bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline Plasma Cell Gene Signature Predicts Improvement in Systemic Sclerosis Skin Scores Following Treatment With Inebilizumab (MEDI‐551) and Correlates With Disease Activity in Systemic Lupus Erythematosus and Chronic Obstructive Pulmonary Disease
Authors: Streicher Katie , Sridhar Sriram , Kuziora Mike , Morehouse Christopher A. , Higgs Brandon W. , Sebastian Yinong , Groves Christopher J. , Pilataxi Fernanda , Brohawn Philip Z. , Herbst Ronald , Ranade Koustubh
Published: June 2018

Objective

B cells impact the progression of systemic sclerosis (SSc; scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice reduced skin thickness, collagen production, and autoantibody levels, consistent with CD19 expression on plasma cells (PCs), the source of antibody production. PC depletion could effectively reduce collagen deposition and inflammation in SSc; therefore, we investigated the effects of PC depletion on SSc disease activity.

Methods

A PC gene signature was evaluated in SSc skin biopsy samples in 2 phase I clinical trials. We assessed microarray data from tissue from public studies of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), dermatomyositis (DM), systemic lupus erythematosus (SLE), and atopic dermatitis, as well as blood from a phase IIb clinical trial in SLE.

Results

The PC signature was elevated in SSc skin specimens compared to healthy donor skin (P = 2.28 × 10−6) and correlated with the baseline modified Rodnan skin thickness score (MRSS) (r = 0.64, P = 0.0004). Patients with a high PC signature at baseline showed greater improvement in the MRSS (mean ± SD change 35 ± 16%; P = 6.30 × 10−4) following anti‐CD19 treatment with inebilizumab (MEDI‐551) than did patients with a low PC signature at baseline (mean ± SD change 8 ± 12%; P = 0.104). The PC signature was overexpressed in tissue from patients with SLE, DM, COPD, interstitial lung disease, and IPF relative to controls (all fold change >2; P < 0.001). The PC signature also differed significantly between SLE patients with mild‐to‐moderate disease and those with severe disease (SLE Disease Activity Index cutoff at 10) (fold change 1.44; P = 3.90 × 10−3) and correlated significantly with the degree of emphysema in COPD (r = 0.53, P = 7.55 × 10−8).

Conclusion

Our results support the notion that PCs have a role in the pathogenesis of SSc and other autoimmune or pulmonary indications. An elevated pretreatment PC signature was associated with increased benefit from MEDI‐551 in SSc.
A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response
Authors: Lyu Xiao‐Ming , Zhu Xiao‐Wei , Zhao Manli , Zuo Xian‐Bo , Huang Zhong‐Xi , Liu Xiao , Jiang Tao , Yang Xue‐Xi , Li Xin , Long Xiao‐Bing , Wang Jian‐Guo , Li Jin‐Bang , Han Ming‐Yu , Wang Shuang , Liu Teng‐Fei , Zhang Bo , Sun Tao , Cheng Zhi , Qiu Mo‐Chang , Dong Lei , Zheng Lu , Zhang Long‐Cheng , Wang Jia‐Hong , Wei Gan‐Guan , Yao Kaitai , Wang Qian , Zheng Hou‐Feng , Li Xin
Published: June 2018

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two‐stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT‐PCR analysis (qRT‐PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10−19). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.
Discovery of a New Class of Inhibitors of Vaccinia Virus Based on (−)‐Borneol from Abies sibirica and (+)‐Camphor
Authors: Sokolova Anastasiya S. , Yarovaya Olga I. , Bormotov Nikolay I. , Shishkina Larisa N. , Salakhutdinov Nariman F.
Published: June 2018

A series of the bornyl ester/amide derivatives with N‐containing heterocycles were designed and synthesized as vaccinia virus (VV) inhibitors. Bioassay results showed that among the designed compounds, derivatives 6, 13, 14, 34, 36 and 37 showed the best inhibitory activity against VV with the IC50 values of 12.9, 17.9, 3.4, 2.5, 12.5 and 7.5 μm, respectively, and good cytotoxicity. The primary structure–activity relationship (SAR) study suggested that the combination of a saturated N‐heterocycle, such as morpholine or 4‐methylpiperidine, and a 1,7,7‐trimethylbicyclo[2.2.1]heptane scaffold was favorable for antiviral activity.
Gold Nanoparticles Incorporated in a Zinc‐Based Metal‐Organic Framework as Multifunctional Catalyst for the Oxygen Reduction and Hydrogen Evolution Reactions
Authors: Yadav Dharmendra K. , Gupta Rupali , Ganesan Vellaichamy , Sonkar Piyush K. , Yadav Mamta
Published: June 2018

