bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Stage I Vulvar Squamous Cell Carcinoma with Early Relapse and Rapid Disease Progression
Authors: Peri Marta , Grassadonia Antonino , Iezzi Laura , Vici Patrizia , De Tursi Michele , Natoli Clara , Tinari Nicola , Zilli Marinella
Published: July 2019

Squamous cell carcinoma (SCC) is the most common subtype of vulvar cancer. Locoregional surgery is often curative when the tumor is diagnosed at an early stage. However, the disease can unexpectedly evolve with a dismal prognosis even after an early diagnosis. We report a case of a woman who experienced a rapid, chemorefractory tumor progression after surgery for stage IB vulvar SCC.
Assessment of Dietary Diversity of Mothers and Children of 6–24 Months from Eastern and Southern Provinces of Zambia
Authors: Alamu Emmanuel Oladeji , Gondwe Therese , Eyinla Toluwalope Emmanuel , Maziya-Dixon Busie
Published: July 2019

In-depth information on dietary diversity and food consumption patterns in Zambian households is still scarce. This study, therefore, probed dietary intakes of mothers and their children living in households of two Zambian districts, Chipata and Monze, located in the eastern and southern provinces of Zambia, respectively. After assessing their diet, Dietary Diversity Scores (DDSs) were calculated and classified into low and high categories, while correlations were used to test determinants of DDS. The assessment revealed that the consumption of cereal-based products ranked highest in frequency. Specifically, the consumption of maize-based foods was highest in Chipata (55.43%) and then in Monze (43.56%) households. There was an observed low preference for mixed dishes that were not either maize or groundnut porridges. We also found positive and negative correlations of DDS with the educational level of household heads and age of mothers, respectively. We, therefore, suggest that increased nutrition education may improve dietary preferences, so also further investigation into other factors hindering low choices for mixed recipes will be useful in increasing overall diet quality.
The Incidence of Non-Tuberculous Mycobacteria in Infants in Kenya
Authors: Kaguthi Grace , Nduba Videlis , Murithi Wilfred , Verver Suzanne
Published: July 2019

There is inadequate understanding of the epidemiology of Non-Tuberculous Mycobacteria (NTM) among infants in high tuberculosis burden countries. The objective of this study was to document the incidence and diversity of NTM disease or colonisation in sputum specimens from infants with presumptive TB, the risk factors, and clinical characteristics, in a high TB and HIV burden setting in Western Kenya. A cohort of 2900 newborns was followed for 1–2 years to assess TB incidence. TB investigations included collection of induced sputa and gastric aspirates for culture and speciation by HAIN®, Tuberculin Skin Testing (TST), HIV testing, and chest radiography. The American Thoracic Society Criteria (ATS) were applied to identify NTM disease. Among 927 (32% of 2900) with presumptive TB, 742 (80%) were investigated. NTM were isolated from 19/742 (2.6%) infants. M. fortuitum was most frequently speciated (32%). Total person-time was 3330 years. NTM incidence was 5.7/1,000 person-years, 95% CI (3.5, 8.7). Infants diagnosed with TB were more likely to have NTM isolation (odds ratio 11.5; 95% CI 3.25, 41.0). None of the infants with NTM isolated met the criteria for NTM disease. The incidence of NTM isolation was comparable to similar studies in Africa. NTM isolation did not meet ATS criteria for disease and could represent colonisation. TB disease appears to be structural lung disease predisposing to NTM colonisation.
Controlled Release of Ropivacaine from Single-Armed (1-PCL) and Four-Armed PCL (4-PCL) Microspheres
Authors: Xiong Wei , Shen Yue-kun , Dong Peng , Xiao Ying , Huang Xiong-qing , Huang Wen-qi , Yang Lu , Feng Xia
Published: July 2019

Sustained release of anesthesia has shown great promise in the treatment of chronic pain in patients. In this research, we used neutralized ropivacaine as an anesthesia and poly(ε-caprolactone) (PCL) with different architectures to systematically study how these architectures affect the release of ropivacaine. After optimizing the parameters of the preparation of microspheres, ropivacaine-loaded 1-PCL microspheres and 4-PCL microspheres were obtained. Fourier Transform infrared spectra (FT-IR) and X-ray diffraction spectra (XRD) confirmed that ropivacaine was encapsulated within the microsphere rather than inserted on the surface of the microsphere. Ropivacaine was found to be buried deeper in the 1-PCL microsphere than in the 4-PCL microsphere. In vitro release assay revealed that small crystalline grains interfered with ropivacaine release in 4-PCL microspheres during the initial release period, but then two kinds of microspheres showed a similar ropivacaine release rate. We basically proved that the architecture of PCL has a negligible effect on ropivacaine release. Cell proliferation test revealed that the release of products from the microspheres resulted in insignificant toxicity towards mammalian cells.
On Calibration and Direction Finding with Uniform Circular Arrays
Authors: Häfner Stephan , Käske Martin , Thomä Reiner
Published: July 2019

