bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk‐adapted adjuvant therapy for squamous cell carcinoma of the head and neck
Authors: Weiss Jared M. , Grilley‐Olson Juneko E. , Deal Allison Mary , Zevallos Jose P. , Chera Bhishamjit S. , Paul Jennifer , Knowles Mary Fleming , Usenko Dmitriy , Weissler Mark C. , Patel Samip , Hayes David N. , Hackman Trevor
Published: May 2018

BACKGROUND

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology‐guided adjuvant therapy to treat transorally resectable squamous head and neck cancer.

METHODS

Patients had squamous head and neck cancer that was resectable by the transoral route and advanced‐stage disease (American Joint Committee on Cancer stage III‐IV, T3‐T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m2, and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility.

RESULTS

Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow‐up has recurred or died. Twenty‐nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved.

CONCLUSIONS

The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk‐adapted adjuvant therapy resulted in high response rates and excellent long‐term outcomes and should be further studied. Cancer 2018;124:2986‐92. © 2018 American Cancer Society.
Development of a novel salivary gland cancer lymph node staging system
Authors: Aro Katri , Ho Allen S. , Luu Michael , Kim Sungjin , Tighiouart Mourad , Clair Jon Mallen‐St. , Yoshida Emi J. , Shiao Stephen L. , Leivo Ilmo , Zumsteg Zachary S.
Published: May 2018

BACKGROUND

Current lymph node (LN) staging for salivary gland cancer (SGC) is extrapolated from mucosal head and neck squamous cell carcinoma. However, given its unique biology and clinical behavior, it is possible that a SGC‐specific LN staging system would be more accurate.

METHODS

Patients from the National Cancer Data Base with nonmetastatic SGC of the head and neck who were diagnosed from 2004 through 2013 and underwent surgical resection and neck dissection removing at least 10 LNs were included. Multivariable models were constructed to assess the association between survival and LN factors, including number of metastatic LNs, extranodal extension, LN size, and lower LN involvement.

RESULTS

Overall, 4520 patients met the inclusion criteria. An increasing number of metastatic LNs was found to be strongly associated with worse survival without plateau. The risk of death increased more rapidly up to 4 LNs (hazard ratio, 1.34; 95% confidence interval, 1.27‐1.41 [P < .001]), and was more gradual for additional LNs >4 (hazard ratio, 1.02; 95% confidence interval, 1.01‐1.03 [P < .001]). LN size, extranodal extension, and lower LN involvement appeared to have no impact on survival when accounting for the number of metastatic LNs. Recursive partitioning analysis was used to create a novel SGC LN staging system in which N0 indicates 0 positive LNs, N1 indicates 1 to 2 positive LNs, N2 indicates 3 to 21 positive LNs, and N3 indicates ≥ 22 positive LNs. This system exhibited greater concordance than the current American Joint Committee on Cancer (eighth edition) system.

CONCLUSIONS

Quantitative LN burden is an important determinant of survival in patients with SGC. Use of this variable may improve SGC staging.Cancer2018.©2018 American Cancer Society.
A 2D finite element model for shear wave propagation in biological soft tissues: Application to magnetic resonance elastography
Authors: Bilasse M. , Chatelin S. , Altmeyer G. , Marouf A. , Vappou J. , Charpentier I.
Published: May 2018

Dynamic elastography is a virtual palpation tool that aims at investigating the mechanical response of biological soft tissues in vivo. The objective of this study is to develop a finite element model (FEM) with low computational cost for reproducing realistically wave propagation for magnetic resonance elastography in heterogeneous soft tissues. Based on the first‐order shear deformation theory for moderately thick structures, this model is developed and validated through comparison with analytical formulations of wave propagating in heterogeneous, viscoelastic infinite medium. This 2D‐FEM is then compared to experimental data and a 3D‐FEM using a commercial software. Our FEM is a powerful promising tool for investigations of magnetic resonance elastography.
A machine learning approach as a surrogate of finite element analysis–based inverse method to estimate the zero‐pressure geometry of human thoracic aorta
Authors: Liang Liang , Liu Minliang , Martin Caitlin , Sun Wei
Published: May 2018

Advances in structural finite element analysis (FEA) and medical imaging have made it possible to investigate the in vivo biomechanics of human organs such as blood vessels, for which organ geometries at the zero‐pressure level need to be recovered. Although FEA‐based inverse methods are available for zero‐pressure geometry estimation, these methods typically require iterative computation, which are time‐consuming and may be not suitable for time‐sensitive clinical applications. In this study, by using machine learning (ML) techniques, we developed an ML model to estimate the zero‐pressure geometry of human thoracic aorta given 2 pressurized geometries of the same patient at 2 different blood pressure levels. For the ML model development, a FEA‐based method was used to generate a dataset of aorta geometries of 3125 virtual patients. The ML model, which was trained and tested on the dataset, is capable of recovering zero‐pressure geometries consistent with those generated by the FEA‐based method. Thus, this study demonstrates the feasibility and great potential of using ML techniques as a fast surrogate of FEA‐based inverse methods to recover zero‐pressure geometries of human organs.
Maskless Spatioselective Functionalization of Silicon Nanowires
Authors: Veerbeek Janneke , Huskens Jurriaan
Published: May 2018

