bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jostling for Position: Optimizing Linker Location in the Design of Estrogen Receptor‐Targeting PROTACs
Authors: Cyrus Kedra , Wehenkel Marie , Choi Eun‐Young , Lee Hyosung , Swanson Hollie , Kim Kyung‐Bo 
Published: May 2010

AbstractEstrogen receptor‐α (ER) antagonists have been widely used for breast cancer therapy. Despite initial responsiveness, hormone‐sensitive ER‐positive cancer cells eventually develop resistance to ER antagonists. It has been shown that in most of these resistant tumor cells, the ER is expressed and continues to regulate tumor growth. Recent studies indicate that tamoxifen initially acts as an antagonist, but later functions as an ER agonist, promoting tumor growth. This suggests that targeted ER degradation may provide an effective therapeutic approach for breast cancers, even those that are resistant to conventional therapies. With this in mind, we previously demonstrated that proteolysis targeting chimeras (PROTACs) effectively induce degradation of the ER as a proof‐of‐concept experiment. Herein we further refined the PROTAC approach to target the ER for degradation. The ER‐targeting PROTACs are composed of an estradiol on one end and a hypoxia‐inducing factor 1α (HIF‐1α)‐derived synthetic pentapeptide on the other. The pentapeptide is recognized by an E3 ubiquitin ligase called the von Hippel Lindau tumor suppressor protein (pVHL), thereby recruiting the ER to this E3 ligase for ubiquitination and degradation. Specifically, the pentapeptide is attached at three different locations on estradiol to generate three different PROTAC types. With the pentapeptide linked through the C7α position of estradiol, the resulting PROTAC shows the most effective ER degradation and highest affinity for the estrogen receptor. This result provides an opportunity to develop a novel type of ER antagonist that may overcome the resistance of breast tumors to conventional drugs such as tamoxifen and fulvestrant (Faslodex).
Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activity
Authors: Tei Lorenzo , Mazooz Galit , Shellef Yael , Avni Reut , Vandoorne Katrien , Barge Alessandro , Kalchenko Vyacheslav , Dewhirst Mark W. , Chaabane Linda , Miragoli Luigi , Longo Dario , Neeman Michal , Aime Silvio 
Published: May 2010

AbstractTransglutaminases, including factor XIII and tissue transglutaminase, participate in multiple extracellular processes associated with remodeling of the extracellular matrix during wound repair, blood clotting, tumor progression and fibrosis of ischemic injuries. The aim of this work was to evaluate a novel substrate analog for transglutaminase optimized by molecular modeling calculations (DCCP16), which can serve for molecular imaging of transglutaminase activity by magnetic resonance imaging and by near‐infrared imaging. Experimental data showed covalent binding of Gd–DCCP16 and DCCP16‐IRIS Blue to human clots, to basement membrane components and to casein in purified systems as well as in three‐dimensional multicellular spheroids. In vivo, DCCP16 showed enhancement with a prolonged retention in clots and tumors, demonstrating the ability to detect both factor XIII and tissue transglutaminase mediated covalent binding of the contrast material. Copyright © 2010 John Wiley & Sons, Ltd.
Clonal origin of multifocal hepatocellular carcinoma
Authors: Hodges Kurt B. , Cummings Oscar W. , Saxena Romil , Wang Mingsheng , Zhang Shaobo , Lopez‐Beltran Antonio , Montironi Rodolfo , Nour Hammam , Cheng Liang 
Published: May 2010

AbstractBACKGROUND:Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain.METHODS:The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin‐fixed, paraffin‐embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations.RESULTS:Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors.CONCLUSIONS:The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin. Cancer 2010. © 2010 American Cancer Society.
A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5‐fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver
Authors: Tsimberidou Apostolia M. , Fu Siqing , Ng Chaan , Lim Jo Ann , Wen Sijin , Hong David , Wheler Jennifer , Bedikian Agop Y. , Eng Cathy , Wallace Michael , Camacho Luis H. , Kurzrock Razelle 
Published: May 2010

