bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplicity Results to a Conformable Fractional Differential Equations Involving Integral Boundary Condition
Authors: Meng Shuman , Cui Yujun
Published: April 2019

In this article, by using topological degree theory couple with the method of lower and upper solutions, we study the existence of at least three solutions to Riemann‐Stieltjes integral initial value problem of the type Dαx(t) = f(t, x),   t ∈ [0,1], , where Dαx(t) is the standard conformable fractional derivative of order α, 0 < α ≤ 1, and . Simultaneously, the fixed point theorem for set‐valued increasing operator is applied when considering the given problem.
Computational Assessment of Thermal Conductivity of Compacted Graphite Cast Iron
Authors: Wu Yue , Li Jianping , Yang Zhong , Ma Zhijun , Guo Yongchun , Tao Dong , Yang Tong , Liang Minxian
Published: April 2019

Two-dimensional FE models of CGI with different pearlite contents for thermal conductivity analysis were established according to the real metallographic images obtained by Pro/E and ANSYS. Meanwhile, thermal conductivity of CGI with different pearlite contents was tested through the laser flash method. It is indicated that the thermal conductivity of CGI declines with the increase of pearlite. When pearlite is increased from 10% to 80%, the experimental values decline from 46.63 W/m·K to 36.86 W/m·K, reducing by 21%. However, this declining tendency becomes gentle and slight when pearlite is more than 40%. In addition, the calculation results with the consideration of interfacial contact thermal conductance (ICTC) and pearlite are much close to experimental values; especially when pearlite is 80%, the difference between them is only about 2%. It can be concluded that the FE models are convenient and reasonable to analyze thermal conductivity of CGI.
New Insights into the Association between Fibrinogen and Coronary Atherosclerotic Plaque Vulnerability: An Intravascular Optical Coherence Tomography Study
Authors: Wang Jun , Jia Lu , Li Xing , Jin Siyu , Li Xiaomei , Liu Fen , Shan Chunfang , Zhang Yu , Yang Yining
Published: April 2019

Background. Fibrinogen levels have been associated with coronary plaque vulnerability in experimental studies. However, it has yet to be determined if serum fibrinogen levels are independently associated with coronary plaque vulnerability as detected by optical coherence tomography (OCT) in patients with coronary heart disease. Methods. Patients with coronary heart disease (CHD) who underwent coronary angiography and OCT in our department from January 2015 to August 2018 were included in this study. Coronary lesions were categorized as ruptured plaque, nonruptured with thin-cap fibroatheroma (TCFA), and nonruptured and non-TCFA. Presence of ruptured plaque and nonruptured with TCFA was considered to be vulnerable lesions. Determinants of coronary vulnerability were evaluated by multivariable logistic regression analyses. Results. A total of 154 patients were included in this study; 17 patients had ruptured plaques, 15 had nonruptured plaques with TCFA, and 122 had nonruptured plaques with non-TCFA. Results of univariate analyses showed that being male, diabetes, current smoking, high body mass index (BMI), and clinical diagnosis of acute coronary syndrome (ACS) were associated with coronary vulnerability. No significant differences were detected in patient characteristics, coronary angiographic findings, and OCT results between patients with higher and normal fibrinogen. Results of multivariate logistic analyses showed that diabetes and ACS were associated with TCFA, while diabetes, higher BMI, and ACS were associated with plaque rupture. Conclusions. Diabetes, higher BMI, and ACS are independently associated with coronary vulnerability as detected by OCT. Serum fibrinogen was not associated with coronary vulnerability in our cohort.
Effect of Sterilization on the Properties of a Bioactive Hybrid Coating Containing Hydroxyapatite
Authors: Baldin E. K. K. , Malfatti C. F. , Rodói V. , Brandalise R. N.
Published: April 2019

The objective of this study was to evaluate the influence of sterilization on a hybrid coating obtained from a sol composed of alkoxysilane tetraethoxysilane (TEOS) and organoalkoxysilane methyltriethoxysilane (MTES) containing 10% (mass) of hydroxyapatite particles. The coating was obtained by dip coating, by applying two layers (protective/bioactive), which were cured at different temperatures (450°C and 60°C). The effects of sterilization on the superficial, electrochemical, bioactive, and mechanical properties of the coating were evaluated by performing different sterilization processes, namely, steam autoclave, hydrogen peroxide plasma, and ethylene oxide. Subsequently, the coating was characterized by using scanning electron microscopy (SEM/FEG), and FTIR measurements were performed to characterize the chemical structure. The bioactivity and degradability of the coating were analyzed by mass variation after immersion in SBF and X-ray diffraction (XRD) analysis. The electrochemical behavior was assessed by open circuit potential (OCP) and potentiodynamic polarization curves and the mechanical behavior by wear resistance. Results showed that all sterilization processes caused significant morphological changes in the hybrid coating. The autoclaved sample presented the highest structural chemical changes, and, consequently, the highest degradability, even though it had a superior bioactive behavior in relation to the other samples. In addition, the sterilization processes influenced the electrochemical behavior of the hybrid coating and altered the mechanical resistance to abrasion, thus presenting lower wear performance in relation to the nonsterilized sample.
Activated Carbon from Prickly Pear Seed Cake: Optimization of Preparation Conditions Using Experimental Design and Its Application in Dye Removal
Authors: El Maguana Y. , Elhadiri N. , Bouchdoug M. , Benchanaa M. , Jaouad A.
Published: April 2019

