bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR-based urine metabolic profiling and immunohistochemistry analysis of nephron changes in a mouse model of hypoxia-induced acute kidney injury
Authors: Chihanga Tafadzwa , Ruby Hannah N. , Ma Qing , Bashir Sabina , Devarajan Prasad , Kennedy Michael A.
Published: July 2018

Acute kidney injury can be caused by multiple factors, including sepsis, respiratory failure, heart failure, trauma, or nephrotoxic medications, among others. Here, a mouse model was used to investigate potential urinary metabolic biomarkers of hypoxia-induced AKI. Urine metabolic profiles of 48 Swiss Webster mice were assessed using nuclear magnetic resonance spectroscopy (NMR) for 7 days following 72 h exposure to a hypoxic 6.5% oxygen environment. Histological analyses indicated a lack of gross nephron structural changes in the aftermath of hypoxia. Immunohistochemical (IHC) analyses, however, indicated elevated expression of protein injury biomarkers in distal and proximal tubules but not glomeruli. Kidney injury molecule-1 levels peaked in distal tubules at 72 h and were still increasing in proximal tubules at 7 days posthypoxia, whereas cystatin C levels were elevated at 24 h but decreased thereafter, and were elevated and still increasing in proximal tubules at 7 days posthypoxia. Neutrophil gelatinase-associated lipocalin levels were modestly elevated from 24 h to 7 days posthypoxia. NMR-based metabolic profiling revealed that urine metabolites involved in energy metabolism and associated biosynthetic pathways were initially decreased at 24 h posthypoxia, consistent with metabolic suppression as a mechanism for cell survival, but were significantly elevated at 48 and 72 h posthypoxia, indicating a burst in organism metabolism associated with reactivation of cellular energetics during recovery after cessation of hypoxia and return to a normoxic environment. The IHC results indicated that kidney injury persists long after plasma and urine biomarkers of hypoxia return to normal values.
In vivo evidence for an interplay of FGF23/Klotho/PTH axis on the phosphate handling in renal proximal tubules
Authors: Ide Noriko , Ye Rui , Courbebaisse Marie , Olauson Hannes , Densmore Michael J. , Larsson Tobias E. , Hanai Jun-ichi , Lanske Beate
Published: July 2018

Phosphate homeostasis is primarily maintained in the renal proximal tubules, where the expression of sodium/phosphate cotransporters (Npt2a and Npt2c) is modified by the endocrine actions of both fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). However, the specific contribution of each regulatory pathway in the proximal tubules has not been fully elucidated in vivo. We have previously demonstrated that proximal tubule-specific deletion of the FGF23 coreceptor Klotho results in mild hyperphosphatemia with little to no change in serum levels of FGF23, 1,25(OH)2D3, and PTH. In the present study, we characterized mice in which the PTH receptor PTH1R was specifically deleted from the proximal tubules, either alone or in combination with Klotho ( PT-PTH1R−/−and PT-PTH1R/KL−/−, respectively). PT-PTH1R−/−mice showed significant increases in serum FGF23 and PTH levels, whereas serum phosphate levels were maintained in the normal range, and Npt2a and Npt2c expression in brush border membrane (BBM) did not change compared with control mice. In contrast, PT-PTH1R/KL−/−mice displayed hyperphosphatemia and an increased abundance of Npt2a and Npt2c in the renal BBM, along with increased circulating FGF23 levels. While serum calcium was normal, 1,25(OH)2D3levels were significantly decreased, leading to extremely high levels of PTH. Collectively, mice with a deletion of PTH1R alone in proximal tubules results in only minor changes in phosphate regulation, whereas deletion of both PTH1R and Klotho leads to a severe disturbance, including hyperphosphatemia with increased sodium/phosphate cotransporter expression in BBM. These results suggest an important interplay between the PTH/PTH1R and FGF23/Klotho pathways to affect renal phosphate handling in the proximal tubules.
Synaptic drive in spinal motoneurons during scratch network activity
Authors: Guzulaitis Robertas , Hounsgaard Jorn
Published: July 2018

Synaptic activity in motoneurons may provide unique insight in the relation between functional network activity and behavior. During scratch network activity in an ex vivo preparation from red-eared turtles ( Trachemys scripta elegans), excitatory and inhibitory synaptic current can be separated and quantified in voltage-clamp recordings. With this technique, we confirm the reciprocal synaptic excitation and inhibition in hip flexor motoneurons during ipsilateral scratching and show that out-of-phase inhibition and excitation also characterize hip extensor motoneurons during ipsi- and contralateral scratching. In contrast, inhibition precedes and partly overlaps excitation in hip flexor-like motoneurons and delays depolarization of membrane potential. We conclude that out-of-phase excitation and inhibition during rhythmic network activity is a common feature in spinal motoneurons.

