bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of OATP transporter‐mediated drug–drug interaction using physiologically‐based pharmacokinetic (PBPK) modeling – a case example
Authors: Chen Yuan , Zhu Rui , Ma Fang , Mao Jialin , Chen Eugene C. , Choo Edna F. , Sahasranaman Srikumar , Liu Lichuan
Published: October 2018

GDC‐0810 was under development as an oral anti‐cancer drug for the treatment of estrogen receptor‐positive breast cancer as a single agent or in combination. In vitro data indicated that GDC‐0810 is a potent inhibitor of OATP1B1/1B3. To assess clinical risk, a PBPK model was developed to predict the transporter drug–drug interaction (tDDI) between GDC‐0810 and pravastatin in human. The PBPK model was constructed in Simcyp® by integrating in vitro and in vivo data for GDC‐0810. The prediction of human pharmacokinetics (PK) was verified using GDC‐0810 phase I clinical PK data. The Simcyp transporter DDI model was verified using known OATP1B1/1B3 inhibitors (rifampicin, cyclosporine and gemfibrozil) and substrate (pravastatin), prior to using the model to predict GDC‐0810 tDDI. The effect of GDC‐0810 on pravastatin PK was then predicted based on the proposed clinical scenarios. Sensitivity analysis was conducted on the parameters with uncertainty. The developed PBPK model described the PK profile of GDC‐0810 reasonably well. In the tDDI verification, the model reasonably predicted pravastatin tDDI caused by rifampicin and gemfibrozil OATP1B1/3 inhibition but under‐predicted tDDI caused by cyclosporine. The effect of GDC‐0810 on pravastatin PK was predicted to be low to moderate (pravastatin Cmax ratios 1.01–2.05 and AUC ratio 1.04–2.23). The observed tDDI (Cmax ratio 1.20 and AUC ratio 1.41) was within the range of the predicted values. This work demonstrates an approach using a PBPK model to prospectively assess tDDI caused by a new chemical entity as an OATP1B1/3 uptake transporter inhibitor to assess clinical risk and to support development strategy.
The effect of emotional analysis on the improvement of experimental e‐learning systems
Authors: Khalfallah Jihen , Ben Hadj Slama Jaleleddine
Published: October 2018

E‐learning, also known as online learning or technology enhanced learning, needs to provide more heterogeneous learning including not only Web‐based courses and virtual classrooms but also remote labs with an affective recognition system. These latter allow students to interact with real experiments conducted from a distance with real‐time facial expression recognition using a webcam. However, multiple systems do not include this kind of learning. Thus, students' motivation, interest, and learning might be negatively affected since there can be no emotional interaction without “on demand” learning. This work analyzes the impact of students' emotions to enhance the learning experience in two aspects: (i) filling the existing gaps of students and (ii) improving the usability and readability of the platform. The overall goal of our research is to build a novel intelligent tutoring system, called “LabTutor,” adapted to the profile of every student. It aims to serve as an experienced teacher for students who access and perform experiments on real laboratory equipment in the field of engineering education.
Rubipodanin B, a New Cytotoxic Cyclopeptide from Rubia podantha
Authors: Hu Yan‐Yun , Feng Li , Wang Jia , Zhang Xue‐Jia , Wang Zhe , Tan Ning‐Hua
Published: October 2018

Using the TLC cyclopeptide protosite detection method, a new cyclohexapeptide named rubipodanin B (1), together with 11 known Rubiaceae‐type cyclopeptides (RAs), RA‐X‐OMe (2), RA‐IV (3), RA‐XI (4), RA‐XIII‐OMe (5), rubiyunnanin C (6), RA‐I (7), RA‐III (8), RA‐V (9), RA‐VII (10), RA‐XII (11) and rubipodanin A (12), were obtained from the roots and rhizomes of Rubia podantha Diels. The structures were determined using various spectroscopic methods. Among them, 2 was firstly identified as a natural product, and 3–6 were firstly isolated from this species. Cytotoxicity and NF‐κB signaling pathway activity of 1, 2, 4, 6, 7 and 9 were evaluated. All these compounds showed cytotoxic activities against three human tumor cell lines, MDA‐MB‐231, SW620 and HepG2, with the IC50 values between 0.015 and 10.27 μm, and only 7 and 9 possessed NF‐κB inhibitory activities with the IC50 values of 2.42 and 0.046 μm, respectively, which demonstrated that 2‐alanine amino acid plays a key role to maintain the RAs bioactivity.
Producing Fatty Acid Methyl Esters from Free Fatty Acids with Ionic Liquids as Catalyst
Authors: Yang Fangxia , Zhang Junhua , Guo Yingjie , Feng Lele , Wei Shijun , Chen Shuai
Published: October 2018

Three Brønsted acidic imidazole dicationic ionic liquids (ILs) with different length of alkyl chains, [Cn(Mim)2][HSO4]2 (n = 3, 6, 12), were prepared and used as catalyst for the esterification reaction of free fatty acids and methanol. Taking oleic acid as model acid, the catalytic performances of the synthesized ILs for the esterification were evaluated. The main physicochemical properties of the ILs, thermal stability, acidity, solubility in common solvents, and causticity on Austenitic stainless steel 316, were examined. [C3(Mim)2][HSO4]2 demonstrated the highest catalytic activity and enabled to assess the preliminary optimum esterification condition of oleic acid and methanol. Under optimized reaction conditions, the yield of oleic acid methyl ester was up to 95 %. The ILs have great potential as catalysts for producing fatty acid methyl esters from long‐chain free fatty acids.
Optimization and Exergy Analysis of Natural Gas Liquid Recovery Processes for the Maximization of Plant Profits
Authors: Hu Haili , Jiang Hong , Jing Jiaqiang , Pu Hongyu , Tan Jiatong , Leng Nanjiang
Published: October 2018