Antenna array calibration methods and narrowband direction finding (DF) techniques will be outlined and compared for a uniform circular array. DF is stated as an inverse problem, which solution requires a parametric model of the array itself. Because real arrays suffer from mechanical and electrical imperfections, analytic array models are per se not applicable. Mitigation of such disturbances by a global calibration matrix will be addressed, and methods to estimate this calibration matrix will be recapped from literature. Also, a novel method will be presented, which circumvents the problem of a changed noise statistic due to calibration. Furthermore, local calibration, where array calibration measurements are incorporated in the DF algorithm, is considered as well. Common DF algorithms will be outlined, their assumptions regarding array properties will be addressed, and required preprocessing steps such as the beam-space transformation will be presented. Also, two novel DF techniques will be proposed, based on the Capon beamformer, but with reduced computational effort and higher resolution for bearing estimation. Simulations are used to exemplary compare calibration and DF methods in conjunction with each other. Furthermore, measurements with a single and two coherent sources are considered. It turns out that global calibration enables computational efficient DF algorithms but causes biased estimates. Furthermore, resolution of two coherent sources necessitates array calibration.
Plasticity of Drug-Naïve and Vemurafenib- or Trametinib-Resistant Melanoma Cells in Execution of Differentiation/Pigmentation Program
Authors: Czyz Malgorzata , Sztiller-Sikorska Malgorzata , Gajos-Michniewicz Anna , Osrodek Marta , Hartman Mariusz L.
Published: July 2019

Melanoma plasticity creates a plethora of opportunities for cancer cells to escape treatment. Thus, therapies must target all cancer cell subpopulations bearing the potential to contribute to disease. The role of the differentiation/pigmentation program in intrinsic and acquired drug resistance is largely uncharacterized. MITF level and expression of MITF-dependent pigmentation-related genes,MLANA,PMEL,TYR,andDCT, in drug-naïve and vemurafenib- or trametinib-treated patient-derived melanoma cell lines and their drug-resistant counterparts were analysed and referred to genomic alterations. Variability in execution of pigmentation/differentiation program was detected in patient-derived melanoma cell lines. Acute treatment with vemurafenib or trametinib enhanced expression of pigmentation-related genes in MITF-Mhighmelanoma cells, partially as the consequence of transcriptional reprograming. During development of resistance, changes in pigmentation program were not unidirectional, but also not universal as expression of different pigmentation-related genes was diversely affected. In selected resistant cell lines, differentiation/pigmentation was promoted and might be considered as one of drug-tolerant phenotypes. In other resistant lines, dedifferentiation was induced. Upon drug withdrawal (“drug holiday”), the dedifferentiation process in resistant cells either was enhanced but reversed by drug reexposure suggesting involvement of epigenetic mechanisms or was irreversible. The irreversible dedifferentiation might be connected with homozygous loss-of-function mutation inMC1R, as MC1RR151C  +/+variant was found exclusively in drug-naïve MITF-Mlowdedifferentiated cells and drug-resistant cells derived from MITFhigh/MC1RWTcells undergoing irreversible dedifferentiation. MC1RR151C  +/+variant might be further investigated as a parameter potentially impacting melanoma patient stratification and aiding in treatment decision.
Distributed Gaussian Granular Neural Networks Ensemble for Prediction Intervals Construction
Authors: Sheng Chunyang , Wang Haixia , Lu Xiao , Zhang Zhiguo , Cui Wei , Li Yuxia
Published: July 2019

To overcome the weakness of generic neural networks (NNs) ensemble for prediction intervals (PIs) construction, a novel Map‐Reduce framework‐based distributed NN ensemble consisting of several local Gaussian granular NN (GGNNs) is proposed in this study. Each local network is weighted according to its contribution to the ensemble model. The weighted coefficient is estimated by evaluating the performance of the constructed PIs from each local network. A new evaluation principle is reported with the consideration of the predicting indices. To estimate the modelling uncertainty and the data noise simultaneously, the Gaussian granular is introduced to the numeric NNs. The constructed PIs can then be calculated by the variance of output distribution of each local NN, i.e., the summation of the model uncertainty variance and the data noise variance. To verify the effectiveness of the proposed model, a series of prediction experiments, including two classical time series with additive noise and two industrial time series, are carried out here. The results indicate that the proposed distributed GGNNs ensemble exhibits a good performance for PIs construction.
Analyses of the Imbalance of Urban Taxis’ High-Quality Customers Based on Didi Trajectory Data
Authors: Hu Beibei , Xia Xuanxuan , Shen Xinyi , Dong Xianlei
Published: July 2019

The distribution of high-quality customers (hereafter HQC) for taxis (including ride-hailing cars) has a significant impact on drivers’ revenue and taxis’ operation efficiency. Based on the taxi global positioning system data, we construct an evaluation model of passengers to discuss the imbalance of consumption in taxi market. The profit margin for each taxi order is calculated, and then a grid-based method is used to distinguish the HQC and the regions with potential higher benefits. We analyze the HQC’s distribution of taxis (including ride-hailing cars) in different areas and in different time periods. We find that the HQC are distributed mainly on the periphery of the main urban area, which indicates that traffic condition is even worse in the urban center because of factors such as congestion. The HQC are more concentrated on workdays and more scattered on nonworkdays, which implies that the public have different travel habits and demands on workdays and nonworkdays. The proportion of HQC in each administrative district or functional zone is not always positively correlated to either the proportion of total orders or the total HQC. This indicates that the distribution of HQC in each administrative district or functional zone is imbalanced. The proportion of orders and that of HQC are roughly the same in the temporal dimension, being higher in the morning and evening rush hours. Compared with the distribution of the HQC of ride-hailing, that of taxis is more imbalanced in the temporal dimension. Relevant departments should further coordinate taxi pricing, strengthen market control, and promote sustainable development in the taxi and ride-hailing markets.
Analysis and Control of Fractional Order Generalized Lorenz Chaotic System by Using Finite Time Synchronization
Authors: Cui Yan , He Hongjun , Sun Guan , Lu Chenhui
Published: July 2019

