bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale integration of single cell biologics discovery processes using optofluidic manipulation and monitoring
Authors: Jorgolli Marsela , Nevill Tanner , Winters Aaron , Chen Irwin , Chong Su , Lin Fen‐Fen , Mock Marissa , Chen Ching , Le Kim , Tan Christopher , Jess Philip , Xu Han , Hamburger Agi , Stevens Jennitte , Munro Trent , Wu Ming , Tagari Philip , Miranda Les P.
Published: May 2019

The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high‐paced workflows necessary to support modern large molecule drug discovery. A high‐level aspiration is a true integration of “lab‐on‐a‐chip” methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development. Several microscale bioprocess technologies have been established that incrementally address these needs, yet each is inflexibly designed for a very specific process thus limiting an integrated holistic application. A more fully integrated nanoscale approach that incorporates manipulation, culture, analytics, and traceable digital record keeping of thousands of single cells in a relevant nanoenvironment would be a transformative technology capable of keeping pace with today's rapid and complex drug discovery demands. The recent advent of optical manipulation of cells using light‐induced electrokinetics with micro‐ and nanoscale cell culture is poised to revolutionize both fundamental and applied biological research. In this review, we summarize the current state of the art for optical manipulation techniques and discuss emerging biological applications of this technology. In particular, we focus on promising prospects for drug discovery workflows, including antibody discovery, bioassay development, antibody engineering, and cell line development, which are enabled by the automation and industrialization of an integrated optoelectronic single‐cell manipulation and culture platform. Continued development of such platforms will be well positioned to overcome many of the challenges currently associated with fragmented, low‐throughput bioprocess workflows in biopharma and life science research.
Agent navigation using deep learning with agent space heat map for crowd simulation
Authors: Oshita Masaki
Published: May 2019

We propose a novel method of crowd simulation that employs a deep learning technique for controlling individual agents. We use a convolutional neural network to learn agent space heat maps that are generated from example crowd animations. A heat map contains the positions and speeds of nearby agents and the temporary target position that indicates an appropriate heading direction for the agent to reach the final target position efficiently. When controlling an agent, an agent space heat map that contains possible temporary target positions is estimated from the trained model and the agent space heat map that contains only the positions and speeds of nearby agents. In addition, evaluation functions are used to choose a temporary target position from the estimated heat map. Individual agents are controlled using a force‐based model so that they move toward the estimated temporary target position. Our approach realizes human‐like navigation by combining the intuitive and logical aspects of decision‐making.
A Novel Aqueous‐based Gelcasting Process to Fabricate Li6.4La3Zr1.4Ta0.6O12 Solid Electrolytes
Authors: Peng Xiang , Zhang Xiaokun , Huang Kai , Song Shipai , Xiang Yong
Published: May 2019

A novel aqueous‐based gelcasting technique is developed to fabricate dense Li6.4La3Zr1.4Ta0.6O12 (LLZTO) electrolytes with complex structures, which is based on an aqueous slurry with a solid LLZTO fraction of 75 wt % and a copolymer of isobutylene and maleic anhydride as dispersant as well as gelling agent. A new recipe is developed by introducing LiOH into the aqueous slurry to suppress the Li+/H+ exchange reaction, ensuring that the gelcasting LLZTO has a pure cubic garnet phase. The gelcasting LLZTO has a high ionic conductivity of 0.74×10−3 S cm−1 (25 °C), an excellent lithium cycling stability, and a wide voltage window up to 5 V, which are comparable with literature reports and can satisfy the requirements of the next‐generation lithium batteries with higher energy densities. The aqueous‐based gelcasting technique is promising in the cost‐efficient and environment‐friendly manufacturing of high‐quality LLZTO solid electrolytes for all‐solid‐state batteries.
Ultrasmall MoS3 Loaded GO Nanocomposites as High‐Rate and Long‐Cycle‐Life Anode Materials for Lithium‐ and Sodium‐Ion Batteries
Authors: Zhou Yanli , Li Yanyan , Wang Qianqian , Wang Qi , Du Rong , Zhang Ming , Sun Xueqin , Zhang Xiaoyu , Kang Litao , Jiang Fuyi
Published: May 2019

MoS3 is a promising anode material due to its high theoretical capacity (838 mAh g−1), high conductivity, low cost, and environmental friendliness. However, the big volume changes upon cycling can induce particle pulverization, leading to a poor cycling performance, especially at high rates. Herein, nanocomposites of amorphous ultrasmall MoS3 nanoparticles and loaded graphene oxide (GO/MoS3) have been prepared via a facile acid precipitation method. Three nanocomposites were obtained by changing the amounts of GO. They were employed as anode materials for both lithium‐ and sodium‐ion batteries. Using GO as the buffer layer, the volume changes can be effectively suppressed. The material exhibits better lithium‐ and sodium‐storage performances than pure MoS3. An optimized nanocomposite containing 30 mg of GO shows the highest specific capacity of 685 mAh g−1 after 1000 cycles, even at 2 A g−1. Different from lithium‐ion batteries, the nanocomposite containing 50 mg of GO demonstrates a superior cycling stability in sodium‐ion batteries in comparison with the other nanocomposites. It delivers a high reversible specific capacity of 272 mAh g−1 after 700 cycles at 1 A g−1. The excellent electrochemical performances of these nanocomposites could be attributed to the synergistic effect of GO and MoS3.
Red‐Shifted Substrates for FAST Fluorogen‐Activating Protein Based on the GFP‐Like Chromophores
Authors: Povarova Natalia V. , Zaitseva Snizhana O. , Baleeva Nadezhda S. , Smirnov Alexander Yu. , Myasnyanko Ivan N. , Zagudaylova Marina B. , Bozhanova Nina G. , Gorbachev Dmitriy A. , Malyshevskaya Kseniya K. , Gavrikov Alexey S. , Mishin Alexander S. , Baranov Mikhail S.
Published: May 2019

