bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutagenesis and Molecular Modeling of the Orthosteric Binding Site of the mGlu2 Receptor Determining Interactions of the Group II Receptor Antagonist 3H‐HYDIA
Authors: Lundström Linda , Kuhn Bernd , Beck Jennifer , Borroni Edilio , Wettstein Joseph G. , Woltering Thomas J. , Gatti Silvia 
Published: April 2009

AbstractBinding of the mGlu2/3 antagonist HYDIA in the closed conformation model of mGlu2 causes repulsive interactions with Y216 in lobe II of the binding pocket, preventing closure of the VFT.magnified imageModulation of metabotropic glutamate 2/3 receptors represents a promising target for the treatment of neuropsychiatric disorders such as schizophrenia and depression. The novel mGlu2/3 ligand HYDIA ((1S,2R,3R,5R,6S)‐2‐amino‐3‐hydroxy‐bicyclo[3.1.0]hexane‐2,6‐dicarboxylic acid) is a conformationally restricted and hydroxylated glutamate analogue. HYDIA is a potent and selective competitive antagonist of L‐glutamate at the mGlu2/3 receptors in spite of being structurally very similar to the bicyclic LY354740, which is a potent and selective mGlu2/3 agonist. By comparing these two ligands, this study delineate the interaction mode of 3H‐HYDIA at the mGlu2 receptor, using both mutagenesis studies and computational modeling. Binding of HYDIA in the closed conformation model of mGlu2 results in repulsive interaction with the Y216 residue, preventing closure of the binding pocket and thus receptor activation. Consequently, HYDIA is proposed to bind in an open conformation model of mGlu2. Mutation of the structurally important Y216 residue in the binding site caused complete loss of affinity of both 3H‐LY354740 and 3H‐HYDIA. T168 in lobe I was shown to have an important role in HYDIA binding, and in the open conformation model this residue is interacting with the amino group of HYDIA. The Y144 residue in lobe I is shown to be engaged in both receptor interlobe binding and ligand interaction. Receptor mutations at this position (Y144G, Y144S and Y144A) showed dramatic impact on binding affinity and functional effect of HYDIA. The mGlu2 receptor mutants with increased structural flexibility at this position, which is crucial for pocket closure, were clearly preferred. These studies highlight the unique properties of the novel 3H‐HYDIA ligand and provide further support to our understanding of binding and signal transduction mechanisms of the mGlu2 receptor.
Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma
Authors: Calabrò Fabio , Lorusso Vito , Rosati Gerardo , Manzione Luigi , Frassineti Luca , Sava Teodoro , Di Paula Eugenio Donato , Alonso Silvia , Sternberg Cora N. 
Published: April 2009

AbstractBACKGROUND:Patients with urothelial carcinoma are not always amenable to cisplatin‐based chemotherapy. The authors previously reported that they achieved a 60% response rate in patients who failed on cisplatin‐based combination chemotherapy (methotrexate, vinblastine, doxorubicin, and cisplatin) by using a convenient outpatient regimen of gemcitabine (G) and paclitaxel (P) every 2 weeks. A multicenter trial was initiated in 5 Italian centers to evaluate this regimen as first‐line chemotherapy.METHODS:From January 2003 to April 2005, 54 patients who had histologically proven, measurable disease (according to Response Evaluation Criteria in Solid Tumors) with a World Health Organization (WHO) performance status (PS) from 0 to 2, metastatic or inoperable urothelial carcinoma, no prior systemic cytotoxic or biologic treatment, a creatinine clearance ≥40 mL per minute, and bilirubin <20 μmol/L received G at a dose of 2500 mg/m2 in 30 minutes and P at a dose of 150 mg/m2 in 3 hours every 2 weeks. Granulocyte–colony‐stimulating factor (G‐CSF) was given for 5 to 7 days for neutropenia toxicity of grade ≥3 (grading determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 guidelines). From 6 to 12 courses were planned. All patients received at least 1 cycle of therapy and were included in all analyses.RESULTS:The median patient age was 67 years (range 34‐78 years), and the median WHO PS was 1 (range, 0‐2). Metastases occurred in the lung in 17 patients (31%), in lymph nodes in 26 patients (54%), in the bladder in 20 patients (37%), in bone in 8 patients (15%), and in the liver in 8 patients (15%). Fifty‐nine percent of patients had >1 site of disease, and 13% of patients had ≥3 sites of disease. In total, 343 cycles were administered. Five patients achieved a complete response, and 15 patients achieved a partial response; thus, the overall response rate was 37% in an intent‐to‐treat analysis. Hematologic toxicity was predominant but manageable. G‐CSF was used in only 6% of cycles. The median survival was 13.2 months, and the median time to disease progression was 5.8 months.CONCLUSIONS:In a multicenter study, G and P was found to be a well–tolerated outpatient regimen. This regimen demonstrated promise and may be considered in patients who are unable to receive cisplatin. Cancer 2009. © 2009 American Cancer Society.
Prognostic factors differ by tumor stage for small cell lung cancer
Authors: Foster Nathan R. , Mandrekar Sumithra J. , Schild Steven E. , Nelson Garth D. , Rowland Kendrith M. , Deming Richard L. , Kozelsky Timothy F. , Marks Randolph S. , Jett James R. , Adjei Alex A. 
Published: April 2009

