bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations into neuroprotectivity, stability, and water solubility of 7‐O‐cinnamoylsilibinin, its hemisuccinate and dehydro derivatives
Authors: Schramm Simon , Gunesch Sandra , Lang Florian , Saedtler Marco , Meinel Lorenz , Högger Petra , Decker Michael
Published: October 2018

Derivatives of the recently described potent neuroprotective 7‐O‐cinnamoylsilibinin ester were prepared: its hemisuccinate to improve water solubility and the dehydrosilibinin ester that was shown to form in assay media to investigate its role in overall neuroprotective effects. 7‐O‐Cinnamoyl‐2,3‐dehydrosilibinin is less neuroprotective than 7‐O‐cinnamoylsilibinin in a murine hippocampal cell line (HT‐22) and we conclude that the dehydrosilibinin derivatives are not the actual carriers of neuroprotective properties, at least in the assay applied. Solubility of the test compounds was determined in shake‐flask experiments and the ester's solubility was greatly improved by introduction of a hemisuccinate at the 23‐position of silibinin. Time–stability curves in assay media were recorded. The hemisuccinate ester did not act as a prodrug to release 7‐O‐cinnamoylsilibinin but is the second ester bond to be cleaved. Nevertheless, it still exhibits significant neuroprotection. Therefore, its greatly increased solubility might effectively counterbalance lower in vitro neuroprotection.
Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus
Authors: Dall'Era Maria , Pauli Mariela L. , Remedios Kelly , Taravati Keyon , Sandova Priscila M. , Putnam Amy L. , Lares Angela , Haemel Anna , Tang Qizhi , Hellerstein Marc , Fitch Marc , McNamara James , Welch Beverly , Bluestone Jeffrey A. , Wofsy David , Rosenblum Michael D. ,   the Autoimmunity Centers of Excellence
Published: October 2018

Objective

Adoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease.

Methods

We describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment.

Results

Deuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon‐γ pathway and a reciprocal augmentation of the interleukin‐17 (IL‐17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL‐17 production.

Conclusion

We report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses.
Aberrant functional connectivity of inhibitory control networks in children with autism spectrum disorder
Authors: Voorhies Willa , Dajani Dina R. , Vij Shruti G. , Shankar Sahana , Turan Turel Ozerk , Uddin Lucina Q.
Published: October 2018

Development of inhibitory control is a core component of executive function processes and a key aspect of healthy development. Children with autism spectrum disorder (ASD) show impairments in performance on inhibitory control tasks. Nevertheless, the research on the neural correlates of these impairments is inconclusive. Here, we explore the integrity of inhibitory control networks in children with ASD and typically developing (TD) children using resting state functional Magnetic Resonance Imagaing (MRI). In a large multisite sample, we find evidence for significantly greater functional connectivity (FC) of the right inferior frontal junction (rIFJ) with the posterior cingulate gyrus, and left and right frontal poles in children with ASD compared with TD children. Additionally, TD children show greater FC of rIFJ with the superior parietal lobule (SPL) compared with children with ASD. Furthermore, although higher rIFJ‐SPL and rIFJ‐IPL FC was related to better inhibitory control behaviors in both ASD and TD children, rIFJ‐dACC FC was only associated with inhibitory control behaviors in TD children. These results provide preliminary evidence of differences in intrinsic functional networks supporting inhibitory control in children with ASD, and provide a basis for further exploration of the development of inhibitory control in children with the disorder. Autism Research 2018, 11: 1468–1478. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Inhibitory control is an important process in healthy cognitive development. Behavioral studies suggest that inhibitory control is impaired in autism spectrum disorder (ASD). However, research examining the neural correlates underlying inhibitory control differences in children with ASD is inconclusive. This study reveals differences in functional connectivity of brain networks important for inhibitory control in children with ASD compared with typically developing children. Furthermore, it relates brain network differences to parent‐reported inhibitory control behaviors in children with ASD. These findings provide support for the hypothesis that differences in brain connectivity may underlie observable behavioral deficits in inhibitory control in children with the disorder.
How Have We Done in Reducing Lead in Water Since the LCR?
Authors: Cornwell David A.
Published: October 2018

With a proposal to update the Lead and Copper Rule expected in 2019, it is a good time to evaluate improvements since the 1991 rule took effect.
Comparison of ELISA and LC‐MS/MS Analytical Methods and Validation of AWWA Hazen‐Adams CyanoTOX
Authors: He Xuexiang , Stanford Benjamin D. , Adams Craig , Rosenfeldt Erik J. , Wert Eric C.
Published: October 2018

A comparison of two applications commonly used to detect cyanotoxins—ELISA and LC‐MS/MS—has the added benefit of providing kinetic data to validate cyanotox V.1.0.
Cognitive achievement of children of immigrants: Evidence from the Millennium Cohort Study and the 1970 British Cohort Study
Authors: Hoffmann Nathan I.
Published: October 2018

