bluuebunny/crossref_metadata_2025 huggingface dataset:
Intersegmental coordination patterns are differently affected in Parkinson’s disease and cerebellar ataxia
Authors: Israeli-Korn Simon D. , Barliya Avi , Paquette Caroline , Franzén Erika , Inzelberg Rivka , Horak Fay B. , Flash Tamar
Published: November 2018

The law of intersegmental coordination (Borghese et al. 1996) may be altered in pathological conditions. Here we investigated the contribution of the basal ganglia (BG) and the cerebellum to lower limb intersegmental coordination by inspecting the plane’s orientation and other parameters pertinent to this law in patients with idiopathic Parkinson’s disease (PD) or cerebellar ataxia (CA). We also applied a mathematical model that successfully accounts for the intersegmental law of coordination observed in control subjects (Barliya et al. 2009). In the present study, we compared the planarity index (PI), covariation plane (CVP) orientation, and CVP orientation predicted by the model in 11 PD patients, 8 CA patients, and two groups of healthy subjects matched for age, height, weight, and gender to each patient group (Ctrl_PD and Ctrl_CA). Controls were instructed to alter their gait speed to match those of their respective patient group. PD patients were examined after overnight withdrawal of anti-parkinsonian medications (PD-off-med) and then on medication (PD-on-med). PI was above 96% in all gait conditions in all groups suggesting that the law of intersegmental coordination is preserved in both BG and cerebellar pathology. However, the measured and predicted CVP orientations rotated in PD-on-med and PD-off-med compared with Ctrl_PD and in CA vs. Ctrl_CA. These rotations caused by PD and CA were in opposite directions suggesting differences in the roles of the BG and cerebellum in intersegmental coordination during human locomotion.

NEW & NOTEWORTHY Kinematic and muscular synergies may have a role in overcoming motor redundancies, which may be reflected in intersegmental covariation. Basal ganglia and cerebellar networks were suggested to be involved in crafting and modulating synergies. We thus compared intersegmental coordination in Parkinson’s disease and cerebellar disease patients and found opposite effects in some aspects. Further research integrating muscle activities as well as biomechanical and neural control modeling are needed to account for these findings.
Application of Finite Mixture of Logistic Regression for Heterogeneous Merging Behavior Analysis
Authors: Li Gen
Published: November 2018

A finite mixture of logistic regression model (FMLR) was applied to analyze the heterogeneity within the merging driver population. This model can automatically provide useful hidden information about the characteristics of the driver population. EM algorithm and Newton-Raphson algorithm were used to estimate the parameters. To accomplish the objective of this study, the FMLR model was applied to a trajectory dataset extracted from the NGSIM dataset and a 2-component FMLR model was identified. The important findings can be summarized as follows: The studied drivers can be classified into two components. One is called Risk-Rejecting Drivers. These drivers are consistent with previous studies and primarily merge in as soon as possible and have a distinct preference for the large gaps. The other is the Risk-Taking Drivers that are much less sensitive to the gap size and pay more attention to surrounding traffic conditions such as the speed of front vehicle in the auxiliary lane and lead space gap between the merging vehicle and its leading vehicles in the auxiliary lane. Risk-Taking Drivers use the auxiliary lane to get to the further downstream or less congested area of the main lane. The proposed model can also produce more precise predicting accuracy than logistic regression model.
The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies
Authors: Sá-Sousa Ana , Fonseca João Almeida , Pereira Ana Margarida , Ferreira Ana , Arrobas Ana , Mendes Ana , Drummond Marta , Videira Wanda , Costa Tiago , Farinha Pedro , Soares José , Rocha Pedro , Todo-Bom Ana , Sokolova Anna , Costa António , Fernandes Beatriz , Chaves Loureiro Carla , Longo Cecília , Pardal Cecília , Costa Célia , Cruz Cíntia , Loureiro Cláudia Chaves , Lopes Cristina , Mesquita Duarte , Faria Emília , Magalhães Eunice , Menezes Fernando , Todo-Bom Filipa , Carvalho Francisca , Regateiro Frederico S. , Falcão Helena , Fernandes Ivone , Gaspar-Marques João , Viana Jorge , Ferreira José , Silva José Manuel , Simão Laura , Almeida Leonor , Fernandes Lígia , Ferreira Lurdes , van Zeller Mafalda , Quaresma Márcia , Castanho Margarida , André Natália , Cortesão Nuno , Leiria-Pinto Paula , Pinto Paula , Rosa Paula , Carreiro-Martins Pedro , Gerardo Rita , Silva Rui , Lucas Susana , Almeida Teresa , Calvo Teresa
Published: November 2018

The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient’s clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients’ electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients’ confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.
Salvaging Digital Replantation and Revascularisation: Efficiency of Heparin Solution Subcutaneous Injection
Authors: Alfeky Haz , McArthur Paul , Helmy Yasser
Published: November 2018

