bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 and GATA4 are new prognostic factors for early‐stage ovarian granulosa cell tumor—a long‐term follow‐up study
Authors: Färkkilä Anniina , Andersson Noora , Bützow Ralf , Leminen Arto , Heikinheimo Markku , Anttonen Mikko , Unkila‐Kallio Leila 
Published: March 2014

AbstractGranulosa cell tumors (GCTs) carry a risk of recurrence also at an early stage, but reliable prognostic factors are lacking. We assessed clinicopathological prognostic factors and the prognostic roles of the human epidermal growth factor receptors (HER 2–4) and the transcription factor GATA4 in GCTs. We conducted a long‐term follow‐up study of 80 GCT patients with a mean follow‐up time of 16.8 years. A tumor‐tissue microarray was immunohistochemically stained for HER2–4 and GATA4. Expression of HER2–4 mRNA was studied by means of real time polymerase chain reaction and HER2 gene amplification was analyzed by means of silver in situ hybridization. The results were correlated to clinical data on recurrences and survival. We found that GCTs have an indolent prognosis, with 5‐year disease‐specific survival (DSS) being 97.5%. Tumor recurrence was detected in 24% of the patients at a median of 7.0 years (range 2.6–18 years) after diagnosis. Tumor stage was not prognostic of disease‐free survival (DFS). Of the molecular prognostic factors, high‐level expression of HER2, and GATA4, and high nuclear atypia were prognostic of shorter DFS. In multivariate analyses, high‐level coexpression of HER2 and GATA4 independently predicted DFS (hazard ratio [HR] 8.75, 95% CI 2.20–39.48, P = 0.002). High‐level expression of GATA4 also predicted shorter DSS (HR 3.96, 95% CI 1.45–12.57, P = 0.006). In multivariate analyses, however, tumor stage (II–III) and nuclear atypia were independent prognostic factors of DSS. In conclusion HER2 and GATA4 are new molecular prognostic markers of GCT recurrence, which could be utilized to optimize the management and follow‐up of patients with early‐stage GCTs.
Substitution Effects on the Formation of T‐Shaped Palladium Carbene and Thioketone Complexes from Li/Cl Carbenoids
Authors: Molitor Sebastian , Feichtner Kai‐Stephan , Kupper Claudia , Gessner Viktoria H. 
Published: March 2014

AbstractThe preparation of palladium thioketone and T‐shaped carbene complexes by treatment of thiophosphoryl substituted Li/Cl carbenoids with a Pd0 precursor is reported. Depending on the steric demand, the anion‐stabilizing ability of the silyl moiety (by negative hyperconjugation effects) and the remaining negative charge at the carbenic carbon atom, isolation of a three‐coordinate, T‐shaped palladium carbene complex is possible. In contrast, insufficient charge stabilization results in the transfer of the sulfur of the thiophosphoryl moiety and thus in the formation of a thioketone complex. While the thioketones are stable compounds the carbene complexes are revealed to be highly reactive and decompose under elimination of Pd metal. Computational studies revealed that both complexes are formed by a substitution mechanism. While the ketone turned out to be the thermodynamically favored product, the carbene is kinetically favored and thus preferentially formed at low reaction temperatures.
Anti‐proliferative Activity of Nano‐Formulated Phenolato Titanium(IV) Complexes Against Cancer Cells
Authors: Meker Sigalit , Margulis‐Goshen Katrin , Weiss Ester , Braitbard Ori , Hochman Jacob , Magdassi Shlomo , Tshuva Edit Y. 
Published: March 2014

