bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of differential BRAFV600E mutational status in multifocal papillary thyroid carcinoma
Authors: Park So Yeon , Park Young Joo , Lee Yu Jin , Lee Hyun Sook , Choi Sung Hee , Choe Gheeyoung , Jang Hak‐Chul , Park Seong Hoe , Park Do Joon , Cho Bo Youn 
Published: September 2006

AbstractBACKGROUND.Papillary thyroid cancers often occur as multiple foci. Multifocal cancers have been considered to have a poor prognosis because they are thought to be the consequence of intrathyroidal spread of the papillary cancer. However, to the authors' knowledge there has been little investigation into whether multifocal thyroid papillary carcinomas arise from the intrathyroidal spread of a single carcinoma or from independent primary tumors. To answer this question, the BRAFV600E mutational status of individual tumor foci was examined. This approach was justified because in the Korean population a high proportion (65%) of papillary carcinomas harbor the BRAF mutation.METHODS.DNA was isolated from paraffin‐embedded tissue samples of multifocal papillary thyroid carcinoma and the BRAF exon 15 was amplified by the polymerase chain reaction (PCR). The PCR product was digested with restriction endonuclease TspRI to test for the presence of the BRAFV600E (T1799A) mutation.RESULTS.In all, 140 cancers from 61 patients diagnosed with multifocal papillary carcinoma were examined. The BRAF mutation was found in all the individual cancers in 29 (47.5%) of the patients (all‐positive group) and the mutation was absent in all the individual cancers in 8 (13.1%) patients (all‐negative group). However, in 24 (39.3%) patients, some of the individual cancers contained the BRAF mutation, whereas others did not (mixed group).CONCLUSIONS.At least 39.3% of the multifocal papillary cancers in the Korean population that were examined could be attributed to independently arising papillary cancers rather than to intrathyroidal spread of single cancers. Cancer 2006. © 2006 American Cancer Society.
Expression of inhibitor of apoptosis proteins in B‐cell non‐Hodgkin and Hodgkin lymphomas
Authors: Akyurek Nalan , Ren Yongsheng , Rassidakis Georgios Z. , Schlette Ellen J. , Medeiros L. Jeffrey 
Published: September 2006

AbstractBACKGROUND.Inhibitor of apoptosis proteins (IAPs) inhibit apoptosis by binding specific caspases, and possibly by other mechanisms. Eight IAPs have been identified in humans, of which cIAP1, cIAP2, and XIAP are well known. IAPs are being investigated as potential treatment targets in cancer patients.METHODS.cIAP1, cIAP2, and XIAP were assessed in lymphoma cell lines, 240 B‐cell non‐Hodgkin lymphoma (NHL) tumors, and 40 Hodgkin lymphoma (HL) tumors.RESULTS.All IAPs were expressed in most NHL and all HL cell lines. In NHL tumors, cIAP1 was expressed in 174 (73%), cIAP2 in 115 (48%), and XIAP in 37 (15%). cIAP1 was positive in all precursor B‐cell lymphoblastic lymphoma/leukemia (LBL) and nodal marginal zone B‐cell lymphoma (MZL), over 90% of follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL), and approximately 50% to 60% of myeloma, Burkitt lymphoma (BL), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM), small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL), extranodal marginal zone B‐cell lymphoma of mucosa associated lymphoid tissue (MALT‐lymphoma), splenic MZL, and mantle cell lymphoma. cIAP2 was positive in all MALT‐lymphoma, over 90% of precursor B‐cell LBL (94%), most BL (75%), LPL/WM (71%), and SLL/CLL (67%), and approximately 40% to 60% of follicular lymphoma, myeloma, and DLBCL. XIAP was positive most cases of precursor B‐cell LBL (57%) and approximately 30% to 40% of nodal MZL, BL, and DLBCL. In HL tumors, cIAP1 was positive in 30 (75%), cIAP2 in 27 (68%), and XIAP in 23 (58%), and did not correlate with histologic type.CONCLUSIONS.Differential expression of IAPs in B‐cell lymphomas suggests differences in pathogenesis that may have implications for novel treatment strategies targeting IAPs. Cancer 2006. © 2006 American Cancer Society.
Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma
Authors: Suppiah Revathi , Shaheen Philip E. , Elson Paul , Misbah Seema A. , Wood Laura , Motzer Robert J. , Negrier Slyvie , Andresen Steven W. , Bukowski Ronald M. 
Published: September 2006

