bluuebunny/crossref_metadata_2025 huggingface dataset:
Solid Superbase‐Catalyzed Stereoselective 1,4‐Addition Reactions of Simple Amides in Batch and Continuous‐Flow Systems
Authors: Borah Parijat , Yamashita Yasuhiro , Kobayashi Shū
Published: June 2019

The utilization of a catalytic solid superbase in fine synthesis is challenging. Here, we employed K/γ‐Al2O3 catalytically as a highly efficient solid superbase to perform direct 1,4‐addition reactions of simple amides with α,β‐unsaturated carbonyls. The desired 1,5‐dicarbonyl compounds were obtained in high yields with excellent anti‐diastereoselectivities. K/γ‐Al2O3 showed a Hammett basicity of 37>H_≥35. The solid base was characterized by using TGA‐DTA, 27Al solid‐state NMR spectroscopy, and XPS to determine the origin of the superbasicity. Continuous‐flow synthesis of a 1,5‐dicarbonyl compound was demonstrated by using the novel solid superbase‐catalyzed 1,4‐addition methodology. We have also uncovered the potential of K/γ‐Al2O3 in asymmetric 1,4‐addition reactions.

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Synthesis of β‐Isoxazole Carbonyl Derivatives and their Analogues via Palladium‐Catalyzed Sequential C(sp2)−O/C(sp2)−C(sp3) Bond Formations
Authors: Wu Wanqing , Li Can , Zhou Fei , Li Jianxiao , Xu Xiaoqing , Jiang Huanfeng
Published: June 2019

An efficient Pd(II)‐catalyzed one‐pot tandem cyclization/alkylation reaction of internal alkynes has been reported. In this reaction, a wide range of structurally diverse β/;‐isoxazole aldehydes/ketones could be obtained in good to excellent yields from various alkynyl oxime ethers and allylic or homoallylic alcohols. The gram‐scale experiment and various transformations of the newly obtained products demonstrated that this method should be a general and useful synthetic tool.

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Asymmetric Vinylogous Mukaiyama‐Mannich Reactions of Heterocyclic Siloxy Dienes with Ellman's Fluorinated Aldimines
Authors: Fustero Santos , Rodenes Miriam , Román Raquel , Sedgwick Daniel M. , Aguado José Enrique , Soloshonok Vadim A. , Han Jianlin , Mei Haibo , Medio‐Simon Mercedes , Barrio Pablo
Published: June 2019

Vinylogous Mukaiyama Mannich reactions of furan and pyrrole based dienoxy silanes with α‐fluoroalkyl sulfinyl imines provide a powerful synthetic access to a variety of amino fluoroalkyl γ‐butenolide‐type and butyrolactam frameworks with high regio‐ and diastereoselectivity. Anti‐configured adducts were obtained in all cases, independent of the nature of the heteroatom (O or N) present in the dienoxy silane. The absolute configuration of the adducts prepared was unequivocally established by X‐ray crystallographic analysis. It is noteworthy that the introduction of substituents at the γ‐position of the heterocyclic partner allows the generation of adducts bearing chiral quaternary centers.

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Synthesis of (Difluoromethyl)cycloalkenes from 2‐Cycloalkenones by Utilizing Phospha‐Brook Rearrangement
Authors: Yamamoto Yoshihiko , Ishida Yuki , Takamizu Yosuke , Yasui Takeshi
Published: June 2019

Difluoromethyl‐substituted allylic phosphates were synthesized from 2‐cycloalkenones through the addition of a (difluoromethyl)phosphonate and subsequent phospha‐Brook rearrangement. The obtained allylic phosphates were converted to the corresponding difluoromethyl‐substituted cycloalkenes using the Cu‐mediated SN2’ reaction of Grignard or organolithium reagents.

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Oxidative Fluorination of Cu/ZnO Methanol Catalysts
Authors: Dybbert Valentin , Fehr Samuel Matthias , Klein Florian , Schaadt Achim , Hoffmann Anke , Frei Elias , Erdem Emre , Ludwig Thilo , Hillebrecht Harald , Krossing Ingo
Published: June 2019

The influence of a mild difluorine treatment on Cu/ZnO precatalysts for methanol synthesis was investigated. It led to the incorporation of 1.2…1.3±0.1 wt % fluoride into the material. Fluorination considerably increased the amount of ZnOx related defect sites on the catalysts and significantly increased the space‐time yields. Although the apparent activation energy EA,app for methanol formation from CO2 and H2 was almost unchanged, the EA,app for the reverse water‐gas shift (rWGS) reaction increased considerably. Overall, fluorination led to a significant gain in methanol selectivity and productivity. Apparently, also the quantity of active sites increased.
Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy
Authors: Kim Jae Hyun , Kim Illan , Song Yeonghun , Kim Min Jung , Kim Sanghee
Published: June 2019

The total synthesis of (+)‐neooxazolomycin was achieved from the amino‐acid d‐serine. The efficiency of this approach is derived from the use of principles of memory of chirality and dynamic kinetic resolution in the intramolecular aldol reaction of a serine derivative to build the densely functionalized lactam framework and to install three contiguous stereocenters. The key intermediate was readily elaborated to the target natural product.
Radical‐Promoted C−C Bond Cleavage: A Deconstructive Approach for Selective Functionalization
Authors: Morcillo Sara P.
Published: June 2019

