bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of new antidiabetic agent by complexity between vanadyl (II) sulfate and vitamin B1: Structural, characterization, anti‐DNA damage, structural alterations and antioxidative damage studies
Authors: El‐Megharbel Samy M. , Hamza Reham Z. , Gobouri Adil A. , Refat Moamen S.
Published: March 2019

Complexity between thiamine (vitamin B1) and VSO4.xH2O salt with the suggest formula, [VO (vitB1)2] has been synthesized by the chemical reaction in neutralization media pH = 7.5 at 70 °C. The assignments of the elemental analysis, conductivity measurements, FT‐IR, UV–Vis, ESR spectroscopy, thermal analyses (TGA‐DTA) and magnetic moment data visualize the stoichiometry, formula and chelation of the vanadyl (II) complex. The spectroscopic analyses revealed that vitamin B1 reacted with vanadyl (II) ions as a bidentate ligand via hydroxyl ethyl‐oxygen and sulfur of the thiazole group. New vanadyl (II) complex has the protective effect against pancreatic toxicity induced by STZ. The target of this investigation was to assess the enhancement effect of new vanadyl (II)complex in two doses on pancreatic toxicity, oxidative stress, DNA damage and hyperglycemia persuade by STZ. The rats were divided into 7 groups; control group, STZ (diabetic untreated group) (50 mg/kg), STZ plus thiamine (10 mg/Kg) (Low dose), STZ plus thiamine (50 mg/Kg) (High dose), STZ plus VSO4. xH2O (15 mg/kg), STZ + vanadyl (II) complex (10 mg/Kg) (Low dose), STZ+ vanadyl (II) complex (50 mg/Kg) (High dose). Vanadyl (II) complex in high dose afforded a significant decline in MDA level parallel to significant elevation in antioxidant enzymes (SOD, CAT, MPO and XO) in pancreas homogenates. It may be due to the capturing activities of reactive oxygen species by the new complex, which reduces oxidative damage and enhance antioxidant capacities. The novel complex succeeded in the restoration of lipid parameters to its normal levels beside lowering TNF‐α and CRP levels. The new complex also reduces hyperglycemia induced by STZ greatly and improve histological and ultrastructure of pancreas and has a high potency in reducing DNA damage in pancreatic tissues.
Development of epoxy‐cyanate ester‐clay nanocomposites offering enhanced thermally stability
Authors: Venkatesh M. , Gouthaman S. , Kanemoto S. O. , Lakshmi M. S. , Hamerton I.
Published: March 2019

The preparation and characterization of blends of a series of dicyanate monomers such as 2,2′‐bis(4‐cyanatophenyl) propane (DCDPP), bis‐4‐cyanato‐biphenyl (DCBP), bis‐4‐cyanatonaphthalene (DCN), 3,3′‐bis(4‐cyanatophenyl)sulphide (DCTDP), 3,3′‐bis(4‐cyanatophenyl)sulphone (DCDPS), and the diglycidyl ether of bisphenol A are reported. These copolymers are combined with a montmorillionite nanoclay and both epoxy‐cyanate blends and epoxy‐cyanate blends‐nanoclay composites are all analyzed for thermal stability, thermal degradation kinetics, flame retardancy, and impact strength. The nanocomposites are further characterized by X‐ray diffraction and SEM to determine morphological features, from which structure–property relationships are determined. Dispersion of the nanoclay is of paramount importance, but its inclusion serves to improve char yield and impact strength, when this is achieved. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47754.
Water and sewer affordability in the United States
Authors: Teodoro Manuel P.
Published: March 2019

The ability of low‐income families to pay for basic water and sewer services is a subject of increasing concern. Large‐scale assessments of affordability across large numbers of American utilities are rare, however, and are limited by poor measurement and biased samples. The present study uses improved metrics and data from an original, representative sample of water and sewer utilities in the United States to calculate the affordability of basic single‐family residential water and sewer service for low‐income households. Results indicate that low‐income households must spend an average of 9.7% of their disposable income and/or work 9.5 h at minimum wage to pay for basic monthly water and sewer service but also that these values vary considerably across the country. Community‐level demographic and economic data are used to identify some correlates of affordability. Region, utility size, and local income inequality emerge as strong correlates of affordability.
Impact of depth filtration on disulfide bond reduction during downstream processing of monoclonal antibodies from CHO cell cultures
Authors: O’Mara Brian , Gao Zhong‐Hua , Kuruganti Manju , Mallett Robert , Nayar Gautam , Smith Laura , Meyer Jeffrey D. , Therriault Jon , Miller Cameron , Cisney John , Fann John
Published: March 2019

Monoclonal antibody interchain disulfide bond reduction was observed in a Chinese Hamster Ovary manufacturing process that used single‐use technologies. A similar reduction has been reported for processes that involved high mechanical shear recovery unit operations, such as continuous flow centrifugation and when the clarified harvest was stored under low dissolved oxygen (DO) conditions (Trexler‐Schmidt et al., 2010. Biotechnology and Bioengineering,
106(3), 452–461). The work described here identifies disposable depth filtration used during cell culture harvest operations as a shear‐inducing unit operation causing cell lysis. As a result, reduction of antibody interchain disulfide bonds was observed through the same mechanisms described for continuous flow centrifugation. Small‐scale depth‐filtration models were developed, and the differential pressure (Δ
P) of the primary depth filter was identified as the key factor contributing to cell lysis. Strong correlations of Δ
P and cell lysis were generated by measuring the levels of lactate dehydrogenase and thiol in the filtered harvest material. A simple risk mitigation strategy was implemented during manufacturing by providing an air overlay to the headspace of a single‐use storage bag to maintain sufficient DO in the clarified harvest. In addition, enzymatic characterization studies determined that thioredoxin reductase and glucose‐6‐phosphate dehydrogenase are critical enzymes involved in antibody reduction in a nicotinamide adenine dinucleotide phosphate (NADP
+)/NADPH‐dependent manner.
Association between polymorphisms in MicroRNA target sites of RAD51D genes and risk of hepatocellular carcinoma
Authors: Jiang Yan‐Ji , Zhong Jian‐Hong , Zhou Zi‐Han , Qiu Mo‐Qin , Zhou Xian‐Guo , Liu Ying‐Chun , Huo Rong‐Rui , Liang Xiu‐Mei , Chen Zhu , Lin Qiu‐Ling , Yu Xiang‐Yuan , Yu Hong‐Ping
Published: March 2019

