bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human
Authors: Wong Yin Cheong , Centanni Maddalena , de Lange Elizabeth C. M. 
Published: January 2019

AbstractReceptor occupancy (RO) is a translational biomarker for assessing drug efficacy and safety. We aimed to apply a physiologically based pharmacokinetic (PBPK) modeling approach to predict the brain dopamine D2 RO time profiles of antipsychotics. Clozapine and risperidone were modeled together with their active metabolites, norclozapine and paliperidone, First, in PK‐Sim a rat PBPK model was developed and optimized using literature plasma PK data. Then, blood‐brain barrier parameters including the expression and efflux transport kinetics of P‐glycoprotein were optimized using literature microdialysis data on brain extracellular fluid (brainECF), which were further adapted when translating the rat PBPK model into the human PBPK model. Based on the simulated drug and metabolite concentrations in brainECF, drug‐D2 receptor binding kinetics (association and dissociation rates) were incorporated in MoBi to predict RO. From an extensive literature search, 32 plasma PK data sets (16 from rat and 16 from human studies) and 23 striatum RO data sets (13 from rat and 10 from human studies) were prepared and compared with the model predictions. The rat PBPK‐RO model adequately predicted the plasma concentrations of the parent drugs and metabolites and the RO levels. The human PBPK‐RO model also captured the plasma PK and RO levels despite the large interindividual and interstudy variability, although it tended to underestimate the plasma concentrations and RO measured at late time points after risperidone dosing. The developed human PBPK‐RO model was successfully applied to predict the plasma PK and RO changes observed after risperidone dose reduction in a clinical trial in schizophrenic patients.
Removal of chlorobenzene using a sequential adsorption–plasma catalytic system over Ag‐, Ce‐ and Mn‐modified activated carbon catalysts
Authors: Jiang Liying , Cao Xiang , Chen Jianmeng , Guo Haiqian , Chen Zhong , Li Sha 
Published: January 2019

AbstractBACKGROUNDA dielectric barrier discharge reactor coupled with a series of activated carbon (AC) catalysts was applied to remove low concentrations of chlorobenzene. The catalysts were prepared via an impregnation method and their adsorption capacity and plasma‐catalytic ability examined in a sequential adsorption–plasma oxidation process.RESULTSAg/AC had the longest breakthrough time and highest breakthrough capacity among the catalysts studied. At the discharge stage, the Ag/AC catalyst had the highest CO2 yield, chlorobenzene mineralization rate and carbon balance, and the lowest emission of chlorobenzene when compared with the other catalysts under the same conditions. However, the Ag/AC catalyst exhibited the worst reducing ozone generation performance, while the Mn/AC catalyst showed the best ozone decomposition ability. The organic intermediates produced using Ag/AC and Ce/AC were simpler and in lower concentrations than those formed using Mn/AC. The adsorption capacity and catalytic activity of the Ag/AC catalyst showed no obvious decrease after five cycles. Fourier transform infrared and scanning electron microscopy–energy dispersive spectroscopy analyses after the reaction showed that some nitrogen organic intermediates and chlorine substances produced via the degradation of chlorobenzene were adsorbed onto the catalyst surface.CONCLUSIONSAg/AC exhibited a longer breakthrough time, higher breakthrough capacity, higher CO2 yield, less chlorobenzene emission and better carbon balance when compared with the other catalysts. © 2019 Society of Chemical Industry
Enzyme immobilization on photopatterned temperature‐response poly (N‐isopropylacrylamide) for microfluidic biocatalysis
Authors: Zhu Lin‐Lin , Zhu Chang‐Tong , Xiong Meng , Jin Chuan‐Qi , Sheng Sheng , Wu Fu‐An , Wang Jun 
Published: January 2019