Just as “Deconstructivism” appeared as a novel movement in architecture in the 1980s, deconstructive approaches have recently emerged as excellent strategies for scaffold hopping modifications in chemistry. The deconstruction and functionalization of cyclic molecules mainly involves the cleavage of the carbon–carbon (C−C) bond followed by the construction of new bonds. The cleavage of inert C−C single bonds, especially in unstrained cycles, and their subsequent functionalization is still one of the most sought‐after challenges in chemistry. In this vein, radical‐mediated strategies provide an excellent approach for achieving this aim. This minireview is an outline of the history of homolytic cleavage and highlights the recent advances in exploring new chemical space by deconstructive functionalization.
A de novo formulation of metformin using chitosan‐based nanomicelles for potential diabetes therapy
Authors: Abbasian Mojtaba , Bighlari Parvaneh , Mahmoodzadeh Farideh , Acar Metin Hayri , Jaymand Mehdi
Published: June 2019

A de novo formulation of metformin (MET) was developed through the physical loading of drug into a chitosan‐grafted‐[poly(acryl amide)‐block‐poly(acrylic acid)] [CS‐g‐(PAAm‐b‐PAA)] terpolymer. For this purpose, CS was functionazed with phthalic anhydride followed by 4‐cyano, 4‐[(phenylcarbothioyl)sulfanyl]pentanoic acid to produc a macro‐RAFT agent (CS‐CTA). Afterward, acryl amide and acrylic acid monomers were graft and block copolymerized onto the synthesized CS‐CTA through a reversible addition–fragmentation chain transfer (RAFT) polymerization technique to afford CS‐g‐PAAm copolymer and CS‐g‐(PAAm‐b‐PAA) terpolymer, respectively. The fabricated CS‐g‐(PAAm‐b‐PAA) terpolymer was loaded with MET as an anti‐diabetic drug, and its drug release behavior was evaluated in the body simulated environment. As results, it was concluded that the fabricated CS‐g‐(PAAm‐b‐PAA) nanosystem has high potential as de novo drug delivery system (DDS) for diabetes therapy, mainly due to controlled drug release profile in comparison with conventional formulations of MET. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48037.
Computational Insights into Mg‐Cl Complex Electrolytes for Rechargeable Magnesium Batteries
Authors: Moss Jared B. , Zhang Liping , Nielson Kevin V. , Bi Yujing , Wu Chao , Scheiner Steve , Liu T. Leo
Published: June 2019

DFT calculations were conducted to provide unprecedented thermodynamic insights on tetrahydrofuran (THF) solvation, isomerization, and complexation of possible Mg−Cl coordination species for popular Mg−Cl electrolytes for magnesium batteries. Computational results using the M06‐2x functional with the 6‐31+G(d) basis set indicate that trigonal bipyramidal e,e‐cis‐tbp‐MgCl2(THF)3 dichloride species and octahedral [MgCl(THF)5]+ monochloride species are the dominant mononuclear species. These two can combine to form the dinuclear species [(μ‐Cl)3Mg2(THF)6]+ with a free energy −6.30 kcal/mol, which is calculated to be the dominant Mg−Cl species in solution. Two mono‐cation species, [(μ‐Cl)3Mg2(THF)6]+ and [MgCl(THF)5]+, have comparable LUMO energies, thus both of them can act as active species for Mg deposition. However, the significant dominance of the dinuclear species in the electrolyte indicates that it is the primary species involved in reversible Mg deposition.
Application of a self‐management intervention to improve data recording of educational care providers
Authors: Gerald Deanna , Keeler Laura , Mackey Kaitlin , Merrill Rebecca , Luiselli James K.
Published: June 2019

The present study evaluated the effects of a self‐management intervention on scheduled data recording by classroom instructors at a school for children with intellectual disability and neurodevelopmental disorders. In a multiple baseline design across two classrooms, the instructors recorded student data according to an established protocol at the school and based on earlier training they had received. During intervention, the instructors self‐monitored implementation of data recording procedures that were prompted by a signal from an automated count‐down timer. The self‐management intervention increased scheduled data recording by participants in both classrooms to 90–100%, and these results were maintained at 1‐ and 2‐month follow‐up assessments. These findings add to the small literature concerning self‐managed approaches to training and performance improvement, extend application within educational settings, and suggest practical advantages for supporting competencies of care providers.
Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study
Authors: Auer Michael , Hegen Harald , Sellner Johann , Oppermann Katrin , Bsteh Gabriel , Di Pauli Franziska , Berger Thomas , Deisenhammer Florian
Published: June 2019

Introduction

Determination of antibodies against the John Cunningham virus (JCV) is an important tool for risk stratification in Natalizumab‐treated multiple sclerosis (MS) patients. Six‐monthly testing has been suggested for anti‐JCV antibody negative patients and patients with low antibody index in order to detect changes of serostatus. We conducted a prospective study with predefined testing intervals in order to investigate the predictability of anti‐JCV antibody status and the intervals for repetitive testing.