In the present study, the experimental design method was used to optimize the preparation conditions of an activated carbon from prickly pear seed cake by phosphoric acid activation. The parameters studied include impregnation ratio, carbonization temperature, and carbonization time. The optimal conditions for the preparation of the activated carbon with high adsorption capacity for methylene blue were identified to be an impregnation ratio of 2.9, carbonization temperature of 541°C, and carbonization time of 88 min. The obtained activated carbon was characterized by SEM/EDX, FTIR, pHpzc, and its capacity to adsorb methylene blue. FTIR analysis and pHPZC showed the acidic character of the activated carbon surface. The adsorption capacity of the optimal activated carbon was found to be 260 mg·g−1 for methylene blue. The adsorption equilibrium of methylene blue was well explained by the pseudo-second-order model and Freundlich isotherm. Furthermore, the performance of the produced activated carbon was examined by the methyl orange removal.
Nanobubbles Water Curcumin Extract Reduces Injury Risks on Drop Jumps in Women: A Pilot Study
Authors: Wang I-Lin , Hsiao Chien-Yu , Li Yu-Heng , Meng Fan-Bo , Huang Chi-Chang , Chen Yi-Ming
Published: April 2019

Purpose. To verify the beneficial effects of Nanobubbles water curcumin extract (NCE) supplementation on health promotion and to demonstrate the application of NCE in reducing the risk of musculoskeletal injury. Methods. In the current study, 12 females were randomly assigned to NCE (15g/day) and maltodextrin groups. Performance and related body composition were evaluated at 2 time points—presupplementation (pre-) and after 4 weeks of postsupplementation (post-). The posttest consists of a set of biochemical parameters for antifatigue activity and injury status evaluation. Results. NCE group exhibited significantly lower levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglycerides (TG), and higher high-density lipoprotein (HDL) after a 4-week supplementation, compared with the placebo group. After a 15-minute session on the spinning bike, serum lactate and ammonia levels were decreased and glucose was economized in the NEC group. 4-week-NCE supplementation was also able to reduce the peak vertical ground reaction force (PVGRF) during drop jump. Therefore, the risk of musculoskeletal system in lower extremity could be reduced. Conclusion. We demonstrate that 4-week-NCE supplementation can also be used in explosiveness exercise for better physiological adaptation. Thus, NCE has potential for use with nutrient supplements toward a variety of benefits for athletics.
Risk Prediction for Contrast-Induced Nephropathy in Cancer Patients Undergoing Computed Tomography under Preventive Measures
Authors: Jeon Junseok , Kim Suhyun , Yoo Heejin , Kim Kyunga , Kim Yaerim , Park Sehoon , Jang Hye Ryoun , Kim Dong Ki , Huh Wooseong , Kim Yoon-Goo , Kim Dae Joong , Oh Ha Young , Lee Jung Eun
Published: April 2019

Background. Contrast-induced nephropathy (CIN) is a major cause of acute kidney injury in chronic kidney disease. Many cancer patients have risk factors for CIN and frequently undergo contrast-enhanced computed tomography (CECT). We aimed to develop a risk prediction model for CIN in cancer patients undergoing CECT. Methods. Between 2009 and 2017, 2,240 cancer patients with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 who underwent CECT with CIN preventive measures were included in a development cohort. Primary outcome was development of CIN, defined as 25% increase in serum creatinine within 2-6 days after contrast exposure. A prediction model was developed using logistic regression analysis. The model was evaluated for prognostic utility in an independent cohort (N = 555). Results. Overall incidence of CIN was 2.5% (55/2,240). In multivariable analysis, eGFR, diabetes mellitus, and serum albumin level were identified as independent predictors of CIN. A prediction model including eGFR, serum albumin level, and diabetes mellitus was developed, and risk scores ranged from 0 to 6 points. The model demonstrated fair discriminative power (C statistic = 0.733, 95% confidence interval [CI] 0.656-0.810) and good calibration (calibration slope 0.867, 95% Cl 0.719-1.015). In the validation cohort, the model also demonstrated fair discriminative power (C statistic = 0.749, 95% CI 0.648-0.849) and good calibration (calibration slope 0.974, 95% CI 0.634-1.315). Conclusions. The proposed model has good predictive ability for risk of CIN in cancer patients with chronic kidney disease. This model can aid in risk stratification for CIN in patients undergoing CECT.
Structural and Mechanistic Bases of Nuclear Calcium Signaling in Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes
Authors: Li Sen , Keung Wendy , Cheng Heping , Li Ronald A.
Published: April 2019

The loss of nonregenerative, terminally differentiated cardiomyocytes (CMs) due to aging or diseases is generally considered irreversible. Human pluripotent stem cells (hPSCs) can self-renew while maintaining their pluripotency to differentiate into all cell types, including ventricular (V) cardiomyocytes (CMs), to provide a potential unlimited ex vivo source of CMs for heart disease modeling, drug/cardiotoxicity screening, and cell-based therapies. In the human heart, cytosolic Ca2+ signals are well characterized but the contribution of nuclear Ca2+ is essentially unexplored. The present study investigated nuclear Ca2+ signaling in hPSC-VCMs. Calcium transient or sparks in hPSC-VCMs were measured by line scanning using a spinning disc confocal microscope. We observed that nuclear Ca2+, which stems from unitary sparks due to the diffusion of cytosolic Ca2+ that are mediated by RyRs on the nuclear reticulum, is functional. Parvalbumin- (PV-) mediated Ca2+ buffering successfully manipulated Ca2+ transient and stimuli-induced apoptosis in hPSC-VCMs. We also investigated the effect of Ca2+ on gene transcription in hPSC-VCMs, and the involvement of nuclear factor of activated T-cell (NFAT) pathway was identified. The overexpression of Ca2+-sensitive, nuclear localized Ca2+/calmodulin-dependent protein kinase II δB (CaMKIIδB) induced cardiac hypertrophy through nuclear Ca2+/CaMKIIδB/HDAC4/MEF2 pathway. These findings provide insights into nuclear Ca2+ signal in hPSC-VCMs, which may lead to novel strategies for maturation as well as improved systems for disease modeling, drug discovery, and cell-based therapies.
Improved Efficiency of Cardiomyocyte-Like Cell Differentiation from Rat Adipose Tissue-Derived Mesenchymal Stem Cells with a Directed Differentiation Protocol
Authors: Ibarra-Ibarra Blanca Rebeca , Franco Martha , Paez Araceli , López Elvira Varela , Massó Felipe
Published: April 2019