In this paper, we present a corresponding fractional order three-dimensional autonomous chaotic system based on a new class of integer order chaotic systems. We found that the fractional order chaotic system belongs to the generalized Lorenz system family by analyzing its linear term and topological structure. We also found that the equilibrium point generated by the fractional order system belongs to the unstable saddle point through the prediction correction method and the fractional order stability theory. The complexity of fractional order chaotic system is given by spectral entropy algorithm andC0algorithm. We concluded that the fractional order chaotic system has a higher complexity. The fractional order system can generate rich dynamic behavior phenomenon with the values of the parameters and the order changed. We applied the finite time stability theory to design the finite time synchronous controller between drive system and corresponding system. The numerical simulations demonstrate that the controller provides fast and efficient method in the synchronization process.
Route Redundancy-Based Network Topology Measure of Metro Networks
Authors: Jing Weiwei , Xu Xiangdong , Pu Yichao
Published: July 2019

The metro system plays a very important role in the urban multimodal transportation system, yet it is susceptible to accidents. A well-designed metro system needs to provide alternative routes to travellers both in the disruptive events and the normal operating conditions for providing rerouting opportunities and balancing crowded lines. This paper provides a new dimension of assessing metro network performance—travellers’ route redundancy (or route diversity), which is defined as the number of behaviourally effective routes between each origin-destination (O-D) pair in the network. The route redundancy of metro network is evaluated by statistical indicators of the distribution of the O-D-level number of effective routes. Compared with the existing connectivity and accessibility measures of topology network performance, route redundancy is also based on the topology network, but it takes the travellers’ route choice into consideration. Specifically, the effective routes between each O-D pair would provide disaggregated information from the travellers’ perspective. Case studies in four metropolises in the world, i.e., Shanghai, Beijing, London, and Tokyo, are conducted to examine the predisaster preparedness of the four metro networks explicitly from the perspective of route redundancy. The results indicate that the London metro network has the best route redundancy performance in terms of the statistical indicators of the distribution of the O-D level number of effective routes. Furthermore, the results of route redundancy are compared with typical measures of topology network performance in terms of measuring connectivity and accessibility of metro networks. Their differences are attributed to the fact that the route redundancy measure considers the travellers’ O-D-level route choice beyond the pure network topology and the shortest path considerations of the existing measures. The route redundancy proposed in this paper could assist in evaluating the predisaster preparedness of current or planning metro networks from O-D level to network level.
Voltammetry Determination of Pb(II), Cd(II), and Zn(II) at Bismuth Film Electrode Combined with 8-Hydroxyquinoline as a Complexing Agent
Authors: Thanh Nguyen Mau , Luyen Nguyen Dinh , Thanh Tam Toan Tran , Hai Phong Nguyen , Van Hop Nguyen
Published: July 2019

A novel method was developed for the simultaneous determination of Pb(II), Cd(II), and Zn(II) based on the cathodic stripping response at a bismuth film electrode associated with oxine as a chelating agent. The developed method provided a high and sharp electrochemical response compared with the method without oxine. A linear response of peak currents was observed for Pb(II), Cd(II), and Zn(II) concentration in the range from 2 ppb to 110 ppb. The detection limits of Pb(II), Cd(II), and Zn(II) were 0.45, 0.17, and 0.78 ppb, respectively. This method was successfully applied to the determination of Pb(II), Cd(II), and Zn(II) in lake-water and river-water samples. The metals were detected at the ultratrace level, showing the feasibility of the proposed method for environmental applications.
Epoxy Resin’s Influence in Metakaolin-Based Geopolymer’s Antiseawater Corrosion Performance
Authors: Bian Wenrui , Wang Zhongchang , Zhang Mo
Published: July 2019

To obtain the influence mechanism of epoxy resin content, curing time, and other external factors on the compressive strength and seawater corrosion resistance of geopolymer, the NaOH and Na2SiO3 were used as activators; the effect of epoxy resin concentration on the corrosion resistance of metakaolin-based geopolymer was investigated by experiments. The mechanism of epoxy resin concentration affecting the polymerization process and the properties of geopolymer was analyzed by X-ray diffraction, scanning electron microscopy-energy spectrum, and Fourier transform infrared spectroscopy. It was shown that the epoxy resin slowed down the polymerization. The presence of epoxy resin had a beneficial effect on compact structure. Furthermore, compared with the noncorrosive specimen, mixed with 30% specimen’s average compressive strength increased by 4.77MPa and 4.24MPa after curing for 1d and 3d and soaking for 56d.
Escherichia coli Nissle 1917 Protects Intestinal Barrier Function by Inhibiting NF-κB-Mediated Activation of the MLCK-P-MLC Signaling Pathway
Authors: Guo Shihao , Chen Shanwen , Ma Ju , Ma Yongchen , Zhu Jing , Ma Yuanyuan , Liu Yucun , Wang Pengyuan , Pan Yisheng
Published: July 2019