Spatioselective functionalization of silicon nanowires was achieved without using a masking material. The designed process combines metal‐assisted chemical etching (MACE) to fabricate silicon nanowires and hydrosilylation to form molecular monolayers. After MACE, a monolayer was formed on the exposed nanowire surfaces. A second MACE step was expected to elongate the nanowires, thus creating two different segments. When monolayers of 1‐undecene or 1‐tetradecyne were formed on the upper segment, however, the second MACE step did not extend the nanowires. In contrast, nanowires functionalized with 1,8‐nonadiyne were elongated, but at an approximately 8 times slower etching rate. The elongation resulted in a contrast difference in high‐resolution scanning electron microscopy (HR‐SEM) images, which indicated the formation of nanowires that were covered with a monolayer only at the top parts. Click chemistry was successfully used for secondary functionalization of the monolayer with azide‐functionalized nanoparticles. The spatioselective presence of 1,8‐nonadiyne gave a threefold higher particle density on the upper segment functionalized with 1,8‐nonadiyne than on the lower segment without monolayer. These results indicate the successful spatioselective functionalization of silicon nanowires fabricated by MACE.
Crisis‐induced coexisting multiple attractors in a second‐order nonautonomous memristive diode bridge‐based circuit
Authors: Xu Q. , Zhang Q.L. , Qian H. , Wu H.G. , Bao B.C.
Published: May 2018

This paper reports a second‐order nonautonomous memristive diode bridge‐based circuit, upon which a system model is established. The AC and DC equilibrium points and their stability evolutions are theoretically analyzed, and the mechanisms of complex dynamical behaviors are explored in detail. Furthermore, the stimulus‐dependent dynamical behaviors are numerically performed by the single‐parameter bifurcation diagrams, Lyapunov exponents, and phase portraits. Of particular concern, it should be highly emphasized that multiple kinds of crisis scenarios associated with the initial conditions are found in a specified parameter region, resulting in that coexisting multiple attractors under different initial conditions are discovered for the fixed system parameters. Additionally, hardware experiments and PSpice circuit simulations are used to confirm the numerically simulated results.
Electric fields and currents in the detached regime of a tokamak
Authors: Rozhansky V. , Kaveeva E. , Senichenkov I. , Sytova E. , Veselova I. , Voskoboynikov S. , Coster D.
Published: May 2018

The structure of currents and electric fields in the edge tokamak plasma is analysed for detached regimes of a tokamak. Strong electric fields in the divertor regions and near the X‐point are typical for detached regimes. It is shown that the value of the poloidal electric field in the regions with the temperature 1–2 eV is determined by the Spitzer conductivity and parallel currents. The latter are a combination of thermal and Pfirsch–Schlüter (PS) currents. The E × B drifts have a significant impact on the distribution of the plasma in the divertor. Stability of the detached regimes with strong electric fields is also analysed. It has been demonstrated that the so‐called PS instability caused by PS current can develop in the cold low‐temperature regions of the detached divertor.
Fluid and kinetic modelling for non‐local heat transport in magnetic fusion devices
Authors: Ciraolo Guido , Bufferand Hugo , Di Cintio Pierfrancesco , Ghendrih Philippe , Lepri Stefano , Livi Roberto , Marandet Yannick , Serre Eric , Tamain Patrick , Valentinuzzi Matteo
Published: May 2018

In order to improve the presently used ad hoc flux limiter treatment of parallel heat flux transport in edge plasma fluid codes, here, we consider a generalized version of the Fourier law implementing a non‐local kernel for the heat flux computation. The Bohm boundary condition at the wall is recovered, introducing a volumetric loss term representing the contribution of suprathermal particles to the energy out flux. As expected, this contribution is negligible in the strongly collisional regime, while it becomes more and more dominant for marginally and low‐collisional regimes. In the second part of the paper, we consider a kinetic approach where collisions are considered using the multi‐particle collision algorithm. Kinetic simulation results at medium and low collisionality are also reported.
SSD‐enhanced uncoded space‐time labeling diversity
Authors: Quazi Tahmid , Xu Hongjun
Published: May 2018

Space‐time labeling diversity (STLD) has been shown to be an efficient technique for improving the bit error rate (BER) performance of an uncoded space‐time coded modulation system. In this paper, signal space diversity (SSD) is incorporated into the uncoded STLD system to further enhance the system BER performance. A tight closed‐form union bound on the BER of the proposed system is derived and is used to optimize the rotation angle of the SSD scheme. Simulation results are used to confirm the theoretical bound derived for the system. The results also show performance gains of approximately 2.0 dB at a BER of 10−6 and 1.6 dB at a BER 10−4 from incorporating SSD into the uncoded STLD system using 16QAM and 64QAM, respectively. Furthermore, a low complexity detection scheme based on orthogonal projection is formulated for the proposed scheme and, in comparison with the optimal maximum‐likelihood detector, is shown to result in a 56% and 95% reduction in computation complexity for the 16QAM and 64QAM versions of the proposed system, respectively.
Multidisciplinary care considerations for gender nonconforming adolescents with eating disorders: A case series
Authors: Donaldson Abigail A. , Hall Allison , Neukirch Jodie , Kasper Vania , Simones Shannon , Gagnon Sherry , Reich Steven , Forcier Michelle
Published: May 2018