Cell-based therapy has become a resource for the treatment of cardiovascular diseases; however, there are some conundrums to achieve. In vitro cardiomyocyte generation could be a solution for scaling options in clinical applications. Variability on cardiac differentiation in previously reported studies from adipose tissue-derived mesenchymal stem cells (ASCs) and the lack of measuring of the cardiomyocyte differentiation efficiency motivate the present study. Here, we improved the ASC-derived cardiomyocyte-like cell differentiation efficiency with a directed cardiomyocyte differentiation protocol: BMP-4 + VEGF (days 0-4) followed by a methylcellulose-based medium with cytokines (IL-6 and IL-3) (days 5-21). Cultures treated with the directed cardiomyocyte differentiation protocol showed cardiac-like cells and “rosette-like structures” from day 7. The percentage of cardiac troponin T- (cTnT-) positive cells was evaluated by flow cytometry to assess the cardiomyocyte differentiation efficiency in a quantitative manner. ASCs treated with the directed cardiomyocyte differentiation protocol obtained a differentiation efficiency of up to 44.03% (39.96%±3.78) at day 15 without any enrichment step. Also, at day 21 we observed by immunofluorescence the positive expression of early, late, and cardiac maturation differentiation markers (Gata-4, cTnT, cardiac myosin heavy chain (MyH), and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCa2)) in cultures treated with the directed cardiomyocyte differentiation protocol. Unlike other protocols, the use of critical factors of embryonic cardiomyogenesis coupled with a methylcellulose-based medium containing previously reported cardiogenic cytokines (IL-6 and IL-3) seems to be favorable for in vitro cardiomyocyte generation. This novel efficient culture protocol makes ASC-derived cardiac differentiation more efficient. Further investigation is needed to identify an ASC-derived cardiomyocyte surface marker for cardiac enrichment.
Safety and Efficacy of a Small J-Tipped Guidewire for Pancreatic Duct Endoscopic Intervention
Authors: Hirose Sumio , Fukasawa Mitsuharu , Takano Shinichi , Kadokura Makoto , Shindo Hiroko , Takahashi Ei , Yokota Yudai , Fukasawa Yoshimitsu , Kawakami Satoshi , Hayakawa Hiroshi , Sato Tadashi , Enomoto Nobuyuki
Published: April 2019

Background and Aims. The insertion of the guidewires (GWs) into the pancreatic duct is technically difficult, and there is a risk of post-ERCP pancreatitis (PEP). The aim of this study was to evaluate the safety and efficacy of a small J-tipped guidewire for pancreatic duct endoscopic intervention. Methods. This single-site retrospective study was conducted to assess the procedural success rate and adverse events of endoscopic transpapillary interventions to the pancreatic duct in 114 cases using the small J-tipped GW and 180 cases using the angle-tipped GW. Results. The procedural success rate was significantly higher in the small J-tipped GW group compared with that in the angle-tipped GW group (76% versus 47%, P < 0.001). The procedural success-related factors were chronic pancreatitis (OR 0.43, 95% CI 0.22–0.82, P = 0.01), flexion angle of the pancreatic duct < 90° (OR 0.50, 95% CI 0.30–0.80, P = 0.01), and use of the small J-tipped GW (OR 4.63, 95% CI 2.61–8.20, P < 0.001). The rates of total post-ERCP pancreatitis were significantly lower in the small J-tipped GW group compared with that in the angle-tipped GW group (3.5% versus 12.2%, P = 0.01). Multivariate analysis of pancreatitis risk factors indicated that only the use of the small J-tipped GW was a factor in decreasing the risk of developing pancreatitis (OR 0.12, 95% CI 0.09–0.85, P = 0.02). Conclusions. Small J-tipped GWs increase the success rate of the pancreatic duct endoscopic intervention as well as a reduced risk of developing postoperative pancreatitis.
Small-Cell Type, Poorly Differentiated Neuroendocrine Carcinoma of the Gallbladder: A Case Report and Review of the Literature
Authors: Kumar Kishore , Tariq Hassan , Ahmed Rafeeq , Chukwunonso Chime , Niazi Masooma , Ihimoyan Ariyo
Published: April 2019

