bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of serious adverse events reporting to academic sponsors of clinical trials: far from optimal
Authors: Crépin Sabrina , Villeneuve Claire , Merle Louis 
Published: February 2016

AbstractPurposeThe purpose of this study is to evaluate the quality of the serious adverse events (SAE) reported to an academic sponsor. Assessing the safety of a clinical trial relies on information gathering the collection of adverse events reported by the investigators to the sponsor. The accuracy of safety evaluation depends in particular on the quality of the reporting.MethodsAll SAE case report forms, reported in 2012 to the sponsor from all clinical trials, were evaluated for completeness and accuracy with a standardized data quality evaluation form. Several items were assessed: regulatory mandatory information and items concerning the reported events. For statistical comparisons, Chi2/exact Fisher test was performed.ResultsInvestigators or patients were not identified in <3% of the reports. The investigational product was not identified in 11.2%. In 3.6% of the reports, the seriousness of the event was unknown. The causality assessment was missing in 9.3%. In 15.0%, the verbatim of the event was considered as not consistent with the description of the event. In 32.4%, the sponsor considered there were insufficient data concerning relevant laboratory/additional examinations performed or relevant history required to help in the assessment. The onset date of SAE was not mentioned in 5.7% of the reports and patient outcome in 12.1%.ConclusionsThis study highlighted the far from optimal quality of reporting both in terms of completeness and accuracy. The accurate coding of the events using MedDRA and the safety evaluation by the sponsor can be difficult. The training of investigators in SAE reporting must be improved. Copyright © 2016 John Wiley & Sons, Ltd.
Prescription patterns of antiepileptic drugs in young women: development of a tool to distinguish between epilepsy and psychiatric disorders
Authors: Naldi Ilaria , Piccinni Carlo , Mostacci Barbara , Renzini Jessica , Accetta Gabriele , Bisulli Francesca , Tappatà Maria , Piazza Antonella , Pagano Paola , Bianchi Stefano , D'Alessandro Roberto , Tinuper Paolo , Poluzzi Elisabetta ,   ESPEA (Emilia‐Romagna Study on Pregnancy and Exposure to Antiepileptic drugs) Group
Published: February 2016

AbstractBackgroundAntiepileptic drugs (AEDs) are also prescribed for therapeutic indications other than epilepsy (EPI), namely, psychiatric disorders (PSY). Our aim was to develop an algorithm able to distinguish between EPI and PSY among childbearing age women based on differences in AED exposure in these patient groups.MethodsTwo groups of women (18–45 years) with EPI or PSY treated with AEDs in the first semester of 2010 or 2011 were extracted from paper or electronic medical charts of specialized centers. Through the prescription database of Bologna Local Health Authority (Italy), AEDs, treatment schedule and co‐treatments were collected for each patient. A prescription‐based hierarchical classification system was developed. The algorithm obtained was subsequently validated on internal and external data.ResultsEighty‐one EPI and 94 PSY subjects were recruited. AED monotherapy was the most common choice in both groups (69% EPI vs 79% PSY). Some AEDs were used only in EPI, others exclusively in PSY. Co‐treatments with antipsychotics (6% vs 67%), lithium (0% vs 9%), and antidepressants (7% vs 70%) were fewer in EPI than in PSY. The hierarchical classification system identified antipsychotics, SSRIs (Selective Serotonin Reuptake Inhibitors), and number of AEDs as variables to discriminate EPI and PSY, with an overall error rate estimate of 9.7% (95%CI: 5.3% to 14.1%).ConclusionAmong the differences between EPI and PSY, prescription data alone allowed an algorithm to be developed to diagnose each childbearing age woman receiving AEDs. This approach will be useful to stratify patients for risk estimates of AED‐treated patients based on administrative databases. Copyright © 2016 John Wiley & Sons, Ltd.
Radiation damage in polymer films from grazing‐incidence X‐ray scattering measurements
Authors: Vaselabadi Saeed Ahmadi , Shakarisaz David , Ruchhoeft Paul , Strzalka Joseph , Stein Gila E. 
Published: February 2016

ABSTRACTGrazing‐incidence X‐ray scattering (GIXS) is widely used to analyze the crystallinity and nanoscale structure in thin polymer films. However, ionizing radiation will generate free radicals that initiate crosslinking and/or chain scission, and structural damage will impact the ordering kinetics, thermodynamics, and crystallinity in many polymers. We report a simple methodology to screen for beam damage that is based on lithographic principles: films are exposed to patterns of X‐ray radiation, and changes in polymer structure are revealed by immersing the film in a solvent that dissolves the shortest chains. The experiments are implemented with high throughput using the standard beam line instrumentation and a typical GIXS configuration. The extent of damage (at a fixed radiation dose) depends on a range of intrinsic material properties and experimental variables, including the polymer chemistry and molecular weight, exposure environment, film thickness, and angle of incidence. The solubility switch for common polymers is detected within 10–60 s at ambient temperature, and we verified that this first indication of damage corresponds with the onset of network formation in glassy polystyrene and a loss of crystallinity in polyalkylthiophenes. Therefore, grazing‐incidence X‐ray “patterning” offers an efficient approach to determine the appropriate data acquisition times for any GIXS experiment. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1074–1086
Assessment of CASP11 contact‐assisted predictions
Authors: Kinch Lisa N. , Li Wenlin , Monastyrskyy Bohdan , Kryshtafovych Andriy , Grishin Nick V. 
Published: February 2016