Gender nonconforming youth are at risk for body dissatisfaction and disordered eating. Currently, only a small body of literature addresses this high‐risk group. The five cases in this series highlight important themes for this patient population from an interdisciplinary perspective. Identified themes include increased risk for self‐harm/suicide, complex psychiatric, and medical implications of delay to treatment for either gender dysphoria or disordered eating, and the importance of collaborative management to maximize care and facilitate healthy development to adulthood. The purpose of this case series is to expand the interdisciplinary discussion regarding the breadth of presentation and management considerations for gender nonconforming adolescents with disordered eating. An interdisciplinary approach to care might enhance access to comprehensive, collaborative treatment for disordered eating, and gender dysphoria in this unique population.
A nuclear DNA barcode for eastern North American oaks and application to a study of hybridization in an Arboretum setting
Authors: Fitzek Elisabeth , Delcamp Adline , Guichoux Erwan , Hahn Marlene , Lobdell Matthew , Hipp Andrew L.
Published: May 2018

DNA barcoding has proved difficult in a number of woody plant genera, including the ecologically important oak genus Quercus. In this study, we utilized restrictionsite‐associated DNA sequencing (RAD‐seq) to develop an economical single nucleotide polymorphism (SNP) DNA barcoding system that suffices to distinguish eight common, sympatric eastern North American white oak species. Two de novo clustering pipelines, PyRAD and Stacks, were used in combination with postclustering bioinformatic tools to generate a list of 291 potential SNPs, 80 of which were included in a barcoding toolkit that is easily implemented using MassARRAY mass spectrometry technology. As a proof‐of‐concept, we used the genotyping toolkit to infer potential hybridization between North American white oaks transplanted outside of their native range (Q. michauxii, Q. montana, Q muehlenbergii/Q. prinoides, and Q. stellata) into a horticultural collection surrounded by natural forests of locally native trees (Q. alba and Q. macrocarpa) in the living collection at The Morton Arboretum (Lisle, IL, USA). Phylogenetic and clustering analyses suggested low rates of hybridization between cultivated and native species, with the exception of one Q. michauxii mother tree, the acorns of which exhibited high admixture from either Q. alba or Q. stellata and Q. macrocarpa, and a hybrid between Q. stellata that appears to have backcrossed almost exclusively to Q. alba. Together, RAD‐seq and MassARRAY technologies allow for efficient development and implementation of a multispecies barcode for one of the more challenging forest tree genera.
Restrictive cardiomyopathy: an unusual phenotype of a lamin A variant
Authors: Paller Mark S. , Martin Cindy M. , Pierpont Mary Ella
Published: May 2018

Most individuals with cardiomyopathy associated with variants of the LMNA (lamin A) gene present with cardiac conduction abnormalities followed by dilated cardiomyopathy and cardiac failure; some also have skeletal muscle weakness. In this report, an individual with restrictive cardiomyopathy presenting with conduction defects followed by cardiac dysfunction of a restrictive nature eventually requiring cardiac transplantation is described. Subsequently, progressive skeletal muscle weakness became evident. The finding of a new LMNA pathologic gene variant in this patient increases the options for genetic testing of individuals with restrictive cardiomyopathy.
Hemin Modified SnO2 Films on ITO‐PET with Enhanced Activity for Electrochemical Sensing
Authors: Panagiotopoulos Apostolos , Gkouma Anthi , Vassi Andriana , Johnson Christopher J. , Cass Anthony E. G. , Topoglidis Emmanuel
Published: May 2018

We present a simple and efficient method for the preparation of hemin‐modified SnO2 films on low cost, flexible, conducting ITO‐PET substrates to enable the development of a sensitive electrochemical sensor for the determination of H2O2. Using a hydrothermal processing method meant that the SnO2 films can be prepared at low temperatures, compatible with the PET substrate. The properties of the electrodes enable a high hemin loading to be achieved in a stable and functional way, allowing the direct reduction and oxidation of the immobilized hemin and maintaining its high electrocatalytic activity in the reduction of H2O2 on the surface. The results showed a sensitive response linearly proportional to the concentration of H2O2 in the range 1.5 to 90 μM.
Hierarchically nested river landform sequences. Part 1: Theory
Authors: Pasternack Gregory B. , Baig Dastagir , Weber Matthew D. , Brown Rocko A.
Published: May 2018

Past river classifications use incommensurate typologies at each spatial scale and do not capture the pivotal role of topographic variability at each scale in driving the morphodynamics responsible for evolving hierarchically nested fluvial landforms. This study developed a new way to create geomorphic classifications using metrics diagnostic of individual processes the same way at every spatial scale and spanning a wide range of scales. We tested the approach on flow convergence routing, a geomorphically and ecologically important process with different morphodynamic states of erosion, routing, and deposition depending on the structure of nondimensional topographic variability. Five nondimensional landform types with unique functionality represent this process at any flow; they are nozzle, wide bar, normal channel, constricted pool, and oversized. These landforms are then nested within themselves by considering their longitudinal sequencing at key flows representing geomorphically important stages. A data analysis framework was developed to answer questions about the stage‐dependent spatial structure of topographic variability. Nesting permutations constrain and reveal how flow convergence routing morphodynamics functions in any river the framework is applied to. The methodology may also be used with other physical and biological datasets to evaluate the extent to which the patterning in that data is influenced by flow convergence routing. Copyright © 2018 John Wiley & Sons, Ltd.
Community‐based observing for social–ecological science: lessons from the Arctic
Authors: Griffith David L , Alessa Lilian , Kliskey Andrew
Published: May 2018