Maximizing the profits of natural gas liquid recovery plants is a challenge. To improve the performance of an existing plant, three process schemes were compared and analyzed with Aspen HYSYS. A high‐pressure absorber (HPA) performed better owing to the added compressor and more reasonable cold energy utilization. The HPA was further optimized by establishing an objective function and identifying and adjusting the main variables on the basis of a new optimization algorithm. The propane recovery of the optimized HPA was 98.8 %, and the plant profitability increased by 3352 million $ a−1. Exergy analysis of the optimum process indicated that the column and air cooler contributed the most to the total exergy destruction. Suggestions for decreasing the exergy destruction of the process are also given.
Fault detection method based on principal component difference associated with DPCA
Authors: Zhang Cheng , Guo Qingxiu , Li Yuan
Published: October 2018

Aiming at the fault detection in a dynamic process with nonlinear or multimodal features, a new fault detection strategy based on principal component difference associated with dynamic PCA (Diff‐DPCA) is proposed in this paper. First, augment the training data set using the time lag, and then obtain an augmented training data set. Second, find the K‐nearest neighbor set of each sample in the augmented training set and calculate the mean of the K nearest neighbor set. Third, calculate the loading and score matrices of the augmented training data set using PCA, and then calculate the scores of the proposed mean above using the loading matrix. Next, calculate the difference between the scores of a sample and its corresponding mean. Finally, 2 new statistics are built in difference subspace and residual subspace respectively. Principal component difference associated with dynamic PCA, which inherit the ability of DPCA monitoring a dynamic process, can improve the fault detection rate in the process with multimodal or nonlinear characteristics; meanwhile, the new statistics present low autocorrelation levels. The proposed method in this paper and other traditional methods are applied to detect faults in 2 cases and the Tennessee Eastman process, such as PCA, DPCA, and FD‐KNN. The experimental results indicate that the proposed method outperforms the conventional PCA, DPCA, and FD‐KNN.
Synthesis and Characterization of Liquid‐Crystalline Tetraoxapentacene Derivatives Exhibiting Aggregation‐Induced Emission
Authors: Hiscock Lana K. , Raycraft Brooke M. , Wałęsa‐Chorab Monika , Cambe Coralie , Malinge Alexandre , Skene W. G. , Taing Hi , Eichhorn S. Holger , Dawe Louise N. , Maly Kenneth E.
Published: October 2018

A series of new tetrakis(dialkoxyphenyl) dicyanotetraoxapentacene derivatives (1 a–c) were prepared by reaction of the appropriate terphenyl diols with tetrafluoroterephthalonitrile in good yields. Compounds 1 b and 1 c, which bear hexyloxy and decyloxy side chains, exhibited columnar hexagonal mesophases, as shown by polarized optical microscopy, variable‐temperature powder X‐ray diffraction, and differential scanning calorimetry. Single‐crystal X‐ray diffraction of methoxy‐substituted 1 a revealed that the dicyanotetraoxapentacene core is highly planar, consistent with the notion that these molecules are able to stack in columnar mesophases. A detailed photophysical characterization showed that these compounds exhibit aggregation‐induced emission in solution, emission in nonpolar solvents, weak emission in polar solvents, and strong emission in the solid state both as powder and in thin films. These observations are consistent with a weakly emissive charge‐transfer state in polar solvents and a more highly emissive locally excited state in nonpolar solvents.
Hydrothermal Dissolution of Low‐Quartz in Sodium Hydroxide Lyes: Kinetics and Equilibrium
Authors: Pfeiffer Thomas , Sander Stephan A. H. , Enke Dirk , Roggendorf Hans
Published: October 2018

Quartz flours were dissolved at temperatures between 100 and 220 °C for up to 7 d in NaOH lyes. The starting materials were characterized by particle size analysis. Liquid and solid reaction products were characterized chemically and structurally. Sodium water glasses with silica concentrations of up to 20 wt % were obtained. Radius reduction of size distributed particle ensembles was calculated to evaluate the concentration control of the dissolution rate which is due to saturation effects. An equilibrium between low‐quartz and the resulting water glass explains the obtained results.
Evolutionary Prediction of Biohydrogen Production by Dark Fermentation
Authors: Akhbari Azam , Ibrahim Shaliza , Zinatizadeh Ali A. , Bonakdari Hossein , Ebtehaj Isa , S. Khozani Zohre , Vafaeifard Mohsen , Gharabaghi Bahram
Published: October 2018