RAD51D (RAD51L3) is a member of the RAD51 gene family which plays important roles in maintaining genomic stability and preventing DNA damage. This study is aimed to investigate the associations between RAD51D polymorphisms and the hereditary susceptibility of hepatocellular carcinoma (HCC). In this study we conducted a hospital–based case‐control study including 805 cases (HCC patients) and 846 controls (nontumor patients) in Guangxi, China. A total of two Single–nucleotide polymorphisms (SNPs) rs12947947 and rs28363292 of RAD51D were selected and genotyped. Although we did not find two SNPs individually that had any significant main effect on risk of HCC, We found that the combined genotypes with 1‐2 risk genotypes were associated with significantly increased overall risk of HCC (OR = 1.462, 95% CI = 1.050‐2.036). According to the results of further stratification analysis, GT/GG genotype of rs28363292 increased HCC risk in zhuang people (OR = 3.913, 95% CI = 1.873‐8.175) and nonhepatitis B virus (HBV) infection population (OR = 1.774, 95% CI = 1.060‐2.969), the combined 1‐2 risk genotypes increased the risk of HCC in zhuang people (OR = 2.817, 95% CI = 1.532‐5.182) and non‐HBV infected population (OR = 1.567, 95% CI = 1.042‐2.358). Our results suggest that rs12947947 and rs28363292 polymorphisms may jointly contribute to the risk of HCC. Further large studies and functional studies are required to validate our findings.
Rutin as Deoxyribonuclease I Inhibitor
Authors: Kolarevic Ana , Pavlovic Aleksandra , Djordjevic Aleksandra , Lazarevic Jelena , Savic Sasa , Kocic Gordana , Anderluh Marko , Smelcerovic Andrija
Published: March 2019

DNase I inhibitory potential of water extract of nine Hypericum species (H. umbellatum, H. barbatum, H. rumeliacum, H. rochelii, H. perforatum, H. tetrapterum, H. olympicum, H. hirsutum, H. linarioides) and the most important Hypericum secondary metabolites (hypericin, hyperforin, quercetin, and rutin) was investigated. All examined Hypericum extracts inhibited DNase I with IC50 below 800 μg/ml, whereby H. perforatum was the most potent (IC50=391.26±68.40 μg/ml). Among the investigated Hypericum secondary metabolites, rutin inhibited bovine pancreatic DNase I in a non‐competitive manner with IC50 value of 108.90±9.73 μm. DNase I inhibitory ability of rutin was further confirmed on DNase I in rat liver homogenate (IC50=137.17±16.65 μm). Due to the involvement of DNase I in apoptotic processes the results of this study indicate the importance of frequent rutin and H. perforatum consumption in daily human nutrition. Rutin is a dietary component that can contribute to male infertility prevention by showing dual mechanism of sperm DNA protection, DNase I inhibition and antioxidant activity.
Polymer‐Based Module for NAD+ Regeneration with Visible Light
Authors: Ma Beatriz C. , Caire da Silva Lucas , Jo Seong‐Min , Wurm Frederik R. , Bannwarth Markus B. , Zhang Kai A. I. , Sundmacher Kai , Landfester Katharina
Published: March 2019

The regeneration of enzymatic cofactors by cell‐free synthetic modules is a key step towards producing a purely synthetic cell. Herein, we demonstrate the regeneration of the enzyme cofactor NAD+ by photo‐oxidation of NADH under visible‐light irradiation by using metal‐free conjugated polymer nanoparticles. Encapsulation of the light‐active nanoparticles in the lumen of polymeric vesicles produced a fully organic module able to regenerate NAD+ in an enzyme‐free system. The polymer compartment conferred physical and chemical autonomy to the module, allowing the regeneration of NAD+ to occur efficiently, even in harsh chemical environments. Moreover, we show that regeneration of NAD+ by the photocatalyst nanoparticles can oxidize a model substrate, in conjunction with the enzyme glycerol dehydrogenase. To ensure the longevity of the enzyme, we immobilized it within a protective silica matrix; this yielded enzymatic silica nanoparticles with enhanced long‐term performance and compatibility with the NAD+‐regeneration system.
Epithelioid glioblastoma presenting as aphasia in a young adult with ovarian cancer: A case report
Authors: Finneran Megan M. , Georges Joseph , Kakareka Michael , Moncman Ryan , Enriquez Miriam , Siegal Todd , Kubicek Gregory , Turtz Alan , Yocom Steven , Goldman H. Warren , Barrese James
Published: March 2019