NEW & NOTEWORTHY During network activity, the firing pattern of individual neurons is shaped by their intrinsic conductances and synaptic input. Quantification of synaptic input is, therefore, essential to understand how the properties of individual neurons contribute to function and help to reveal the structure of the network. Here, we show how a combination of recording techniques can be used to quantify and compare the pattern of synaptic activity in different groups of motoneurons during rhythmic network activity.
Using gaze behavior to parcellate the explicit and implicit contributions to visuomotor learning
Authors: de Brouwer Anouk J. , Albaghdadi Mohammed , Flanagan J. Randall , Gallivan Jason P.
Published: July 2018

Successful motor performance relies on our ability to adapt to changes in the environment by learning novel mappings between motor commands and sensory outcomes. Such adaptation is thought to involve two distinct mechanisms: an implicit, error-based component linked to slow learning and an explicit, strategic component linked to fast learning and savings (i.e., faster relearning). Because behavior, at any given moment, is the resultant combination of these two processes, it has remained a challenge to parcellate their relative contributions to performance. The explicit component to visuomotor rotation (VMR) learning has recently been measured by having participants verbally report their aiming strategy used to counteract the rotation. However, this procedure has been shown to magnify the explicit component. Here we tested whether task-specific eye movements, a natural component of reach planning, but poorly studied in motor learning tasks, can provide a direct readout of the state of the explicit component during VMR learning. We show, by placing targets on a visible ring and including a delay between target presentation and reach onset, that individual differences in gaze patterns during sensorimotor learning are linked to participants’ rates of learning and their expression of savings. Specifically, we find that participants who, during reach planning, naturally fixate an aimpoint rotated away from the target location, show faster initial adaptation and readaptation 24 h later. Our results demonstrate that gaze behavior cannot only uniquely identify individuals who implement cognitive strategies during learning but also how their implementation is linked to differences in learning.

NEW & NOTEWORTHY Although it is increasingly well appreciated that sensorimotor learning is driven by two separate components, an error-based process and a strategic process, it has remained a challenge to identify their relative contributions to performance. Here we demonstrate that task-specific eye movements provide a direct read-out of explicit strategies during sensorimotor learning in the presence of visual landmarks. We further show that individual differences in gaze behavior are linked to learning rate and savings.
Neuromuscular determinants of slip-induced falls and recoveries in older adults
Authors: Sawers Andrew , Bhatt Tanvi
Published: July 2018

Is there a neuromuscular basis for falls? If so, it may provide new insight into falls and their assessment and treatment. We hypothesized that falls and recoveries from a laboratory-induced slip would be characterized by differences in multimuscle coordination patterns. Using muscle synergy analysis, we identified different multimuscle coordination patterns between older adults who fell and those who recovered from a laboratory-induced “feet-forward” slip. Participants who fell recruited fewer muscle synergies than participants who recovered. This suggests that a fall may result from recruitment of an inadequate number of muscle synergies to produce the necessary mechanical functions required to maintain balance. Participants who fell also recruited different muscle synergies, including one with high levels of coactivity consistent with a startle-like response. These differences in multimuscle coordination between slip outcomes were not accompanied by differences in slip difficulty or gait kinematics before or during the slip response. The differences in neuromuscular control may therefore reflect differences in sensorimotor control rather than kinematic constraints imposed by the slip, or the musculoskeletal system. Further research is required to test the robustness of these results and their interpretation with respect to additional mechanical variables (e.g., joint torques, ground reaction forces), responses to other fall types (e.g., trips), and within rather than between individuals.

NEW & NOTEWORTHY Do falls and recoveries possess distinct neuromuscular features? We identified differences in neuromuscular control between older adults who fell and those who recovered from a “feet-forward” slip. Differences in neuromuscular control were not accompanied by differences in gait or slip kinematics before or during the slip response, suggesting differences in sensorimotor control rather than kinematics dictated the observed differences in neuromuscular control. An analysis of additional mechanical variables is required to confirm this interpretation.
A quantitative framework for motion visibility in human cortex
Authors: Birman Daniel , Gardner Justin L.
Published: July 2018

Despite the central use of motion visibility to reveal the neural basis of perception, perceptual decision making, and sensory inference there exists no comprehensive quantitative framework establishing how motion visibility parameters modulate human cortical response. Random-dot motion stimuli can be made less visible by reducing image contrast or motion coherence, or by shortening the stimulus duration. Because each of these manipulations modulates the strength of sensory neural responses they have all been extensively used to reveal cognitive and other nonsensory phenomena such as the influence of priors, attention, and choice-history biases. However, each of these manipulations is thought to influence response in different ways across different cortical regions and a comprehensive study is required to interpret this literature. Here, human participants observed random-dot stimuli varying across a large range of contrast, coherence, and stimulus durations as we measured blood-oxygen-level dependent responses. We developed a framework for modeling these responses that quantifies their functional form and sensitivity across areas. Our framework demonstrates the sensitivity of all visual areas to each parameter, with early visual areas V1–V4 showing more parametric sensitivity to changes in contrast and V3A and the human middle temporal area to coherence. Our results suggest that while motion contrast, coherence, and duration share cortical representation, they are encoded with distinct functional forms and sensitivity. Thus, our quantitative framework serves as a reference for interpretation of the vast perceptual literature manipulating these parameters and shows that different manipulations of visibility will have different effects across human visual cortex and need to be interpreted accordingly.