Although numerous studies have described the educational attainment of ethnic minorities in the UK, few have focused specifically on children born in the UK to two immigrant parents. First, using ordinary least squares (OLS) estimation, this article examines the cognitive assessment scores of children of immigrants in the 1970 British Cohort Study (BCS70) and the Millennium Cohort Study (MCS). It then exploits the richer data of the MCS to construct multilevel models for children of immigrants in this more recent cohort. In the BCS70, children of immigrants show significant gaps at ages 5 and 10 in both reading and maths scores. Even when controls are included in the OLS model for the BCS70, children of Caribbean immigrants are expected to perform worse in both assessments. In the raw MCS data, on the other hand, nearly no gap remains in age‐11 and ‐14 assessments. Although Bangladeshi children of immigrants in the MCS have negative coefficients in the OLS analysis, in the final multilevel model for the MCS, all children of immigrants follow positive trajectories wherein no group attains distinguishably lower scores than their peers in later assessments, and Indian children of immigrants even outperform their peers in the MCS model's predictions.
Experiences of using a game for improving learning in software requirements elicitation
Authors: Garcia Ivan , Pacheco Carla , León Andrés , Calvo‐Manzano Jose A.
Published: October 2018

Many recent studies have demonstrated that the traditional methods used in teaching software requirements elicitation are ineffective because they frequently produce unskilled graduates who are inappropriately trained to apply their practical knowledge in the workplace. Therefore, the combination of traditional teaching approaches and modern learning tools has been used to better prepare undergraduate students. Biyubi is a game that has been developed to complement traditional teaching in order to facilitate the learning of requirements elicitation activities on an undergraduate Software Engineering course. Biyubi provides a simulated environment for students so that they can explore, analyze, and discover the wishes and needs of the correct stakeholders. This game has been tested and validated by undergraduate students from the NovaUniversitas University, Mexico. The use of Biyubi achieved an increase in the motivation, satisfaction, and learning experience of students in requirements elicitation. The game has the potential to better explain the proper use of a requirements elicitation technique while the technical skills of the students are also improved.
Strain Redistribution in Metal‐Sulfide‐Composite Anode for Enhancing Volumetric Lithium Storage
Authors: Xie Dong , Yuan Yingdong , Xiao Li , Cheng Faliang , Zhang Min , Fan Hongbo , Ge Xiang
Published: October 2018

Volumetric capacity, though being the most important metric for batteries, remains difficult to improve. This work demonstrates that the large volume expansion of active materials can be buffered when they are loaded on a backbone with medium volume expansion during lithium insertion, thus achieving a high volumetric specific capacity with acceptable cycling stability. Specifically, we imbedded SnS inside a MoS2@C brochosome‐like matrix. The composite delivers tremendously improved volumetric specific capacity due to the synergy between the high‐capacity SnS with alloy‐type lithium storage mechanism and the MoS2@C brochosome‐like backbone with moderate lithium storage capability and stable structure. This composite delivers highly reversible capacity and excellent capacity retention (720 mAh cm−3 after 200 cycles at 200 mA g−1), and superior rate capacity of 465 mAh cm−3 at 4 A g−1. Such structure, involving a porous, stable and active matrix and a high‐capacity filler in the pores, could be a general structural guidance for making electrode materials with high volumetric specific capacity.
Zinc Oxide‐Catalyzed Dehydrogenation of Primary Alcohols into Carboxylic Acids
Authors: Monda Fabrizio , Madsen Robert
Published: October 2018

Zinc oxide has been developed as a catalyst for the dehydrogenation of primary alcohols into carboxylic acids and hydrogen gas. The reaction is performed in mesitylene solution in the presence of potassium hydroxide, followed by workup with hydrochloric acid. The transformation can be applied to both benzylic and aliphatic primary alcohols and the catalytically active species was shown to be a homogeneous compound by a hot filtration test. Dialkylzinc and strongly basic zinc salts also catalyze the dehydrogenation with similar results. The mechanism is believed to involve the formation of a zinc alkoxide which degrades into the aldehyde and a zinc hydride. The latter reacts with the alcohol to form hydrogen gas and regenerate the zinc alkoxide. The degradation of a zinc alkoxide into the aldehyde upon heating was confirmed experimentally. The aldehyde can then undergo a Cannizzaro reaction or a Tishchenko reaction, which in the presence of hydroxide leads to the carboxylic acid.
Circulating markers of collagen types I, III, and IV in patients with dilated cardiomyopathy: relationships with myocardial collagen expression
Authors: Nagao Kazuya , Inada Tsukasa , Tamura Akinori , Kajitani Kenji , Shimamura Kiyotaka , Yukawa Hiroshi , Aida Kenji , Sowa Naoya , Nishiga Masataka , Horie Takahiro , Makita Toshinori , Ono Koh , Tanaka Masaru
Published: October 2018

Aims

Collagen‐derived peptides such as collagen I C‐terminal telopeptide (CITP) and procollagen III N‐terminal propeptide (PIIINP) have been conventionally used as markers of cardiac fibrosis. Collagen IV 7S domain (P4NP 7S) has been recently reported to be correlated with haemodynamics in patients with acute heart failure. We investigated whether these markers reflect cardiac remodelling and myocardial collagen expression.