Successful synthesis of gold nanoparticles incorporated in a zinc‐based metal‐organic framework (Au@Zn‐MOF) is reported in this paper. The synthesis of Au@Zn‐MOF is confirmed by UV‐Vis, FT‐IR and X‐ray photoelectron spectroscopy (XPS) studies. The Au@Zn‐MOF catalyst demonstrates electrocatalytic activity towards the oxygen reduction reaction (ORR) and the hydrogen evolution reaction (HER). The relative catalytic performance of Au@Zn‐MOF towards ORR and HER has been studied under acidic condition. ORR proceeds via a two electron and two proton mechanism with hydrogen peroxide as the end product, while HER follows the Volmer mechanism i. e., adsorption of H+ on the catalyst's active sites. Au@Zn‐MOF exhibits an ORR onset potential of 0.45 V (vs. RHE) with two different Tafel slopes, −93 and −103.6 mV in acidic solution. Further, an excellent catalytic activity is observed for HER with an onset potential of 0.02 V (vs. RHE) and a Tafel slope of 87 mV in N2 saturated 0.1 M HClO4 solution. However, in O2 saturated 0.1 M HClO4 solution, a HER onset potential of 0.04 V (vs. RHE) is observed with two different Tafel slopes, 610 and 220 mV. The value of Tafel slopes in the presence of O2 advocates the diminution of the ORR activity because of the HER. Thus, Tafel slope values of HER and ORR suggest that protons and O2 compete to reach the electrode surface for getting reduced.
Chemical Kinetics of Radiolabelling Reactions
Authors: Holland Jason P.
Published: June 2018

The application of chemical kinetics is one of the most powerful and versatile tools for investigating reaction mechanisms in complex mixtures. Kinetic studies are commonplace in traditional synthetic chemistry but are seldom used in radiopharmaceutical sciences. When deriving standard reaction rate laws, the focus is normally placed on calculating the chemical concentration of different species over time. In radiopharmaceutical synthesis, the desired product is one of the radioactive components of the mixture. Reaction conditions are optimised to obtain the radioactive product in the highest activity yield. When short‐lived radionuclides are used, radioactive decay during the reaction window means that the maximum activity yield does not necessarily coincide with the chemical or decay‐corrected radiochemical yields. To account for this difference in the kinetic models, it is shown how standard integrated rate laws can be modified to incorporate the contribution from radioactive decay. An example is then presented to show how radiochemical kinetics can be used to model complex systems, like [18F]FDG radiosynthesis, that involve parallel or competing reactions at the different chemical scales of the radionuclide and substrate. Increased knowledge of reaction rates, and a more wide‐spread application of radiochemical kinetics, can facilitate the development of new radiolabelling reactions. Accurate identification of maximum activity yields using kinetic models also has the potential to improve the optimisation and radiochemical efficiency of all current and future radiopharmaceutical syntheses.
Resolution of Viable and Membrane‐Compromised Free Bacteria in Aquatic Environments by Flow Cytometry
Authors: Grégori Gérald , Denis Michel , Sgorbati Sergio , Citterio Sandra
Published: June 2018

In aquatic environments, free heterotrophic bacteria play an extremely important role due to their high biomass, wide panel of metabolisms, and ubiquity, as well as the toxicity of certain species. This unit presents a nucleic‐acid double‐staining protocol (NADS) for flow cytometry that can distinguish fractions of viable, damaged, or membrane‐compromised cells within the free‐bacterial community. The NADS protocol is based on the simultaneous utilization of two nucleic acid stains—membrane‐permeant SYBR Green and membrane‐impermeant propidium iodide (PI). The efficiency of the double staining on fresh samples is magnified by the FRET from SYBR Green to PI when both are bound to the nucleic acids. Full quenching of SYBR Green fluorescence by PI identifies cells with a compromised membrane, partial quenching indicates cells with a slightly damaged membrane, and lack of quenching characterizes cells with an intact membrane. Samples do not require any pretreatment and this protocol can be performed almost anywhere. © 2018 by John Wiley & Sons, Inc.
Energy router with virtual inertia control schemes and concurrency operation
Authors: Lv Zhipeng , Wu Ming , Liu Lan , Liu Haitao , Song Zhenhao , Sun Lijing
Published: June 2018

The energy router is one unified interface solution for organizing distributed energy running in a microgrid operation mode. Because of its flexible and controllable features, this model is expected to become an important scheme for the electricity market liberalization process. Power electronic equipment could not provide inertia and damping like that of the traditional synchronous grid, which leads to poor grid‐tied integrity and reliability. This paper proposes an energy router microgrid‐operation model in which the AC‐interface and DC‐interface conventional control strategies are replaced by a virtual synchronous generator (motor) and virtual DC motor control strategy such that the energy router can mimic the inertia and damping characteristics of a rotating motor in order to improve the stability of the distributed power network. The simulation results prove the effectiveness of the energy router microgrid running mode and the control strategy.
Network selection in heterogeneous access networks simultaneously satisfying user profile and QoS
Authors: Ali Javid , Ahmad Raja Wasim , Maqsood Tahir , Rodrigues Joel J. P. C. , Ul Haq Nuhman , Sarwar Shahzad , Iqbal Tassawar , Madani Sajjad A.
Published: June 2018

Multimode capability empowers mobile devices to select the appropriate network to meet the requirements of user and applications. However, network selection is a challenging task owing to heterogeneous nature of network access links. At the same time, pervasiveness of mobile communication networks accompanied by the advances in wireless devices has raised the user expectations of persistent service and quality. Therefore, it is important for a mobile device to take situation‐based and timely decisions while selecting an access network to ensure both user's and operator's demand. The existing standard, called IEEE 802.21 (media‐independent handover), considers mobile device signal‐strength parameter for network selection from a list of networks. This research has proposed a ranking algorithm to rank heterogeneous networks based on a set of parameters including user profile and QoS. It selects most suitable network owing to multiple handover scenarios. The simulation results have shown that the proposed scheme has successfully satisfied apparently the contradictory requirements related to user profiles and QoS simultaneously.
Molecular Electrostatic Potential as a Predictor of Supramolecular Synthons in Non‐Hydrogen‐Bonded Systems: Application to Heavier p‐Block Systems
Authors: Haynes Delia A. , Rawson Jeremy M.
Published: June 2018