NEW & NOTEWORTHY Manipulations of motion visibility have served as a key tool for understanding the neural basis for visual perception. Here we measured human cortical response to changes in visibility across a comprehensive range of motion visibility parameters and modeled these with a quantitative framework. Our quantitative framework can be used as a reference for linking human cortical response to perception and underscores that different manipulations of motion visibility can have greatly different effects on cortical representation.
The parieto-insular vestibular cortex in humans: more than a single area?
Authors: Frank Sebastian M. , Greenlee Mark W.
Published: July 2018

Here, we review the structure and function of a core region in the vestibular cortex of humans that is located in the midposterior Sylvian fissure and referred to as the parieto-insular vestibular cortex (PIVC). Previous studies have investigated PIVC by using vestibular or visual motion stimuli and have observed activations that were distributed across multiple anatomical structures, including the temporo-parietal junction, retroinsula, parietal operculum, and posterior insula. However, it has remained unclear whether all of these anatomical areas correspond to PIVC and whether PIVC responds to both vestibular and visual stimuli. Recent results suggest that the region that has been referred to as PIVC in previous studies consists of multiple areas with different anatomical correlates and different functional specializations. Specifically, a vestibular but not visual area is located in the parietal operculum, close to the posterior insula, and likely corresponds to the nonhuman primate PIVC, while a visual-vestibular area is located in the retroinsular cortex and is referred to, for historical reasons, as the posterior insular cortex area (PIC). In this article, we review the anatomy, connectivity, and function of PIVC and PIC and propose that the core of the human vestibular cortex consists of at least two separate areas, which we refer to together as PIVC+. We also review the organization in the nonhuman primate brain and show that there are parallels to the proposed organization in humans.
A Novel Control Strategy on Multiple‐Mode Application of Electric Vehicle in Distributed Photovoltaic Systems
Authors: Zhong Qianwen , Sun Yize , Peng Lele
Published: July 2018

Considering the booming development of electric vehicle (EV), this article presents a novel control scheme analyzing EV multiple‐mode application in a number of distributed photovoltaic (PV) systems, which rationalizes the energy flow among the energy system participants containing a power grid, a grid‐connected PV system, power consumption devices, storage batteries, and EV. Based on the control scheme, the authors propose two day‐ahead optimal control strategies with different objective functions: one is minimizing the daily electricity expense of an individual distributed PV system and the other is minimizing the daily total expense of distributed PV systems which EV can be connected to. The model has been verified by the actual data and forecast data, respectively. The results show under the individual objective, in the distributed PV system with EV, the electricity expense can obtain an annual reduction of 27.18%. Furthermore, in the distributed PV system with a storage battery as well as EV, the electricity expense can obtain an annual reduction from 30.67% to 81.49% with a storage battery capacity changing from 1 kWh to 20 kWh. Under the total objective, the total expense and even the individual expense have different degrees of reduction. However, the specific benefits should be rerationally distributed by balancing the interests of all the distributed PV systems. In addition, besides the application in the distributed PV systems, this model may have some potential on the development of a regional energy system.
Exploring the Therapeutic Ability of Fenugreek against Type 2 Diabetes and Breast Cancer Employing Molecular Docking and Molecular Dynamics Simulations
Authors: Rampogu Shailima , Parameswaran Saravanan , Lemuel Mary Rampogu , Lee Keun Woo
Published: July 2018

Fenugreek (Trigonella foenum‐graecum) is used as a spice throughout the world. It is known for its medicinal properties such as antidiabetic, anticarcinogenic, and immunological activities. The present study shows the properties and the nutritional quality of fenugreek seed extract and focuses on screening of active compounds in drug designing for type 2 diabetes and breast cancer. Quantitative analysis was used to calculate the percentages of protein, carbohydrates moisture, fatty acid, galactomannan, oil, and amino acid. Phytochemical analysis revealed the presence of flavonoids, terpenoids, phenols, proteins, saponins, and tannins in fenugreek seed extracts. Molecular docking and molecular dynamics simulation‐based computational drug discovery methods were employed to address the role of fenugreek seed constituents against type 2 diabetes and breast cancer. The computational results reveal that the compound galactomannan can be ascribed as potential drug candidate against breast cancer and type 2 diabetes rendered by higher molecular dock scores, stable molecular dynamics (MD) simulations results, and lower binding energy calculations.
Influence Factors on the Properties of Ultrahigh‐Performance Fiber‐Reinforced Concrete Cured under the Condition of Room Temperature
Authors: Zhang Pu , Huang Yiliang , Li Yongqi , Zhao Jun , Dong Hengqian , Chen Tao
Published: July 2018

Ultrahigh‐performance fiber‐reinforced concrete (UHPFRC) is a new type of concrete with excellent performance and good application prospects. However, expensive heat curing or high‐pressure curing was often adopted to ensure the sufficient compressive strength. This study focuses on improving the compressive strength and workability of UHPFRC by changing the composition materials and the mixture ratios under standard curing conditions. The 0‐1 mm and 1∼3 mm sintered bauxite was adopted as coarse aggregate. UHPFRC with high compressive strength and good workability was developed by changing the water‐binder ratios, by adding ground‐granulated blast furnace slag (GGBFS) or fly ash, and by changing the bauxite content of different particle sizes. When the volume ratio of steel fiber was 3%, the recommend water to binder ratio was 0.194 according to this experiment, the dosage of GGBFS‐replaced cement is recommended as 20%, the dosage of fly ash instead of silica fume is recommended as 30%. The recommend ratio of 0‐1 mm and 1∼3 mm sintered bauxite was 1.51 : 1. Finally, a kind of UHPFRC material with a compressive strength of 152.4 MPa and a slump of 120 mm was developed under the standard curing conditions.
Bufadienolides from Venenum Bufonis Inhibit mTOR‐Mediated Cyclin D1 and Retinoblastoma Protein Leading to Arrest of Cell Cycle in Cancer Cells
Authors: Chang Huamei , Li Juan , Cao Yajun , Liu Tiantian , Shi Suofang , Chen Wenxing
Published: July 2018