The poorly differentiated small-cell type, neuroendocrine carcinoma (NEC) of the gallbladder is a very uncommon subtype of a neuroendocrine tumor of the gastrointestinal tract. Nonsecretory NEC by virtue of its nonspecific and subtle clinical presentation of the tumor is usually diagnosed at an advance stage with presenting symptoms related to either locally advance disease or from metastatic disease. Though the radiologic imaging does identify the gall bladder cancer, the tumor lacks a specific diagnostic test; therefore, the diagnosis is almost always confirmed on histopathologic and immunohistochemical staining. We present a case of a poorly differentiated, small-cell neuroendocrine tumor of the gallbladder. The patient died within 3 months after the definitive diagnosis was made. Survival from this deadly malignancy can be improved with aggressive surgical treatment followed by chemotherapy and radiotherapy on a case-by-case scenario. The systemic chemotherapy remained the treatment of choice for an unresectable tumor (Chen et al., 2014).
Upgrading Bio-Oil Produced from Corn Cobs and Cedrela odorata via Catalytic Olefination and Esterification with 3,7-Dimethyloct-1-ene and Butanol
Authors: Dawodu Folasegun A. , Ayodele Olubunmi O. , Akintola John O. , Obembe Oluwamayokun A. , Sanni Ameerah O. , Agbejinmi Bosede D.
Published: April 2019

In this study, corn cobs (CC) and Cedrela odorata (CO) sawdust which are common waste materials in Nigeria were used as raw materials in the production of bio-oil through pyrolysis at 500°C, for 2 h. The biochar produced in the process was sulfonated with concentrated sulfuric acid under reflux at 150°C for 6 h and used as a solid acid catalyst for bio-oil upgrading. The bio-oil was upgraded by simultaneous olefination and esterification using 3,7-dimethyloct-1-ene and butanol which served as a reagent and cosolvent. FT-IR spectra of the activated biochar from CC and CO raw materials showed an absorbance in the range of 1032–1180 cm−1, which is indicative of asymmetric S=O bonds, and the spectra also revealed a band between 3400 and 3700 cm−1, which indicated presence of hydrogen-bonded hydroxyl groups and thus successful activation of the biochar. This observed IR absorbance was absent in the nonactivated biochar. Proximate analysis of upgraded bio-oils revealed a significant reduction in percentage water and oxygen contents, an increase in the high heating value (HHV) and flammability. The chemical composition of the bio-oils was determined using GC-MS, and it showed significant reduction in oxygenated compounds in the upgraded bio-oil as against their high composition in raw bio-oils.
A Framework and Numerical Solution of the Drying Process in Porous Media by Using a Continuous Model
Authors: Vu Hong Thai , Tsotsas Evangelos
Published: April 2019

The modelling and numerical simulation of the drying process in porous media are discussed in this work with the objective of presenting the drying problem as the system of governing equations, which is ready to be solved by many of the now widely available control-volume-based numerical tools. By reviewing the connection between the transport equations at the pore level and their up-scaled ones at the continuum level and then by transforming these equations into a format that can be solved by the control volume method, we would like to present an easy-to-use framework for studying the drying process in porous media. In order to take into account the microstructure of porous media in the format of pore-size distribution, the concept of bundle of capillaries is used to derive the needed transport parameters. Some numerical examples are presented to demonstrate the use of the presented formulas.
Nutrition Knowledge and Satisfaction Levels of Postbariatric Surgery Adults in the United Arab Emirates: A Pilot Study
Authors: Alia Souheir , Ali Habiba I. , Zoubeidi Taoufik , Ahmed Mariam
Published: April 2019

Research assessing the nutrition knowledge of postbariatric surgery patients is limited, although this category of patients is predisposed to malnutrition. In this pilot study, we explored postbariatric nutrition knowledge, satisfaction levels with dietitian nutrition counseling, and decision to undergo bariatric surgery of 83 patients who attended a postbariatric outpatient nutrition clinic in Dubai, United Arab Emirates (UAE). A cross-sectional design involving gender-stratified random sampling method was used to recruit 83 postbariatric surgery participants. A self-administered questionnaire was employed to collect information about nutrition knowledge related to dietary recommendations after bariatric surgery as well as participant views on dietitian nutrition counseling, their decision to undergo bariatric surgery, and nutrition-related complications experienced after the surgery. The mean (SD) knowledge score of postbariatric diet was 9.7 (2.05) out of a maximum possible score of 14. The majority of the participants (78.3%) correctly identified which foods are recommended during the first stage of the postbariatric surgery diet, and more than 90% knew about the importance of high-protein supplements after bariatric surgery. Female participants had significantly higher mean knowledge score compared to males (p=0.02). Although nearly 80% of the participants reported regular follow-up with their dietitian, only 10.8% reported high adherence to the dietitian’s instructions. Moreover, more than two-thirds of the participants (71.1%) rated dietary advice provided by dietitians as vague. The most common complication experienced by the participants after bariatric surgery was nausea (61.4%). Furthermore, the majority of the participants (83.4%) found their daily and leisure activities to be more enjoyable after bariatric surgery. Ways of improving the quality of information delivery by dietitians should be explored to enhance patient comprehension and adherence to postbariatric surgery diet recommendations. Future research involving a larger and more representative sample to extend our findings are needed.
An Adverse Outcome Pathway Linking Organohalogen Exposure to Mitochondrial Disease
Authors: McMinn Brooke , Duval Alicia L. , Sayes Christie M.
Published: April 2019

