bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevation of Liver Enzymes in Multiple Dose Trials During Placebo Treatment: Are They Predictable?
Authors: Merz M. , Seiberling M. , Höxter G. , Hölting M. , Wortha H.P. 
Published: March 2013

The present study examined the increase in transaminases, especially in ALT in young healthy males during placebo treatment in phase I multiple dose trials. The primary objective was to investigate whether volunteers showing increasing ALT levels also present characteristic patterns of demographic data, laboratory parameters, and vital signs. The secondary objective was to determine whether there is a possibility to predict increases of ALT during a trial by analyzing demographic data and baseline levels of routine safety laboratory parameters and vital signs. In a meta‐analysis of 13 placebo‐controlled multiple dose phase I studies, volunteers showing elevations of ALT during placebo treatment were compared with those presenting no clinically significant changes of ALT levels. Demographic data as well as routine safety laboratory values and vital signs measured at screening and on the first day of the in‐house stay were subject to the analysis. Using Wilcoxon's rank sum test, significant differences between ALT‐susceptibles and ALT‐nonsusceptibles were found for baseline values (mean values of screening and the first day of the in‐house stay) of ALT, γGT, AST/ALT, and AST/γGT. Differences found for the screening values of the heart rate were statistically rather than clinically significant.Cut‐off values were found for baseline levels of ALT and AST/ALT ratio. Their use resulted in a sensitivity of 73% and a specificity of 74% with regard to predictability of ALT levels increasing during the trial.
Pharmacokinetics of Fosinoprilat in Chinese and Whites After Intravenous Administration
Authors: Hu Oliver Yoa‐Pu , Ding Philip Y. A. , Huang Christine Shu‐hui , Hwang Giann Ming , Chu Kai‐Min 
Published: March 2013

The pharmacokinetics of fosinoprilat was studied in 12 healthy Chinese men after a 7.5 mg intravenous dose of fosinoprilat. The data were compared with those from an earlier study using the same protocol in nine healthy white men.Blood and urine samples were obtained before and at various time intervals after fosinoprilat administration up to 24 hours and 48 hours, respectively. Pharmacokinetic parameters were calculated by fitting the plasma or serum concentrations to a three‐compartment model. The total clearance (Clt), renal clearance (ClT), and nonrenal clearance (ClNR) were significantly lower in Chinese (16.29 ± 6.92, 6.85 ± 2.97, and 9.44 ± 5.08 mL · hr−1 · kg−1) than those obtained in whites (29.88 ± 6.36, 13.55 ± 3.45, and 16.33 ± 5.07 mL · hr−1 · kg−1)). The Chinese subjects had a significantly lower volume of distribution (Vc [volume of distribution of central compartment] and Vdss [volume of distribution at steady state]) (29.38 ± 21.12 and 73.67 ± 40.20 mL/kg) than white men (58.14 ± 15.01 and 152.49 ± 24.89 mL/kg). The Chinese men also had a shorter elimination half‐life than whites, although not statistically significant. The respective half‐lives in Chinese and whites were 5.51 ± 1.53 and 8.24 ± 4.99 hours. The significant differences in ClNR and ClR may be related to lower liver elimination function and lower kidney excretory function, respectively. Plasma protein binding may contribute to part of the difference in the volume of distribution. Chinese men have smaller volume of distribution and clearances of fosinoprilat after intravenous administration compared with white men. The cumulative urine excretion of fosinoprilat was not different between Chinese and whites. Chinese may require a lower fosinoprilat dosage to obtain plasma concentrations similar to whites after intravenous administration. However, since a relatively high variation was found in fosinopril oral absorption, the oral dosage of fosinopril for Chinese and whites may not be different. Further study is obviously needed to elucidate whether the pharmacodynamic effect may be different between Chinese and whites.
The Interplay of Photophysical Properties in Carbazole Fluorescent Oligomers
Authors: Hsu Chung‐Yi , Hsieh Mu‐Tao , Chen Yen‐Fu , Hsu Chun‐Chia , Hung Tzu‐Lin , Chen Chun‐Shuo , Whang Thou‐Jen 
Published: March 2013