Key Clinical Message

Our patient's clinical history and preoperative radiographic evaluation suggested central nervous system (CNS) metastatic disease. Ultimately, final pathology revealed epithelioid glioblastoma (eGBM), a newly classified CNS primary tumor. This reinforces the importance of direct tissue sampling and including eGBM on the differential for young patients with histories of systemic cancer presenting with new CNS lesions.
Agostic Interactions in Early Transition‐Metal Complexes: Roles of Hyperconjugation, Dispersion, and Steric Effect
Authors: Lin Xuhui , Wu Wei , Mo Yirong
Published: March 2019

The agostic interaction is a ubiquitous phenomenon in catalytic processes and transition‐metal complexes, and hyperconjugation has been well recognized as its origin. Yet, recent studies showed that either short‐range London dispersion or structural constraints could be the driving force, although proper evaluation of the role of hyperconjugation therein is needed. Herein, a simple variant of valence bond theory was employed to study a few exemplary Ti complexes with α‐ or β‐agostic interactions and interpret the agostic effect in terms of the steric effect, hyperconjugation, and dispersion. For the complexes [MeTiCl3(dmpe)] and [MeTiCl3(dhpe)] with α‐agostic interactions, hyperconjugation plays the dominant role with comparable magnitudes in both systems, but dispersion is solely responsible for the stronger agostic interaction in the former compared with the latter. For the complexes [EtTiCl3(dmpe)] and [EtTiCl3(dhpe)] with β‐agostic interactions, however, hyperconjugation and dispersion play comparable roles, and the weaker steric repulsion leads to a stronger agostic effect in the former than in the latter. Thus, the present study clarifies the variable and sensitive roles of steric, hyperconjugative, and dispersion interactions in the agostic interaction.
Luminescent Graphene‐Based Materials via Europium Complexation on Dipyridylpyridazine‐Functionalized Graphene Sheets
Authors: Amaro‐Gahete Juan , Kaczmarek Anna M. , Esquivel Dolores , Jiménez‐Sanchidrián César , Van Der Voort Pascal , Romero‐Salguero Francisco J.
Published: March 2019

Graphene‐based materials exhibit outstanding physical properties and so are potentially applicable in a great variety of fields. Unlike their corresponding oxides, graphite and graphene are not prone to functionalization. Diels–Alder reactions are among the scarce reactions that they can occur without disrupting their conjugated sp2 systems. Herein, the reaction between graphite and 3,6‐di(2‐pyridyl)‐1,2,4,5‐tetrazine under different conditions affords several graphene‐based materials consisting of dipyridylpyridazine‐functionalized few‐layer graphene, multilayer graphene and graphite, the sheets of which act as ligands for the grafting of a europium complex. These three materials show strong red emission under 365 nm UV radiation. Their emitting particles can be visualized by confocal microscopy. The rich coordination chemistry of dipyridylpyridazine ligands has potential novel properties for similarly functionalized graphene‐based materials grafted with other metal complexes.
Revisiting Bond Breaking and Making in EuCo2P2: Where are the Electrons?
Authors: Yannello Vincent , Guillou Francois , Yaroslavtsev Alexander A. , Tener Zachary P. , Wilhelm Fabrice , Yaresko Alexander N. , Molodtsov Serguei L. , Scherz Andreas , Rogalev Andrei , Shatruk Michael
Published: March 2019

Invited for the cover of this issue are the groups of Michael Shatruk at Florida State University, Andrei Rogalev at the European Synchrotron Radiation Facility, and colleagues. The image depicts the detective work by the authors while trying to interpret their experimental results. Read the full text of the article at 10.1002/chem.201900244.
Statistical Thermodynamics Unveils How Ions Influence an Aqueous Diels‐Alder Reaction
Authors: Reid Joshua E. S. J. , Aquino Pedro H. G. , Walker Adam J. , Karadakov Peter B. , Shimizu Seishi
Published: March 2019

The kinetics of Diels‐Alder (DA) reactions in water has been known to be altered by salts for a long time. Yet the question how salts influence the reaction rate, either as rate‐enhancing or rate‐reducing additives, has so far remained unresolved. Conflicting hypotheses involve (i) indirect salt contributions through the modulation of internal pressure and (ii) making (or breaking) of the so‐called “water‐structure” by salts that strengthen (or weaken) the hydrophobic effect. In contrast to the qualitative nature of these hypotheses, here we answer this question quantitatively through a combination of transition state theory and fluctuation adsorption‐solvation theory (FAST) using the DA reaction between anthracene‐9‐carbinol and N‐ethylmaleimide as an example. We show that rate enhancement is driven by the salting out of the hydrophobic reactant, while rate‐enhancing salts exhibit stronger affinity to the transition state.
Does religion benefit corporate social responsibility (CSR)? Evidence from China
Authors: Su Kun
Published: March 2019

Corporate social responsibility (CSR) has been attracting ever considerable attention from practice and academia, but the determinants of CSR remain unclear, especially in transitional economies. Using firm‐level data of listed firms in China and constructing the variable of religion through the geographic proximity method, this study investigates the relationship between religion and CSR and further explores the differences between low‐ and high‐polluting industries. Our empirical results demonstrate that religious atmosphere (Buddhism and Taoism as a whole) in a region can induce managers to be less selfish and to care more about other stakeholders, which is potentially beneficial to a firm's CSR. This effect is stronger in high‐polluting industries and less pronounced in low‐polluting industries. Also, my findings demonstrate that the above conclusions apply only for Buddhism, indicating that different religions have an asymmetric effect on CSR. This work enriches and expands the research on CSR and religion, which has important implications on the value of religion in business practice.
RhIII‐Catalyzed Asymmetric Transfer Hydrogenation of α‐Methoxy β‐Ketoesters through DKR in Water: Toward a Greener Procedure
Authors: He Bin , Zheng Long‐Sheng , Phansavath Phannarath , Ratovelomanana‐Vidal Virginie
Published: March 2019

