bluuebunny/crossref_metadata_2025 huggingface dataset:
Video podcast and illustrated text feedback in a web‐based formative assessment environment
Authors: Letón Emilio , Molanes‐López Elisa M. , Luque Manuel , Conejo Ricardo
Published: September 2017

It is well known that computer‐based formative assessment and timely feedback enhance effective student learning but there is still a debate about what type of feedback should be given, being the text‐based the most used feedback in practice. Although the use of video content as a learning resource has recently increased in both educational and non‐educational contexts, there is very little research on its effectiveness as assessment feedback and the existing results are contradictory. For that reason, we have combined in this work the use of a web‐based formative assessment system (Siette) where we have integrated a specific type of video podcast (“modular teaching mini‐videos”: MTMs) and equivalent illustrated text. We have carried out two experiments with a twofold purpose, first to compare the effect of video feedback versus correct response feedback alone and secondly to compare the effect of video feedback versus equivalent illustrated text feedback. In the context of our research, a Statistic Course at university level, our results show, as expected, that there is a statistically significant positive effect in favor of video feedback over correct response feedback alone. Surprisingly, in contrast to our expectations, based on our context of acquisition of procedural knowledge, there is a statistically non‐significant effect of video feedback versus equivalent illustrated text feedback. From the students’ satisfaction survey, there is not statistically significant differences in the overall score of the activity based on video podcast feedback or equivalent illustrated text, which is an indication that we have really obtained equivalent feedback materials.
Role of macrophage migration inhibitory factor (MIF) in the effects of oxidative stress on human retinal pigment epithelial cells
Authors: Ko Ji‐Ae , Sotani Yasuyuki , Ibrahim Diah Gemala , Kiuchi Yoshiaki
Published: September 2017

Proliferative vitreoretinopathy (PVR) is the major cause of treatment failure in individuals who undergo surgery for retinal detachment. The epithelial‐mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells contributes to the pathogenesis of PVR. Oxidative stress is thought to play a role in the progression of retinal diseases including PVR. We have now examined the effects of oxidative stress on the EMT and related processes in the human RPE cell line. We found that H2O2 induced the contraction of RPE cells in a three‐dimensional collagen gel. Analysis of a cytokine array revealed that H2O2 specifically increased the release of macrophage migration inhibitory factor (MIF) from RPE cells. Reverse transcription–polymerase chain reaction and immunoblot analyses showed that H2O2 increased the expression of MIF in RPE cells. Immunoblot and immunofluorescence analyses revealed that H2O2 upregulated the expression of α–SMA and vimentin and downregulated that of ZO‐1 and N‐cadherin. Consistent with these observations, the transepithelial electrical resistance of cell was reduced by exposure to H2O2. The effects of oxidative stress on EMT‐related and junctional protein expression as well as on transepithelial electrical resistance were inhibited by antibodies to MIF, but they were not mimicked by treatment with recombinant MIF. Finally, analysis with a profiling array for mitogen‐activated protein kinase signalling revealed that H2O2 specifically induced the phosphorylation of p38 mitogen‐activated protein kinase. Our results thus suggest that MIF may play a role in induction of the EMT and related processes by oxidative stress in RPE cells and that it might thereby contribute to the pathogenesis of PVR. Proliferative vitreoretinopathy is a major complication of rhegmatogenous retinal detachment, and both oxidative stress and induction of the EMT in RPE cells are thought to contribute to the pathogenesis of this condition. We have now examined the effects of oxidative stress on the EMT and related processes in the human RPE cell line ARPE19. Our results thus implicate MIF in induction of the EMT and related processes by oxidative stress in RPE cells and the regulated expression of EMT markers. They further suggest that MIF may play an important role in the pathogenesis of PVR.
Intermolecular C−C Coupling between 1‐Methyl‐1,2,3‐Triazole and 2,2′‐Bipyridine or 1,10‐Phenanthroline in MoII Complexes
Authors: Fombona Sergio , Pérez Julio , Díaz Jesús , Riera Lucía
Published: September 2017

Unsupported 1‐methyl‐1,2,3‐triazole has been coordinated to {Mo(η3‐methallyl)(CO)2(N‐N)} (N‐N=2,2′‐bipyridine, bipy; or 1,10‐phenanthroline, phen) fragments, yielding cationic complexes that can be regarded as metalated triazolium salts. Their reactivity towards a strong base led to the deprotonation of the C5−H group of the triazole moiety, followed by an intermolecular nucleophilic attack to the ortho CH group of a bipy or phen ligand affording cyclic, bimetallic dearomatized C−C coupling products. The reaction of the neutral bipy derivative with an acid led to the formation of dihydropyridyl units by protonation of a CH group of the dearomatized rings, the dimeric nature of complexes being mantained upon protonation.
Overview of Methods and Strategies for Conducting Virtual Small Molecule Screening
Authors: Fradera Xavier , Babaoglu Kerim
Published: September 2017