Escherichia coli Nissle 1917 (EcN), a kind of probiotic, has been reported to have a protective effect on the intestinal barrier function and can ameliorate certain gastrointestinal disorders. In this study, the potential protective effect of EcN on the intestinal barrier function in a septic mouse model induced by cecal ligation and puncture (CLP) operation was investigated. FITC-Dextran 4,000 Da (FD-4) flux and the expression levels of tight junction (TJ) proteins were measured to evaluate the protective effect of EcN on the intestinal barrier function. Then, Caco-2 monolayers were utilized to further investigate the protective effect of the EcN supernatant (EcNsup) on the barrier dysfunction induced by TNF-α and IFN-γ in vitro; the plasma level of both the cytokines increased significantly during sepsis. Transepithelial electrical resistance (TEER) and FD-4 transmembrane flux were measured, and the localization of ZO-1 and Occludin was investigated by immunofluorescence. The expression of MLCK and the phosphorylation of MLC were detected by western blot. The activation of NF-κB was explored by immunofluorescence, and CHIP assays were performed to investigate the conjunction of NF-κB with the promoter of MLCK. The results indicated that EcN protected the intestinal barrier function in sepsis by ameliorating the altered expression and localization of TJ proteins and inhibiting the NF-κB-mediated activation of the MLCK-P-MLC signaling pathway which might be one of the mechanisms underlying the effect of EcN.
Arterial Calcification on Wrist Radiographs May Suggest Need for Evaluation of Atherosclerosis in Asymptomatic Individuals
Authors: Watchmaker Lauren E. , Watchmaker Jennifer M. , Watchmaker Greg P.
Published: July 2019

Asymptomatic individuals with significant coronary artery disease (CAD) are at risk for unanticipated cardiac events including myocardial infarction (MI). Laboratory studies, stress tests, and coronary artery imaging including coronary artery calcium (CAC) scoring evaluate at-risk individuals. Hand and wrist x-rays demonstrating significant arterial wall calcification may provide an additional means to identify asymptomatic individuals at risk for cardiac events. Here we report a case series of patients without known cardiac disease who demonstrated significant calcium deposits in the radial and/or ulnar arteries in radiographs performed for evaluation of their hand conditions. Each series patient was subsequently found to have calcification on coronary artery imaging and an elevated risk of future cardiac events. Our series suggests that peripheral arterial calcifications observed by radiologists and hand specialists may warrant systemic evaluation for atherosclerosis in other areas of the body.
An Approach Enabling Various Queries on Encrypted Industrial Data Stream
Authors: Wang Tao , Yang Bo , Qiu Guoyong , Zhang Lina , Yu Yong , Zhou Yanwei , Guo Juncai
Published: July 2019

Massive data are generated and collected by devices in the industrial Internet of Things. Data sources would encrypt the data and send them to the data center through the gateway. For some supervision purpose, the gateway needs to observe the encrypted data stream and label the suspicious data. Instead of decrypting ciphertext at the gateway, which is not efficient, this paper presents a Φ-searchable functional encryption scheme that supports inner product evaluations on encrypted data. Based on this scheme, an approach enabling various queries on the encrypted industrial data stream is proposed. The adaptive security of our proposed underlying functional encryption scheme can be proven under general subgroup decision assumptions, and our scheme has the smaller public key, the smaller secret key, and the smaller ciphertext size compared to the related schemes. In addition, the experimental results show that our proposed scheme is efficient. Especially for the gateway, querying on the encrypted data only needs less than 20ms, which is practical for industrial data stream auditing scenario.
Cloud Manufacturing Service Composition Optimization with Improved Genetic Algorithm
Authors: Li Yongxiang , Yao Xifan , Liu Min
Published: July 2019

Aiming at the problems in which there exists collocation between services and manufacturing tasks, multiobjective cloud manufacturing service composition optimization seldom considers the synergy degree of composite cloud services and the complexity of service composition, so a novel service composition optimization approach, called improved genetic algorithm based on entropy (IGABE), is put forward. First, the mathematical expressions of service collocation degree, composition synergy degree, composition entropy, and their related influence factors of the service composition are analyzed, and their definitions and calculation methods are given. Then, a multiobjective cloud manufacturing service composition optimization mathematical model is established. Moreover, crossover and mutation operators are improved by introducing normal cloud model theory and piecewise function, and improved roulette selection method is used to perform the selection operation. And the fitness function of the proposed IGABE is designed by combining Euclidean deviation with angular deviation. Finally, the manufacturing task of a wheeled cleaning robot is exemplified to verify the correctness of the proposed multiobjective optimization model for cloud manufacturing service composition and the effectiveness of the proposed algorithm, compared with Standard Genetic Algorithm (SGA), Hybrid Genetic Algorithm (HGA), and Cloud‐entropy Enhanced Genetic Algorithm (CEGA). The studied results show that IGABE converges faster than SGA and HGA and can analyze and reflect the content difference expressed by the objective functions of service composition scheme and its approximation degree to the corresponding dimensions of the ideal point vector more comprehensively than CEGA. As such, the optimal service composition obtained by IGABE algorithm can better meet the complex needs of users.
The Sensitivity of Temperature to Tachyhydrite Formation: Evidence from Evaporation Experiments of Simulated Brines Based on Compositions of Fluid Inclusions in Halite
Authors: Cheng Huaide , Hai Qingyu , Li Jun , Song Jianguo , Ma Xuehai
Published: July 2019