Methods and results

In 80 patients with dilated cardiomyopathy, relationships of CITP, PIIINP, and P4NP 7S to clinical and echocardiographic variables were analysed. CITP and PIIINP were inversely correlated with estimated glomerular filtration rate (r = −0.41, P < 0.001 and r = −0.32, P = 0.004, respectively); P4NP 7S was positively correlated with B‐type natriuretic peptide (r = 0.32, P = 0.003) and γ‐glutamyltransferase (r = 0.38, P < 0.001). These correlations were significant even after adjustment by potential confounders, whereas all three collagen markers were not independently correlated with ejection fraction nor with left ventricular (LV) diastolic diameter. In 33 patients undergoing endomyocardial biopsy, myocardial collagen I and III mRNA expressions were correlated with LV end‐diastolic volume index (r = 0.42, P = 0.02 and r = 0.54, P = 0.002, respectively), whereas myocardial collagen IV mRNA expression was not correlated with LV end‐diastolic volume index nor with ejection fraction. Each collagen‐derived peptide was not significantly correlated with the myocardial expression of their corresponding collagen mRNA.

Conclusions

Our study shows that CITP, PIIINP, and P4NP 7S do not reflect myocardial collagen mRNA expression but presumably reflect extra‐cardiac organ injury in heart failure.
Copper‐Catalyzed (Di)Arylmethylation of Phosphorylamides Under Oxidative Conditions
Authors: Zhao Zijian , Liu Xiaobo , Hou Anguo , Lian Yan
Published: October 2018

A compatible and practical (di)arylmethylation of phosphorylamides was successfully accessed in the presence of copper iodide as the catalyst, azodiisobutyronitrile as the radical initiator, and di‐tert‐butyl peroxide as the oxidant. Both methylarenes and diaryl methanes were compatible under the oxidative conditions, enjoying broad functional groups tolerance (51 examples) and good efficiency (up to 90 % yields).
Comparative tissue distribution and depuration characteristics of copper nanoparticles and soluble copper in rainbow trout (Oncorhynchus mykiss)
Authors: Lindh Stina , Razmara Parastoo , Bogart Sarah , Pyle Gregory
Published: October 2018

The continuously growing number of products containing nanoparticles (NPs) makes their presence in the environment inevitable, and given the well-known toxicity of dissolved metals, concerns regarding the toxicity of metal-based NPs have been raised. Whether metal-based NPs present similar or different toxicological effects compared with metal salts is an emerging field. In the present study, rainbow trout were intraperitoneally injected with CuSO4 or copper NPs (CuNPs) to investigate tissue distribution and depuration characteristics. Fish injected with Cu showed an initial accumulation of Cu in the liver, kidney, gills, intestine, and carcass. The Cu concentration in the liver of CuNP-injected fish increased over time. It appears as though CuNPs accumulated in the liver at a greater rate than they were excreted. In livers of fish injected with CuSO4, the Cu concentration appeared to increase and reach an equilibrium, suggesting that copper was accumulated and excreted at the same rate. The possibility that CuNPs can accumulate at a higher rate than it is excreted in the liver warrants further investigation. The present study demonstrates the possibility of dietary uptake of CuNPs because elevated Cu concentrations were observed in carcass, gills, kidney, and intestine of fish gavaged with CuNPs. In conclusion, the results suggest that dietary CuNPs are taken up by the gut and preferentially accumulate in the liver. Environ Toxicol Chem 2019;38:80–89. © 2018 SETAC

Abstract

It appears as though copper nanoparticles accumulated in the liver at a greater rate than they were excreted. In livers of fish injected with CuSO4, the Cu concentration appeared to increase and reach an equilibrium, suggesting that Cu was accumulated and excreted at the same rate. CuNP = copper nanoparticle.
Development of a water‐permeable annular gap fill for single‐shell drained segmental linings
Authors: Thienert Christian , Leismann Frank , Edelhoff Dennis , Valentini Heiko , Hörlein Norbert , Kleen Eugen
Published: October 2018

Nowadays, tunnels with single‐shell segmental lining are often constructed pressure‐tight using gaskets. The economic application limit of this construction type is about 50 metres head of water. If the water pressure exceeds this value, considerably more complex – and thus more expensive – two‐shell construction with an additional drainage layer between the inner and the outer lining is required. To extend the field of application of mechanized tunnelling with single shell lining in mid‐mountain formations, an innovative approach was developed based on the application of a drainage layer in the annular gap fill with a water permeability kF >10–4 m/s. The basic idea of the newly developed water‐permeable material for annular gap grouting is the use of a foam generator without a disturbing body, which foams the cement suspension in a defined way with sufficient compressive strength. Complex interrelations of material, process engineering and construction had to be considered comprehensively. The overall suitability of the developed process has been demonstrated in an extensive experimental program including field tests. The present paper focuses on the development of the construction material.
Semmering Base Tunnel – Geotechnical models in design and construction
Authors: Lenz Gerold , Poisel Alexander , Brandtner Markus , Goricki Andreas , Wagner Oliver K.
Published: October 2018