We show that the αi and βj parameters developed by Hunter to describe the hydrogen‐bond donor and acceptor properties of particular functional groups can be successfully applied to understand favourable intermolecular interactions between molecules containing heavier p‐block elements, notwithstanding the increasing dispersion terms associated with these elements. Although dispersion is an important contribution to the dimerisation enthalpy of dithiadiazolyls, we show that many aspects of the crystal packing of dimers can successfully be interpreted through such an electrostatic analysis. This approach is exemplified through analysis of the crystal structures of a series of fluoro‐ and trifluoromethyl‐substituted 1,2,3,5‐dithiadiazolyl radicals. Comparison of fluoro‐ and trifluoromethyl‐substituted aryl dithiadiazolyls reveals that the trifluoromethyl group has a pronounced electron‐withdrawing effect, enhancing the electrostatic contribution, but also adding steric bulk. The possible intermolecular interactions between these molecules are close in energy, resulting in structural diversity and at least one case of polymorphism. Despite neglecting the significant favourable dimerisation enthalpy in the analysis of the electrostatic potential, this approach provides a very clear rationalisation of many aspects of the observed crystal structures.||||||
Development of a Palladium‐Catalyzed Process for the Synthesis of Z‐Alkenes by Sequential Sonogashira–Hydrogenation Reaction
Authors: Hancker Sören , Neumann Helfried , Beller Matthias
Published: June 2018

A novel and selective sequential one‐pot protocol for the synthesis of Z‐alkenes via Sonogashira–semihydrogenation is reported. The efficiency of the methodology is increased by utilizing PdCl2/BuPAd2 as homogeneous catalyst for the Sonogashira coupling and subsequently transforming the transition metal complex into a heterogeneous Pd hydrogenation catalyst. This methodology represents one of the rare examples directly combining homogeneous and heterogeneous catalysis.
Warm‐, hot‐ and pain‐related neural activities depending on baseline skin temperatures
Authors: Nakata H. , Kakigi R. , Shibasaki M.
Published: June 2018

Background

This study investigated the characteristics of temperature‐related evoked neural activities to baseline skin temperatures on target and adjacent sites using contact heat evoked potentials (CHEPs).

Methods

Contact heat evoked potentials were recorded from 12 normal subjects during three stimuli: target temperatures for “warm”, “hot” and “pain” were set at 41, 46 and 51 °C, respectively. The baseline temperature was separately set at 30, 35 and 40 °C under all conditions, and a heat pulse was delivered over the right forearm at 41 °C under the warm condition, at 46 °C under the hot condition and at 51 °C under the pain condition.

Results

The N2‐P2 amplitude was significantly larger at the 40 °C baseline than at the 30 and 35 °C baselines during the pain condition, whereas no significant differences were observed during the hot and warm conditions. In addition, the effects of an interference warm stimulation to adjacent sites were examined; however, no significant effects were observed.

Conclusions

These results suggest that the priming effects of temperature on CHEPs were only observed under the pain condition, indicating the specificity of thermal pain, as well as a difference in the neural mechanisms responsible for thermal noxious and innocuous processing in human brains.

Significance

This study using CHEPs shows the importance of baseline and target skin temperatures to investigate the characteristics of temperature‐related neural activities. This measure may contribute to understanding of warm‐, hot‐, and pain‐related neural activities in human brains.
Effects of repeated conditioning pain modulation in healthy volunteers
Authors: Hoegh M. , Petersen K.K. , Graven‐Nielsen T.
Published: June 2018

Background

Conditioned pain modulation (CPM) may be impaired in chronic pain patients compared with healthy subjects. The CPM‐effect is the difference between pain sensitivity assessments (test‐stimuli) with and without a painful conditioning stimulus. CPM has been extensively explored but effects of repeated CPM‐effects and differences between repeated CPM assessments and comparable control conditions are less studied.

Methods

In 20 healthy men, four 5‐min bouts with a test‐stimulus in the beginning and midway were applied by cuff‐algometry to the dominant leg. The 2nd test‐stimulus in each bout was conditioned in parallel by a painful cuff pressure on the contralateral leg. A control‐session was performed without conditioning. The conditioning intensity was 70% of the pressure‐pain tolerance threshold (PTT) assessed at baseline. Pain detection threshold (PDT) was extracted from test‐stimuli. CPM/Control‐effects were calculated as second minus first test‐stimulus, and netCPM‐effects were calculated as the difference between CPM‐effects and Control‐effects.

Results

Pain detection threshold increased in all four bouts (p < 0.02) compared to the unconditioned test‐stimulus and compared to the 2nd test‐stimulus in bout1, bout3 and bout4 of the control‐session (p < 0.04). In the control‐session, the 1st test‐stimulus PDT increased from bout1 to bout2, bout3 and bout4 (p < 0.03). The netCPM‐effect increased progressively over the four bouts (p = 0.03).