Environmental monitoring and observation by members of local communities have become increasingly common in the US and Canada over the past several decades. During the same period, social–ecological systems (SES) science has been developed to explain and predict human and environmental interactions, but empirical methods to generate matched social and ecological datasets are uncommon. Community‐based observing (CBO) methodologies were developed in the Arctic to allow for production of environmental data in a social context and are also well suited to provide empirical data for SES science. Community‐based observing networks and systems (CBONS) and community observer forums (COF) are methodologies developed from collaborations between community members, researchers, and government agencies. Here, we describe CBONS and COF methodologies, provide examples of their usage, and suggest ways in which they can benefit empirical SES science. We conclude by outlining efforts to expand the use of CBO to new knowledge and geographic domains.
Analysis of the continuous mode conversion of Lamb waves in fiber composites by a stochastic material model and laser vibrometer experiments
Authors: Zimmermann Eugen , Eremin Artem , Lammering Rolf
Published: May 2018

The complex internal structure of modern laminate composite materials, for example, carbon fiber reinforced plastics (CFRP), has a pronounced influence on the propagation of elastic guided waves (GWs). Along with the well‐known anisotropy‐conditioned amplitude and dispersion directivity of source‐induced wavefields and their remarkable attenuation due to the polymer matrix viscosity, continuous mode conversion (CMC) of GWs in multilayered composites fabricated from unidirectional prepregs has been recently observed experimentally. The latter means that the symmetric fundamental mode continuously converts into the antisymmetric one without passing a damage, that is, even in an intact structure. Being strongly related to the inhomogeneous CFRP microstructure and possessing remarkable intensity for specific propagation directions, this phenomenon should be accounted for in ultrasonic nondestructive testing and structural health monitoring systems. In this work, we investigate the CMC phenomenon in an important class of laminates, namely cross‐ply ones, experimentally as well as numerically. In the computational model it is addressed through the concept of spatially varying material properties, and the finite element method (FEM) is employed for the GW propagation simulation. Experimental measurements are performed for piezoelectrically excited GWs with scanning laser Doppler vibrometry technique, allowing clear visualization of the CMC phenomenon and confirming theoretically predicted dependence of its intensity from propagation direction.
Distribution and geochemical fractionation of lead in the continental shelf sediments around India
Authors: Chakraborty Sucharita , Chakraborty Parthasarathi , Sarkar Arindam , Kazip Armoury , Mascarenhas‐Pereira M.B.L. , Nagender Nath B.
Published: May 2018

This study provides the first, preliminary data on geochemical distribution and fractionation of Pb (a toxic heavy metal) in continental shelf sediments around India and identifies the factors that control geochemical fractionation processes of Pb in convoluted coastal marine sediments. For the sake of clarity, the long coastline (~7,000 km) of India was divided into 6 coastal regions in this study. The total concentration of sedimentary Pb showed regional variation along the coast. The highest median concentration of Pb was found in the sediments collected from the north‐east region (26.5 mg/kg) followed by the north‐west (21.4 mg/kg) > central‐east (20.6 mg/kg) > south‐west (13.7 mg/kg) > south‐east (13.3 mg/kg) > central‐west (12.5 mg/kg) regions. Geochemical fractionation study suggested that the concentration of sedimentary Fe–Mn in oxyhydroxide form and the nature of sedimentary organic matters determined the geochemical distribution and fractionation of Pb in the shelf sediments. The major Pb hosting phases in the shelf sediments were the Fe–Mn oxyhydroxide phase followed by the sedimentary organic matter binding phases. The concentration of nonresidual Pb complexes in the shelf sediment was found to depend on the total sedimentary Pb loading. This study suggests that increase of anthropogenic Pb input and expansion of reduced oxygen levels in the coastal marine environment may have detrimental effects on the increasing mobility and bioavailability of Pb in the coastal areas around India.
White matter tract network disruption explains reduced conscientiousness in multiple sclerosis
Authors: Fuchs Tom A. , Dwyer Michael G. , Kuceyeski Amy , Choudhery Sanjeevani , Carolus Keith , Li Xian , Mallory Matthew , Weinstock‐Guttman Bianca , Jakimovski Dejan , Ramasamy Deepa , Zivadinov Robert , Benedict Ralph H.B.
Published: May 2018