AbstractThe photophysical properties and the organic synthesis using effective palladium‐catalyzed Suzuki coupling reactions from a series of carbazole derivatives are described and the relationships of the donor and acceptor groups are also investigated. The purification of the materials and its applications along with the corresponding photo‐physical characterizations were presented. With the advantages gained from 2D‐COSY spectra, which provide more correlated information between immediate atoms than 1H‐NMR spectra and a series of further investigations were undertaken including powder X‐ray diffraction analysis, Infrared and Raman spectroscopy, constructing the composition conformation and chemical structure of the materials is more easily to achieve. Additionally, the optimized structure of the minimized energy geometries and spatial distributions of carbazole derivatives was calculated using density functional theory (DFT), new materials can be developed and designed selectively based on the method proposed in this work.
Computational Study of the Substitution Effect on the Mechanism for the Gold(I)‐Catalyzed Ring Expansions of Unactivated Alkynylcyclopropanes
Authors: Kuo Tzu‐Nung , Liao Hsin‐Yi 
Published: March 2013

AbstractThe ring expansion reactions of unactivated alkynylcyclopropanes X‐C≡C‐C3H5 → X‐C=C4H5 (X = H, F, Cl, Me, OMe, NMe2, CMe3) were examined using the density functional theory calculations. All of the structures were completely optimized at the B3LYP/6‐311++G** level of theory. For clarify the effect of the cationic gold(I), we also added AuPH3+ as the catalyst into the system and the structures for Au were calculated at the B3LYP/LANL2DZ level of theory. The main finding of this work is that the singlet‐triplet splitting of X‐C≡C‐C3H5 play an important role in determining the kinetic and thermodynamic stability of the unactivated ring expansion reactions. When X‐C≡C‐C3H5 with a smaller singlet‐triplet splitting is utilized, the reaction has a smaller activation energy and a larger exothermicity.
Synthesis, Characterization and Oxide Ionic Conductivity of Binary δ‐(Bi2o3)1‐x(Lu2o3)x System
Authors: Öztürk Esra , Kalaycioglu Nilgun Ozpozan 
Published: March 2013

AbstractIn this study, after doping Lu2O3 to α‐Bi2O3 in the range of 11% ≤ n ≤ 20% in a series of different mole ratios, heat treatment was performed by applying a cascade temperature rise in the range of 700‐800 °C for 72 hours and new phases were obtained in the (Bi2o3)1‐x(Lu2o3)x system. After 72 hours of heat treatment at 800 °C, mixtures containing 14‐16% Lu2O3 formed a face‐centered cubic phase. Mixtures containing 11– 13%, 17%, 18% mole Lu2O3 were subjected to a quenching process at 825 °C and face‐centered cubic phases were obtained. With the help of XRD, the crystal systems and lattice parameters of the solid solutions were obtained and their characterization was carried out. Thermal measurements were made by using a simultaneous DTA/TG system. The total conductivity (σT) in the δ‐Bi2O3 doped with Lu2O3 system was measured using the four‐probe DC method. Keywords: Bismuth oxide; lutesium oxide; oxygen ionic conductivity; X‐ray techniques; thermal analysis.
Photolysis of Dibenzo[a,d]cycloheptene Dimer
Authors: Chang Meng‐Yang , Huang Yu‐Ping 
Published: March 2013

AbstractPhotolysis reaction of dibenzo[a,d]cycloheptene dimer 3 provides three dibenzo[a,d]cycloheptyl dimers 4, 5 and 6 under different irradiation conditions via the intramolecular degradative cyclodimerization. A tetracyclic benzo[4,5]cyclohepta[1,2,3‐de]naphthalene core is also synthesized.
Nonnative Pacific salmon alter hot spots of sediment nitrification in Great Lakes tributaries
Authors: Levi Peter S. , Tank Jennifer L. 
Published: March 2013