AbstractBACKGROUNDMicrofluidic chips have gained growing attention from the scientific community due to their large surface/interface area and fast mass transfer. However, their application is challenged by the instability of enzymes and time‐consuming catalytic process. Poly (N‐isopropylacrylamide) (PNIPAAm) coupled with photopatterning technology was applied to immobilize an enzyme on the microchannel surface to realize the biotransformation in this study.RESULTSThe photopattern‐immobilized naringinase on a microchip achieved a yield of 93.63 ± 1.12% for isoquercitrin production within 5 min. The production of unit time per unit enzyme (g g−1 h−1) increased 2.1‐fold whereas the reaction time decreased to 1/12 of the time required in a batch reactor. The enzyme was absorbed and desorbed at 40 and 25 °C, respectively, and the release efficiency of immobilized naringinase reached 80.57%, indicating that most of the enzymes were replaced with fresh enzymes to proceed each enzymatic reaction. Six cycles of enzymatic hydrolysis reactions were completed successively, maintaining >60% of relative enzymatic activity.CONCLUSIONThe results indicated that using the immobilized enzyme on the photopatterned PNIPAAm in the enzymatic hydrolysis of rutin was an efficient and simple way to achieve a high yield of isoquercitrin. Thus, this approach represents a convenient and cost‐saving method to produce fine chemicals using microfluidic biocatalysis. © 2019 Society of Chemical Industry
Ankyrin repeat domain 1: A novel gene for cardiac septal defects
Authors: Yang Yongchao , Xia Yu , Wu Yueheng , Huang Shufang , Teng Yun , Liu Xiaobing , Li Ping , Chen Jimei , Zhuang Jian 
Published: January 2019

AbstractIntroductionCardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (ANKRD1) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the ANKRD1 mutation and cardiac septal defects has not been described.MethodsWe examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation.ResultsA heterozygous, missense variant of ANKRD1 (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co‐activated with NKX2.5, ANKRD1 repressed ANF expression as assessed by a dual‐luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318 ± 0.018 versus 0.564 ± 0.048, p < 0.01). A real‐time polymerase chain reaction confirmed that p.S187F mutation of ANKRD1 decreased the expression of endogenous ANF (0.85 ± 0.05 versus 0.61 ± 0.04, p < 0.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of ANKRD1.ConclusionsThe present study is the first to identify the p.S187F mutant of ANKRD1, which is associated with cardiac septal defects.
Diffusion kurtosis imaging in mild traumatic brain injury and postconcussional syndrome
Authors: Karlsen Rune Hatlestad , Einarsen Cathrine , Moe Hans Kristian , Håberg Asta Kristine , Vik Anne , Skandsen Toril , Eikenes Live 
Published: January 2019

AbstractAims of this study were to investigate white matter (WM) and thalamus microstructure 72 hr and 3 months after mild traumatic brain injury (TBI) with diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI), and to relate DKI and DTI findings to postconcussional syndrome (PCS). Twenty‐five patients (72 hr = 24; 3 months = 23) and 22 healthy controls were recruited, and DKI and DTI data were analyzed with Tract‐Based Spatial Statistics (TBSS) and a region‐of‐interest (ROI) approach. Patients were categorized into PCS or non‐PCS 3 months after injury according to the ICD‐10 research criteria for PCS. In TBSS analysis, significant differences between patients and controls were seen in WM, both in the acute stage and 3 months after injury. Fractional anisotropy (FA) reductions were more widespread than kurtosis fractional anisotropy (KFA) reductions in the acute stage, while KFA reductions were more widespread than the FA reductions at 3 months, indicating the complementary roles of DKI and DTI. When comparing patients with PCS (n = 9), without PCS (n = 16), and healthy controls, in the ROI analyses, no differences were found in the acute DKI and DTI metrics. However, near‐significant differences were observed for several DKI metrics obtained in WM and thalamus concurrently with symptom assessment (3 months after injury). Our findings indicate a combined utility of DKI and DTI in detecting WM microstructural alterations after mild TBI. Moreover, PCS may be associated with evolving alterations in brain microstructure, and DKI may be a promising tool to detect such changes.
Information, beliefs, and motivation: The antecedents to human resource attributions
Authors: Hewett Rebecca , Shantz Amanda , Mundy Julia 
Published: January 2019