Conclusion

Conditioned pain modulation‐effects were maintained over four consecutive bouts and in the control‐session repeated pain thresholds assessments habituated more than in the CPM‐session leading to an increase in netCPM‐effect over the four bouts.

Significance

Conditioning pain modulation can be assessed in 5‐min intervals by cuff algometry with a fixed conditioning stimulus. Without applying conditioning stimuli the pain sensitivity of test‐stimuli habituated. As a consequence, it can be speculated that the conditioning stimulus may negate the temporal habituation effects during repeated sessions, whereas this may not be the case for unconditioned stimuli. Applying both conditioned and unconditioned repeated test‐stimuli may be a way to assess different parts of the pain modulatory system, and a model for measuring a netCPM‐effect, which could indicate a balance between habituation and sensitization, is proposed.
Quantification of cliff retreat in coastal Quaternary sediments using anatomical changes in exposed tree roots
Authors: Lopez‐Saez Jérôme , Corona Christophe , Morel Pauline , Rovéra Georges , Dewez Thomas J.B. , Stoffel Markus , Berger Frédéric
Published: June 2018

Sea cliffs represent 80% of the world's coasts and can be found virtually in all types of morphogenetic environments. Most studies on rocky environments focused on the impacts of modern sea level rise on cliff stability derived from sequential surveys, direct measurements or erosional features in anthropogenic structures. In this study, we explore the potential of dendrogeomorphic techniques to quantify multidecadal changes in coastal environments on Porquerolles Island (France). We sampled a total of 56 cross‐sections from 16 Pinus halepensis Mill. roots growing on former alluvial deposits and on sandy‐gravelly cliffs to quantify mean annual cliff retreat rates as well as changes in cliff geometry. Anatomical changes in roots have been used successfully in the past to quantify continuous denudation rates on slopes, channel incision and gullying processes but the approach has not been used so far in a coastal cliff context. At Porquerolles Island, reconstructed rates of cliff retreat cover 30–40 years and show average erosion rates between 0.6 and 3.9 cm yr−1 (average: 2.1 cm yr−1). Highest rates are observed at Pointe de la Tufière (2.6–3.9 cm yr−1), a small rock promontory that is more exposed to wave and storm surges than the remainder of the study area. By contrast, lower erosion rates are recorded at cliffs protected by the La Courtade pocket beach (0.6–1.9 cm yr−1). This contribution demonstrates that dendrogeomorphic analyses of roots clearly have a significant potential and that they are a powerful tool for the quantification of multidecadal rates of cliff retreat in areas where measurements of past erosion are lacking. More specifically, the approach also has clear advantages over the shorter time series obtained with repeat monitoring (e.g. terrestrial laser scanning, sensors, erosion pins) or over longer, but more coarsely resolved records obtained from aerial photographs or radio‐nuclides. © 2018 John Wiley & Sons, Ltd.
Increased fMRI activity correlations in autobiographical memory versus resting states
Authors: Warren Kristen N. , Hermiller Molly S. , Nilakantan Aneesha S. , O'Neil Jonathan , Palumbo Robert T. , Voss Joel L.
Published: June 2018

Autobiographical memory retrieval is associated with activity of a distributed network that is similar to the default‐mode network (DMN) identified via activity correlations measured during rest. We tested whether activity correlations could be used to identify the autobiographical network during extended bouts of retrieval. Global‐correlativity analysis identified regions with activity correlation differences between autobiographical‐retrieval and resting states. Increased correlations were identified for retrieval versus resting states within a distributed network that included regions prototypical for autobiographical memory. This network segregated into two subnetworks comprised of regions related to memory versus cognitive control, suggesting greater functional segregation during autobiographical retrieval than rest. DMN regions were important drivers of these effects, with increased correlations between DMN and non‐DMN regions and segregation of the DMN into distinct subnetworks during retrieval. Thus, the autobiographical network can be robustly identified via activity correlations and retrieval is associated with network functional organization distinct from rest.
Nonlinear neuroplasticity corresponding to sports experience: A voxel‐based morphometry and resting‐state functional connectivity study
Authors: Chang Chih‐Yen , Chen Yin‐Hua , Yen Nai‐Shing
Published: June 2018

We aimed to investigate the structural neuroplasticity associated with different levels of sports experience and its effect on the corresponding resting‐state functional circuitry. We recruited 18 skilled baseball batters (SB), 19 intermediate baseball batters (IB), and 17 healthy controls (HC), and used magnetic resonance imaging methods to compare their regional gray‐matter volume (GMV) and seed‐based resting‐state functional connectivity (rsFC). Our results revealed that a quadratic function could better depict intergroup differences in regional GMV than a linear function. In particular, the IB showed lower or higher regional GMV than the other two groups. The difference in GMV in the supplementary motor area and areas belonging to the ventral stream, including the middle temporal gyrus and middle temporal pole, might be possibly related to baseball‐specific motor and perceptual experience, such as inhibitory action control and pitch identification. On the other hand, the stronger rsFC seeded from the right middle temporal pole to the default mode network, particularly in the precuneus, in the SB and IB relative to that in the HC might be possibly associated with the theory of mind, such as deciding whether to swing or not against the pitcher by detecting the spatial information of pitches. In conclusion, our three‐group design enabled the capture of the unique and transient changes that occur during the intermediate phase of expertise development. Our findings indicated that structural and functional brain changes do not necessarily linearly increase as a function of experience as previously suggested by the literature.
Language network measures at rest indicate individual differences in naming decline after anterior temporal lobe resection
Authors: Audrain Samantha , Barnett Alexander J. , McAndrews Mary P.
Published: June 2018