AbstractBACKGROUND:An analysis of 14 small cell lung cancer (SCLC) trials was performed to improve the current understanding of potential prognostic factors for overall survival (OS) and progression‐free survival (PFS) in groups of patients with limited‐stage disease SCLC (LD‐SCLC) and extensive‐stage disease SCLC (ED‐SCLC) separately.METHODS:Data on 688 patients with LD‐SCLC and 910 patients with ED‐SCLC were included. Clinical and laboratory factors were tested for their prognostic significance using Cox regression models that were stratified by protocol. Recursive partitioning and amalgamation (RPA) analyses were used to identify prognostic subgroups.RESULTS:Poorer performance status (PS) led to worse OS and PFS in the ED‐SCLC group but not in the LD‐SCLC group. The prognostic impact of PS was strong for men but weak for women in the ED‐SCLC group (interactionPvalue <.012 for OS and PFS). Other negative prognostic factors included increased age and men for the LD‐SCLC group and increased age, men, increased number of metastatic sites at baseline, and increased creatinine levels for the ED‐SCLC group. In patients with the ED‐SCLC, RPA analyses identified 5 subgroups with different prognosis based on baseline PS, creatinine levels, sex, and the number of metastatic sites.CONCLUSIONS:The current pooled analysis identified baseline creatinine levels and the number of metastatic sites as important prognostic factors in patients with ED‐SCLC in addition to the well established factors of sex, age, and PS. There was a significant interaction between sex and PS within the ED‐SCLC group, suggesting that PS is highly prognostic in men but has no significant impact in women. Within the LD‐SCLC group, only age and sex were identified as important prognostic factors. RPA analyses confirmed many of these findings. Cancer 2009. © 2009 American Cancer Society.
Clinical outcomes of molecularly confirmed clear cell sarcoma from a single institution and in comparison with data from the Surveillance, Epidemiology, and End Results registry
Authors: Blazer Dan G. , Lazar Alexander J. , Xing Yan , Askew Robert L. , Feig Barry W. , Pisters Peter W. T. , Pollock Raphael E. , Lev Dina , Hunt Kelly K. , Cormier Janice N. 
Published: April 2009

AbstractBACKGROUND:The authors compared disease‐specific survival (DSS) in stage‐specific subgroups of patients with clear cell sarcoma, including those with lymph node metastases (N1M0) and those with distant metastases (N0M1).METHODS:Clinical data regarding soft tissue sarcoma patients were obtained from The University of Texas M. D. Anderson Cancer Center (MDACC) (1980‐2007) and the Surveillance, Epidemiology, and End Results (SEER) registry (1988‐2004). When possible, clear cell sarcoma diagnoses were confirmed using fluorescence in situ hybridization or reverse‐transcription polymerase chain reaction. Kaplan‐Meier estimates were used to calculate DSS, and Cox multivariate analysis was performed to identify prognostic factors.RESULTS:Fifty‐two patients at MDACC and 130 SEER patients were diagnosed with clear cell sarcoma. Five‐year DSS for the MDACC and SEER cohorts were 67% and 62%, respectively. Patients with N1M0 and N0M1 disease demonstrated significant differences in 5‐year DSS: 74% versus 14% at MDACC (P= .014) and 52% versus 0% in SEER (P= .014). After adjustment, the hazards ratio (HR) for dying was 2.79 for N1M0 disease (95% confidence interval [95% CI], 1.32‐5.91) and 11.37 (95% CI, 5.19‐24.91) for N0M1 disease compared with stage II disease (P< .001). Non‐Caucasian ethnicity (HR, 3.99; 95% CI, 2.27‐6.99 [P< .001]) and truncal tumor site (HR, 2.41; 95% CI, 1.15‐5.05 [P= .02]) were also found to be predictors of decreased DSS.CONCLUSIONS:The findings of the current study suggest that patients with N1M0 clear cell sarcoma have 5‐year DSS that is more similar to that of patients with stage III than stage IV soft tissue sarcoma. Cancer 2009. © 2009 American Cancer Society.
Treatment of fludarabine‐refractory chronic lymphocytic leukemia
Authors: Tsimberidou Apostolia‐Maria , Keating Michael J. 
Published: April 2009