The asymmetric reduction of α‐methoxy β‐ketoesters through transfer hydrogenation with a new rhodium(III) complex was developed. The reaction was efficient in 2‐MeTHF with formic acid/triethylamine or in water with sodium formate. The corresponding syn α‐methoxy β‐hydroxyesters were obtained with high diastereoselectivities and excellent levels of enantioselectivity through a dynamic kinetic resolution process.
Review of energy storage and transportation of energy
Authors: Khan Nasrullah , Dilshad Saad , Khalid Rashida , Kalair Ali Raza , Abas Naeem
Published: March 2019

Energy storage and transportation are essential keys to make sure the continuity of energy to the customer. Electric power generation is changing dramatically across the world due to the environmental effects of Greenhouse gases (GHG) produced by fossil fuels. The unpredictable daily and seasonal variations in demand for electrical energy can be tackled by introducing the energy storage systems (ESSs) and hence mitigating the extra GHG emission in the atmosphere. Energy storage techniques can be mechanical, electro‐chemical, chemical, or thermal, and so on. The most popular form of energy storage is hydraulic power plants by using pumped storage and in the form of stored fuel for thermal power plants. The classification of ESSs, their current status, flaws and present trends, are presented in this article. The present state of fossil fuel reserves, their production, consumption, and as a consequence of these the CO2emissions are also discussed. The primary energy carriers coal, oil and gas are not evenly distributed along the globe. Long distances are involved in transporting these energy carriers and transportation and delivery of these key resources to the prime customers is always necessary. The different methods to transport the energy from the source end to demand end is also discussed in this article. The assessment of various energy storage methods on the basis of several factors and present status and development of storage and transportation of energy in Pakistan is discussed.
Analysis of Keystroke Sequences in Writing Logs
Authors: Zhu Mengxiao , Zhang Mo , Deane Paul
Published: March 2019

The research on using event logs and item response time to study test‐taking processes is rapidly growing in the field of educational measurement. In this study, we analyzed the keystroke logs collected from 761 middle school students in the United States as they completed a persuasive writing task. Seven variables were extracted from the keystroke logs and compared with different score and gender groups. Group comparisons were also made using methodologies borrowed from sequence mining. Students' composition strategies over the course of the writing process were also investigated. The findings of this study have implications for gaining deeper understanding of observed group differences and for designing interventions to close the achievement gaps among population groups.
Clustering‐Based Resource Allocation mechanism in Long Term Evolution Advanced networks with auto‐encoder for feature learning
Authors: Santos Einar C.
Published: March 2019

Clustering‐Based Resource Allocation (CBRA) is a relatively recent approach applied in some communication network technologies that executes resource allocation rules by following patterns discovered in the user and traffic flow information. It is a useful option for classifying traffic and detecting the most suitable Quality‐of‐Service parameters to perform improved resource allocation, especially in mobile systems such as Long Term Evolution Advanced, which are growing in user demand. An open issue in the CBRA approach is the necessity to perform feature engineering manually (feature selection), which may cause loss of relevant system information and consequent deterioration of performance. In this research article, we present a novel CBRA mechanism that implements an auto‐encoder to perform feature learning, thus avoiding feature selection. The auto‐encoder, deployed at the early stages of the CBRA mechanism, transforms the user and traffic flow data into a shortened representation, preventing the curse of dimensionality while capturing the nonlinear correlations of the data. The simulation results indicate better cluster formation and performance improvement for real‐time video applications using the proposed mechanism.
Joint relay selection and energy‐efficient power allocation strategies in energy‐harvesting cooperative NOMA networks
Authors: Baidas Mohammed W. , Alsusa Emad , Hamdi Khairi A.
Published: March 2019

In this paper, the problem of joint relay selection and energy‐efficient power allocation (J‐RS‐EE‐PA) in energy‐harvesting cooperative nonorthogonal multiple‐access networks is considered. In particular, a base station communicates with multiple users via a selected energy‐harvesting relay, such that energy efficiency (EE) is maximized, subject to quality‐of‐service constraints. Four different EE power allocation strategies are considered, namely, global energy efficiency, minimum energy efficiency, product energy efficiency, and sum energy efficiency. For all the aforementioned strategies, the J‐RS‐EE‐PA problem happens to be nonconvex and, thus, is computationally prohibitive. In turn, the J‐RS‐EE‐PA problem is decoupled into two subproblems: (1) relay selection and (2) energy‐efficient power allocation. Different relay selection strategies are explored, and then, computationally efficient algorithms are devised to optimally solve the different EE power allocation strategies for the selected relay. In addition, a low‐complexity solution procedure is proposed to solve the J‐RS‐EE‐PA problem. Simulation results are presented to evaluate the resulting EE of the different relay selection and power allocation strategies in comparison to the formulated J‐RS‐EE‐PA problem. More importantly, the proposed solution procedure is shown to be superior to the different explored relay selection strategies as well as yielding the global optimal solution of the J‐RS‐EE‐PA problem for the global energy efficiency, minimum energy efficiency, product energy efficiency, and sum energy efficiency strategies, while satisfying quality‐of‐service requirements.
Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct‐Acting Antiviral Treatment Failure in Patients With Hepatitis C?
Authors: Piecha Felix , Gänßler Jan‐Michael , Jordan Sabine , Ergen Can , Ittrich Harald , Kluwe Johannes , Pischke Sven , Lohse Ansgar W. , Schulze zur Wiesch Julian
Published: March 2019