A genetically encoded fluorescent tag for live cell microscopy is presented. This tag is composed of previously published fluorogen‐activating protein FAST and a novel fluorogenic derivative of green fluorescent protein (GFP)‐like chromophore with red fluorescence. The reversible binding of the novel fluorogen and FAST is accompanied by three orders of magnitude increase in red fluorescence (580–650 nm). The proposed dye instantly stains target cellular proteins fused with FAST, washes out in a minute timescale, and exhibits higher photostability of the fluorescence signal in confocal and widefield microscopy, in contrast with previously published fluorogen:FAST complexes.
Investigating Electronic Communications in meso–meso Ethene‐Bridged Unsymmetrical Diporphyrins
Authors: Zieleniewska Anna , Guldi Dirk M.
Published: May 2019

At the focal point of this work is the photophysical characterization of three meso–meso ethene‐bridged diporphyrins featuring a diverse metallation pattern. Detailed investigations by means of cyclic voltammetry, absorption, fluorescence, and femto‐/nanosecond transient absorption spectroscopy revealed the impact of open‐shell nickel(II) on the electronic communication in ethene‐bridged heterobimetallic diporphyrins.
High‐Performance RuCl3 Catalyst Systems for Hydro‐Esterification of Methyl Formate and Ethylene
Authors: Li Yan‐Ru , Xu Zhong‐Ning , Bai Bing , Wang Zhi‐Qiao , Guo Guo‐Cong
Published: May 2019

Summary of main observation and conclusion

RuCl3 catalyst system has many advantages for the hydro‐esterification of methyl formate and ethylene to methyl propionate. However, the unsatisfied performance restricts the development of this route. In this work, high‐performance RuCl3 catalyst systems (RuCl3‐[PPN]Cl‐Et4NI and RuCl3‐NaI) are firstly reported for this reaction. In RuCl3‐[PPN]Cl‐Et4NI catalyst system, the conversion of methyl formate and the selectivity to methyl propionate are 93.9% and 90.9% at mild reaction conditions (165°C, 2.5 MPa), respectively. Noticeably, a simple inorganic RuCl3‐NaI catalyst system achieves 88.8% conversion of methyl formate and 97.6% selectivity to methyl propionate (86.7% yield) at same conditions. NaI, as a promoter, may inhibit the decomposition of methyl formate and be conducive to the formation of methyl propionate. The effects of solvents and promoters are investigated in detail. In addition, the reaction mechanism has been also analyzed. It is hoped to lay a certain foundation for further industrial application.
Similarity joins for high‐dimensional data using Spark
Authors: Rong Chuitian , Cheng Xiaohai , Chen Ziliang , Huo Na
Published: May 2019

Similarity join on high‐dimensional data is a primitive operation. It is used to find all data pairs that with distance no more than ϵ from the given data set according to a specific distance measure. As the data set scale and dimension increase, computation cost increases vastly. Hadoop and Spark have become the popular platforms for big‐data analysis. Because Spark has native advantages in iterative computations, we adopted it as our platform to perform similarity joins on high‐dimensional data sets. In order to resolve problems such as data imbalance, data duplication, and redundant computation of existing works, we have proposed a new algorithm based on Symbolic aggregation and vertical decomposition. We first conduct dimension‐reduction using symbolic aggregation method. Then, we applied vertical partition operation on processed data. The join operations are performed on each vertical partition in parallel manner and the proposed new filters are utilized to prune false positives in early stage. Finally, the partial results generated from each partition will be aggregated and verified to get final results. Our proposed algorithm can significantly improve the efficiency of similarity joins on high‐dimensional data. In order to verify the efficiency and scalability of our methods, we implemented it using MapReduce and Spark. We compared our methods with existing works on public data sets, and the experimental results showed that the new methods were more efficient and scalable under different running environments.
Milk in the prevention and management of type 2 diabetes: The potential role of milk proteins
Authors: Hidayat Khemayanto , Du Xuan , Shi Bi‐Min
Published: May 2019

Globally, diabetes mellitus is not only considered a leading cause of mortality and morbidities but has also created a substantial economic burden. There is growing evidence that foods and their components can be implemented in the prevention and management of type 2 diabetes mellitus (T2DM). Increased dairy consumption has been linked to a lower risk of T2DM. The protective role of dairy foods in the development of T2DM is thought to be largely attributable to dairy nutrients, one of them being dairy protein. There is considerable evidence that milk proteins increase the postprandial insulin response and lower the postprandial blood glucose response in both healthy subjects and patients with T2DM. The exact mechanisms by which milk proteins lower postprandial glucose levels are yet to established; however, the amino acids and bioactive peptides derived from milk proteins are thought to modify a physiological milieu, which includes delayed gastric emptying and the enhancement of incretin and insulin responses, consequently leading to lower postprandial glucose levels. The present review will focus on providing a clear presentation of the potential implementation of milk proteins as a dietary supplement in the prevention and management of T2DM by summarizing the relevant supporting evidence for this particular topic.
Porphyrin‐Stabilized Transition Metal Nanoparticles and Their Applications in the Reduction of 4‐Nitrophenol and the Generation of Hydroxyl Radicals
Authors: Yan Jiaying , Liu Genjiang , Li Ning , Zhang Nuonuo , Liu Xiang
Published: May 2019