The present work is a study of the performance and effect of operational parameters on biohydrogen production from palm oil mill effluent by dark fermentation in batch mode. The process parameters examined are pH (5, 5.5, and 6), temperature (30, 35, and 40 °C), substrate concentration (5000, 12 500, and 20 000 mg L−1) and inoculum volume (20, 25, and 30 mL). The inoculum concentration prepared was 10 000 mg L−1 volatile suspended solids. The experiments were designed by response surface methodology (RSM). The highest chemical oxygen demand (COD) removal, hydrogen percentage (H2%) and hydrogen yield (HY) obtained were 58.3%, 80%, and 4.83 mol H2/mole of COD consumed, respectively. Based on the experimental data obtained with the RSM design, gene expression programming (GEP) was developed to predict the COD removal, hydrogen production, and hydrogen yield as process responses. The projected models were assessed based on the correlation coefficient (R2), root mean square error, mean absolute relative error, scatter index, and BIAS. The results demonstrate that the GEP model outperformed the RSM model and was superior in predicting the response variables. Partial derivative sensitivity analysis was also employed to assess the effect of each variable on COD%, H2%, and HY prediction. The prediction uncertainty for COD%, H2%, and HY was quantified, and the results were ±0.11, ±0.17, and 0.015, respectively. According to the results, the GEP model is more efficient than the RSM model in predicting the experimental data for biological hydrogen production in the dark fermentation process.
Phenotypic Prioritization of Diphyllin Derivatives That Block Filoviral Cell Entry by Vacuolar (H+)‐ATPase Inhibition
Authors: Lindstrom Aaron , Anantpadma Manu , Baker Logan , Raghavendra N. M. , Davey Robert , Davisson Vincent Jo
Published: October 2018

Many viruses use endosomal pathways to gain entry into cells and propagate infection. Sensing of endosomal acidification is a trigger for the release of many virus cores into the cell cytosol. Previous efforts with inhibitors of vacuolar ATPase have been shown to block endosomal acidification and affect viral entry, albeit with limited potential for therapeutic selectivity. In this study, four novel series of derivatives of the vacuolar ATPase inhibitor diphyllin were synthesized to assess their potential for enhancing potency and anti‐filoviral activity over cytotoxicity. Derivatives that suitably blocked cellular entry of Ebola pseudotyped virus were further evaluated as inhibitors of endosomal acidification and isolated human vacuolar ATPase activity. Several compounds with significant increases in potency over diphyllin in these assays also separated from cytotoxic doses in human cell models by >100‐fold. Finally, three derivatives were shown to be inhibitors of replication‐competent Ebola viral entry into primary macrophages with similar potencies and enhanced selectivity toward antiviral activity.
In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors
Authors: Eubanks Amber L. , Perkins Marisha M. , Sylvester Kayla , Ganley Jack G. , Posfai Dora , Sanschargrin Paul C. , Hong Jiyong , Sliz Piotr , Derbyshire Emily R.
Published: October 2018

An in silico screen of 350 000 commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind to the Plasmodium falciparum protein kinase 5 (PfPK5) ATP‐binding site. PfPK5 is a cyclin‐dependent kinase‐like protein with high sequence similarity to human cyclin‐dependent kinase 2 (HsCDK2), but its precise role in cell‐cycle regulation remains unclear. After two‐dimensional fingerprinting of the top scoring compounds, 182 candidates were prioritized for biochemical testing based on their structural diversity. Evaluation of these compounds demonstrated that 135 bound to PfPK5 to a similar degree or better than known PfPK5 inhibitors, confirming that the library was enriched with PfPK5‐binding compounds. A previously reported triazolodiamine HsCDK2 inhibitor and the screening hit 4‐methylumbelliferone were each selected for an analogue study. The results of this study highlight the difficult balance between optimization of PfPK5 affinity and binding selectivity for PfPK5 over its closest human homologue HsCDK2. Our approach enabled the discovery of several new PfPK5‐binding compounds from a modest screening campaign and revealed the first scaffold to have improved PfPK5/HsCDK2 selectivity. These steps are critical for the development of PfPK5‐targeting probes for functional studies and antimalarials with decreased risks of host toxicity.
Suicide risk among cancer survivors: Head and neck versus other cancers
Authors: Osazuwa‐Peters Nosayaba , Simpson Matthew C. , Zhao Longwen , Boakye Eric Adjei , Olomukoro Stephanie I. , Deshields Teresa , Loux Travis M. , Varvares Mark A. , Schootman Mario
Published: October 2018

Background

Cancer survivors face psychosocial issues that increase their risk of suicide. This study examined the risk of suicide across cancer sites, with a focus on survivors of head and neck cancer (HNC).

Methods

The Surveillance, Epidemiology, and End Results 18‐registry database (from 2000 to 2014) was queried for the top 20 cancer sites in the database, including HNC. The outcome of interest was suicide as a cause of death. The mortality rate from suicide was estimated for HNC sites and was compared with rates for 19 other cancer sites that were included in the study. Poisson regression was used to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for 1) HNC versus non‐HNC sites (the other 19 cancer sites combined), and 2) HNC versus each individual cancer site. Models were stratified by sex, controlling for race, marital status, age, year, and stage at diagnosis.

Results

There were 404 suicides among 151,167 HNC survivors from 2000 to 2014, yielding a suicide rate of 63.4 suicides per 100,000 person‐years. In this timeframe, there were 4493 suicides observed among 4219,097 cancer survivors in the study sample, yielding an incidence rate of 23.6 suicides per 100,000 person‐years. Compared with survivors of other cancers, survivors of HNC were almost 2 times more likely to die from suicide (aRR, 1.97; 95% CI, 1.77‐2.19). There was a 27% increase in the risk of suicide among HNC survivors during the period from 2010 to 2014 (aRR, 1.27; 95% CI, 1.16‐1.38) compared with the period from 2000 to 2004.

