bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peficitinib, a JAK Inhibitor, in the Treatment of Moderate‐to‐Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate
Authors: Kivitz A. J. , Gutierrez‐Ureña S. R. , Poiley J. , Genovese M. C. , Kristy R. , Shay K. , Wang X. , Garg J. P. , Zubrzycka‐Sienkiewicz A. 
Published: October 2016

ObjectiveTo evaluate the efficacy and safety of orally administered once‐daily peficitinib in combination with methotrexate (MTX) in patients with moderate‐to‐severe rheumatoid arthritis (RA) who had an inadequate response to MTX.MethodsIn this multinational, phase IIb, randomized, double‐blind, placebo‐controlled, dose‐ranging trial, patients with RA (n = 378) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg plus MTX, or matching placebo plus MTX once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12.ResultsACR20 response rates at week 12 were 43.9%, 61.5% (P < 0.05 versus placebo), 46.4%, 57.7%, and 44.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Significant decreases from baseline in the Disease Activity Score in 28 joints using the C‐reactive protein level were seen in the peficitinib 50 mg (P < 0.05) and 150 mg (P < 0.01) groups compared with placebo at week 12. Overall, the incidence of adverse events (AEs) was similar between peficitinib and placebo. The most common AEs were urinary tract infection (n = 22 [6%]), upper respiratory tract infection (n = 16 [4%]), and diarrhea (n = 16 [4%]). There were 3 cases of herpes zoster infection (2 in the peficitinib 100 mg group and 1 in the 150 mg group) and 2 cases of serious infection (viral infection in the peficitinib 100 mg group and erysipelas in the 150 mg group).ConclusionThe ACR20 response rate in the group receiving peficitinib 50 mg plus MTX was significantly different compared with the rate in patients receiving placebo, but there were no apparent dose‐dependent responses, and the placebo response rate was high. Peficitinib plus MTX in patients with moderate‐to‐severe RA was well tolerated, with limited safety signals emerging.
Specific growth rate and multiplicity of infection affect high‐cell‐density fermentation with bacteriophage M13 for ssDNA production
Authors: Kick Benjamin , Hensler Samantha , Praetorius Florian , Dietz Hendrik , Weuster‐Botz Dirk 
Published: October 2016

ABSTRACTThe bacteriophage M13 has found frequent applications in nanobiotechnology due to its chemically and genetically tunable protein surface and its ability to self‐assemble into colloidal membranes. Additionally, its single‐stranded (ss) genome is commonly used as scaffold for DNA origami. Despite the manifold uses of M13, upstream production methods for phage and scaffold ssDNA are underexamined with respect to future industrial usage. Here, the high‐cell‐density phage production with Escherichia coli as host organism was studied in respect of medium composition, infection time, multiplicity of infection, and specific growth rate. The specific growth rate and the multiplicity of infection were identified as the crucial state variables that influence phage amplification rate on one hand and the concentration of produced ssDNA on the other hand. Using a growth rate of 0.15 h−1 and a multiplicity of infection of 0.05 pfu cfu−1 in the fed‐batch production process, the concentration of pure isolated M13 ssDNA usable for scaffolded DNA origami could be enhanced by 54% to 590 mg L−1. Thus, our results help enabling M13 production for industrial uses in nanobiotechnology. Biotechnol. Bioeng. 2017;114: 777–784. © 2016 Wiley Periodicals, Inc.
Enhanced detection of lymphovascular invasion in small rectal neuroendocrine tumors using D2‐40 and Elastica van Gieson immunohistochemical analysis
Authors: Kitagawa Yoshiyasu , Ikebe Dai , Hara Taro , Kato Kazuki , Komatsu Teisuke , Kondo Fukuo , Azemoto Ryousaku , Komoda Fumitake , Tanaka Taketsugu , Saito Hirofumi , Itami Makiko , Yamaguchi Taketo , Suzuki Takuto 
Published: October 2016

AbstractRectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin–eosin (HE) stain, the D2‐40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow‐up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2‐40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2‐40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long‐term follow‐up and outcomes.
Synthesis of Asymmetrical Monobenzo‐Substituted Cobalt Thioporphyrazines and Their Biomimetic Catalytic Property
Authors: Zhou Peng , Jin Juanjuan , Zhang Bingguang , Yang Changjun , Zhang Zehui , Li Zhe , Deng Kejian 
Published: October 2016