SummaryDespite significant interest in the attributions employees make about their organization's human resource (HR) practices, there is little understanding of the antecedents of HR attributions. Drawing on attribution theory, we suggest that HR attributions are influenced by information (perceptions of distributive and procedural fairness), beliefs (organizational cynicism), and motivation (perceived relevance). We test a model through a two‐wave survey of 347 academic faculty in the United Kingdom, examining their attributions of the purpose of their institution's workload management framework. After two preliminary studies (an interview study and a cross‐sectional survey) to establish contextually relevant attributions, we find that fairness and cynicism are important for the formation of internal attributions of commitment but less so for cost‐saving or exploitation attributions. Fairness and cynicism also interact such that distributive fairness buffers the negative attributional effect of cynicism, and individuals are more likely to attribute fair procedures to external forces if they are cynical about their organization. This study furthers the application of attribution theory to the organizational domain while making significant contributions to our understanding of the HR‐performance process.
Nutrient flows and balances in intensively managed vegetable production of two West African cities
Authors: Akoto-Danso Edmund Kyei , Manka'abusi Delphine , Steiner Christoph , Werner Steffen , Haering Volker , Lompo Désiré J.-P. , Nyarko George , Marschner Bernd , Drechsel Pay , Buerkert Andreas 
Published: January 2019

AbstractThis study reports and analyzes nutrient balances in experimental vegetable production systems of the two West African cities of Tamale (Ghana) and Ouagadougou (Burkina Faso) over a two‐year period comprising thirteen and eleven crops, respectively. Nutrient‐use efficiency was also calculated. In Tamale and Ouagadougou, up to 2% (8 and 80 kg N ha−1) of annually applied fertilizer nitrogen were leached. While biochar application or wastewater irrigation on fertilized plots did not influence N leaching in both cities, P and K leaching, as determined with ion‐absorbing resin cartridges, were reduced on biochar‐amended plots in Tamale. Annual nutrient balances amounted to +362 kg N ha−1, +217 kg P ha−1, and –125 kg K ha−1 in Tamale, while Ouagadougou had balances of up to +692 kg N ha−1, +166 kg P ha−1, and –175 kg K ha−1 y−1. Under farmers' practice of fertilization, agronomic nutrient‐use efficiencies were generally higher in Tamale than in Ouagadougou, but declined in both cities during the last season. This was the result of the higher nutrient inputs in Ouagadougou compared to Tamale and relatively lower outputs. The high N and P surpluses and K deficits call for adjustments in local fertilization practices to enhance nutrient‐use efficiency and prevent risks of eutrophication.
Comparative assessment of drug‐induced sleep endoscopy scoring systems in pediatric sleep apnea
Authors: Tejan Joseph , Medina Melecio , Ulualp Seckin O. 
Published: January 2019

Objectives/HypothesisA wide variety of drug‐induced sleep endoscopy (DISE) scoring systems has been used to evaluate sites of upper airway obstruction in children and adults; however, a universally accepted DISE scoring system dedicated to children has not been developed. We evaluated the utility of DISE scoring systems in the assessment of obstructive sleep apnea (OSA) using a single cohort of pediatric patients.Study DesignRetrospective chart review.MethodsThe medical records of surgically naïve–healthy children with OSA who had undergone DISE were reviewed. Information about demographics, past medical history, and severity of OSA were obtained. A literature review was conducted to identify DISE scoring systems used in children with OSA. Recordings of DISE were analyzed without knowledge of patient information and severity of OSA. The effect of age, obesity, severity of OSA, and oxygen nadir on DISE score was assessed.ResultsSixty‐eight patients (46 male, 22 female, age range: 19 months–18 years) were included. Forty‐three patients were obese and 25 were nonobese. The severity of OSA was mild in 12 patients, moderate in 13 patients, and severe in 43 patients. DISE scoring systems did not document differences among the groups of patients with mild OSA, moderate OSA, and severe OSA (P > .05). DISE scores were not different among the studied age and weight categories (P > .05).ConclusionsThe DISE scoring systems did not show differences in DISE scores in surgically naïve–healthy children with varying age, weight, and OSA severity categories. Our findings provide preliminary evidence for the need of a universally applicable pediatric DISE scoring system for OSA.Level of Evidence4Laryngoscope, 129:2195–2198, 2019
Tracking three decades of land use and land cover transformation trajectories in China's large river deltas
Authors: Ma Tiantian , Li Xiaowen , Bai Junhong , Cui Baoshan 
Published: January 2019