AbstractBiogeochemical transformations may represent an important pathway influencing the fate of nutrient subsidies in stream ecosystems. Pacific salmon (Oncorhynchus spp.) provide an ammonium (NH4+) subsidy to streams during their annual spawning runs, which may be transformed to nitrate (NO3−) via sediment nitrification. Increases in either forms of dissolved inorganic nitrogen may have ecosystem effects both at the reach and watershed scales, including the fertilization of algal biofilms and elevated export of nutrients to downstream ecosystems. In the nonnative range of salmon, where spawning runs are a relatively new phenomenon, few studies have explored the effect of introduced salmon on ecosystem processes. To assess the effect of nonnative salmon on dissolved inorganic nitrogen dynamics in Great Lakes tributaries, we quantified sediment nitrification in five streams before, during, and after the spawning run in 2009. Overall, sediment nitrification rates were higher in the channel thalweg (mean ± SE = 1.9 ± 0.1 mg N/gAFDM/d) compared to channel margins (mean ± SE = 0.9 ± 0.1 mg N/gAFDM/d). In the two streams with the largest salmon runs, nitrification was highest in the channel thalweg prior to salmon, but margin sediments had higher nitrification during the run. Among all streams, variation in nitrification rates was habitat specific, predicted by exchangeable NH4+ in sediments from the thalweg and predicted by salmon biomass for sediments in the channel margin. Nonnative salmon provide a pulsed source of inorganic nitrogen to Great Lakes tributaries, yet dissimilatory biogeochemical transformations such as nitrification may alter the form of the NH4+ subsidy and potentially influence downstream lakes via export of both NH4+ and NO3−.
EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee
Authors: Chen Ying Ju , Tsai Keh Sung , Chiu Chen Yuan , Yang Ting Hua , Lin Tzu Hung , Fu Wen Mei , Chen Cheng Feng , Yang Rong Sen , Liu Shing Hwa 
Published: March 2013

ABSTRACTOsteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti‐inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)‐ and IL‐1β‐induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX‐2 and iNOS in human chondrocytes. LPS was also seen to up‐regulate the expressions of toll‐like receptor‐4 (TLR4), its downstream signal TNF receptor‐associated factor 6 (TRAF6), and nuclear factor (NF)‐κB signaling. These LPS‐induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL‐1β as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX‐2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti‐inflammatory effects on human articular chondrocytes and OA rats. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1032–1038, 2013
Autostereoscopic 3D pictures on optically rewritable electronic paper
Authors: Wang Xiaoqian , Wang Lu , Sun Jiatong , Srivastava Abhishek K. , Chigrinov Vladimir G. , Kwok Hoi Sing 
Published: March 2013

AbstractIn this article, we disclose a method to fabricate the three‐dimensional (3D) image on an optically rewritable (ORW) electronic paper (e‐paper) by deploying the lenticular lenses array on the top of the ORW e‐paper. Unlike other autostereoscopic 3D liquid crystal displays, our autostereoscopic 3D ORW e‐paper is actually a green technology, which is without electrode and voltage. No electricity is needed to maintain the 3D image on the ORW e‐paper. We can easily change a 3D image by erasing and rewriting with photoalignment technology.
Salvage Circular Laryngopharyngectomy and Radial Forearm Free Flap for Recurrent Hypopharyngeal Cancer
Authors: Fakhry Nicolas , Chamorey Emmanuel , Michel Justin , Collet Charles , Santini Laure , Poissonnet Gilles , Santini José , Dessi Patrick , Giovanni Antoine , Dassonville Olivier , Bozec Alexandre 
Published: March 2013

AbstractObjectives/Hypothesis:To evaluate surgical and long‐term oncologic outcomes in a series of patients who underwent circular total laryngopharyngectomy with tubed radial forearm free flap as salvage surgery.Study Design:Retrospective study in two tertiary referral centers.Methods:Twenty‐one patients who underwent surgery between 2001 and 2010 were included in the study. All patients underwent surgery for recurrence of advanced hypopharyngeal squamous cell carcinoma previously treated by chemoradiotherapy (CRT) or surgery followed by postoperative radiotherapy or CRT. Overall survival (OS) and disease‐free survival (DFS) were determined by Kaplan‐Meier analysis. The search for parameters that could influence long‐term oncologic outcomes was carried out by univariate and multivariate analysis using log‐rank test and Cox regression models.Results:Median follow‐up was 30 months. The 1, 2, and 5‐year OS rates were 46%, 40%, and 16%, and the DFS rates were 42%, 30%, and 15%, respectively. Free flap failure (P [log rank] = .014 and P [Cox] = .016) and positive margins (P [log rank] = .001 and P [Cox] = .001) were found to have a significant negative impact on both OS and DFS in both univariate and multivariate analysis.Conclusions:Salvage surgery remains the only curative option as treatment of recurrent hypopharyngeal squamous cell carcinoma and should be offered to patients when possible. However, selection of patients eligible for this type of surgery and the choice of reconstructive procedure are crucial since long‐term survival is clearly correlated with the presence of clear margins and the absence of free flap failure.
Smoking and malignancy in sinonasal inverted papilloma
Authors: Hong Sung‐Lyong , Kim Bae‐Hyun , Lee Jung‐Hoon , Cho Kyu‐Sup , Roh Hwan‐Jung 
Published: March 2013