AbstractBACKGROUND.It has been suggested that thrombocytosis, as defined by a platelet count >400,000/μL, is a negative predictor for survival among patients with metastatic renal cell carcinoma. However, this has not been a uniform finding.METHODS.To address this issue, retrospective analysis of 700 previously untreated patients entering on institution review board‐approved phase 1, 2, or 3 clinical trials in the United States and Europe was conducted between 1982 and 2002.RESULTS.Thrombocytosis was present at study entry in 25% of patients. Median baseline platelet count was 304,000/μL (range, 86–1,420,000/μL). Eighty‐seven percent of patients died with a median survival of 13.0 months. Median follow‐up for patients not known to have died was 2.4 years. On univariate analysis, patients with elevated platelet counts had significantly shorter survival than patients with normal platelet counts; median survivals of 8.4 and 14.6 months, respectively, P < .001. However, platelet count was associated with several clinical and biochemical factors, including gender, age, performance status, time from diagnosis to study entry, prior radiotherapy or nephrectomy, presence of liver metastasis, number of metastatic sites, amount of hemoglobin, white blood cell count, amount of lactate dehydrogenase, and amount of serum alkaline phosphatase. Several of these factors have previously been reported as prognostic indicators for survival, and, therefore, multivariable analyses were conducted to determine whether thrombocytosis is an independent predictor of survival. After adjusting for multiple factors, thrombocytosis continued to impact negatively on survival, P < .001.CONCLUSIONS.Thrombocytosis was found to be an independent prognostic factor for survival in patients with metastatic renal cell carcinoma. Cancer 2006. © 2006 American Cancer Society.
Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain
Authors: Krown Susan E. , Niedzwiecki Donna , Hwu Wen‐Jen , Hodgson Lydia , Houghton Alan N. , Haluska Frank G. ,   for the Cancer and Leukemia Group B
Published: September 2006

AbstractBACKGROUND.Preliminary studies suggesting that extended‐dose temozolomide with thalidomide is safe and active in patients with metastatic melanoma have led to frequent use of this oral regimen. To confirm these observations the combination was tested in a multicenter Phase II trial in patients with melanoma brain metastases.METHODS.Eligible patients had melanoma brain metastases, with or without systemic metastases. The primary endpoint was response rate in brain metastases. Patients received temozolomide at a dose of 75 mg/m2/day for 6 weeks with a 2‐week rest between cycles, and thalidomide (escalated to 400 mg/day for patients age <70 years or to 200 mg/day for patients age ≥70 years). A 2‐stage design required ≥3 responses in the first 21 patients before enrolling 29 additional patients in the second stage.RESULTS.Sixteen eligible patients were enrolled. No objective responses were observed. The median survival was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were removed during Cycle 1 because of adverse events, including allergic reaction (1 patient), severe fatigue (1 patient), sudden death (1 patient), and thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis in 1 patient); 2 patients withdrew when the study was suspended and subsequently closed. No associations could be established between baseline characteristics and toxicity.CONCLUSIONS.The proportion of patients with lethal or potentially life‐threatening adverse events was high (0.31, 95% confidence interval, 0.11–0.59), and the absence of objective responses made it unlikely that further accrual would demonstrate the efficacy of the regimen. These observations provide little support for the use of this combination for melanoma brain metastases unless safe and effective methods to prevent thrombosis are developed. Cancer 2006. © 2006 American Cancer Society.
Rank‐based ant colony algorithms for truss weight minimization with discrete variables
Authors: Capriles Priscila V. S. Z. , Fonseca Leonardo G. , Barbosa Helio J. C. , Lemonge Afonso C. C. 
Published: September 2006

AbstractOne variant of the ant colony optimization (ACO) metaheuristic, known as rank‐based ant system (RBAS), is proposed for weight minimization of structures involving discrete design variables. Stress and displacements constraints are handled using a penalty technique, and the structural analysis is performed by the finite element method.Results obtained for several discrete weight minimization problems show that the RBAS algorithm implemented is effective and competitive when compared with results found by genetic algorithms and another RBAS variant. Copyright © 2006 John Wiley & Sons, Ltd.
The radial integration method applied to dynamic problems of anisotropic plates
Authors: Albuquerque E. L. , Sollero P. , Portilho de Paiva W. 
Published: September 2006