AbstractTwo novel monobenzo porphyrazines bearing nitro and methoxyl respectively on fused benzene ring were successfully synthesized. Also, an asymmetrical porphyrazine with one butylthio branch at the pyrrolic β‐position substituted by hydrogen atom was successfully isolated in the course of synthesis of symmetric octakis(butylthio) porphyrazine. Their corresponding cobalt complexes were subsequently obtained and characterized. Their catalytic ability was assessed by aerobic oxidation of benzoin, showing the highest benzil yield of 95.2% for 60 min. A possible mechanism was also presented from the in‐situ UV‐Vis spectra, in which a novel and characteristic absorption peak of metal‐oxo was observed. At the same time, similar results of the extended oxidation of benzyl alcohol also confirmed the reactive mechanism.
Synthesis and Electrochemistry of Aryl‐Substituted Tripyrrinone Copper Complexes. Comparison of Redox Properties to Structurally Related Porphyrins and Corroles
Authors: Wang Wenda , Ou Zhongping , Ye Lina , Fang Yuanyuan , Xue Songlin , Song Yang , Kadish Karl M. 
Published: October 2016

AbstractFour aryl‐substituted tripyrrinone copper(II) complexes were synthesized and characterized as to their electrochemical and spectroelectrochemical properties. The examined compounds are represented as (YPh)3TPO2Cu, where TPO2 is a dianion of the tripyrrinone and Y is a CH3O, CH3, H or Cl substituent on the para‐position of each phenyl ring of the compound. The neutral compounds are ESR active and show a typical d9 Cu(II) signal in frozen CH2Cl2 solution. Each Cu(II) compound undergoes three reductions between −0.61 and −1.90 V and two oxidations between 1.00 and 1.24 V in CH2Cl2 containing 0.1 mol/L tetra‐n‐butylammonium perchlorate. The potentials for oxidation are similar to those of copper tetraarylporphyrins but the reduction potentials are positively shifted as compared to the corresponding tetraarylporphyrins. Thus, the potential difference between the first one‐electron oxidation and first one‐electron reduction (the HOMO‐LUMO gap) of (YPh)3TPO2Cu, which ranges from 1.68 to 1.75 V, is similar to that of copper corroles (1.73–1.85 V), but smaller than the separation of 2.30–2.37 V for the copper tetraarylporphyrins under the same solution conditions.
Stability of Odd‐ Versus Even‐Electron Gas‐Phase (Quasi)Molecular Ions Derived from Pyridine‐Substituted N‐Heterotriangulenes
Authors: Hitzenberger Jakob F. , Dral Pavlo O. , Meinhardt Ute , Clark Timothy , Thiel Walter , Kivala Milan , Drewello Thomas 
Published: October 2016

AbstractElectrospray ionisation of N‐heterotriangulenes (i.e., dimethylmethylene‐bridged triphenylamines) with up to three pyridyl groups at their periphery, produces the true radical cation ([M]+.) and the protonated molecule ([M+H]+) simultaneously. These ions are studied as model systems to illustrate the stability alternation of odd‐ versus even‐electron ions in energy‐dependent collision‐induced dissociation (CID) experiments. All ions show the same fragmentation pattern, the consecutive loss of three methyl radicals (.CH3) from the dimethylmethylene bridges of the central triangulene core. [M]+. ions dissociate at much lower collision energies than their [M+H]+ counterparts. The radical cation forms a singlet fragment with an extended aromatic system that is energetically favoured. Ab initio and density functional theory calculations support this interpretation and allow the assignment of the electronic structure of the fragment ions. Consecutive collision‐induced dissociations provide a better match with theory when studied with an ion trap, rather than a linear quadrupole. This is attributed to the resonant nature of the excitation of intermediate ions.
NbCl5‐Promoted Synthesis of Fluorescein Dye Derivatives: Spectroscopic and Spectrometric Characterization and Their Application in Dye‐Sensitized Solar Cells
Authors: da Silva Bruno Henrique Sacoman Torquato , Bregadiolli Bruna Andressa , Graeff Carlos Frederico de Oliveira , da Silva‐Filho Luiz Carlos 
Published: October 2016