Direct‐acting antiviral (DAA) therapies have revolutionized the treatment of chronic hepatitis C virus infection, achieving sustained virological response (SVR) rates of >90% even in patients with advanced liver cirrhosis. Having observed an unusual case of repeated DAA therapy failures in a patient with a transjugular intrahepatic portosystemic shunt (TIPS), we assessed a possible association between prior TIPS placement and DAA failure. A structured search of our clinical database revealed 10 patients who had received DAA therapy after TIPS placement. At the time of therapy, most patients (8; 80%) presented with a Child‐Pugh score B, and the following DAA regimens were used: sofosbuvir/ledipasvir ± ribavirin (5 patients), sofosbuvir/daclatasvir ± ribavirin (3), sofosbuvir/velpatasvir (2), and sofosbuvir/velpatasvir/voxilaprevir (1). In total, 5 patients (50%) achieved an SVR, whereas a virological relapse occurred in the other half of the cases, including 2 patients with multiple relapses. In this patient cohort, SVR rates were unusually low for all regimens: sofosbuvir/ledipasvir ± ribavirin, 3/5 (60%); sofosbuvir/daclatasvir ± ribavirin, 2/3 (66%); sofosbuvir/velpatasvir, 0/2 (0%); and sofosbuvir/velpatasvir/voxilaprevir, 0/1 (0%), and patients with a TIPS made up a relevant proportion of DAA failures in patients with cirrhosis at our center: sofosbuvir/ledipasvir, 2/18 (11%); sofosbuvir/daclatasvir, 1/4 (25%); sofosbuvir/velpatasvir, 2/3 (66%); and sofosbuvir/velpatasvir/voxilaprevir, 1/1 (100%). Conclusion: We observed a high rate of virological relapse in patients with a TIPS who received DAA treatment and therefore postulate that TIPS placement may be a possible risk factor for DAA failure due to the profound hemodynamic changes evoked by the intervention. Longer treatment duration or addition of ribavirin might be warranted in these patients.
Whole Effluent Toxicity Data and Discharge Volumes to Assess the Likelihood that Environmental Risks of Offshore Produced Water Discharges Are Adequately Controlled
Authors: Karman Chris C , Smit Mathijs GD
Published: March 2019

In 2012, the Oslo–Paris (OSPAR) Commission adopted Recommendation 2012/5 for a risk-based approach (RBA) to the management of produced water discharges from offshore installations. As part of this recommendation, OSPAR requires that the environmental risk of the discharge of produced water is characterized based on whole effluent toxicity (WET) studies and/or on a substance-based assessment. In this paper we describe an assessment of the likelihood that the environmental risk of produced water discharges is adequately controlled based on WET data for 19 oil- and gas-producing platforms and their discharge volumes. Our analysis shows that, with the selected risk criterion of predicted exposure concentration (PEC)/predicted no-effect concentration (PNEC) should not exceed 1 at 500 m, there is a mean likelihood of 99.5% (or more) that the environmental risk from the produced water discharges is adequately controlled for installations that discharge 30 × 103 m3/y (or less). The method presented in this paper can be used for screening purposes to ensure that efforts are directed toward installations with a high likelihood that risk is not adequately controlled. Integr Environ Assess Manag 2019;15:584–595. © 2019 SETAC
Science-based Targets for Antibiotics in Receiving Waters from Pharmaceutical Manufacturing Operations
Authors: Tell Joan , Caldwell Daniel J , Häner Andreas , Hellstern Jutta , Hoeger Birgit , Journel Romain , Mastrocco Frank , Ryan Jim J , Snape Jason , Straub Jürg Oliver , Vestel Jessica
Published: March 2019

In 2016, the United Nations declared the need for urgent action to combat the global threat of antimicrobial resistance (AMR). In support of this effort, the pharmaceutical industry has committed to measures aimed at improving the stewardship of antibiotics both within and outside the clinic. Notably, a group of companies collaborated to specifically address concerns related to antibiotic residues being discharged from manufacturing sites. In addition to developing a framework of minimum environmental expectations for antibiotic manufacturers, science-based receiving water targets were established for antibiotics discharged from manufacturing operations. This paper summarizes the holistic approach taken to derive these targets and includes previously unpublished, company-generated, environmental toxicity data.
Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study
Authors: Kim Eun Young , Chang Yoosoo , Lee Kwan Ho , Yun Ji‐Sup , Park Yong Lai , Park Chan Heun , Ahn Jiin , Shin Hocheol , Ryu Seungho
Published: March 2019

The impact of variations in serum thyroid hormone concentration within the euthyroid range on breast cancer risk remains unclear. We investigated the effect of serum thyrotropin (TSH) and thyroid hormone concentration on breast cancer risk. This cohort study involved 62,546 Korean women, aged ≥40 years, who were free of breast cancer at baseline and underwent health examination with determination of free thyroxine (FT4) and TSH. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI). During a median follow‐up of 4.8 years (interquartile range: 2.8–7.3 years), 834 incident breast cancers were identified. Compared to normal FT4 level, abnormally high serum FT4 level was associated with an increased risk of incident breast cancer with a corresponding multivariable aHR (95% CI) of 1.98 (1.02–3.83). This association tended to be stronger in postmenopausal women than in premenopausal women. Within the euthyroid range, the highest TSH tertile was associated with a lower risk of breast cancer than the lowest TSH tertile with a corresponding aHR (95% CI) of 0.68 (0.55–0.84). In contrast, highest FT4 tertile was associated with a higher risk of breast cancer than the lowest FT4 tertile. Abnormally high FT4 as well as higher FT4 within the euthyroid range were positively associated with breast cancer risk, while higher TSH concentration within the euthyroid range was negatively associated with breast cancer risk. Our findings indicate that thyroid function within both the abnormal and euthyroid ranges may contribute to the development of breast cancer.
Microneedles of chitosan‐porous carbon nanocomposites: Stimuli (pH and electric field)‐initiated drug delivery and toxicological studies
Authors: Gaware Shankar A. , Rokade Kasturi A. , Bala Preetam , Kale Sangeeta N.
Published: March 2019