Adverse outcome pathways (AOPs) are pragmatic tools in human health hazard characterization and risk assessment. As such, one of the main goals of AOP development is to provide a clear, progressive, and linear mechanistic representation of pertinent toxicological key events (KEs) occurring along the different levels of biological organization. Here, we present an AOP framework that depicts how exposure to organohalogens can lead to mitochondrial disease. Organohalogens are disinfectant by-products (DBPs) found in our drinking water. Chloroform, trichloroacetic acid, and trichlorophenol were selected to represent specific types of organohalogens for the development of this AOP. Although each of these compounds contains chlorine atoms, they differ in aromaticity and solubility, which have a significant impact on their potency. This AOP consists of two main pathways, both of which are triggered by the molecular initiating event (MIE) of excessive reactive oxygen species generation. Pathway 1 details the downstream consequences of oxidative stress, which include mitochondrial DNA damage, protein aggregation, and depolarization of the mitochondrial membrane. Pathway 2 shows the KEs that result from inadequate supply of glutathione, including calcium dysregulation and ATP depletion. Pathways 1 and 2 converge at a common KE: opening of the mitochondrial membrane transition pore (mPTP). This leads to the release of cytochrome c, caspase activation, apoptosis, and mitochondrial disease. This AOP was developed according to the Organisation for Economic Co-operation and Development guidance, including critical consideration of the Bradford Hill criteria for Weight of Evidence assessment and key questions for evaluating confidence. The presented AOP is expected to serve as the basis for designing new toxicological tests as well as the characterization of novel biomarkers for disinfectant by-product exposure and adverse health effects.
Experimental Verification of Impact of Sprinkled Area Length on Heat Exchange Coefficient
Authors: Kracik Petr , Balas Marek , Lisy Martin , Pospisil Jiri
Published: April 2019

On a sprinkled tube bundle, liquid forms a thin liquid film, and, in the case of boiling liquid, the liquid phase can be quickly and efficiently separated from the gas phase. There are several effects on the ideal flow mode and the heat transfer from the heating to the sprinkling liquid. The basic quantity is the flow rate of the sprinkling liquid, but also diameter of the tubes, pipe spacing of the tube bundle, and physical state of the sprinkling and heating fluid. Sprinkled heat exchangers are not a new technology and studies have been carried out all over the world. However, experiments (tests) have always been performed under strict laboratory conditions on one to three relatively short tubes and behaviour of the flowing fluid on a real tube bundle has not been taken into account, which is the primary aim of our research. In deriving and comparing the results among the studies, the mass flow rate based on the length of the sprinkled area is used, thus trying to adjust the different length of the heat exchanger. This paper presents results of atmospheric pressure experiments measured on two devices with different lengths of the sprinkled area but with the same number of tubes in the bundle with same pitch and surface at a temperature gradient of 15/40°C, where 15°C is the sprinkling water temperature at the outlet of the distribution pipe and 40°C is the temperature of heating water entering the bundle.
Soft Palate Modification Using a Collagen Crosslinking Reagent for Equine Dorsal Displacement of the Soft Palate and Other Upper Airway Breathing Disorders
Authors: Hunt Stephanie , Kuo Jonathan , Aristizabal Fabio A. , Brown Matt , Patwardhan Abhijit , Hedman Thomas
Published: April 2019

The mechanical properties of the soft palate can be associated with breathing abnormalities. Dorsal displacement of the soft palate (DDSP) is a naturally occurring equine soft palate disorder caused by displacement of the caudal edge of the soft palate. Snoring and a more serious, sometimes life-threatening, condition called obstructive sleep apnea (OSA) are forms of sleep-related breathing disorders in humans which may involve the soft palate. The goal of this study was to investigate the effect of injecting the protein crosslinker genipin into the soft palate to modify its mechanical properties for the treatment of equine DDSP with potential implications for the treatment of snoring and OSA in humans. Ex vivo experiments consisted of mechanical testing and a wind tunnel study to examine the effect of genipin on the mechanical properties, displacement, and vibration of equine soft palates. A pilot in vivo study was completed using DDSP and control horses to test the safety and effectiveness of injecting a genipin reagent into the soft palate. The wind tunnel testing demonstrated a greater than 50% decrease in transient deformation and a greater than 33% decrease in steady-state vibrations for all doses of genipin tested. Ultimate tensile stress, yield stress, and Young’s modulus were higher in the genipin-treated distal soft palate specimens by 52%, 53%, and 63%, respectively. The pilot in vivo study showed a reduction of snoring loudness in all DDSP horses and elimination of DDSP in at least one of three horses. The difficulty of using a 1-meter-long endoscopic injection needle contributed to a consistent overinjection of the equine soft palates, causing excessive stretching (pillowing) and related degradation of the tissue. These ex vivo and in vivo results demonstrated reduced vibration amplitude and flaccidity and increased strength of genipin-treated soft palates, suggesting that genipin crosslinking could become an effective and safe treatment for soft palate related breathing abnormalities.
Concurrent, Performance-Based Methodology for Increasing the Accuracy and Certainty of Short-Term Neural Prediction Systems
Authors: Milić Miljana , Milojković Jelena , Marković Ivan , Nikolić Petar
Published: April 2019

Accurate prediction of the short time series with highly irregular behavior is a challenging task found in many areas of modern science. Such data fluctuations are not systematic and hardly predictable. In recent years, artificial neural networks have widely been exploited for those purposes. Although it is possible to model nonlinear behavior of short time series by using ANNs, very often they are not able to handle all events equally well. Therefore, alternative approaches have to be applied. In this study, a new, concurrent, performance-based methodology that combines best ANN topologies in order to decrease the forecasting errors and increase the forecasting certainty is proposed. The proposed approach is verified on three different data sets: the Serbian Gross National Income time series, the municipal traffic flow for a particular observation point, and the daily electric load consumption time series. It is shown that the method can significantly increase the forecasting accuracy of the individual networks, regardless of their topologies, which makes the methodology more applicable. For quantitative comparison of the accuracy of the proposed methodology with that of similar methodologies, a series of additional forecasting experiments that include a state-of-the-art ARIMA modelling and a combination of ANN and linear regression forecasting have been conducted.
Bifurcation, Chaos, and Pattern Formation for the Discrete Predator-Prey Reaction-Diffusion Model
Authors: Meng Lili , Han Yutao , Lu Zhiyi , Zhang Guang
Published: April 2019