AbstractFluorescein has several applications owing to its properties, such as high molar absorptivity, high fluorescence quantum yield, high photostability, and wavelengths of absorption and emission in the visible region. The syntheses of fluorescein derivatives between phenol and anhydride derivatives by using NbCl5 as a Lewis acid is described. The products have high yields and short reaction times are observed. The study of the UV/Vis and fluorescence spectra of these derivatives and their application in dye‐sensitized solar cells is also described.
Relevance of cardiac parvovirus B19 in myocarditis and dilated cardiomyopathy: review of the literature
Authors: Verdonschot Job , Hazebroek Mark , Merken Jort , Debing Yannick , Dennert Robert , Brunner‐La Rocca Hans‐Peter , Heymans Stephane 
Published: October 2016

AbstractOver the last decade, parvovirus B19 (B19V) has frequently been linked to the pathogenesis of myocarditis (MC) and its progression towards dilated cardiomyopathy (DCM). The exact role of the presence of B19V and its load remains controversial, as this virus is also found in the heart of healthy subjects. Moreover, the prognostic relevance of B19V prevalence in endomyocardial biopsies still remains unclear. As a result, it is unclear whether the presence of B19V should be treated. This review provides an overview of recent literature investigating the presence of B19V and its pathophysiological relevance in MC and DCM, as well as in normal hearts. In brief, no difference in B19V prevalence is observed between MC/DCM and healthy control hearts. Therefore, the question remains open whether and how cardiac B19V may be of pathogenetic importance. Findings suggest that B19V is aetiologically relevant either in the presence of other cardiotropic viruses, or when B19V load is high and/or actively replicating, which both may maintain myocardial (low‐grade) inflammation. Therefore, future studies should focus on the prognostic relevance of the viral load, replicative status and virus co‐infections. In addition, the immunogenetic background of MC/DCM patients that makes them susceptible to develop heart failure upon presence of B19V should be more thoroughly investigated.
Determinants and prognostic implications of the negative diastolic pulmonary pressure gradient in patients with pulmonary hypertension due to left heart disease
Authors: Nagy Anikó Ilona , Venkateshvaran Ashwin , Merkely Béla , Lund Lars H. , Manouras Aristomenis 
Published: October 2016

AbstractAimsThe diastolic pulmonary pressure gradient (DPG) has recently been introduced as a specific marker of combined pre‐capillary pulmonary hypertension (Cpc‐PH) in left heart disease (LHD). However, its diagnostic and prognostic superiority compared with traditional haemodynamic indices has been challenged lately. Current recommendations explicitly denote that in the normal heart, DPG values are greater than zero, with DPG ≥7 mmHg indicating Cpc‐PH. However, clinicians are perplexed by the frequent observation of DPG <0 mmHg (DPGNEG), as its physiological explanation and clinical impact are unclear to date. We hypothesized that large V‐waves in the pulmonary artery wedge pressure (PAWP) curve yielding asymmetric pressure transmission might account for DPGNEG and undertook this study to clarify the physiological and prognostic implications of DPGNEG.Methods and resultsRight heart catheterization and echocardiography were performed in 316 patients with LHD due to primary myocardial dysfunction or valvular disease. A total of 256 patients had PH‐LHD, of whom 48% demonstrated DPGNEG. The V‐wave amplitude inversely correlated with DPG (r = −0.45, P < 0.001) in patients with low pulmonary vascular resistance (PVR), but not in those with elevated PVR (P > 0.05). Patients with large V‐waves had negative and lower DPG than those without augmented V‐waves (P < 0.001) despite similar PVR (P >0.05). Positive, but normal DPG (0–6 mmHg) carried a worse 2‐year prognosis for death and/or heart transplantation than DPGNEG (hazard ratio 2.97; P < 0.05).ConclusionOur results advocate against DPGNEG constituting a measurement error. We propose that DPGNEG can partially be ascribed to large V‐waves and carries a better prognosis than DPG within the normal positive range.
Comparison of the oxidative stability of cold‐pressed rapeseed oil using Pressure Differential Scanning Calorimetry and Rancimat methods
Authors: Symoniuk Edyta , Ratusz Katarzyna , Krygier Krzysztof 
Published: October 2016