Conclusions

Although survival rates in cancer have improved because of improved treatments, the risk of death by suicide remains a problem for cancer survivors, particularly those with HNC.
Obtaining a Genetic Family History Using Computer‐Based Tools
Authors: Li Weilong , Murray Michael F. , Giovanni Monica A.
Published: October 2018

Family health history has long been known to be a powerful predictor of individual disease risk. It can be obtained prior to DNA sequencing in order to examine inheritance patterns, to be used as a proxy for genetic information, or as a tool to guide decision‐making on the utility of diagnostic genetic testing. Increasingly, it is also being obtained retrospectively from sequenced individuals to examine familial disease penetrance and to identify at‐risk relatives for cascade testing. The collection of adequate family history information to screen patients for disease risk and guide decision‐making is a time‐consuming process that is difficult to accomplish exclusively through discussion between patients and their providers. Engaging individuals and families in data collection and data entry has the potential to improve data accuracy through re‐iterative review with family members and health care providers, and to empower patients in their healthcare. In addition, electronic datasets can be shared amongst relatives and stored in electronic health records or personal files, enabling portability of family history information. The U.S. Surgeon General, the Centers for Disease Control and Prevention (CDC), and others have developed tools for electronic family history collection to help families and providers obtain this useful information in an efficient manner. This unit describes the utility of the web‐based My Family Health Portrait (https://familyhistory.hhs.gov) as the prototype for patient‐entered family history. © 2018 by John Wiley & Sons, Inc.
Photochromic Ionic Liquids Containing Cationic Spiropyran Derivatives
Authors: Funasako Yusuke , Okada Hirochika , Inokuchi Makoto
Published: October 2018

Ionic liquids containing photochromic spiropyran derivatives have been synthesized. The salts with octyl functional groups are viscous liquids at room temperature and exhibit drastic color changes between yellow and purple when irradiated with UV and visible light. The salts with butyl and methyl functional groups are solids with no photochromic properties.
Perceived oral health in patients after bariatric surgery using oral health‐related quality of life measures
Authors: Karlsson Lena , Carlsson Johanna , Jenneborg Kristina , Kjaeldgaard Marianne
Published: October 2018

Obesity is an increasing problem of the 21st century. A frequent intervention is bariatric surgery. The impact of bariatric surgery on oral health is largely unknown. The aim of the present case–control study was to survey the perceived oral health amongst individuals that had undergone bariatric surgery and compare the measures with two cohorts consisting of healthy individuals with respectively at or below versus above a body mass index score of 30. Study volunteers were recruited from interest group on the Internet. The study participants completed online a validated oral health‐related quality of life scale, that is, OHIP‐S. The three cohorts consisted of individuals that had undergone bariatric surgery (OS, n = 77) and the healthy obese (ONS, n = 45) and nonobese individuals (HNS, n = 71). Nonparametric Kruskal–Wallis rank sum tests were used to estimate likelihood of nondifference amongst the three cohorts. Individuals that had undergone bariatric surgery reported significant more oral health problems than the study participants in with the two other cohorts. Their perception of oral health‐related quality of life was higher or similar to the obese study participants and lower than for nonobese study participants. Perceived oral health problems appear to be more frequent amongst individuals that have undergone bariatric surgery in comparison with healthy obese and nonobese individuals. Bariatric surgery may be consider a risk marker for impaired oral health.
Immunophenotypic Profile of CD34+ Subpopulations and Their Role in the Diagnosis and Prognosis of Patients with De‐Novo, Particularly Low‐Grade Myelodysplastic Syndromes
Authors: Gardikas Nikolaos , Vikentiou Myrofora , Konsta Evgenia , Kontos Christos K. , Papageorgiou Sotirios G. , Spathis Aris , Bazani Efthimia , Bouchla Anthi , Kapsimali Violetta , Psarra Katherina , Foukas Periklis , Dimitriadis George , Pappa Vasiliki
Published: October 2018

Background

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders with unknown aetiology. Multiparameter flow cytometry (MFC) is being evaluated for the diagnosis and prognosis of MDS.

Methods

In the present study, five‐color MFC was performed on bone marrow aspirates of 50 untreated patients, newly diagnosed with MDS and 27 age matched control samples. Patients were classified according to World Health Organization 2016, International Prognostic Scoring System (IPSS), and Revised IPSS (IPSS‐R).

Results

Significantly higher CD133+/CD90‐CD45weak, CD117+/TdT‐CD45weak, and CD33+/MPO‐neutrophil precursor percentages on CD34+ cells, as well as a significant decrease of lymphoid and erythroid precursors were observed in the group of MDS patients in comparison to controls. A new scoring system was based on these findings, which can be helpful in discriminating lower risk MDS patients, including those with normal karyotype (a subgroup of MDS with diagnostic challenges). In addition, an increased level of apoptosis of CD34+/CD117+ cells was identified as an independent favorable prognostic factor both for the risk of transformation to acute myeloid leukemia and for overall survival.

