenol Extracts fromSolanum tuberosumspp.tuberosumand spp.andigenaCultivars onEscherichia coliand Human Neuroblastoma SH-SY5Y CellsIn Vitro
Authors: Silveyra María Ximena , Lanteri María Luciana , Damiano Rocío Belén , Andreu Adriana Balbina
Published: March 2018

Potatoes (Solanum tuberosumL.) are a good source of dietary antioxidant polyphenols. This study investigated the potential antioxidant, bactericidal, and cytotoxic activitiesin vitroof the phenolic compounds present in tubers of oneS. tuberosumspp.tuberosum(Summerside), and threeS. tuberosumspp.andigena(landraces Moradita, Waicha, and Santa María) cultivars. Both the content of phenolic acids, chlorogenic acids (CGAs) being the most abundant, and the antioxidant activity were higher in extracts from skin than from flesh. Extracts from Moradita flesh and Summerside skin showed bactericidal activity againstEscherichia coliATCC 25922 but failed to inhibit pathogenicE. coliO157. Both extracts lack pigmentation but do contain 5-CGA, caffeic, and ferulic acids. Positive control with gentamicin and commercial 5-CGA resulted in a complete inhibition of bacterial growth. In addition, all potato extracts and commercial 5-CGA diminished dose-dependently human neuroblastoma SH-SY5Y cell viability. Skin extracts were more potent than flesh extracts. Among flesh extracts, Moradita was the most potent. Together, our results suggest that Moradita flesh could provide a desirable source of important health-promoting substances. Findings indicate that the biological activity of potato extracts is a combination of various bioactive compounds and contribute to the revalorization of potato as a functional food.
Polyphenolic Compounds, Antioxidant, and Cardioprotective Effects of Pomace Extracts from Fetească Neagră Cultivar
Authors: Balea Ştefania Silvia , Pârvu Alina Elena , Pop Nastasia , Marín Fernando Zamora , Pârvu Marcel
Published: March 2018

Grape pomace is a potential source of natural antioxidant agents. Phenolic compounds and antioxidant and cardioprotective properties of fresh and fermented pomace extracts obtained from Vitis vinifera L. red variety Fetească neagră grown in Romania in 2015 were investigated. Grape pomace extracts total phenolic index, total tannins, total anthocyanins, proanthocyanidins, flavan‐3‐ol monomers, stilbenes, and DPPH free radical scavenger were measured. The effect of a seven‐day pretreatment with grape pomace extracts on the isoprenaline‐induced infarct‐like lesion in rats was assessed by ECG monitoring, serum levels of creatine kinase, aspartate transaminase, and alanine transaminase. Total serum oxidative status, total antioxidant response, oxidative stress index, malondialdehyde, total thiols, and nitric oxide have been also assessed. Higher phenolic content and antioxidant activity were found in fermented pomace extracts when compared to fresh pomace extracts. Pretreatment with grape pomace extracts significantly improved cardiac and oxidative stress parameters. In conclusion, Fetească neagră pomace extracts had a good in vitro antioxidant activity due to an important phenolic content. In vivo, the extracts had cardioprotective effects against isoprenaline‐induced infarct‐like lesion by reducing oxidative stress, fresh pomace extracts having a better effect.
Structural Characterization and Magnetic Properties of Undoped and Ti-Doped ZnO Nanoparticles Prepared by Modified Oxalate Route
Authors: Etape Ekane Peter , Foba-Tendo Josepha , Ngolui Lambi John , Namondo Beckley Victorine , Yollande Fomogne Cyrille , Nguimezong Marius Borel Nguefack
Published: March 2018

Ti-doped zinc oxide and pure zinc oxide nanoparticles were synthesized by a modified oxalate route using Averrhoa carambola fruit juice as a natural source of oxalate. The characteristics of the precursors have been investigated by FTIR, TGA, and XRD. The results from the investigation revealed that the precursors are zinc oxalate and Ti-doped zinc oxalate which readily decompose at 450°C. The as-prepared precursors were calcined at 450°C for 4 hours, and the decomposition products have been characterized by XRD, SEM, EDX, and VSM. XRD results revealed crystallinity with hexagonal wurtzite structure, while the average grain size was found to be 26 nm for Ti-doped ZnO and 29 nm for ZnO, using calculations based on Debye-Scherrer equation. Furthermore, the morphological studies by SEM showed particle agglomeration, while the presence of Ti3+ in the zinc oxide lattice is indicated by EDS analysis. Finally the hysteresis loop from VSM results shows that Ti-doped ZnO exhibits ferromagnetism.
Resveratrol‐Induced Downregulation of NAF‐1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways
Authors: Cheng Liang , Yan Bin , Chen Ke , Jiang Zhengdong , Zhou Cancan , Cao Junyu , Qian Weikun , Li Jie , Sun Liankang , Ma Jiguang , Ma Qingyong , Sha Huanchen
Published: March 2018

