bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imposed registries within the European postmarketing surveillance system: Extended analysis and lessons learned for regulators
Authors: Pacurariu Alexandra , Plueschke Kelly , Olmo Carla Alonso , Kurz Xavier 
Published: May 2018

AbstractPurposeBuilding on previous research, we examined whether delayed study start and low patient accrual rates found in 31 postauthorization registry‐based studies requested by European Medicines Agency (EMA) are maintained after 2 additional years of follow‐up.MethodThe registries identified in the previous EMA study and the same methodology were used. The follow‐up was extended from June 2015 to November 2017. The information available for the following variables was updated: marketing authorization status, study and registry status, study end date, planned duration, number of patients planned to be enrolled, and actual patients enrolled. Data were collected from several nonpublic in‐house sources such as the study protocols, interim and final study reports, risk management plans, and periodic safety update reports.ResultsAs of November 2017, 10 (32.2%) studies were finalized (vs. 9.7% as of June 2015), 14 (45.2%) were still ongoing (vs. 64.5%). Four of the ongoing studies had patients' accrual lower than 50%. Six of the finalized studies had a delayed completion, with a median delay of 3 years. As of November 2017, the median patients' accrual percentages were 24% for ongoing studies (vs. 8.5%) and 101% for finalized studies (vs. 24%).ConclusionOverall, the rate of recruitment and timely finalization were improved after 2 years of additional follow‐up but show that further work is needed to facilitate use of registry data for regulatory purposes, a work that has started via the EMA registry initiative.
Identification of an IDR peptide formulation candidate that prevents peptide aggregation and retains immunomodulatory activity
Authors: Haney Evan F. , Wuerth Kelli C. , Rahanjam Negin , Safaei Nikouei Nazila , Ghassemi Arvin , Alizadeh Noghani Mahsa , Boey Anthony , Hancock Robert E. W. 
Published: May 2018

AbstractSynthetic peptides derived from naturally occurring host defence peptides (HDPs) have garnered significant attention as novel pharmaceuticals, particularly as alternatives to antibiotics and for immunomodulatory applications. One of the barriers to advancing synthetic peptides for therapeutic applications is their tendency to aggregate under specific ionic conditions similar to those they would encounter in vivo. Formulating peptides with biocompatible excipients that prevent solvent‐induced peptide aggregation represents a possible solution to this aggregation issue; however, this strategy has not been systematically explored. In the present work, we describe the screening of various polymeric substances (including hyaluronic acid, carboxymethyl cellulose and hydroxypropyl methyl cellulose) as formulation candidates for HDPs and identified derivatized hyperbranched polyglycerols (dHPGs) as a biocompatible excipient that limits peptide aggregation. Notably, the immunomodulatory activity of a synthetic innate defence regulator peptide, IDR‐1018, formulated with dHPG was retained when evaluated against both peripheral blood mononuclear cells and human bronchiolar epithelial cells in vitro. Further characterization of dHPG polymers revealed that decreasing the negative charge density on the polymer surface potentiated the cytotoxic effects of IDR‐1018, emphasizing the need to optimize this parameter for future peptide delivery formulations. Importantly, the dHPG formulated IDR‐1018 inhibited peptide aggregation in vitro in the presence of mucin as well as in vivo when injected subcutaneously into CD1 mice. This study highlights the potential use of dHPGs as formulation candidates for synthetic HDPs and identifies important considerations regarding their physico‐chemical properties and relevance to immunomodulatory applications.
Molecular identification of cultivable bacteria in the gut of adult Bactrocera tau (Walker) and their trapping effect
Authors: Luo Mijuan , Zhang Hehe , Du Yinggang , Idrees Atif , He Longyan , Chen Jiahua , Ji Qing′e 
Published: May 2018