AbstractNanoparticles of titanium(IV) complexes of phenolato ligands were formed and evaluated for cytotoxicity toward human HT‐29 colon cancer, murine T‐25 lymphoma, and murine HU‐2 multidrug‐resistant (MDR) cells. The nano‐formulation, besides increasing the complexes′ shelf lives, is particularly efficient in overcoming limitations in solubility and cell‐penetration, thus enhancing biological accessibility; large complexes that were inactive when measured in a non‐formulated form showed marked activity when nano‐formulated. For active and accessible small complexes, the effect of the formulation was negligible. Most complexes showed similar activity toward MDR cells and their drug‐sensitive analogues, further increasing their therapeutic potential. An exception is a particularly hydrophobic complex, which is presumably more accessible to interaction with the membrane ABCB1 (MDR1) transporter active in the multidrug resistance of HU‐2 cells. The most efficient compound is a mononuclear complex of a single hexadentate ligand, combining particularly high activity and hydrolytic stability with accessibility aided by the nano‐formulation.
Pharmacokinetics and pharmacodynamics of guanfacine extended release in adolescents aged 13–17 years with attention‐deficit/hyperactivity disorder
Authors: Martin Patrick , Satin Lawrence , Vince Bradley D. , Padilla Americo F. , White Carla , Corcoran Mary , Stevenson Annette , Ermer James 
Published: March 2014

AbstractThe safety and efficacy of guanfacine extended release (up to 4 mg/day) for attention‐deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6–17 years is well documented. Data suggest that weight‐adjusted doses of guanfacine extended release >0.08 mg/kg but ≤0.12 mg/kg, if tolerated, may provide additional clinical benefits. For many adolescents, such dosing would exceed 4 mg/day, the highest approved dose. This open‐label multicenter study evaluated the safety, tolerability, and steady‐state pharmacokinetics of guanfacine extended release at escalated forced doses ≤9 mg/day in adolescents (N = 31) aged 13–17 years with ADHD. Following doses of approximately 0.12 mg/kg, the highest weight group (>70–90 kg) exhibited lower mean clearance at steady‐state than the lowest weight group (≥30–50 kg). Consistent with its known antihypertensive effects, guanfacine extended release was associated with dose‐dependent decreases in blood pressure (BP) and heart rate (HR). The physiologic response of increased BP upon standing was blunted in a dose‐related manner while the physiologic response of increased HR upon standing was not substantively affected. The most common treatment‐emergent adverse events were somnolence, dizziness, and sinus bradycardia. These results, and those from prior studies, support further examination of the efficacy and safety of higher weight‐adjusted doses of guanfacine extended release for ADHD.
Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients
Authors: Kim Sang Soo , Song Sang Heon , Kim In Joo , Kim Won Jin , Jeon Yun Kyung , Kim Bo Hyun , Kwak Ihm Soo , Lee Eun Kyung , Kim Yong Ki 
Published: March 2014

ABSTRACTAimThe aim of this study was to evaluate the association between urinary nonalbumin protein (NAP) and urinary tubular markers in early diabetic nephropathy.MethodsUrinary NAP was measured in 118 patients with type 2 diabetes with estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2. Urine levels of tubular markers [kidney injury molecule (KIM)‐1, neutrophil gelatinase‐assoicated lipocalin (NGAL) and liver‐type fatty acid‐binding protein (L‐FABP)] were measured by using an Enzyme‐linked immunosorbent assay (ELISA). Patients were divided into three groups according to urinary NAP values.ResultsThe urine levels of KIM‐1, NGAL and L‐FABP were significantly higher in the third tertile group than in the first tertile group (all p < 0.001). There was a significant positive correlation between NAP and each tubular marker (KIM‐1, NGAL and L‐FABP) in univariate analysis (all p < 0.001). Urinary NAP was positively correlated with all urinary tubular markers after adjustment for age, duration of diabetes, systolic blood pressure, eGFR, low‐density lipoprotein cholesterol, HbA1c and albumin‐to‐creatinine ratio (KIM‐1 r = 0.170, p < 0.001; NGAL r = 0.142, p < 0.015 and L‐FABP r = 0.262, p < 0.001). In normoalbuminuric patients (n = 58), urinary NAP was also significantly correlated with NGAL and L‐FABP in multivariate regression analyses (r = 0.302, p = 0.030 and r = 0.430, p = 0.001).ConclusionsThese findings suggest that urinary NAP reflects tubular damage in the early‐stage type 2 diabetic nephropathy (eGFR ≥ 60 mL/min/1.73 m2). We suggest that urinary NAP could be used as a biomarker for tubular damage in clinical practice. Copyright © 2014 John Wiley & Sons, Ltd.
Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy
Authors: Stavniichuk Roman , Shevalye Hanna , Lupachyk Sergey , Obrosov Alexander , Groves John T. , Obrosova Irina G. , Yorek Mark A. 
Published: March 2014