Background. Distal digital replantation and revascularisation remains one of the demanding microsurgical procedures due to the difficulty of vascular anastomosis. Venous congestion is the most commonly encountered problem after replantation due to the difficulty of venous anastomosis in traumatic injuries. Heparin, among other drugs, is commonly used to facilitate venous drainage and prevent thrombosis. However, systemic heparin can be contraindicated in some patients. The senior author has experience of subcutaneous heparin injection for venous congestion in thirteen patients. Methods. An amount of 1 ml of calcium heparin (25,000 U) was mixed in 2.4 ml of normal saline making a solution that has 1000 U per 0.1 ml. 1000 U (0.1 ml) of the solution was injected directly into the congested replanted digits. This was repeated twice daily until venous congestion improved. Results. All the congested replanted digits survived without systemic side effects. There were no local side effects of the treatment. The PT and APTT have shown slight increase but they remained within the normal range. Haemoglobin levels have dropped slightly but no patients were at any risk of developing anaemia or needed blood transfusion. Conclusions. Subcutaneous heparin injections can salvage the replanted digits when venous congestion is a warning flag for replantation failure. It is safe and very efficient in patients where systemic heparin cannot be administered. However, this article shows the results in only thirteen patients which is a small number to show the efficacy, safety, and side effects.
The Role of Tomographic Ultrasonography in Conduit Mapping before Coronary Artery Bypass Grafting
Authors: Hussain Syed Mohammad Asim
Published: November 2018

Objective. To assess the performance of tomographic ultrasonography (TUS) in providing images that will enable optimum choice of vein segment to harvest for coronary artery bypass grafting (CABG). Methods. This was a prospective study of diagnostic accuracy. The index test was tomographic ultrasonography. The reference standard was intraoperative observation. The study was performed at the Vascular Imaging and Cardiothoracic Department at Wythenshawe Hospital, Manchester. Patients undergoing CABG who require vein mapping were included in the study. The main outcome measures were the number of tributaries identified in harvested vein segments, presence of varicosities, and usable length of vein. Results. The TUS correctly identified 89 out of 111 vein tributaries in 10 patients resulting in a sensitivity of 80.2%. This resulted in a p value of 0.000001 using an exact binomial test, with a prior probability of 0.5. TUS had a sensitivity of 66.7% and a specificity of 100% in the identification of varicosities over 14 patients. TUS had 90% agreement with intraoperative observation in assessing usable length of vein over 14 patients. Conclusions. Our results show that TUS has a high sensitivity in identifying vein tributaries. This can be used to select veins with fewer tributaries for harvesting should TUS be used for preoperative vein mapping before CABG.
Experimental and Numerical Analysis of Nonlinear Flexural Behaviour of Lattice‐Web Reinforced Foam Core Composite Sandwich Panels
Authors: Chen Jiye , Fang Hai , Liu Weiqing , Qi Yujun , Zhu Lu
Published: November 2018

This paper conducted experimental and numerical analysis of the nonlinear flexural behaviour of lattice‐web reinforced foam core composite sandwich panels. Composite sandwich panels composed of a polyurethane (PU) foam core with glass fibre‐reinforced polymer (GFRP) composites as the face sheets and lattice webs were fabricated through the vacuum infusion moulding process (VIMP). The flexural behaviour of these composite sandwich panels were experimentally investigated under both uniformly distributed and concentrated loading scenarios. The results showed that reinforced lattice webs can significantly increase the flexural stiffness and load‐carrying capacity of sandwich panels and effectively postpone the onset of interfacial debonding failure between the face sheets and core. The effects of the lattice‐web height and spacing on the ductility and load‐carrying capacities of the sandwich panels were also analysed. Several numerical simulations on lattice‐web reinforced foam core composite sandwich panels under concentrated loadings were also conducted. The effectiveness of the finite element (FE) model was validated by the experimental work. Parametric studies indicated that thicker face sheets and lattice webs can remarkably increase the load‐carrying capacity. Moreover, the load‐carrying capacity and midspan deflection were hardly affected by the foam density.
Health Service Seeking Behavior among Migrant Workers in Small and Medium-Sized Enterprises in Guangdong, China: Does Family Migration Matter?
Authors: Dang Yuewen , Zou Guanyang , Peng Boli , Ling Li
Published: November 2018

Objective. This study aims to understand the health service seeking behavior of migrant workers and explore its association with their living status (i.e., living with family members or not), in Guangdong, China. Methods. This was a cross-sectional survey conducted with 912 migrant workers in 2012 using a structured questionnaire adapted from the National Health Service Survey. Data were analyzed using the multivariable logistic regression. Results. Of all migrant workers, 58% lived with at least one family member in the host city. Most of the respondents rated their health status being “very good or good” (58%). Fifty-four percent of the respondents reported having at least one disease in the past 12 months. Sixty-two percent of those who reported at least one disease visited doctors in the past 12 months. Of these, 22% returned to their hometown for medical treatment. Logistic regression showed that migrant workers living with families rated themselves as having better health status (P<0.05) but had more diseases (P>0.05) and had higher doctor visitation rate than those living with alone (58% vs. 66%, P<0.05). Conclusion. The Andersen health service utilization model helps to understand the health seeking behavior of the migrant workers in the host cities. Migrant workers living with family members were positively associated with self-rated health status and health service seeking behavior in small and medium-sized enterprises. Our findings suggest the importance of the assistance programs and social support to improve seeking of healthcare services among migrant groups, especially those who live alone in the host cities.
Aggregate Evolution Mechanism during Ion‐Adsorption Rare Earth Ore Leaching
Authors: Zhao Kui , Zhuo Yulong , Wang Xiaojun , Zhong Wen
Published: November 2018