AbstractThe development of resistance to purine analogs defines a poor‐risk subset of patients with chronic lymphocytic leukemia (CLL). Although in recent years chemoimmunotherapeutic combinations such as fludarabine, cyclophosphamide, and rituximab have induced response rates of 95% in previously untreated patients and increased the rates of failure‐free survival, CLL remains incurable for many patients because of a lack of disease response or the development of refractoriness to fludarabine. Fludarabine‐refractory disease is defined as CLL that does not respond to fludarabine or that recurs within 6 months of treatment with a fludarabine‐containing regimen. The natural course of the disease is associated with poor survival. Salvage therapeutic strategies include alemtuzumab‐containing regimens, targeted agents, and allogeneic stem cell transplantation. Single‐agent alemtuzumab induces response in up to 40% of patients with fludarabine‐refractory CLL, but responses are not durable, and the median survival is approximately 1 to 2 years. Alemtuzumab is also combined with fludarabine, cyclophosphamide, and/or rituximab, and other agents such as lenalidomide and flavopiridol, as well as targeted agents, and used in fludarabine‐refractory CLL. Cumulative evidence suggests that allogeneic stem cell transplantation is an efficacious therapeutic strategy for patients who do not respond to fludarabine or who develop disease recurrence within 12 months after purine analog treatment. In conclusion, chemoimmunotherapy regimens that include alemtuzumab and/or rituximab and allogeneic stem cell transplantation improve the prognosis of this disease, but there is a continued need for novel, more effective therapies. Cancer 2009. © 2009 American Cancer Society.
Radiotherapy in adrenocortical carcinoma
Authors: Polat Buelent , Fassnacht Martin , Pfreundner Leo , Guckenberger Matthias , Bratengeier Klaus , Johanssen Sarah , Kenn Werner , Hahner Stefanie , Allolio Bruno , Flentje Michael 
Published: April 2009

AbstractAdrenocortical carcinoma (ACC) is a rare malignancy, and patients with ACC have a poor prognosis. Even after radical surgery, up to 85% of patients develop recurrent disease. Systemic treatment options still have limited efficacy. Because the role of radiotherapy is not defined well and because ACC often is considered radioresistant, the authors reviewed the available data on radiotherapy for ACC. Original articles and reviews were identified using a PubMed search strategy that included the period up to July 2008. Ten articles were identified that covered radiotherapy in a total of 129 patients with ACC (64 patients received postoperative irradiation, and 65 patients received palliative therapy for advanced disease). In addition, 26 patients were identified in the German ACC Registry who received palliative radiotherapy. Furthermore, patterns of failure after adjuvant radiotherapy were investigated, and the authors provided recommendations for patient selection, treatment planning, and treatment protocols. In an adjuvant setting, postoperative radiotherapy was able to prevent local recurrence in the majority of patients. In those with advanced disease, a response to radiotherapy was observed in 57% of patients who received palliative radiotherapy. Therefore, the authors concluded that radiotherapy may play an important role in the care of patients with ACC. Until better evidence is available, the authors recommended the following approach: Adjuvant radiotherapy to the tumor bed should be considered in patients at high risk for local recurrence (eg, incomplete/R1 resection); a total dose of >40 grays (Gy) with single fractions of 1.8 Gy to 2 Gy should be administered (including a boost volume to reach from 50 Gy to 60 Gy in individual patients); and radiotherapy in a palliative setting may be used for symptomatic metastases to bone, brain, or vena cava obstruction. With state‐of‐the‐art technology, acute and long‐term toxicities mostly were mild to moderate. However, the authors concluded that prospective investigations would be required to fully define the therapeutic potential of this important treatment option. Cancer 2009. © 2009 American Cancer Society.
Incidence and mortality rates for colorectal cancer in Puerto Rico and among Hispanics, non‐Hispanic whites, and non‐Hispanic blacks in the United States, 1998‐2002
Authors: Soto‐Salgado Marievelisse , Suárez Erick , Calo William , Cruz‐Correa Marcia , Figueroa‐Vallés Nayda R. , Ortiz Ana P. 
Published: April 2009