An average of concentrations of Na+, Mg2+, Ca2+, K+, and Cl– in fluid inclusions, from the Khorat Plateau evaporite primary halite, was employed. The evaporation–crystallization sequence and paths were obtained under various temperature conditions for the quinary system, Na+, K+, Mg2+, Ca2+//Cl–-H2O. The results showed (1) a halite, sylvite, and carnallite stage at 25°C; (2) a halite, sylvite, carnallite, and bischofite stage at 35°C; and (3) a halite, sylvite, carnallite, bischofite, and tachyhydrite stage at 50°C. These results indicated that (1) a hot state is favorable for tachyhydrite formation, (2) tachyhydrite occurs in the late evaporation stage, and (3) the stability field of tachyhydrite increases with increasing temperature. The crystallization paths were plotted by the application of Jänecke phase diagram at 25°C, 35°C, and 50°C involving the system Na+, K+, Mg2+, Ca2+//Cl–-H2O. The crystallization sequence predicted on the Jänecke phase diagram showed a good agreement with the experimental crystallization sequences and paths. Tachyhydrite precipitate more easily from a high Ca concentration solution during the late evaporation stage with increasing temperature under the same relative humidity condition. The evaporite mineral succession in the Khorat Plateau, Sergipe, and Congo basins agrees well with the mineral precipitation sequences predicted from their own fluid inclusions in halite. This is confirmed by the simulation of the Jänecke phase diagram at 50°C involving the system Na+, K+, Mg2+, Ca2+//Cl–-H2O. The precipitation of tachyhydrite was sensitive to the temperature, and that the thermal resource may originate from a temperature profile in the solar pond. This study presented a simulated approach that can help in understanding similar cases that studies the sensitivity of temperature to salt formation.
A QR Code Secret Hiding Scheme against Contrast Analysis Attack for the Internet of Things
Authors: Zhao Qinglan , Yang Shuntong , Zheng Dong , Qin Baodong
Published: July 2019

Due to the advantages of larger content and error correction capability, quick response (QR) code is commonly used as a tagging technology for the Internet of Things (IoT) recently. However, the cover message of QR code can be easily decoded by a QR code reader, which causes the security and privacy of the cover message to raise the important issues. In this paper we present a new secret hiding scheme based on QR code. The proposed scheme has low computational complexity and is suitable for low-power devices in IoT systems because of utilizing the error correction property of QR code to hide secret information. The proposed scheme hides the secret information without changing the cover message of QR code and the user can get the cover message by using a general scanner, which contributes to reducing attacker’s curiosity. The hidden secret information can be read by a special scanner with the help of the user key. One thing which is better than other known schemes is that the proposed scheme can resist contrast analysis attack. In addition, experimental results show the proposed scheme has feasibility, low computational complexity, and high hiding payload.
Determining the Effective Electromagnetic Parameters of Photonic Crystal by Phase Unwrapping and Denoising Method
Authors: Lu Guizhen , Duan Zhonghang , Yin Hongcheng , Xiao Zhihe , Zhang Jing
Published: July 2019

The electromagnetic parameters of the dispersion material and metamaterial are vital in the engineering. The phase unwrapping method is proposed to deal with the phase ambiguity of the transmission and reflection method in electromagnetic (EM) parameters extraction. The computed results demonstrate that the proposed method can give the correct effective parameters. In dealing with scattering parameters with noise, the wavelet transform method is utilized to remove the noise added to the scattering parameters. The simulated results show that the correct material parameters can be obtained by wavelet denoising method. Finally, the proposed method is used to extract the parameters of the photonic crystal. The effective parameter gives a different aspect in explanation to the function for the photonic crystal.
Optimal Coordination of Last Trains for Maximum Transfer Accessibility with Heterogeneous Walking Time
Authors: Chen Yao , Mao Baohua , Bai Yun , Ho Tin Kin , Li Zhujun
Published: July 2019

Last train coordination aims to synchronize the arrival and departure times of the last feeder trains and the last connecting trains at transfer stations to improve the transfer accessibility of urban rail networks. This study focuses on the transfer accessibility between last trains with considering heterogeneous transfer walking time. Three mathematical models are developed on the last train timetable optimization. The first model fine-tunes the last train timetable under the given bound of the dwell time. The second one aims to allow the mutual transfers with the prolonged dwell time to maximize the transfer accessibility. A biobjective function is proposed to seek the trade-off between the maximal transfer accessibility and the minimal extension of dwell time. The third model considers the heterogeneity of transfer walking time that is represented as a random variable following a probability distribution. A discrete approximation method is proposed to reformulate the nonlinear model. The embedded Branch & Cut algorithm of CPLEX is applied to solve the models. A real case on the Shenzhen metro network is conducted to demonstrate the performance of the models. The three models all provide better last train timetable than the current timetable in practice. The sensitivity analysis manifests that the third model are always advantageous in the optimization of successful transfer passengers.
In Vivo ERK1/2 Reporter Predictively Models Response and Resistance to Combined BRAF and MEK Inhibitors in Melanoma
Authors: Sanchez Ileine M. , Purwin Timothy J. , Chervoneva Inna , Erkes Dan A. , Nguyen Mai Q. , Davies Michael A. , Nathanson Katherine L. , Kemper Kristel , Peeper Daniel S. , Aplin Andrew E.
Published: July 2019