AbstractIn this paper, the radial integration method is applied to transform domain integrals into boundary integrals in a boundary element formulation for anisotropic plate bending problems. The inertial term is approximated with the use of radial basis functions, as in the dual reciprocity boundary element method. The transformation of domain integrals into boundary integrals is based on pure mathematical treatments. Numerical results are presented to verify the validity of this method for static and dynamic problems and a comparison with the dual reciprocity boundary element method is carried out. Although the proposed method is more time‐consuming, it presents some advantages over the dual reciprocity boundary element method as accuracy and the absence of particular solutions in the formulation. Copyright © 2006 John Wiley & Sons, Ltd.
Peptide‐doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor
Authors: Lee Gee Young , Song Ji‐hye , Kim Sang Yoon , Park Kyeongsoon , Byun Youngro 
Published: September 2006

AbstractSpecific peptide‐doxorubicin conjugates were developed for targeting matrix metalloproteinases (MMPs) expressed from tumors. The peptide‐doxorubicin conjugates were designed to be cleaved by MMP‐2 and MMP‐9 in order that doxorubicin or the active form that acts as an anticancer agent was released free from the peptide fragment at the tumor site. Three types of peptide‐doxorubicin conjugates were synthesized using the peptides: GPLG (Gly‐Pro‐Leu‐Gly), GPLGV (Gly‐Pro‐Leu‐Gly‐Val), and GPLGPAG (Gly‐Pro‐Leu‐Gly‐Pro‐Ala‐Gly). The synthesized peptide‐doxorubicin conjugates were characterized for their degradation behavior and bioactivity in vitro, and their antitumoral activity was assessed using the Lewis lung carcinoma (LLC) model, which expresses MMP‐2 and MMP‐9. After incubation with active MMP‐2 for 24 h, GPLG‐doxorubicin was barely degraded, whereas GPLGV‐doxorubicin and GPLGPAG‐doxorubicin were considerably degraded by active MMP‐2. Consequently, all peptide‐doxorubicin conjugates had significantly low cytotoxicity compared to doxorubicin, but tumor growth suppression was exhibited only by GPLGV‐doxorubicin and GPLGPAG‐doxorubicin. The tumor growth suppression by the two conjugates was higher compared to control, although it did not exceed the suppression level shown by doxorubicin. The low toxicity exhibited by peptide‐doxorubicin conjugates resulted in only slight body weight loss in mice, whereas doxorubicin greatly reduced body weight and induced severe side effects. Therefore, we propose MMPs‐specific peptide‐doxorubicin conjugates in targeting anti‐cancer drug delivery that could reduce systemic toxicities. Drug Dev. Res. 67:438–447, 2006. © 2006 Wiley‐Liss, Inc.
A reporter gene cellular model for evaluating induction of CYP3A4 by new chemical entities
Authors: Enoru‐Eta Julius , Yengi Lilian G. , Kao John , Scatina JoAnn 
Published: September 2006

AbstractA cell‐based reporter gene assay to study CYP3A4 induction was developed in the present study. The pregnane X receptor (PXR) gene or variant (PXR2) was cloned into the pSG5 vector and cotransfected into HepG2 cells, with a construct, pGL3‐3A4‐Luc, containing the promoter/enhancer region of the CYP3A4 gene. The two systems were validated using rifampicin (RIF). The variant, PXR2, did not mediate induction of CYP3A4 by rifampicin (10 µM) whereas PXR showed dose‐dependent induction of CYP3A4, with a fold change of 40–60, compared to the vehicle control, 0.1% dimethylsulfoxide (DMSO). Further validation of the PXR/3A4 system was performed using other inducers of CYP3A4, after which CYP3A4 inducibility by a Wyeth compound, Tanaproget (TNPR), and the synthetic steroid, 3‐ketodesogestrel (3‐KDG), were assessed. At the highest concentrations tested, troleandomycin (TROL) and phenobarbital (PB) induced CYP3A4 by 15–25‐fold, while carbamazepine (CMZ), dexamethasone (DEX), and erythromycin (ERY) produced fold induction of <3. Pregnenolone 16‐α carbonitrile (PCN), a rat‐specific CYP3A inducer, did not induce CYP3A4. TNPR did not induce CYP3A4 at concentrations up to 10 µM while 3‐KDG produced a concentration‐dependent induction, with a fold change of 14 at 20 µM. These data show that the variant PXR2 is not activated by rifampicin. The PXR/3A4 system described can be used to study CYP3A4 induction and provides a robust, specific, and reproducible in vitro system that can be used to assess CYP3A4 inducibility by compounds in the drug development process. Drug Dev. Res. 67:470–475, 2006. © 2006 Wiley‐Liss, Inc.
Transmembrane TNF protects mutant mice against intracellular bacterial infections, chronic inflammation and autoimmunity
Authors: Alexopoulou Lena , Kranidioti Ksanthi , Xanthoulea Sofia , Denis Maria , Kotanidou Anastasia , Douni Eleni , Blackshear Perry J. , Kontoyiannis Dimitris L. , Kollias George 
Published: September 2006