AbstractBACKGROUND:Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Puerto Rico (PR). In the United States, the incidence and mortality rates of CRC have great variation by sex and race/ethnicity. Age‐standardized incidence and mortality rates of CRC in PR were assessed and compared with the rates among US Hispanics (USH), non‐Hispanic whites (NHW), and non‐Hispanic blacks (NHB) in the United States for the period from 1998 through 2002. Incidence and mortality trends and relative differences among racial/ethnic groups by sex and age were determined.METHODS:Age‐standardized rates using the world standard population (ASR[World]) were based on cancer incidence and mortality data from the PR Central Cancer Registry and from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program using the direct method. The annual percentage changes (APC) and relative risks (RR) were calculated using Poisson regression models.RESULTS:During 1998 through 2002, the APC of CRC incidence and mortality increased for men in PR, whereas descending trends were observed for other racial/ethnic groups. Overall period rates indicated that, in both sexes, Puerto Ricans had CRC incidence and mortality rates similar to those for USH, but their rates were lower than those for NHW and NHB. However, Puerto Rican men and women ages 40 years to 59 years had the greatest risk of incidence and mortality compared with their USH counterparts.CONCLUSIONS:Areas of concern include the increasing trends of CRC in PR and the higher burden of the disease among young Puerto Ricans compared with the USH population. The authors concluded that further research should be performed to guide the design and implementation of CRC prevention and education programs in PR. Cancer 2009. © 2009 American Cancer Society.
LC‐active VCO for CMOS RF transceivers
Authors: Zito Domenico , Pepe Domenico 
Published: April 2009

AbstractA novel fully integrated CMOS LC tank VCO is presented. The LC tanks are implemented by exploiting the active circuit ‘boot‐strapped inductor’ (BSI), which behaves like a high‐quality factor inductor. Particularly, the LC tanks have been implemented by introducing a new version of the CMOS BSI circuit, which provides better versatility and design reliability.In order to verify the effectiveness of such an approach, a case study for 5–6 GHz direct‐conversion multi‐standard WLAN transceivers is presented. The VCO has been designed in a 0.35µm standard CMOS technology. The new BSI exhibits a high‐quality factor (higher than 25 over the all frequency range) and provides a high selectivity without introducing a relevant excess of noise, for a better spectral purity and a lower phase noise (PN) of the VCO. The overall VCO circuit consumes 9 mW. The VCO produces an oscillation in the tuning range from 4.91 to 5.93 GHz (nearly equal to 19%). The circuit exhibits a PN of −129dBc/Hz at 1 MHz of frequency offset from the central frequency (5.4 GHz) and a FOM equal to 189.5 dBc/Hz at 100 kHz and 194.1 dBc/Hz at 1 MHz of frequency offset, respectively. Copyright © 2009 John Wiley & Sons, Ltd.
Sinusoidal oscillators with lower gain requirements at higher frequencies based on an explicit tanh(x) nonlinearity
Authors: Elwakil A. S. , Ozoguz S. , Salama K. N. 
Published: April 2009

AbstractTwo novel sinusoidal oscillator structures with an explicit tanh(x) nonlinearity are proposed. The oscillators have the attractive feature: the higher the operating frequency, the lower the necessary gain required to start oscillations. A nonlinear model for the two oscillators is derived and verified numerically. Spice simulations using AMS BiCMOS 0.35µ model parameters and experimental results are shown. Copyright © 2009 John Wiley & Sons, Ltd.
Synchronization of identical neural networks and other systems with an adaptive coupling strength
Authors: Liu Xiwei , Chen Tianping 
Published: April 2009

AbstractIn this paper, a new scheme to synchronize linearly or nonlinearly coupled identical circuit systems, which include neural networks and other systems, with an adaptive coupling strength is proposed. Unlike other adaptive schemes that synchronize coupled circuit systems to a specified trajectory (or an equilibrium point) of the uncoupled node by adding negative feedbacks adaptively, here the new adaptive scheme for the coupling strength is used to synchronize coupled systems without knowing the final synchronization trajectory. Moreover, the adaptive scheme is applicable when the coupling matrix is unknown or time‐varying. The validity of the new adaptive scheme is also proved rigorously. Finally, several numerical simulations to synchronize coupled neural networks, Chua's circuits and Lorenz systems, are also given to show the effectiveness of the theory. Copyright © 2009 John Wiley & Sons, Ltd.
Meta‐analysis of the effectiveness of psychological and pharmacological treatments for binge eating disorder
Authors: Vocks Silja , Tuschen‐Caffier Brunna , Pietrowsky Reinhard , Rustenbach Stephan Jeff , Kersting Anette , Herpertz Stephan 
Published: April 2009