Virtual screening (VS) in the context of drug discovery is the use of computational methods to discover novel ligands with a desired biological activity from within a larger collection of molecules. These techniques have been in use for many years, there is a wide range of methodologies available, and many successful applications have been reported in the literature. VS is often used as an alternative or a complement to High‐throughput screening (HTS) or other methods to identify ligands for target validation or medicinal chemistry projects. This unit does not present an exhaustive review of available methods, or document specific instructions on use of individual software packages. Rather, a general overview of the methods available are presented and general strategies are described for VS based on accepted practices and the authors’ experience as computational chemists in an industrial research laboratory. First, the most common methods available for VS are reviewed, categorized as either receptor‐ or ligand‐based. Subsequently, strategic considerations are presented for choosing a VS method, or a combination of methods, as well as the necessary steps to prepare, run, and analyze a VS campaign. © 2017 by John Wiley & Sons, Inc.
Mammalian MSC from selected species: Features and applications
Authors: Uder Christiane , Brückner Sandra , Winkler Sandra , Tautenhahn Hans‐Michael , Christ Bruno
Published: September 2017

Mesenchymal stromal/stem cells (MSC) are promising candidates for cellular therapy of different diseases in humans and in animals. Following the guidelines of the International Society for Cell Therapy, human MSC may be identified by expression of a specific panel of cell surface markers (CD105+, CD73+, CD90+, CD34‐, CD14‐, or CD11b‐, CD79‐ or CD19‐, HLA‐DR‐). In addition, multiple differentiation potential into at least the osteogenic, adipogenic, and chondrogenic lineage is a main criterion for MSC definition. Human MSC and MSC of a variety of mammals isolated from different tissues meet these criteria. In addition to the abovementioned, they express many more cell surface markers. Yet, these are not uniquely expressed by MSC. The gross phenotypic appearance like marker expression and differentiation potential is similar albeit not identical for MSC from different tissues and species. Similarly, MSC may feature different biological characteristics depending on the tissue source and the isolation and culture procedures. Their versatile biological qualities comprising immunomodulatory, anti‐inflammatory, and proregenerative capacities rely largely on the migratory and secretory capabilities of MSC. They are attracted to sites of tissue lesion and secrete factors to promote self‐repair of the injured tissue. This is a big perspective for clinical MSC applications in both veterinary and human medicine. Phase I/II clinical trials have been initiated to assess safety and feasibility of MSC therapies in acute and chronic disease settings. Yet, since the mode of MSC action in a specific disease environment is still unknown at large, it is mandatory to unravel the response of MSC from a given source onto a specific disease environment in suitable animal models prior to clinical applications. © 2017 International Society for Advancement of Cytometry
Climate variation alters the synchrony of host–parasitoid interactions
Authors: Wetherington Miles T. , Jennings David E. , Shrewsbury Paula M. , Duan Jian J.
Published: September 2017

Observed changes in mean temperature and increased frequency of extreme climate events have already impacted the distributions and phenologies of various organisms, including insects. Although some research has examined how parasitoids will respond to colder temperatures or experimental warming, we know relatively little about how increased variation in temperature and humidity could affect interactions between parasitoids and their hosts. Using a study system consisting of emerald ash borer (EAB), Agrilus planipennis, and its egg parasitoid Oobius agrili, we conducted environmentally controlled laboratory experiments to investigate how increased seasonal climate variation affected the synchrony of host–parasitoid interactions. We hypothesized that increased climate variation would lead to decreases in host and parasitoid survival, host fecundity, and percent parasitism (independent of host density), while also influencing percent diapause in parasitoids. EAB was reared in environmental chambers under four climate variation treatments (standard deviations in temperature of 1.24, 3.00, 3.60, and 4.79°C), while O. agrili experiments were conducted in the same environmental chambers using a 4 × 3 design (four climate variation treatments × 3 EAB egg densities). We found that EAB fecundity was negatively associated with temperature variation and that temperature variation altered the temporal egg laying distribution of EAB. Additionally, even moderate increases in temperature variation affected parasitoid emergence times, while decreasing percent parasitism and survival. Furthermore, percent diapause in parasitoids was positively associated with humidity variation. Our findings indicate that relatively small changes in the frequency and severity of extreme climate events have the potential to phenologically isolate emerging parasitoids from host eggs, which in the absence of alternative hosts could lead to localized extinctions. More broadly, these results indicate how climate change could affect various life history parameters in insects, and have implications for consumer–resource stability and biological control.
Pellets of proof: First glimpse of the dietary composition of adult odonates as revealed by metabarcoding of feces
Authors: Kaunisto Kari M. , Roslin Tomas , Sääksjärvi Ilari E. , Vesterinen Eero J.
Published: September 2017