While anterior temporal lobe (ATL) resection is an effective treatment for temporal lobe epilepsy, surgery on the dominant hemisphere is associated with variable decline in confrontation naming. Accurate prediction of naming impairment is critical to inform clinical decision making, and while there has been some degree of success using task‐based functional MRI (fMRI) paradigms, there remains a growing interest in the predictive utility of resting‐state connectivity as it allows for relatively shorter scans with low task demands. Our objective was to assess the relationship between measures of preoperative resting‐state connectivity and postoperative naming change in patients following left ATL resection. We compared the resting language network connectivity of each patient to a normative healthy control template using a novel measure called “matrix similarity,” and found that patients with more abnormal global language‐network connectivity—particularly of regions spared from surgery—showed greater postoperative naming decline than those with normative patterns of connectivity. When we interrogated the degree centrality of to‐be‐resected regions in a more targeted approach of the pathological temporal lobe, we found that greater functional integration of those regions with the rest of the language network at rest was related to greater decline in naming following surgery. Finally, we found that matrix similarity was a better predictor of postoperative outcome than degree within to‐be‐resected regions, network clustering, modularity, and language task fMRI laterality. We provide some of the first evidence that using this novel measure, a relatively short preoperative resting scan can be exploited to inform naming ability following ATL resection.
The consequence of cerebral small vessel disease: Linking brain atrophy to motor impairment in the elderly
Authors: Su Ning , Liang Xinyu , Zhai Fei‐Fei , Zhou Li‐Xin , Ni Jun , Yao Ming , Tian Feng , Zhang Shu‐Yang , Jin Zheng‐Yu , Cui Li‐Ying , Gong Gaolang , Zhu Yi‐Cheng
Published: June 2018

In the elderly, brain structural deficits and gait disturbances due to cerebral small vessel disease (CSVD) have been well demonstrated. The relationships among CSVD, brain atrophy, and motor impairment, however, are far from conclusive. Particularly, the effect of CSVD on subcortical nuclear atrophy, motor performance of upper extremities, and associating patterns between brain atrophy and motor impairment remains largely unknown. To address these gaps, this study recruited 770 community‐dwelling subjects (35–82 years of age), including both CSVD and non‐CSVD individuals. For each subject, four motor tests involving upper and lower extremities were completed. High‐resolution structural MRI was applied to extract gray matter (GM) volume, white matter volume, cortical thickness, surface area, and subcortical nuclear (caudate, putamen, pallidum, and thalamus) volumes. The results showed worse motor performance of lower extremities but relatively preserved performance of upper extremities in the CSVD group. Intriguingly, there was a significant association between the worse performance of upper extremities and atrophy of whole‐brain GM and pallidum in the CSVD group but not in the non‐CSVD group. In addition, mediation analysis confirmed a functional CSVD‐to‐“brain atrophy”‐to‐“motor impairment” pathway, that is, a mediating role of thalamic atrophy in the CSVD effect on walking speed in the elderly, indicating that CSVD impairs walking performance through damaging the integrity of the thalamus in aging populations. These findings provide important insight into the functional consequences of CSVD and highlight the importance of evaluating upper extremities functions and exploring their brain mechanisms in CSVD populations during aging.
Treatment effect estimators for count data models
Authors: Hasebe Takuya
Published: June 2018

In this paper, we consider a switching regression model with count data outcomes, where the possible outcome differs across two alternate states and individuals endogenously select one of the states. We assume lognormal latent heterogeneity. Building on the switching regression model, we derive estimators of various treatment effects: the average treatment effect, the average treatment effect on the treated, the local average treatment effect, and the marginal treatment effect. We illustrate an application that examines the effects of public insurance on the number of doctor visits using the data employed by previous studies.
Quantitative analysis of riverbank groundwater flow for the Qinhuai River, China, and its influence factors
Authors: Lu Chengpeng , Chen Shuai , Jiang Yong , Shi Junchao , Yao Congcong , Su Xiaoru
Published: June 2018