The synthesis of robust transition metal nanoparticles (TMNPs) are still intensively investigated because of multiple up‐to date applications in catalysis, solar cells, nonlinear optics, biological labeling, nanoelectronics, medicine and energy storage devices. Here we report synthesis of tetrahydroxyphenylporphyrin (TPP‐OH)‐stabilized TMNPs (including AuNPs, AgNPs and PdNPs) by mixing TPP‐OH and simple commercial metal salt and followed by the addition of sodium borohydride at 0 °C. The as‐synthesized nanocomposites show high catalytic activity in the reduction of 4‐nitrophenol, a pertinacious pollutant occurring in industrial waste water. In addition, it is evident that a drastic absorption change has been observed in UV/Vis spectra, confirming that generation of hydroxyl radicals induced by AgNPs and further oxidized methylene blue (MB) to hydroxymethylene blue (MB‐OH).
Trinuclear and Mononuclear Lanthanoid Complexes Containing 2‐Methyl‐8‐quinolinolate: Synthesis, Structures, and Magnetic Properties
Authors: Ghazali Nurul F. , Phonsri Wasinee , Murray Keith S. , Junk Peter C. , Deacon Glen B. , Turner David R.
Published: May 2019

Two series of new lanthanoid complexes containing 2‐methyl‐8‐quinolinolate (MQ–) have been prepared at elevated temperatures. Lighter elements yield trinuclear complexes [Ln3(MQ)9(HMQ)]·5H2O·3MeOH (1Ln, where Ln = Pr, Eu, Gd, Tb, Dy and Ho) by solvothermal reactions, and heavier lanthanoids yield the mononuclear complexes [Ln(MQ)3(HMQ)]·HMQ·MeOH (2Ln, where Ln = Dy, Ho, Er and Yb), with overlap between the two series found in the cases of Dy and Ho. Magnetic studies reveal that 1Tb, 1Dy, and 2Er show distinct slow magnetic relaxation under external DC fields. The magnetic data for 1Gd yielded the J value for weak antiferromagnetic coupling and the magnetocaloric –ΔSm value of 20 J kg–1 K–1 at 2 K and ΔH = 5 T.
Allyl Palladium Complexes of Cycloheptatrienyl‐Cyclopentadienyl Phosphane Ligands in Buchwald‐Hartwig Amination Reactions
Authors: Tröndle Sabrina , Freytag Matthias , Jones Peter G. , Tamm Matthias
Published: May 2019

Invited for the cover of this issue is the group of Matthias Tamm (pictures of first and last authors above) from the Technische Universität Braunschweig, Germany. The cover image shows the selective construction of allyl palladium complexes containing ancillary phosphane ligands based on [(η7‐C7H7)Ti(η5‐C5H5)] (“troticene”).
Mechanisms and Activity of 1‐Phenylethanol Dehydrogenation Catalyzed by Bifunctional NHC‐IrIII Complex
Authors: Wang Qiong , Guo Cai‐Hong , Zhang Xiang , Zhu Mi , Jiao Haijun , Wu Hai‐Shun
Published: May 2019

Acceptorless dehydrogenation of 1‐phenylethanol to acetophenone catalyzed by OH‐functionalized N‐heterocyclic carbene Cp*Ir(NHC) complexes under base‐free condition as well as under the promotion of protic co‐solvent tBuOH were investigated using density functional theory including solvation and van der Waals dispersion corrections. The first step is the 1‐phenylethanol dehydrogenation, which is more favored via an inner‐sphere over an outer‐sphere mechanism. The second step is H2 formation from Ir–H and O–H functionalities, which is the rate‐determining step, in agreement with the observed kinetic isotopic effect. The protic co‐solvent and 1‐phenylethanol act as a shuttle for proton transfer for the formation of H2.
Modular 3D Printed Compressed Air Driven Continuous‐Flow Systems for Chemical Synthesis
Authors: Penny Matthew R. , Rao Zenobia X. , Peniche Bruno Felício , Hilton Stephen T.
Published: May 2019

In this present study, we describe the development of a low‐cost, small‐footprint and modular 3D printed continuous‐flow system that readily attaches to existing stirrer hotplates. Flow‐rates are controlled by compressed air that is typically present in all fume hoods, making it suitable for use by synthetic chemists. The length of the flow‐path and reaction residence time is regulated by control of the air‐flow and pressure and by addition of one or more 3D printed polypropylene (PP) circular disk reactors that were designed to fit a DrySyn Multi‐E base, which is found in most synthetic laboratories. The ease of use of the system, the facile control of flow‐rates and the solvent resistance of the PP reactors was demonstrated in a range of SNAr reactions to produce substituted ether derivatives highlighting the utility and modularity of the system.
Phosphane‐Catalyzed [3+2] Annulation of Allenoates with 3‐Nitro‐2H‐chromenes: Synthesis of Tetrahydrocyclopenta[c]chromenes
Authors: Soares Maria I. L. , Gomes Clara S. B. , Nunes Sandra C. C. , Pais Alberto A. C. C. , Pinho e Melo Teresa M. V. D.
Published: May 2019