The phenomenon of particle aggregation occurs when ammonium chloride is used as a leaching reagent to infiltrate rare earth samples. To reveal the formation and evolution mechanisms of aggregates, a self‐developed column leaching experimental device was employed in conjunction with nuclear magnetic resonance technology. The relationships among the amount of rare earth leaching, the evolution of the microscopic pore structure, the porosity, and the leaching time were obtained. A comparative analysis of pure water and ammonium chloride test groups revealed that aggregates were present only in the latter. Consequently, the results of comprehensive analyses indicate that the formation of aggregates is a temporary particle deposition phenomenon caused by the settling of fine soil particles migrating from the top to the bottom of a sample. Furthermore, chemical exchanges constitute the main cause of aggregate formation.
Nucleoredoxin‐Dependent Targets and Processes in Neuronal Cells
Authors: Urbainsky Claudia , Nölker Rolf , Imber Marcel , Lübken Adrian , Mostertz Jörg , Hochgräfe Falko , Godoy José R. , Hanschmann Eva-Maria , Lillig Christopher Horst
Published: November 2018

Nucleoredoxin (Nrx) is an oxidoreductase of the thioredoxin family of proteins. It was shown to act as a signal transducer in some pathways; however, so far, no comprehensive analysis of its regulated substrates and functions was available. Here, we used a combination of two different strategies to fill this gap. First, we analyzed the thiol‐redox state of the proteome of SH‐SY5Y neuroblastoma cells depleted of Nrx compared to control cells using a differential thiol‐labeling technique and quantitative mass spectrometry. 171 proteins were identified with an altered redox state; 161 of these were more reduced in the absence of Nrx. This suggests functions of Nrx in the oxidation of protein thiols. Second, we utilized the active site mutant Cys208Ser of Nrx, which stabilizes a mixed disulfide intermediate with its substrates and therefore trapped interacting proteins from the mouse brain (identifying 1710 proteins) and neuronal cell culture extracts (identifying 609 proteins). Profiling of the affected biological processes and molecular functions in cells of neuronal origin suggests numerous functions of Nrx in the redox regulation of metabolic pathways, cellular morphology, and signal transduction. These results characterize Nrx as a cellular oxidase that itself may be oxidized by the formation of disulfide relays with peroxiredoxins.
Influence of the Addition of Potato, Okara, and Konjac Flours on Antioxidant Activity, Digestibility, and Quality of Dumpling Wrappers
Authors: Jiang Yongli , Zhao Yimeng , Wang Danfeng , Deng Yun
Published: November 2018

To improve the antioxidant activity (AA), digestibility, and quality of fiber-rich dumpling wrappers, potato, okara, and konjac flours were added to wheat flour. The contents of these additional ingredients in the dumpling wrapper were optimized using the response surface methodology and the synthetic evaluation method. The dietary fiber content (DFC) and AA of blend flours and the optimized cooking time (OCT), cooking loss (CL), hardness, chewiness, firmness, color, and sensory evaluation (SE) of dumpling wrappers were evaluated as response quality parameters. The optimized flour was identified containing 17.5 g of potato flour, 8.5 g of okara flour, and 1.2 g of konjac flour per 100 g of blend flour, which resulted in a higher synthetic evaluation index value (0.71 compared with 0.68 for wheat flour). The qualities of the optimized flour dumpling wrappers were compared with those of wheat flour dumpling wrappers to verify the practicality of the optimized flour. The results showed that the optimized flour showed better comprehensive qualities, especially regarding DFC (9.59%, fourfold higher than that of wheat flour) and AA. Furthermore, the predicted glycemic index (GI) of the optimized flour (74.93%) was lower than that of the wheat flour (81.47%). Overall, the addition of potato, okara, and konjac flours can significantly (P<0.05) improve DFC, AA, and digestibility of wheat flour. The optimized flour not only maintains excellent dumpling wrapper quality but also increases the utilization of potato and okara flours, which has great potential for industrial applications.
Cutting Edge: Biomarkers for Chronic Spontaneous Urticaria
Authors: Folci Marco , Heffler Enrico , Canonica Giorgio W. , Furlan Raffaello , Brunetta Enrico
Published: November 2018