AbstractLarge river deltas are characterized by complicated land use/land cover (LULC) dynamics driven by intertwined natural and anthropogenic processes. Understanding spatiotemporal LULC dynamics associated with multiple drivers can help mitigate the adverse ecological impacts resulting from human activities. This research tracked spatiotemporal LULC trajectories in relation to multiple natural and anthropogenic driving processes and explored their correlations within four large river deltas (the Liaohe River Delta [LRD], Yellow River Delta [YRD], Yangtze River Delta [YtRD], and Pearl River Delta [PRD]) in China from 1980 to 2010. The results showed that the coastal wetlands had undergone transformations with 39% in LRD, 85.1% in YRD, 96.5% in YtRD, and 100% in PRD, respectively. The LULC transformations were linked with six major driving processes (accretion, erosion, reclamation, restoration, succession, and regressive succession) and were impacted by complex coupled effects between natural and anthropogenic drivers. Reclamation‐related LULC transformation types dominated in the four river deltas and had greater spatiotemporal interactions than the other driving processes. Reclamation and restoration as well as accretion and erosion showed high positive correlations in all four river deltas, but other pairwise correlations of driving processes presented regional variations. This study presents an overview of the patterns and processes of complex multitemporal LULC dynamics and can be replicated elsewhere in areas where land reclamation activities are entangled with natural processes. A ‘scrolling’ development pattern with reasonable magnitudes of land reclamation for the river deltas is proposed as a spatial strategy to minimize the adverse ecological impacts of human activity.
Evaluating the desertification vulnerability of a semiarid landscape under different land uses with the environmental sensitivity index
Authors: Gül Ebru , Erşahin Sabit 
Published: January 2019

AbstractThe objective of this study was to evaluate the desertification vulnerability of an approximately 1,000‐ha area in Anatolia, Turkey, comprising semiarid oak (Quercusspp.) and pine (Pinusspp.) forests and the adjacent cultivated lands by using the environmental sensitivity index (ESI). We calculated the ESI values for 632 randomly selected sites in the study area by entering the desertification indicators vegetation cover, plant type, soil depth, rock fragments, soil texture, slope gradient, drainage, parent material, mean annual precipitation, slope aspect, aridity index, land use intensity, and policy enforcement into the web‐based model Desertification Indicator System for Mediterranean Europe. The spatial structure of the ESI values was then evaluated using semivariograms and kriging‐interpolated surface maps. The mean ESI value was significantly greater in the cultivated areas (1.47; range = 1.25–1.61) than in the pine (1.32; 1.03–1.45) and oak (1.28; 1.18–1.57) forests (P < 0.01). The ESI was moderately spatially dependent in the oak forests and cultivated areas and strongly spatially dependent in the pine forests, as evidenced by the corresponding semivariograms. The ordinary kriging‐interpolated maps showed that most of the cultivated areas were critically vulnerable to desertification, whereas the majority of the forested areas were moderately vulnerable. We examined how the ESI values varied with soil organic matter (OM) content as an independent variable and found that the OM content was significantly moderately correlated with the ESI (n = 632,r = −0.51,P < 0.01), suggesting that the ESI could be used to evaluate the desertification vulnerability of similar landscapes across Turkey.
Practices for rehabilitating bauxite‐mined areas and an integrative approach to monitor soil quality
Authors: Borges Silvano R. , Santos Rafael S. , Oliveira Dener M. S. , Souza Ivan F. , Verburg Ernst E. J. , Pimentel Laisa G. , Cruz Rogério S. , Silva Ivo R. 
Published: January 2019