Methods

Our study included 109 patients at the MS Clinic of the Departments of Neurology, Medical Universities of Innsbruck and Salzburg. Blood withdrawals were performed at five time points: baseline, month 1, 3, 6, and 12. Patients’ sera were sent to Unilabs, Copenhagen, Denmark, where anti‐JCV antibodies were tested by a two‐step enzyme‐linked immunosorbent assay. Qualitative (negative/positive) and quantitative results (anti‐JCV antibody index) were used for statistical analyses.

Results

In our cohort, 52.3% of the patients were positive for anti‐JCV antibodies at baseline, with a significant correlation with age, but no association with sex or prior disease‐modifying therapy. Seven patients converted and reverted from negative to positive status and vice versa around the cut‐off index of 0.4, but no patient showed a permanent seroconversion from negative to highly positive anti‐JCV antibody status.

Conclusion

Long‐term anti‐JCV antibody status, including seroconverters/‐reverters around the cut‐off index, is highly predictable by testing three times within short intervals, however, we cannot suggest clearly defined intervals for repetitive testing. The rate of real seroconverters, i.e., new infections with JCV, per year seems lower than previously described.
PtII‐Catalyzed Hydroxylation of Terminal Aliphatic C(sp3)−H Bonds with Molecular Oxygen
Authors: Janssen Michiel , De Vos Dirk E.
Published: June 2019

The practical application of Shilov‐type Pt catalysis to the selective hydroxylation of terminal aliphatic C−H bonds remains a formidable challenge, due to difficulties in replacing PtIV with a more economically viable oxidant, particularly O2. We report the potential of employing FeCl2 as a suitable redox mediator to overcome the kinetic hurdles related to the direct use of O2 in the Pt reoxidation. For the selective conversion of butyric acid to γ‐hydroxybutyric acid (GHB), a significantly enhanced catalyst activity and stability (turnover numbers (TON)>30) were achieved under 20 bar O2 in comparison to current state‐of‐the‐art systems (TON<10). In this regard, essential reaction parameters affecting the overall activity were identified, along with specific additives to attain catalyst stability at longer reaction times. Notably, deactivation by reduction to Pt0 was prevented by the addition of monodentate pyridine derivatives, such as 2‐fluoropyridine, but also by introducing varying partial pressures of N2 in the gaseous atmosphere. Finally, stability tests revealed the involvement of PtII and FeCl2 in catalyzing the non‐selective overoxidation of GHB. Accordingly, in situ esterification with boric acid proved to be a suitable strategy to maintain enhanced selectivities at much higher conversions (TON>60). Altogether, a useful catalytic system for the selective hydroxylation of primary aliphatic C−H bonds with O2 is presented.
Impact of Paper Mill Waste on Physicochemical Properties of Soil, Crop Yield, and Chemical Composition of Plants
Authors: Żołnowski Andrzej Cezary , Sądej Wiera , Suski Marta Sylwia , Wyrwas Adrian , Skrocki Dariusz
Published: June 2019

Paper production is among the industrial branches generating significant amounts of waste. Organic waste from paper manufacturing is mostly used in gardening and agriculture or converted for energy purposes, while inorganic waste, including green liquor dregs (GLD), is usually deposited on landfills. GLD has a highly alkaline reaction, suggestive of its possible utilization for land reclamation or for improvement of soil's physico‐chemical properties. The research results originate from a pot experiment with maize as the test plant. GLD was added to soil in doses 10–40 t ha−1. The trials consisted of two series: with and without tree bark (TB). GLD contributed to neutralization of the soil's acidic pH, enrichment of the sorption complex with alkaline cations, and to greater salinity of the soil. In the series with TB, it is demonstrated that GLD led to a decrease in the soil content of total organic carbon; while the content of total nitrogen increased, the C:N ratio is considerably narrowed. In response to GLD, the greenness of leaves significantly improves, but this does not translate into an increase in the yield of plants. Regarding the chemical composition of plants grown in soil treated with elevated GLD doses, the content of N and Na is demonstrably higher, although no such effect is discernible in the case of P and K. For the environment, safe doses of the applied waste, not causing significant deterioration of soil properties or depressing crop yields, are 10 and 20 t GLD ha−1.
Canopy disturbance and gap partitioning promote the persistence of a pioneer tree population in a near‐climax temperate forest of the Qinling Mountains, China
Authors: Guo Yaoxin , Zhao Peng , Yue Ming
Published: June 2019

An unresolved question of temperate forests is how pioneer tree species persist in mature forests. In order to understand the responsible mechanisms, we investigated a near‐climax mixed temperate forest dominated by Betula albosinensis in the Qinling Mountains of China. Through establishing four 50 m × 50 m plots, we examined the canopy disturbance characteristics and its effects on tree recruitments. We further test the intra‐ and interspecific effects on the recruitment of B. albosinensis. The obtained data demonstrated canopy disturbance was frequent but most small‐sized. The canopy gaps are caused mainly by adult B. albosinensis by snapping. The regeneration of coexistent tree species shows a distinct preference for gap size. B. albosinensis were clumped at the juvenile stage and small scales. B. albosinensis juveniles were positively associated with B. utilis juveniles and negatively associated with the conspecific and B. utilis large trees. In addition, B. albosinensis juveniles showed negative associations with contemporary other tree species. Our results suggested that canopy disturbance caused by canopy trees and gap partitioning among the coexistent tree species are important for the persistence of the mixed forest. As a main gapmaker, B. albosinensis appear to develop a self‐perpetuating life‐history trait and allow them to persist.
Designing network‐connected systems for ecological research and education
Authors: Kubizňák Petr , Hochachka Wesley M. , Osoba Vlastimil , Kotek Tomáš , Kuchař Jan , Klapetek Václav , Hradcová Kateřina , Růžička Jan , Zárybnická Markéta
Published: June 2019

