bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis for valproate screening targets with liquid chromatography–high resolution mass spectrometry with positive electrospray ionization: An omics‐based approach
Authors: Mollerup Christian Brinch , Rasmussen Brian Schou , Johansen Sys Stybe , Mardal Marie , Linnet Kristian , Dalsgaard Petur Weihe 
Published: November 2018

AbstractLiquid chromatography coupled with high‐resolution mass spectrometry (LC–HRMS) is an important analytical tool in the systematic toxicological analysis performed in forensic toxicology. However, some important compounds, such as the antiepileptic drug valproate (valproic acid; VPA), cannot be directly detected with positive electrospray ionization (ESI+) due to poor ionization. Here we demonstrate an omics‐based retrospective analysis for the identification of indirect screening targets for VPA in whole blood with LC–ESI+–HRMS. Analysis was performed utilizing data acquired across four years from LC–ESI+–HRMS, with VPA results from a quantitative LC–MS/MS method. The combined data with VPA results were split into an exploration set (n = 68; 28% positive) and a test set (n = 37; 32% positive). Eight indirect targets for VPA were identified in the exploration set. The evaluation of these targets was confirmed with retrospective target analysis of the test set. Using a combination of two out of the eight indirect targets, we attained a sensitivity of 92% (n = 12; VPA concentration range: 4.4–29.7 mg/kg) and 100% specificity (n = 25) for VPA with LC–ESI+–HRMS. VPA screening targets were identified with retrospective data analysis and could be appended to the existing screening procedure. A sensitive and specific screening with LC–ESI+–HRMS was achieved with targets corresponding to the sodium adducts of C7H14O3 and C8H14O3. Three chromatographic resolved isomer peaks were observed for the latter, and the consistently most intense peak was tentatively identified as 3‐hydroxy‐4‐en‐VPA.
Effects of glial glutamate transporter activator in formalin‐induced pain behaviour in mice
Authors: Alotaibi Ghallab , Rahman Shafiqur 
Published: November 2018

AbstractBackgroundNociceptive pain remains a prevalent clinical problem and often poorly responsive to the currently available analgesics. Previous studies have shown that astroglial glutamate transporter‐1 (GLT‐1) in the hippocampus and anterior cingulate cortex (ACC) is critically involved in pain processing and modulation. However, the role of astroglial GLT‐1 in nociceptive pain involving the hippocampus and ACC remains unknown. We investigated the role of 3‐[[(2‐Methylphenyl) methyl]thio]‐6‐(2‐pyridinyl)‐pyridazine (LDN‐212320), a GLT‐1 activator, in nociceptive pain model and hippocampal‐dependent behavioural tasks in mice.MethodsWe evaluated the effects of LDN‐212320 in formalin‐induced nociceptive pain model. In addition, formalin‐induced impaired hippocampal‐dependent behaviours were measured using Y‐maze and object recognition test. Furthermore, GLT‐1 expression and extracellular signal‐regulated kinase phosphorylation (pERK1/2) were measured in the hippocampus and ACC using Western blot analysis and immunohistochemistry.ResultsThe LDN‐212320 (10 or 20 mg/kg, i.p) significantly attenuated formalin‐evoked nociceptive behaviour. The antinociceptive effects of LDN‐212320 were reversed by systemic administration of DHK (10 mg/kg, i.p), a GLT‐1 antagonist. Moreover, LDN‐212320 (10 or 20 mg/kg, i.p) significantly reversed formalin‐induced impaired hippocampal‐dependent behaviour. In addition, LDN‐212320 (10 or 20 mg/kg, i.p) increased GLT‐1 expressions in the hippocampus and ACC. On the other hand, LDN‐212320 (20 mg/kg, i.p) significantly reduced formalin induced‐ERK phosphorylation, a marker of nociception, in the hippocampus and ACC.ConclusionThese results suggest that the GLT‐1 activator LDN‐212320 prevents nociceptive pain by upregulating astroglial GLT‐1 expression in the hippocampus and ACC. Therefore, GLT‐1 activator could be a novel drug candidate for nociceptive pain.SignificanceThe present study provides new insights and evaluates the role of GLT‐1 activator in the modulation of nociceptive pain involving hippocampus and ACC. Here, we provide evidence that GLT‐1 activator could be a potential therapeutic utility for the treatment of nociceptive pain.
Doesn't Get Better With Age: Predicting Millennials' Disconnection
Authors: Millett Catherine M. , Kevelson Marisol J. C. 
Published: November 2018