The synthesis of carbocyclic‐fused chromene derivatives based on allene chemistry is described. The phosphane‐catalyzed [3+2] annulation reactions of allenic esters with 3‐nitrochromenes have been established affording 3a‐nitro‐tetrahydrocyclopenta[c]chromenes in good yields (up to 87 %) with high stereo‐ and regioselectivity. Quantum chemical calculations, carried out at the DFT level of theory, were in agreement with the observed selectivity. The trichlorosilane‐mediated reduction of the 3a‐nitro‐tetrahydrocyclopenta[c]chromenes into the corresponding amines is also reported.
Predictors of treatment outcome in children with medically unexplained pain seeking primary care: A prospective cohort study
Authors: Wager Julia , Szybalski Katharina , Schenk Sabrina , Frosch Michael , Zernikow Boris
Published: May 2019

Background

Medically unexplained pain in children and adolescents is a common and increasing health care problem. Primary care is usually the first point of contact for these patients. It is the overall objective of this study to investigate treatment outcome of medically unexplained pain in paediatric primary care and to identify predictors of treatment failure.

Method

In a prospective observational cohort study with three assessments over 6 months, N = 266 children (6–17 years) presenting to paediatric primary care due to medically unexplained pain were included. The primary outcome is treatment failure after 6 months defined as disabling chronic pain. Risk factors for treatment failure were identified by means of logistic regression analyses.

Results

At the 6‐months follow‐up, treatment proved unsuccessful in 22.6% of patients. In patients with headaches, high functional impairment and strong emotional pain burden at study inclusion, the risk for treatment failure was increased. However, when also including data on the initial treatment response, pain location and functional impairment were no longer significant. Patients who did not respond to treatment within the first 3 months were more likely to experience treatment failure (OR = 203.7 ; p < 0.001) at 6 months, as were children with a higher emotional pain burden at study inclusion (OR = 1.3; p = 0.007; R2 = 0.781).

Conclusions

This study indicates that paediatric primary care is not sufficient for nearly one‐quarter of the children with medically unexplained pain. Individuals without a positive treatment response after 3 months are at increased risk for treatment failure.

Significance

This study investigates the treatment outcome of medically unexplained pain in paediatric primary care. Individuals with a higher emotional pain burden at the first visit and those without positive treatment response after 3 months are at increased risk for treatment failure. Therefore, a stepped‐care approach seems warranted. After an insufficient primary care trial of 3 months, patients should be transferred to pain specialists for a more intense treatment.
Optimization of DNA extraction from dental remains
Authors: Cafiero Concetta , Re Agnese , Stigliano Egidio , Bassotti Ezio , Moroni Rossana , Grippaudo Cristina
Published: May 2019

Efficient DNA extraction procedures is a critical step involved in the process of successful DNA analysis of such samples. Various protocols have been devised for the genomic DNA extraction from human tissues and forensic stains, such as dental tissue that is the skeletal part that better preserves DNA over time. However DNA recovery is low and protocols require labor‐intensive and time‐consuming step prior to isolating genetic material. Herein, we describe an extremely fast procedure of DNA extraction from teeth compared to classical method. Sixteen teeth of 100‐year‐old human remains were divided into two groups of 8 teeth and we compared DNA yield, in term of quantity and quality, starting from two different sample preparation steps. Specifically, teeth of group 1 were treated with a classic technique based on several steps of pulverization and decalcification, while teeth of group 2 were processed following a new procedure to withdraw dental pulp. In the next phase, the samples of both group underwent the same procedure of extraction, quantification and DNA profile analysis. Our findings provide an alternative protocol to obtain a higher amount of good quality DNA in a fast time procedure, helpful for forensic and anthropological studies.
The evolution of price discovery in us equity and derivatives markets
Authors: Wallace Damien , Kalev Petko S. , Lian Guanhua
Published: May 2019

This study considers the evolution of price discovery in the S&P 500 E‐mini futures and the corresponding exchange traded fund (SPY ETF) over the period January 2002 through December 2013. The study reports evidence that the E‐mini futures dominate price discovery at the beginning of the sample period. However, from 2007 onward both the SPY ETF and E‐mini futures contribute similar portions to the price discovery process. The level of price discovery is significantly influenced by volume measures and relative levels of transaction costs for both securities.
The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements
Authors: Suurmeijer Albert J. , Dickson Brendan C. , Swanson David , Zhang Lei , Sung Yun‐Shao , Huang Hsuan‐Ying , Fletcher Christopher D. , Antonescu Cristina R.
Published: May 2019