While networked sensors are becoming a ubiquitous part of many human lives, their applications to the study of wild animals have been largely limited to off‐the‐shelf and stand‐alone technologies such as web cameras. However, purpose‐designed systems, applying features found in Internet‐of‐Things devices, enable more efficient gathering, managing, and disseminating of a diverse array of data needed to study the life histories of wild animals. We illustrate these claims based on our development of a system of networked nest boxes that we created to study nesting birds in urban environments. This system uses general‐purpose processors within nest boxes to perform edge computing to control data acquisition, processing, and management from multiple sensors. A central data‐management system permits easy access to all data, once downloaded, which has facilitated our uses to date of this system for formal university‐ and school‐level education, and informal science education.
Incorporating citizen science data in spatially explicit integrated population models
Authors: Sun Catherine C. , Royle J. Andrew , Fuller Angela K.
Published: June 2019

Information about population abundance, distribution, and demographic rates is critical for understanding a species’ ecology and for effective conservation and management. To collect data over large spatial and temporal extents for such inferences, especially for species with low densities or wide distributions, citizen science can be an efficient approach. Integrated models have also emerged as an important methodology to estimate population parameters by combining multiple types of data, including citizen science data. We developed a spatially explicit integrated model that combines opportunistically collected presence–absence (PA) data, commonly collected in citizen science efforts, with systematically collected spatial capture–recapture (SCR) data, which are often limited to small spatial and temporal extents. We conducted single and multi‐season simulations with parameters informed by North American black bear (Ursus americanus) populations, to evaluate the influence of varying amounts of opportunistic PA data collected at larger spatial and temporal extents on the estimation of population‐level parameters. Integrating opportunistic PA data increased the precision and accuracy of posterior estimates of abundance, and survival and recruitment rates. In some cases, adding PA locations improved abundance estimates more than increasing PA detection probability. Posterior estimates were as precise and unbiased as when higher quality, but sparse, SCR data were available. We also applied the integrated model to SCR and citizen science PA data collected on black bears in New York, with results consistent with our simulations. Our findings indicate that citizen science in integrated models can be a cost‐efficient way to improve estimates of population parameters and increase the spatiotemporal extent of inference. Continued developments with integrated models and citizen science data will offer additional ways to improve our understanding of population structure and demographics.
Pyridine‐Stabilized Rhodium Nanoparticles in Ionic Liquids as Selective Hydrogenation and Transfer Hydrogenation Catalysts
Authors: Serrano‐Maldonado Alejandro , Martin Erika , Guerrero‐Ríos Itzel
Published: June 2019

Invited for the cover of this issue is Itzel Guerrero‐Ríos from Universidad Nacional Autónoma de México. The cover image shows a drop of ionic liquid containing pyridine‐stabilized rhodium nanoparticles, whose performance as hydrogenation and transfer hydrogenation catalyst has been investigated.
Cauliflower‐like Platinum Particles Decorated Reduced Graphene Oxide for Sensitive Determination of Acetaminophen
Authors: Pham Tien Song Hiep , Mahon Peter J. , Lai Guosong , Fu Li , Lin Cheng‐Te , Yu Aimin
Published: June 2019

Over the past years, the development of electrochemical sensing platforms for the sensitive detection of drug molecules have received great interests. In this research study, we introduced cauliflower‐like platinum particles decorated reduced graphene oxide modified glassy carbon electrode (Pt−RGO/GCE) as an electrochemical sensing platform for highly sensitive determination of acetaminophen (ACTM). The sensor was prepared via a simple and environmentally friendly two‐step electrodeposition method at room temperature. The combination of conductive RGO nanosheets and unique structured Pt particles (average 232 nm in diameter) provided an efficient interface with large effective surface area which greatly facilitated the electron transfer of ACTM. The experimental conditions that might affect the drug detection were studied in detail and optimized for best performance. The Pt−RGO/GCE was able to detect ACTM up to the limit of 2.2 nM with a linear concentration range from 0.01 to 350 μM. With its high reproducibility, excellent stability and selectivity, the as‐fabricated sensor was successfully applied to the ACTM content measurement in commercial tablets.
Trend assessment for daily snow depths with changepoint considerations
Authors: Lee J. , Lund R. , Woody J. , Xu Y.
Published: June 2019