An array of microneedles (MNs) of chitosan‐graphene assembled in porous carbon (CS‐GAPC) nanocomposites has been synthesized and evaluated. The safety of the formulated system has been ensured using detailed in vivo toxicological studies and efficacy has been ensured by evaluating the stimuli (pH and electric field) initiated drug delivery properties. Drug cephalexin has been incorporated in these MNs. In vivo toxicological studies of CS‐GAPC nanocomposite were performed on Sprague rats, using acute dermal and subacute dermal (ADT& SADT) test, histopathological studies, biochemical studies, and AMES tests. ADT and SADT studies showed that median lethal dose (LD50) was found greater than 2000 mg/kg body weight; with no abnormal weight gain and food consumption, during the study period of 28 days. This study showed that administration of CS‐GAPC did not cause any substantial alterations in hematological and biochemical parameters of the animals. Histopathological studies showed no significant changes in the control and CS‐GAPC administered groups. AMES tests reveal that CS‐GAPC nanocomposite is nonmutagenic against the Salmonella thyphimurium strains. No abnormalities were observed in the animal's chromosomal aberrations and clastogenic values when the animals were treated with CS‐GAPC. At acidic pH of 4, the encapsulated drug was completely released, indicating that the drug release from the prepared nanocomposite is pH dependent. An electric field of 5 V showed optimum drug release, as a function of applied electric pulses. A biologically safe drug encapsulation model system is hence projected for smart drug delivery (pH dependent and electric field triggered) using the microneedle approach. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1582–1596, 2019.
Blockchain: The Introduction and Its Application in Financial Accounting
Authors: Yu Ting , Lin Zhiwei , Tang Qingliang
Published: March 2019

Blockchain, as a decentralized ledger technology with characteristics of transparent, secure, permanent and immutable, has been applied in many fields such as cryptocurrency, equity financing, and corporate governance. However, the blockchain technology is in the experimental stage and has several problems to be solved including limited data processing capacity, information confidentiality, and regulatory difficulties. This study sheds light on the potential application of blockchain technology in financial accounting and its possible impacts. We argue that in the short run the public blockchain could be used as a platform for firms to voluntarily disclose information. In the long run, the application could effectively reduce errors in disclosure and earnings management, increase the quality of accounting information and mitigate information asymmetry. We also discuss potential impacts that the application will have on independent auditors and financial accountants. © 2019 Wiley Periodicals, Inc.
Identification of potential hub‐lncRNAs in ischemic stroke based on Subpathway‐LNCE method
Authors: Zheng Yanhua , Sun Shaopeng , Yu Miao , Fu Xiuxin
Published: March 2019

Ischemic stroke is a devastating condition with a high burden of neurological disability and death. The aim of this study was to explore the potential long noncoding RNA (lncRNA) biomarkers underlying the mechanism of stroke. The Subpathway‐LNCE method, which was specifically designed to identify lncRNAs competitively regulated functions in diseases, was applied in ischemic stroke dataset to identify ischemic‐stroke‐associated dysfunctional subpathway that regulated by lncRNAs. At first, based on the shared microRNA (miRNA) between miRNA‐messenger RNA (mRNA) and lncRNA‐miRNA interactions, lncRNA‐mRNA interactions were constructed. Then, the transcription profiling of 18 631 genes was downloaded from Array Express database and was preprocessed, including normalization and gene expression difference (DEG) analysis, to identify candidate differential pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Next, the pathway‐lncRNA‐mRNA networks were constructed by linking lncRNAs to candidate differential pathways. At last, there were 11 lncRNAs were identified in the top three subpathways as hub‐lncRNAs totally, including LINC00240, LINC00472, LINC00265, LINC00473, MIR497HG, NEXN‐AS1, HCG17, MEG8, EPB41L4A‐AS1, SNHG7, and BCYRN1, five of which were validated to be very effective stroke biomarker by RT‐PCR. In conclusion, we applied Subpathway‐LNCE method and experimental verification to identify five lncRNAs, including LINC00265, LINC00473, NEXN‐AS1, HCG17, and MEG8, which were considered as important lncRNAs biomarkers in ischemic stroke.
Pharmacokinetics of Ursodeoxycholic Acid in Elderly Volunteers Compared With Younger Adults in a Korean Population
Authors: Lee Soyoung , Yoon Seonghae , Chung Hyewon , Ji Sang Chun , Yoon Seo Hyun , Yu Kyung‐Sang , Cho Joo‐Youn , Chung Jae‐Yong
Published: March 2019