Objective. Bufadienolides, the main components in Venenum Bufonis secreted from toads, have been proved to be with significant anticancer activity aside from the positive inotropic action as cardenolides. Here an underlying anticancer mechanism was further elucidated for an injection made from Venenum Bufonis containing nine bufadienolides. Methods. One solution reagent and cell cycle analyses were for determining effect of bufadienolides on cancer cells. Western blotting was used for protein expression. Results. Bufadienolides inhibit cell proliferation and arrest cells in G1 phase. Bufadienolides also inhibit the mammalian target of rapamycin (mTOR) signaling pathway, which is evidenced by the data that bufadienolides inhibit type I insulin‐like growth factor‐ (IGF‐1‐) activated phosphorylation of mTOR by a concentration‐ and time‐dependent way, as well as phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E‐BP1). Subsequent results indicated that cyclin D1 expression and phosphorylation of retinoblastoma protein (Rb)—two characterized regulators in cell cycle of G1—are also inhibited and the process is dependent on mTOR pathway. Conclusion. Bufadienolides inhibit proliferation partially due to arresting cell cycle in G1 phase, which is mediated by inhibiting mTOR‐cyclin D1/Rb signal pathway.
Heuristic Localization Algorithm with a Novel Error Control Mechanism for Wireless Sensor Networks with Few Anchor Nodes
Authors: Sun Yujia , Wang Xiaoming , Yu Jiyan , Wang Yu
Published: July 2018

A novel iterative localization algorithm with high accuracy and low anchor node dependency for large-scale wireless sensor networks is proposed in this paper. At each iteration, blind nodes are located using a weighted linear least squares-based algorithm. To prevent errors in the blind nodes from propagating and accumulating throughout the network, an anchor geometric feature-based error control mechanism is used to select the nodes that participate in the localization and to estimate the localization confidence. The simulation results show that the algorithm can be used when only a few anchor nodes are involved. This algorithm is more advanced than traditional methods, which often require a large number of well-placed anchor nodes to operate appropriately. By optimizing the decision parameter v of the algorithm, the average localization error of the algorithm is approximately 0.43 meters. When the ratio of anchor nodes (the ratio of the number of anchor nodes to the number of sensor nodes in the network) is 1.25% (i.e., 5 anchor nodes for 400 sensor nodes), the received signal strength indicator (RSSI) variance is 8 dBm, and the radio range is 50 meters. A comparison of the proposed algorithm with global localization methods, including multidimensional scaling (MDS), semidefinite programming (SDP), and shortest-path access (SPA), shows that the proposed algorithm achieves higher location accuracy and stability when the number of anchor nodes is varied. The efficiency of the proposed localization algorithm is evaluated in a real sensor network, and the accuracy is high and robust to radio channel variance.
Combination of Epicatechin 3‐Gallate from Euphorbia hirta and Cefepime Promotes Potential Synergistic Eradication Action against Resistant Clinical Isolate of Pseudomonas aeruginosa
Authors: Perumal Shanmugapriya , Mahmud Roziahanim , Mohamed Nornisah
Published: July 2018

Pseudomonas aeruginosa is naturally resistant to many classes of antipseudomonal antibiotics due to the species ability to easily acquire resistance. Plant‐based antibacterial agent in combination with the existing antibiotic proposes an alternative treatment regimen for the eradication of resistant bacterial infections. The antibacterial effects of the isolated epicatechin 3‐gallate compound from Euphorbia hirta in combination with cefepime were investigated in vitro against resistant P. aeruginosa. The fractional inhibitory concentration index of the combination was determined using checkerboard broth microdilution method. Epicatechin 3‐gallate combined with cefepime had produced synergistic effect against P. aeruginosa (with average FIC index of 0.24). The MIC of epicatechin 3‐gallate was effectively reduced to MIC/4, MIC/8, MIC/16, and MIC/32 in the presence of cefepime. Time‐kill study of epicatechin 3‐gallate combined with cefepime exhibited remarkable bactericidal activity where the eradication of P. aeruginosa occurred within 4 h of treatment. Scanning electron micrographs revealed apparent cell membrane damage and leakage of cytoplasmic contents from P. aeruginosa cells which eventually led to the cell lysis after the combination treatment of epicatechin 3‐gallate and cefepime. The potential of epicatechin 3‐gallate to act synergistically with cefepime against clinically resistant P. aeruginosa strain possibly will maximize the successful outcomes when choosing empirical antibiotic treatment in hospitals or health care institutions.
Effectiveness and Safety of Compound Chinese Medicine plus Routine Western Medicine in In‐Stent Restenosis: A Meta‐Analysis and Systematic Review
Authors: Liu Lu , Liu Jing , Gao Qun , Wu Yang , Lu Jinjin , Wan Jie , Li Yan , Cui Xiaoyun , Zhou Kun , Jia Wenhao , Huang Yanchao , Qu Wenbai , Lin Qian
Published: July 2018