AbstractRecent research has highlighted the critical problem of high rates of “disconnected youth”—youth and young adults who are neither employed nor in school. Practitioners, scholars, policymakers, and a range of stakeholders express mounting concern that disconnected youth are a societal burden that costs countries trillions of dollars. This phenomenon could threaten social cohesion and social development, in addition to costing large amounts of money in the forms of foregone labor productivity and tax revenues and increased incarceration and social services uptake rates. Whereas other studies explore disconnection among a cross‐sectional sample of U.S. young adults, we set out to document the longitudinal education and employment pathways of a nationally representative cohort of U.S. millennial young adults from approximately age 16 to age 26. Our results highlight that both socioeconomic status (SES) and high school academic abilities are associated with disconnection from society at ages 18, 20, and 26. However, these associations diminish over time, and by age 26 SES is a weaker predictor of disconnection than having been on a college preparatory track (e.g., taking practice college entrance examinations) or having special educational needs in high school. At the same time, high school literacy and mathematics skills and grades are unrelated to disconnection at age 26. Prior disconnection remains one of the strongest predictors of disconnection at ages 20 and 26, highlighting the problem of repeated disconnection experienced by a small group of youth and young adults (only 0.6% of our full sample, or 11.1% of high school leavers). Finally, the odds of dropping out of the labor force—not seeking employment—are most strongly explained by gender and having dependent children, and to a lesser extent by race and high school region and urbanicity. Recommendations for supporting those most at risk of disconnection are discussed in relation to our findings.
A decentralized channel assignment and power control approach using noncooperative game and Vickrey auction in relay‐aided MC‐CDMA IoT networks
Authors: Shokrnezhad Masoud , Khorsandi Siavash 
Published: November 2018

AbstractInternet of things (IoT) is a global infrastructure, providing ubiquitous intelligence by enabling seamless data flows between physical and virtual objects based on existing and evolving interoperable communication technologies. It is expected that the demand for wireless resources will rapidly increase in future IoT networks, and hence, the utilization of the wireless medium needs to be highly improved by efficiently allocating the resources. In this work, we investigate the problem of allocating wireless network resources in a multicarrier code‐division multiple access relay‐aided wireless IoT network, considering both channel assignment and power control, to satisfy the signal‐to‐interference ratio requirement of the devices with the objective of supporting as many devices as possible. The primary problem, named power control and channel assignment, is formulated as a mixed integer linear programming problem. Due to its complexity, three practical suboptimal solution approaches with different applications are developed. First, the Lagrangian relaxation and the dual decomposition methods are employed, and the problem is divided into two pure integer programming and linear programming subproblems, which are then solved using an iterative subgradient‐based algorithm that converges to a near‐optimal solution. Next, a greedy heuristic algorithm based on the Gaussian elimination method is proposed to efficiently find a suboptimal solution. In addition, a two‐phase second‐price auction‐based channel assignment and noncooperative game‐based power control algorithm is proposed to allocate resources in an iterative, distributed, and scalable manner. In the distributed scheme, no information about path gains is required. The numerical results show that the difference between the optimal solution and our approaches is negligible, so they can be efficiently employed in real‐world scenarios.
Spontaneous astrocytic Ca2+ activity abounds in electrically suppressed ischemic penumbra of aged mice
Authors: Fordsmann Jonas Christoffer , Murmu Reena Prity , Cai Changsi , Brazhe Alexey , Thomsen Kirsten Joan , Zambach Stefan Andreas , Lønstrup Micael , Lind Barbara Lykke , Lauritzen Martin 
Published: November 2018