Objectives/HypothesisThe authors investigated clinical features of squamous cell carcinomas (SCC) arising in sinonasal inverted papillomas (IP) and risk factors responsible for their malignant transformation.Study DesignRetrospective analysis.MethodsIn total, 162 patients diagnosed with sinonasal IP and treated between 1998 and 2009 at Pusan National University Hospital were enrolled. Their demographic data, information about previous surgery, smoking history, treatment modalities, follow‐up duration, recurrence, and presence of malignancy were reviewed retrospectively.ResultsSeventeen patients (10.5%) were diagnosed with SCC arising in sinonasal IPs. Among them, nine (9/162, 5.6%; 9/17, 52.9%) were diagnosed with synchronous malignancies and three (3/162, 1.8%; 3/17, 17.6%) were diagnosed with metachronous malignancies. In five cases (5/162, 3.1%; 5/17, 29.4%), we could not determine whether their malignancies were synchronous or metachronous. Among 53 smokers, 14 (26.4%) had malignant transformation, while only three (2.8%) in 109 nonsmokers had malignant transformation (Odds ratio = 12.7; P < .001). The mean follow‐up in the 17 patients with malignancy was 47.0 months. Three patients did not receive surgical treatment and died of progression of SCC. Among the other 14 patients who underwent curative surgeries, four (28.6%) had recurrences, and their mean period to cancer recurrence was 6.3 months. Two of them died of progression of the cancer. Mean survival of the five patients who died was 14.0 months. They all belonged to T4 stage.ConclusionsSmoking history is associated with malignant transformation of sinonasal IP. It suggests that close follow‐up be required in smokers with sinonasal IP in order not to overlook the malignant transformation.Level of Evidence2b.
Polytetrafluoroethylene‐covered nitinol stent graft for treatment of carotid artery blowout syndrome in head and neck cancer patients
Authors: Hakime Antoine , Khoury Elias , Hameg Amine , Liberge Renan , Deschamps Frederic , Farouil Geoffroy , Joskin Julien , Tselikas Lambros , Temam Stephane , Janot François , De Baere Thierry 
Published: March 2013

Objectives/HypothesisTo evaluate the efficacy, tolerance, and outcomes of covered stents in the treatment of carotid blowout syndrome (CBS) in head and neck cancer patients.Study DesignIndividual retrospective cohort study.MethodsWe retrospectively reviewed the medical and image files of all 20 consecutive head and neck cancer patients treated with covered stent grafts for CBS. Six acute, 12 impending, and two threatened cases of CBS were treated in patients who all had previously received radiation therapy. We evaluated the feasibility, hemostatic efficacy, survival without bleeding, and complications.ResultsThe etiologies of CBS were as follows: group 1, 13 carotid axis (common or internal carotid artery) pseudoaneurysms and one rupture; group 2, six patients with no identifiable source of bleeding on angiography but with a threatened carotid axis on computed tomography (CT). In all patients, a polytetrafluoroethylene‐covered nitinol stent graft (Fluency; Bard/Angiomed GmbH & Co, Karlsruhe, Germany) was successfully placed. All of the stents were patent at the end of the procedure. Immediate hemostasis was achieved in the six hemorrhagic cases. Immediate transient ischemic attacks were observed in two patients, and carotid sinus syndrome was observed in one patient. Post‐treatment bleeding was observed in five patients in group 2 and no patients in group 1. Survival without bleeding was 251 days in group 1 and 35 days in group 2. During follow‐up, three asymptomatic stent thromboses occurred at a mean of 58 days.ConclusionsCovered stent placement is highly feasible and proved effective without major complications in CBS due to carotid axis bleeding.Level of Evidence4. Laryngoscope, 2013
Doxorubicin‐Induced Cardiotoxicity: From Bioenergetic Failure and Cell Death to Cardiomyopathy
Authors: Carvalho Filipa S. , Burgeiro Ana , Garcia Rita , Moreno António J. , Carvalho Rui A. , Oliveira Paulo J. 
Published: March 2013