NAF‐1 (nutrient‐deprivation autophagy factor‐1), which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF‐1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF‐1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling. In addition, the knockdown of NAF‐1 activates apoptosis and impedes the proliferation of pancreatic cancer cells. More importantly, the targeting of NAF‐1 by resveratrol can improve the sensitivity of pancreatic cancer cells to gemcitabine. These results highlight the significance of strategies that target NAF‐1, which may enhance the efficacy of gemcitabine in pancreatic cancer therapy.
Design of a Clinical Decision Support System for Fracture Prediction Using Imbalanced Dataset
Authors: Chen Yung-Fu , Lin Chih-Sheng , Wang Kuo-An , Rahman La Ode Abdul , Lee Dah-Jye , Chung Wei-Sheng , Lin Hsuan-Hung
Published: March 2018

More than 1 billion people suffer from chronic respiratory diseases worldwide, accounting for more than 4 million deaths annually. Inhaled corticosteroid is a popular medication for treating chronic respiratory diseases. Its side effects include decreased bone mineral density and osteoporosis. The aims of this study are to investigate the association of inhaled corticosteroids and fracture and to design a clinical support system for fracture prediction. The data of patients aged 20 years and older, who had visited healthcare centers and been prescribed with inhaled corticosteroids within 2002–2010, were retrieved from the National Health Insurance Research Database (NHIRD). After excluding patients diagnosed with hip fracture or vertebrate fractures before using inhaled corticosteroid, a total of 11645 patients receiving inhaled corticosteroid therapy were included for this study. Among them, 1134 (9.7%) were diagnosed with hip fracture or vertebrate fracture. The statistical results showed that demographic information, chronic respiratory diseases and comorbidities, and corticosteroid-related variables (cumulative dose, mean exposed daily dose, follow-up duration, and exposed duration) were significantly different between fracture and nonfracture patients. The clinical decision support systems (CDSSs) were designed with integrated genetic algorithm (GA) and support vector machine (SVM) by training and validating the models with balanced training sets obtained by random and cluster-based undersampling methods and testing with the imbalanced NHIRD dataset. Two different objective functions were adopted for obtaining optimal models with best predictive performance. The predictive performance of the CDSSs exhibits a sensitivity of 69.84–77.00% and an AUC of 0.7495–0.7590. It was concluded that long-term use of inhaled corticosteroids may induce osteoporosis and exhibit higher incidence of hip or vertebrate fractures. The accumulated dose of ICS and OCS therapies should be continuously monitored, especially for patients with older age and women after menopause, to prevent from exceeding the maximum dosage.
False-Positive Plasma Genotyping Due to Clonal Hematopoiesis
Authors: Hu Yuebi , Ulrich Bryan C. , Supplee Julianna , Kuang Yanan , Lizotte Patrick H. , Feeney Nora B. , Guibert Nicolas M. , Awad Mark M. , Wong Kwok-Kin , Jänne Pasi A. , Paweletz Cloud P. , Oxnard Geoffrey R.
Published: March 2018

Purpose: Plasma cell-free DNA (cfDNA) genotyping is increasingly used in cancer care, but assay accuracy has been debated. Because most cfDNA is derived from peripheral blood cells (PBC), we hypothesized that nonmalignant mutations harbored by hematopoietic cells (clonal hematopoiesis, CH) could be a cause of false-positive plasma genotyping.

Experimental Design: We identified patients with advanced non–small cell lung cancer (NSCLC) with KRAS, JAK2, or TP53 mutations identified in cfDNA. With consent, PBC DNA was tested using droplet digital PCR (ddPCR) or next-generation sequencing (NGS) to test for CH-derived mutations.