NTRK3‐rearranged tumors other than infantile fibrosarcomas (IFSs) harboring the canonical ETV6‐NTRK3 fusions are uncommon, and include mainly inflammatory myofibroblastic tumors and gastrointestinal stromal tumors. Herein, we describe an additional subset of seven tumors sharing NTRK3 gene rearrangements. The cohort included five females and two males (age range 1‐67 years). Tumors were located in extremities, trunk, retroperitoneum, or intra‐abdominal. In all tumors, fluorescence in situ hybridization (FISH) revealed rearrangements in NTRK3 accompanied by NTRK3 amplification in two cases. In three cases, RNA sequencing identified a fusion transcript composed of NTRK3 exon 14 fused to ETV6, TFG, and TPM4, respectively, retaining the NTRK3 kinase domain. All tumors were positive for pan‐TRK by immunohistochemistry (IHC). Two cases showed low‐ to intermediate‐grade histology composed of monomorphic spindle cells arranged in a patternless architecture, stromal bands, and perivascular rings of hyalinized collagen and coexpression of S100 and CD34. The remaining five cases were high‐grade fascicular monomorphic spindle cell sarcomas, morphologically somewhat reminiscent of either malignant peripheral nerve sheath tumors (MPNSTs) or fibrosarcomas (FSs). Two high‐grade NTRK3 sarcomas showed aggressive clinical behavior with development of lung metastases. Identification of high‐grade NTRK3‐rearranged sarcomas is clinically important, since the development of selective NTRK inhibitors has opened new avenues for targeted therapy. Although IHC for pan‐TRK can be applied as a screening tool, molecular studies are recommended for a conclusive diagnosis of NTRK‐rearranged neoplasms.
A comprehensive review of sectorial contribution towards greenhouse gas emissions and progress in carbon capture and storage in Pakistan
Authors: Hussain Mudassar , Butt Abdul R. , Uzma Faiza , Ahmed Rafay , Islam Tahir , Yousaf Balal
Published: May 2019

The extreme amount of greenhouse gases (GHGs) being released into the atmosphere has proved to be a globally challenging phenomenon that leads to changes in the climate and global warming. The amount of GHGs in the atmosphere has escalated immensely, with a substantial growth of 5.8% in 2010; a similar increase was observed in Pakistan as well. In Pakistan, carbon dioxide (CO2) emissions stand at 54% of total GHG emissions whereas methane, nitrous oxide, carbon monoxide and volatile organic carbon contribute to emissions at 36%, 9%, 0.75% and 0.3%, respectively. One of the key reasons for climatic changes is GHG emission generation from human interventions and activities related to transportation, urban development, industrialization, energy sources, farming and agriculture, waste's improper management, land use and forestry. In 2011, Pakistan's entire GHG emissions were a whopping 347 Mt of CO2‐eq, and by 2050, they are estimated to reach 4621 Mt CO2‐eq. This review evaluates and assesses GHG emissions generating from various sectors in Pakistan, in a socio‐scientific prospect that is caused by human activities and interventions in different economic sectors in Pakistan, endangering the environment across the country. Additionally, the review examines the current level of GHG emissions while accounting for China–Pakistan Economic Corridor–based emissions, abatement strategies including development of a state‐of‐the‐art technique for carbon capture and storage/utilization technologies in Pakistan. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
A new permeation model in porous filler–based mixed matrix membranes for CO2 separation
Authors: Moftakhari Sharifzadeh Mohammad Mehdi , Zamani Pedram Mona , Ebadi Amooghin Abtin
Published: May 2019

In this paper, a novel comprehensive permeation model for mixed matrix membranes (MMMs) is introduced. This model shows the importance of understanding and developing a more reliable model for the permeation behavior of MMMs containing porous filler nanoparticles. A new method is established to provide a more precise/large‐scale three‐dimensional MMMs geometry. The required number of spherical porous fillers in random/nonuniform positions in the polymer matrix is calculated. Interfacial equilibrium constant (K) at the polymer/filler interfaces was adjusted as the concentration ratio of the diffusing penetrants (C2 and C1) at the interface, respectively. In this case, the K values are changed by varying the intended gaseous concentration due to their permeation through the MMM. Hence, its effect on penetrants effective diffusion coefficient was examined. Then, the obtained results were evaluated with similar experimental data, which showed much consistency. Therefore, the accurate calculation method for MMMs permeability was governed for the entire range of the operating pressures in MMMs. The results showed that the permeability of MMMs increases with increasing filler particle size. On the other hand, variations that occur in the MMM permeability at various particle size were much more distinct at higher loadings. Moreover, some well‐known analytical permeation models were used to compare and validate the model's permeability results. It can be concluded that this model provides a method for more precise and realistic design of MMMs as well as to better construe the large number of related experimental data. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Online information and support for carers of people with young‐onset dementia: A multi‐site randomised controlled pilot study
Authors: Metcalfe Anna , Jones Bridget , Mayer Johannes , Gage Heather , Oyebode Jan , Boucault Sarah , Aloui Sabrina , Schwertel Uta , Böhm Markus , Tezenas du Montcel Sophie , Lebbah Said , De Mendonça Alexandre , De Vugt Marjolein , Graff Caroline , Jansen Sabine , Hergueta Thierry , Dubois Bruno , Kurz Alexander
Published: May 2019

Objectives

The European RHAPSODY project sought to develop and test an online information and support programme for caregivers of individuals diagnosed with young onset dementia. The objectives were to assess user acceptability and satisfaction with the programme and to test outcome measures for a larger effectiveness study.

Design

A pilot randomised controlled trial in England, France, and Germany was conducted with 61 caregivers for adults with young onset Alzheimer's disease or frontotemporal degeneration. Evaluations at baseline, week 6, and week 12 assessed user acceptability and satisfaction. Use of the programme was measured from online back‐end data. Qualitative feedback on user experiences was collected via semi‐structured interviews. Measures of caregiver well‐being (self‐efficacy, stress, burden, frequency of patient symptoms, and caregiver reactions) were explored for use in a subsequent trial.