AbstractBACKGROUND:Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases.METHODS:Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m2 to 175 mg/m2 and intra‐arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m2 intravenously (iv) and 5‐fluorouracil 300 mg/m2 bolus plus 600 mg/m2 iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3). A conventional “3 + 3” design was used.RESULTS:Fifty‐seven patients were treated, including 30 women and 27 men. The median age was 57 years, and the patients had received a median of 3 prior therapies (range, 1‐7 prior therapies). The most common cancer was colorectal (n = 29). Overall, 204 cycles were administered (median per patient, 2 cycles; range, 1‐17 cycles). The maximum tolerated dose (MTD) of HAI oxaliplatin was 140 mg/m2. Dose‐limiting toxicities were grade 4 thrombocytopenia (n = 1) and grade 4 hypokalemia (n = 1) at 150 mg/m2 (n = 5). Thirty‐three patients (58%) had no toxicity greater than grade 1. The most common toxicities were thrombocytopenia (n = 19), fatigue (n = 15), nausea/vomiting (n = 6), constipation (n = 6), and diarrhea (n = 4). Of 55 patients who were evaluable for response (according to Response Evaluation Criteria in Solid Tumors), 4 patients (7%) had a partial response (PR), and 32 patients (58%) had stable disease (SD), including 15 patients (48%) who had SD for ≥4 months. Of 28 patients with colorectal cancer, 3 patients (11%) had a PR, and 9 patients (32%) had SD for ≥4 months.CONCLUSIONS:HAI oxaliplatin combined with systemic 5‐fluorouracil, leucovorin, and bevacizumab had antitumor activity in patients with advanced cancer and liver metastases, and the current results indicated that this combination warrants further study. Cancer 2010. © 2010 American Cancer Society.
Predictors and outcome of acute kidney injury in patients with acute myelogenous leukemia or high‐risk myelodysplastic syndrome
Authors: Lahoti Amit , Kantarjian Hagop , Salahudeen Abdulla K. , Ravandi Farhad , Cortes Jorge E. , Faderl Stefan , O'Brien Susan , Wierda William , Mattiuzzi Gloria N. 
Published: May 2010

AbstractBACKGROUND:Acute kidney injury (AKIis a common complication in the treatment of patients with acute myelogenous leukemia (AML) or high‐risk myelodysplastic syndrome (HR‐MDS), but, to the authors' knowledge, its clinical relevance has not been detailed to date. The objective of the current study was to identify the incidence, predictors, and outcome for AKI in patients with AML and HR‐MDS.METHODS:Data were analyzed from 537 patients with AML or HR‐MDS undergoing induction chemotherapy from 1999 to 2007. Predictors for AKI were identified by logistic regression. Eight‐week mortality of patients was estimated by the Kaplan‐Meier method stratified by the RIFLE criteria, a novel multilevel classification system for AKI based on the percent rise in serum creatinine from baseline (Risk, >50%; Injury, >100%; and Failure, >200% or requiring dialysis).RESULTS:A total of 187 patients (36%) developed AKI. Significant independent risk factors for AKI included the following: age ≥55 years (odds ratio [OR], 1.8), mechanical ventilation (OR, 16), use of vancomycin (OR, 2.3), diuretics (OR, 3.0), amphotericin B lipid formulation (OR, 2.7), vasopressors (OR, 4.9), leukopenia (OR, 1.9), hypoalbuminemia (OR, 1.4), and use of non‐fludarabine–based chemotherapy (OR, 2.7). The 8‐week mortality rates were 3.8%, 13.6%, 19.6%, and 61.7% for the non‐RIFLE, Risk, Injury, and Failure categories, respectively. Patients requiring dialysis (8%) had a median survival of 33 days. Survival of patients who achieved complete remission was favorable, regardless of degree of AKI.CONCLUSIONS:The RIFLE classification for AKI appears to have prognostic utility in predicting mortality in patients with AML or HR‐MDS. Relatively mild elevations in creatinine are associated with higher mortality. Strategies to avoid nephrotoxic drugs or fluid overload may be of benefit. Cancer 2010. © 2010 American Cancer Society.
Telecytopathology for immediate evaluation of fine‐needle aspiration specimens
Authors: Alsharif Mariam , Carlo‐Demovich Jamie , Massey Caroline , Madory James E. , Lewin David , Medina Ana‐Maria , Recavarren Rosemary , Houser Patricia M. , Yang Jack 
Published: May 2010