The article describes the fundamental geotechnical model assumptions in the design phase of the Semmering Base Tunnel. Two selected case studies show the verification of the geotechnical model during tunnel construction. The verification process is essentially based on geotechnical monitoring in combination with specific back analyses. It is shown that particularly in complex geotechnical conditions, such as deep tunnels in weak rock mass, the designer can only assess a range of expected behaviour. Most information about system behaviour and thus about the geotechnical model conceptions can only be gained during construction. An improved understanding of the geotechnical model provides the potential to identify and minimize geotechnical risks earlier and to adapt excavation and support measures to the actual conditions.
Tunnel pre‐support using pipe umbrellas – Technical developments and their advantages
Authors: Volkmann Günther M.
Published: October 2018

Pipe umbrella support systems have been used successfully for tunnelling in challenging ground conditions since the 1970s. The single umbrella pipes are installed stepwise and parallel to the later installed saw‐tooth shaped primary lining by connecting pipe pieces to each other. The connections are the weakest link of the support system, so recent developments in this field also have an effect on system performance. The development of both machinery and connection types have a major influence on pipe umbrella design for tunnelling. This includes not only simple parameters like installation length or tube dimension but also the connection type. So a conventional pipe umbrella design is not as cost‐efficient as current technical possibilities allow, because material as well as time savings are missed. This article explains possible optimisations for pipe umbrella supported tunnels with simple examples to show cost‐optimised design principles regarding time and material.
Semmering Base Tunnel – Design and construction of the shaft head caverns under difficult conditions
Authors: Wieland Gerd , Prall Karoline , Lenz Gerold , Schachinger Tobias , Gobiet Gerhard
Published: October 2018

In contract SBT1.1 of the Semmering Base Tunnel, the single‐track main tunnels are being driven from the portal in Gloggnitz and from a temporary intermediate starting point in Göstritz. The temporary intermediate starting point in Göstritz is being constructed in order to reduce the risk to the tunnel construction time for the Graßberg‐Schlagl fault system. During the construction phase, the contractor developed optimisations of the planned logistics concept for the intermediate access point in Göstritz, which led to a redesign of the shaft head cavern system. Shortly before the excavation of the shaft head cavern, an unexpected and geotechnically relevant fault zone was encountered in the access tunnel. In order to investigate the geological situation in the area of the shaft head, extensive additional investigation measures were carried out. Due to the updated geological forecast, the layout of the shaft head cavern and the support concept had to be changed. Thanks to the measures taken, the shaft head cavern system cold be successfully excavate without any damage to the support.
The use of TBM process data as a normative basis of the contractual advance classification for TBM advances in hard rock
Authors: Bach Dietmar , Holzer Wolfgang , Leitner Wolfgang , Radončić Nedim
Published: October 2018

In April 2016 a newly formed working group began with the revision of the Austrian standard ÖNORM B 2203‐2. The goal of the group was the establishment of a practicable advance classification scheme, which would be applicable both for the design and for the construction phase. In addition, a clear separation should be established between a regular advance, which is clearly described and can be calculated by the bidding contractor, and a ”hindered advance“, which cannot clearly be described and calculated. The contractual framework is used to compensate for the regular advance, and hindering occurrences such as water ingress or increased wear are compensated by additional contractual time‐dependent costs. Fair compensation regulations for hindered advance (such as an advance through blocky rock mass, mixed face conditions, swelling, squeezing ground, major face instabilities, increased adhesion and stickiness of muck, obstacles and suspension losses) are to be defined as well. The method presented in this paper and based on systematic TBM data evaluation achieves both the goal of contractual advance classification and the goal of establishing a simple threshold differentiating regular advance and hindered advance.
New testing method for the prediction of the dispersion of soil in slurry shield tunnelling
Authors: Weiner Thorsten , Thewes Markus
Published: October 2018

In this contribution, we present a new testing method for the prediction of the dispersion of soil in slurry shield tunnelling. It is based on the proven slake durability test equipment but differs substantially regarding the procedure for testing and evaluation. With the results, a substantial data analysis was conducted searching for correlations with typical characteristic soil parameters. For the first time in tunnelling practice, the test enables a qualitative assessment and therefore a prognosis of the expected dispersion based on quantitative values determined in a traceable and reproducible testing method. In addition the test allows for an estimation of the dispersion tendency based on figures for the plasticity and consistency, which are usually collected anyway in the preliminary stages of a tunnelling project. Contractual recommendations are also provided concerning the topic of dispersion.
A cost‐effectiveness threshold based on the marginal returns of cardiovascular hospital spending
Authors: van Baal Pieter , Perry‐Duxbury Meg , Bakx Pieter , Versteegh Matthijs , van Doorslaer Eddy , Brouwer Werner
Published: October 2018