Quantifying white matter (WM) tract disruption in people with multiple sclerosis (PwMS) provides a novel means for investigating the relationship between defective network connectivity and clinical markers. PwMS exhibit perturbations in personality, where decreased Conscientiousness is particularly prominent. This trait deficit influences disease trajectory and functional outcomes such as work capacity. We aimed to identify patterns of WM tract disruption related to decreased Conscientiousness in PwMS. Personality assessment and brain MRI were obtained in 133 PwMS and 49 age‐ and sex‐matched healthy controls (HC). Lesion maps were applied to determine the severity of WM tract disruption between pairs of gray matter regions. Next, the Network‐Based‐Statistics tool was applied to identify structural networks whose disruption negatively correlates with Conscientiousness. Finally, to determine whether these networks explain unique variance above conventional MRI measures and cognition, regression models were applied controlling for age, sex, brain volume, T2‐lesion volume, and cognition. Relative to HCs, PwMS exhibited lower Conscientiousness and slowed cognitive processing speed (p = .025, p = .006). Lower Conscientiousness in PwMS was significantly associated with WM tract disruption between frontal, frontal‐parietal, and frontal‐cingulate pathways in the left (p = .02) and right (p = .01) hemisphere. The mean disruption of these pathways explained unique additive variance in Conscientiousness, after accounting for conventional MRI markers of pathology and cognition (ΔR2 = .049, p = .029). Damage to WM tracts between frontal, frontal‐parietal, and frontal‐cingulate cortical regions is significantly correlated with reduced Conscientiousness in PwMS. Tract disruption within these networks explains decreased Conscientiousness observed in PwMS as compared with HCs.
Hippocampal place cell dysfunction and the effects of muscarinic M1 receptor agonism in a rat model of Alzheimer's disease
Authors: Galloway Claire R. , Ravipati Kaushik , Singh Suyashi , Lebois Evan P. , Cohen Robert M. , Levey Allan I. , Manns Joseph R.
Published: May 2018

Alzheimer's disease (AD) is a neurodegenerative disease that disproportionately impacts memory and the hippocampus. However, it is unclear how AD pathology influences the activity of surviving neurons in the hippocampus to contribute to the memory symptoms in AD. One well‐understood connection between spatial memory and neuronal activity in healthy brains is the activity of place cells, neurons in the hippocampus that fire preferentially in a specific location of a given environment (the place field of the place cell). In the present study, place cells were recorded from the hippocampus in a recently‐developed rat model of AD (Tg‐F344 AD) at an age (12–20 months) at which the AD rats showed marked spatial memory deficits. Place cells in the CA2 and CA3 pyramidal regions of the hippocampus in AD rats showed sharply reduced spatial fidelity relative to wild‐type (WT) rats. In contrast, spiking activity of place cells recorded in region CA1 in AD rats showed good spatial fidelity that was similar to CA1 place cells in WT rats. Oral administration of the M1 muscarinic acetylcholine receptor agonist VU0364572 impacted place cell firing rates in CA1 and CA2/3 hippocampal regions, but did not improve the spatial fidelity of CA2/3 hippocampal place cells in AD rats. The results indicated that, to the extent the spatial memory impairment in AD rats was attributable to hippocampal dysfunction, the memory impairment was more attributable to dysfunction in hippocampal regions CA2 and CA3 rather than CA1.
A feature weighting and selection method for improving the homogeneity of regions in regionalization of watersheds
Authors: Ahani Ali , Mousavi Nadoushani S. Saeid , Moridi Ali
Published: May 2018

The method used for feature selection or feature weighting in regionalization of watersheds may affect the results of regionalization methods considerably. It can play a key role in forming hydrologically homogeneous regions for regional flood frequency analysis. In this study, a method based on exploring the nearest and farthest neighbours of data points is introduced for identifying salient features for regionalization of watersheds. The method includes options to relate watershed features to flood data records in order to increase the homogeneity of the regions. The nearest and farthest neighbours are identified based on the criteria such as the mutual information criterion and Spearman's rank correlation coefficient. Then, the watershed features more able to explain the relationships between the nearest and farthest neighbours are identified as salient features to form homogeneous features for regional flood frequency analysis. The results show that the optimum option of the proposed method improves the performances of the hard and fuzzy clustering algorithms in more than half of the cases based on the cluster validity indices. Furthermore, the results reveal that the optimum option can increase the number of the homogeneous regions formed by clustering algorithms to a great extent. By using the optimum option with 5 nearest and 5 farthest neighbours, longitude, drainage area, and run‐off coefficient are identified as the salient features to regionalize Sefidrud basin. The results show that the proposed method can be considered as an efficient method to form homogeneous regions for regional flood frequency analysis.
Effectiveness of landscape‐based green infrastructure for stormwater management in suburban catchments
Authors: Woznicki Sean A. , Hondula Kelly L. , Jarnagin S. Taylor
Published: May 2018