This paper develops methods to estimate a long‐term trend in a daily snow depth record. The methods use a storage equation model for the daily snow depths that allows for seasonality, support set features (snow depths cannot be negative), correlation, and mean level shift changepoint features. Changepoints can occur in snow processes whenever observing stations move or station instrumentation is changed; they are critical features to consider when estimating a long‐term trend. A likelihood objective function is developed for the storage model and is used to estimate model parameters. Genetic algorithms are used to optimize a minimum descriptive length model selection criterion that estimates the changepoint numbers and locations. The methods are applied in the analysis of a daily series recorded near Warm Lake, Idaho, from 1948 to 2009.
Altered cortical folding and reduced sulcal depth in adults with anorexia nervosa
Authors: Nickel Kathrin , Joos Andreas , Tebartz van Elst Ludger , Holovics Lukas , Endres Dominique , Zeeck Almut , Maier Simon
Published: June 2019

Objective

Previous studies on anorexia nervosa (AN) focused on cortical volume and mainly reported grey matter reduction. They also investigated cortical surface parameters, for example, absolute mean curvature (AMC) providing information on cortical folding or sulcal depth (SD). For the first time, we also analysed cortical complexity using fractal dimension (FD) in AN.

Method

In a cross‐sectional study, we performed surface analyses (AMC, SD, and FD) on 34 women with AN, 24 recovered from AN (REC), and 41 healthy controls (HC). Structural MR data was processed using the Computational Anatomy Toolbox and statistically compared across groups on a vertex‐ and region‐of‐interest‐wise level using statistical parametric mapping.

Results

We found a lower AMC and SD in AN, especially in temporal areas. FD was increased in the left precentral gyrus in AN. No differences of the parameters AMC, SD, or FD were evident between REC and HC participants.

Conclusions

Alterations in AMC, SD, and FD in AN patients, but not between the REC and HC groups, suggest that these alterations are state related. The findings concur with other structural AN studies that suggest restitution with clinical recovery. The changes may be due to malnutrition, dehydration, osmotic dysregulation, or hormonal aberrations during the acute stage.
Online, real‐time, and direct use of SIFT‐MS to measure garlic breath deodorization: a review
Authors: Castada Hardy Z. , Barringer Sheryl Ann
Published: June 2019

This review summarizes the application of selected‐ion flow‐tube mass spectrometry (SIFT‐MS) to recent deodorization studies of garlic‐derived volatile organosulphur compounds. Briefly, organosulphur chemistry, proposed theories on deodorization mechanisms, and technical aspects of SIFT‐MS were revisited. The most effective deodorization treatments from various food and food components were identified, which include whole milk, parsley, spinach, mint, and apple; however, chlorophyll and whey protein did not provide effective deodorization. The extent of deodorization by each of the treatments varies according to the active components that are either able to bind, capture, oxidize, or reduce specific sulphur compounds, leading to deodorization. It was determined that certain varieties (cultivars) of food produce more effective deodorization than other varieties. In addition, the effectiveness of enzymes for deodorization could depend upon the rate of enzymatic activity, which catalyses the subsequent oxidation of phenolic compounds to initiate deodorization. Moreover, the high phenolic content of a food did not automatically correlate with greater deodorization, although the type of phenolic compound could be an important factor for providing effective deodorization. Finally, other challenges and considerations were suggested for further advancement of the research on deodorization of malodorous garlic breath using food and food components
Childhood Socioeconomic Disadvantage and Risk of Fatty Liver in Adulthood: The Cardiovascular Risk in Young Finns Study
Authors: Laitinen Tomi T. , Vahtera Jussi , Pahkala Katja , Magnussen Costan G. , Nuotio Joel , Hutri‐Kähönen Nina , Kivimäki Mika , Lehtimäki Terho , Jokinen Eero , Laitinen Tomi , Tossavainen Päivi , Pentti Jaana , Viikari Jorma S.A. , Juonala Markus , Raitakari Olli T.
Published: June 2019

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3‐18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow‐up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents’ socioeconomic position and socioeconomic circumstances in participants’ residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow‐up (2011) at ages 34‐49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18‐1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09‐1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.
Organoids are promising tools for species‐specific in vitro toxicological studies
Authors: Augustyniak Justyna , Bertero Alessia , Coccini Teresa , Baderna Diego , Buzanska Leonora , Caloni Francesca
Published: June 2019

Organoids are three‐dimensional self‐aggregating structures generated from stem cells (SCs) or progenitor cells in a process that recapitulates molecular and cellular stages of early organ development. The differentiation process leads to the appearance of specialized mature cells and is connected with changes in the organoid internal structure rearrangement and self‐organization. The formation of organ‐specific structures in vitro with highly ordered architecture is also strongly influenced by the extracellular matrix. These features make organoids as a powerful model for in vitro toxicology. Nowadays this technology is developing very quickly. In this review we present, from a toxicological and species‐specific point of view, the state of the art of organoid generation from adult SCs and pluripotent SCs: embryonic SCs or induced pluripotent SCs. The current culture organoid techniques are discussed for their main advantages, disadvantages and limitations. In the second part of the review, we concentrated on the characterization of species‐specific organoids generated from tissue‐specific SCs of different sources: mammary (bovine), epidermis (canine), intestinal (porcine, bovine, canine, chicken) and liver (feline, canine).
A deep learning based pipeline for optical coherence tomography angiography
Authors: Liu Xi , Huang Zhiyu , Wang Zhenzhou , Wen Chenyao , Jiang Zhe , Yu Zekuan , Liu Jingfeng , Liu Gangjun , Huang Xiaolin , Maier Andreas , Ren Qiushi , Lu Yanye
Published: June 2019