AbstractBackgroundPeroxynitrite, a product of the reaction of superoxide with nitric oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP‐ribosylation), mitochondrial dysfunction and impaired stress signalling, as well as protein nitration. In this study, we sought to determine the effect of preventing protein nitration or increasing peroxynitrite decomposition on diabetic neuropathy in mice after an extended period of untreated diabetes.MethodsC57Bl6/J male control and diabetic mice were treated with the peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS, 10 mg/kg/day) or protein nitration inhibitor (−)‐epicatechin gallate (20 mg/kg/day) for 4 weeks, after an initial 28 weeks of hyperglycaemia.ResultsUntreated diabetic mice developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia and loss of intraepidermal nerve fibres. Both FeTMPS and epicatechin gallate partially corrected sensory nerve conduction slowing and small sensory nerve fibre dysfunction without alleviation of hyperglycaemia. Correction of motor nerve conduction deficit and increase in intraepidermal nerve fibre density were found with FeTMPS treatment only.ConclusionsPeroxynitrite injury and protein nitration are implicated in the development of diabetic peripheral neuropathy. The findings indicate that both structural and functional changes of chronic diabetic peripheral neuropathy can be reversed and provide rationale for the development of a new generation of antioxidants and peroxynitrite decomposition catalysts for treatment of diabetic peripheral neuropathy. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.
Electrochemiluminescence Sensor for Selective Preconcentration and Sensitive Detection of Napropamide Using Water‐Soluble Sulfonated Graphene
Authors: Wang ShiRu , Wang Sui , Guo ZhiYong 
Published: March 2014

AbstractA novel electrochemiluminescence (ECL) sensor for napropamide determination was prepared using the water‐soluble sulfonated graphene (sulfonated‐G) as solid‐phase microextraction (SPME) material, based on selective preconcentration of target onto an electrode and followed by luminol ECL detection. The effects of pH, adsorption time, buffer solution and the luminescence agent on ECL intensity were optimized. Under the optimized conditions (pH 6; adsorption time 5 min; buffer solution pH 11.0 Na2CO3aHCO3; luminescence agent luminol; stirring speed 400 rpm), the lowest detection limits (1.0 µg L−1) and good linear range (r2≥0.99) were obtained for the analyte, indicating the superior performance of Nafion/sulfonated‐G/GCE for detecting napropamide.
Growth and survival of pacific coho salmon smolts exposed as juveniles to pesticides within urban streams in western Washington, USA
Authors: King Kerensa A. , Grue Christian E. , Grassley James M. , Fisk Robert J. , Conquest Loveday L. 
Published: March 2014

Abstract

Pesticides are frequently detected in urban streams, with concentrations often exceeding those reported in surface waters within agricultural areas. The authors studied growth, survival, and return rates of coho salmon (Oncorhynchus kisutch) smolts exposed to a pesticide mixture (“cocktail”) representative of the pesticides most frequently reported within urban streams in western Washington State, USA, in fall through early spring. Exposure concentrations were selected to represent a reasonable worst-case scenario based on field monitoring data. Smolts were continuously exposed to pulses of the cocktail either from fertilization through swim-up (2007–2008) or from fertilization through smoltification (2007–2008 and 2008–2009), coded wire tagged, and released in 2008 and 2009. Pre-release endpoints (growth, survival, sex ratio, brain acetylcholinesterase activity, and gonado- and hepatosomatic indices) were not affected. However, the number of returning adults exposed to the cocktail to swim-up (0.90%, n = 42) was more than double that of unexposed controls (0.38%, n = 26) in 2008, whereas in 2009, fish exposed through smoltification returned in lower numbers (0.15%, n = 18) than controls (0.37%, n = 30). Variability in return rates among treatments between years was comparable to that observed in previous whole life cycle studies with Pacific salmon and other contaminants. Results suggest that exposure to pesticides in urban streams does not directly impair early life stages of coho salmon, and that additional studies incorporating releases of larger numbers of smolts across several years are necessary to adequately quantify effects on return rates. Environ Toxicol Chem 2014;33:???–???. © 2014 SETAC
Information‐centric networking for multimedia, social and peer‐to‐peer communications
Authors: Anadiotis Angelos‐Christos G. , Patrikakis Charalampos Z. , Murat Tekalp A. 
Published: March 2014