Land cover changes associated with urbanization have negative effects on downstream ecosystems. Contemporary urban development attempts to mitigate these effects by designing stormwater infrastructure to mimic predevelopment hydrology, but their performance is highly variable. This study used in situ monitoring of recently built neighbourhoods to evaluate the catchment‐scale effectiveness of landscape decentralized stormwater control measures (SCMs) in the form of street connected vegetated swales for reducing runoff volumes and flow rates relative to curb‐and‐gutter infrastructure. Effectiveness of the SCMs was quantified by monitoring runoff for 8 months at the outlets of 4 suburban catchments (0.76–5.25 ha) in Maryland, USA. Three “grey” catchments installed curb‐and‐gutter stormwater conveyances, whereas the fourth “green” catchment built parcel‐level vegetated swales. The catchment with decentralized SCMs reduced runoff, runoff ratio, and peak runoff compared with the grey infrastructure catchments. In addition, the green catchment delayed runoff, resulting in longer precipitation–runoff lag times. Runoff ratios across the monitoring period were 0.13 at the green catchment and 0.37, 0.35, and 0.18 at the 3 grey catchments. Runoff only commenced after 6 mm of precipitation at the decentralized SCM catchment, whereas runoff occurred even during the smallest events at the grey catchments. However, as precipitation magnitudes reached 20 mm, the green catchment runoff characteristics were similar to those at the grey catchments, which made up 37% of the total precipitation in only 10 of 72 events. Therefore, volume‐based reduction goals for stormwater using decentralized SCMs such as vegetated swales require additional redundant SCMs in a treatment train as source control and/or end‐of‐pipe detention to capture a larger fraction of runoff and more effectively mimic predevelopment hydrology for the relatively rare but larger precipitation events.
Ethnicity‐related trends in gynecologic malignancies in Israel, 1993–2013
Authors: Michaan Nadav , Gortzak‐Uzan Limor , Grisario Dan , Laskov Ido
Published: May 2018

Objective

To describe trends and ethnic differences in incidence of gynecologic cancer in Israel.

Methods

In the present retrospective epidemiologic study, age‐standardized rates (ASRs) rates of gynecologic malignancies that occurred between January 1, 1993, and December 31, 2013, were extracted from the Israeli National Cancer Registry. The annual percent change (APC) was calculated separately for Jewish and Arab patients for ovarian, endometrial, and cervical cancers.

Results

Among Jewish patients, the ASR of ovarian cancer decreased (APC −2.27%, 95% confidence interval [CI], −2.7 to −1.84; P<0.001), the ASR of endometrial cancer increased (APC 1.50%, 95% CI 0.87–2.14; P<0.001), and the ASR of cervical cancer did not change (P=0.737). Among Arab patients, the ASRs of ovarian and cervical cancer did not change (P=0.181 and P=0.575, respectively), and the ASR of endometrial cancer increased (APC 1.98%, 95% CI 0.15–3.85; P=0.021).

Conclusions

Between 1993 and 2013, the incidence of gynecologic malignancies showed different trends among Jewish and Arab populations. Endometrial cancer increased among both populations and ovarian cancer decreased among Jewish patients. ASR of cervical cancer was low and stable among both Jewish and Arab groups. These trends could reflect differences in lifestyle and exposure to risk factors associated with each malignancy.
Reconstruction and analysis of the aberrant lncRNA‐miRNA‐mRNA network based on competitive endogenous RNA in CESC
Authors: Song Jukun , Ye Aizhu , Jiang Enli , Yin Xinhai , Chen Zhu , Bai Guohui , Zhou Yu , Liu Jianguo
Published: May 2018

A growing body of studies has demonstrated that long non‐coding RNA (lncRNA) are regarded as the primary section of the ceRNA network. This is thought to be the case owing to its regulation of protein‐coding gene expression by functioning as miRNA sponges. However, functional roles and regulatory mechanisms of lncRNA‐mediated ceRNA in cervical squamous cell carcinoma (CESC), as well as their use for potential prediction of CESC prognosis, remains unknown. The aberrant expression profiles of mRNA, lncRNA, and miRNA of 306 cervical squamous cancer tissues and three adjacent cervical tissues were obtained from the TCGA database. A lncRNA‐mRNA‐miRNA ceRNA network in CESC was constructed. Meanwhile, Gene Ontology (GO) and KEGG pathway analysis were performed using Cytoscape plug‐in BinGo and DAVID database. We identified a total of 493 lncRNA, 70 miRNA, and 1921 mRNA as differentially expressed profiles. An aberrant lncRNA‐mRNA‐miRNA ceRNA network was constructed in CESC, it was composed of 50 DElncRNA, 18 DEmiRNA, and 81 DEmRNA. According to the overall survival analysis, 3 out of 50 lncRNA, 10 out of 81 mRNA, and 1 out of 18 miRNA functioned as prognostic biomarkers for patients with CESC (P value < 0.05). We extracted the sub‐network in the ceRNA network and found that two novel lncRNA were recognized as key genes. These included lncRNA MEG3 and lncRNA ADAMTS9‐AS2. The present study provides a new insight into a better understanding of the lncRNA‐related ceRNA network in CESC, and the novel recognized ceRNA network will help us to improve our understanding of lncRNA‐mediated ceRNA regulatory mechanisms in the pathogenesis of CESC.
Proteasome inhibition promotes autophagy and protects from endoplasmic reticulum stress in rat alveolar macrophages exposed to hypoxia‐reoxygenation injury
Authors: Fan Tao , Huang Zhixin , Wang Wei , Zhang Boyou , Xu Yao , Mao Zhangfan , Chen Lei , Hu Hao , Geng Qing
Published: May 2018