Results

Participants logged in online on average once a week over a 6‐week period, consulting approximately 31% of programme content. Seventy percent of participants described the programme as useful and easy to use. Eighty‐five percent expressed intent to use the resource in the future. Reductions in reported levels of stress and caregivers' negative reactions to memory symptoms were observed following use of the programme.

Conclusions

Results indicated that the RHAPSODY programme was acceptable and useful to caregivers. The programme may be complementary to existing services in responding to the specific needs of families affected by young onset dementia. Distribution of the programme is underway in England, France, Germany, and Portugal.
Brain biomarkers and cognition across adulthood
Authors: Tsapanou Angeliki , Habeck Christian , Gazes Yunglin , Razlighi Qolamreza , Sakhardande Jayant , Stern Yaakov , Salthouse Timothy A.
Published: May 2019

Understanding the associations between brain biomarkers (BMs) and cognition across age is of paramount importance. Five hundred and sixty‐two participants (19–80 years old, 16 mean years of education) were studied. Data from structural T1, diffusion tensor imaging, fluid‐attenuated inversion recovery, and resting‐state functional magnetic resonance imaging scans combined with a neuropsychological evaluation were used. More specifically, the measures of cortical, entorhinal, and parahippocampal thickness, hippocampal and striatal volume, default‐mode network and fronto‐parietal control network, fractional anisotropy (FA), and white matter hyperintensity (WMH) were assessed. z‐Scores for three cognitive domains measuring episodic memory, executive function, and speed of processing were computed. Multiple linear regressions and interaction effects between each of the BMs and age on cognition were examined. Adjustments were made for age, sex, education, intracranial volume, and then, further, for general cognition and motion. BMs were significantly associated with cognition. Across the adult lifespan, slow speed was associated with low striatal volume, low FA, and high WMH burden. Poor executive function was associated with low FA, while poor memory was associated with high WMH burden. After adjustments, results were significant for the associations: speed‐FA and WMH, memory‐entorhinal thickness. There was also a significant interaction between hippocampal volume and age in memory. In age‐stratified analyses, the most significant associations for the young group occurred between FA and executive function, WMH, and memory, while for the old group, between entorhinal thickness and speed, and WMH and speed, executive function. Unique sets of BMs can explain variation in specific cognitive domains across adulthood. Such results provide essential information about the neurobiology of aging.
YouTube marketing communication demographic and usage variables influence on Gen Y's cognitive attitudes in South Africa and Romania
Authors: Duffett Rodney Graeme , Edu Tudor , Negricea Iliuta Costel
Published: May 2019

The primary purposes of this study are to consider the influence of YouTube marketing communication (YMC) on awareness and knowledge among Generation (Gen) Y cohort respondents in South Africa (SA) and Romania (RO) and to establish if country, demographic, and usage (independent) variables have an effect on this cognitive attitudinal association. Multistage sampling was employed, and a survey was conducted among 400 respondents in SA and 400 respondents in RO. Structural equation modelling was used to investigate the hypothesized associations. The findings confirm that awareness had a favorable influence on knowledge for the total sample, SA and RO. The results also show that awareness displayed a significantly larger positive effect on knowledge among Romanian Gen Y in comparison with South African Gen Y. This study confirms that age (demographic variable) and access, usage length, log‐on frequency, log‐on duration, and advertisement viewership numbers (usage variables) have a significant effect on cognitive attitudinal responses due to YMC among Gen Y in SA and RO. Organizations should consider adapting YMC strategies to stimulate awareness, which will stimulate favorable knowledge attitudinal responses, as well as consider the aforementioned demographic and usage variables when targeting the infamously unpredictable Gen Y due to the positive cognitive attitudinal association in developing countries.
Pharmacy driven assessment of appropriate antibiotic selection in patients with reported beta‐lactam allergy
Authors: Holmes Ashley K. , Bennett Nicholas T. , Berry Timothy P.
Published: May 2019

Background

Reported beta‐lactam (BL) antibiotic allergies lead to the avoidance of BL antibiotics. Despite that less than 10% of patients reporting have a true allergy, the documentation often leads to an increased use of alternative antibiotics. These nonpreferred antibiotics (NPA) have a significant impact on cost, clinical outcomes, and antimicrobial resistance.

Objective

The primary objective of this study was to assess the impact of a pharmacy‐driven assessment on the prescribing frequency of penicillin or cephalosporin antibiotics in patients with a reported BL allergy.

Methods

This retrospective cohort analysis evaluated the effect of a best practice alert (BPA) and subsequent allergy assessment on BL use in patients with reported allergies at an integrated health system. The BPA notified pharmacy staff that a patient with a documented BL allergy was receiving a NPA. Pharmacy staff assessed previous BL tolerance and clarified reaction, severity, and timing of the documented allergy. Patients were identified for analysis if they had a documented BL allergy within the electronic medical record and received at least one antibiotic during the study period.

Results

A total of 418 patients were included in this analysis (180 preimplementation, 238 postimplementation). In the pharmacy‐driven assessment group, BL antibiotic use increased by 12.9% (P = .008) in patients with a previously documented BL allergy with the largest use increase in 3rd/4th generation cephalosporins (P = .045). Days of therapy for NPAs decreased in the postimplementation group, including aztreonam (P = .006) and vancomycin (P = .009).