Interactions of surface water and groundwater (SW–GW) play an important role in the physical, chemical, and ecological processes of riparian zones. The main objective of this study was to describe the two‐dimensional characteristics of riverbank SW–GW interactions and to quantify their influence factors. The SW–GW exchange fluxes for six sections (S1 to S6) of the Qinhuai River, China, were estimated using a heat tracing method, and field hydrogeological and thermodynamic parameters were obtained via inverse modelling. Global sensitivity analysis was performed to compare the effects of layered heterogeneity of hydraulic conductivity and river stage variation on SW–GW exchange. Under the condition of varied river stage, only the lateral exchange fluxes at S1 apparently decreased during the monitoring period, probably resulting from its relatively higher hydraulic conductivity. Meanwhile, the SW–GW exchanges for the other five sections were quite stable over time. The lateral exchange fluxes were higher than the vertical ones. The riverbank groundwater flow showed different spatial variation characteristics for the six sections, but most of the higher exchange fluxes occurred in the lower area of a section. The section with larger hydraulic conductivity has an apparent dynamic response to surface water and groundwater level differences, whereas lower permeabilities severely reduced the response of groundwater flow. The influence of boundary conditions on SW–GW interactions was restricted to a limited extent, and the impact extent will expand with the increase of peak water level and hydraulic conductivity. The SW–GW head difference was the main influence factors in SW–GW interactions, and the influence of both SW–GW head difference and hydraulic conductivity decreased with an increase of the distance from the surface water boundary. For each layer of riverbank sediment, its hydraulic conductivity had greater influence on its groundwater flow than the other layers, whereas it had negligible effects on its overlying/underlying layers. Consequently, the variations in river stage and hydraulic conductivity were the main factors influencing the spatial and temporal characteristics of riverbank groundwater flow, respectively.
A simple approach to estimating freshwater discharge in branched estuarine systems
Authors: Nguyen Duc Hoang , Nguyen Duc Anh
Published: June 2018

In tidal estuaries, quantifying freshwater discharge is still a difficult problem that has not yet been overcome due to the inherent difficulty in measuring and analysing the tidal discharge, especially during periods of low river flow. Because observations are often made in the stations further upstream, where the ratio of river to tidal discharge is large, it remains difficult to determine the discharge rate in the saline region. Freshwater discharge estimation is even more difficult in a branched estuary system having multiple diversion channels that connect with each other at a junction. To date, several methods have been developed for estimating freshwater discharge in estuaries. The most widely used are analytical and conceptual models that employ salinity as the principal trace and numerical simulations. However, these methods are very time consuming and costly as they require large sets of observations before the computations can take place. This paper presents a simple approach to investigating the discharge distribution over branched channels by considering the energy loss due to friction. We develop an analytical model that can obtain the discharge rate quantitatively at a junction where the main flow bifurcates into two branches. The model uses the bed roughness, tidal water level, and cross‐sectional profile under tidally averaged conditions as input data. Two selected estuarine systems in the Hiroshima delta in Japan and the Mekong delta in Vietnam have been investigated. Computations of the newly developed model show good agreement with earlier published results computed by sophisticated analytical and numerical models.
Ability of women to self‐classify into the Robson ten‐group classification system
Authors: Cal Margarida , Meira Alexandra , Clode Nuno
Published: June 2018

Objective

Recent guidelines from WHO and the International Federation of Gynecology and Obstetrics (FIGO) state that the Robson ten‐group classification system (TGCS) should be universally applied to pregnant women. Such information might enable women to make an informed decision about the place and mode of delivery. We assessed whether women could self‐classify correctly according to the TGCS.

Methods

A prospective study was conducted in a tertiary level maternity hospital between March 6 and July 31, 2017. We included post‐partum women admitted to the puerperium ward. Participants were instructed to complete a multiple‐choice questionnaire with a simplified description of TGCS and to classify themselves into one of the ten groups. A practitioner reclassified women into the correct TGCS group. Cohen κ was applied to measure the rate of agreement between these two evaluations.

Results

400 women were enrolled, with a global rate of agreement of 81.8% between women's self‐evaluation and the evaluation by the practitioner. A subanalysis showed that the highest rate of agreement was among the group with higher level education (84.0%).

Conclusion

Women of different ages and education backgrounds were able to correctly classify themselves into the TGCS. The higher the educational level, the greater the rate of agreement.
In vivo assay of the potential gadolinium‐induced toxicity for sensory hair cells using a zebrafish animal model
Authors: Rah Yoon Chan , Han Eun Jung , Park Saemi , Rhee Jihye , Koun Soonil , Park Hae‐Chul , Choi June
Published: June 2018

Recently, intratympanic injection of gadolinium‐based contrast agent (GdC) is growing in use to visualize the endolymphatic hydrops. Although GdC has been quite safely used over 20 years through intravenous injection, the biological influence of GdC on sensory hair cells needs to be thoroughly assessed for wider clinical application of it through intratympanic injection. In this in vivo experimental study, the summated number of sensory hair cells (SO1, SO2, O1 and OC1 neuromasts) showed a steep decrease in the group exposed to 10% and 20% GdC (35.7 ± 7.3, 15.09 ± 10.82, respectively, P < .01) compared with the control group (47.18 ± 2.30). An increase in apoptosis was also observed in the group exposed to 20% gadolinium (7.20 ± 5.56), as compared with the control group (0.08 ± 0.72) or the group exposed to 10% gadolinium (3.48 ± 3.32). A significant reduction in the viable cytoplasmic mitochondria was observed in embryos exposed to 20% GdC (369 ± 124 μm2, P = .01) as compared with control embryos (447 ± 118 μm2) or embryos exposed to 10% GdC (420 ± 108 μm2). GdC administration did not impact peripheral neural structures. GdC caused a significant reduction in sensory hair cell counts in response to high concentrations along with increased apoptosis and mitochondrial damage. However, it may not be likely that GdC will lead to hair cell toxicity, as the estimated concentration in the inner ear after clinically tried intratympanic injection is far more diluted than the non‐toxic concentration (0.625%) that was tested in this study.
Quick screening of true tyrosinase inhibitors from natural products using tyrosinase‐immobilized magnetic nanoparticles and a magnetic microplate
Authors: Chen Chia‐Yi , Lu Yi‐Hsuan , Lin Jau‐Tien , Hu Chao‐Chin , Fuh Chwan‐Bor , Tsai Hweiyan
Published: June 2018