Results: We first studied plasma ddPCR results from 58 patients with EGFR-mutant NSCLC. Two had KRAS G12X detected in cfDNA, and both were present in PBC, including one where the KRAS mutation was detected serially for 20 months. We then studied 143 plasma NGS results from 122 patients with NSCLC and identified 5 JAK2 V617F mutations derived from PBC. In addition, 108 TP53 mutations were detected in cfDNA; for 33 of the TP53 mutations, PBC and tumor NGS were available for comparison, and 5 were present in PBC but absent in tumor, consistent with CH.

Conclusions: We find that most JAK2 mutations, some TP53 mutations, and rare KRAS mutations detected in cfDNA are derived from CH not tumor. Clinicians ordering plasma genotyping must be prepared for the possibility that mutations detected in plasma, particularly in genes mutated in CH, may not represent true tumor genotype. Efforts to use plasma genotyping for cancer detection may need paired PBC genotyping so that CH-derived mutations are not misdiagnosed as occult malignancy. Clin Cancer Res; 24(18); 4437–43. ©2018 AACR.

See related commentary by Bauml and Levy, p. 4352
Attenuation of MicroRNA-495 Derepressed PTEN to Effectively Protect Rat Cardiomyocytes from Hypertrophy
Authors: Fu Jie , Chen Yiwei , Li Fen
Published: March 2018

Background: The effect of microRNA (miR)-495 on cardiomyocyte hypertrophy was explored by investigating the expression of proteins in the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway. Methods: The study used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) administration (60 mg/kg) for 2 weeks. Arterial wall thickness and right ventricular hypertrophy were examined by hematoxylin and eosin (HE) staining in the lungs and hearts. The expression level of miR-495 and PTEN was analyzed by quantitative (q)PCR and Western blotting. From the cellular level, we used loss-of-function approaches to investigate the functional roles of miR-495 in cardiac hypertrophy induced by angiotensin II (Ang II) with immunoﬂuorescence, qPCR, and Western blotting. Results: The results showed that upregulation of miR-495 markedly influenced the expression of hypertrophic markers, including the induction of nppa and the inhibition of myh6. In contrast, a reduction in the level of miR-495 attenuated an Ang II-induced hypertrophic reaction. Furthermore, PTEN was identified as a potential target of miR-495 by a bioinformatics algorithm. Luciferase analysis and Western blot analysis confirmed that the contribution of miR-495 to cardiomyocyte hypertrophy may partly be through targeting PTEN. Conclusions: Attenuation of miR-495 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy.
Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer Screening: A Diagnostic Accuracy Study
Authors: Prigenzi Karla Calaça Kabbach , Heinke Thaís  , Salim Rafael Calil , Focchi Gustavo Rubino de Azevedo
Published: March 2018

Objective: Our objective was to verify the sensitivity and specificity of dual immunocytochemistry staining for p16 and Ki-67 in liquid-based samples (the “dual” assay) for cervical lesion screening, compared to biopsy findings and human papillomavirus (HPV) DNA molecular detection. Study Design: Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for the “dual immunocytochemistry assay” were calculated and compared to histopathological results and to high-risk HPV DNA detection in adult women or teenagers submitted to cervical cancer screening. Results: A total of 151 women were included. The majority (96.2%) of those with negative dual assay results had lower biopsy grades (p < 0.001). Women with cytology results suggestive of cervical cancer had positive dual immunocytochemistry assay results more frequently (p < 0.001), and these positive results were also significantly associated with biopsy findings (p < 0.001) and with high-risk genotype HPV infection (p = 0.007). Specificity and PPV for the dual assay were 0.972 (0.855–0.999) and 0.800 (0.284–0.995), respectively, and 1.000 (0.590–1.000) and 1.000 (0.631–1.000) for HPV detection. Conclusions: The dual immunocytochemistry assay had high specificity and PPV. It reveals a persistent HPV infection, avoiding the need for new tissue collections for biopsies or hybrid capture.
Long-Term Follow-Up of Congenital Simple Hamartoma of the Retinal Pigment Epithelium: A Case Report
Authors: Ito Yuka , Ohji Masahito
Published: March 2018