Conclusions

A new scoring system based on the expression of immature cell antigens on CD34+ cells (by itself or in combination with the Ogata score) can discriminate lower risk MDS patients, including those with normal karyotype, from the normal control group. © 2018 International Clinical Cytometry Society
Swarm intelligence‐based radio resource management for V2V‐based D2D communication
Authors: Feki Souhir , Masmoudi Ahlem , Belghith Aymen , Zarai Faouzi , Obaidat Mohammad S.
Published: October 2018

Internet of Things is a promising paradigm that provides the future network of interconnected devices. Device‐to‐Device (D2D) communication, which is considered as an enabler for vehicle‐to‐everything applications, has become an emerging technology to optimize network performance. In this paper, we study the Radio Resource Management (RRM) issue for D2D‐based Vehicle‐to‐Vehicle communication. The RRM key role is to assure the proficient exploitation of available resources while serving users according to their quality of service parameters. An Ant Colony Optimization (ACO)‐based Resource Allocation (ACORA) scheme is proposed in this paper. Swarm intelligence algorithm ACO is adopted to reduce the computational complexity while realizing satisfactory performance. Simulation results show promising performance of our proposed ACORA scheme.
Plasticity in nesting adaptations of a tidal marsh endemic bird
Authors: Benvenuti Bri , Walsh Jennifer , O'Brien Kathleen M. , Kovach Adrienne I.
Published: October 2018

If individuals can perceive and manage risks, they may alter their behaviors based on prior experience. This expectation may apply to nest site selection of breeding birds, for which adaptive behavioral responses may enhance fitness. Birds that nest in tidal marshes have adapted to the challenges posed primarily by periodic, monthly tidal flooding and secondarily by predation. We investigated adaptive responses in nesting behavior of the saltmarsh sparrow (Ammospiza caudacutus), an obligate tidal‐marsh‐breeding bird, using 536 nests monitored across 5 years. Using linear mixed effects models, we tested whether nest characteristics differed among nests that were successful, depredated, or flooded, and we investigated whether females made changes in nest structure and placement according to outcome of their previous nesting attempt. Nest characteristics differed among females with different nest fates. Fledged and depredated nests were built higher in the vegetation and in higher elevation areas of the marsh than those that flooded. Successful nests had more canopy cover and were comprised of a lower proportion of high marsh vegetation (Spartina patens) than those that were flooded or depredated. Females with nests that failed due to flooding constructed subsequent nests higher in the vegetation and at higher elevation than those that were successful in their prior attempt, consistent with a response to previous experience. Eighty‐five percent of females renested within the average home range core area distance (77 m), indicating a high degree of nest placement fidelity. Females for which nests were depredated in their prior nesting attempt renested at a greater distance than females for which the previous nesting attempts were successful. Our findings suggest saltmarsh sparrows exhibit plasticity in nesting behavior, which may be important for balancing selective pressures in a dynamic environment. This plasticity, however, is insufficient to enable them to adapt to the increased flooding predicted with sea‐level rise.
Forest disturbance and arthropods: Small‐scale canopy gaps drive invertebrate community structure and composition
Authors: Perry Kayla I. , Wallin Kimberly F. , Wenzel John W. , Herms Daniel A.
Published: October 2018

In forest ecosystems, disturbances that cause tree mortality create canopy gaps, increase growth of understory vegetation, and alter the abiotic environment. These impacts may have interacting effects on populations of ground‐dwelling invertebrates that regulate ecological processes such as decomposition and nutrient cycling. A manipulative experiment was designed to decouple effects of simultaneous disturbances to the forest canopy and ground‐level vegetation to understand their individual and combined impacts on ground‐dwelling invertebrate communities. We quantified invertebrate abundance, richness, diversity, and community composition via pitfall traps in response to a factorial combination of two disturbance treatments: canopy gap formation via girdling and understory vegetation removal. Formation of gaps was the primary driver of changes in invertebrate community structure, increasing activity‐abundance and taxonomic richness, while understory removal had smaller effects. Families of Collembola and Diplopoda, as well as some families of Coleoptera, increased in combined canopy and understory disturbance treatments, whereas Curculionidae and Nitidulidae were more abundant in undisturbed forest. Gaps increased light availability, height and cover of understory vegetation, and soil moisture levels, and decreased depth and cover of leaf litter compared to undisturbed forest. Decoupling of canopy and understory vegetation disturbances revealed gap formation as an important short‐term driver of ground‐dwelling invertebrate community structure and composition. Our findings increase understanding of how ground‐dwelling invertebrate communities respond to disturbance and inform sustainable management of forest ecosystems to foster biodiversity and resilience.
Aluminum Complexes of Octahydrophenanthroline‐Based Salophan Ligands: Coordination Chemistry and Activity in the Ring‐Opening Polymerization of Lactide
Authors: Rosen Tomer , Goldberg Israel , Kol Moshe
Published: October 2018

Salophan ligands featuring the octahydrophenanthroline core are described for the first time. Two ligand precursors featuring either di‐tert‐butylphenolate or dichlorophenolate were prepared by 1,10‐phenanthroline hydrogenation followed by reaction with bromomethyl‐substituted phenols. The ligand precursors react with AlMe3 to give the [{ONNO}Al‐Me]‐type complexes as single stereoisomers of averaged Cs‐symmetry on the NMR timescale. The reactivity of the methylaluminum complexes depends strongly on the phenolate substituents: The complex of the bulky ligand is inert towards alcohols and inactive in the ring‐opening polymerization of rac‐LA, whereas the complex of the non‐bulky ligand reacts readily with benzyl alcohol to yield the corresponding [{ONNO}Al‐OBn] complex, which polymerizes rac‐LA to give isotactically inclined PLA.
Interfacial Chemistry of Low‐Dimensional Systems for Applications in Nanocatalysis
Authors: Agnoli Stefano
Published: October 2018