Recent advances in molecular techniques allow us to resolve the diet of unstudied taxa. Odonates are potentially important top‐down regulators of many insects. Yet, to date, our knowledge of odonate prey use is based mainly on limited observations of odonates catching or eating their prey. In this study, we examine the potential use of metabarcoding in establishing the diet of three adult odonate species (Lestes sponsa, Enallagma cyathigerum, and Sympetrum danae) at a site in southwestern Finland. To this purpose, we compared three different methods for extracting DNA from fecal samples: the Macherey‐Nagel Nucleospin XS kit, a traditional salt extraction, and the Zymo Research Fecal Microprep kit. From these extracts, we amplified group‐specific mitochondrial markers (COI and 16S rRNA) from altogether 72 odonate individuals, and compared them to comprehensive reference libraries. The three odonate species show major overlap in diet, with no significant differences between individuals of different size and/or gender, reflecting opportunistic foraging of adult odonates. Of a total of 41 different prey species detected, the most frequently consumed ones were Diptera, with additional records of six other orders. Based on our data, the best DNA extraction method is the traditional salt extraction, as it provides the most information on prey content while also being the most economical. To our knowledge, this is the first study to resolve the species‐level diet of adult odonates. Armed with the appropriate methodological caveats, we are ready to examine the ecological role of odonates in both terrestrial and aquatic food webs, and in transferring subsidies between these two realms.
Assessing recovery of in vitro steroid production in male rainbow darter (Etheostoma caeruleum) in response to municipal wastewater treatment plant infrastructure changes
Authors: Marjan Patricija , Van Der Kraak Glen J. , MacLatchy Deborah L. , Fuzzen Meghan L.M. , Bragg Leslie M. , McMaster Mark E. , Tetreault Gerald R. , Servos Mark R.
Published: September 2017

The present study examined in vitro 11-ketotestosterone and testosterone production by the testes of rainbow darter (Etheostoma caeruleum) collected from selected reference sites and downstream of 2 municipal wastewater treatment plants (MWWTPs; Waterloo and Kitchener) on the central Grand River (Ontario, Canada), over a 6-yr period (2011–2016). The main objective was to investigate if infrastructure upgrades at the Kitchener MWWTP in 2012 resulted in a recovery of this response in the post-upgrade period (2013–2016). Two supporting studies showed that the fall season is appropriate for measuring in vitro sex steroid production because it provides stable detection of steroid patterns, and that the sample handling practiced in the present study did not introduce a bias. Infrastructure upgrades of the Kitchener MWWTP resulted in significant reductions in ammonia and estrogenicity. After the upgrades, 11-ketotestosterone production by MWWTP-exposed fish increased in 2013 and it continued to recover throughout the study period of 2014 through 2016, returning to levels measured in reference fish. Testosterone production was less sensitive and it lacked consistency. The Waterloo MWWTP underwent some minor upgrades but the level of ammonia and estrogenicity remained variable over time. The production of 11-ketotestosterone and testosterone in rainbow darter below the Waterloo MWWTP was variable and without a clear recovery pattern over the course of the present study. The results of the present study demonstrated that measuring production of sex steroids (especially 11-ketotestosterone) over multiple years can be relevant for assessing responses in fish to environmental changes such as those resulting from major infrastructure upgrades. Environ Toxicol Chem 2018;37:501–514. © 2017 SETAC
A phosphoarray platform is capable of personalizing kinase inhibitor therapy in head and neck cancers
Authors: Klinghammer Konrad , Keller James , George Jonathan , Hoffmann Jens , Chan Edward L. , Hayman Michael J.
Published: September 2017

Tyrosine kinase inhibitors are effective treatments for cancers. Knowing the specific kinase mutants that drive the underlying cancers predict therapeutic response to these inhibitors. Thus, the current protocol for personalized cancer therapy involves genotyping tumors in search of various driver mutations and subsequently individualizing the tyrosine kinase inhibitor to the patients whose tumors express the corresponding driver mutant. While this approach works when known driver mutations are found, its limitation is the dependence on driver mutations as predictors for response. To complement the genotype approach, we hypothesize that a phosphoarray platform is equally capable of personalizing kinase inhibitor therapy. We selected head and neck squamous cell carcinoma as the cancer model to test our hypothesis. Using the receptor tyrosine kinase phosphoarray, we identified the phosphorylation profiles of 49 different tyrosine kinase receptors in five different head and neck cancer cell lines. Based on these results, we tested the cell line response to the corresponding kinase inhibitor therapy. We found that this phosphoarray accurately informed the kinase inhibitor response profile of the cell lines. Next, we determined the phosphorylation profiles of 39 head and neck cancer patient derived xenografts. We found that absent phosphorylated EGFR signal predicted primary resistance to cetuximab treatment in the xenografts without phosphorylated ErbB2. Meanwhile, absent ErbB2 signaling in the xenografts with phosphorylated EGFR is associated with a higher likelihood of response to cetuximab. In summary, the phosphoarray technology has the potential to become a new diagnostic platform for personalized cancer therapy.
Outage analysis of nonorthogonal in‐band relay‐aided device‐to‐device communications in Rayleigh fading channels
Authors: Shirvani Moghaddam Shahriar
Published: September 2017

Minimizing the outage probability and/or maximizing the throughput, optimally realize relay‐aided nonorthogonal in‐band (NO‐IB) device‐to‐device (D2D) communications. In this letter, we derive closed‐form expressions for the outage probability of NO‐IB amplify‐and‐forward (AF) and decode‐and‐forward (DF) relay‐aided D2D communications in Rayleigh fading channels. Numerical analyses show that the closed‐form formulas are in close agreement with the simulation results. Furthermore, we investigate the effect of signal‐to‐noise ratio and the distances between D2D pairs and relay nodes as well as cellular users. First results show that in the low‐noise regime, AF outperforms DF while they perform very close in the moderate noise level and DF outperforms AF in the high‐noise power. Second, we indicate that the relay‐aided AF/DF D2D communications is more reliable than the direct one when the TX/RX nodes of a D2D pair is distant approximately more than half of the cell radius.
Bioequivalence of Intravenous and Oral Rolapitant: Results From a Randomized, Open‐Label Pivotal Study
Authors: Wang Xiaodong , Zhang Zhi‐Yi , Powers Daniel , Wang Jing , Lu Sharon , Arora Sujata , Hughes Lorraine , Christensen Jennifer , Kansra Vikram
Published: September 2017