Background: Congenital simple hamartoma of the retinal pigment epithelium (CSHRPE) is a rare benign tumor of the retinal pigment epithelium characterized by a focal, darkly pigmented nodule in the macular lesion in healthy persons. We report a case of CSHRPE with long-term follow-up. Case: A 41-year-old Japanese woman was incidentally discovered to have a dark lesion on the fundus of the left eye. We evaluated the patient by measuring her best-corrected visual acuity (BCVA) and by slit-lamp biomicroscopy, fundus color photography, and optical coherence tomography (OCT) over a 10-year period. The BCVA gradually declined during the early follow-up period, having decreased from 1.2 to 0.8 in the left eye 3 years after the initial examination, and then has been maintained for the following 7 years. The lesion did not show a change in OCT 10 years after the first examination. Conclusion: It is important to follow a CSHRPE carefully over the long term because visual acuity might decrease.
Gastritis Can Cause and Trigger Chronic Spontaneous Urticaria Independent of the Presence of Helicobacter pylori
Authors: Zheleznov Semen , Urzhumtseva Galina , Petrova Natalia , Sarsaniia Zhanna , Didkovskii Nikolai , Dörr Tamara , Zuberbier Torsten
Published: March 2018

Background/Aim: In chronic spontaneous urticaria (CSU), Helicobacter pylori (HP) has been discussed as a cause, but it is unknown whether the bacterium itself or concomitant inflammation is causing the urticaria. Our aim was to investigate HP and upper gastrointestinal lesions as signs of inflammation independently of each other in the pathogenesis of CSU. Methods: A total of 36 prospectively enrolled CSU patients from Moscow were investigated by gastroscopy and screened for the presence of HP and/or upper gastrointestinal lesions. Those having a positive result were treated according to the Maastricht III recommended guidelines for eradication therapy, and success was assessed by a follow-up gastroscopy. Simultaneously, the activity of CSU was measured before and after therapy of the gastrointestinal condition. Results: HP was observed in 26 of the 36 patients. Erosions or ulcers were found in 18 of the 36 patients, 14 of whom were also positively tested for HP. There was a significant difference in improvement of urticarial symptoms between those who succeeded in healing the erosions and those who did not succeed (p < 0.01) independent of the presence of HP. No significant difference in symptom relief was observed between those who had successful eradication and those in whom HP eradication failed. Conclusions: Upper gastrointestinal inflammatory disorders can cause CSU and trigger exacerbations independently of HP. This might imply that also in HP-positive patients, urticaria is not based on an immunological reaction against the germ but rather on the underlying inflammation. These findings also strengthen the importance of a gastroenterological workup of patients with CSU.
Adult Coats Disease Presenting as Subfoveal Nodule
Authors: Asaad Salim Z. , Hussain Nazimul
Published: March 2018

A 21-year-old female presented with decreased vision in the right eye. Best corrected visual acuity was 6/60 in the right eye and 6/6 in the left eye. Funduscopy of the right eye revealed a subfoveal nodule with surrounding exudates and temporal peripheral retinal vessel telangiectasia with exudation. The patient underwent retinal laser in the areas of telangiectatic vessels and capillary non-perfusion as seen on fundus fluorescein angiography. It was combined with an intravitreal injection of bevacizumab which was repeated twice at monthly intervals. The macular lesion and peripheral vessels along with subretinal exudates showed resolution during the course of treatment. However, the patient was lost to follow-up and returned 5 months later when examination revealed increased macular fibrosis. In the literature, the reported presentation of subfoveal nodule in Coats disease is during the first decade. It progresses to macular fibrosis within a few months. This case illustrates that subfoveal nodule before macular fibrosis in Coats disease may present later, even up to the third decade.
Incidental Squamous Cell Carcinoma in an Epidermal Inclusion Cyst: A Case Report and Review of the Literature
Authors: Frank Ethan , Macias David , Hondorp Brian , Kerstetter Justin , Inman Jared C.
Published: March 2018