AbstractBACKGROUNDIt has been shown that some bacteria can attract their hosts. Our research aimed to identify cultivable bacterial isolates in the guts of sexually mature adult female and male Bactrocera tau and to evaluate their utility in trapping of B. tau.RESULTSForty‐one strains of bacteria were isolated and identified from B. tau with morphological, physiological, biochemical and 16S rDNA analysis. The dominant bacterial genera shared by both females and males were Enterobacter, Providencia and Serratia. Thirteen bacterial isolates selected from female and male B. tau adults were cultured, and the attractiveness of bacterial fermented liquid and autoclaved supernatants from these strains to B. tau adults was tested. The laboratory test showed that both the autoclaved supernatants and fermented liquid could attract male and female B. tau, and the former was substantially more effective, with the autoclaved supernatants from all strains being significantly more attractive to adult B. tau. BF16, BF(12), BF23 and BF(32) were the most attractive bacteria to 8‐day‐old and sexually mature B. tau. Furthermore, the results of a subsequent field cage test showed that BF(12), BF23, and BF(32) were significantly more attractive to B. tau adults.CONCLUSIONThese results provide useful information for the development of bacterial biocontrol agents and their application as insecticides. © 2018 Society of Chemical Industry
Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry
Authors: Kennedy Joseph H. , Palaty Jan , Gill Chris G. , Wiseman Justin M. 
Published: May 2018

RationaleDrug overdose deaths due to fentanyls and other novel psychoactive substances (NPS) are on the rise. The higher potencies of fentanyl analogs compared with morphine require new technologies to identify and quantitate NPS.MethodsPaper spray tandem mass spectrometry (MS/MS) and high‐resolution mass spectrometry were used to identify and measure fentanyl analogs as well as common drugs of abuse in urine samples from substance use disorder clinics. Ten‐microliter urine samples were deposited directly on paper spray cartridges previously loaded with internal standards, dried, and analyzed with no other sample treatment. Quantitative results were obtained using MS/MS. Individual drugs were identified using high‐resolution accurate mass spectrometry, and confirmed by data‐dependent MS/MS.ResultsCalibration curves in urine were linear over a range of 0.5–50 ng/mL with R2 of 0.99 or better for eight representative fentanyl analogs. Cartridges preloaded with internal standards demonstrated satisfactory quantitative results compared with LC/MS. Direct identification and confirmation of fentanyl analogs and other common drugs of abuse in urine using high‐resolution accurate mass and MS/MS fragmentation were demonstrated at low picogram levels.ConclusionsPaper spray mass spectrometry can reliably identify and quantitate fentanyl analogs and other drugs of abuse in urine. Using paper spray cartridges as collection devices reduces exposure and transportation risks associated with biological fluids. Cartridges preloaded with labeled internal standards can be effective for targeted screening of fentanyl analogs and other drugs of abuse.
Coupling trapped ion mobility spectrometry to mass spectrometry: trapped ion mobility spectrometry–time‐of‐flight mass spectrometry versus trapped ion mobility spectrometry–Fourier transform ion cyclotron resonance mass spectrometry
Authors: Tose Lilian V. , Benigni Paolo , Leyva Dennys , Sundberg Abigail , Ramírez César E. , Ridgeway Mark E. , Park Melvin A. , Romão Wanderson , Jaffé Rudolf , Fernandez‐Lima Francisco 
Published: May 2018

RationaleThere is a need for fast, post‐ionization separation during the analysis of complex mixtures. In this study, we evaluate the use of a high‐resolution mobility analyzer with high‐resolution and ultrahigh‐resolution mass spectrometry for unsupervised molecular feature detection. Goals include the study of the reproducibility of trapped ion mobility spectrometry (TIMS) across platforms, applicability range, and potential challenges during routine analysis.MethodsA TIMS analyzer was coupled to time‐of‐flight mass spectrometry (TOF MS) and Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR MS) instruments for the analysis of singly charged species in the m/z 150–800 range of a complex mixture (Suwannee River Fulvic Acid Standard). Molecular features were detected using an unsupervised algorithm based on chemical formula and IMS profiles.ResultsTIMS‐TOF MS and TIMS‐FT‐ICR MS analysis provided 4950 and 7760 m/z signals, 1430 and 3050 formulas using the general CxHyN0–3O0–19S0–1 composition, and 7600 and 22 350 [m/z; chemical formula; K; CCS] features, respectively.ConclusionsTIMS coupled to TOF MS and FT‐ICR MS showed similar performance and high reproducibility. For the analysis of complex mixtures, both platforms were able to capture the major trends and characteristics; however, as the chemical complexity at the level of nominal mass increases with m/z (m/z >300–350), only TIMS‐FT‐ICR MS was able to report the lower abundance compositional trends.
Fragmentation pathways arising from protonation at different sites in aminoalkyl‐substituted 3‐hydroxy‐1,2,5‐oxadiazoles (3‐hydroxyfurazans)
Authors: Grossert J. Stuart , Boschi Donatella , Lolli Marco L. , White Robert L. 
Published: May 2018