ABSTRACTInformation‐centric networking (ICN) is an emerging networking paradigm, which is considered as a possible solution for the next generation Internet. Several research projects have been funded by the state and the industry towards the specification and implementation of ICN solutions, whereas Internet Research Task Force has established a research group for this reason, the Information‐Centric Networking Research Group. However, the use of ICN in action will be decided on the basis of its performance in several disciplines that, eventually, concern the users expectations from their applications over the future Internet. Currently, statistics suggest that, in the near future, the Internet bandwidth will be mainly consumed by multimedia and peer‐to‐peer applications. Furthermore, social networking applications become more and more popular both to end‐users and businesses. This special issue includes papers illustrating how information‐centric networks can effectively address practical issues rising in ICN deployments considering multimedia applications and social networking technologies. Copyright © 2014 John Wiley & Sons, Ltd.
Experimental and rate‐based modeling study of CO2 capture by aqueous monoethanolamine
Authors: Li Xiaofei , Wang Shujuan , Chen Changhe 
Published: March 2014

AbstractReducing high energy consumption is one of the greatest challenges facing CO2 capture by aqueous monoethanolamine. The regeneration energy and its energy components (sensible heat, heat of reaction, and water vaporization heat) were evaluated experimentally in a bench‐scale regeneration system. A rate‐based model was developed in an Aspen Plus simulator to simulate the desorption process. The results predicted by the rate‐based model are in good agreement with experimental data. The operational parameters for the standard absorption/desorption process for CO2 capture are then optimized to reduce the energy consumption. The results show that for a 30 wt% MEA solution with 90% removal efficiency, the optimum operational parameters are an L/G ratio of 2.90 kg/kg, a lean loading of 0.24 mol/mol, a 5 °C temperature approach to the heat exchanger and a stripper operating pressure of 180 kPa with a 119 °C reboiler temperature. A minimum energy consumption of 3.52 GJ/tonCO2 was achieved. Under the optimal process conditions, the enthalpy of absorption is the main contribution to the total regeneration energy followed by the water vaporization heat and sensible heat.
CO2 geological storage: hydro‐chemo‐mechanical analyses and implications
Authors: Kim Seunghee , Santamarina J. Carlos 
Published: March 2014

AbstractThe injectivity of CO2 and the integrity of the reservoir‐caprock system are affected by CO2 invasion, water‐CO2‐mineral reactions, and ensuing mineral dissolution and precipitation. We identify different zones around an injection well and investigate the effects of these hydro‐chemo‐mechanical interactions. Geochemical analyses combine a comprehensive mass balance formulation with chemical calculations using published equations and PHREEQC. This analysis framework is used to assess near‐well, pool, and far‐field conditions, and to determine species concentrations, pH, changes in brine density, and changes in mineral and fluid volume in the reservoir. Results show that the brine density may increase by as much as 1.2% and can sustain convective flow of CO2 dissolved brine; the characteristic time scale for convection can be as short as a few years in some permeable formations currently being considered for storage. The precipitation of secondary minerals near the injection well increases the mineral volume by a maximum of 5%, yet, only a minor decrease in CO2 permeability is anticipated. Dissolution may result in unsupported caprock (the span should not exceed 20% of the caprock thickness to prevent failure), and may cause compaction‐driven shear failure of the reservoir. Finally, the analysis of lateral capillary trapping shows that the CO2 pool is only a few meters thick in leveled caprock interfaces and in the absence of geometric traps.
Joint geriatric and old‐age psychiatric wards in the UK, 1940s–early 1990s: a historical study
Authors: Hilton Claire 
Published: March 2014