Epidermal inclusion cysts are common lesions that rarely develop into squamous cell carcinoma (SCC). Neoplastic change in these cysts can be associated with prominent symptoms such as pain, rapid growth, or ulceration. This study describes the case of a 64-year-old woman with a 4-year history of a largely asymptomatic neck mass, which after routine excision was found to be an epidermal inclusion cyst harboring well-differentiated SCC. The diagnosis was made incidentally after routine cyst bisection and hematoxylin and eosin staining. Given the potential for variable presentation and low cost of hematoxylin and eosin analysis, we recommend a low threshold for a comprehensive pathological search for malignancy in excised cysts when appropriate.
Clinicopathological Characteristics, Surgical Treatments, and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumor
Authors: Zhang Shuisheng , Tian Yuan , Chen Yingtai , Zhang Jianwei , Zheng Cuiling , Wang Chengfeng
Published: March 2018

Background: Duodenal gastrointestinal stromal tumors (GISTs) are rare and their clinicopathological features have not been completely described. In this retrospective study, we examined the characteristics and long-term outcomes of patients who underwent surgical treatment for duodenal GISTs. Methods: We examined patients surgically treated for duodenal GISTs from 1999 to 2016 at the China National Cancer Center. We analyzed patient characteristics, treatments, histological examinations, and survival outcomes. Results: The 52 surgeries performed included 14 pancreaticoduodenectomies (26.9%), 37 limited resections (71.2%), and one palliative bypass procedure (1.9%). No surgery-related death occurred. The complication rate in patients who underwent pancreaticoduodenectomy was slightly higher than that in patients who underwent limited resection. The 5-year overall survival and progression-free survival rates for patients with duodenal adenocarcinoma were 89.1 and 72.9%, respectively. The overall survival and progression-free survival rates were not significantly related to surgical methods. Large tumor size and high mitotic rate were associated with poor overall survival outcomes. However, no independent factor was associated with prognosis, which may be due to the small sample size. Conclusion: The prognosis of duodenal gastrointestinal stromal tumors was good. Limited resection seems to be oncologically feasible, with outcomes being less worse than those of pancreaticoduodenectomy.
Cardiac-Specific Overexpression of Silent Information Regulator 1 Protects Against Heart and Kidney Deterioration in Cardiorenal Syndrome via Inhibition of Endoplasmic Reticulum Stress
Authors: Huang Dong , Yan Mei-ling , Chen Kan-kai , Sun Rong , Dong Zhi-feng , Wu Peng-long , Li Shuai , Zhu Guang-shuo , Ma Shi-xin , Pan Ye-sheng , Pan Jing-wei , Zhu Wei , Xu Jun , Wei Meng , Li Jing-bo
Published: March 2018

Background/Aims: Increased endoplasmic reticulum (ER) stress contributes to development of cardiorenal syndrome (CRS), and Silent Information Regulator 1 (SIRT1), a class III histone deacetylase, may have protective effects on heart and renal disease, by reducing ER stress. We aimed to determine if SIRT1 alleviates CRS through ER stress reduction. Methods: Wild type mice (n=37), mice with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and corresponding controls, were randomized into four groups: sham MI (myocardial infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx) and myocardial infarction (MI) (induced by ligation of the left anterior descending (LAD) coronary artery) were performed successively to establish CRS model. At week 8, the mice were sacrificed after sequential echocardiographic and hemodynamic studies, and then pathology and Western-blot analysis were performed. Results: Neither MI nor STNx alone significantly influenced the other healthy organ. However, in MI groups, STNx led to more severe cardiac structural and functional deterioration, with increased remodeling, increased BNP levels, and decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups. Conversely, in STNx groups, MI led to renal structural and functional deterioration, with more severe morphologic changes, augmented desmin and decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx groups, SIRT1 knockout led to more severe cardiac structural and functional deterioration, with higher Masson-staining score and BNP levels, and lower EF, FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater structural and functional deterioration, as evidenced by more severe morphologic changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-β expression, while SIRT1 overexpression resulted in less severe morphologic changes and increased nephrin expression without significant influence on BUN or SCr levels. The SIRT1 knockout but not overexpression resulted in increased myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or overexpression resulted in increased or decreased renal expression of CHOP, Bax, and p53 respectively. Conclusions: Myocardial SIRT1 activation appears protective to both heart and kidney in CRS models, probably through modulation of ER stress.
The Antimuscarinic Agent Tolterodine Regulates Bladder Extracellular Matrix in Partial Bladder Outlet Obstruction in Rats
Authors: Yang Tong-Xin , Luo De-Yi , Lin Yi-Fei , Liu Qiang , Cai Xiang , Ai Jian-Zhong , Li Hong , Shen Hong , Wang Kun-Jie
Published: March 2018