In this paper, a discrete predator-prey system with the periodic boundary conditions will be considered. First, we get the conditions for producing Turing instability of the discrete predator-prey system according to the linear stability analysis. Then, we show that the discrete model has the flip bifurcation and Turing bifurcation under the critical parameter values. Finally, a series of numerical simulations are carried out in the Turing instability region of the discrete predator-prey model; some new Turing patterns such as striped, bar, and horizontal bar are observed.
Melittin Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation and Epithelial-Mesenchymal Transition through Suppression of HIF-1α/Akt Pathway in Liver Cancer
Authors: Chen Qunwei , Lin Wanfu , Yin Zifei , Zou Yong , Liang Shufang , Ruan Shanming , Chen Peifeng , Li Shu , Shu Qijin , Cheng Binbin , Ling Changquan
Published: April 2019

In this study, we investigated whether melittin could suppress hypoxia-induced vasculogenic mimicry (VM) formation in liver cancer and explored the underlying mechanisms. Melittin significantly inhibited the proliferation of liver cancer cells with or without CoCl2presence. Melittin also significantly inhibited CoCl2-induced migration, invasion, and VM formation of liver cancer cells. CoCl2treatment suppressed the expression of E-cadherin and elevated the expression of N-cadherin and Vimentin. Melittin reversed the changes in the protein and mRNA levels of these epithelial-mesenchymal transition (EMT) markers. CoCl2-induced accumulation of HIF-1αincreased the level of phosphorylated Akt and upregulated the expression of VEGF and MMP-2/9. Melittin decreased the HIF-1αlevel and thereby suppressed the levels of p-Akt, VEGF, and MMP-2/9. In addition, the inhibitor of PI3K/Akt also suppressed CoCl2-induced EMT and liver cancer cells migration, and the activator of Akt, SC-79, partly blocked the effect of melittin on CoCl2-induced EMT and liver cancer cells migration. In the xenograft tumor model in nude mice, melittin treatment significantly suppressed the tumor growth, VM formation, and HIF-1αexpression in the tumor. In conclusion, this study indicates melittin may inhibit hypoxia-induced VM formation and EMT in liver cancer through inhibiting HIF-1α/Akt pathway.
The Chinese Association for the Study of Pain (CASP): Expert Consensus on the Cervicogenic Headache
Authors: Xiao Hong , Peng Baogan , Ma Ke , Huang Dong , Liu Xianguo , Lu Yan , Liu Qing , Lu Lijuan , Liu Jingfeng , Li Yimei , Song Tao , Tao Wei , Shen Wen , Yang Xiaoqiu , Wang Lin , Zhang Xiaomei , Zhuang Zhigang , Liu Hui , Liu Yanqing
Published: April 2019

Cervicogenic headache is a relatively common but unique form of headache, and in China, as well as in several other countries, both diagnosis and a clear evidence-based treatment plan remain controversial. Therefore, the Chinese Association for the Study of Pain organized a meeting of pain management experts and created an expert consensus on the diagnosis and treatment of cervicogenic headache in China. This article summarizes the conclusions of the consensus group regarding the epidemiology, etiology, clinical features, diagnosis, differential diagnosis, treatment, and rehabilitation of cervicogenic headache in China.
EPLC: An Efficient Privacy-Preserving Line-Loss Calculation Scheme for Residential Areas of Smart Grid
Authors: Xiong Yinqiao , Zhu Peidong , Liu Zhizhu , Yin Hui , Deng Tiantian
Published: April 2019

Recently, smart grid is considered as the next generation of power grid by introducing information and communication technologies. Line-loss is an important synthetic indicator which can directly reflect the energy efficiency and power management level of smart grid enterprises. In order to obtain all residential areas, line-loss requires obtaining electricity consumption of each user. However, data about users’ electricity consumption could reveal sensitive information; a sophisticated adversary can use some data analysis methods to deduce economic situation, habits, lifestyles, etc. In order to solve the problem, we propose an Efficient Privacy-preserving scheme for Line-loss Calculation, named EPLC. In our scheme, a data item is reading from one smart meter which implies the energy consumption in a time period of the user who owns it, and each user lives in a residential area. For each user, we encrypt user’s data based on Paillier cryptosystem by using two Horner parameters, by leveraging homomorphism, and each residential area gateway calculates relevant data about corresponding line-loss and control center hides the area-level polynomial into the final output for representing line-loss of all residential areas which are both in the form of ciphertext. Finally, we can still recover each residential area line-loss with possessing private keys and Horner parameters. Moreover, EPLC adopts the batch verification technique to lower authentication cost. Finally, our analysis indicates that EPLC is not only efficient but also can protect individual user’s electricity consumption privacy, and the flexibility and expansibility of EPLC are very suitable for smart grid.
Bifurcation Based‐Delay Feedback Control Strategy for a Fractional‐Order Two‐Prey One‐Predator System
Authors: Li Shuai , Huang Chengdai , Song Xinyu
Published: April 2019

The issue of bifurcation control for a novel fractional‐order two‐prey and one‐predator system with time delay is dealt with in this paper. Firstly, the characteristic equation is investigated by picking time delay as the bifurcation parameter, and some conditions for the appearance of Hopf bifurcation are obtained. It is shown that time delay can give rise to periodic oscillations and each order has an important impact on the occurrence of Hopf bifurcation for the controlled system. Then, it is illustrated that the control result is obviously influenced by the feedback gain. It is also noted that the inception of the bifurcation can be postponed if the feedback gain decreases. Finally, two simulation examples are carried out to verify the chief theoretical results.
Dermatological Disorders following Liver Transplantation: An Update
Authors: Yadav Dipesh Kumar , Bai Xue li , Liang Tingbo
Published: April 2019