Invited for the cover of this issue is Stefano Agnoli from the University of Padova, Italy. The cover image shows hoodoo rock formations in Arizona, illustrating the resulting structures from the interfaces of composite materials.
Transition‐Metal‐Free C(sp3)–S Coupling in Water: Synthesis of Benzyl Dithiocarbamates Using Thiuram Disulfides as an Organosulfur Source
Authors: Peng Han‐Ying , Dong Zhi‐Bing
Published: October 2018

A simple, highly efficient and environmentally benign method for the synthesis of benzyl dithiocarbamates was reported. Without addition of metal catalyst, a series of 34 benzyl dithiocarbamates were obtained in good to excellent yields by treating benzyl halides with tetraalkylthiuram disulfides in water. The protocol allows easy access to C(sp3)–S bond formation, features the advantages of easy performance, environmental friendliness, good to excellent yields, and good functional tolerance, showing potential value for the preparation of some biologically active compounds.
Using a gene expression biomarker to identify DNA damage‐inducing agents in microarray profiles
Authors: Corton J. Christopher , Williams Andrew , Yauk Carole L.
Published: October 2018

High‐throughput transcriptomic technologies are increasingly being used to screen environmental chemicals in vitro to provide mechanistic context for regulatory testing. The TGx‐DDI biomarker is a 64‐gene expression profile generated from testing 28 model chemicals or treatments (13 that cause DNA damage and 15 that do not) in human TK6 cells. While the biomarker is very accurate at predicting DNA damage inducing (DDI) potential using the nearest shrunken centroid method, the broad utility of the biomarker using other computational methods is not fully known. Here, we determined the accuracy of the biomarker used with the Running Fisher test, a nonparametric correlation test. In TK6 cells, the methods could readily differentiate DDI and non‐DDI compounds with balanced accuracies of 87–97%, depending on the threshold for determining DDI positives. The methods identified DDI agents in the metabolically competent hepatocyte cell line HepaRG (accuracy = 90%) but not in HepG2 cells or hepatocytes derived from embryonic stem cells (60 and 80%, respectively). DDI was also accurately classified when the gene expression changes were derived using the nCounter technology (accuracy = 89%). In addition, we found: (1) not all genes contributed equally to the correlations; (2) the minimal overlap in genes between the biomarker and the individual comparisons required for significant positive correlation was 10 genes, but usually was much higher; and (3) different sets of genes in the biomarker can by themselves contribute to the significant correlations. Overall, these results demonstrate the utility of the biomarker to accurately classify DDI agents. Environ. Mol. Mutagen. 59:772–784, 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Therapist adherence and therapeutic alliance in individual cognitive‐behavioural therapy for adolescent binge‐eating disorder
Authors: Puls Hans‐Christian , Schmidt Ricarda , Hilbert Anja
Published: October 2018

To evaluate psychological treatments for adolescent binge‐eating disorder (BED), reliable information on therapeutic process factors is needed. This study examines therapist adherence and therapeutic alliance and their associations in cognitive‐behavioural therapy (CBT) for adolescents with BED. In a randomised‐controlled efficacy trial, adherence and alliance were objectively determined based on 247 audio‐taped CBT sessions from a sample of N = 64 adolescents with BED. Variability of adherence and alliance, explained by treatment module, patient, and therapist were examined using multilevel modeling. Although adherence and alliance were excellent and unaffected by treatment module and therapist, there was significant between‐patient variability for both concepts. Adherence was negatively associated with patient's treatment expectation. Alliance was negatively associated with the number of loss of control eating episodes and positively associated with adherence. Excellent adherence supported the internal validity of CBT for adolescent BED. Associations between process factors and patient characteristics demand adequate supervision in CBT.
Symptoms of disordered eating among adult international adoptees: A population‐based cohort study
Authors: Strand Mattias , von Hausswolff‐Juhlin Yvonne , Fredlund Peeter , Lager Anton
Published: October 2018

Objective

There is a paucity of data on disordered eating among adoptees. The aim of the present study was to explore the prevalence of symptoms of disordered eating and body image concerns among international adoptees in a large representative community survey on health‐related behaviours.

Method

Combining survey data from the Stockholm Public Health Cohort and Swedish population data, adult international adoptees were compared with total participant data to assess differences in disordered eating and body dissatisfaction.

Results

International adoptee women displayed significantly higher levels of self‐induced vomiting, loss‐of‐control eating, food preoccupation, underweight, and wish for thinness compared with nonadoptee women, albeit with small or very small effect sizes. No significant differences were found in terms of mean body mass index, cognitive restraint, or emotional eating.