ABSTRACTWe present an overview of contact‐assisted predictions in the eleventh round of critical assessment of protein structure prediction (CASP11), which included four categories: predicted contacts (Tp), correct contacts (Tc), simulated sparse NMR contacts (Ts), and cross‐linking contacts (Tx). Comparison of assisted to unassisted model quality highlighted a relatively poor overall performance in CASP11 using predicted Tp and crosslinked Tx contact information. However, average model quality significantly improved in the correct Tc and simulated NMR Ts categories for most targets, where maximum improvement of unassisted models reached an impressive 70 GDT_TS. Comparison of the performance in the correct Tc category to CASP10 suggested the improvement in CASP11 model quality originated from an increased number of provided contacts per target. Group rankings based on a combination of scores used in the CASP11 free modeling (FM) assessment for each category highlight four top‐performing groups, with three from the Lee lab and one from the Baker lab. We used the overall performance of these groups in each category to develop hypotheses for their relative outperformance in the correct Tc and simulated NMR Ts categories, which stemmed from the fraction of correct contacts provided (correct Tc category) and a reduced fraction of correct contacts offset by an increased coverage of the correct contacts (simulated NMR Ts category). Proteins 2016; 84(Suppl 1):164–180. © 2016 Wiley Periodicals, Inc.
Hog1p activation by marasmic acid through inhibition of the histidine kinase Sln1p
Authors: Jacob Stefan , Schüffler Anja , Thines Eckhard 
Published: February 2016

AbstractBACKGROUNDThe histidine kinase (HK) MoHik1p within the high‐osmolarity glycerol (HOG) pathway is known to be the target of the fungicide fludioxonil. Treatment of the fungus with fludioxonil causes an uncontrolled hyperactivation of the pathway and cell death. In this study, we used a target‐based in vivo test system with mutant strains of the rice blast fungus Magnaporthe oryzae to search for new fungicidal compounds having various target locations within the HOG pathway. Mutants with inactivated HOG signalling are resistant to fungicides having the target located in the HOG pathway.RESULTSThe HK MoSln1p was identified as being involved in the new antifungal mode of action of marasmic acid, as single inactivation of the genes MoSLN1, MoSSK1, MoSSK2, MoPBS2 and MoHOG1 resulted in mutant strains resistant against the sesquiterpenoid, whereas the wild‐type strain and the ΔMohik1 mutant were susceptible. Western blot analysis of phosphorylated MoHog1p confirmed the hypothesis that marasmic acid interferes with the HOG pathway, as a strong phosphorylation of MoHog1p was detectable after sesquiterpenoid treatment in the wild‐type strain but not in the ΔMosln1 mutant.CONCLUSIONThis study provides evidence for marasmic acid activating the HOG pathway via the HK MoSln1p, and we propose that the sesquiterpenoid has a new mode of action in M. oryzae that differs from that of known HOG inhibitors, e.g. fludioxonil. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
RNAi‐mediated plant protection against aphids
Authors: Yu Xiu‐Dao , Liu Zong‐Cai , Huang Si‐Liang , Chen Zhi‐Qin , Sun Yong‐Wei , Duan Peng‐Fei , Ma You‐Zhi , Xia Lan‐Qin 
Published: February 2016

AbstractAphids (Aphididae) are major agricultural pests that cause significant yield losses of crop plants each year by inflicting damage both through the direct effects of feeding and by vectoring harmful plant viruses. Expression of double‐stranded RNA (dsRNA) directed against suitable insect target genes in transgenic plants has been shown to give protection against pests through plant‐mediated RNA interference (RNAi). Thus, as a potential alternative and effective strategy for insect pest management in agricultural practice, plant‐mediated RNAi for aphid control has received close attention in recent years. In this review, the mechanism of RNAi in insects and the so far explored effective RNAi target genes in aphids, their potential applications in the development of transgenic plants for aphid control and the major challenges in this regard are reviewed, and the future prospects of using plant‐mediated RNAi for aphid control are discussed. This review is intended to be a helpful insight into the generation of aphid‐resistant plants through plant‐mediated RNAi strategy. © 2016 Society of Chemical Industry
The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano
Authors: Tu Lv‐Ying , Bai Hai‐Hua , Cai Ji‐Ye , Deng Sui‐Ping 
Published: February 2016