RationaleThe gas‐phase fragmentation chemistry of multifunctional cations is highly influenced by the site of protonation. Possible relationships between protonation site and fragmentation processes were studied using 4‐aminoalkyl‐3‐hydroxyfurazans. For these heterocyclic amines, the starting points for competing fragmentation pathways varied with protonation at multiple sites in two tautomers.MethodsMass spectra were acquired using electrospray ionization (positive mode) coupled to triple quadrupole and ion trap mass spectrometers; precursor–product ion relationships were studied by collision‐induced dissociation. Quantum mechanical computations were performed at the MP2/6–311++G(2d,p)//ωB97X‐D/6–311+G(d) level of theory.ResultsProminent successive losses of NO and CO and competing losses of CH2=NH or NH3 were observed as fragmentation processes. The lowest barrier computed for the initial step in a fragmentation pathway was associated with the [M + H]+ ion protonated at N5 in the heterocyclic ring, whereas an alternative ring cleavage leading to complementary product ions was initiated by protonation of the ring at N2. Side‐chain protonation led to loss of NH3 without cleavage of the 3‐hydroxyfurazan ring.ConclusionsThe product ions obtained by the competing fragmentation processes varied with the site of protonation. Interestingly, the most abundant product ions observed at low collision energies were formed by cleavage of protonated molecules possessing more internal energy than other isomers.
Hydrodynamic behaviour of European black poplar (Populus nigra L.) under coppice management along Mediterranean river ecosystems
Authors: Pasquino V. , Saulino L. , Pelosi A. , Allevato E. , Rita A. , Todaro L. , Saracino A. , Chirico G.B. 
Published: May 2018

AbstractThis study examined the hydrodynamic behaviour of European black poplar (Populus nigra L.) under coppice management in riparian areas with a multidisciplinary approach. An innovative procedure on the basis of the combination of plant allometric relations and hydrodynamic models was applied to assess drag forces and plant hydrodynamic bending as function of the basal diameter and module of elasticity, with a probabilistic approach. Cuttings of European black poplar from 2 close riverine environments of Southern Italy have been planted and subjected to the same coppice management strategy. The 2 different 3‐year‐old shoot poplar ensembles exhibited statistically similar morphological traits but stems with different module of elasticity. Drag forces were simulated with a model on the basis of the vegetative Cauchy number. Plant deformation under the hydrodynamic load was modelled as a base‐mounted cantilever beam. The differences in the observed elasticity were verified to be also significant from a hydrodynamic perspective. Diagrams were drawn to describe plant bending, drag forces, and basal momentum as function of basal diameter, accounting for the uncertainty in the module of elasticity. These results can be exploited for identifying objective hydrodynamic criteria to be adopted for coppice management of riparian woody vegetation in human controlled river ecosystems.
Effects of Sodium Hydroxyethyl Sulfonate on Improving the Ductility of the Copper Films Deposited by Electroless Plating from High‐Speed Plating Baths
Authors: Wu Minxian , Xu Chao , Wang Wenchang , Mitsuzaki Naotoshi , Chen Zhidong 
Published: May 2018

AbstractThe copper films that electroless plated from the formaldehyde‐based solutions frequently suffer from the internal stress. The internal stress leads to a poor ductility of the plated films. To lower internal stress and improve ductility of copper films, sodium hydroxyethyl sulfonate was used as a surfactant to promote the detachment of hydrogen bubbles. The folding tests showed that the copper film deposited from the solution containing 3 mL L−1 25% sodium hydroxyethyl sulfonate (EHS) had the best ductility. The internal stresses of the copper films were measured using X‐ray diffraction technique and the stress decreased from 100 MPa to 30 MPa as the EHS concentration increased from 0 to 3 mL L−1. Sodium hydroxyethyl sulfonate had little influence on the film morphology and crystal size. High plating rates (> 8 μm h−1) were obtained from the solution containing sodium hydroxyethyl sulfonate.
Investigation of the Enzyme‐Catalysed Transesterification of Methyl Acrylate and Sterically Hindered Alcohol Substrates
Authors: Bauwelinck Jordy , Cornet Iris , Wijnants Marc , Dams Rudolf , Tavernier Serge 
Published: May 2018