Rolapitant, a selective and long‐acting neurokinin‐1 receptor antagonist, is approved in an oral formulation for the prevention of delayed chemotherapy‐induced nausea and vomiting in adults. The objective of this pivotal study was to assess the bioequivalence of a single intravenous infusion of rolapitant versus a single oral dose of rolapitant. In this randomized, open‐label phase 1 study, healthy volunteers were administered rolapitant as a 180‐mg oral dose or a 30‐minute 166.5‐mg intravenous infusion. Blood samples for pharmacokinetic analysis were collected predose and at points up to 912 hours postdose. Criteria for bioequivalence of the intravenous dose versus the oral dose were met if the 90% confidence intervals (CIs) for the ratios of the geometric least‐squares means (GLSMs) for the area under the plasma concentration‐time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0–t) and AUC from time 0 extrapolated to infinity (AUC0–∞) for rolapitant were within 0.80–1.25. Mean rolapitant systemic exposure and half‐lives were similar in the oral (n = 62) and intravenous (n = 61) rolapitant groups. The 90%CIs of the ratio of GLSMs were within the 0.80–1.25 range for AUC0–t (0.94–1.09) and AUC0–∞ (0.93–1.10). The incidence of treatment‐emergent adverse events, all mild or moderate in severity, was similar in the intravenous and oral groups. A 166.5‐mg intravenous infusion of rolapitant met the bioequivalence criteria based on AUC to a 180‐mg oral dose and was well tolerated.
Inclusion of MERS‐spike protein ELISA in algorithm to determine serologic evidence of MERS‐CoV infection
Authors: Trivedi Suvang , Miao Congrong , Al‐Abdallat Mohammad M. , Haddadin Aktham , Alqasrawi Sultan , Iblan Ibrahim , Nsour Mohannad A. , Alsanouri Tarek , Ali Sami S. , Rha Brian , Gerber Susan I. , Payne Daniel C. , Tamin Azaibi , Thornburg Natalie J.
Published: September 2017

The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS‐CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or microneutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS‐CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.
Application of power ultrasound on the convective drying of fruits and vegetables: effects on quality
Authors: Rodríguez Óscar , Eim Valeria , Rosselló Carmen , Femenia Antoni , Cárcel Juan A , Simal Susana
Published: September 2017

Drying gives rise to products with a long shelf life by reducing the water activity to a level that is sufficiently low to inhibit the growth of microorganisms, enzymatic reactions and other deteriorative reactions. Despite the benefits of this operation, the quality of heat sensitive products is diminished when high temperatures are used. The use of low drying temperatures reduces the heat damage but, because of a longer drying time, oxidation reactions occur and a reduction of the quality is also observed. Thus, drying is a method that lends itself to being intensified. For this reason, alternative techniques are being studied. Power ultrasound is considered as an emerging and promising technology in the food industry. The potential of this technology relies on its ability to accelerate the mass transfer processes in solid–liquid and solid–gas systems. Intensification of the drying process with power ultrasound can be achieved by modifying the product behavior during drying, using pre‐treatments such as soaking in a liquid medium assisted acoustically or, during the drying process itself, by applying power ultrasound in the gaseous medium. This review summarises the effects of the application of the power ultrasound on the quality of different dried products, such as fruits and vegetables, when the acoustic energy is intended to intensify the drying process, either when the application is performed before pretreatment or during the drying process. © 2017 Society of Chemical Industry
Changes in phytochemical composition, bioactivity and in vitro digestibility of guayusa leaves (Ilex guayusa Loes.) in different ripening stages
Authors: Villacís‐Chiriboga José , García‐Ruiz Almudena , Baenas Nieves , Moreno Diego A , Meléndez‐Martínez Antonio J , Stinco Carla M , Jerves‐Andrade Lourdes , León‐Tamariz Fabián , Ortiz‐Ulloa Johanna , Ruales Jenny
Published: September 2017

BACKGROUND

Guayusa (Ilex guayusa Loes.) leaves, native of the Ecuadorian Amazon, are popularly used for preparing teas. This study aimed to assess the influence of leaf age on the phenolic compounds and carotenoids and the bioactivity and digestibility (in vitro) of aqueous and hydroalcoholic leaf extracts.