Chronic spontaneous urticaria (CSU) is defined by the appearance of wheals and a variable presence of angioedema which persists for at least 6 weeks. It represents the most common subtype of chronic urticaria and is gaining importance in civil society because of its association with impaired quality of life. Moreover, CSU has a growing impact on national health systems representing a great burden due to its variable rate of response to the approved therapies. In this scenario, the identification of clinical and molecular biomarkers is of pivotal importance. Some groups are trying to detect molecules which would be able to help clinicians in reaching a proper diagnosis; additionally, the opportunity to describe disease severity which leads to cluster patients in different groups could fill the gap in the numerous unmet clinical needs. Several biomarkers are currently being studied with the purpose to predict the response to a defined therapy; unfortunately, none of them are ready to be translated from bench to bedside.
Joint High-Resolution Range and DOA Estimation via MUSIC Method Based on Virtual Two-Dimensional Spatial Smoothing for OFDM Radar
Authors: Zhang Rui , Quan Ying-Hui , Zhu Sheng-Qi , Yang Lei , Li Ya-chao , Xing Meng-Dao
Published: November 2018

For the purpose of target parameter estimation of the orthogonal frequency-division multiplexing (OFDM) radar, a high-resolution method of joint estimation on range and direction of arrival (DOA) based on OFDM array radar is proposed in this paper. It begins with the design and analysis of an echo model of OFDM array radar. Since there is no coupling between range and angle parameter estimation for a narrow-band signal, a method which exploits the data of one snapshot to estimate the range and angle of the target by means of multiple signal classification (MUSIC) based on virtual two-dimensional spatial smoothing in range and angle dimensions is devised. The proposed method is capable of joint estimating the range and DOA of the target in a high resolution under a single snapshot circumstance. Simulation experiments demonstrate the validity of the proposal.
Passenger Mobility in a Discontinuous Space: Modelling Access/Egress to Maritime Barrier in a Case Study
Authors: Birgillito G. , Rindone C. , Vitetta A.
Published: November 2018

The present study analyses a transport system in a discontinuous space. Classical specifications of transport models cannot be applied directly when evaluating the influence of territorial discontinuity and related barriers on user behaviour. Adjustments are required for this specific case because studies relative to discontinuous spaces are limited. The influence concerns the different travel components (access, barrier, on board, and egress) and could impact travel choices (departure time, destination, mode, and path). In this paper, the models refer to access and egress components with a focus on the mode of travel choice level. The paper focusses on the influence of discontinuity, introducing some adjustments to the classical demand models used to simulate discontinuity crossing. The main variables influencing the user’s choice, and their relative weight in discontinuous space, are investigated. These elements are fundamental for any planning and design procedures to improve the quality of mobility. In the paper, the case study of the Strait of Messina in southern Italy is analysed. In this case, the barrier is constituted by the sea that physically separates the two shores. In this work, only strait crossings via hydrofoil, from Reggio Calabria to Messina, are considered in random sample interviews.
Interleukin‐4 Boosts Insulin‐Induced Energy Deposits by Enhancing Glucose Uptake and Lipogenesis in Hepatocytes
Authors: Yang Ching-Ping , Shiau Ming-Yuh , Lai Yi-Ren , Ho Kuo-Ting , Hsiao Chiao-Wan , Chen Chun-Jung , Lo Yu-Li , Chang Yih-Hsin
Published: November 2018

Type 2 diabetes mellitus (T2DM), with dysregulated hepatic gluconeogenesis as the major cause of fasting hyperglycemia, is closely associated with chronic inflammation. We previously demonstrated interleukin‐4 (IL‐4) improves insulin sensitivity and glucose tolerance while reducing lipid deposits. The present study examined the in vitro effects of IL‐4 on insulin signaling molecules, glucose uptake, and lipid metabolism in hepatocytes, as well as in vivo effects on hepatic adiposity, for elucidating the roles of IL‐4 in hepatic energy metabolism. Potential interaction between IL‐4 and insulin in regulating hepatic metabolism was also investigated. Our results showed that IL‐4 enhanced Akt and GSK‐3α/β phosphorylations, which in turn promoted glycogen synthesis. IL‐4 not only potentiated basal glucose uptake by upregulating glucose transporter 2 expression but also promoted insulin‐induced glucose uptake. Additionally, IL‐4 increased triglyceride contents through facilitating free fatty acid uptake and expression/activity of lipogenic enzymes. The major effects of IL‐4 on the liver were to promote energy storage by boosting insulin‐stimulated glucose uptake and lipid synthesis. This study provides evidence to implicate the novel roles of IL‐4 in mediating hepatic glucose and lipid metabolism, interactions between immune responses and metabolic homeostasis, and the involvement of IL‐4 in metabolic abnormalities.
The Effect of Smoking Behavior on Alveolar Bone Marrow Mesenchymal Stem Cells of Clinical Implant Patient
Authors: Zhao Xicong , Zhu Bin , Duan Yan , Wang Xin. , Li Dehua
Published: November 2018