Objective. To examine the effects and safety of oral compound Chinese medicine (CCM) plus routine western medicine (RWM) in in‐stent restenosis (ISR). Methods. Various electronic databases (CBM, CNKI, VIP, Wanfang, PubMed, EMBASE, and Cochrane Library) were searched until April 2017. The quality of the included studies was evaluated, and meta‐analyses were performed using RevMan5.3 and STATA 12.0 software. Moreover, funnel plot and Egger’s publication bias plots were analysed to identify publication bias and adverse reactions were reported. A sensitive analysis was carried out according to the quality score. Results. In all, 40 RCTs involving 4536 patients were selected for this review. The pooled estimates of three studies showed that the benefit to the number of ISRs (NoR) was more substantial for CCM plus RWM than for RWM alone (RR 0.24, 95% CI 0.10 to 0.57, P = 0.001; I2 = 0%, P = 0.81). The rate of ISR was significantly lower for CCM plus RWM than for the same RWM alone (RR 0.44, 95% CI 0.37 to 0.53, P < 0.00001; I2 = 0%, P = 0.95). CCM plus RWM benefitted the rate of ISR when a CM placebo plus RWM was used as the control intervention (RR 0.34, 95% CI 0.20 to 0.57, P < 0.0001; I2 = 0%, P = 0.95). The difference of adverse reactions was not significant. For secondary outcomes, the CCM plus RWM group did not reduce the rates of revascularization and cardiac death, but it did reduce the rate of recurrent angina over the results observed in the RWM alone group. In addition, funnel plot and Egger’s publication bias plot indicated that there was publication bias. The association between the use of CCM plus RWM and RWM alone remained significant after the sensitivity analysis excluding studies with low quality score (quality score ⩽ 4) with a pooled RR of 0.41 (95% CI, 0.34–0.50). Conclusion. Oral CCM plus RWM clearly benefitted patients with percutaneous coronary intervention (PCI) because it prevented and treated ISR better than was observed for either RWM alone or a CM placebo plus RWM.
Crack Width and Load-Carrying Capacity of RC Elements Strengthened with FRP
Authors: Slaitas Justas , Daugevičius Mykolas , Valivonis Juozas , Grigorjeva Tatjana
Published: July 2018

The present study focuses on a prediction of crack width and load-carrying capacity of flexural reinforced concrete (RC) elements strengthened with fibre-reinforced polymer (FRP) reinforcements. Most studies on cracking phenomena of FRP-strengthened RC structures are directed to empirical corrections of crack-spacing formula given by design norms. Contrary to the design norms, a crack model presented in this paper is based on fracture mechanics of solids and is applied for direct calculation of flexural crack parameters. At the ultimate stage of crack propagation, the load-carrying capacity of the element is achieved; therefore, it is assumed that the load-carrying capacity can be estimated according to the ultimate crack depth (directly measuring concrete’s compressive zone height). An experimental program is presented to verify the accuracy of the proposed model, taking into account anchorage and initial strain effects. The proposed analytical crack model can be used for more precise predictions of flexural crack propagation and load-carrying capacity.
Automatic Recognition of Asphalt Pavement Cracks Based on Image Processing and Machine Learning Approaches: A Comparative Study on Classifier Performance
Authors: Hoang Nhat-Duc , Nguyen Quoc-Lam
Published: July 2018

Periodic surveys of asphalt pavement condition are very crucial in road maintenance. This work carries out a comparative study on the performance of machine learning approaches used for automatic pavement crack recognition. Six machine learning approaches, Naïve Bayesian Classifier (NBC), Classification Tree (CT), Backpropagation Artificial Neural Network (BPANN), Radial Basis Function Neural Network (RBFNN), Support Vector Machine (SVM), and Least Squares Support Vector Machine (LSSVM), have been employed. Additionally, Median Filter (MF), Steerable Filter (SF), and Projective Integral (PI) have been used to extract useful features from pavement images. In the feature extraction phase, performance comparison shows that the input pattern including the diagonal PIs enhances the classification performance significantly by creating more informative features. A simple moving average method is also employed to reduce the size of the feature set with positive effects on the model classification performance. Experimental results point out that LSSVM has achieved the highest classification accuracy rate. Therefore, this machine learning algorithm used with the feature extraction process proposed in this study can be a very promising tool to assist transportation agencies in the task of pavement condition survey.
Fulminant Cerebral Fat Embolism: Case Description and Review of the Literature
Authors: Berlot Giorgio , Bussani Rossana , Shafiei Vennus , Zarrillo Nadia
Published: July 2018

The release of fat and bone marrow fragments is a common occurrence following traumatic and nontraumatic events. In most cases, they go symptomless or cause only minor disturbances, but occasionally they can determine a multiorgan dysfunction whose severity ranges from mild to fatal. The authors describe the case of a patient who became deeply comatose and ultimately died after a traffic accident in which he suffered the exposed right femoral and tibial fracture in the absence of other injuries. He underwent the external fixation of the fractured bones 2 hours after the admission under general anesthesia. Three hours later, he failed to awake at the suspension of the anesthetic agents and became anisocoric; a CT scan demonstrated a diffuse cerebral edema with the herniation of the cerebellar tonsils; these abnormalities were unresponsive to the treatment and the brain death was one day later. The causes, the mechanisms, the symptoms, the prevention, and the treatment of the syndrome are reviewed and discussed.
Abyssinone V‐4’ Methyl Ether Isolated from Erythrina droogmansiana (Leguminosae) Inhibits Cell Growth and Mammary Glands Hyperplasia Induced in Swiss Mice by the 7,12‐Dimethylbenz(a)anthracene
Authors: Tueche Alain Brice , Zingue Stephane , Tchoupang Edwige Nana , Gueyo Telesphore Nanbo , Gbaweng Yaya Abel Joël , Njuh Amstrong Nang , Ntsa Dieudonnée Mireille , Njamen Dieudonné
Published: July 2018