Traditionally, threshold levels of cost‐effectiveness have been derived from willingness‐to‐pay studies, indicating the consumption value of health (v‐thresholds). However, it has been argued that v‐thresholds need to be supplemented by so‐called k‐thresholds, which are based on the marginal returns to health care. The objective of this research is to estimate a k‐threshold based on the marginal returns to cardiovascular disease (CVD) hospital care in the Netherlands. To estimate a k‐threshold for hospital care on CVD, we proceed in two steps: First, we estimate the impact of hospital spending on mortality using a Bayesian regression modelling framework, using data on CVD mortality and CVD hospital spending by age and gender for the period 1994–2010. Second, we use life tables in combination with quality of life data to convert these estimates into a k‐threshold expressed in euros per quality‐adjusted life year gained. Our base case estimate resulted in an estimate of 41,000 per quality‐adjusted life year gained. In our sensitivity analyses, we illustrated how the incorporation of prior evidence into the estimation pushes estimates downwards. We conclude that our base case estimate of the k‐threshold may serve as a benchmark value for decision making in the Netherlands as well as for future research regarding k‐thresholds.
A healthy weight improves life satisfaction
Authors: Habibov Nazim , Auchynnikava Alena , Luo Rong , Fan Lida
Published: October 2018

In this study, we examine the effects of having a healthy weight in form of a healthy body mass index (BMI) on life satisfaction using the data from a diverse sample of 27 post‐communist transitional countries. We find that a healthy BMI significantly raises life satisfaction, while an increase in BMI reduces life satisfaction. We also find that the positive effect of a healthy BMI on life satisfaction substantially diminishes as the political and economic situation improves. Equally, the positive effect of healthy BMI on life satisfaction is considerably lower for those who exhibit higher levels of institutional trust and express trust in government, parliament, and political parties. Classic regression models such as ordinary least squares (OLS) and ordered probit significantly underestimate the true effect of healthy BMI on life satisfaction. Such results suggest that unobserved confounders, measurement error, or their interplay appear to be the main source (s) of bias that eventually lead to a significant underestimation of the true effect of BMI on life satisfaction through classic regression models.
Comparison of polyglycolic acid, polycaprolactone, and collagen as scaffolds for the production of tissue engineered intestine
Authors: Liu Yanchun , Nelson Tyler , Chakroff Jason , Cromeens Barrett , Johnson Jed , Lannutti John , Besner Gail E.
Published: October 2018

Cell‐seeded scaffolds play critical roles in the production of tissue engineered intestine (TEI), a potential strategy for the treatment of short bowel syndrome. The current study compares polyglycolic acid (PGA), polycaprolactone (PCL), and collagen as scaffolds for TEI production. Tubular PGA scaffolds were prepared from nonwoven BIOFELT®. Tubular PCL scaffolds were fabricated by electrospinning. Tubular collagen scaffolds were prepared using CollaTape, a wound dressing material. Both PGA and collagen were coated with poly‐l‐lactic acid (PLLA) to improve scaffold mechanical properties. Pore size, porosity, microstructure, mechanical properties (suture retention strength and ultimate compressive force) were determined. The scaffolds were first seeded with crypt stem cells isolated from 1 to 3 day old rat pups and then implanted into the peritoneal cavity of nude rats. After 4 weeks ofin vivoincubation, these cell‐seeded scaffolds were harvested for assessment of the TEI produced. Of the three materials compared, PLLA coated tubular PGA scaffolds had the appropriate pore size, mechanical properties and degradation rate leading to the production of TEI with an architecture similar to that of native rat intestine. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 750–760, 2019.
An on‐site preparable, novel bone‐grafting complex consisting of human platelet‐rich fibrin and porous particles made of a recombinant collagen‐like protein
Authors: Tsukioka Tsuneyuki , Hiratsuka Takahiro , Nakamura Masayuki , Watanabe Taisuke , Kitamura Yutaka , Isobe Kazushige , Okudera Toshimitsu , Okudera Hajime , Azuma Akihiko , Uematsu Kohya , Nakata Koh , Kawase Tomoyuki
Published: October 2018