Objective. The hazardous effects of smoking on the alveolar bone healing after implant surgery and nicotine on the biofunction of human alveolar bone marrow mesenchymal stem cells (hABMMSCs) were reported. There was little direct evidence regarding the specific detrimental effects of the smoking on hABMMSCs. The aim of this study was to test the influence of smoking behavior on hABMMSCs and the osseointegration situation after implant surgery.Methods. hABMMSCs from 6 dental implant patients randomly (3 smokers and 3 nonsmokers) were compared. The cell viability, colony forming unit, and cell cycle were performed to assay proliferation capacity. The Oil Red O staining, Alizarin Red staining, alkaline phosphatase staining and activity, adipogenic and osteogenic gene expressions in vitro, and bone formation ectopically in vivo were performed under proper inductions, respectively, to assay multilineage differentiation. Besides the implant stability quotient and marginal bone loss were checked in both groups.Results. Smoking hABMMSCs showed lower proliferation in vitro and poorer bone regeneration capacity in vivo. Moreover, smokers performed worse on bone healing after implant surgery.Conclusions. Our results suggested smoking had the detrimental genetic effect on proliferation and osteogenesis of hABMMSCs and the decreased biofunction of hABMMSCs was positively related with bone healing.Clinical Significance. The present study provided direct evidence about hazardous effects of smoking behavior on hABMMSCs. Smoking decreased the osteogenesis and proliferation of hABMMSCs in vivo and in vitro, and smoking was positively related with osseointegration reduction. Prevention of smoking behavior may promote biofunction of hABMMSCs and successful rate of dental implant.
An Integrated Approach for Shift Scheduling and Rostering Problems with Break Times for Inbound Call Centers
Authors: Türker Turgay , Demiriz Ayhan
Published: November 2018

It may be very difficult to achieve the optimal shift schedule in call centers which have highly uncertain and peaked demand during short time periods. Overlapping shift systems are usually designed for such cases. This paper studies shift scheduling and rostering problems for inbound call centers where overlapping shift systems are used. An integer programming model that determines which shifts to be opened and how many operators to be assigned to these shifts is proposed for the shift scheduling problem. For the rostering problem both integer programming and constraint programming models are developed to determine assignments of operators to all shifts, weekly days-off, and meal and relief break times of the operators. The proposed models are tested on real data supplied by an outsource call center and optimal results are found in an acceptable computation time. An improvement of 15% in the objective function compared to the current situation is observed with the proposed model for the shift scheduling problem. The computational performances of the proposed integer and constraint programming models for the rostering problem are compared using real data observed at a call center and simulated test instances. In addition, benchmark instances are used to compare our Constraint Programming (CP) approach with the existing models. The results of the comprehensive computational study indicate that the constraint programming model runs more efficiently than the integer programming model for the rostering problem. The originality of this research can be attributed to two contributions: (a) a model for shift scheduling problem and two models for rostering problem are presented in detail and compared using real data and (b) the rostering problem is considered as a task-resource allocation and considerably shorter computation times are obtained by modeling this new problem via CP.
A Model‐Based Unloaded Test Method for Analysis of Braking Capacity of Elevator Brake
Authors: Peng Qifeng , Li Zhongxing , Yuan Hong , Huang Guojian , Li Shanqing , Sun Xueli
Published: November 2018

In order to improve the inspection efficiency and accuracy of the braking capacity of the elevator brake being used, a novel method for analyzing the full‐loaded braking performance by using the unloaded braking performance is proposed, and a set of methods for measuring the braking torque is designed. Based on the analysis of the key factors that affect the mechanical performance of the elevator brake, the calculation model of the braking torque in the process of the emergency braking with the traction ratio of 2 : 1 is established, and the relationship between the braking torque and acceleration under different working conditions is analyzed. It is shown that, for the model assumed, the emergency braking torque is 1.56 times that of the static braking torque under 1.25 times the rated load. The braking torque increases linearly with the increase of braking acceleration. An elevator model being used is tested and calculated. The experimental results show that the braking acceleration measured by the experiment is 11.95% less than the theoretical value. And the analysis shows that, comparing with the traditional test method, the braking torque test method designed in this paper is more accurate and safe.
Adipocytokines in Rheumatoid Arthritis: The Hidden Link between Inflammation and Cardiometabolic Comorbidities
Authors: Ruscitti Piero , Di Benedetto Paola , Berardicurti Onorina , Liakouli Vasiliki , Carubbi Francesco , Cipriani Paola , Giacomelli Roberto
Published: November 2018