There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. The present study was designed to evaluate the in vitro and in vivo antiproliferative effects of Abyssinone V‐4’ methyl ether (AVME) on breast tissue of mice. The cytotoxicity of AVME was evaluated using MTT assay in four cancer cell lines (DU145, PC3, HepG2, and MCF‐7). Further, a protective effect of AVME was evaluated on 7,12‐dimethylbenz(a)anthracene‐ (DMBA‐) induced breast tumor in Swiss mice. Incidence, burden, volume, and histological analysis of mammary tumors were measured. As a result, AVME inhibits DU145, PC3, HepG2, and MCF‐7 cells growth. In vivo, no tumor was detected in mice from the normal group as compared to those of DMBA group. Moreover, AVME inhibits the DMBA‐induced mammary glands hyperplasia in mice at the dose of 10 mg/kg, evidenced by a decrease of tumor incidence, tumor weight, and volume as well as a protective effect against the lobular alveolar hyperplasia. Taken all together, these results suggest that Abyssinone V‐4’ methyl ether is endowed with antitumor properties and could be a source of traditional medicine which deserves to be more elucidated and explored in the foreseeable future.
Adaptive Barrier Control for Nonlinear Servomechanisms with Friction Compensation
Authors: Wang Shubo , Yu Haisheng , Gao Xuehui , Wang Na
Published: July 2018

This paper proposes an adaptive barrier controller for servomechanisms with friction compensation. A modified LuGre model is used to capture friction dynamics of servomechanisms. This model is incorporated into an augmented neural network (NN) to account for the unknown nonlinearities. Moreover, a barrier Lyapunov function (BLF) is utilized to each step in a backstepping design procedure. Then, a novel adaptive control method is well suggested to ensure that the full‐state constraints are within the given boundary. The stability of the closed‐loop control system is proved using Lyapunov stability theory. Comparative experiments on a turntable servomechanism confirm the effectiveness of the devised control method.
Emulsion Cross-Linking Technique for Human Fibroblast Encapsulation
Authors: Chaemsawang Watcharaphong , Prasongchean Weerapong , Papadopoulos Konstantinos I. , Sukrong Suchada , Kao W. John , Wattanaarsakit Phanphen
Published: July 2018

Microencapsulation with biodegradable polymers has potential application in drug and cell delivery systems and is currently used in probiotic delivery. In the present study, microcapsules of human fibroblast cells (CRL2522) were prepared by emulsion cross-linking technique. Tween 80 surfactant at a 2% concentration through phase inversion resulted in the most efficient and stable size, morphology, and the cells survival at least 50% on day 14. Emulsion cross-linking microcapsule preparation resulted in smaller and possibly more diverse particles that can be developed clinically to deliver encapsulated mammalian cells for future disease treatments.
Chaihu‐Shugan‐San Decoction Modulates Intestinal Microbe Dysbiosis and Alleviates Chronic Metabolic Inflammation in NAFLD Rats via the NLRP3 Inflammasome Pathway
Authors: Liang Yinji , Zhang Yupei , Deng Yuanjun , Liang Shu , He Yifang , Chen Yanning , Liu Chan , Lin Chenli , Han Li , Tu Guifang , Yang Qinhe
Published: July 2018

We evaluate the effects of the Chaihu‐Shugan‐San decoction on intestinal microbe dysbiosis and chronic metabolic inflammation via the NLRP3 pathway in NAFLD rats that were fed a high‐fat diet. Twenty‐four SD rats (male, six weeks old, 200 ± 20 g) were randomly divided into three groups: normal control group (NC group), high‐fat diet‐fed group (HFD group), and Chaihu‐Shugan‐San decoction intervention group (CH group). The NC group rats were given standard feed, the HFD group rats were all fed a high‐fat diet (83% standard feed + 10% lard oil + 5% sucrose + 1.5% cholesterol + 0.5% cholate), and the CH group rats were given a HFD plus Chaihu‐Shugan‐San at 9.6 g•kg−1•d−1. Body composition, serum and liver lipids, inflammatory markers, intestinal microbial population, and the NLRP3 pathway‐associated protein were assessed. The results showed that Chaihu‐Shugan‐San decoction significantly reduced body weight and total fat mass and the levels of serum LPS, TG, TNF‐α, IL‐1β, and IL‐18, as well as liver TC, TG, TNF‐α, IL‐1β, and IL‐18 (P < 0.05). The abundance of Enterobacteriaceae (0.375% versus 0.064%, P < 0.05), Staphylococcaceae families (0.049% versus 0.016%, P < 0.05) and Veillonella genus (0.096% versus 0.009%, P < 0.01) significantly decreased, whereas the abundance of Anaeroplasma genus (0.0005% versus 0.0178%, P < 0.01) significantly increased. The expression levels of NLRP3, ASC, and Caspase‐1 were changed significantly (P < 0.05). In summary, the Chaihu‐Shugan‐San decoction modulated intestinal microbe dysbiosis, reduced fat accumulation, and alleviated inflammatory factor expression, which are all processes related to the NLRP3 inflammasome pathway in NAFLD rats.
Thymosin β4 Prevents Oxidative Stress, Inflammation, and Fibrosis in Ethanol‐ and LPS‐Induced Liver Injury in Mice
Authors: Shah Ruchi , Reyes-Gordillo Karina , Cheng Ying , Varatharajalu Ravi , Ibrahim Joseph , Lakshman M. Raj
Published: July 2018