AbstractExperimental focal cortical ischemic lesions consist of an ischemic core and a potentially salvageable peri‐ischemic region, the ischemic penumbra. The activity of neurons and astrocytes is assumed to be suppressed in the penumbra because the electrical function is interrupted, but this is incompletely elucidated. Most experimental stroke studies used young adult animals, whereas stroke is prevalent in the elderly population. Using two‐photon imaging in vivo, we here demonstrate extensive but electrically silent, spontaneous Ca2+ activity in neurons and astrocytes in the ischemic penumbra of 18‐ to 24‐month‐old mice 2–4 hr after middle cerebral artery occlusion. In comparison, stroke reduced spontaneous Ca2+ activity in neurons and astrocytes in adult mice (3–4 months of age). In aged mice, stroke increased astrocytic spontaneous Ca2+ activity considerably while neuronal spontaneous Ca2+ activity was unchanged. Blockade of action potentials and of purinergic receptors strongly reduced spontaneous Ca2+ activity in both neurons and astrocytes in the penumbra of old stroke mice. This indicates that stroke had a direct influence on mechanisms in presynaptic terminals and on purinergic signaling. Thus, highly dynamic variations in spontaneous Ca2+ activity characterize the electrically compromised penumbra, with remarkable differences between adult and old mice. The data are consistent with the notion that aged neurons and astrocytes take on a different phenotype than young mice. The increased activity of the aged astrocyte phenotype may be harmful to neurons. We suggest that the abundant spontaneous Ca2+ activity in astrocytes in the ischemic penumbra of old mice may be a novel target for neuroprotection strategies.A video abstract of this article can be found at https://youtu.be/AKlwKFsz1qE.
Numerical investigation of non‐Newtonian nanofluid mixed convection in a two‐opposite direction lid‐driven cavity with variable properties
Authors: Nazari Saeed , Akbari Ehsan 
Published: November 2018

AbstractThe mixed convection fluid flow in a square cavity filled with AL2O3‐water non‐Newtonian nanofluid is numerically analyzed. The left and right vertical boundaries of the enclosure have been kept in the constant temperature. Remaining walls of the cavity have been considered to have adiabatic boundary condition. Two different cases have been considered. In the first case, left and right side walls have been moved vertically with constant speed Vb in opposite directions. In the second case, the directions of their motions have been reversed. The transport equations, written in terms of the primitive variables for the non‐Newtonian nanofluid, have been solved numerically using the finite volume method. The shear stresses were calculated using the Ostwald‐de Waele model for the shear‐thinning nanofluid. The model introduced by Patel et al was used to obtain the thermal conductivity of the nanofluid. The variation of the fluid flow with respect to the Richardson number and volume fraction of the nanoparticles was investigated through a parametric study. Even though increasing the volume fraction of nanoparticles leads to heat transfer enhancement, for the second case of this study, for Ri = 1, the average Nusselt number initially drops sharply by increasing the volume fraction of nanoparticles, then remains constant.
The serotonin transporter and the activity regulated cytoskeleton‐associated protein genes in antidepressant response and resistance: 5‐HTTLPR and other variants
Authors: Calabrò Marco , Fabbri Chiara , Crisafulli Concetta , Albani Diego , Forloni Gianluigi , Kasper Siegfried , Sidoti Antonina , Velardi Elvira , Zohar Joseph , Juven‐Wetzler Alzbeta , Souery Daniel , Montgomery Stuart , Mendlewicz Julien , Serretti Alessandro 
Published: November 2018

AbstractObjectivePrevious evidence suggested the involvement of serotonin transporter (SLC6A4) and activity regulated cytoskeleton‐associated protein (ARC) in antidepressant action. This study investigated their role in antidepressant efficacy and treatment‐resistant depression (TRD).MethodsThree samples (n total = 648) were investigated to test the association between treatment outcomes (response, remission, symptom improvement, and TRD) and 11 polymorphisms within SLC6A4 and ARC genes. The possible modulating effect of age and gender was considered. Response and remission were also investigated using a fixed‐effects meta‐analysis of the three samples.ResultsSLC6A4 5‐HTTLPR/rs25531 effects on symptom improvement were modulated by age (better improvement in L/LA carriers in older subjects) and gender (better improvement in L/LA female carriers). SLC6A4 STin2 long alleles were associated with remission and lower risk of TRD. Preliminary evidence of association between ARC rs11167152/rs10110456 and different outcomes was found.Conclusions5‐HTTLPR/rs25531 effect on antidepressant efficacy was modulated by age, in line with previous literature data. STin2 effect on antidepressant efficacy was in line with previous meta‐analyses. A new possible effect of ARC variants on antidepressant efficacy was observed; however, further studies in larger samples are needed to confirm their role.
Importance of geological information for assessing drain flow in a Danish till landscape
Authors: Hansen Anne Lausten , Storgaard Anne , He Xin , Højberg Anker Lajer , Refsgaard Jens Christian , Iversen Bo Vangsø , Kjaergaard Charlotte 
Published: November 2018