RESULTS

In total, 14 phenolic compounds were identified and quantified. Chlorogenic acid and quercetin‐3‐O‐hexose were the main representatives of the hydroxycinnamic acids and flavonols respectively. Seven carotenoids were quantified, lutein being the main compound. Ripening affected phenolic content significantly, but there was no significant difference in carotenoid content. Antioxidant capacity, measured by the DPPH• method, was also significantly affected by leaf age. The measurement of in vitro digestibility showed a decrease in phenolic content (59%) as well as antioxidant capacity, measured by the ABTS•+ method, in comparison with initial conditions of the guayusa infusion. Antibacterial and anti‐inflammatory activities were assayed with young leaves owing to their higher phenolic contents. Guayusa did not show any antibacterial activity against Escherichia coli ATCC 25922 or Staphylococcus aureus ATCC 25923. Finally, the hydroalcoholic and aqueous extracts exhibited high in vitro anti‐inflammatory activity (>65%).

CONCLUSION

Young guayusa leaves have potential applications as a functional ingredient in food and pharmaceutical industries. © 2017 Society of Chemical Industry
Remarks on the qualitative behavior of the undamped Klein‐Gordon equation
Authors: Esquivel‐Avila Jorge A.
Published: September 2017

We consider the undamped Klein‐Gordon equation in bounded domains with homogeneous Dirichlet boundary conditions. For any real value of the initial energy, particularly for supercritical values of the energy, we give sufficient conditions to conclude blow‐up in finite time of weak solutions. The success of the analysis is based on a detailed analysis of a differential inequality. Our results improve previous ones in the literature.
Neutron damage induced in cardiovascular implantable electronic devices from a clinical 18 MV photon beam: A Monte Carlo study
Authors: Ezzati Ahad Ollah , Studenski Matthew T.
Published: September 2017

Purpose

The purpose of this study was to quantify the relative neutron damage induced in CIEDs from clinical 18 MV photon beams for varying field sizes, depths, and off axis distances.

Methods and Materials

Damage was assessed using silicon damage response functions and ICRP neutron dose conversion factors in MCNPX. Particular attention was devoted to the modelling of the Varian 2100C/D linear accelerator to ensure accurate contamination neutron spectra. Neutron dose, fluence and relative damage to CIEDs was calculated.

Results

CIED damage from neutrons is related to the neutron dose rather than the neutron fluence. As field size increases, the region of high damage probability extends to a greater distance beyond the edge of the field than with smaller fields. At a distance greater than 50 cm or from the central axis or a depth deeper than 10 cm, the probability of damage is less than 10% of the central axis damage probability for all field sizes.

Conclusions

Clinically, increasing the depth or the distance from the central axis to the CIED will reduce the probability of damage from neutrons. Care must be taken when treating large fields as the overall probability of damage increase as does the distance the higher probability of damage extends beyond the field edge.
Joint arterial input function and tracer kinetic parameter estimation from undersampled dynamic contrast‐enhanced MRI using a model consistency constraint
Authors: Guo Yi , Lingala Sajan Goud , Bliesener Yannick , Lebel R. Marc , Zhu Yinghua , Nayak Krishna S.
Published: September 2017

Purpose

To develop and evaluate a model‐based reconstruction framework for joint arterial input function (AIF) and kinetic parameter estimation from undersampled brain tumor dynamic contrast‐enhanced MRI (DCE‐MRI) data.

Methods

The proposed method poses the tracer‐kinetic (TK) model as a model consistency constraint, enabling the flexible inclusion of different TK models and TK solvers, and the joint estimation of the AIF. The proposed method is evaluated using an anatomic realistic digital reference object (DRO), and nine retrospectively down‐sampled brain tumor DCE‐MRI datasets. We also demonstrate application to 30‐fold prospectively undersampled brain tumor DCE‐MRI.

Results

In DRO studies with up to 60‐fold undersampling, the proposed method provided TK maps with low error that were comparable to fully sampled data and were demonstrated to be compatible with a third‐party TK solver. In retrospective undersampling studies, this method provided patient‐specific AIF with normalized root mean‐squared‐error (normalized by the 90th percentile value) less than 8% at up to 100‐fold undersampling. In the 30‐fold undersampled prospective study, the proposed method provided high‐resolution whole‐brain TK maps and patient‐specific AIF.

Conclusion

The proposed model‐based DCE‐MRI reconstruction enables the use of different TK solvers with a model consistency constraint and enables joint estimation of patient‐specific AIF. TK maps and patient‐specific AIF with high fidelity can be reconstructed at up to 100‐fold undersampling in k,t‐space. Magn Reson Med 79:2804–2815, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Resting‐state functional connectivity in the rat cervical spinal cord at 9.4 T
Authors: Wu Tung‐Lin , Wang Feng , Mishra Arabinda , Wilson George H. , Byun Nellie , Chen Li Min , Gore John C.
Published: September 2017

Purpose

Numerous studies have adopted resting‐state functional MRI methods to infer functional connectivity between cortical regions, but very few have translated them to the spinal cord, despite its critical role in the central nervous system. Resting‐state functional connectivity between gray matter horns of the spinal cord has previously been shown to be detectable in humans and nonhuman primates, but it has not been reported previously in rodents.

Methods

Resting‐state functional MRI of the cervical spinal cord of live anesthetized rats was performed at 9.4 T. The quality of the functional images acquired was assessed, and quantitative analyses of functional connectivity in C4‐C7 of the spinal cord were derived.