Optical coherence tomography angiography (OCTA) is a relatively new imaging modality that generates microvasculature map. Meanwhile, deep learning has been recently attracting considerable attention in image‐to‐image translation, such as image denoising, super‐resolution and prediction. In this paper, we propose a deep learning based pipeline for OCTA. This pipeline consists of three parts: training data preparation, model learning and OCTA predicting using the trained model. To be mentioned, the datasets used in this work were automatically generated by a conventional system setup without any expert labeling. Promising results have been validated by in‐vivo animal experiments, which demonstrate that deep learning is able to outperform traditional OCTA methods. The image quality is improved in not only higher signal‐to‐noise ratio but also better vasculature connectivity by laser speckle eliminating, showing potential in clinical use. Schematic description of the deep learning based optical coherent tomography angiography pipeline.
Improving skin integration around long‐term percutaneous devices using fibrous scaffolds in a reconstructed human skin equivalent model
Authors: Bolle Eleonore C. L. , Bartnikowski Nicole , Haridas Parvathi , Parker Tony J. , Fraser John F. , Gregory Shaun D. , Dargaville Tim R.
Published: June 2019

The interface between synthetic percutaneous devices and skin is a common area for bacterial infection, which may ultimately result in failure of the device. Better integration of percutaneous devices with skin may help reduce infection rates due to the creation of a dermal seal. However, the mismatch in material and chemical properties of devices and skin presents a challenge for closing the dermal gap at the skin–device interface. Here, we have used a tissue engineering approach to tissue integration by creating a highly fibrous poly(ε‐caprolactone) scaffold using melt electrowriting and seeding this with dermal fibroblasts, followed by maturation and insertion into a full‐thickness defect made in an ex vivo skin model. The integration of seeded scaffolds was compared with controls including a non‐seeded scaffold and a polymer tube with a smooth surface. Dermal fibroblast inclusion in the scaffold and epidermal upgrowth versus downgrowth/marsupialization around the device were used as measures of integration. Based on these measures, almost all pre‐seeded scaffolds performed better than both the non‐seeded scaffolds and smooth tubes. The hypothesis is that the fibroblasts act as a barrier to epithelial downward migration, and provide healthy tissue for nascent epidermal development.
A 7‐lncRNA signature predict prognosis of Uterine corpus endometrial carcinoma
Authors: Ouyang Dong , Li Ruyi , Li Yaxian , Zhu Xueqiong
Published: June 2019

Current research indicate that long noncoding RNAs (lncRNAs) are associated with the progression of various cancers and can be used as prognostic biomarkers. This study aims to construct a prognostic lncRNA signature for the risk assessment of Uterine corpus endometrial carcinoma (UCEC). The RNA‐Seq expression profile and corresponding clinical data of UCEC patients obtained from The Cancer Genome Atlas database. First, some prognosis‐related lncRNAs were obtained by univariate Cox analysis. The minimum absolute contraction and selection operator (LASSO) regression and the Cox proportional hazard regression method were used to further identify the lncRNA prognostic model. Finally, seven lncRNAs (AC110491.1, AL451137.1, AC005381.1, AC103563.2, AC007422.2, AC108025.2, and MIR7‐3HG) were identified as potential prognostic factors. According to the model constructed by the above analysis, the risk score of each UCEC patient was calculated, and the patients were classified into high and low‐risk groups. The low‐risk group had significant survival benefits. Moreover, we constructed a nomogram that incorporated independent prognostic factors (age, tumor stage, tumor grade, and risk score). The c‐index value for evaluating the predictive nomogram model was 0.801. The area under the curve was 0.797 (3‐year survival). The calibration curve also showed that there was a satisfactory agreement between the predicted and observed values in the probability of 1‐, 3‐, and 5‐year overall survival. On the basis of the coexpression relationship, we established a coexpression network of lncRNA‐messenger RNA (mRNA) of the 7‐lncRNA. The Kyoto Encyclopedia of Genes and Genomes analysis of the coexpressing mRNAs showed that the main pathways related to the 7‐lncRNA signature were neuroactive ligand‐receptor interaction, serotonergic synapse, and gastric cancer pathway. Therefore, our study revealed that the 7‐lncRNA could be used to predict the prognosis of UCEC and for postoperative treatment and follow‐up.
Identification of key genes and pathways of thyroid cancer by integrated bioinformatics analysis
Authors: Liu Lu , He Chen , Zhou Qing , Wang Ganlu , Lv Zhiwu , Liu Jintao
Published: June 2019