Patients undergoing liver transplantation (LT) are at a high risk of dermatological complications compared to the general population as a result of long-term use of immunosuppressant. However, the risk is not as high as other solid organ transplantations (SOT), particularly for skin cancer. The liver is considered as an immune privileged organ since it has a low prevalence of humoral rejection in contrast to other SOT, and thus, LT requires a minimal amount of immunosuppressants compared to other SOT recipients. However, because of the large volume of the liver, patients with LT have higher donor lymphocytes that sometimes may trigger graft-versus-host-disease, yet it is rare. On the other hand, the vast majority of the nonspecific dermatological lesions linked with cirrhosis improve after removal of diseased liver or due to the immunosuppressant used after LT. Nevertheless, dermatological infections related to bacteria, viruses, and fungus after LT are not uncommon. Additionally, the incidence of IgE-mediated food allergies develops in 12.2% of LT patients and may present as life-threatening conditions such as urticaria and/or angioedema and hypersensitivity. Moreover, skin malignancies after LT are a matter of concern. Thus, posttransplant dermatological care should be provided to all LT patients for any suspicious dermatological lesions. Our goal is to give an outline of the dermatological manifestation associated with LT for the clinicians by collecting the published data from all archived case reports.
Solid Tumor–Induced Immune Regulation Alters the GvHD/GvT Paradigm after Allogenic Bone Marrow Transplantation
Authors: Dang Nana , Lin Yuan , Rutgeerts Omer , Sagaert Xavier , Billiau An D. , Waer Mark , Sprangers Ben
Published: April 2019

Growth of solid tumors is often associated with the development of an immunosuppressive tumor microenvironment (TME). It has been suggested that the influence of the TME may extend beyond the local tumor and results in systemic immunosuppression. Here, we utilize two murine cancer models to explore the influence of solid tumors on the occurrence of alloreactivity-driven GvHD and graft-versus-solid tumor (GvT) effects following MHC-mismatched allogeneic bone marrow transplantation (allo-BMT). Melanoma- or colon carcinoma–bearing C57BL/6 mice did not develop GvHD after BMT even when the bone marrow inoculum was supplemented with donor-type splenocytes. This protection against GvHD required the presence of tumors because its resection prior to allo-BMT promptly resulted in development of GvHD. In addition, tumor-bearing mice given T-cell–depleted allo-BMT (allo-TCD-BMT) failed to develop GvHD and also showed significantly stronger GvT effects than mice given allo-BMT. The GvT effects in allo-TCD-BMT recipients were associated with profound changes in tumor-infiltrating cells compared with that in allo-BMT recipients, with significantly reduced donor-derived regulatory T cells (Treg), increased cytotoxic effector (IFNγhi) CD8 T cells, and increased M1 macrophages (iNOShi, arginaselo, and IL10lo); the use of macrophage-depleted bone marrow abrogated the GvT effects. Collectively, these results indicate that the presence of M1 macrophages may disrupt the generation of donor-type Treg cells so that the immunomodulatory effect of the TME can affect systemic immunity.

Significance:

These findings show that cells such as T cells or macrophages in the bone marrow inoculum may interfere with the systemic and local immune reactivity against tumors.
Breast Cancer Risk and Insulin Resistance: Post Genome-Wide Gene–Environment Interaction Study Using a Random Survival Forest
Authors: Jung Su Yon , Papp Jeanette C. , Sobel Eric M. , Yu Herbert , Zhang Zuo-Feng
Published: April 2019

Obesity–insulin connections have been considered potential risk factors for postmenopausal breast cancer, and the association between insulin resistance (IR) genotypes and phenotypes can be modified by obesity-lifestyle factors, affecting breast cancer risk. In this study, we explored the role of IR in those pathways at the genome-wide level. We identified IR-genetic factors and selected lifestyles to generate risk profiles for postmenopausal breast cancer. Using large-scale cohort data from postmenopausal women in the Women's Health Initiative Database for Genotypes and Phenotypes Study, our previous genome-wide association gene–behavior interaction study identified 58 loci for associations with IR phenotypes (homeostatic model assessment–IR, hyperglycemia, and hyperinsulinemia). We evaluated those single-nucleotide polymorphisms (SNP) and additional 31 lifestyles in relation to breast cancer risk by conducting a two-stage multimodal random survival forest analysis. We identified the most predictive genetic and lifestyle variables in overall and subgroup analyses [stratified by body mass index (BMI), exercise, and dietary fat intake]. Two SNPs (LINC00460 rs17254590 and MKLN1 rs117911989), exogenous factors related to lifetime cumulative exposure to estrogen, BMI, and dietary alcohol consumption were the most common influential factors across the analyses. Individual SNPs did not have significant associations with breast cancer, but SNPs and lifestyles combined synergistically increased the risk of breast cancer in a gene–behavior, dose-dependent manner. These findings may contribute to more accurate predictions of breast cancer and suggest potential intervention strategies for women with specific genetic and lifestyle factors to reduce their breast cancer risk.