Results

Robust gray matter horn‐to‐horn connectivity patterns were found that were statistically significant when compared with adjacent control regions. Specifically, dorsal–dorsal and ventral–ventral connectivity measurements were most prominent, while ipsilateral dorsal–ventral connectivity was also observed but to a lesser extent. Quantitative evaluation of reproducibility also revealed moderate robustness in the bilateral sensory and motor networks that was weaker in the dorsal–ventral connections.

Conclusions

This study reports the first evidence of resting‐state functional circuits within gray matter in the rat spinal cord, and verifies their detectability using resting‐state functional MRI at 9.4 T. Magn Reson Med 79:2773–2783, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
u‐p semi‐Lagrangian reproducing kernel formulation for landslide modeling
Authors: Siriaksorn Thanakorn , Chi Sheng‐Wei , Foster Craig , Mahdavi Ashkan
Published: September 2017

This paper presents a u‐p (displacement‐pressure) semi‐Lagrangian reproducing kernel (RK) formulation to effectively analyze landslide processes. The semi‐Lagrangian RK approximation is constructed based on Lagrangian discretization points with fixed kernel supports in the current configuration. As a result, it tracks state variables at discretization points while allowing extreme deformation and material separation that is beyond the capability of Lagrangian formulations. The u‐p formulation following Biot theory is incorporated into the formulation to describe poromechanics of saturated geomaterials. In addition, a stabilized nodal integration method to ensure stability of the domain integration and kernel contact algorithms to model contact between bodies are introduced in the u‐p semi‐Lagrangian RK formulation. The proposed method is verified with several numerical examples and validated with an experimental result and the field data of an actual landslide.
The Relationship between Provision of Membership Benefits and Fulfillment of Representational Roles in Nonprofit Advocacy Membership Organizations
Authors: Yoshioka Takayuki
Published: September 2017

This article explores the ways nonprofit advocacy membership organizations can manage their resource dependence on members and fulfill the organizations' representational roles, focusing on the provision of membership benefits. Membership organizations rely on financial or other resources from members and thus are constrained by them. For a nonprofit that aims to primarily speak for members, constraints by members may help to focus organizational attention on members' interests. Contrarily, for a nonprofit that aims to mainly represent broader constituents, members' constraints may hamper an organization's ability to advocate for broader constituents because members do not necessarily share the same policy goals with broader constituents. The provision of membership benefits can be a useful strategy for organizations to fulfill their representational roles and to satisfy and engage members, because people often join an organization to enjoy certain membership benefits. For an empirical analysis, this study collected a large‐scale data set through web and mail surveys of nonprofit advocacy organizations across the United States. The mixed‐mode surveys achieved a 57.5 percent response rate (729 responses). The survey and regression analysis results show that member‐serving nonprofits providing members with opportunities to participate in advocacy work are more likely to represent members' interests directly. Although broader constituency‐serving nonprofits tend to prioritize members' opinions, these organizations are more likely to adhere to the mandates of broader constituents when providing selective material membership benefits. However, when providing purposive membership benefits, these nonprofits are more likely to represent members' opinions.
Superconvergent estimates of conforming finite element method for nonlinear time‐dependent Joule heating equations
Authors: Shi Dongyang , Yang Huaijun
Published: September 2017

In this article, we study the superconvergence analysis of conforming bilinear finite element method (FEM) for nonlinear Joule heating equations. Based on the rigorous estimates together with high accuracy analysis of this element, mean value technique and interpolation postprocessing approach, the superclose and superconvergent estimates about the related variables in H1‐norm are derived for semidiscrete and a linearized backward Euler fully discrete schemes, which extends the results of optimal estimates obtained for conforming FEMs in the previous literature. At last, a numerical experiment is performed to verify the theoretical analysis.
Tandem thiotepa with autologous hematopoietic cell rescue in patients with recurrent, refractory, or poor prognosis solid tumor malignancies
Authors: Osorio Diana S. , Dunkel Ira J. , Cervone Kelly Ann , Goyal Rakesh K. , Steve Lo K. M. , Finlay Jonathan L. , Gardner Sharon L.
Published: September 2017

Background: The purpose of this study was to determine the feasibility and tolerability of tandem courses of high‐dose thiotepa with autologous hematopoietic cell rescue (AHCR) in patients with recurrent, refractory solid tumors who were ineligible for a single course of high‐dose therapy due to greater than minimal residual disease. Patients with decreased hearing or poor renal function were eligible. Procedure: Thiotepa was administered intravenously at a dose of 200 mg/m2/day (6.67 mg/kg/day) daily for 3 days followed by AHCR. A second course of thiotepa was given 4 weeks later provided blood counts recovered sufficiently without evidence of tumor progression. Results: Fifty‐eight patients received 96 courses. Thirty‐eight (65%) patients received two courses of therapy. Twenty‐seven courses (28%) were administered completely in the outpatient setting. A toxic mortality rate of 3.4% was observed. Five of 26 patients with medulloblastoma were alive at a median of 35 months, whereas 21 patients died at a median of 11.7 months. Four of five patients with central nervous system germ cell tumors (CNS GCT) were alive 68–103 months following AHCR. Conclusions: Two cycles of high‐dose thiotepa with AHCR were well tolerated even in these heavily pretreated patients. This therapy may provide prolonged survival in patients with recurrent malignant brain tumors, particularly medulloblastoma and CNS GCT.
Consensus and controversies regarding the treatment of rhabdomyosarcoma
Authors: Borinstein Scott C. , Steppan Diana , Hayashi Masanori , Loeb David M. , Isakoff Michael S. , Binitie Odion , Brohl Andrew S. , Bridge Julia A. , Stavas Mark , Shinohara Eric T. , Meyer William H. , Reed Damon R. , Wagner Lars M.
Published: September 2017