Combined BRAF and MEK inhibition is a standard of care in patients with advanced BRAF-mutant melanoma, but acquired resistance remains a challenge that limits response durability. Here, we quantitated in vivo ERK1/2 activity and tumor response associated with resistance to combined BRAF and MEK inhibition in mutant BRAF xenografts. We found that ERK1/2 pathway reactivation preceded the growth of resistant tumors. Moreover, we detected a subset of cells that not only persisted throughout long-term treatment but restored ERK1/2 signaling and grew upon drug removal. Cell lines derived from combination-resistant tumors (CRT) exhibited elevated ERK1/2 phosphorylation, which were sensitive to ERK1/2 inhibition. In some CRTs, we detected a tandem duplication of the BRAF kinase domain. Monitoring ERK1/2 activity in vivo was efficacious in predicting tumor response during intermittent treatment. We observed maintained expression of the mitotic regulator, polo-like kinase 1 (Plk1), in melanoma resistant to BRAF and MEK inhibitors. Plk1 inhibition induced apoptosis in CRTs, leading to slowed growth of BRAF and MEK inhibitor–resistant tumors in vivo. These data demonstrate the utility of in vivo ERK1/2 pathway reporting as a tool to optimize clinical dosing schemes and establish suppression of Plk1 as potential salvage therapy for BRAF inhibitor and MEK inhibitor–resistant melanoma.
Anti-GPRC5D/CD3 Bispecific T-Cell–Redirecting Antibody for the Treatment of Multiple Myeloma
Authors: Kodama Tatsushi , Kochi Yu , Nakai Waka , Mizuno Hideaki , Baba Takeshi , Habu Kiyoshi , Sawada Noriaki , Tsunoda Hiroyuki , Shima Takahiro , Miyawaki Kohta , Kikushige Yoshikane , Mori Yasuo , Miyamoto Toshihiro , Maeda Takahiro , Akashi Koichi
Published: July 2019

Although treatment advances over recent decades have significantly improved survival of patients with multiple myeloma, there is still an unmet medical need for more effective treatments. In this study, we identified G-protein–coupled receptor family C group 5 member D (GPRC5D) expression on the surface of malignant cells involved in multiple myeloma, but except for plasma cells and B cells, not at appreciable levels on normal hematopoietic cells and bone marrow progenitors, including hematopoietic stem cells. In addition, we constructed IgG-based anti-GPRC5D/CD3 bispecific T-cell–redirecting antibodies (GPRC5D TRAB), which suppressed the tumor growth of GPRC5D-positive myeloma cells through the activation of T cells in vitro and in vivo in xenograft models. Collectively, these findings suggest that GPRC5D is an antigen specific to multiple myeloma and a potential target of TRAB therapy.
Autophagy in Skin Diseases
Authors: Guo Yeye , Zhang Xu , Wu Tianhao , Hu Xing , Su Juan , Chen Xiang 
Published: July 2019

Autophagy, or self-eating, is an evolutionarily conserved process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for the degradation and recycling of cytoplasmic components in eukaryotes. It is well recognized that autophagy plays an important role in maintaining cellular homeostasis under physiological and pathophysiological con­ditions and the upregulation of autophagy may serve as an adaptive process to provide nutrients and energy when under stresses. Recently, studies have illustrated that autophagy is intricately related to skin diseases. This review provides a brief synopsis of the process of autophagy and aims to elucidate the roles of autophagy in different skin diseases and to highlight the need for increased research in the field.
One-Step verse Step-Up Laparoscopic-Assisted Necrosectomy for Infected Pancreatic Necrosis
Authors: Cao Feng , Duan Ning , Gao Chongchong , Li Ang , Li Fei
Published: July 2019

Background: Percutaneous or endoscopic drainage was usually performed as the first step in step-up approach for infected pancreatic necrosis (IPN). However, drainage was unnecessary or unavailable in some patients. Objective: To estimate the safety and effect of one-step laparoscopic-assisted necrosectomy in IPN patients. Methods: A retrospective analysis of IPN patients received surgical therapy in our center between January 2015 and December 2017 was performed. Patients were assigned to either one-step or step-up groups according to the received therapeutic approach. Incidence of complications, death, total number of interventions, and total hospital stay were compared. Logistic regression and nomogram were used to explore the risk factors and probability for patients undergoing interventions ≥3 times. Results: There were 45 and 49 patients included in one-step and step-up groups, respectively. No significant difference between groups in terms of new organ failure (14.29 vs. 14.33%, p = 0.832), death (8.89 vs.8.17%, p = 0.949), and long-term complications (18.37 vs. 15.56%, p = 0.717). However, the number of interventions in one-step group was significantly less than in step-up group with shorter hospital stay. After multivariate analysis, C-reactive protein, interleukin-6, and surgical approach were independent predicators for patients undergoing interventions ≥3. A nomogram was built with area under ROC curve 0.891. Conclusion: Compared with step-up approach, one-step surgery was safe and effective in selected IPN patients with less interventions and shorter hospital stay.
Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder
Authors: Yang Bo , Lin Lin , Bazinet Richard P. , Chien Yu-Chuan , Chang Jane Pei-Chen , Satyanarayanan Senthil Kumaran , Su Huanxing , Su Kuan-Pin
Published: July 2019