Platelet‐rich fibrin (PRF) is widely used in regenerative medicine. Nonetheless, major issues include its controversial effects on bone regeneration and a lack of quality‐assured glass tubes required for coagulation. We used porous particles (FBG) comprising a recombinant RGD motif‐enriched collagen I‐like protein to activate the coagulation pathway and examined the effects of the resulting PRF–FBG complex on bone regeneration. Human whole‐blood samples were mixed with FBG in plastic tubes and centrifuged to prepare a PRF–FBG complex. Platelet‐derived growth factor‐BB (PDGF‐BB) levels and cell growth activity were determined by ELISA and a bioassay using osteoblasts. Bone regenerative activity was assessed using a mouse model of calvarial bone defect. FBG facilitated PRF‐like matrix formation during centrifugation. In this PRF–FBG complex, the microstructure of fibrin fibers was similar to that of PRF prepared conventionally in glass tubes. PDGF‐BB levels and mitogenic action were not significantly influenced by FBG. In the bone defect model, although PRF did not exert any significant positive effects on its own, in combination with FBG, it synergistically stimulated new bone formation. This study demonstrated that incorporation of FBG into whole‐blood samples induces PRF formation without the aid of glass tubes. The resulting PRF–FBG complex could be a promising bone grafting material in clinical settings. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1420–1430, 2019.
p‐Hydroxybenzyl alcohol inhibits four obesity‐related enzymes in vitro
Authors: Choi Jun‐Hui , Yeo Soo‐Hwan , Kim Myung‐Kon , Lee Hyo‐Jeong , Kim Seung
Published: October 2018

Recently, antiobesity studies using the method of inhibiting enzymatic activity of obesity‐related enzymes as targets have received considerable attention. The aims of the current study were to investigate whether p‐hydroxybenzyl alcohol (HBA), identified from Cudrania tricuspidata fruits with antiobesity effects, inhibits the activity of digestive and obesity‐related enzymes and acts as an inhibitor against four target enzymes in kinetic studies. In vitro enzyme assays showed HBA at the highest concentration significantly reduced the enzymatic activity of four targets: pancreatic lipase (IC50 = 2.34‐3.70 μM), α‐glycosidase (IC50 = 9.08 μM), phosphodiesterase IV (IC50 = 4.99 μM), and citrate synthase (IC50 = 2.07 μM) enzymes. Based on the results of kinetic assays, the types of inhibition were investigated. Our findings indicate that HBA could have antiobesity efficacy, and it deserves further study.
Salidroside attenuates interleukin‐1β‐induced inflammation in human osteoarthritis chondrocytes
Authors: Zhang Yuan , Zhao Qing
Published: October 2018

Salidroside, a bioactive constituent isolated from Rhodiola rosea, has been reported to have anti‐inflammatory effects. However, the effects of salidroside on interleukin (IL)‐1β‐stimulated osteoarthritis (OA) chondrocytes remain to be elucidated. Thus, this study aimed to evaluate the anti‐inflammatory effects of salidroside on IL‐1β‐stimulated human OA chondrocytes and explore its underlying mechanisms. Our results showed that salidroside significantly inhibited the production of nitric oxide and prostaglandin E‐2, as well as suppressed the expression of inducible nitric oxide synthase and cyclooxygenase‐2 in IL‐1β‐stimulated chondrocytes (
P < .05). In addition, salidroside also suppressed IL‐1β‐induced matrix metalloproteinases production in human OA chondrocytes (
P < .05). Furthermore, pretreatment with salidroside prevented IL‐1β‐induced NF‐κB activation in OA chondrocytes (
P < .05). In conclusion, the current study demonstrated that salidroside inhibited the IL‐1β‐induced inflammatory response in OA chondrocytes via inhibition of NF‐κB activation.
Dual‐specificity phosphatase 6 deletion protects the colonic epithelium against inflammation and promotes both proliferation and tumorigenesis
Authors: Beaudry Katia , Langlois Marie‐Josée , Montagne Amélie , Cagnol Sébastien , Carrier Julie C. , Rivard Nathalie
Published: October 2018

The Ras/mitogen‐activated protein kinase (MAPK) pathway controls fundamental cellular processes such as proliferation, differentiation, and apoptosis. The dual‐specificity phosphatase 6 (DUSP6) regulates cytoplasmic MAPK signaling by dephosphorylating and inactivating extracellular signal‐regulated kinase (ERK1/2) MAPK. To determine the role of DUSP6 in the maintenance of intestinal homeostasis, we characterized the intestinal epithelial phenotype of
Dusp6 knockout (KO) mice under normal, oncogenic, and proinflammatory conditions. Our results show that loss of Dusp6 increased crypt depth and epithelial cell proliferation without altering colonic architecture. Crypt regeneration capacity was also enhanced, as revealed by ex vivo
Dusp6 KO organoid cultures. Additionally, loss of Dusp6 induced goblet cell expansion without affecting enteroendocrine and absorptive cell differentiation. Our data also demonstrate that
Dusp6 KO mice were protected from acute dextran sulfate sodium‐induced colitis, as opposed to wild‐type mice. In addition,
Dusp6 gene deletion markedly enhanced tumor load in
Apc
Min/+ mice. Decreased DUSP6 expression by RNA interference in HT29 colorectal cancer cells enhanced ERK1/2 activation levels and promoted both anchorage‐independent growth in soft agar as well as invasion through Matrigel. Finally,
DUSP6 mRNA expression in human colorectal tumors was decreased in advanced stage tumors compared with paired normal tissues. These results demonstrate that DUSP6 phosphatase, by controlling ERK1/2 activation, regulates colonic inflammatory responses, and protects the intestinal epithelium against oncogenic stress.
Transitivity as Skinnerian problem solving controlled by self‐constructed relational stimuli
Authors: Moustakis Ioannis S. , Mellon Robert C.
Published: October 2018