AbstractThere has, in recent years, been an increasing interest in developing nutrient load mitigation measures focussing on tile drains. To plan the location of such tile drain measures, it is important to know where in the landscape drain flow is generated and to understand the key factors governing drain flow dynamics. In the present study, we test two approaches to assess spatial patterns in drain flow generation and thereby assess the importance of including geological information. The approaches are the widely used topographical wetness index (TWI), based solely on elevation data, and hydrological models that include the subsurface geology. We set‐up an ensemble of 20 hydrological models based on 20 stochastically generated geological models to predict drain flow dynamics in the clay till Norsminde catchment in Denmark and test the results against TWI. We find that the hydrological models predict observed daily drain flow reasonably well. High drain flow volumes were found in stream valleys and in wetlands and lower drain flow volumes in the more hilly parts of the catchment. In spite of the apparent connection to the landscape, there was no statistically significant correlation between TWI and drain flow at grid scale (100 × 100 m). TWI was therefore not found to be a sufficient index on its own to assess where drain flow is generated, especially in the highlands of the catchment. The geology below 3 m was found to have a large impact on the drain flow, and correlations between sand percentage in the subsurface geology and drain flow volume were found to be statistically significant. Geological uncertainty therefore give rise to uncertainty on simulated drain flow, and this uncertainty was found to be high at the model grid scale but decreasing with increasing scale.
An empirical investigation of direct and iterated multistep conditional forecasts
Authors: McCracken Michael W. , McGillicuddy Joseph T. 
Published: November 2018

SummaryWhen constructing unconditional point forecasts, both direct and iterated multistep (DMS and IMS) approaches are common. However, in the context of producing conditional forecasts, IMS approaches based on vector autoregressions are far more common than simpler DMS models. This is despite the fact that there are theoretical reasons to believe that DMS models are more robust to misspecification than are IMS models. In the context of unconditional forecasts, Marcellino et al. (Journal of Econometrics, 2006, 135, 499–526) investigate the empirical relevance of these theories. In this paper, we extend that work to conditional forecasts. We do so based on linear bivariate and trivariate models estimated using a large dataset of macroeconomic time series. Over comparable samples, our results reinforce those in Marcellino et al.: the IMS approach is typically a bit better than DMS with significant improvements only at longer horizons. In contrast, when we focus on the Great Moderation sample we find a marked improvement in the DMS approach relative to IMS. The distinction is particularly clear when we forecast nominal rather than real variables where the relative gains can be substantial.
Food colorant Sunset Yellow (E110) intervenes developmental profile of zebrafish (Danio rerio)
Authors: Joshi Vani , Pancharatna Katti 
Published: November 2018