Oxidative stability of cold‐pressed rapeseed oil was determined using two accelerated methods—Pressure Differential Scanning Calorimetry (PDSC) and Rancimat. Tests were carried out at six different temperatures (90–140°C), and the induction time (PDSC τmax, Rancimat τon) was a result. Based on the induction times, the Arrhenius equation and the activated complex theory, frequency factors (Z), constant reaction rate (k) for all temperatures, activation energies (Ea), Q10 numbers, activation enthalpies (ΔH‡), and activation entropies (ΔS‡) for cold‐pressed rapeseed oils oxidative stability were calculated. The activation energy values of rapeseed oil oxidation in PDSC and Rancimat method ranged from 86.71 to 90.54 kJ mol−1 and from 75.73 to 77.64 kJ mol−1, respectively. The Q10, ΔH‡, and ΔS‡ values for analyzed rapeseed oil were between 2.00 and 2.07, 83.48 and 87.31 kJ mol−1, −61.30 and −51.40 J molK−1 calculated for PDSC measurements, and from 1.84 to 1.86, 72.50 to 74.41 kJ mol−1, −66.30 to −60.84 J molK−1 for Rancimat measurements, respectively.Practical applications: This research present the differences in the oxidative stability of cold‐pressed rapeseed oil using PDSC and Rancimat method. The results of the PDSC test may be recommended as an appropriate objective method for assessing the oxidative stability of cold‐pressed rapeseed oil. Also, results of kinetic oxidation parameters may be helpful to predicting the oil oxidative stability at different temperatures of oxidation process.The study evaluate the oxidative stability of cold‐pressed rapeseed oils using Pressure Differential Scanning Calorimetry (PDSC) and Randimat method. The research shows a correlation (r = 0.9975) between two accelerated methods (PDSC and Rancimat) of assessing lipid oxidative stability.
Label‐free Electrochemical Sensor for Ex‐vivo Monitoring of Alzheimer's Disease Biomarker
Authors: El‐Said Waleed A. , Abd El‐Hameed Kawthar , Abo El‐Maali Nagwa , Sayyed Hayam G. 
Published: October 2016

AbstractThe beta‐amyloid (Aβ) peptide was used as an important biomarker for Alzheimer's disease (AD) diagnosis. The development of an accurate, selective, rapid, and highly sensitive technique for detecting of Aβ level is an important issue in biology, and medicine to assess human health risks. Here, gold nanoparticles (Au NPs) with different size were electrochemically deposited onto the indium tin oxide (ITO) substrate in the presence of different molecular weights of surfactants. The modified substrates were used as a high sensitive electrochemical sensor of in‐vitro as well as ex‐vivo monitoring of Aβ based on cyclic voltammetry and square wave voltammetry techniques. Our findings revealed that the modification of ITO electrode with Au NPs could enhance its sensor performance with high sensitivity for low concentration levels of Aβ over a wide linear range with a detection limit of about 20.7 ng/g, which is less than the concentration of insoluble Aβ40 (105.4±40.2 μg/g) in brain of AD induced. In addition, Au NPs/ITO modified electrodes have demonstrated ability to monitor Aβ in the brain extracted samples without any potential interference with other components. Raman spectroscopy has been used to confirm the presence of Aβ in the AD‐induced samples. Thus, it is applicable for analyzing ex‐vivo samples.
Long‐Term Interactions between the Roman City of Ostia and Its Paleomeander, Tiber Delta, Italy
Authors: Salomon Ferréol , Goiran Jean‐Philippe , Pannuzi Simona , Djerbi Hatem , Rosa Carlo 
Published: October 2016

This study examines the long‐term interactions between the well‐known Roman city of Ostia and a river meander. Located at the mouth of the Tiber river, Ostia was a major harbor city that connected Rome to the Mediterranean Sea. Based on aerial photography and borehole analysis, the paleodynamics of the Fiume Morto's paleomeander are understood to be linked to the urban evolution of the city of Ostia. Four periods of evolution have been identified as a result of this interdisciplinary work: (1) the foundation of Ostia's urban center, in the 4th to 3rd century BC, occurred when the meander already existed; (2) between the 4th century BC and the 3rd century AD, human/environmental interactions contributed to the compound growth of the meander that possibly eroded an important Roman road linking Ostia to Rome; (3) from the Imperial period until the meander was cut off in AD 1557–1562, the constricted meander channel at the apex led to the stability of the downstream river channel; (4) the cutoff of the paleomeander was completed in 1562, leading to the filling of the paleochannel. These successive phases of channel evolution mark changing fluvial risks from the Roman period to today.
Two Coupled Forced‐Convection Boundary Layers of Counter‐Flow
Authors: El‐sayed Mosaad Mohamed 
Published: October 2016