AbstractObjective:The aim of this study was to compute and compare mean effects of various treatments for binge eating disorder.Method:A total of 38 studies with 1973 participants fulfilled the defined inclusion criteria. Effect sizes, odds ratios, and simple rates were integrated in fixed and random (mixed) effects categorical models.Results:From randomized controlled trials, psychotherapy and structured self‐help, both based on cognitive behavioral interventions, were found to have large effects on the reduction of binge eating. Regarding pharmacotherapy, mainly comprising antidepressants, randomized controlled trials revealed medium effects for the reduction of binge eating. Uncontrolled studies on weight‐loss treatments demonstrated moderate reductions of binge eating. Combination treatments did not result in higher effects compared with single‐treatment regimens. Except for weight‐loss treatment, none of the interventions resulted in a considerable weight reduction.Discussion:Psychotherapy and structured self‐help, both based on cognitive‐behavioral interventions, should be recommended as the first‐line treatments. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010
Tuning the Emission Color of Iridium(III) Complexes with Ancillary Ligands: A Combined Experimental and Theoretical Study
Authors: Gu Xin , Fei Teng , Zhang Houyu , Xu Hai , Yang Bing , Ma Yuguang , Liu Xiaodong 
Published: April 2009

AbstractA series of iridium(III) complexes [Ir(dfppy)2(LX)] {dfppy = 2‐(2,4‐difluorophenyl)pyridine, LX = acac, FIr(acac); dbm, FIr(dbm); natfac, FIr(natfac); acac = acetylacetonate, dbm = dibenzoylmethanane, natfac = 1‐naphthoyl‐3,3,3‐trifluoroacetone} have been synthesized and characterized by elemental analysis, NMR and IR spectroscopy, and mass spectrometry. The cyclic voltammetric, absorption, and emission properties of these complexes have been systematically investigated. Density functional theory (DFT) and time‐dependent DFT (TD‐DFT) calculations have been performed to investigate the ground‐ and excited‐state properties of these complexes to provide an insight into their structural, electronic, and optical properties. The results of this work provide further evidence regarding how and to what extent the substituents on the ancillary ligand LX influence the emission properties of [Ir(dfppy)2(LX)] complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Microwave‐Promoted Synthesis of N‐Heterocycles by Tandem Imination/Annulation of γ‐ and δ‐Ketoalkynes in the Presence of Ammonia
Authors: Alfonsi Maria , Dell'Acqua Monica , Facoetti Diego , Arcadi Antonio , Abbiati Giorgio , Rossi Elisabetta 
Published: April 2009

AbstractThe synthesis of 3‐substituted 1‐methylpyrrolo[1,2‐a]pyrazines and 3‐substituted isoquinolines was achieved by the intramolecular cyclisation of 2‐acetyl‐1‐propargylpyrroles and 2‐alkynylbenzaldehydes, respectively, in the presence of ammonia under microwave heating. The tandem imination/annulation of 2‐alkynylbenzaldehydes was easily accomplished under standard conditions, while TiCl4 was used to achieve pyrrolo[1,2‐a]pyrazines. The reaction mechanism and the regioselectivity were discussed on the basis of theoretical calculations and spectroscopic data. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
New Options for the Reactivity of the Burgess Reagent with Epoxides in Both Racemic and Chiral Auxiliary Modes – Structural and Mechanistic Revisions, Computational Studies, and Application to Synthesis
Authors: Leisch Hannes , Sullivan Bradford , Fonovic Branden , Dudding Travis , Hudlicky Tomas 
Published: April 2009

AbstractThe reaction of the chiral auxiliary version of the Burgess reagent with epoxides yields diastereomeric pairs of sulfamidates, which lead to cis and trans amino alcohols in each enantiomeric series. Experimental and spectral details are provided for all new sulfamidates and the products derived from them. Structure revisions have been made for several previously reported products from the reactions of the Burgess reagent with cyclic oxiranes and styrene diols. Considerable revisions are also suggested for the possible mechanisms operating in the reactions of the Burgess reagent with 1,2‐diols and epoxides. Finally, a Density Functional Theory (DFT) study for the interaction of the achiral version of the Burgess reagent with oxiranes is included along with an explanation of the lack of asymmetric induction observed in reactions conducted in a catalytic mode with C2‐symmetric catalysts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)