Tyrosinase inhibitors from natural products have applications in the pharmaceutical, food, and cosmetic industries because of the functions of tyrosinase in skin disorders and in the enzymatic browning of fruits. Current in vitro inhibitor screening assays are based on the inhibition of the oxidation of l‐3,4‐dihydroxyphenylalanine (l‐DOPA) mediated by a mushroom tyrosinase. However, in these assays, a tyrosinase inhibitor or an antioxidant could inhibit dopaquinone formation. In this study, we aimed to eliminate this ambiguity by using a microplate assay integrating tyrosinase‐immobilized magnetic nanoparticles (TYR‐MNPs) and a homemade magnetic microplate for high‐throughput screening. After incubating extracts of natural products with TYR‐MNPs, the magnetic nanoparticles are attracted to the bottoms of wells, the extracts are rinsed, and TYR‐MNPs react with l‐DOPA. This method can be used to screen compounds that interact with the active sites of the enzyme, or copper chelators that bind more strongly than tyrosinase to copper ions, distinguishing them from antioxidants or tyrosinase substrates. Integration with the homemade magnetic microplate enables high‐throughput inhibitor screening. Aloe vera flowers are crop by‐products, and litchi flowers fall after the blossom. Our work demonstrated that these flowers have tyrosinase inhibitory effects, thus increasing their value.
Electrochemical recognition of taurine biomarker in unprocessed human plasma samples using silver nanoparticlebased nanocomposite: A new platform for early stage diagnosis of neurodegenerative diseases of the nervous system
Authors: Hasanzadeh Mohammad , Javidi Elnaz , Jouyban Abolghasem , Mokhtarzadeh Ahad , Shadjou Nasrin , Mahboob Soltanali
Published: June 2018

The rapid and accurate determination of the level of taurine biomarker in various tissues and body fluids can be of great interest in the early diagnosis of several important pathologies and diseases. In the present study, an innovative electrochemical interface for quantitation of taurine based on ternary signal amplification strategy was fabricated. In this work, silver nanoparticles were electrodeposited onto green and biocompatible nanocomposite containing α‐cyclodextrin as conductive matrix. Therefore, a double layer film based on α‐cyclodextrin and silver nanoparticles was exploited to develop a highly sensitive electrochemical sensor for detection of taurine. Fully electrochemical methodology was used to prepare a transducer on a glassy carbon electrode which provided a high surface area towards sensitive detection of taurine biomarker. The surface morphology of electrode surface was characterized by high‐resolution field emission scanning electron microscope (FE‐SEM). The proposed sensing platform provides a simple tool for taurine detection. The calibration curve for taurine concentration was linear in 0.7 nM to 0.1 mM with low limit of quantification of 0.7 nM. The practical analytical utility of the modified electrode was illustrated by determination of taurine in unprocessed human plasma samples with recovery of 90.8% to 104%.
Evaluation of spatial and temporal relationships between large‐scale atmospheric oscillations and meteorological drought indexes in Turkey
Authors: Tosunoglu Fatih , Can Ibrahim , Kahya Ercan
Published: June 2018

Spatial and temporal linkages between large‐scale atmospheric oscillations, namely, North Atlantic Oscillation (NAO), Southern Oscillation (SO) and North Sea–Caspian Pattern (NCP), and meteorological droughts in Turkey were investigated in this study. The corresponding oscillation indexes (NAOI, SOI and NCPI) were considered as monthly time indicators of the oscillations while the Standard Precipitation Index (SPI) obtained from 148 stations was used to define meteorological droughts. The suitability of various probability distributions was evaluated to obtain precise estimations of SPI values. Correlation analyses were then conducted to assess spatial and temporal distribution of the relationship between the oscillation and drought indexes. The linkages between the NAOI, NCPI and SPI were found to be more significant at the lag‐0, while the SOI had significant positive and negative correlations with SPI series at lag‐1–2. Moreover, our results revealed that the NAO is more dominant in the west and in the central Anatolia regions while the NCP has more influence on the northern and eastern regions.
Platelet‐rich fibrin/biphasic calcium phosphate impairs osteoclast differentiation and promotes apoptosis by the intrinsic mitochondrial pathway in chronic periodontitis
Authors: Kumar Anil , Mahendra Jaideep , Samuel Shila , Govindraj Jayamathi , Loganathan Tholcopiyan , Vashum Yaongamphi , Mahendra Little , Krishnamoorthy Thiagarajan
Published: June 2018

Background

The study explored the effect of platelet‐rich fibrin/biphasic calcium phosphate (PRF/BCP) on differentiation and survival of osteoclasts obtained from peripheral blood of CP patients.