Conclusion

International adoptee women were disproportionally affected on several measures of disordered eating, although the magnitude of these differences were generally small in absolute terms.
Antifatigue and antiaging effects of Chinese rice wine in mice
Authors: Zhao Pan , Wang Jing , Zhao Wei , Ma Xiaoli , Sun Haiji
Published: October 2018

Chinese rice wine (CRW) is widely known for keeping good health and commonly used in the traditional Chinese medicine prescription guiding drug. This study assesses the effects of CRW on antifatigue and antiaging activities in mice models. Mice were randomly divided into four groups performing with 0.25 ml of distilled water, 0.15, 0.25, and 0.4 ml of CRW for 15 consecutive days. The CRW could obviously increase the content of liver glycogen (LG) and decrease the levels of blood lactic acid (BLA)and blood urea nitrogen (BUN) to improve antifatigue ability. In antiaging assay, CRW significantly increased the activity of SOD in liver, the activities of GSH‐Px and CAT in brain cortex, body quality, thymus index, and spleen index, and decreased liver MDA levels, liver total cholesterol content, and AChE levels in hippocampus. The CRW has potent antifatigue ability and could minimize the occurrence of age‐associated disorders.
Finite sections: A functional analytic perspective on approximation methods
Authors: Lindner Marko , Seifert Christian
Published: October 2018

We review approximation methods and their stability and applicability. We then focus on the finite section method and Galerkin methods and show that on separable Hilbert spaces either one can be interpreted as the other. In the end we demonstrate that well‐known methods such as the finite element method and polynomial chaos expansion are particular examples of the finite section method; their applicability can therefore be studied via the latter.
ComPaSS‐GWAS: A method to reduce type I error in genome‐wide association studies when replication data are not available
Authors: Sabourin Jeremy A. , Cropp Cheryl D. , Sung Heejong , Brody Lawrence C. , Bailey‐Wilson Joan E. , Wilson Alexander F.
Published: October 2018

Results from association studies are traditionally corroborated by replicating the findings in an independent data set. Although replication studies may be comparable for the main trait or phenotype of interest, it is unlikely that secondary phenotypes will be comparable across studies, making replication problematic. Alternatively, there may simply not be a replication sample available because of the nature or frequency of the phenotype. In these situations, an approach based on complementary pairs stability selection for genome‐wide association study (ComPaSS‐GWAS), is proposed as an ad‐hoc alternative to replication. In this method, the sample is randomly split into two conditionally independent halves multiple times (resamples) and a GWAS is performed on each half in each resample. Similar in spirit to testing for association with independent discovery and replication samples, a marker is corroborated if its p‐value is significant in both halves of the resample. Simulation experiments were performed for both nongenetic and genetic models. The type I error rate and power of ComPaSS‐GWAS were determined and compared to the statistical properties of a traditional GWAS. Simulation results show that the type I error rate decreased as the number of resamples increased with only a small reduction in power and that these results were comparable with those from a traditional GWAS. Blood levels of vitamin pyridoxal 5′‐phosphate from the Trinity Student Study (TSS) were used to validate this approach. The results from the validation study were compared to, and were consistent with, those obtained from previously published independent replication data and functional studies.
Managing the cervical spine in multiple myeloma patients
Authors: Cawley Derek T. , Butler Joseph S. , Benton Adam , Altaf Farhaan , Rezajooi Kia , Kyriakou Charalampia , Selvadurai Susanne , Molloy Sean
Published: October 2018

Discuss the relevant literature on surgical and nonsurgical treatments for multiple myeloma (MM) and their complementary effects on overall treatment. Existing surgical algorithms designed for neoplasia of the spine may not suit the management of spinal myeloma. Less than a fifth of metastatic, including myelomatous lesions, occur in the cervical spine but have a poorer prognosis and surgery in this area carries a higher morbidity. With the advances of chemotherapy, early access to radiotherapy, early orthosis management, and high definition imaging, including CT and MRI, surgical indications in MM have changed. Medical decompression (or oncolysis), including in the presence of neurological deficit and orthotic stabilization, are proving viable nonsurgical options to manage MM. A key to decision making is the assessment and monitoring of biomechanical spinal stability as part of a multidisciplinary approach.
Research on heat transfer law of cement clinker accumulation body in grate cooler based on lattice Boltzmann method
Authors: Wen Yan , Ju Yan‐Xu , Yuan Lin
Published: October 2018

In view of the porous media characteristics of the clinker accumulation body in the cement cooler, this paper combined the seepage heat transfer theory with the lattice Boltzmann method (LBM) to analyze the heat transfer of the particle accumulation body. According to the principle of nonmutation of permeability, the minimum feature unit model of cement particles was established, and its heat transfer law was analyzed by LBM. The heat transfer law of the boundary of the feature unit was obtained, and it was used to analyze the heat transfer law of the whole accumulation body by using the double‐loop nesting algorithm. The correctness of this study result was verified by particle heat transfer experiments.
Revealing the nexus between oil and exchange rate in the major emerging markets—The timescale analysis
Authors: Živkov Dejan , Njegić Jovan , Balaban Suzana
Published: October 2018

This paper investigates the interrelationship between Brent oil price and exchange rate in 10 emerging markets of East Europe, Asia, Africa, and South America. For computational purpose, we apply two innovative methodologies—wavelet coherence and phase difference that are capable of observing different frequency scales. Wavelet coherence results suggest that strong coherence is present during world financial crisis (WFC) in the oil‐exporting countries and in majority of the oil‐importing countries. Phase arrows as well as phase difference suggest negative coherence between oil and exchange rates in the oil‐importing countries during WFC. Negative coherence is found in these countries because currency depreciation was accompanied by immense oil price drop in WFC period. In addition, phase difference has relatively stable in‐phase dynamics in long term in the oil‐importing countries during tranquil periods, which confirms theoretical stance that higher oil prices cause currency depreciation and vice versa. As for the oil‐exporting countries, we find constant and relatively long‐lasting anti‐phase pattern in Russian and Nigerian cases for long‐term horizons but not for Brazilian one.
Cost‐minimization analysis in the Indian subcontinent for treating Guillain Barre Syndrome patients with therapeutic plasma exchange as compared to intravenous immunoglobulin
Authors: Maheshwari Ashish , Sharma Ratti R. , Prinja Shankar , Hans Rekha , Modi Manish , Sharma Navneet , Marwaha Neelam
Published: October 2018