SummaryKaempferol has been identified as a potential cancer therapeutic agent by an increasing amount of evidences. However, the changes in the topography of cell membrane induced by kaempferol at subcellular‐ or nanometer‐level were still unclear. In this work, the topographical changes of cytomembrane in human cervical cancer cell (SiHa) induced by kaempferol, as well as the role of kaempferol in apoptosis induction and its possible mechanisms, were investigated. At the macro level, MTT assays showed that kaempferol inhibited the proliferation of SiHa cells in a time‐ and dose‐dependent manner. Flow cytometry analysis demonstrated that kaempferol could induce SiHa cell apoptosis, mitochondrial membrane potential disruption, and intracellular free calcium elevation. At the micro level, fluorescence imaging by laser scanning confocal microscopy (LSCM) indicated that kaempferol could also destroy the networks of microtubules. Using high resolution atomic force microscopy (AFM), we determined the precise changes of cellular membrane induced by kaempferol at subcellular or nanometer level. The spindle‐shaped SiHa cells shrank after kaempferol treatment, with significantly increased cell surface roughness. These data showed structural characterizations of cellular topography in kaempferol‐induced SiHa cell apoptosis and might provide novel integrated information from macro to nano level to assess the impact of kaempferol on cancer cells, which might be important for the understanding of the anti‐cancer mechanisms of drugs. SCANNING 38:644–653, 2016. © 2016 Wiley Periodicals, Inc.
An energy efficient encryption method for secure dynamic WSN
Authors: Elhoseny Mohamed , Yuan Xiaohui , El‐Minir Hamdy K. , Riad Alaa Mohamed 
Published: February 2016

AbstractClustering methods have been developed to improve network life of wireless sensor network (WSN), yet the dynamic nature of sensor clusters and limited memory and processing power make security a much more challenging problem, and most conventional cryptography methods are ill suited to WSNs. In this paper, we propose a novel encryption method to secure data transmission in WSN with dynamic sensor clusters. Our method leverages elliptic curve cryptography algorithm to generate binary strings for each sensor and combines with node ID, distance to the cluster head, and the index of transmission round to form unique 176‐bit encryption keys. Using exclusive OR, substitution, and permutation operations, encryption and decryption are achieved efficiently. Compared with the state‐of‐the‐art methods, our simulation results demonstrated that the proposed method exhibited much improved network lifetime and reduced the energy consumption most evenly among all sensor nodes. More importantly, it overcame many security attacks including brute‐force attack, HELLO flood attack, selective forwarding attack, and compromised cluster head attack. Copyright © 2016 John Wiley & Sons, Ltd.
Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands
Authors: Pringle Sarah , Maimets Martti , van der Zwaag Marianne , Stokman Monique A. , van Gosliga Djoke , Zwart Erik , Witjes Max J.H. , de Haan Gerald , van Os Ronald , Coppes Rob P. 
Published: February 2016

Abstract
Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia.
BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation
Authors: Reddy Vishruth K. , Short Sarah P. , Barrett Caitlyn W. , Mittal Mukul K. , Keating Cody E. , Thompson Joshua J. , Harris Elizabeth I. , Revetta Frank , Bader David M. , Brand Thomas , Washington M. Kay , Williams Christopher S. 
Published: February 2016

Abstract
Blood vessel epicardial substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves–/– mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wild-type (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves–/– mice. To examine stem cell function after BVES deletion, we used ex vivo 3D-enteroid cultures. Bves–/– enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar “CBC” and “+4” stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves–/– enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves–/– mice demonstrated significantly greater SI crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves–/– mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis.
Experimental evaluation of optimized strut‐and‐tie models for a dapped beam
Authors: Oviedo Rodrigo , Gutiérrez Sergio , Santa María Hernán 
Published: February 2016

AbstractStrut‐and‐tie modelling constitutes a powerful tool for the design of complex structural reinforced concrete elements. It has been proved numerically that strut‐and‐tie (ST) models obtained using structural optimization methods produce designs that are more efficient. However, to the best of the authors' knowledge, no experimental evidence of such results has been published. This paper presents experimental results for nine test specimens; five of them were designed using optimal models derived from a full homogenization structural optimization algorithm, and the remaining four using conventional ST models for comparison purposes. Although all specimens carry loads higher than the factored design load, specimens based on ST models derived using full homogenization with reinforcement parallel to the ties exhibit better structural performance regarding crack growth control, more ductile modes of failure and a greater increase in load capacity.
NMDA receptors amplify mossy fiber synaptic inputs at frequencies up to at least 750 Hz in cerebellar granule cells
Authors: Baade Carolin , Byczkowicz Niklas , Hallermann Stefan 
Published: February 2016