Thymosin beta 4 (Tβ4), an actin‐sequestering protein, is involved in tissue development and regeneration. It prevents inflammation and fibrosis in several tissues. We investigated the role of Tβ4 in chronic ethanol‐ and acute lipopolysaccharide‐ (LPS‐) induced mouse liver injury. C57BL/6 mice were fed 5% ethanol in liquid diet for 4 weeks plus binge ethanol (5 g/kg, gavage) with or without LPS (2 mg/kg, intraperitoneal) for 6 hours. Tβ4 (1 mg/kg, intraperitoneal) was administered for 1 week. We demonstrated that Tβ4 prevented ethanol‐ and LPS‐mediated increase in liver injury markers as well as changes in liver pathology. It also prevented ethanol‐ and LPS‐mediated increase in oxidative stress by decreasing ROS and lipid peroxidation and increasing the antioxidants, reduced glutathione and manganese‐dependent superoxide dismutase. It also prevented the activation of nuclear factor kappa B by blocking the phosphorylation of the inhibitory protein, IκB, thereby prevented proinflammatory cytokine production. Moreover, Tβ4 prevented fibrogenesis by suppressing the epigenetic repressor, methyl‐CpG‐binding protein 2, that coordinately reversed the expression of peroxisome proliferator‐activated receptor‐γ and downregulated fibrogenic genes, platelet‐derived growth factor‐β receptor, α‐smooth muscle actin, collagen 1, and fibronectin, resulting in reduced fibrosis. Our data suggest that Tβ4 has antioxidant, anti‐inflammatory, and antifibrotic potential during alcoholic liver injury.
A Tidal Level Prediction Approach Based on BP Neural Network and Cubic B-Spline Curve with Knot Insertion Algorithm
Authors: Wang Wenjuan , Yuan Hongchun
Published: July 2018

Tide levels depend on both long-term astronomical effects that are mainly affected by moon and sun and short-term meteorological effects generated by severe weather conditions like storm surge. Storm surge caused by typhoons will impose serious security risks and threats on the coastal residents’ safety in production, property, and life. Due to the challenges of nonperiodic and incontinuous tidal level record data and the influence of multimeteorological factors, the existing methods cannot predict the tide levels affected by typhoons precisely. This paper targets to explore a more advanced method for forecasting the tide levels of storm surge caused by typhoons. First, on the basis of successive five-year tide level and typhoon data at Luchaogang, China, a BP neural network model is developed using six parameters of typhoons as input parameters and the relevant tide level data as output parameters. Then, for an improved forecasting accuracy, cubic B-spline curve with knot insertion algorithm is combined with the BP model to conduct smooth processing of the predicted points and thus the smoothed prediction curve of tidal level has been obtained. By using the data of the fifth year as the testing sample, the predicted results by the two methods are compared. The experimental results have shown that the latter approach has higher accuracy in forecasting tidal level of storm surge caused by typhoons, and the combined prediction approach provides a powerful tool for defending and reducing storm surge disaster.
Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105
Authors: Liu Yingmiao , Starr Mark D. , Brady John C. , Rushing Christel , Pang Herbert , Adams Bonne , Alvarez Delia , Theuer Charles P. , Hurwitz Herbert I. , Nixon Andrew B.
Published: July 2018

TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy. Upon treatment with BEV and TRC105, pharmacodynamic changes in response to both BEV (PlGF increase) and TRC105 (soluble endoglin increase) were noted. In addition, distinct patterns of change were identified (similar, opposing, neutralizing). Similar patterns were observed when the combination elicited similar effects to those observed with monotherapy treatment (i.e., decreases of Ang-2, increases of IL6 and VCAM-1). Opposing patterns were observed when the combination led to opposing effects compared with monotherapy treatment (i.e., TGFβ1, PDGF-AA and PDGF-BB, PAI-1). Lastly, neutralizing patterns were observed when one drug led to increase, whereas the other drug led to decrease, and the combination elicited no overall effect on the marker (i.e., VEGF-A, VEGF-D, and IGFBP-3). Patients achieving partial responses or stable disease from the combination exhibited significantly lower expression of E-Cadherin, HGF, ICAM-1, and TSP-2 at baseline. Taken together, the novel biomarker modulations identified may deepen our understanding of the underlying biology in patients treated with BEV and TRC105 compared with either drug alone. Mol Cancer Ther; 17(10); 2248–56. ©2018 AACR.
Endovascular Therapy versus Thrombolysis in Patients with Mild Strokes and Large Vessel Occlusions within the Anterior Circulation
Authors: Kastrup Andreas , Brunner Freimuth , Hildebrandt Helmut , Roth Christian , Winterhalter Michael , Giessing Carsten , Papanagiotou Panagiotis
Published: July 2018