Alveolar macrophages play vital roles in acute lung injury, and macrophage response to hypoxia play relevant roles to disease mechanisms. There is growing evidence that cell death pathways play crucial roles in physiological and pathological settings and that the ubiquitin‐proteasome system is involved in the regulation of these processes. However, the functional role of proteasome in alveolar macrophages exposed to hypoxia‐reoxygenation (H/R) injury is unknown. We aimed to investigate the function of proteasome on alveolar macrophages exposed to H/R and the underlying mechanisms. NR8383 cells were pretreated with proteasome activator sulforaphane (SFN) or inhibitor MG‐132 for 1 hr, and then submitted to 2/6 hr, 4/6 hr, and 6/6 hr H/R treatment. Cell viability was assessed with MTT assay. Autophagy was monitored using electron transmission microscope and flow cytometry and western blotting. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways were equally analyzed by western blotting. Cell apoptosis was detected by immunohistochemistry, caspase3/7 activity, and western blotting. The viability of NR8383 cells exposed to H/R was affected by proteasome activity and proteasome inhibition significantly inhibited cell death. Treatment with MG‐132 led to autophagy activation and induced the survival of NR8383 cells exposed to H/R. Pretreatment with SFN significantly decreased cell autophagy and induced cell death. ER stress was activated in H/R‐treated NR8383 cells, and SFN further promoted ER stress whereas proteasome inhibition led to contrary results. Proteasome inhibtion hindered cell apoptosis as demonstrated by decreased caspase‐3/7 activity, immunolabelling, and western blot results. Proteasome inhibition might be a promising approach for treating H/R injury‐related lung diseases.
Curcumin alleviates ischemia reperfusion‐induced late kidney fibrosis through the APPL1/Akt signaling pathway
Authors: Hongtao Chen , Youling Fan , Fang Huang , Huihua Peng , Jiying Zhong , Jun Zhou
Published: May 2018

As a major cause of renal failure, transient renal ischemia and reperfusion induce both acute kidney injury and late fibrosis, which are the common pathological manifestations of end‐stage renal disease. Curcumin is a biologically active polyphenolic compound found in turmeric. Increasing evidence has demonstrated that curcumin has a protective action against renal fibrosis, whereas mechanisms underlying the anti‐fibrosis role of curcumin remain poorly defined. Here, we found that APPL1, an important intracellular binding partner for AdipoR, was involved in the pathogenesis of acute injury or fibrosis and was significantly upregulated by curcumin in a mouse model of ischemia reperfusion‐induced late kidney fibrosis. Moreover, Akt signaling was the specific signaling pathway identified downstream of APPL1 in the pathogenesis of fibrosis. Our in vitro experiment demonstrated that curcumin alleviates ischemia reperfusion‐induced late kidney fibrosis via the APPL1/Akt pathway. These data are helpful for understanding the anti‐fibrosis mechanism of curcumin in the pathogenesis of AKI‐induced late fibrosis.
Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL
Authors: Hassanzadeh Ali , Farshdousti Hagh Majid , Alivand Mohammad Reza , Akbari Ali Akbar Movassaghpour , Shams Asenjan Karim , Saraei Raedeh , Solali Saeed
Published: May 2018

Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL‐R1 (death receptor 4, DR4), TRAIL‐R2 (death receptor 5, DR5), TRAIL‐R3 (decoy receptor 1, DcR1), TRAIL‐R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis‐inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely. According to diverse ranges of examinations, intracellular anti‐apoptotic proteins, such as cellular‐FLICE inhibitory protein (c‐FLIP), apoptosis inhibitors (IAPs), myeloid cell leukemia sequence 1 (MCL‐1), BCL‐2, BCL‐XL, and survivin play key role in cancer cells resistance to TRAIL. These proteins attenuate cancer cells sensitivity to TRAIL via various functions, importantly through caspase cascade suppression. The c‐FLIP avoids from caspase 8 activation by FADD via binding to caspase 8 cleavage of FADD. Moreover, it activates signaling pathways that involved in cancer cells survival and proliferation. Intriguingly, it appears that the down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP is effectiveness goal for TRAIL‐resistant cancers therapy, because their up‐regulation in association with poor prognosis has been observed in various types of TRAIL‐resistant cancers. In this review, we tried to collect and examine investigations that researchers have been able to sensitize cancer cells to TRAIL through targeting of c‐FLIP alone or with other intracellular anti‐apoptotic proteins directly or indirectly. It seems that co‐treatment of resistant cells by TRAIL with other therapeutic agents with the aim of intracellular anti‐apoptotic proteins inhibition is hopeful and attractive approach to overcome various TRAIL‐resistant cancers.
Gp78 involvement in cellular proliferation: Can act as a promising modulator for cell cycle regulatory proteins?
Authors: Joshi Vibhuti , Upadhyay Arun , Chhangani Deepak , Amanullah Ayeman , Sharan Rajesh N. , Mishra Amit
Published: May 2018