Rheumatoid arthritis is a chronic autoimmune disease affecting typically synovial joints and leading to progressive articular damage, disability, and reduced quality of life. Despite better recent therapeutic strategies improving long-term outcomes, RA is associated with a high rate of comorbidities, infections, malignancies, and cardiovascular disease (CVD). Remarkably, some well-known pathogenic proinflammatory mediators in RA, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), may play a pivotal role in the development of CVD. Interestingly, different preclinical and clinical studies have suggested that biologic agents commonly used to treat RA patients may be effective in improving CVD. In this context, the contribution of adipocytokines has been suggested. Adipocytokines are pleiotropic molecules, mainly released by white adipose tissue and immune cells. Adipocytokines modulate the function of different tissues and cells, and in addition to energy homeostasis and metabolism, amplify inflammation, immune response, and tissue damage. Adipocytokines may contribute to the proinflammatory state in RA patients and development of bone damage. Furthermore, they could be associated with the occurrence of CVD. In this study, we reviewed available evidence about adipocytokines in RA, because of their involvement in disease activity, associated CVD, and possible biomarkers of prognosis and treatment outcome and because of their potential as a possible new therapeutic target.
Seepage Law of Injected Water in the Coal Seam to Prevent Rock Burst Based on Coal and Rock System Energy
Authors: Lan Tianwei , Fan Chaojun , Zhang Hongwei , Batugin A. S. , Ruibin Luo , Yang Yu , Jia Ce
Published: November 2018

Rock burst is one of the typical dynamic disasters in coal mining. In order to reveal the mechanism of rock burst from the energy view point, the relationships between the maximum, minimum, and intermediate principal stresses and the concentration coefficients of the gravity stress k1, k2, and k3 are determined through the geostress measurement combined with engineering practice of coal mining. The coal and rock system model based on the tectonic stress is established. The relationship between energy and scale radius of the coal and rock system is determined to reveal the law of energy accumulation, release, and transfer in the coal and rock system. In view of the characteristics of the porous medium in the coal seam, the measures of water injection are put forward to relieve pressure in the coal seam, and the law of water seepage in the process of water injection in the coal seam is studied based on the seepage mechanics. The result shows that the trend of released energy of damaged coal has good consistency with the variation of permeability, and water injection can reduce the stress concentration and energy concentration of the rock burst system. The engineering practice of the rock burst prevention was taken in Yuejin Coal Mine. The energy characteristics of the coal and rock system in the working face are analyzed, and the measures of water injection and the corresponding parameters are determined.
Oscillatory Patterns of Phase Cone Formations near to Epileptic Spikes Derived from 256-Channel Scalp EEG Data
Authors: Ramon Ceon , Holmes Mark D. , Wise Mackenzie V. , Tucker Don , Jenson Kevin , Kinn Samuel R.
Published: November 2018

Our objective was to determine if there are any distinguishable phase cone clustering patterns present near to epileptic spikes. These phase cones arise from episodic phase shifts due to the coordinated activity of cortical neurons at or near to state transitions and can be extracted from the high-density scalp EEG recordings. The phase cone clustering activities in the low gamma band (30–50 Hz) and in the ripple band (80–150 Hz) were extracted from the analytic phase after taking Hilbert transform of the 256-channel high density (dEEG) data of adult patients. We used three subjects in this study. Spatiotemporal contour plots of the unwrapped analytic phase with 1.0 ms intervals were constructed using a montage layout of 256 electrode positions. Stable phase cone patterns were selected based on the criteria that the sign of the spatial gradient did not change for at least three consecutive time samples and the frame velocity was within the range of propagation velocities of cortical axons. These plots exhibited dynamical formation of phase cones which were higher in the seizure area as compared with the nearby surrounding brain areas. Spatiotemporal oscillatory patterns were also visible during ±5 sec period from the location of the spike. These results suggest that the phase cone activity might be useful for noninvasive localization of epileptic sites and also for examining the cortical neurodynamics near to epileptic spikes.
Studies on the Climate Effects of Black Carbon Aerosols in China and Their Sensitivity to Particle Size and Optical Parameters
Authors: Ma Xingxing , Liu Hongnian , Wang Xueyuan , Peng Zhen
Published: November 2018

In this paper, based on the principle of Mie scattering, we calculated the optical parameters of BC aerosols at different scales and then applied the new optical parameters to simulate the BC aerosols concentration distribution, radiative forcing, and their climate effects. We also compared the results of optical parameters of BC aerosols with homogeneous scales and analyzed the effect on climate. Compared with the conventional uniform-scheme optical parameterization, the concentrations of the first mode of BC aerosols simulated with the optical parameters that were recalculated based on the particle size are significantly higher, while the concentrations of the other modes and the total of BC aerosols are lower. In the respective of statistics, the changes of column burdens of BC in four modes are 0.085, −0.095, −0.089, −0.054 mg/m2. The clear-sky TRF of BC are weakened in the value of 0.03 W/m2 averaged over the domain, while the all-sky TRF of BC are enhanced of  0.06 W/m2 in general. The warming effect of BC becomes weaker when using the new scheme by −0.04 K to −0.24 K. When using the new optical parameters scheme, the regional average surface concentrations of BC in four modes are 0.372, 0.264, 0.055 and 0.004 μg/m3, respectively. Especially, the first and the second mode account for as large as 53% and 38%. The surface concentration and column burden of total BC are 0.69 μg/m3 and 0.28 mg/m2 can be dropped. The regional average direct RFs of BC at the top of the atmosphere are 0.49 W/m2 under clear-sky and 0.36 W/m2 under all-sky averaged over the domain. Over most areas of central China, North China, and East China, BC may increase the temperature in a range of 0.05∼0.15 K, while over South China, BC shows cooling effect. In average, the precipitation variations caused by BC over East China, North China, South China, and Northeast China are −0.83, −0.05, −0.11, and −0.13 mm/d, respectively. As a whole, the variations of circulation, pressure, and temperature show a good correspondence.
Effect of Freeze-Thaw Pretreatment on Extraction Yield and Antioxidant Bioactivity of Corn Carotenoids (Lutein and Zeaxanthin)
Authors: Jiao Yan , Li Dajing , Chang Ying , Xiao Yadong
Published: November 2018