Optimal treatment of rhabdomyosarcoma (RMS) requires multidisciplinary approach, incorporating chemotherapy with local control. Although current therapies are built on cooperative group trials, a comprehensive standard of care to guide clinical decision making has been lacking, especially for relapsed patients. Therefore, we assembled a panel of pediatric and adolescent and young adult sarcoma experts to develop treatment guidelines for managing RMS and to identify areas in which further research is needed. We created algorithms incorporating evidence‐based care for patients with RMS, emphasizing the importance of clinical trials and close integration of all specialties involved in the care of these patients.
Benefits and Limitations of DNA Barcoding and Metabarcoding in Herbal Product Authentication
Authors: Raclariu Ancuta Cristina , Heinrich Michael , Ichim Mihael Cristin , de Boer Hugo
Published: September 2017

Introduction

Herbal medicines play an important role globally in the health care sector and in industrialised countries they are often considered as an alternative to mono‐substance medicines. Current quality and authentication assessment methods rely mainly on morphology and analytical phytochemistry‐based methods detailed in pharmacopoeias. Herbal products however are often highly processed with numerous ingredients, and even if these analytical methods are accurate for quality control of specific lead or marker compounds, they are of limited suitability for the authentication of biological ingredients.

Objective

To review the benefits and limitations of DNA barcoding and metabarcoding in complementing current herbal product authentication.

Method

Recent literature relating to DNA based authentication of medicinal plants, herbal medicines and products are summarised to provide a basic understanding of how DNA barcoding and metabarcoding can be applied to this field.

Results

Different methods of quality control and authentication have varying resolution and usefulness along the value chain of these products. DNA barcoding can be used for authenticating products based on single herbal ingredients and DNA metabarcoding for assessment of species diversity in processed products, and both methods should be used in combination with appropriate hyphenated chemical methods for quality control.

Conclusions

DNA barcoding and metabarcoding have potential in the context of quality control of both well and poorly regulated supply systems. Standardisation of protocols for DNA barcoding and DNA sequence‐based identification are necessary before DNA‐based biological methods can be implemented as routine analytical approaches and approved by the competent authorities for use in regulated procedures. © 2017 The Authors. Phytochemical Analysis Published by John Wiley & Sons Ltd.
Residual orientation in injection‐moulded plaques of atactic‐polystyrene II: The effect of molecular weight
Authors: Healy John , Knott Robert , Edward Graham
Published: September 2017

Injection moulding of polymers is a well‐established technique for the production of increasingly complex articles, and residual molecular orientation is a matter of considerable interest. A single matrix of commercial atactic polystyrene was systematically blended with deuterated polystyrene chains of five different weight fractions and the orientation investigated using small angle neutron scattering (SANS), optical birefringence and thermal shrinkage. The strengths and limitations of the experimental techniques used to measure residual orientation are explored and highlighted the unique contribution of SANS to observe ensemble averaged molecular orientation using deuterated polymers. The residual molecular orientation was found to vary with the molecular weight of the deuterated chains with an increase with increasing molecular weight. The observed correlations lead to a better understanding of the processing parameters that influence the degree of residual orientation on the molecular scale. Such information is valuable in the selection of the polymer matrix, mould design, and processing conditions. POLYM. ENG. SCI., 58:1332–1341, 2018. © 2017 Society of Plastics Engineers
Quality of life outcomes following pediatric lung transplantation
Authors: Lazor Tanya , Grasemann Hartmut , Solomon Melinda , Anthony Samantha J.
Published: September 2017

Purpose

Compared to other solid organs, survival after lung transplantation (LTx) is still poor. Discussions on survival benefits following LTx in children, however, have largely concentrated on medical outcome data. Little research describes quality of life (QoL) of pediatric LTx recipients, which is partly due to the small number of pediatric LTxs performed. Only two centers worldwide performed >10 pediatric LTxs in 2013, making data on QoL in this population difficult to obtain. The primary objective was to examine the impact of LTx on QoL of pediatric recipients.

Methods

LTx recipients aged 8‐17 years and their parents were recruited from a Canadian pediatric transplant centre. Participants completed the PedsQL 4.0 Generic Core Scales, a validated health‐related QoL patient‐reported outcome measure for children and adolescents, pre‐transplant and two times post‐transplant. Pre‐LTx QoL scores were compared with initial assessment scores post‐LTx and changes in QoL over time were described. Correlations between self‐ and proxy‐reports were also discussed.