Conclusions

Our data suggests that a pharmacy‐driven allergy assessment using a BPA can increase appropriate use of BL antibiotics for hospitalized patients.
Regulatory role of Golgi brefeldin A resistance factor‐1 in amyloid precursor protein trafficking, cleavage and Aβ formation
Authors: Liu Kaifei , Liu Ying , Xu Yanting , Nandakumar Kutty Selva , Shen Xiaoyan , Lin Jiahe , Li Cuixian , He Chonghua , Zhou Chun
Published: May 2019

β‐amyloid peptide (Aβ) deposition derived from sequential cleavage of the amyloid precursor protein (APP) through the amyloidogenic pathway is an important characteristic feature of Alzheimer's disease (AD). During this process, cellular trafficking plays a crucial role. A large Sec7‐domain containing ADP‐ribosylation factor guanine nucleotide exchange factor (ARF‐GEF), Golgi brefeldin A resistance factor 1 (GBF1) has been reported to initiate the ADP‐ribosylation factor (Arf) activation cascade at trans‐Golgi network, which plays a crucial function at the endoplasmic reticulum‐Golgi interface. In this study, we investigated the role of GBF1 in APP transmembrane transport and Aβ formation. Using APP/PS1 (presenilin 1) overexpressing transgenic mice, we demonstrate that GBF1 has upregulated the expression of APP, indicating a role for GBF1 in APP physiological process. Knocking down of GBF1 using small interfering has significantly increased the intracellular but not the surface expression of APP. In contrast, overexpression of wild‐type (WT) and guanine nucleotide exchange factor (GEF) in the activated form but not the GEF deficient mutation induced continuous activation of GBF1, which subsequently increased the surface level of APP. Interestingly, inhibition of GBF1 by c(BFA) also impaired APP trafficking and induced endoplasmic reticulum (ER) stress in SH‐SY5Y cells. Our results thus for identified the role of GBF1 in APP trafficking and cleavage, and provide evidence for GBF1 as a possible therapeutic target in AD.
Biological and anti‐vascular activity evaluation of ethoxy‐erianin phosphate as a vascular disrupting agent
Authors: Yuan Wenshuang , Su Chang , Yang Xiaotong , Li Yueqi , Cao Yiou , Liang Xin , Liu Jianwen
Published: May 2019

The effects of ethoxy‐erianin phosphate (EBTP) on cell proliferation, mitotic cell arrest, migration, infiltration, and endothelial tubular structures were evaluated in this study. The antiproliferative activity of EBTP and combretastatin A‐4P (CA4P) was analyzed on several tumor cells (including MCF‐7, HeLa, 2LL, and 2LL‐IDO) and on an endothelial cell (human umbilical vein endothelial cells [HUVECs]) as well as a human normal liver cell (L02). The results showed that EBTP possessed antiproliferative activity in the micromole range and was relatively less toxic than CA4P. Treating HUVECs with EBTP caused cell accumulation in the G2/M phase, and wound‐healing assays indicated that EBTP inhibited cell migration. Furthermore, EBTP and CA4P destroyed the vasculature in endothelial cells and showed vascular disrupting activity of the chorioallantoic membrane in fertilized chicken eggs. In addition, we found that EBTP suppressed the expression of indoleamine 2,3‐dioxygenase (IDO) and significantly inhibited IDO‐induced migration and infiltration of 2LL‐IDO cells. Administration of EBTP blocked vasculogenic mimicry in 2LL‐IDO cells, which was typically observed in tube formation assays of 2LL‐IDO cells. Moreover, the results of Lewis lung carcinoma in mice showed a high inhibition rate of EBTP. EBTP is an effective vascular disrupting agent that is superior to CA4P and may prevent and treat malignancy by inhibiting the expression of IDO.
Inhibition of CTRP6 prevented survival and migration in hepatocellular carcinoma through inactivating the AKT signaling pathway
Authors: Wan Xiaolong , Zheng Caixia , Dong Lei
Published: May 2019

C1qTNF‐related proteins (CTRPs) are a member of the adiponectin paralogs family, which are implicated in regulation of various biological processes. Recently, CTRP6 was found upregulated in human hepatocellular carcinomas (HCC). However, the specific roles and molecular mechanisms of CTRP6 in HCC remain unclear. Here, we investigated the effects of CTRP6 on the vitality, apoptosis, migration, and invasion of HCC cells. Firstly, we measured the levels of CTRP6 in HCC tissues and cell lines. Our results showed that CTRP6 was markedly upregulated in HCC tissues and Hep3B cells. Then, the CTRP6 siRNA was transfected into Hep3B cells. Cell counting kit‐8 (CCK‐8) assay and flow cytometry analysis revealed that silencing CTRP6‐induced cell viability inhibition, and apoptosis. The wound‐healing and transwell assay showed that CTRP6 deficiency suppressed the migration and invasion of Hep3B cells. Meanwhile, the AKT phosphorylation level was reduced by CTRP6 silencing. Next, Hep3B cells were pretreated with insulin‐like growth factor‐1 (IGF‐1) (an activator of AKT), and then transfected with CTRP6 siRNA, and the cell vitality, apoptosis, migration, and invasion were measured again. We found that all these alterations caused by CTRP6 inhibition could be reversed by IGF‐1 treatment. Taken together, CTRP6 suppression blocked cell survival, migration, and invasion and promoted cell apoptosis through inactivating the AKT signaling pathway. Our findings present a novel potential molecular target for HCC therapy.
EMP1 regulates cell proliferation, migration, and stemness in gliomas through PI3K‐AKT signaling and CD44
Authors: Wang Junxiang , Li Xuetao , Wu Haibin , Wang Hao , Yao Lin , Deng Zhitong , Zhou Youxin
Published: May 2019