In tests of the derivation of complex relations such as transitivity, extant cues might fail to evoke effective responding, necessitating the construction of supplemental stimuli prior to their solution. The significance of this process was investigated by within‐subject manipulation of an instructional variable designed to produce different levels of construction of supplemental stimulation concerning relationships among stimulus elements of concatenated conditional discriminations. In two experimental sessions, serial training of three 5‐member stimulus classes occurred, either with the instruction to simply name the component stimuli or to both name them and generate a tale serially linking the stimuli named; such constructed stimuli might be spontaneously reconstructed by precurrent acts in subsequent tests of “emergent” relations. Participants whose supplemental stimulus construction at the first session was limited to name‐giving derived significantly more relations when, in training at session two, they generated tales linking stimulus elements; this same near‐errorless derivation was obtained at the first session whenever relational stimuli beyond bidirectional naming were constructed. In some cases the uninstructed construction of supplementary relational stimuli occurred at the first session, to equivalent effect; such construction might constitute a typically unobserved component of the derivation of relations among stimulus elements entailed in multiple conditional discriminations.
Thinking “Outside the Box”: Unconstrained Creative Generation in Adults with Attention Deficit Hyperactivity Disorder
Authors: White Holly A.
Published: October 2018

Creative generation is structured around existing knowledge and task examples, yet overreliance on specific examples may limit imagination (Ward, T. B., Finke, R. A., & Smith, S. M., 1995). The constraining influence of knowledge during creative generation may be offset by conceptual expansion, a process of thinking outside traditional conceptual boundaries, which may be heightened by distractibility and mild executive dysfunction (Abraham, A., Windmann, S., Daum, I., & Güntürkün, O., 2005). The present study explored the constraining effects of knowledge in adults with Attention Deficit Hyperactivity Disorder (ADHD), a disorder characterized by impaired attention and inhibitory control (Barkley, R. A., 1997). College students with and without ADHD were compared on two creative generation measures: an alien fruit invention task that required participants to imagine fruit that might exist on another planet (Ward, T.B., 1994), and a product label invention task wherein the goal was to invent product names without using elements of task examples (Kray, L.J., Galinski, A.D. & Wong, E.M., 2006). ADHD participants created alien fruit that diverged more from Earth fruit and labels that conformed less to examples, relative to non‐ADHD peers. Results suggest that adults with ADHD may be less constrained by knowledge during creative generation. Findings are discussed in terms of theoretical import and practical implications for individuals with ADHD.
Novel mutation in Teneurin 3 found to co‐segregate in all affecteds in a multi‐generation family with developmental dysplasia of the hip
Authors: Feldman George , Kappes Dietmar , Mookerjee‐Basu Jayati , Freeman Theresa , Fertala Andrzej , Parvizi Javad
Published: October 2018

DDH is a debilitating condition characterized by incomplete formation of the acetabulum leading to dislocation of the hip, suboptimal joint function and accelerated wear of the articular cartilage resulting in early onset crippling arthritis of the hip in 20–40 year olds. Current diagnostic tests in newborns using physical manipulation of the femur or ultrasound either under or over‐diagnose this condition. Developing an accurate, cost effective diagnostic test is a goal of this study. To better understand the biologic pathways involved in acetabular development, DNA from severely affected individuals in a four generation family that showed inter‐generational transmission of the disorder was isolated and whole exome sequenced. A novel A to C transversion at position 183721398 on human chromosome four was found to co‐segregate with the affected phenotype in this family. This mutation encodes a glutamine to proline change at position 2665 in the Teneurin 3 (TENM3) gene and was judged damaging by four prediction programs. Eight week old knock‐in mutant mice show delayed development of the left acetabulum and the left glenoid fossa as shown by the presence of more Alcian blue staining on the socket rims of both the hip and the shoulder. We hypothesize that mutated TENM3 will slow chondrogenesis. MMP13 has been shown to impair extracellular matrix remodeling and suppress differentiation. Bone marrow cells from the knock‐in mouse were found to overexpress MMP13 with or without BMP2 stimulation. This variant may elucidate pathways responsible for normal hip development and become part of an accurate test for DDH. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Radiostereometric analysis of the initial stability of internally fixed femoral neck fractures under differential loading
Authors: Finnilä Sami , Moritz Niko , Strandberg Niko , Alm Jessica J. , Aro Hannu T.
Published: October 2018