AbstractUsing targeted mutagenesis in mice, we have blocked shedding of endogenous murine TNF by deleting its cleavage site. Mutant mice produce physiologically regulated levels of transmembrane TNF (tmTNF), which suffice to support thymocyte proliferation but cannot substitute for the hepatotoxic activities of wild‐type TNF following LPS/D‐galactosamine challengein vivoand are not sufficient to support secondary lymphoid organ structure and function. Notably, however, tmTNF is capable of exerting anti‐Listerial host defenses while remaining inadequate to mediate arthritogenic functions, as tested in the tristetraprolin‐deficient model of TNF‐dependent arthritis. Most interestingly, in the EAE model of autoimmune demyelination, tmTNF suppresses disease onset and progression and retains the autoimmune suppressive properties of wild‐type TNF. Together, these results indicate that tmTNF preserves a subset of the beneficial activities of TNF while lacking detrimental effects. These data support the hypothesis that selective targeting of soluble TNF may offer several advantages over complete blockade of TNF in the treatment of chronic inflammation and autoimmunity.
Imputation methods to improve inference in SNP association studies
Authors: Dai James Y. , Ruczinski Ingo , LeBlanc Michael , Kooperberg Charles 
Published: September 2006

AbstractMissing single nucleotide polymorphisms (SNPs) are quite common in genetic association studies. Subjects with missing SNPs are often discarded in analyses, which may seriously undermine the inference of SNP‐disease association. In this article, we develop two haplotype‐based imputation approaches and one tree‐based imputation approach for association studies. The emphasis is to evaluate the impact of imputation on parameter estimation, compared to the standard practice of ignoring missing data. Haplotype‐based approaches build on haplotype reconstruction by the expectation‐maximization (EM) algorithm or a weighted EM (WEM) algorithm, depending on whether case‐control status is taken into account. The tree‐based approach uses a Gibbs sampler to iteratively sample from a full conditional distribution, which is obtained from the classification and regression tree (CART) algorithm. We employ a standard multiple imputation procedure to account for the uncertainty of imputation. We apply the methods to simulated data as well as a case‐control study on developmental dyslexia. Our results suggest that imputation generally improves efficiency over the standard practice of ignoring missing data. The tree‐based approach performs comparably well as haplotype‐based approaches, but the former has a computational advantage. The WEM approach yields the smallest bias at a price of increased variance. Genet. Epidemiol. © 2006 Wiley‐Liss, Inc.
The 2‐dimensional rigidity of certain families of graphs
Authors: Jackson Bill , Servatius Brigitte , Servatius Herman 
Published: September 2006

AbstractLaman's characterization of minimally rigid 2‐dimensional generic frameworks gives a matroid structure on the edge set of the underlying graph, as was first pointed out and exploited by L. Lovász and Y. Yemini. Global rigidity has only recently been characterized by a combination of two results due to T. Jordán and the first named author, and R. Connelly, respectively. We use these characterizations to investigate how graph theoretic properties such as transitivity, connectivity and regularity influence (2‐dimensional generic) rigidity and global rigidity and apply some of these results to reveal rigidity properties of random graphs. In particular, we characterize the globally rigid vertex transitive graphs, and show that a random d‐regular graph is asymptotically almost surely globally rigid for all d ≥ 4. © 2006 Wiley Periodicals, Inc. J Graph Theory 54: 154–166, 2007
Effect of the type and concentration of lubricating additives on the antiwear and extreme pressure properties and rolling fatigue life of a four‐ball tribosystem
Authors: Tuszyński Waldemar , Piekoszewski Witold 
Published: September 2006