Background/Aims: Antimuscarinic agents can delay the progression of bladder dysfunction caused by bladder outlet obstruction (BOO). To date, the relationship between muscarinic receptor activity and the bladder extracellular matrix (ECM) remains unclear. Thus, an animal model of partial BOO (PBOO) in female rats was established to explore the variation in bladder wall ECM proteins under PBOO conditions with antimuscarinic agent administration. Methods: Rats were randomly divided into three groups: sham, PBOO, and PBOO plus tolterodine. Picrosirius red staining was used to examine the smooth muscle and collagen content of bladder samples. Gene microarray and RT-PCR were performed to survey the expression of ECM proteins, receptors, and metabolism regulators in the rat bladder. Positive results were further evaluated by immunohistochemistry. Results: Picrosirius red staining showed that smooth muscle volume significantly increased in the PBOO and PBOO plus tolterodine groups (p < 0.05), while collagen significantly increased in the PBOO group (p < 0.05) but not in the PBOO plus tolterodine group. Gene microarray and RT-PCR revealed that none of the collagen subtypes exhibited significant changes after PBOO establishment and tolterodine administration. However, matrix metalloproteinases (MMPs) increased significantly in the PBOO plus tolterodine group (p < 0.05). Additionally, PBOO inhibited the expression of non-collagen ECM proteins in the rat bladder wall, while tolterodine induced the expression of non-collagen ECM proteins and ECM receptors. Conclusions: Tolterodine decreased the volume of collagen in PBOO rat bladder wall, possibly via MMPs, and regulated the expression of ECM proteins and receptors.
The Immunogenicity and Anti-Tumor Efficacy of a Rationally Designed EGFR Vaccine
Authors: Cheng Chao , Deng Li , Li Rongxiu
Published: March 2018

Background/Aims: The abnormally activated EGFR promotes tumor growth, invasion and metastasis. Current therapeutics targeting EGFR have markedly improved the clinical outcome, but they are limited in use due to transient efficacy, frequent administration, high cost and significant toxicity. Methods: We rationally designed a multiepitope immunogen against EGFR, named as DEGFRm. The immunogen is composed of an epitope peptide (EGFR265-283) and the extracellular domain III (EGFR334-505) of mouse EGFR. EGFR265-283 is grafted onto the translocation domain of diphtheria toxin (DTT), and EGFR334-505 is fused to C-terminal of DTT. Next, the immunogenicity and anti-tumor efficacies of DEGFRm vaccine were examined in mouse tumor models. Results: When formulated with Alum and CpG, DEGFRm vaccine elicits Th 1 immune responses and inhibits tumor growth in both prophylactic and therapeutic mouse tumor models. Moreover, the tumor microvasculature is markedly reduced and the tumor infiltration of CD8+ T lymphocytes is greatly enhanced. Conclusions: These data suggest that active immunization with DEGFRm vaccine is a promising strategy for therapy of various EGFR+ cancers.
Роль дисфункції щитоподібної залози у патогенезі генералізованого пародонтиту (огляд літератури)
Authors: Shcherba V. V. , Korda M. M.
Published: March 2018

Summary. Endocrine diseases are an actual medical and social problem of modern society. Changes in the activity of the thyroid gland inevitably affect the various systems of the organism, including the function and morphology of the organs and tissues of the oral cavity.The aim of the study – to determine the influence of thyroid gland dysfunction on the course of chronic inflammatory diseases of the periodontium, based on the analysis of the literature data.Materials and Methods. The bibliosemantic and analytical methods have been used.Results and Discussion. The article presents modern data on the course of chronic generalized periodontitis in case of hyperthyroidism and hypothyroidism. At the moment there is no definitive opinion regarding the influence of thyroid hormones on bone metabolism, since the duality of their effects is proved. Various studies show ambiguous data on metabolic changes in periodontal tissues in case of dysfunction of the thyroid gland.Conclusion. An analysis of the results of research by scientists suggests that dysfunction of the thyroid gland adversely affects the course of chronic inflammatory diseases of the periodontium. Despite the large number of studies, the molecular mechanisms of the influence of thyroid hormones on bone metabolism in general and the state of periodontal tissues, in particular, have not been completely studied.
GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to Right-Left Type Bicuspid Aortic Valve
Authors: Gharibeh Lara , Komati Hiba , Bossé Yohan , Boodhwani Munir , Heydarpour Mahyar , Fortier Megan , Hassanzadeh Romina , Ngu Janet , Mathieu Patrick , Body Simon , Nemer Mona ,   On behalf of the Bicuspid Aortic Valve Consortium
Published: March 2018