Background: Endocannabinoids (ECs) are one type of bioactive endogenous neuroinflammatory mediator derived from polyunsaturated fatty acids (PUFAs), which may regulate the emotional processes. Here, we assessed the effect of ω–3 PUFAs on EC levels, which may be the novel targets for the ω–3 PUFAs’ antidepressive effects. Methods: We conducted a 12-week double-blind, nonplacebo, randomized controlled trial. Eighty-eight major depressive disorder (MDD) participants were randomly assigned to receive eicosapentaenoic acid (EPA, 3.0 g/day), docosahexaenoic acid (DHA, 1.4 g/day), or a combination of EPA (1.5 g/d) and DHA (0.7 g/day). Eighty-five participants completed the trial, and their clinical remission and plasma PUFA-derived EC levels (pmol/mL) were measured. Results: The cumulative rates of clinical remission were significantly higher in the EPA and EPA + DHA groups than the DHA group (51.85 and 53.84 vs. 34.37%; p =0.027 and p =0.024, respectively). EPA and EPA + DHA treatments increased the eicosapentaenoylethanolamide (EPEA) levels compared to DHA treatment (0.33 ± 0.18 and 0.35 ± 0.24 vs. 0.08 ± 0.12; p =0.002 and p =0.001, respectively), while EPA + DHA treatment increased the docosahexaenoylethanolamide levels more than EPA treatment (1.34 ± 2.09 vs. 0.01 ± 1.79; p =0.006). Plasma EPEA levels were positively correlated with rates of clinical remission (hazard ratio: 1.60, 95% confidence interval: 1.08–2.39). Conclusions: Treatments enriched with EPA increased plasma EPEA levels, which was positively associated with clinical remission. This finding may suggest that levels of plasma EPEA play a potential novel endogenous therapeutic target in MDD.
Robotic-Assisted versus Laparoscopic Distal Pancreatectomy: The Results of a Case-Matched Analysis from a Tertiary Care Center
Authors: Marino Marco Vito , Mirabella Antonello , Gomez Ruiz Marcos , Komorowski Andrzej Lech
Published: July 2019

Background: Laparoscopic distal pancreatectomy (LDP) has been adopted relatively slowly despite the benefits of minimally invasive approach. The robotic approach can overcome the limitations of LDP, thus increasing the acceptance of minimally invasive distal pancreatectomy. Methods: We performed a 1:1 retrospective case-matched comparison among 2 groups of 35 patients who underwent robotic-assisted distal pancreatectomy (RDP) or LDP from August 2014 to April 2017. Results: The operative time was similar in both groups (230 RDP vs. 205 LDP min, p = 0.382). The robotic group had a lower estimated blood loss (95 vs. 275 mL, p = 0.035). The spleen preservation rate was higher in the RDP group (100 vs. 66.7%, p = 0.027), while the conversion rate to open surgery was higher in the laparoscopic group (14.3 vs. 2.9%, p = 0.048). The overall complication rate was lower in the robotic group (25.7 vs. 37.1%, p = 0.044). There was no statistically significant difference in oncologic outcomes between the groups in terms of R0 resection rate (100% RDP vs. 85% LDP, p = 0.233) and number of harvested lymph nodes (14.4 RDP vs. 10.8 LDP, p = 0.678). Conclusions: The RDP showed a lower estimated blood loss, conversion, and morbidity rate. It offered a higher spleen preservation rate in comparison to LDP while maintaining comparable oncologic outcomes.
Acute Kidney Injury following Cardiac Surgery: A Clinical Model
Authors: Billings IV Frederic T.
Published: July 2019

Background: Scientists use preclinical models of acute kidney injury (AKI) to decipher mechanisms and develop therapy, but translation of therapies to patients remains poor. Models that better resemble patients, including those within clinical care, should be considered. Summary: Mice provide many advantages to the study of human disease including an ability to dictate precise experimental conditions. To best isolate and measure phenomena, scientists reduce experimental variability – identical animals, environmental conditions, experimental exposures, and outcome assessments. This technique reduces effect size variability and increases power but dissociates these model organisms from the clinical patients they intend to represent, potentially accounting for the poor translation of findings into patient care. Clinical research, conversely, is often plagued by heterogeneous patients, heterogenous environmental factors, and heterogenous renal insults. A compromise between these 2 extremes – a model of AKI that is more similar to human disease but still provides opportunities for rigorous investigation – should be utilized. Cardiac surgery provides a clinical model for the study of AKI due to mechanism overlap it shares with other clinical conditions (improved generalizability) and characteristics that provide distinct opportunities for research. The high rate of AKI following cardiac surgery and the relative homogeneity (decreased variability) of cardiac surgery subjects, their environment, and renal insults increase power and the opportunity to make discoveries and advance care. Moreover, the elective nature of cardiac surgery provides opportunities to perform detailed baseline assessments and pretreat select patients. Key Messages: Models that better reflect clinical AKI are needed to decipher mechanisms and develop effective treatments. Cardiac surgery is an important clinical model form for the study of AKI.
El tema de la “Doctrina transcendental del método”
Authors: Martínez Luciana
Published: July 2019

En este artículo se sostiene que la “Doctrina transcendental del método” es un texto en el que Kant examina las condiciones formales de la metafísica. En esa sección, el filósofo no ofrece indicaciones metodológicas referidas a la Crítica de la razón pura, que es una propedéutica, sino al sistema de conocimientos por razón pura. En segundo término, por medio del seguimiento de una de las indicaciones de la “Doctrina transcendental del método”, se muestra que, si bien esas indicaciones no están dirigidas a especificar la metodología crítica, el desarrollo del texto kantiano es consecuente con ellas.
HIV Infection and Incidence of Cardiovascular Diseases: An Analysis of a Large Healthcare Database
Authors: Alonso Alvaro , Barnes A. Elise , Guest Jodie L. , Shah Amit , Shao Iris Yuefan , Marconi Vincent
Published: July 2019

Background

People living with
HIV
(
PLWH
) experience higher risk of myocardial infarction (
MI
) and heart failure (
HF
) compared with uninfected individuals. Risk of other cardiovascular diseases (
CVD
s) in
PLWH
has received less attention.