Ursodeoxycholic acid (UDCA) is a secondary bile acid component used for treating primary biliary cirrhosis. This study evaluated and compared the pharmacokinetic (PK) profiles of UDCA and its conjugates glyco‐UDCA (G‐UDCA) and tauro‐UDCA (T‐UDCA) in healthy elderly subjects and younger adults. In this randomized, open‐label, 2‐treatment, 1‐sequence, and parallel study, subjects received 400 or 800 mg UDCA on day 1, followed by 200 mg UDCA twice daily for 2 weeks. Blood samples were obtained up to 24 hours after the first UDCA dose. Changes in miRNA‐122, γ‐glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase levels from baseline were assessed to determine the safety and pharmacological effects of UDCA. This study examined the outcomes of 16 elderly subjects and 16 younger adults. Dose‐normalized peak concentration of and systemic exposure to UDCA were 2 to 4 times higher, and the corresponding values of G‐UDCA and T‐UDCA were 1.7 times higher in the elderly subjects than in the younger adults. The subjects in both groups showed multiple peak profiles of UDCA and its conjugates. The miRNA‐122 levels and hepatic enzyme test results were within the normal range in the elderly subjects after multiple administration of UDCA. This study is the first to confirm that the PK measurements of UDCA were higher in elderly subjects than in younger adults, which may improve the clinical outcomes of elderly subjects.
Analysis of efficacy of the self‐assembling peptide‐based remineralization agent on artificial enamel lesions
Authors: Üstün Nilüfer , Aktören Oya
Published: March 2019

The objective of this in vitro study was to analyze and compare the biomimetic remineralizing efficacy of the self‐assembling peptide (P11‐4) with agents containing casein phoshopeptide‐amorhous calcium phosphate fluoride (CPP‐ACFP) and sodium fluoride (NaF) on artificial caries lesions using DIAGNOdent and micro‐computed tomography (μCT). Artificial enamel lesions were prepared on extracted impacted sound mandibular third molars. The samples were randomly allocated to four groups (n = 8): Group 1, P11‐4 (Curodont Repair, Credentis AG, Switzerland); Group 2, CPP‐ACFP (MI Varnish, GCCo., Japan); Group3, NaF (Duraphat Varnish, Colgate, Colgate‐Palmolive, NY, USA); Group 4, artificial saliva (control). The agents were applied to demineralized surfaces according to manufacturers' instructions; all specimens were stored in artificial saliva for 1 month. Demineralization and remineralization on enamel surfaces were analyzed and quantified by DIAGNOdent (KaVo, Germany) and μCT (SkyScan1174, Belgium) for lesion depth/area/volume/mineral density (MD). The remineralization efficacy of the agents was evaluated by DIAGNOdent on 1st, 7th, 30th days and by μCT on 30th day. Data were statistically analyzed by ANOVA, Kruskal–Wallis, T test, and Wilxocon tests. The highest remineralization efficacy findings in all periods were determined in Group 1, followed by Groups 2, 3, and 4. The remineralization findings for fluorescence, MD, lesion depth in Group 1 were found significantly higher (p < 0.01) than Group 3; and no significant differences (p > 0.05) were found between Groups 1–2 and Groups 2–3. The area and volume change values in Groups 1, 2, and 3 have shown no significancy (p > 0.05). A significant correlation (p < 0.01) was found between μCT and DIAGNOdent methods. The data of this study have demonstrated that P11‐4 has showed the best remineralization efficacy, followed by CPP‐ACFP and NaF. It is concluded that self‐assembling peptide‐based remineralization agent can be used successfully for biomimetic remineralization of enamel subsurface lesions.
Rainbow triangles and the Caccetta‐Häggkvist conjecture
Authors: Aharoni Ron , DeVos Matthew , Holzman Ron
Published: March 2019

A famous conjecture of Caccetta and Häggkvist is that in a digraph on vertices and minimum outdegree at least n/r there is a directed cycle of length or less. We consider the following generalization: in an undirected graph on vertices, any collection of disjoint sets of edges, each of size at least n/r, has a rainbow cycle of length or less. We focus on the case and prove the existence of a rainbow triangle under somewhat stronger conditions than in the conjecture. In our main result, whenever is larger than a suitable polynomial in , we determine the maximum number of edges in an ‐vertex edge‐colored graph where all color classes have size at most and there is no rainbow triangle. Moreover, we characterize the extremal graphs for this problem.
Mapping spatial variability of annual rainfall under different return periods in Turkey: The application of various distribution functions and model selection techniques
Authors: Tosunoglu Fatih , Gurbuz Faruk
Published: March 2019

The objectives of the paper are to determine the best‐fitted probability distribution functions for annual rainfall in Turkey and to provide more accurate estimates of rainfall quantiles under different return periods. To achieve these aims, 10 popular and widely used probability distributions: gamma, generalized extreme value, Gumbel, normal, logistic, log‐logistic, two‐parameter log‐normal, three‐parameter log‐normal, Pearson type III and Weibull, are considered for modelling annual rainfall data covering the period 1975–2014 from 155 gauge stations uniformly distributed across Turkey. Unlike previous studies, the performances of the candidate probability distributions were evaluated by various model selection techniques: Akaike information criterion (AIC), Bayesian information criterion (BIC), Anderson–Darling (AD) criterion, the Cramér–von Mises test (CvM) and the Kolmogorov–Smirnov test (KS). According to the ranking‐based scoring evaluation, the gamma, log‐logistic, two‐parameter log‐normal, normal and Weibull distributions, which show the best fit for 78% of the data series, were mainly found to be the most suitable distributions. T year (25, 50 and 100) rainfall quantiles were then estimated using the best‐fitted distributions. Finally, the universal Kriging method, which is an effective interpolation method, was used to map the estimated rainfall quantiles.
ER visits reveal chance to screen preteens for suicide risk
Authors: Canady Valerie A.
Published: March 2019

While acknowledging that suicidal thoughts and behaviors are typically seen in older teens, researchers have examined suicide risk screening of youth in emergency departments (EDs) and say that their findings point to the importance of prescreening patients as young as 10.
Enteroids for Nutritional Studies
Authors: Yin Yue‐Bang , de Jonge Hugo R. , Wu Xin , Yin Yu‐Long
Published: March 2019