Background:

Bicuspid aortic valve (BAV), the most common congenital heart defect affecting 1% to 2% of the population, is a major risk factor for premature aortic valve disease and accounts for the majority of valve replacement. The genetic basis and mechanisms of BAV etiology and pathogenesis remain largely undefined.

Methods:

Cardiac structure and function was assessed in mice lacking a
Gata6
allele. Human
GATA6
gene variants were analyzed in 452 BAV cases from the BAV consortium and 1849 controls from the Framingham GWAS (Genome Wide Association Study). GATA6 expression was determined in mice and human tissues using quantitative real-time polymerase chain reaction and immunohistochemistry. Mechanistic studies were carried out in cultured cells.

Results:

Gata6
heterozygous mice have highly penetrant right-left (RL)-type BAV, the most frequent type in humans. GATA6 transcript levels are lower in human BAV compared with normal tricuspid valves. Mechanistically,
Gata6
haploinsufficiency disrupts valve remodeling and extracellular matrix composition through dysregulation of important signaling molecules, including matrix metalloproteinase 9. Cell-specific inactivation of
Gata6
reveals an essential role for GATA6 in secondary heart field myocytes because loss of 1
Gata6
allele from
Isl
-
1
-positive cells—but not from endothelial or neural crest cells—recapitulates the phenotype of
Gata6
heterozygous mice.

Conclusions:

The data identify a new cellular and molecular mechanism underlying BAV. The availability of an animal model for the most frequent human BAV opens the way for the elucidation of BAV pathogenesis and the development of much needed therapies.
Improving Community Stroke Preparedness in the HHS (Hip-Hop Stroke) Randomized Clinical Trial
Authors: Williams Olajide , Leighton-Herrmann Quinn Ellyn , Teresi Jeanne , Eimicke Joseph P. , Kong Jian , Ogedegbe Gbenga , Noble James
Published: March 2018

Background and Purpose—

Deficiencies in stroke preparedness cause major delays to stroke thrombolysis, particularly among economically disadvantaged minorities. We evaluated the effectiveness of a stroke preparedness intervention delivered to preadolescent urban public school children on the stroke knowledge/preparedness of their parents.

Methods—

We recruited 3070 fourth through sixth graders and 1144 parents from 22 schools into a cluster randomized trial with schools randomized to the HHS (Hip-Hop Stroke) intervention or attentional control (nutrition classes). HHS is a 3-hour culturally tailored, theory-based, multimedia stroke literacy intervention targeting school children, which systematically empowers children to share stroke information with parents. Our main outcome measures were stroke knowledge/preparedness of children and parents using validated surrogates.

Results—

Among children, it was estimated that 1% (95% confidence interval [CI], 0%–1%) of controls and 2% (95% CI, 1%–4%;
P
=0.09) of the intervention group demonstrated optimal stroke preparedness (perfect scores on the knowledge/preparedness test) at baseline, increasing to 57% (95% CI, 44%–69%) immediately after the program in the intervention group compared with 1% (95% CI, 0%–1%;
P
<0.001) among controls. At 3-month follow-up, 24% (95% CI, 15%–33%) of the intervention group retained optimal preparedness, compared with 2% (95% CI, 0%–3%;
P
<0.001) of controls. Only 3% (95% CI, 2%–4%) of parents in the intervention group could identify all 4 letters of the stroke FAST (Facial droop, Arm weakness, Speech disturbance, Time to call 911) acronym at baseline, increasing to 20% at immediate post-test (95% CI, 16%–24%) and 17% at 3-month delayed post-test (95% CI, 13%–21%;
P
=0.0062), with no significant changes (3% identification) among controls. Four children, all in the intervention group, called 911 for real-life stroke symptoms, in 1 case overruling a parent’s wait-and-see approach.

Conclusions—

HHS is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01497886.