Glioblastoma multiforme (GBM) is an intracranial tumor; the feature is higher malignant and poorer prognosis. The search for therapeutic targets for gliomas has always been a focus of research in the field of neurology. The unusual expression of epithelial membrane protein 1 (EMP1) has been proved in most tumors. In our study, we determined the expression level of EMP1 expression in glioma tissues. There were higher levels of EMP1 in glioma tissues—particularly GBM tissues—than those in normal brain tissues. Then we discovered that silencing EMP1 inhibited glioma cell invasion and proliferation through inhibiting the PI3K‐AKT signaling pathway. Subsequently, we investigated the function of EMP1 on glioma stem cells and found that it regulates the expression of CD44 in such cells to promote stemness. Taken together, the new strategies for the treatment of glioma may be provided by these finding, thereby improving the prognosis associated with it.
MicroRNA‐628‐5p inhibits cell proliferation in glioma by targeting DDX59
Authors: Xie Peng , Wang Yan , Liao Yuanmei , Han Qiu , Qiu Zhichao , Chen Yinbing , Zuo Xiaohua
Published: May 2019

Recent study has reported that microRNA‐628‐5p (miR‐628‐5p) is involved in the development of epithelial ovarian cancer; however, the mechanisms of miR‐628‐5p in glioma remain unclear. In this study, we explored the potential biological roles of miR‐628‐5p in glioma. First, we found that miR‐628‐5p was decreased in the tissues and cells (U87 and T98) of glioma. Second, overexpressing miR‐628‐5p reduced the ability of glioma cells' proliferation and induced glioma cells' cycle arrest in G1. Then, we found that miR‐628‐5p directly bound to the 3′‐untranslated region of DDX59 and decreased the protein level of DDX59. The decrease of DDX59 was found to lead to the decrease of p‐AKT. Mechanistic studies revealed that restoring the expression of DDX59 alleviated miR‐628‐5p‐induced inhibition of proliferation of glioma. These findings suggest that the miR‐628‐5p/DDX59 axis has a key role in the development of glioma, and miR‐628‐5p might be a new therapeutic target against glioma.
Long noncoding RNA CPS1‐IT1 suppresses melanoma cell metastasis through inhibiting Cyr61 via competitively binding to BRG1
Authors: Zhou Xiaobo , Rao Yamin , Sun Qilin , Liu Yang , Chen Jun , Bu Wenbo
Published: May 2019

Long noncoding RNA CPS1‐IT1 is recently recognized as a tumor suppressor in several cancers. Here, we investigate the role of CPS1‐IT1 in human melanoma. Presently, our study reveals the low expression of CPS1‐IT1 in human melanoma tissues and cell lines, which is significantly associated with metastasis and tumor stage. Besides, the potential of CPS1‐IT1 as a prognosis‐predictor is strongly indicated. Functionally, CPS1‐IT1 overexpression inhibits cell migration, invasion, epithelial–mesenchymal transition, and angiogenesis in melanoma cells. CYR61, an angiogenic factor that participates in tumor metastasis as well as a recognized oncogene in melanoma, is shown to be confined under CPS1‐IT1 overexpression in melanoma cells. Furthermore, enforced expression of Cyr61 in CPS1‐IT1‐silenced melanoma cells dramatically normalized the protein level of Cyr61 and that of its downstream targets vascular endothelial growth factor and matrix metalloproteinase‐9, as well as the repressive effect of CPS1‐IT1 overexpression on melanoma cell metastasis. BRG1, a core component of SWI/SNF complex, is implied to interact with both CPS1‐IT1 and Cyr61 in melanoma cells. Moreover, CPS1‐IT1 negatively regulates Cyr61 expression by blocking the binding of BRG1 to Cyr61 promoter. Jointly, CPS1‐IT1 controls melanoma metastasis through impairing Cyr61 expression via competitively binding with BRG1, uncovering a novel potential therapeutic and prognostic biomarker for patients with melanoma.
CCL5 secreted by senescent theca‐interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis
Authors: Shen Lu , Chen Yuan , Cheng Jing , Yuan Suzhen , Zhou Su , Yan Wei , Liu Junfeng , Luo Aiyue , Wang Shixuan
Published: May 2019

As a fundamental aging mechanism, cellular senescence causes chronic inflammation via the senescence‐associated secretory phenotype (SASP). Theca‐interstitial cells are an essential but little‐studied component of follicle development in the ovarian microenvironment. In the present study, we observed significant cellular senescence in theca‐interstitial cells and secretion of chemokine (C‐C motif) ligand 5 (CCL5) by these cells during aging. Furthermore, we aimed to investigate whether and how senescence‐associated secretory phenotype (SASP)‐associated CCL5 may be involved in follicle development. Increased levels of CCL5 in the microenvironment of follicles attenuated preantral follicle growth, survival, and estradiol secretion. Oocyte maturation and the expression of zona pellucida 3 and differentiation factor 9 (GDF9) were also inhibited by CCL5. Granulosa cell apoptosis in follicles was promoted by CCL5, accompanied by the phosphorylation of nuclear factor‐κB by CCL5 and inhibition of the PI3K/AKT pathway. These results suggest that SASP‐associated CCL5 produced by senescent theca‐interstitial cells may impair follicle development and maturation during ovarian aging by promoting granulosa cell apoptosis.