In cells, protein synthesis and degradation are normal processes, which are tightly regulated by various cellular metabolic pathways. Cellular protein quality control (PQC) mechanisms always present a continuous and rigorous check over all intracellular proteins before they can participate in various cellular physiological processes with the help of PQC pathways like autophagy and ubiquitin proteasome system (UPS). The UPS employs few selective E3 ubiquitin ligases for the intracellular degradation of cyclin‐dependent kinase inhibitor 1B (p27Kip1) that tightly controls cell cycle progression. But, the complex mechanistic interactions and the interplay between E3 ubiquitin ligases involved in the functional regulation as well as expression of p27 are not well known. Here, we demonstrate that cell surface glycoprotein Gp78, a putative E3 ubiquitin ligase, is involved in the stabilization of intracellular steady‐state levels of p27. Transient overexpression of Gp78 increases the accumulation of p27 in cells in the form of massive inclusions like structures, which could be due to its cumulative increased stability in cells. We have also monitored how under stress condition, E3 ubiquitin ligase Gp78 regulates endogenous levels of p27 in cells. ER stress treatment generates a marginal increase in Gp78 endogenous levels, and this elevation effect was prominent for intracellular accumulation of p27 in cells. Taken together, our current findings suggest a valuable multifactorial regulatory mechanism and linkage of p27 with UPS pathway.
GADD45β plays a protective role in acute lung injury by regulating apoptosis in experimental sepsis in vivo
Authors: Moon Sung‐Je , Kim Hyun‐Yong , Kim Yong‐Hoon , Kim Kyoung‐Shim , Noh Jung‐Ran , Kim Hyun‐Jong , Choi Ji‐Hyun , Hwang Jung H. , Lee Chul‐Ho
Published: May 2018

Sepsis is a systemic inflammatory response syndrome due to microbial infection. Growth arrest and DNA‐damage‐inducible 45 beta (GADD45β) are induced by genotoxic stress and inflammatory cytokines. However, the role of GADD45β during bacterial infection remains unclear. This study was aimed at investigating the role of GADD45β in sepsis. We used GADD45β‐knockout (KO) mice and C57BL/6J wild‐type (WT) mice. Experimental sepsis was induced by lipopolysaccharide (LPS) administration or cecal ligation and puncture (CLP). Sepsis‐induced mortality was higher in GADD45β‐KO mice than in WT mice. Histopathological data demonstrated LPS treatment markedly increased lung injury in GADD45β‐KO mice as compared to that in WT mice; however, no significant difference was observed in the liver and kidney. Further, mRNA levels of inflammatory cytokines, such as Il‐1β, Il‐6, Il‐10, and Tnf‐α, were higher in the lungs of LPS‐treated GADD45β‐KO mice than in WT mice. Interestingly, plasma levels of these inflammatory cytokines were decreased in LPS‐administered GADD45β‐KO mice. A significant increase in lung cell apoptosis was observed at early time points in GADD45β‐KO mice after administration of LPS as compared to that in WT mice. In line with LPS‐induced apoptosis, JNK, and p38 activity was higher in the lung of GADD45β‐KO mice at 3 hr after LPS treatment than that in WT mice. In summary, this study is the first to demonstrate the protective role of GADD45β in sepsis and the results suggest that GADD45β could be used as a novel therapeutic target to cure sepsis.
N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system
Authors: Nejabati Hamid Reza , Mihanfar Aynaz , Pezeshkian Masoud , Fattahi Amir , latifi Zeinab , Safaie Naser , Valiloo Mohammad , Jodati Ahmad Reza , Nouri Mohammad
Published: May 2018

Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N‐methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1‐methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti‐inflammatory and anti‐thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions.
The trophic effect of nerve growth factor in primary cultures of rat hippocampal neurons is associated to an anti‐inflammatory and immunosuppressive transcriptional program
Authors: Maino Barbara , Spampinato Antonio G. , Severini Cinzia , Petrella Carla , Ciotti Maria Teresa , D'Agata Velia , Calissano Pietro , Cavallaro Sebastiano
Published: May 2018

Nerve growth factor, the prototype of a family of neurotrophins, elicits differentiation and survival of peripheral and central neuronal cells. Although its neural mechanisms have been studied extensively, relatively little is known about the transcriptional regulation governing its effects. We have previously observed that in primary cultures of rat hippocampal neurons treatment with nerve growth factor for 72 hr increases neurite outgrowth and cell survival. To obtain a comprehensive view of the underlying transcriptional program, we performed whole‐genome expression analysis by microarray technology. We identified 541 differentially expressed genes and characterized dysregulated pathways related to innate immunity: the complement system and neuro‐inflammatory signaling. The exploitation of such genes and pathways may help interfering with the intracellular mechanisms involved in neuronal survival and guide novel therapeutic strategies for neurodegenerative diseases.
Heteronuclear 5‐Fluoroisatin Dimers: Design, Synthesis, and Evaluation of Their In Vitro Anti‐mycobacterial Activities
Authors: Deng Jia‐Lun , Liu Xiao‐Cheng , Cai Guang‐Wei , Zhang Gang , Hu Li , Qiu Li , Li Zi‐Yong , Xu Zhi
Published: May 2018

A series of novel heteronuclear 5‐fluoroisatin dimers 4a–j tethered through ethylene were designed, synthesized, and examined for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H37Rv and multi‐drug resistant tuberculosis (MDR‐TB). All hybrids exhibited potential anti‐mycobacterial activities against the tested two strains with minimum inhibitory concentration (MIC) in a range of 25 to 256 μg/mL. In particular, the heteronuclear 5‐fluoroisatin dimer 4a (MIC: 25 and 32 μg/mL) was most active against Mycobacterium tuberculosis H37Rv and MDR‐TB strains, which was twofold and greater than fourfold more potent than rifampicin (MIC: 64 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, warrant further optimization.