AbstractIn this study, the conjugate heat transfer problem of two forced‐convection boundary layers of counter‐laminar flow on plate sides is analyzed by employing the integral method. The analysis is conducted in a dimensionless way to generalize the solution. The dimensionless parameters governing the thermal coupling between the two convection layers are revealed from the analysis. These parameters give a measure of the relative importance of interactive heat transfer modes. Mean Nusselt number results are obtained for a wide range of the governing parameters.
Nacre, a natural, multi‐use, and timely biomaterial for bone graft substitution
Authors: Zhang Ganggang , Brion Alice , Willemin Anne‐Sophie , Piet Marie‐Hélène , Moby Vanessa , Bianchi Arnaud , Mainard Didier , Galois Laurent , Gillet Pierre , Rousseau Marthe 
Published: October 2016

AbstractDuring the past two decades, with a huge and rapidly increasing clinical need for bone regeneration and repair, bone substitutes are more and more seen as a potential solution. Major innovation efforts are being made to develop such substitutes, some having advanced even to clinical practice. It is now time to turn to natural biomaterials. Nacre, or mother‐of‐pearl, is an organic matrix‐calcium carbonate coupled shell structure produced by molluscs. In vivo and in vitro studies have revealed that nacre is osteoinductive, osteoconductive, biocompatible, and biodegradable. With many other outstanding qualities, nacre represents a natural and multi‐use biomaterial as a bone graft substitute. This review aims at summarising the current needs in orthopaedic clinics and the challenges for the development of bone substitutes; most of all, we systematically review the physiological characteristics and biological evidence of nacre's effects centred on osteogenesis, and finally we put forward the potential use of nacre as a bone graft substitute. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 662–671, 2017.
One Year of Abaloparatide, a Selective Activator of the PTH1 Receptor, Increased Bone Formation and Bone Mass in Osteopenic Ovariectomized Rats Without Increasing Bone Resorption
Authors: Varela Aurore , Chouinard Luc , Lesage Elisabeth , Smith Susan Y , Hattersley Gary 
Published: October 2016

ABSTRACT

Abaloparatide is a novel 34-amino acid peptide selected to be a potent and selective activator of the parathyroid hormone receptor (PTH1R) signaling pathway with 41% homology to PTH(1-34) and 76% homology to PTHrP(1-34). A 12-month treatment study was conducted in osteopenic ovariectomized (OVX) rats to characterize the mechanisms by which abaloparatide increases bone mass. Sprague-Dawley (SD) rats were subjected to OVX or sham surgery at age 6 months and left untreated for 3 months to allow OVX-induced bone loss. Ten OVX rats were euthanized after this bone depletion period, and the remaining OVX rats received daily subcutaneous injections of vehicle (n = 18) or abaloparatide at 1, 5, or 25 μg/kg/d (n = 18/dose level) for 12 months. Sham controls (n = 18) received vehicle daily. Bone densitometry and biochemical markers of bone formation and resorption were assessed longitudinally, and L3 vertebra and tibia were collected at necropsy for histomorphometry. Abaloparatide increased biochemical bone formation markers without increasing bone resorption markers or causing hypercalcemia. Abaloparatide increased histomorphometric indices of bone formation on trabecular, endocortical, and periosteal surfaces without increasing osteoclasts or eroded surfaces. Abaloparatide induced substantial increases in trabecular bone volume and density and improvements in trabecular microarchitecture. Abaloparatide stimulated periosteal expansion and endocortical bone apposition at the tibial diaphysis, leading to marked increases in cortical bone volume and density. Whole-body bone mineral density (BMD) remained stable in OVX-Vehicle controls while increasing 25% after 12 months of abaloparatide (25 μg/kg). Histomorphometry and biomarker data suggest that gains in cortical and trabecular bone mass were attributable to selective anabolic effects of abaloparatide, without evidence for stimulated bone resorption. © 2016 American Society for Bone and Mineral Research.