AbstractMining activities cause severe impacts to soil, the restoration of which requires specific management, and proper evaluation and monitoring. In this research, our objectives were to study recovery strategies and integrate indicators for monitoring the reclamation of an agricultural soil after bauxite mining. Distinct fertilizations (nonfertilized control [CT], poultry litter [PL], chemical fertilization [CF], and PL + CF combined) and intercrops (bare soil with no intercrops [NI], grass [G], legume [L], and G + L combined) treatments were used as recovery strategies to restore soil capacity to sustain a coffee plantation. We selected 27 quality indicators to compare the premining condition, postmining (reconfigured topsoil), and 19 months after the application of fertilization/intercrops treatments. We used univariate statistics to select soil quality indicators and multivariate analyses to group the selected indicators into organic, chemical, physical, and microbiological properties. From each group, one representative attribute was selected, and its averaged weight was summarized into a soil quality index (SQI). In postmining, the estimated SQI was approximately 65% lower than in premining. The SQI recalculated 19 months after the application of fertilization (PL or PL + CF) and intercrops (G, L, or G + L) was 23% higher than in postmining and showed strong correlation with coffee bean yield (at 27 months). Coffee bean yield was highest in plots with L or G + L receiving PL or PL + CF. We conclude that organic amendments and intercrops are suitable approaches to recover soil following bauxite mining, and soil indicators can be integrated to properly monitor the land reclamation progress.
Seasonality of pCO2 in a hard‐water lake of the northern Great Plains: The legacy effects of climate and limnological conditions over 36 years
Authors: Finlay Kerri , Vogt Richard J. , Simpson Gavin L. , Leavitt Peter R. 
Published: January 2019

AbstractBiogeochemical processes are active year‐round in ice‐covered lakes, such that processes in one season can affect limnological conditions in subsequent seasons. However, the extent and nature of these legacy effects are poorly understood, particularly for the CO2 content of lakes and when considering gas exchange with the atmosphere. Here, we used a unique 36‐yr dataset of weekly limnological measurements of Buffalo Pound Lake in the northern Great Plains to assess seasonal changes in CO2 concentration and flux and determine how dependent lake pCO2 is on limnological conditions of previous seasons. We found that the lake was a net source of CO2 to the atmosphere (mean 18.5 ± 7.4 mol CO2 m−2 yr−1), with spring potentially accounting for the majority (~ 64% ± 20%) of CO2 efflux, assuming ice in spring was permeable to gas exchange (32.9% ± 19.8% if not). Analysis with generalized additive models (GAMs) demonstrated that current and antecedent seasonal conditions combined to explain 72.6% of deviance in spring pCO2, but that the strength of model predictions and the importance of antecedent conditions diminished in GAMs of summer (43.6%) and fall (23.3%) CO2 levels. This research suggests that pCO2 is regulated by a combination of coeval and historical environmental conditions and shows that quantification of seasonal and annual fluxes requires a mechanistic understanding of the legacy effects of preceding time intervals.
Intramolecular hydrogen bonding: An opportunity for improved design in medicinal chemistry
Authors: Caron Giulia , Kihlberg Jan , Ermondi Giuseppe 
Published: January 2019

AbstractRecent literature shows that intramolecular hydrogen bond (IMHB) formation can positively impact upon the triad of permeability, solubility, and potency of drugs and candidates. IMHB modulation can be applied to compounds in any chemical space as a means for discovering drug candidates with both acceptable potency and absorption, distribution, metabolism, and excretion‐Tox profiles. Integrating IMHB formation in design of drugs is, therefore, an exciting and timely challenge for modern medicinal chemistry. In this review, we first provide some background about IMHBs from the medicinal chemist's point of view and highlight some IMHB‐associated misconceptions. Second, we propose a classification of IMHBs for drug discovery purposes, review the most common in silico tactics to include IMHBs in lead optimization and list some experimental physicochemical descriptors, which quantify the propensity of compounds to form IMHBs. By focusing on the compounds size and the number of IMHBs that can potentially be formed, we also outline the major difficulties encountered when designing compounds based on the inclusion of IMHBs. Finally, we discuss recent case studies illustrating the application of IMHB to optimize cell permeability and physicochemical properties of small molecules, cyclic peptides and macrocycles.