As a green and low-energy pretreatment method, the effect of freeze-thaw (FT) pretreatment on extraction yield and antioxidant bioactivity of carotenoids of the corn gluten meal (CGM) were evaluated in this study. The CGM particles ruptured in FT treatment due to the repeated damage caused by FT to CGM particles. The carotenoid compounds of pretreated CGM were lutein, zeaxanthin, β-carotene, and cryptoxanthin. Among them, the major carotenoids are lutein and zeaxanthin. The optimized FT pretreatment conditions included freezing temperature of −20°C, moisture content of 100%, and 2 cycles. An increase in the yield of lutein and zeaxanthin was observed in the range of 2.23–16.39 µg/g and 4.66–36.3 µg/g as a result of pretreatment as against 1.17 and 2.52 µg/g of the untreated sample, respectively. Moreover, the release of lutein and zeaxanthin from CGM was facilitated by FT pretreatment and increased the antioxidant activity of the carotenoids.
Combined Mineral Intakes and Risk of Colorectal Cancer in Postmenopausal Women
Authors: Swaminath Samyukta , Um Caroline Y. , Prizment Anna E. , Lazovich DeAnn , Bostick Roberd M.
Published: November 2018

Background:

Despite considerable biological plausibility, other than for calcium, there are few reported epidemiologic studies on mineral intake–colorectal cancer associations, none of which investigated multiple minerals in aggregate.

Methods:

Accordingly, we incorporated 11 minerals into a mineral score and investigated its association with incident colorectal cancer in the Iowa Women's Health Study, a prospective cohort study of 55- to 69-year-old women who completed a food frequency questionnaire in 1986. In the analytic cohort (n = 35, 221), 1,731 incident colorectal cancer cases were identified via the State Health Registry of Iowa. Participants' calcium, magnesium, manganese, zinc, selenium, potassium, and iodine intakes were ranked 1 to 5, with higher ranks indicating higher, potentially anticarcinogenic, intakes, whereas for iron, copper, phosphorus, and sodium intakes, the rankings were reversed to account for their possible procarcinogenic properties. The rankings were summed to create each woman's mineral score. The mineral score–incident colorectal cancer association was estimated using multivariable Cox proportional hazards regression.

Results:

There was decreasing risk with an increasing score (Ptrend = 0.001). The hazard ratios and 95% confidence intervals (CI) for those in mineral score quintiles 2 to 5 relative to those in the lowest were 0.91 (CI, 0.88–1.08), 0.85 (CI, 0.75–0.95), 0.86 (CI, 0.75–0.97), and 0.75 (CI, 0.71–0.95), respectively.

Conclusions:

Our findings suggest that a predominance of putative anti- relative to pro-colorectal carcinogenic mineral intakes may be inversely associated with colorectal cancer risk.

Impact:

These results support further investigation of colorectal cancer etiology using composite mineral intake scores.
Trends in Pediatric Central Nervous System Tumor Incidence in the United States, 1998–2013
Authors: Withrow Diana R. , de Gonzalez Amy Berrington , Lam Clara J.K. , Warren Katherine E. , Shiels Meredith S.
Published: November 2018

Background:

Brain and other central nervous system (CNS) cancers are the leading cause of U.S. pediatric cancer mortality. Incidence trends can provide etiologic insight. We report trends in incidence rates of pediatric malignant CNS cancers and pilocytic astrocytoma (nonmalignant but historically registered) in the United States.

Methods:

Age-standardized incidence rates and annual percent changes (APC) in rates during 1998 to 2013 were calculated for children aged 0 to 19, stratified by subtype, age, sex, and for gliomas, histology and location. We estimated the absolute change in number of cases diagnosed U.S.-wide during 2013 compared with the expected number of cases had 1998 rates remained stable.

Results:

Rates of all pediatric malignant CNS cancer combined (n = 18,612) did not change [APC: 0.16; 95% confidence interval (CI): −0.21–0.53]. There were statistically significant changes in several subtypes; however, glioma incidence (n = 10,664) increased by 0.77% per year (95% CI: 0.29–1.26), embryonal cancer rates (n = 5,423) decreased by 0.88% per year (95% CI: −1.33 to −0.43), and pilocytic astrocytoma rates (n = 6,858) increased by 0.89% per year (95% CI: 0.21–1.58). Of the 1,171 malignant tumors and 450 pilocytic astrocytomas diagnosed in U.S. children in 2013, we estimated 120 excess gliomas, 94 excess pilocytic astrocytomas, and 72 fewer embryonal CNS tumors than would be expected had 1998 rates remained stable.