Nutritional studies are greatly hampered by a paucity of proper models. Previous studies on nutrition have employed conventional cell lines and animal models to gain a better understanding of the field. These models lack certain correlations with human physiological responses, which impede their applications in this field. Enteroids are cultured from intestinal stem cells and include enterocytes, enteroendocrine cells, goblet cells, Paneth cells, and stem cells, which mimic hallmarks of in vivo epithelium and support long‐term culture without genetic or physiological changes. Enteroids have been used as models to study the effects of diet and nutrients on intestinal growth and development, ion and nutrient transport, secretory and absorption functions, the intestinal barrier, and location‐specific functions of the intestine. In this review, the existing models for nutritional studies are discussed and the importance of enteroids as a new model for nutritional studies is highlighted. Taken together, it is suggested that enteroids can serve as a potential model system to be exploited in nutritional studies.
Combined diffusion‐relaxometry MRI to identify dysfunction in the human placenta
Authors: Slator Paddy J. , Hutter Jana , Palombo Marco , Jackson Laurence H. , Ho Alison , Panagiotaki Eleftheria , Chappell Lucy C. , Rutherford Mary A. , Hajnal Joseph V. , Alexander Daniel C.
Published: March 2019

Purpose

A combined diffusion‐relaxometry MR acquisition and analysis pipeline for in vivo human placenta, which allows for exploration of coupling between and apparent diffusion coefficient (ADC) measurements in a sub 10‐minute scan time.

Methods

We present a novel acquisition combining a diffusion prepared spin echo with subsequent gradient echoes. The placentas of 17 pregnant women were scanned in vivo, including both healthy controls and participants with various pregnancy complications. We estimate the joint ‐ADC spectra using an inverse Laplace transform.

Results

‐ADC spectra demonstrate clear quantitative separation between normal and dysfunctional placentas.

Conclusions

Combined ‐diffusivity MRI is promising for assessing fetal and maternal health during pregnancy. The ‐ADC spectrum potentially provides additional information on tissue microstructure, compared to measuring these two contrasts separately. The presented method is immediately applicable to the study of other organs.
The placebo response in myasthenia gravis assessed by quantitative myasthenia gravis score: A meta‐analysis
Authors: Frisaldi Elisa , Shaibani Aziz , Vollert Jan , Ferrero Bruno , Carrino Roberta , Ibraheem Hayan Dhamer , Vase Lene , Benedetti Fabrizio
Published: March 2019

Introduction

This meta‐analysis investigates the placebo response in generalized myasthenia gravis (MG) trials by means of Quantitative Myasthenia Gravis (QMG) scores.

Methods

PubMed, Scopus, Web of Science, Cochrane Controlled Trial Register, and EMBASE were searched. QMG score, dropouts rate, adverse events (AEs), and AEs responsible for dropouts were examined, together with treatment moderators.

Results

The magnitude of placebo response showed an effect size of 0.24, which was significantly lower than 0.67 of the drug response (P = 0.019). Furthermore, the forest plot revealed that, overall, active treatments showed a significantly higher impact on QMG scores than placebos.

Conclusions

Placebo and drug responses in MG trials are small and moderate, respectively. The lack of MG trials with a pure placebo arm or a no‐treatment control arm made it impossible to disentangle improvements due to the placebo psychological effect from other effects such as natural history and/or regression to the mean. Muscle Nerve 59:671–678, 2019
Statin‐associated muscle symptoms: Does the benefit outweigh the risk factor?
Authors: Laboy Shannon M. , PULLEY Michael T.
Published: March 2019

See article on pages 537–543 in this issue.
Applying spaced practice in the schools to teach math vocabulary
Authors: Petersen‐Brown Shawna , Lundberg Ashlee R. , Ray Jannine E. , Dela Paz Iwalani N. , Riss Carrington L. , Panahon Carlos J.
Published: March 2019

Spaced practice, or the distribution of practice opportunities across time, is a well‐known and effective practice for improving retention. However, spaced practice is not effectively implemented in schools, perhapsl as a result of a lack of educationally relevant research in the area. We conducted an educationally relevant investigation of the spaced practice. Using a quasi‐experimental between‐subjects design, we taught 62 third‐ and fourth‐grade students eight math vocabulary words under two patterns of spaced practice (fixed interval and expanded interval) and massed practice. Results showed a benefit of spaced practice over massed practice, but no difference between fixed interval and expanded interval spaced practice. The findings suggest that spaced practice may be implemented to improve the retention of math vocabulary words; however, more research is needed to provide guidelines to support educators in implementing spaced practice in schools.
Fungal Extracellular Vesicles with a Focus on Proteomic Analysis
Authors: Bleackley Mark R. , Dawson Charlotte S. , Anderson Marilyn A.
Published: March 2019

Extracellular vesicles (EVs) perform crucial functions in cell–cell communication. The packaging of biomolecules into membrane‐enveloped vesicles prior to release into the extracellular environment provides a mechanism for coordinated delivery of multiple signals at high concentrations that is not achievable by classical secretion alone. Most of the understanding of the biosynthesis, composition, and function of EVs comes from mammalian systems. Investigation of fungal EVs, particularly those released by pathogenic yeast species, has revealed diverse cargo including proteins, lipids, nucleic acids, carbohydrates, and small molecules. Fungal EVs are proposed to function in a variety of biological processes including virulence and cell wall homeostasis with a focus on host–pathogen interactions. EVs also carry signals between fungal cells allowing for a coordinated attack on a host during infection. Research on fungal EVs in still in its infancy. Here a review of the literature thus far with a focus on proteomic analysis is provided with respect to techniques, results, and prospects.