Methods and Results

We studied 19 798
PLWH
and 59 302 age‐ and sex‐matched uninfected individuals identified from the MarketScan Commercial and Medicare databases in the period 2009 to 2015. Incidence of
CVD
s, including
MI
,
HF
, atrial fibrillation, peripheral artery disease, stroke and any
CVD
‐related hospitalization, were identified using validated algorithms. We used adjusted Cox models to estimate hazard ratios and 95%
CI
s of
CVD
end points and performed probabilistic bias analysis to control for unmeasured confounding by race. After a mean follow‐up of 20 months, patients experienced 154
MI
s, 223
HF
, 93 stroke, 397 atrial fibrillation, 98 peripheral artery disease, and 935
CVD
hospitalizations (rates per 1000 person‐years: 1.2, 1.7, 0.7, 3.0, 0.8, and 7.1, respectively). Hazard ratios (95%
CI
) comparing
PLWH
with uninfected controls were 1.3 (0.9–1.9) for
MI
, 3.2 (2.4–4.2) for
HF
, 2.7 (1.7–4.0) for stroke, 1.2 (1.0–1.5) for atrial fibrillation, 1.1 (0.7–1.7) for peripheral artery disease, and 1.7 (1.5–2.0) for any
CVD
hospitalization. Adjustment for unmeasured confounding led to similar associations (1.2 [0.8–1.8] for
MI
, 2.8 [2.0–3.8] for
HF
, 2.3 [1.5–3.6] for stroke, 1.3 [1.0–1.7] for atrial fibrillation, 0.9 [0.5–1.4] for peripheral artery disease, and 1.6 [1.3–1.9] for
CVD
hospitalization).

Conclusions

In a large health insurance database,
PLWH
have an elevated risk of
CVD
, particularly
HF
and stroke. With the aging of the
HIV
population, developing interventions for cardiovascular health promotion and
CVD
prevention is imperative.
Windkessel Measures Derived From Pressure Waveforms Only: The Framingham Heart Study
Authors: Behnam Vira , Rong Jian , Larson Martin G. , Gotal John D. , Benjamin Emelia J. , Hamburg Naomi M. , Vasan Ramachandran S. , Mitchell Gary F.
Published: July 2019

Background

Waveform parameters derived from pressure‐only Windkessel models are related to cardiovascular disease risk and could be useful for understanding arterial system function. However, prior reports varied in their adjustment for potential confounders.

Methods and Results

Carotid tonometry waveform data from 2539 participants (mean age 63±11 years, 58% women) of the Framingham Heart Study were used to derive Windkessel measures using pressure and assuming a linear model with fixed diastolic time constant (τ
dias
) and variable asymptotic pressure (P
inf
, median 54.5; 25th, 75th percentiles: 38.4, 64.9 mm Hg) or nonlinear model with inverse pressure‐dependent τ
dias
and fixed P
inf
(20 mm Hg). During follow‐up (median 15.1 years), 459 (18%) participants had a first cardiovascular disease event. In proportional hazards models adjusted for age, sex, total cholesterol, high‐density lipoprotein cholesterol, smoking, antihypertensive medication use, diabetes mellitus, and physician‐acquired systolic blood pressure, only the systolic time constant (τ
sys
) derived from the nonlinear model was related to risk for cardiovascular disease events (hazard ratio=0.91 per 1 SD, 95% CI=0.84–0.99,
P
=0.04). When heart rate was added to the model, τ
sys
(hazard ratio=0.92, CI=0.84–1.00,
P
=0.04) and reservoir pressure amplitude (hazard ratio=1.14, CI=1.01–1.28,
P
=0.04) were related to events. In contrast, measures derived from the linear model were not related to events in models that adjusted for risk factors including systolic blood pressure (
P
>0.31) and heart rate (
P
>0.19).

Conclusions

Our results suggest that pressure‐only Windkessel measures derived by using a nonlinear model may provide incremental risk stratification, although associations were modest and further validation is required.
What Marxist Tax Policies Actually Look Like
Authors: Ireland David
Published: July 2019

‘Marx on tax’ as an effective antidote to inequality is an overlooked theme within his own output, but also for our own time. Marx theorising on tax is seen even by pre-eminent Marxists as an empty box, but Marx and Engels in fact had plenty to say about tax. Their coverage embraces progressive taxes, both on capital and income, a strong preference for direct over indirect taxation, inheritance tax, land-value tax, taxes on financial transactions, and state finances around the world. Tax also provides the battleground for a rare sight of Marx as campaigning activist, in 1848, matched in the same period by close ally Wilhelm Wolff. The tax policies of Marx and Engels have been neglected because they are primarily to be found in their journalism and letters. They are no anachronistic curiosity but perfectly applicable to the income and wealth inequalities of our own era.
The Long Brazilian Crisis: A Forum
Authors: Grigera Juan , Webber Jeffery R. , Abilio Ludmila , Antunes Ricardo , Mattos Marcelo Badaró , Fernandes Sabrina , Nunes Rodrigo , Paulani Leda , Purdy Sean
Published: July 2019

The coming to office of Jair Bolsonaro in Brazil has brought to the fore the need to understand the rise of the far right and to come to terms with the conflicted legacies of more than a decade of rule under the Workers’ Party. This forum brings together six leading intellectuals from different traditions on the left and introduces their reflections on the contradictions and complexities of the Workers’ Party, the 2008 crisis, the June 2013 protests, the weakness of the Brazilian left, corruption, and on how to characterise Bolsonaro’s regime. Their interventions offer crucial insights that are relevant today not just to Brazil, or even Latin America, but to the politics of the left worldwide.