AbstractBACKGROUND:On‐site evaluation of fine‐needle aspiration (FNA) specimens by a pathologist is essential to obtain adequate samples and provide a preliminary diagnosis. Distance from the laboratory can make this difficult. The authors present their experience with on‐site evaluation using telecytopathology.METHODS:Dynamic images of cytology smears were captured and processed with a Nikon digital camera system for microscopy and transmitted via Ethernet. A pathologist accessed the real‐time images on a computer and interpreted them while communicating with on‐site operators over the telephone. Sample adequacy and accuracy of preliminary diagnosis were compared with those obtained by regular on‐site evaluation.RESULTS:A total of 429 telecytopathology cases and 363 conventional on‐site cases were compared. Specimens were mainly from the pancreas, gastrointestinal tract, liver, and lymph nodes. Adequacy rate was 94.0% for telecytopathology and 97.7% for conventional cases. Preliminary diagnoses of unsatisfactory, adequate (defer), negative/benign, atypical, neoplasm, suspicious, and positive for malignancy were 6.3%, 13.5%, 14.9%, 17.9%, 7.2%, 8.6%, and 31.5% for telecytopathology and 3.9%, 30.6%, 21.5%, 9.6%, 5.0%, 5.2%, and 24.2% for conventional cases. Preliminary and final diagnoses were discrepant in 7 (1.8%) of 371 telecytopathology cases, and in 8 (3.1%) of 252 conventional cases. Difficulty was encountered in some cases in distinguishing pancreatic endocrine neoplasm from lymphoid proliferations, and low grade pancreatic tumors from chronic pancreatitis via telecytopathology.CONCLUSIONS:On‐site evaluation of FNA specimens via telecytopathology assures sample adequacy and accurate preliminary diagnosis compared with the conventional method. It allows pathologists to use their time more efficiently and makes on‐site evaluations at remote locations possible. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Gold Nanoelectrode Arrays and their Evaluation by Impedance Spectroscopy and Cyclic Voltammetry
Authors: Lantiat David , Vivier Vincent , Laberty‐Robert Christel , Grosso David , Sanchez Clément 
Published: May 2010

AbstractA sol–gel strategy is developed to fabricate highly regular Au nanoelectrode arrays (NEAs) consisting of a nanoperforated ultrathin membrane of ZrO2, which exhibits a well‐ordered array of pores (65±5) nm in diameter with a mean center‐to‐center distance of (110±10) nm, on a polycrystalline gold surface. The structural properties are investigated by field‐emission scanning electron microscopy (FE‐SEM), while grazing incidence small‐angle X‐ray scattering (GISAXS) is used to assess the thickness homogeneity and the period of the array of electrodes. In addition, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) are carried out to describe quantitatively the accessibility, electrochemical behavior, and diffusion processes of the gold NEA. A model applying parameters obtained from FE‐SEM, CV, and EIS analyses is proposed to simulate the experimental results. A fairly good agreement between the experimental and the simulated data is obtained, thus allowing the deconvolution of the different diffusion regimes at the NEA.
Self–other disagreement in personality assessment: significance and prognostic value
Authors: Mosterman R. M. , Hendriks A. A. Jolijn 
Published: May 2010

AbstractThe feasibility of the use of multiple informant reports in clinical practice was examined in a sample of 105 psychiatric outpatients who provided self‐ratings and (2–3) informants' reports on the Five Factor Personality Inventory. The response rate was 97%. The patients assessed themselves as less extraverted and more emotionally stable than their proxies did. In addition, the significance of self–other disagreement was investigated. Our first hypothesis, stating that self–other disagreement would correlate with (personality) pathology, was confirmed: self–other disagreement predominantly occurred in introverted, shy, hostile and depressed persons who tended to have more personality problems and co‐morbidity. We found no support for our second hypothesis, stating that self–other disagreement would predict a diminished therapy effect. An important finding, however, was that self–other disagreement proved to be a strong predictor of dropout. Furthermore, a decrease in depression, hostility and shyness was positively correlated with a decrease in self–other disagreement. Copyright © 2010 John Wiley & Sons, Ltd.Key Practitioner Message:• The use of multiple informants in personality assessment is a feasible enterprise in clinical practice.• Self–other disagreement in personality assessment predominantly occurs in introverted, shy, hostile and depressed patients.• Self–other disagreement is found more often in patients with personality problems and co‐morbidity.• Self–other disagreement, in particular on conscientiousness, proves to be a strong predictor of dropout.
A High Heat of Adsorption for Hydrogen in Magnesium Formate
Authors: Schmitz Barbara , Krkljus Ivana , Leung Emi , Höffken Hans Wolfgang , Müller Ulrich , Hirscher Michael 
Published: May 2010