AbstractFor industrial production of valuable building blocks, the use of enzymes as green catalysts has gained a lot of interest recently. In this paper, research on the enzymatic transesterification of methyl esters with different alcohols for the production of high valuable monomers is presented. After screening for the most suitable enzyme catalyst, the influence of the molecular structure of both substrates on the reaction kinetics was investigated. For the best performing substrate, the reaction was optimised. Novozym 435 displays the highest activity for linear as well as for bulkier substrates and has therefore been chosen for the optimisation experiments. Enzymatic transesterification with highly branched and bulky alcohol substrates (e. g. 2‐hexyl‐1‐decanol) resulted in much lower conversion and reaction rates compared to linear and shorter substrates (e. g. octanol). Similar effects were observed when various methyl ester substrates were compared. Furthermore, it was observed that a molar substrate ratio of 3:1 methyl acrylate to alcohol and a substrate to enzyme ratio of 0.1 mol.g−1 resulted in an optimal conversion. It was also found that reactions using nonpolar solvents (e. g. hexane, heptane, toluene) reached the highest conversion rates. Generally, it can be concluded that enzymatic synthesis of highly specific and bulky alkyl acrylates is possible. However, the structures of both the alcohol and acrylate substrate have an important impact on the reaction rate.
Computational Design of Quaterpyridine‐Based Fe/Mn–Complexes for the Direct Hydrogenation of CO2 to HCOOH: A Direction for Atom‐Economic Approach
Authors: Biswas Santu , Pramanik Anup , Sarkar Pranab 
Published: May 2018

AbstractOn the basis of first principle calculations, we propose a new class of earth‐abundant quaterpyridine complexes for the direct hydrogenation of CO2 to HCOOH. The mechanistic studies reveal that the complexes are advantageous in many aspects. First of all, they can perform both in added‐base and base‐free conditions, the latter being atom‐economic as well as a greener way. Most effectively, the energy barrier for the heterolytic hydrogen cleavage and hydride transfer processes could easily be monitored by changing the π‐acidic character of the axial ligand, solvent polarity of the medium and also by ligand modification through substitution.
Oxygen Evolution Reaction on Ni‐based Two‐dimensional (2D) Titanate Nanosheets: Investigation on Effect of Fe Co‐doping and Fe Incorporation from Electrolyte on the Activity
Authors: Ramesh Rahul , Lee Seonggyu , Kim Seongbeen , Park Jinkyu , Lee Seunghyun , Kim Min Su , Baek Minki , Yong Kijung , Ye Youngjin , Lee Jinwoo 
Published: May 2018

AbstractIn this paper, Ni‐based titanate nanosheets are used as a model system to reveal how incorporation of Fe affects their catalytic ability for the oxygen evolution reaction (OER). The Fe incorporation effects are studied without structural and morphological changes due to the rigid framework of TiO2 based nanosheets. Transition metal doped titanate nanosheets are prepared by cation‐assisted exfoliation of protonated layered potassium titanate. Fe incorporation within the lattice of Ni doped titanate nanosheets by co‐doping stabilizes nickel ions in lower oxidation state by charge transfer effect, caused increased OER activity at Ni sites by the electronic interaction. In contrast, incorporation of Fe from the electrolyte, highly‐active Fe sites at edges or corners of Ni doped titanate nanosheets are formed by electrochemical cycling in Fe‐containing electrolyte rather than electronic effects on Ni. Through this work, Fe incorporation effects are experimentally revealed without crystal structural or morphological changes, and a method to produce a highly active and stable OER catalyst is provided.
A Domino Reaction of Pyridinium Salts: Efficient Synthesis of 4,5‐Disubstituted 1,2,3‐(NH)‐Triazoles
Authors: Wu Guang‐Long , Wu Qin‐Pei 
Published: May 2018

AbstractA one‐pot mild and metal‐free procedure for efficient synthesis of 4,5‐disubstituted 1,2,3‐(NH)‐triazoles has been developed through the sequentially reaction of pyridinium salts with aldehydes and sodium azide. In the presence of L‐proline, a key intermediate, an olefinic pyridinium‐salt, is in situ generated via coupling of pyridinium salts with aldehydes and cyclizes with azide ion to form a triazole ring.
New remains of the aquatic turtle Hydromedusa casamayorensis (Pleurodira, Chelidae) from the middle Eocene of Patagonia: taxonomic validation and phylogenetic relationships
Authors: Maniel Ignacio J. , de la Fuente Marcelo S. , Sterli Juliana , Jannello Juan M. , Krause J. Marcelo 
Published: May 2018