ObjectiveThis study aims to investigate the history of joint geriatric‐psychiatric units. For policy making and planning of high‐quality clinical service models, clinical and social contexts need to be considered. Longitudinal, contextual information can be provided by historical analyses, including the successes and failures of earlier, similar services. Historical analyses complement clinical, randomised controlled studies and may contribute to ensuring optimum outcomes for future schemes.MethodsStandard historical methodology was used, including searching published sources and institutional and personal archives and conducting a ‘witness seminar’ and individual oral history interviews.ResultsProposals to create joint units have existed since 1947. Most clinically successful units were led by enthusiastic, dedicated clinicians. Joint units had the potential to provide appropriate assessment and treatment for patients with multiple disorders and education for staff and students. Joint units never became widespread.ConclusionsReasons for the limited success of joint geriatric‐psychiatric units might have included personalities of individuals, administrative boundaries separating geriatrics and medicine, unequal numbers of geriatricians and old‐age psychiatrists, varying professional ideologies about the meaning of ‘integrated’ services, lack of reciprocity for each other's inpatients and lack of government support.Identified stumbling blocks need to be considered when planning joint clinical schemes. If current research indicates benefits of integrated wards for patients and their families, there needs to be ways to ensure that personal factors and fashions of management or government re‐prioritisation will not lead to their premature termination. Copyright © 2014 John Wiley & Sons, Ltd.
Concordance between 99mTc‐ECD SPECT and 18F‐FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA‐AA criteria
Authors: Ito Kimiteru , Shimano Yasumasa , Imabayashi Etsuko , Nakata Yasuhiro , Omachi Yoshie , Sato Noriko , Arima Kunimasa , Matsuda Hiroshi 
Published: March 2014

ObjectivesThe purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon‐emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging‐Alzheimer's Association Workshop.MethodsFifty‐five patients with “AD and mild cognitive impairment (MCI)” (n = 40) and “non‐AD” (n = 15) were evaluated with 18F‐FDG PET and 99mTc‐ethyl cysteinate dimer (ECD) SPECT during an 8‐week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake.ResultsThe regions with better interobserver reliability between 18F‐FDG PET and 99mTc‐ECD SPECT were the frontal, parietal, and temporal lobes. The 99mTc‐ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F‐FDG PET and 99mTc‐ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of “AD and MCI” ranged from 60% to 70% in both of the techniques.ConclusionsThe degree of uptake on 18F‐FDG PET and 99mTc‐ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F‐FDG PET and 99mTc‐ECD SPECT for “AD and MCI,” when diagnosed according to the National Institute of Aging‐Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.
Glycine N‐methyltransferase expression in the hippocampus and its role in neurogenesis and cognitive performance
Authors: Carrasco Manuel , Rabaneda Luis G. , Murillo‐Carretero Maribel , Ortega‐Martínez Sylvia , Martínez‐Chantar María L. , Woodhoo Ashwin , Luka Zigmund , Wagner Conrad , Lu Shelly C. , Mato José M. , Micó Juan A. , Castro Carmen 
Published: March 2014

ABSTRACTThe hippocampus is a brain area characterized by its high plasticity, observed at all levels of organization: molecular, synaptic, and cellular, the latter referring to the capacity of neural precursors within the hippocampus to give rise to new neurons throughout life. Recent findings suggest that promoter methylation is a plastic process subjected to regulation, and this plasticity seems to be particularly important for hippocampal neurogenesis. We have detected the enzyme GNMT (a liver metabolic enzyme) in the hippocampus. GNMT regulates intracellular levels of SAMe, which is a universal methyl donor implied in almost all methylation reactions and, thus, of prime importance for DNA methylation. In addition, we show that deficiency of this enzyme in mice (Gnmt−/−) results in high SAMe levels within the hippocampus, reduced neurogenic capacity, and spatial learning and memory impairment. In vitro, SAMe inhibited neural precursor cell division in a concentration‐dependent manner, but only when proliferation signals were triggered by bFGF. Indeed, SAMe inhibited the bFGF‐stimulated MAP kinase signaling cascade, resulting in decreased cyclin E expression. These results suggest that alterations in the concentration of SAMe impair neurogenesis and contribute to cognitive decline. © 2014 Wiley Periodicals, Inc.