Results

Ten pediatric LTx recipients (six male, mean age = 13.3 years) and their parents were enrolled. Assessments were completed pre‐LTx (mean months = 4.8) and two times post‐LTx (mean months 8.7 and 24.6, respectively). Pre‐ and post‐transplant total scores differed significantly for both self‐ and proxy‐report, which remained consistent at a second assessment post‐transplant (P = 0.018 and 0.028, respectively).

Conclusions

Findings highlight the importance of QoL outcomes when exploring LTx as a treatment option. Future research should explore long‐term QoL outcomes post‐LTx and examine standardized integration of patient‐reported outcomes into clinical practice.
Pharmacokinetics of single‐dose ceftaroline fosamil in children with cystic fibrosis
Authors: Le Jennifer , Bradley John S. , Hingtgen Sara , Skochko Shannon , Black Nanette , Jones Ronald N. , Lim Meerana , Capparelli Edmund V.
Published: September 2017

Background

Single‐dose pharmacokinetics (PK) and safety of ceftaroline fosamil with population pharmacokinetic/pharmacodynamic (PK/PD) modeling for staphylococcal pneumonia was performed in children with CF.

Methods

Subjects between 6 and 18 years old were evaluated in this phase 1, open‐label, single‐dose, prospective study using 10 mg/kg (up to 600 mg). Non‐compartmental analysis and population‐based PK analyses with Monte Carlo simulation (for doses 8‐20 mg/kg every 8 h, infused over 1‐4 h) were conducted.

Results

A total of 20 subjects were enrolled. The median age and weight were 12 yr (range 6.3‐17.4) and 38.7 kg (range 17.8‐94.3), respectively. A 3‐compartment linear model incorporating age and weight provided the best fit for the data. Comparing children 6 to <12 years to those 12 to <18 years, the mean posthoc Bayesian parameter estimates for total volume of distribution (VT) were 0.32 ± 0.05 L/kg versus 0.32 ± 0.04 L/kg, P = 0.7; and total Clearance (CLT), 0.50 ± 0.10 L/h/kg versus 0.30 ± 0.07 L/h/kg, P = 0.001. Using susceptibility data from pediatric MRSA lower respiratory tract isolates, 8 mg/kg (maximum of 1000 mg per dose) infused over 1 h every 8 h achieved free‐drug plasma concentrations above the minimum inhibitory concentration for ≥60% of the dosing interval in at least 95% of virtual subjects.

Conclusions

Since children with CF have increased ceftaroline CL compared with published data from non‐CF children; greater dosages may be required in children with CF to achieve adequate exposure in the treatment of MRSA pneumonia. Pharmacodynamic‐based dosing predicts that dosing should also be based on the patient's MRSA MIC.
Modeling CAPRI targets 110‐120 by template‐based and free docking using contact potential and combined scoring function
Authors: Kundrotas Petras J. , Anishchenko Ivan , Badal Varsha D. , Das Madhurima , Dauzhenka Taras , Vakser Ilya A.
Published: September 2017

The paper presents analysis of our template‐based and free docking predictions in the joint CASP12/CAPRI37 round. A new scoring function for template‐based docking was developed, benchmarked on the Dockground resource, and applied to the targets. The results showed that the function successfully discriminates the incorrect docking predictions. In correctly predicted targets, the scoring function was complemented by other considerations, such as consistency of the oligomeric states among templates, similarity of the biological functions, biological interface relevance, etc. The scoring function still does not distinguish well biological from crystal packing interfaces, and needs further development for the docking of bundles of α‐helices. In the case of the trimeric targets, sequence‐based methods did not find common templates, despite similarity of the structures, suggesting complementary use of structure‐ and sequence‐based alignments in comparative docking. The results showed that if a good docking template is found, an accurate model of the interface can be built even from largely inaccurate models of individual subunits. Free docking however is very sensitive to the quality of the individual models. However, our newly developed contact potential detected approximate locations of the binding sites.
Misunderstanding the preorganization concept can lead to confusions about the origin of enzyme catalysis
Authors: Jindal Garima , Warshel Arieh
Published: September 2017

Understanding the origin of the catalytic power of enzymes has both conceptual and practical importance. One of the most important finding from computational studies of enzyme catalysis is that a major part of the catalytic power is due to the preorganization of the enzyme active site. Unfortunately, misunderstanding of the nontrivial preorganization idea lead some to assume that it does not consider the effect of the protein residues. This major confusion reflects a misunderstanding of the statement that the interaction energy of the enzyme group and the transition state (TS) is similar to the corresponding interaction between the water molecules (in the reference system) and the TS, and that the catalysis is due to the reorganization free energy of the water molecules. Obviously, this finding does not mean that we do not consider the enzyme groups. Another problem is the idea that catalysis is due to substrate preorganization. This more traditional idea is based in some cases on inconsistent interpretation of the action of model compounds, which unfortunately, do not reflect the actual situation in the enzyme active site. The present article addresses the above problems, clarifying first the enzyme polar preorganization idea and the current misunderstandings. Next we take a specific model compound that was used to promote the substrate preorganization proposal and establish its irrelevance to enzyme catalysis. Overall, we show that the origin of the catalytic power of enzymes cannot be assessed uniquely without computer simulations, since at present this is the only way of relating structure and energetics.