AbstractTests were performed on two different four‐ball testers. The first was used to determine antiwear (AW) and extreme pressure (EP) properties at sliding friction. The second was used to assess the surface fatigue (pitting) life at rolling movement. Lubricating oils of various chemical compositions were tested. A base mineral oil was blended with two different commercial packages of lubricating additives of AW and EP types. The AW additives contained ZDDP and were blended with the base oil at 0.2 and 3wt %. The EP additives were organic compounds of sulphur and phosphorus, blended with the base oil at 1 and 10wt %. It is shown that AW additives not only improve AW and EP properties but also — at 0.2% — are beneficial for the fatigue life. An increase in the concentration of AW additives leads to an improvement of AW and EP properties but — for one of the packages — reduces the fatigue life. EP additives — at 1% concentration — significantly improve EP properties, and to a lesser extent AW properties. Such a concentration of EP additives has no influence on the fatigue life. An increase in the concentration of EP additives leads to a further improvement of EP and AW properties. However, this is accompanied by a considerable decrease in the fatigue life. By using a scanning electron microscope and energy dispersive spectrometer for analysis of the worn surface, mechanisms of action of various lubricating additives under different friction conditions were identified. Copyright © 2006 John Wiley & Sons, Ltd.
Tetrabenazine for hyperglycemic‐induced hemichorea–hemiballismus
Authors: Sitburana Oraporn , Ondo William G. 
Published: September 2006

AbstractWe reported a 74‐year‐old woman with new‐onset diabetes mellitus who presented with the sudden onset of mild left hemiparesis and marked left hemichorea–hemiballismus. Brain CT scan and MRI showed T1W, T2W, and DWI lesions in the right putamen and caudate, which have been previously reported in cases of hyperglycemic‐induced hemichorea–hemiballismus (HIHH). The patient dramatically responded to tetrabenazine within a day. Subsequent dose reductions lead to a reemergence of symptoms. Tetrabenazine improves a variety of hyperkinetic movement disorders but, to our knowledge, its use has never been reported for HIHH. © 2006 Movement Disorder Society
Fully balanced steady‐state 3D‐spin‐echo (bSSSE) imaging at 3 Tesla
Authors: Krug R. , Han E.T. , Banerjee S. , Majumdar S. 
Published: September 2006

AbstractIn this work a 3D fully balanced steady‐state spin‐echo sequence (bSSSE) was designed and implemented on a 3‐Tesla whole‐body MR scanner. In contrast to previously introduced nonbalanced SSSE (nbSSSE) sequences, bSSSE features fully rewound imaging gradients. Additionally, all phase encodings and the readout prephasing are performed after the refocusing pulse. Its performance was compared with previously used gradient‐echo (GE) and nbSSSE sequences. The signal response of each sequence was simulated by numerical solution of the Bloch equation. All sequences were then optimized based on these simulations for high‐resolution (HR) imaging of tissues with short relaxation times and applied to in vivo HR‐MRI of trabecular bone. bSSSE outperformed nbSSSE sequences in terms of SNR and SNR efficiency. Measurements of structural bone parameters revealed thinner trabeculae and a lower bone/bone‐marrow fraction for the bSSSE sequence compared to the nbSSSE sequence. By applying a parallel imaging technique based on generalized autocalibrating partially parallel acquisition (GRAPPA) with a reduction factor of 2, we were able to maintain a clinically feasible scan time using bSSSE. Comparisons of structural bone parameters revealed a difference of less than 3% for all structural parameters between parallel and conventional imaging. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Early proactive management improves upper urinary tract function and reduces the need for surgery in patients with myelomeningocele
Authors: Kessler Thomas M. , Lackner Jakob , Kiss Gustav , Rehder Peter , Madersbacher Helmut 
Published: September 2006

AbstractAimsTo investigate whether upper urinary tract function and the need for surgery in patients with myelomeningocele depends on the timing of initiating neurourological management.Patients and MethodsOne hundred thirty‐three patients with myelomeningocele were included in our retrospective study. The patients were divided based on age at the initial evaluation into three categories: from day of birth to age 2 (group 1, n = 67), from age 3 to age 10 (group 2, n = 44), and after age 10 (group 3, n = 22). Upper urinary tract function and the need for surgery with the intention to preserve or normalize the upper urinary tract function were compared between the three groups.ResultsMean follow‐up was 11, 10, and 9 years in group 1, 2, and 3, respectively. The upper urinary tract function was normal in 91%, 80%, and 82% at the initial evaluation (P = 0.194) and in 99%, 86%, and 86% at the last follow‐up (P = 0.012) in group 1, 2, and 3, respectively. Following failure of conservative therapy only, the proportions of patients undergoing surgical interventions with the intention to preserve or normalize the upper urinary tract function was significantly (P = 0.0002) different among the three groups: 15%, 34%, and 59%, respectively.ConclusionsEarly proactive management improves upper urinary tract function and reduces the need for surgery in patients with myelomeningocele in the long‐term. Therefore, initiation of proactive neurourological management as early as possible, ideally from the day of birth, is strongly recommended. Neurourol. Urodynam. 25:758–762, 2006. © 2006 Wiley‐Liss, Inc.