Background: In patients with large vessel occlusions, endovascular treatment (ET) has been shown to be superior to intravenous thrombolysis (IVT) in recent trials. However, it is currently unclear if patients with mild strokes also benefit from ET. Methods: We compared the discharge rates of good outcome (modified Rankin scale [mRS] ≤2), very good outcome (mRS 0–1), symptomatic intracranial hemorrhages (SICH), and infarct sizes in patients with mild strokes (admission National Institutes of Health Stroke Scale ≤10) and distal intracranial carotid artery, M1, and M2 occlusions during two time periods. Results: From 1/2008 to 10/2012 160 patients (mean age: 72 ± 12 years) were treated with IVT, and from 11/2012 to 11/2016 145 patients (mean age: 71 ± 13 years,) received ET with or without IVT. The clinical results were comparable between both treatment groups (59% after ET vs. 56% after IVT, p = 0.5 for an mRS 0–2) and (38% after ET vs. 32% after IVT, p = 0.3 for an mRS 0–1). In the subgroup of patients with an mRS ≤6, the early outcome did not differ significantly between ET and IVT either. The rates of SICH as well as the infarct sizes were not significantly different after ET compared with IVT. Conclusion: Compared with IVT, the routine use of ET did not significantly improve the early clinical or radiological outcome in patients with mild strokes and anterior circulation large vessel occlusions. Further randomized trials are urgently needed to determine the role of ET in this cohort.
Cost of Hospitalizations due to Exacerbation in Patients with Non-Cystic Fibrosis Bronchiectasis
Authors: de la Rosa Carrillo David , Navarro Rolon Annie , Girón Moreno Rosa Maria , Montull Veiga Beatriz , Olveira Fuster Casilda , Padilla Galo Alicia , Prados Sánchez Concepción , Quintana Gallego Esther , Sibila Vidal Oriol  , Celorrio Jiménez Nuria , Ruiz Peña Antonio , Torres Martí Antoni , Avilés Inglés Maria Jesús , Blanco Aparicio Marina , García-Clemente Marta , Golpe Gómez Rafael , Gómez Bonilla Ainhoa , Gómez González Cristina , Leal Arranz Maria Victoria , Mínguez Clemente Patricia , López Muñiz Belén , Máiz Carro Luis , Pando Sandoval Ana , Rodríguez Hermosa Juan Luis , Uranga Echeverria Ane , Núñez Ares Ana , López Roldán Lorena , Abellán Martínez Carmen , Martínez García Abel Jesús , Michel de la Rosa Francisco Javier , Godoy Mayoral Raúl , Martínez-García Miguel Ángel
Published: July 2018

Background: Knowing the cost of hospitalizations for exacerbation in bronchiectasis patients is essential to perform cost-effectiveness studies of treatments that aim to reduce exacerbations in these patients. Objectives: To find out the mean cost of hospitalizations due to exacerbations in bronchiectasis patients, and to identify factors associated with higher costs. Methods: Prospective, observational, multicenter study in adult bronchiectasis patients hospitalized due to exacerbation. All expenses from the patients’ arrival at hospital to their discharge were calculated: diagnostic tests, treatments, transferals, home hospitalization, admission to convalescence centers, and hospitals’ structural costs for each patient (each hospital’s tariff for emergencies and 70% of the price of a bed for each day in a hospital ward). Results: A total of 222 patients (52.7% men, mean age 71.8 years) admitted to 29 hospitals were included. Adding together all the expenses, the mean cost of the hospitalization was EUR 5,284.7, most of which correspond to the hospital ward (86.9%), and particularly to the hospitals’ structural costs. The adjusted multivariate analysis showed that chronic bronchial infection by Pseudomonas aeruginosa, days spent in the hospital, and completing the treatment with home hospitalization were factors independently associated with a higher overall cost of the hospitalization. Conclusions: The mean cost of a hospitalization due to bronchiectasis exacerbation obtained from the individual data of each episode is higher than the cost per process calculated by the health authorities. The most determining factor of a higher cost is chronic bronchial infection due to P. aeruginosa, which leads to a longer hospital stay and the use of home hospitalization.
Palmitic Acid Increases Endothelin-1 Expression in Vascular Endothelial Cells through the Induction of Endoplasmic Reticulum Stress and Protein Kinase C Signaling
Authors: Zhang Juan , Zhao Wen-Shu , Wang Xin , Xu Lin , Yang Xin-Chun
Published: July 2018

Objective: We investigated the regulation of endothelin-1 (ET-1) expression in in vivo high-fat diet (HFD)-fed mice and in vitro cultured human aortic endothelial cells (HAECs). Methods: Male C57BL/6 mice were fed on standard chow, serum was prepared, and ET-1 levels were analyzed using an ELISA kit. Quantitative PCR was performed using iQ SYBR Green Supermix. Statistical significance was assessed using SPSS, with p < 0.05 considered significant. Results: The serum ET-1 content and endothelial expression of ET-1 mRNA were increased in the HFD-fed mice compared to the chow-fed control mice. Moreover, the mRNA expression of ET-1 was significantly increased in cultured HAECs in response to acute (< 24 h) and chronic (12–16 days) treatments with palmitic acid (PA), one of the most abundant saturated fatty acids in obesity. We found that the induction of ET-1 expression by PA was abolished by pretreating the cells with the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid or the protein kinase C (PKC) inhibitor Gö 6850. Conclusion: Our findings demonstrate for the first time that PA increases ET-1 expression in endothelial cells through the induction of ER stress and the activation of PKC, providing novel mechanistic insights into the pathogenesis of obesity-associated hypertension and cardiovascular diseases.