We examined the feasibility of radiostereometric analysis (RSA) in the assessment of the initial stability of internally fixed femoral neck fractures. The study included 16 patients (mean age 73 years). During surgery, multiple RSA‐beads were inserted on both sides of the fracture. Radiographs for RSA were taken in the supine position within the first 3 days and 6, 12, 24, and 52 weeks after surgery. To detect any inducible motion at the fracture‐site, radiographs for RSA were taken with the patient resting or applying a load through the fracture. Fracture loading was achieved by the patient pressing the ipsilateral foot as much as tolerated on a force plate while providing a counterforce through both hands. Micromotion exceeding the precision values of RSA (≥0.3 mm for the translation vector and/or ≥1.2 degrees for the rotation vector) was considered significant. Permanent three‐dimensional fracture‐site displacement was also recorded. Voluntary loading induced fracture‐site micromotion, which exhibited a dichotomous distribution. In patients with uncomplicated fracture union, inducible micromotion was detectable only at baseline—if at all. Conversely, fractures that developed a nonunion were characterized by the continuation of inducible micromotion beyond baseline. Permanent fracture‐site displacement was, on average, nearly an order of magnitude greater than the inducible micromotion. Fracture unions were characterized by the cessation of permanent fracture‐site displacement by 12 weeks. Nonunions presented as outliers in permanent fracture‐site displacement. Large‐scale studies are warranted to evaluate whether the detection of inducible micromotion beyond baseline could serve as an indicator of insufficient fixation stability. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society.
Deep eutectic solvent‐based extraction of polyphenolic antioxidants from onion (Allium cepa L.) peel
Authors: Pal Chandra Bhushan T , Jadeja Girirajsinh C
Published: October 2018

BACKGROUND

Biomass waste, including fruit and vegetable residues, poses a serious challenge to the environment. This demands novel approaches for handling and disposing of it in a safe manner. However, such waste is extremely rich in bioactive components, which are considered to have a beneficial impact on health. This has led to the recovery of high‐value compounds from biomass waste before finally disposing of it. The present investigation reveals the use of green solvents such as eutectic mixtures composed of choline chloride with three different hydrogen bond donors like sucrose (4:1), urea (1:2), and sorbitol (3:1) as extractants for recovering valuable phenolic antioxidants from onion peel.

RESULTS

A deep eutectic solvent system consisting of choline chloride:urea (ChCl:urea) showed the best result for total phenolic content from onion peel while the other two eutectic mixtures showed relatively lower extraction efficiency. Experiments were performed with different molar ratios of ChCl:U (1:1–1:3) and liquid–solid ratios (10:1–60:1) under a temperature range (50–90 °C) and a time range (60–150 min). Taguchi's method was employed to maximize the extraction of polyphenolic antioxidants from onion peel, resulting in optimal conditions: extraction temperature 60 °C, time 120 min, liquid to solid ratio 50:1 and molar ratio of ChCl:U as 1:2. Under optimum conditions, the corresponding TPC value of the extract was found to be highest at 222.97 mg gallic acid equivalent (GAE) g−1 dw.

CONCLUSION

Major flavonoids – quercetin, kaempferol, and myricetin – were identified and quantified in the extracts. Moreover, high reducing power (PR) value was reported in the case of ChCl:U extract, and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity was found to be higher in ChCl:So extract. © 2018 Society of Chemical Industry
Enhanced bioactivity and efficient delivery of quercetin through nanoliposomal encapsulation using rice bran phospholipids
Authors: Rodriguez Evelyn B , Almeda Ronaniel A , Vidallon Mark Louis P , Reyes Charisse T
Published: October 2018

BACKGROUND

Quercetin is a phenolic compound occurring in many food plants and agricultural crops. It is reported to possess various health‐promoting properties. However, the poor bioavailability of quercetin, due to its low aqueous solubility and its degradation during digestion, limits its nutraceutical applications. This study aimed to encapsulate quercetin in nanoliposomes using rice‐bran phospholipids for its efficient delivery and controlled release, the protection of its structural stability, and enhancement of its bioactivity.

RESULTS

Nanoliposomal encapsulation of quercetin by thin film‐sonication method yielded spherical nanoparticles (157.33 ± 23.78 nm) with high encapsulation efficiency (84.92 ± 0.78%). Storage stability studies showed that nanoliposomal quercetin was stable at 4 °C and 27 °C for 6 and 5 months, respectively, as indicated by unchanged antioxidant activity and quercetin retention. Nanoliposomal quercetin showed a slow, limited release pattern in simulated gastric fluid (SGF), and an initial burst release followed by a slow constant releasing pattern in simulated intestinal fluid (SIF). A 1004‐fold increase in 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical‐scavenging activity was observed in quercetin nanoliposomes (SC50 = 4.04 ± 0.01 ppm) compared to non‐encapsulated quercetin (SC50 = 4053.03 ± 5.61 ppm). Similarly, the anti‐angiogenic activity of quercetin, as evaluated by duck embryo chorioallantoic membrane (CAM) assay, was enhanced twofold to fivefold by nanoliposomal encapsulation.

CONCLUSION

This study showed that nanoliposomal encapsulation in rice‐bran phospholipids enhanced the radical‐scavenging and anti‐angiogenic activities of quercetin. Furthermore, this study demonstrated that nanoliposomes can serve as efficient oral delivery system for quercetin. © 2018 Society of Chemical Industry