Background

Therapeutic Plasma Exchange (TPE) and Intravenous Immunoglobulin both are first‐line treatments for Guillain Barre Syndrome; however, there is a significant difference in cost. We undertook this study to assess the cost minimization for treating Guillain Barre Syndrome patients.

Methods

A prospective randomized controlled trial was undertaken, in which 40 Guillain Barre Syndrome (GBS) patients with a GBS disability score of grade four and five were enrolled. A societal perspective was adopted for the analysis and assessment of both the health system cost and out‐of‐pocket expenditures. Cost‐minimization analysis was undertaken as both the treatments were equally effective at the end of 12 weeks.

Results

No statistically significant differences were observed in the GBS Disability scores during overall treatment course in both treatment groups. The Out‐of‐pocket cost for the immunoglobulin (IVIG) group was INR 219 247 (4298 USD) and for the TPE group was INR 104 070 (2040.5 USD). Overall INR 86 685 ($1700), that is, 53% higher cost was observed in IVIG group without any concomitant health outcome benefit.

Conclusion

In comparison with IVIG, TPE appears to be the better option for treatment of GBS in cost‐constraint countries like ours to provide an economic treatment option to most average people.
Berberrubine and its analog, hydroxypropyl‐berberrubine, regulate LDLR and PCSK9 expression via the ERK signal pathway to exert cholesterol‐lowering effects in human hepatoma HepG2 cells
Authors: Cao Shijie , Xu Peixiang , Yan Jiankun , Liu Hui , Liu Lu , Cheng Lina , Qiu Feng , Kang Ning
Published: October 2018

Berberine (BBR), the major isoquinoline alkaloid in Chinese herb Rhizoma coptidis, has significant lipid‐lowering effect by upregulating hepatic low‐density lipoprotein receptor (LDLR) expression. In a previous study, we have indicated that berberrubine (M3), a major metabolite of BBR in vivo, displays the most potential hypolipidemic effects via upregulating LDLR expression in human hepatoma (HepG2) cells compared with BBR and 3 other metabolites. Accordingly, 9 M3 analogs (A1‐A9) were modified at the C9 position. We aimed to find a new promising agent by evaluating the cholesterol‐lowering effect and clarifying the related molecular mechanism. In the current study, the cellular cholesterol content was assayed with a commercial cholesterol assay kit. Real‐time polymerase chain reaction and Western blot assay were used to explore the molecular mechanism of M3 and its analogs on the hypolipidemic effect. Among M3 and its analogs, hydroxypropyl‐berberrubine (A8) exhibited the highest potential effects on the upregulation of LDLR expression, which was accompanied by a steady decline of proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA and protein levels. Furthermore, inhibition of extracellular signal‐regulated kinase (ERK) activity with PD98059 prevented the upregulation of LDLR and downregulation of PCSK9 induced by A8. The current study revealed that M3 and its structurally modified analog, A8, could regulate hepatic LDLR and PCSK9 expression to exert lipid‐lowering effects via the ERK signal pathway, while A8 showed a stronger effect and might be a promising drug candidate against hyperlipidemia.
Molecular and disease association of gestational diabetes mellitus affected mother and placental datasets reveal a strong link between insulin growth factor (IGF) genes in amino acid transport pathway: A network biology approach
Authors: Rout Madhusmita , Lulu S Sajitha
Published: October 2018

Discerning the relationship between molecules involved in diseases based on their underlying biological mechanisms is one of the greatest challenges in therapeutic development today. Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, which adversely affects both mothers and offspring during and after pregnancy. We have constructed two datasets of (GDM associated genes from affected mother and placenta to systematically analyze and evaluate their interactions like gene–gene, gene–protein, gene–microRNA (miRNA), gene–transcription factors, and gene‐associated diseases to enhance our current knowledge, which may lead to further advancements in disease diagnosis, prognosis, and treatment. The results identify the key genes with respect to maternal dataset as insulin receptor, insulin (INS), leptin (LEP), glucokinase, and hepatocyte nuclear factor 1 alpha, whereas from placenta include insulin‐like growth factor 1, growth hormone receptor, and breast cancer anti‐estrogen resistance protein 1, which are found to be highly enriched in pancreas, ovary, adipocyte, heart, and placental tissues. The key transcription factors include Sp1 transcription factor, pancreatic and duodenal homeobox 1, and hepatocyte nuclear factor 4 alpha, whereas miRNA includes has‐miR‐5699‐5p and has‐miR‐3158‐3p. The study also reveals that GDM has associations with diseases like type I and II diabetes mellitus, obesity, and preeclampsia. More significantly, we could trace out a significant connection between the key molecules like LEP and placental growth hormone from mother and placental dataset, which plays a critical role in INS secretion, INS signaling, and β‐cell dysfunction pathways.