ABSTRACTNeuronal integration of high‐frequency signals is important for rapid information processing. Cerebellar mossy fiber axons (MFs) can fire action potentials (APs) at frequencies of more than one kilohertz. However, it is unclear whether and how the postsynaptic cerebellar granule cells (GCs) are able to process these high‐frequency MF inputs. Here, we measured AP firing in GCs during high‐frequency MF stimulation and show that GC firing frequency increased non‐linearly when MF stimulation frequency was increased from 100 to 750 Hz. To investigate the mechanisms enabling such high‐frequency signaling, we analyzed the role of N‐methyl‐d‐aspartate receptors (NMDARs), which have been implicated in synaptic signaling at lower frequencies. Application of D‐2‐amino‐5‐phosphonopentanoic acid (APV), a potent inhibitor of NMDARs, strongly impaired the GC firing frequency during high‐frequency MF stimulation. APV had no significant effect on single excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) evoked at 1 Hz at resting membrane potentials. However, the time course of EPSCs evoked at 1 Hz at depolarized potentials or following high‐frequency MF stimulation was accelerated by APV. Thus, our results show that NMDAR‐mediated currents amplify high‐frequency MF inputs by prolonging the time courses of synaptic inputs, thereby causing greater synaptic summation of inputs. Hence, NMDARs support the integration of MF synaptic input at frequencies up to at least 750 Hz. Synapse 70:269–276, 2016. © 2016 Wiley Periodicals, Inc.
Picture Books in the Digital Age
Authors: Serafini Frank , Kachorsky Danielle , Aguilera Earl 
Published: February 2016

AbstractThe design, publication, and features of contemporary narrative picturebooks have been impacted by the digital revolution and the emerging popularity of digital reading devices. Considering both the affordances and the limitations of digital picturebook apps can help readers, teachers, parents, and other educators make better decisions about the value and use of such apps for different purposes.
Synthesis and Characterization of the Rubidium Thiophosphate Rb6(PS5)(P2S10) and the Rubidium Silver Thiophosphates Rb2AgPS4, RbAg5(PS4)2 and Rb3Ag9(PS4)4
Authors: Alahmari Fatimah , Davaasuren Bambar , Khanderi Jayaprakash , Rothenberger Alexander 
Published: February 2016

AbstractThe metal thiophosphates Rb2AgPS4 (2), RbAg5(PS4)2 (3), and Rb3Ag9(PS4)4 (4) were synthesized by stoichiometric reactions, whereas Rb6(PS5)(P2S10) (1) was prepared with excess amount of sulfur. The compounds crystallize as follows: 1 monoclinic, P21/c (no. 14), a = 17.0123(7) Å, b = 6.9102(2) Å, c = 23.179(1) Å, β = 94.399(4)°; 2 triclinic, P (no. 2), a = 6.600(1) Å, b = 6.856(1) Å, c = 10.943(3) Å, α = 95.150(2)°, β = 107.338(2)°, γ = 111.383(2)°; 3 orthorhombic, Pbca (no. 61), a = 12.607(1) Å, b = 12.612(1) Å, c = 17.759(2) Å; 4 orthorhombic, Pbcm (no. 57), a = 6.3481(2) Å, b = 12.5782(4) Å, c = 35.975(1) Å. The crystal structures contain discrete units, chains, and 3D polyanionic frameworks composed of PS4 tetrahedral units arranged and connected in different manner. Compounds 1–3 melt congruently, whereas incongruent melting behavior was observed for compound 4. 1–4 are semiconductors with bandgaps between 2.3 and 2.6 eV and thermally stable up to 450 °C in an inert atmosphere.
“I Feel Lucky” – Gratitude Among Young Adults with Phenylketonuria (PKU)
Authors: Diesen Plata Sofie 
Published: February 2016

AbstractIf persons with phenylketonuria (PKU) do not start a protein restricted diet in early infancy, they will suffer severe brain damage. Previous qualitative research on adults and adolescents with PKU has identified stigmatization, uncertain risk perceptions, considerable time spent on preparing food, and incongruence between the PKU diet and certain lifestyle demands. The aim of this study was to explore young and early treated Norwegian adults’ experiences, by conducting in‐depth interviews in 2011 with 11 adults with PKU, aged 20–30. Being the first qualitative study on people with PKU in Norway, the process was inspired by grounded theory. All participants reflected on their own health and existence by expressing positive counterfactual thoughts. They considered themselves lucky to have had parents who had managed the diet, they were grateful for the time and place they were born, and for information and treatment availability, although the results also show some ambiguous attitudes towards the hospital which provided the treatment. The expression of gratitude in association with having PKU suggests a major positive coping strategy. It contributes to a more holistic understanding of the experiences and attitudes of young, Norwegian adults with PKU, as it provides a counterweight to the negative experiences.