Thyroid cancer is a common endocrine malignancy with a rapidly increasing incidence worldwide. Although its mortality is steady or declining because of earlier diagnoses, its survival rate varies because of different tumour types. Thus, the aim of this study was to identify key biomarkers and novel therapeutic targets in thyroid cancer. The expression profiles of GSE3467, GSE5364, GSE29265 and GSE53157 were downloaded from the Gene Expression Omnibus database, which included a total of 97 thyroid cancer and 48 normal samples. After screening significant differentially expressed genes (DEGs) in each data set, we used the robust rank aggregation method to identify 358 robust DEGs, including 135 upregulated and 224 downregulated genes, in four datasets. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses of DEGs were performed by DAVID and the KOBAS online database, respectively. The results showed that these DEGs were significantly enriched in various cancer‐related functions and pathways. Then, the STRING database was used to construct the protein–protein interaction network, and modules analysis was performed. Finally, we filtered out five hub genes, including LPAR5, NMU, FN1, NPY1R, and CXCL12, from the whole network. Expression validation and survival analysis of these hub genes based on the The Cancer Genome Atlas database suggested the robustness of the above results. In conclusion, these results provided novel and reliable biomarkers for thyroid cancer, which will be useful for further clinical applications in thyroid cancer diagnosis, prognosis and targeted therapy.
Mixed methods analysis strategies in program evaluation beyond “a little quant here, a little qual there”
Authors: Reeping David , Taylor Ashley R. , Knight David B. , Edwards Cherie
Published: June 2019

Background

Mixed methods research designs in engineering education often frame the “mixed” aspect of the design from the perspective of data collection. However, intentional mixing throughout the research design—particularly during data analysis—may enable richer meta‐inferences about a phenomenon.

Purpose

This paper provides examples of strategies for mixing during data analysis in mixed methods program evaluation in engineering education. Although the context is program evaluation, the procedures are applicable in engineering education research more broadly.

Scope/Method

This review presents examples of mixed methods analysis strategies in the context of a data set with qualitative and quantitative data from a global engineering program at a large Mid‐Atlantic university. The structure of the examples presents mixed research questions, pragmatic purposes for such studies, and examples of different mixing strategies for the analysis stage. The mixing strategies highlighted include extreme case sampling, converting, creating a blended variable, blending variables and themes across strands, and cross‐case comparison.

Conclusions

This review of mixed methods in program evaluation prompted a reflection of processes in the design of studies, how the designs are described beyond the usual taxonomies in the mixed methods literature, and implications for the greater community of engineering education researchers. Five mixed methods designs were formulated around the mixing strategies.
Characterizing the interplay of cognitive and metacognitive knowledge in computational modeling and simulation practices
Authors: Magana Alejandra J. , Fennell Hayden W. , Vieira Camilo , Falk Michael L.
Published: June 2019

Background

Modeling and simulation practices have become commonplace in modern engineering, but in‐depth research on the development of modeling and simulation expertise is needed to identify the learning processes involved in successfully acquiring these skills.

Purpose

This study investigated student dimensions of expertise when engaged in modeling and simulation practices. The guiding research question was “How do students use cognitive and metacognitive knowledge when engaged with computational modeling and simulation practices?”

Design/Method

This study included 11 undergraduate engineering students enrolled in a course on computational materials science. Data were collected from one of five computational challenges administered during the course. Students' cognitive and metacognitive knowledge use was first analyzed using thematic analysis and then through a phenomenographic approach. Findings were interpreted using the lens of adaptive expertise.

Results

Results describe how students used their cognitive and metacognitive knowledge to approach the computational challenge. Two categories in the cognitive dimension were identified: implementation‐oriented and knowledge‐oriented. Two categories identified in the metacognitive dimension were plan‐oriented and action‐oriented approaches. These categories are further presented as an outcome space by aligning them with the dimensions of adaptive expertise.

Conclusions

Results indicated that students in the action/implementation‐oriented category exhibited many of the qualities expected of inexperienced novices, while students in the plan/knowledge‐oriented category demonstrated more of the qualities expected of adaptive experts. However, results were less conclusive for students in the two intermediate thematic categories, who often exhibited some but not all of the qualities of both novices and experts.
Microscopic skin laceration segmentation and classification: A framework of statistical normal distribution and optimal feature selection
Authors: Afza Farhat , Khan Muhammad A. , Sharif Muhammad , Rehman Amjad
Published: June 2019

Among precision medical techniques, medical image processing is rapidly growing as a successful tool for cancer detection. Skin cancer is one of the crucial cancer types. It is identified through computer vision (CV) techniques using dermoscopic images. The early diagnosis skin cancer from dermoscopic images can be decrease the mortality rate. We propose an automated system for skin lesion detection and classification based on statistical normal distribution and optimal feature selection. Local contrast is controlled using a brighter channel enhancement technique, and segmentation is performed through a statistical normal distribution approach. The multiplication law of probability is implemented for the fusion of segmented images. In the feature extraction phase, optimized histogram, optimized color, and gray level co‐occurrences matrices features are extracted and covariance‐based fusion is performed. Subsequently, optimal features are selected through a binary grasshopper optimization algorithm. The selected optimal features are finally fed to a classifier and evaluated on the ISBI 2016 and ISBI 2017 data sets. Classification accuracy is computed using different Support Vector Machine (SVM) kernel functions, and the best accuracy is obtained for the cubic function. The average accuracies of the proposed segmentation on the PH2 and ISBI 2016 data sets are 93.79 and 96.04%, respectively, for an image size 512 × 512. The accuracies of the proposed classification on the ISBI 2016 and ISBI 2017 data sets are 93.80 and 93.70%, respectively. The proposed system outperforms existing methods on selected data sets.
Synthesis of Hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1′‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones] from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione Using Fe3O4@Cu(OH)x as a Nanocatalyst
Authors: Baradarani Mehdi M. , Saatluo Bahman Ebrahimi , Ghabeli Shiva , Shokri Zahra , Shahbazi Masoumeh , Joule John A.
Published: June 2019