Methods

Peripheral blood mononuclear cells (PBMCs) from 25 patients with chronic periodontitis (CP) and 25 healthy individuals were assayed for cluster of differentiation14+ (CD14+) expression and monocytes were induced to differentiate into osteoclasts for 21 days in‐vitro in the presence of macrophage colony stimulating factor (M‐CSF) and receptor activator of nuclear factor‐kappa B ligand (RANKL). We assessed the number of osteoclasts by tartrate‐acid resistant acid phosphatase (TRAP)‐positivity. The mechanism of apoptosis was studied with reference to expression of Bcl‐2, Bax, Bcl‐xL, nuclear factor kappa‐light chain enhancer of activated B cells (NF‐κB), caspase 3/9 and DNA fragmentation.

Results

We observed a relative increase in the proportion of circulating osteoclasts in test group than control group (healthy individuals). In addition, osteoclast precursors in untreated cells (CP) were more osteoclastogenic as compared to cells treated with PRF/BCP and hence, there was a significant increase in the number of osteoclasts in CP. In PRF/BCP treated cells, we found a direct inhibition of transcription factor NF‐κB with an increased caspase 3/9 levels and caspase 3 activity. Additionally, the protein expression and transcriptional profile of Bax was upregulated and Bcl‐2 and Bcl‐xL levels were down‐regulated on treatment with PRF/BCP.

Conclusion

Our results revealed that the PRF/BCP displayed an inhibitory role in osteoclasts formation and its molecular mechanism of action was related to the apoptosis induction through intrinsic mitochondrial pathway.
Graphene‐coated magnetic‐sheet solid‐phase extraction followed by high‐performance liquid chromatography with fluorescence detection for the determination of aflatoxins B1, B2, G1, and G2 in soy‐based samples
Authors: Nouri Nina , Sereshti Hassan , Farahani Ali
Published: June 2018

A new method named graphene‐coated magnetic‐sheet solid‐phase extraction based on a magnetic three‐dimensional graphene sorbent was developed for the extraction of aflatoxins prior to high‐performance liquid chromatography with fluorescence detection. The use of a perforated magnetic‐sheet for fixing the magnetic nanoparticles is a new feature of the method. Hence, the adsorbent particles can be separated from sample solution without using an external magnetic field. This made the procedure very simple and easy to operate so that all steps of the extraction process (sample loading, washing, and desorption) were carried out continuously using two lab‐made syringe pumps. The factors affecting the performance of extraction procedure such as the extraction solvent, adsorbent dose, sample loading flow rate, ionic strength, pH, and desorption parameters were investigated and optimized. Under the optimal conditions, the obtained enrichment factors and limits of detection were in the range of 205–236 and 0.09–0.15 μg/kg, respectively. The relative standard deviations were <3.4 and 7.5% for the intraday (n = 6) and interday (n = 4) precisions, respectively. The developed method was successfully applied to determine aflatoxins B1, B2, G1, and G2 in different soy‐based food samples.
Dimensions of Growth? Examining the Distinctiveness of the Five Factors of the Posttraumatic Growth Inventory
Authors: Silverstein Madison W. , Witte Tracy K. , Lee Daniel J. , Kramer Lindsay B. , Weathers Frank W.
Published: June 2018

Posttraumatic growth, defined as positive transformation following trauma, is commonly measured using the Posttraumatic Growth Inventory (PTGI; Tedeschi & Calhoun, 1996) and is postulated to comprise five distinct domains: Changes in Relationships, Life Possibilities, Personal Strength, Spirituality, and Appreciation of Life. However, research has indicated that the model fit is not good and the factors are highly intercorrelated. Further, no studies have formally examined the heterogeneity of correlations of the five factors with external constructs. In an effort to examine the construct validity of the five‐factor model of the PTGI, the present study aimed to examine the degree to which the theorized five factors demonstrate meaningful differential associations with relevant external correlates. Participants were 400 undergraduate students who reported having experienced a stressful event and completed the Life Events Checklist forDSM‐5, PTGI, Posttraumatic Stress Disorder Checklist forDSM‐5, Grit Scale‐12, Connor‐Davidson Resilience Scale‐10, and Work and Social Adjustment Scale. We found few instances of significant differentiation, and effect sizes for pairwise comparisons were generally small, Cohen'sqs = 0.01–0.35. Although factor analytic evidence suggests there are five distinct underlying constructs, our results indicated that these factors do not significantly differ in their associations with external correlates. Implications for use of the PTGI and future research directions are discussed.
Discovering cellular protein‐protein interactions: Technological strategies and opportunities
Authors: Titeca Kevin , Lemmens Irma , Tavernier Jan , Eyckerman Sven
Published: June 2018

The analysis of protein interaction networks is one of the key challenges in the study of biology. It connects genotypes to phenotypes, and disruption often leads to diseases. Hence, many technologies have been developed to study protein‐protein interactions (PPIs) in a cellular context. The expansion of the PPI technology toolbox however complicates the selection of optimal approaches for diverse biological questions. This review gives an overview of the binary and co‐complex technologies, with the former evaluating the interaction of two co‐expressed genetically tagged proteins, and the latter only needing the expression of a single tagged protein or no tagged proteins at all. Mass spectrometry is crucial for some binary and all co‐complex technologies. After the detailed description of the different technologies, the review compares their unique specifications, advantages, disadvantages, and applicability, while highlighting opportunities for further advancements.