Conclusions:

The gradual changes in incidence we observed for specific types of pediatric CNS cancers are likely due to a combination of changes in classification and diagnosis and true changes in CNS cancer.

Impact:

Continued surveillance of pediatric CNS tumors should remain a priority, given their significant contribution to pediatric cancer–related deaths.
Cancer-associated Fibroblast–promoted LncRNA DNM3OS Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma
Authors: Zhang Hongfang , Hua Yuhui , Jiang Zhenzhen , Yue Jing , Shi Ming , Zhen Xiaoli , Zhang Xiaoyan , Yang Ling , Zhou Rongjing , Wu Shixiu
Published: November 2018

Purpose:

Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC).

Experimental Design: By use of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and in situ hybridization assay. The association of DNM3OS and tumor radioresistance was investigated in vitro and in vivo. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation.

Results:

Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance in vitro and in vivo by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFβ/PDGFRβ/FOXO1 signaling pathway–dependent manner. FOXO1, a transcription factor downstream of PDGFβ/PDGFRβ signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter.

Conclusions:

Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.
Biological Consequences of MHC-II Expression by Tumor Cells in Cancer
Authors: Axelrod Margaret L. , Cook Rebecca S. , Johnson Douglas B. , Balko Justin M.
Published: November 2018

Immunotherapy has emerged as a key pillar of cancer treatment. To build upon the recent successes of immunotherapy, intense research efforts are aimed at a molecular understanding of antitumor immune responses, identification of biomarkers of immunotherapy response and resistance, and novel strategies to circumvent resistance. These studies are revealing new insight into the intricacies of tumor cell recognition by the immune system, in large part through MHCs. Although tumor cells widely express MHC-I, a subset of tumors originating from a variety of tissues also express MHC-II, an antigen-presenting complex traditionally associated with professional antigen-presenting cells. MHC-II is critical for antigen presentation to CD4+ T lymphocytes, whose role in antitumor immunity is becoming increasingly appreciated. Accumulating evidence demonstrates that tumor-specific MHC-II associates with favorable outcomes in patients with cancer, including those treated with immunotherapies, and with tumor rejection in murine models. Herein, we will review current research regarding tumor-enriched MHC-II expression and regulation in a range of human tumors and murine models, and the possible therapeutic applications of tumor-specific MHC-II.
First CAR to Pass the Road Test: Tisagenlecleucel's Drive to FDA Approval
Authors: Geyer Mark B.
Published: November 2018

In August 2017, the FDA took historic action in granting the first approval of gene therapy to tisagenlecleucel. This landmark step brought CAR T-cell therapy to the commercial space and heralded a new era in managing refractory B-cell malignancies and FDA oversight of gene-modified therapies.

See related article by O'Leary et al., p. 1142
Activation of AXL as a Preclinical Acquired Resistance Mechanism Against Osimertinib Treatment inEGFR-Mutant Non–Small Cell Lung Cancer Cells
Authors: Namba Kei , Shien Kazuhiko , Takahashi Yuta , Torigoe Hidejiro , Sato Hiroki , Yoshioka Takahiro , Takeda Tatsuaki , Kurihara Eisuke , Ogoshi Yusuke , Yamamoto Hiromasa , Soh Junichi , Tomida Shuta , Toyooka Shinichi
Published: November 2018

Osimertinib (AZD9291) has an efficacy superior to that of standard EGFR-tyrosine kinase inhibitors for the first-line treatment of patients with EGFR-mutant advanced non–small cell lung cancer (NSCLC). However, patients treated with osimertinib eventually acquire drug resistance, and novel therapeutic strategies to overcome acquired resistance are needed. In clinical or preclinical models, several mechanisms of acquired resistance to osimertinib have been elucidated. However, the acquired resistance mechanisms when osimertinib is initially used for EGFR-mutant NSCLC remain unclear. In this study, we experimentally established acquired osimertinib-resistant cell lines from EGFR-mutant NSCLC cell lines and investigated the molecular profiles of resistant cells to uncover the mechanisms of acquired resistance. Various resistance mechanisms were identified, including the acquisition of MET amplification, EMT induction, and the upregulation of AXL. Using targeted next-generation sequencing with a multigene panel, no secondary mutations were detected in our resistant cell lines. Among three MET-amplified cell lines, one cell line was sensitive to a combination of osimertinib and crizotinib. Acquired resistance cell lines derived from H1975 harboring the T790M mutation showed AXL upregulation, and the cell growth of these cell lines was suppressed by a combination of osimertinib and cabozantinib, an inhibitor of multiple tyrosine kinases including AXL, both in vitro and in vivo. Our results suggest that AXL might be a therapeutic target for overcoming acquired resistance to osimertinib.

Implications:

Upregulation of AXL is one of the mechanisms of acquired resistance to osimertinib, and combination of osimertinib and cabozantinib might be a key treatment for overcoming osimertinib resistance.