The tricyclic isatin, 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione, undergoes three‐component, one‐pot reactions with 1‐aryl‐3‐methylpyrazole‐5‐amines and cyclohexane‐1,3‐diones producing hexacyclic spiro products, hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones]. Comparable spiro condensation products are also obtained using 4‐hydroxy‐2H‐1‐benzopyran‐2‐one in place of cyclohexane‐1,3‐diones.
Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst
Authors: Grondman Inge , Arts Rob J W , Koch Rebecca M , Leijte Guus P , Gerretsen Jelle , Bruse Niklas , Kempkes Rosalie W M , ter Horst Rob , Kox Matthijs , Pickkers Peter , Netea Mihai G , Gresnigt Mark S
Published: June 2019

Secondary infections are a major complication of sepsis and associated with a compromised immune state, called sepsis-induced immunoparalysis. Molecular mechanisms causing immunoparalysis remain unclear; however, changes in cellular metabolism of leukocytes have been linked to immunoparalysis. We investigated the relation of metabolic changes to antimicrobial monocyte functions in endotoxin-induced immunotolerance, as a model for sepsis-induced immunoparalysis. In this study, immunotolerance was induced in healthy males by intravenous endotoxin (2 ng/kg, derived from Escherichia coli O:113) administration. Before and after induction of immunotolerance, circulating CD14+ monocytes were isolated and assessed for antimicrobial functions, including cytokine production, oxidative burst, and microbial (Candida albicans) killing capacity, as well metabolic responses to ex vivo stimulation. Next, the effects of altered cellular metabolism on monocyte functions were validated in vitro. Ex vivo lipopolysaccharide stimulation induced an extensive rewiring of metabolism in naive monocytes. In contrast, endotoxin-induced immunotolerant monocytes showed no metabolic plasticity, as they were unable to adapt their metabolism or mount cytokine and oxidative responses. Validation experiments showed that modulation of metabolic pathways, affected by immunotolerance, influenced monocyte cytokine production, oxidative burst, and microbial (C. albicans) killing in naive monocytes. Collectively, these data demonstrate that immunotolerant monocytes are characterized by a loss of metabolic plasticity and these metabolic defects impact antimicrobial monocyte immune functions. Further, these findings support that the changed cellular metabolism of immunotolerant monocytes might reveal novel therapeutic targets to reverse sepsis-induced immunoparalysis.
A proposal for the adsorption of anastrozole anticancer drug on gold nanoparticle surfaces
Authors: Teixeira Raïssa A.R. , Costa Luiz Antônio S. , Sant'Ana Antonio C.
Published: June 2019

Anastrozole is a well‐known anticancer drug used in aromatase‐dependent cancer chemotherapy as a nonsteroidal aromatase inhibitor. Investigations involving the adsorption of anastrozole on gold surfaces are on demand, because gold nanoparticles (AuNPs) have been used as nanocarriers of drugs, and such a compound can be used against aromatase‐expressing neoplastic cells. In this work, surface‐enhanced Raman scattering (SERS) spectroscopy was used to investigate the interaction between anastrozole and the surfaces of AuNPs. Density functional theory (DFT) calculations were used to simulate the molecular interactions with gold atom through two possible ways, triazole or nitrile moieties. Experimental results, supported by DFT calculations to assign main vibrational modes, indicate that the nitrile groups are the most preferred anchorage moieties for the adsorption.
At‐line multi‐angle light scattering detector for faster process development in enveloped virus‐like particle purification
Authors: Pereira Aguilar Patricia , González‐Domínguez Irene , Schneider Tobias Amadeus , Gòdia Francesc , Cervera Laura , Jungbauer Alois
Published: June 2019

At‐line static light scattering and fluorescence monitoring allows direct in‐process tracking of fluorescent virus‐like particles. We have demonstrated this by coupling at‐line multi‐angle light scattering and fluorescence detectors to the downstream processing of enveloped virus‐like particles. Since light scattering intensity is directly proportional to particle concentration, our strategy allowed a swift identification of product containing fractions and rapid process development. Virus‐like particles containing the Human Immunodeficiency Virus‐1 Gag protein fused to the Green Fluorescence protein were produced in Human Embryonic Kidney 293 cells by transient transfection. A single‐column anion‐exchange chromatography method was used for direct capture and purification. The majority of host‐cell protein impurities passed through the column without binding. Virus‐like particles bound to the column were eluted by linear or step salt gradients. Particles recovered in the step gradient purification were characterized by nanoparticle tracking analysis, size exclusion chromatography coupled to multi‐angle light scattering and fluorescence detectors and transmission electron microscopy. A total recovery of 66% for the fluorescent particles was obtained with a 50% yield in the main product peak. Virus‐like particles were concentrated 17‐fold to final a concentration of 4.45 × 1010 particles/mL. Simple buffers and operation make this process suitable for large scale purposes.