Significance:

These findings identify insulin resistance SNPs in combination with lifestyle as synergistic factors for breast cancer risk, suggesting lifestyle changes can prevent breast cancer in women who carry the risk genotypes.
Remodeling Collapsed DNA Replication Forks for Cancer Development
Authors: Sotiriou Sotirios K. , Halazonetis Thanos D.
Published: April 2019

DNA replication stress is prevalent in human cancers, but absent in normal cells, suggesting that proteins involved in the cellular response to DNA replication stress could be potential therapeutic targets. SMARCAL1 and ZRANB3 are annealing helicases that mediate the repair of collapsed DNA replication forks. In a study in this issue of Cancer Research, Puccetti and colleagues report that mice lacking either SMARCAL1 or ZRANB3 activity have delayed development of MYC-induced B-cell lymphomas. Thus, inhibiting the response to DNA replication stress could benefit patients with cancer.

See related article by Puccetti et al., p. 1612
Early Modeled Longitudinal CA-125 Kinetics and Survival of Ovarian Cancer Patients: A GINECO AGO MRC CTU Study
Authors: Colomban Olivier , Tod Michel , Leary Alexandra , Ray-Coquard Isabelle , Lortholary Alain , Hardy-Bessard Anne Claire , Pfisterer Jacobus , Du Bois Andreas , Kurzeder Christian , Burges Alexander , Péron Julien , Freyer Gilles , You Benoit
Published: April 2019

Purpose:

Regarding cancer antigen 125 (CA-125) longitudinal kinetics during chemotherapy, the actual predictive value of the Gynecologic Cancer Intergroup (GCIG) CA-125 response criterion is questioned. The modeled CA-125 elimination rate constant KELIM exhibited higher prognostic value in patients with recurrent ovarian cancer enrolled in the CALYPSO trial. The objective was to validate the higher predictive and prognostic values of KELIM during first-line treatments.

Experimental Design:

Data from three large phase III trials were analyzed: AGO OVAR 9 [learning set: carboplatin-paclitaxel (CP) ± gemcitabine; n = 1,288]; AGO OVAR 7 (validation set: CP ± topotecan; n = 192); and ICON7 (validation set: CP ± bevacizumab; n = 1,388). The CA-125 profiles were fit with a nonlinear mixed-effect model during the first 100 days, and the individual KELIM were calculated. KELIM prognostic and predictive values for survival were assessed against GCIG criterion and other prognostic factors in univariate/multivariate analyses.

Results:

The GCIG CA-125 endpoint provided no meaningful predictive/prognostic information. C-index analyses confirmed the higher predictive value of KELIM compared with GCIG criterion for progression-free survival and overall survival (OS). KELIM provided reproducible prognostic information. Patients with favorable KELIM ≥ upper tercile (0.0711 per days) consistently experienced better OS, with HRs between 0.44 and 0.58 (e.g., median OS >65 months vs. <35 months).

Conclusions:

Modeled KELIM provides higher predictive and prognostic information based on CA-125 longitudinal kinetics compared with GCIG response criteria during first-line chemotherapy. Integration of this endpoint in guidelines may be considered. Individual KELIM and survival simulations can be calculated at http://www.biomarker-kinetics.org/. Further assessment of the surrogate value of KELIM treatment–related variations in a GCIG meta-analysis is warranted.

See related commentary by Maitland et al., p. 5182
Combined MAPK Pathway and HDAC Inhibition Breaks Melanoma
Authors: Lombard David B. , Cierpicki Tomasz , Grembecka Jolanta
Published: April 2019

In this issue, Maertens and colleagues demonstrate that HDAC3 inhibition potentiates the effects of MAPK pathway inhibitors in melanoma, including difficult-to-treat NRAS- and NF1-driven tumors, with MGMT expression serving as a biomarker for responsiveness to the BRAF/MEK/HDAC inhibitor combination. Mechanistically, this triple cocktail suppresses expression of genes involved in DNA repair, leading to enhanced killing of melanoma cells.

See related article by Maertens et al., p. 526.
Similar Airway Function after Volitional Hyperpnea in Mild-Moderate Asthmatics and Healthy Controls
Authors: Eichenberger Philipp A. , Kurzen Andrea C. , Rijks Laura , Diener Stephanie N. , Scherer Thomas A.  , Spengler Christina M.
Published: April 2019

Background: The beneficial effects of exercise training for asthmatics might relate to repetitive airway stretching. Thus, a training with more pronounced airway stretch using isolated, volitional hyperpnea (HYP) might be similarly or more effective. However, in healthy subjects, a bout of HYP training is known to cause an acute FEV1 decline. Objective: The aim of the present study was therefore to test whether these changes are more pronounced in asthmatics, possibly putting them at risk with HYP training. Methods: Nine subjects with mild-moderate asthma (confirmed by mannitol challenge) and 11 healthy subjects performed six 5-min bouts (with 6-min breaks; HYP1) and one 30-min bout (HYP2) of normocapnic HYP at 60% of maximal voluntary ventilation using warm and humid air. FEV1 and airway resistance (R5) were measured before, in breaks (HYP1), and immediately after HYP, and during 60 min of recovery. Results: In both groups, a significant and similar decrease in FEV1 during HYP1 (asthmatics: –3 ± 3%; healthy subjects: –2 ± 3%), after HYP1 (asthmatics: –2 ± 5%; healthy subjects: –1 ± 4%), and after HYP2 (asthmatics: –4 ± 5%; healthy subjects: –3 ± 3%), and an increase in R5 during and after both HYPs were observed. Maximal changes in FEV1 and R5 did not correlate with baseline lung function or responsiveness to mannitol. Conclusions: A bout of HYP does not lead to relevant bronchoconstriction and the observed changes in lung function and airway resistance are neither of the magnitude of clinical relevance, nor do they differ from responses in healthy individuals. Thus, HYP training can safely be tested as an airway-specific exercise training alternative (or add-on) modality to regular aerobic exercise training.