AbstractDoxorubicin (DOX) is an anticancer anthracycline that presents a dose‐dependent and cumulative cardiotoxicity as one of the most serious side effects. Several hypotheses have been advanced to explain DOX cardiac side effects, which culminate in the development of life‐threatening cardiomyopathy. One of the most studied mechanisms involves the activation of DOX molecule into a more reactive semiquinone by mitochondrial Complex I, resulting in increased oxidative stress. The present review describes and critically discusses what is known about some of the potential mechanisms of DOX‐induced cardiotoxicity including mitochondrial oxidative damage and loss of cardiomyocytes. We also discuss alterations of mitochondrial metabolism and the unique characteristics of DOX delayed toxicity, which can also interfere on how the cardiac muscle handles a “second‐hit stress.” We also present pharmaceutical and nonpharmaceutical approaches that may decrease DOX cardiac alterations in animal models and humans and discuss the limitations of each strategy.
Diffusion kurtosis imaging to detect amyloidosis in an APP/PS1 mouse model for Alzheimer's disease
Authors: Vanhoutte Greetje , Pereson Sandra , Delgado y Palacios Rafael , Guns Pieter‐Jan , Asselbergh Bob , Veraart Jelle , Sijbers Jan , Verhoye Marleen , Van Broeckhoven Christine , Van der Linden Annemie 
Published: March 2013

PurposeAmyloid deposition in the brain is considered an initial event in the progression of Alzheimer's disease. We hypothesized that the presence of amyloid plaques in the brain of APP/presenilin 1 mice leads to higher diffusion kurtosis measures due to increased microstructural complexity. As such, our purpose was to provide an in vivo proof of principle for detection of amyloidosis by diffusion kurtosis imaging (DKI).MethodsAPPKM670/671NL/presenilin 1 L166P mice (n = 5) and wild‐type littermates (n = 5) underwent DKI at the age of 16 months. Averaged diffusion and diffusion kurtosis parameters were obtained for multiple regions (hippocampus–cortex–thalamus–cerebellum). After DKI, mice were sacrificed for amyloid staining.ResultsHistograms of the frequency distribution of the DKI parameters tended to shift to higher values. After normalization of absolute values to the cerebellum, a nearly plaque‐free region, mean, radial, and axial diffusion kurtosis were significantly higher in APP/presenilin 1 mice as compared to wild‐type in the cortex and thalamus, regions demonstrating substantial amyloid staining.ConclusionThe current study, although small‐scale, suggests increased DKI metrics, in the absence of alterations in diffusion tensor imaging metrics in the cortex and thalamus of APP/presenilin 1 mice with established amyloidosis. These results warrant further investigations on the potential of DKI as a sensitive marker for Alzheimer's disease. Magn Reson Med 69:1115–1121, 2013. © 2013 Wiley Periodicals, Inc.
Spectrally resolved fully phase‐encoded three‐dimensional fast spin‐echo imaging
Authors: Artz Nathan S. , Hernando Diego , Taviani Valentina , Samsonov Alexey , Brittain Jean H. , Reeder Scott B. 
Published: March 2013

PurposeTo develop and test the feasibility of a spectrally resolved fully phase‐encoded (SR‐FPE) three‐dimensional fast spin‐echo technique and to demonstrate its application for distortion‐free imaging near metal and chemical species separation.MethodsIn separate scans at 1.5 T, a hip prosthesis phantom and a sphere filled with gadolinium solution were imaged with SR‐FPE and compared to conventional three‐dimensional‐fast spin‐echo. Spectral modeling was performed on the SR‐FPE data to generate the following parametric maps: species‐specific signal (ρspecies), B0 field inhomogeneity, and R*2. The prosthesis phantom was also scanned using a 16‐channel coil at 1.5 T. The fully sampled k‐space data were retrospectively undersampled to demonstrate the feasibility of parallel imaging acceleration in all three phase‐encoding directions, in combination with corner‐cutting and half‐Fourier sampling. Finally, SR‐FPE was performed with an acetone/water/oil phantom to test chemical species separation.ResultsHigh quality distortion‐free images and parametric maps were generated from SR‐FPE. A 4 h SR‐FPE scan was retrospectively accelerated to 12 min while preserving spectral information and 7.5 min without preserving spectral data. Chemical species separation was demonstrated in the acetone/water/oil phantom.ConclusionThis work demonstrates the feasibility of SR‐FPE to perform chemical species separation and spectrally resolved imaging near metal without distortion, in scan times appropriate for the clinical setting. Magn Reson Med 71:681–690, 2014. © 2013 Wiley Periodicals, Inc.