AbstractIn this study, we tested the teratogenic/embryotoxic potentials of food colorant, Sunset Yellow (E110) using zebrafish embryos as a model. Laboratory‐raised developing embryos of Danio rerio were exposed to graded concentrations (00, 0.1, 1.0, 2.0, 3.0, 4.0, 5.0, 10, 20, 30, 40, 50 and 100 mm) of E110 from gastrulation stage (~6 hours post‐fertilization [hpf]) up until hatching. The developmental trajectory of each embryo and post‐hatched larva was traced from 24 to 168 hpf. The no observed effect concentration (NOEC), median effective concentration (EC50), median lethal concentration (LC50) and teratogenic index were determined. In the 0.1 mm E110‐exposed embryos, the development proceeded as in controls (NOEC), while, exposure of embryos to 1‐5 mm of E110 led to a decrease in body size, dry body mass of resultant larvae along with appearance of morphological deformities such as, microphthalmia, pericardial edema, yolk sac edema and spinal curvature. Larvae of 10‐50 mm E110‐exposed embryos exhibited increased cellular apoptosis in the cardiac region with significantly declined heartbeats and elevated mortality rates, in addition to the above‐mentioned abnormalities. In the 100 mm exposure group, all embryos succumbed to death within 24 hpf. The NOEC and LC50 recorded were at 0.1 and 42.57 mm respectively. EC50 (96 hpf) recorded for pericardial edema and yolk sac edema was 19.41 and 39.84 mm with teratogenic index quotient 2.1 and 1.06 respectively The study provides direct evidence for the developmental toxicity/teratogenic potential of E110.
The role of tumor suppressor of resveratrol and prednisolone by downregulation of YKL‐40 expression in CCRF‐CEM cell line
Authors: Zadi Heydarabad Milad , Baharaghdam Sina , Azimi Ako , Mohammadi Hamed , Eivazi Ziaei Jamal , Yazdanpanah Behruz , Zak Mohsen Sharif , Farahani Mohammad Esfini , Dohrabpour Aghdas , Partash Nasim , Talebi Mehdi 
Published: November 2018

AbstractBackgroundAcute lymphoblastic leukemia (ALL) is characterized by excessive accumulation of lymphoblast and progenitors. Leukemia is the most common cancer in children and ALL is the most common subtype. Many studies have shown that the YKL‐40 gene is one of the most widely expressed genes in tumors, including leukemia, but not in healthy blood cells. Clinical studies have shown that serum YKL‐40 levels have a positive correlation with tumor expansion, in addition to being a prognostic agent independent of a short relapse‐free interval, as well as a brief overall survival in patients with various cancers. The previous study shows that YKL‐40 is closely related to the degree of pathology or degree of human leukemia pathology and plays an important role in cell proliferation. Hence, the YKL‐40 can be an attractive target in designing anticancer therapies.MethodsCCRF‐CEM cells were treated with resveratrol and prednisolone. For analysis of YKL‐40 expression changes under medication, real‐time polymerase chain reaction (PCR) and Western blot techniques were used at resonating intervals of 24 and 48 hours.ResultsThe effect of 15, 50, and 100 μM resveratrol and 700 μM of prednisolone on CCRF‐CEM cells reduced YKL‐40. The YKL‐40 gene was quantitatively measured using RT‐PCR. The Western blot method was used to evaluate changes in the expression of YKL‐40 protein.ConclusionIn this study, we first evaluated YKL‐40 expression and resveratrol and prednisolone effect on YKL‐40 in ALL. This finding supports the idea of targeting YKL‐40 as a new drug treatment of ALL and extends the use of resveratrol in antileukemia research.
Systematic analysis of multigene predictors in gastric cancer exploiting gene expression signature
Authors: Ai Kuankuan , Jia Yanli , Li Jin , Wang Chong , Wang Yan 
Published: November 2018

AbstractGastric cancer (GC) is the second most common cause of cancer death worldwide but could be more curable if diagnosed at an earlier stage. At present, the capability to predict the efficaciousness of molecular diagnosis for GC for each patient remains elusive. The purpose of this study was to identify tumor biomarkers through systems analysis of multigene predictors exploiting the available data resource. In this study, we investigated the top 10% overexpressed genes in GC from five data sets of the Oncomine platform, with 265 GC samples versus 174 normal gastric mucosa samples. Sixteen candidate genes were identified as predictors of GC, of which 14 genes were verified through the comparison of expression levels in specimens from normal (chronic gastritis, 21 samples) and GC groups (38 samples). In addition, unique molecular portraits of diffuse adenocarcinoma (DA), intestinal adenocarcinoma (IA), and mixed adenocarcinoma (MA) were studied through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, where DA showed higher extracellular matrix alteration while IA and MA showed higher cell‐cycle alteration than other types. We also found that the elevated expressions of genes during GC progression were independent of gene mutations, and high core‐binding factor subunit β expression is correlated with a high overall survival rate in GC patients. Our research may provide an efficient clinical diagnosis of GC at an early stage with high accuracy and thus help improve the overall survival rate through early therapeutic interventions.