AbstractTwenty‐seven new specimens recovered from lower levels of the Sarmiento Formation (Casamayoran SALMA, middle Eocene) in the ‘Cañadón Hondo’ area, Chubut (Argentina), bring new information on the Palaeogene long‐necked chelid Hydromedusa casamayorensis. The discovery of cranial and postcranial remains allows a complete description of the only known extinct species of the genus Hydromedusa recognizing diagnostic characters that revalidate the taxonomic status of this species. Hydromedusa casamayorensis is incorporated into a cladistic framework of chelid turtles. The unconstrained and constrained phylogenetic analyses recovered H. casamayorensis as a sister taxon of Hydromedusa maximiliani plus H. tectifera. A Danian age is proposed at least for the origin of the Hydromedusa clade, while a Late Cretaceous age is suggested for the split from the Yaminuechelys clade. Great differences in size are documented for H. casamayorensis based on the various specimens recovered from this study. The osteohistological study in H. casamayorensis and H. tectifera shows similarities in the internal cortex and cancellous bone of both taxa, but some differences are observed in the external cortex of H. casamayorensis (e.g. a parallel fibred bone on the more external surface of this cortex).
Ist die ausdrückliche Regelung sozialrechtlicher Leistungsansprüche für Personen mit hohen und moderaten Risiken geboten?
Authors: Meier Friedhelm , Harney Anke , Rhiem Kerstin , Neumann Anja , Neusser Silke , Braun Matthias , Wasem Jürgen , Schmutzler Rita , Huster Stefan , Dabrock Peter 
Published: May 2018

Zusammenfassung
In diesem Kapitel wird aus medizinischer, sozialrechtlicher, gesundheitsökonomischer und ethischer Perspektive erörtert, warum überhaupt ein sozialrechtlicher Leistungsanspruch für Personen mit hohen und moderaten Risiken geboten ist.
Empfehlungen
Authors: Meier Friedhelm , Harney Anke , Rhiem Kerstin , Neumann Anja , Neusser Silke , Braun Matthias , Wasem Jürgen , Schmutzler Rita , Huster Stefan , Dabrock Peter 
Published: May 2018

Zusammenfassung
Dieses Kapitel leitet aus der dargelegten Argumentation konkrete Empfehlungen für die Entscheidungsträgerinnen und Entscheidungsträger ab und kann somit erste Schritte zur Realisierung einer adäquaten sozialrechtlichen Berücksichtigung von Personen mit hohen und moderaten (Brustkrebs-)Risiken aufzeigen.
Effect of 0.25 and 2.0 MeV He-Ion Irradiation on Short-Range Ordering in Model (EFDA) Fe-Cr Alloys
Authors: Dubiel Stanisław M. , Żukrowski Jan , Serruys Yves 
Published: May 2018

Abstract
The effects of He+ irradiation on a distribution of Cr atoms in Fe100−x
Cr
x
(x = 5.8, 10.75, 15.15) alloys were studied by 57Fe Conversion Electron Mössbauer Spectroscopy (CEMS). The alloys were irradiated with doses up to 12 × 1016 ions/cm2 with 0.25 and 2.0 MeV He+ ions. The distribution of Cr atoms within the first two coordination shells around Fe atoms was expressed with short-range order parameters α
1 (first-neighbor shell, 1NN), α
2 (second-neighbor shell, 2NN), and α
12 (1NN + 2NN). In non-irradiated alloys, α
1 >0 and α
2 <0 was revealed for all three samples. The value of α
12 ≈0, i.e., the distribution of Cr atoms averaged over 1NN and 2NN, was random. The effect of the irradiation of the Fe94.2Cr5.8 alloy was similar for the two energies of He+, viz., increase of number of Cr atoms in 1NN and decrease in 2NN. Consequently, the degree of ordering increased. For the other two samples, the effect of the irradiation depends on the composition, and is stronger for the less energetic ions where, for Fe89.25Cr10.75 alloy, the disordering disappeared and some traces of Cr clustering appeared. In Fe84.85Cr15.15 alloy, the clustering was clear. In the samples irradiated with 2. 0 MeV He+ ions, the ordering also survived in the samples with x = 10.75 and 15.15, yet its degree became smaller than in the Fe94.2Cr5.8 alloy.