AbstractThe hydrogen adsorption and desorption properties of a microporous metal–organic framework, magnesium formate, are investigated. The material has channel‐like pores of approximately 3.4 Å diameter. The pore size is below the kinetic diameter of nitrogen and causes a breakdown of the linear relationship between maximum hydrogen uptake and specific surface area measured by nitrogen adsorption. From the experimental isotherms the isosteric heat of adsorption for hydrogen is calculated with very high accuracy over a wide range of surface coverage, up to 80 %. The isosteric heat of adsorption is 6.5–7 kJ mol−1 which is one of the highest values ever observed over the whole range of surface coverage.
Imidate–Phosphanes as Highly Versatile N,P Ligands and Their Application in Palladium‐Catalyzed Asymmetric Allylic Alkylation Reactions
Authors: Noël Timothy , Bert Katrien , Van der Eycken Erik , Van der Eycken Johan 
Published: May 2010

AbstractChiral imidate–phosphanes were developed as a new type of N,P ligands. These ligands are easily accessible through a one‐step procedure starting from a commercially available chiral aminophosphane and an imidate precursor. Excellent performance of the catalyst system was observed with various carbon nucleophiles in the Pd0‐catalyzed asymmetric allylic alkylation (up to 99 % yield and >99 % ee). Moreover, good to excellent enantioselectivities could also be obtained in the allylic alkylation of more difficult linear unhindered substrates and cyclic substrates, demonstrating that this new catalyst system has a broad substrate scope.
The Ribosome Comes Alive
Authors: Frank Joachim 
Published: May 2010

AbstractAbstract: This essay is a reflection on the ways the X‐ray structures of the ribosome are helping in the interpretation of cryogenic electron microscopy (cryo‐EM) density maps showing the translating ribosome in motion. Through advances in classification methods, cryo‐EM and single‐particle reconstruction methods have recently evolved to the point where they can yield an array of structures from a single sample (“story in a sample”), providing snapshots of an entire subprocess of translation, such as translocation or decoding.
Neuroserpin regulates the density of dendritic protrusions and dendritic spine shape in cultured hippocampal neurons
Authors: Borges Victor M. , Lee Tet W. , Christie David L. , Birch Nigel P. 
Published: May 2010

AbstractNeuroserpin is a member of the serpin superfamily that is expressed principally in neurons of the central and peripheral nervous systems. Neuroserpin's spatial‐temporal expression during development and in the adult brain suggests possible roles in synaptogenesis and synaptic plasticity. This is supported by behavioral changes in transgenic mice overexpressing neuroserpin. We have used an embryonic rat primary hippocampal neuron culture model to investigate whether neuroserpin can regulate elements of synaptic morphology that may be involved in these changes in cognitive function. Neuroserpin localized to axonal and dendritic compartments in cultured neurons and accumulated in synapsin‐positive presynaptic terminals. Increased expression of neuroserpin resulted in an increase in the density of dendritic protrusions and alterations in dendritic spine shape. Our results identify neuroserpin as a new regulator of structural plasticity and suggest a cellular mechanism that may contribute to neuroserpin's effects on cognition. © 2010 Wiley‐Liss, Inc.
Gas chromatography‐mass spectrometric method for the screening and quantification of illicit drugs and their metabolites in human urine using solid‐phase extraction and trimethylsilyl derivatization
Authors: Cheong Jae Chul , Suh Sung Ill , Jun Ko Beom , Kim Jin Young , In Moon Kyo , Cheong Won Jo 
Published: May 2010

AbstractA simple and rapid GC‐MS method has been developed for the screening and quantification of many illicit drugs and their metabolites in human urine by using automatic SPE and trimethylsilylation. Sixty illicit drugs, including parent drugs and their metabolites that are possibly abused in Korea, can be monitored by this method. Among them, 24 popularly abused illicit drugs were selected for quantification. Very delicate optimizations were carried out in SPE, trimethylsilylation derivatization, and GC/MS to enable such remarkable achievements. Trimethylsilylated analytes were well separated within 21 min by GC‐MS. In the validation results, the LOD of all the analytes were in the range of 2–75 ng/mL. The LOQ of the quantified analytes were in the range of 5–98 ng/mL. The linearity (r2) of the quantified analytes ranged 0.990–1.000 in each concentration range between 10 and 1000 ng/mL. The mean recoveries ranged from 62 to 126% at three different concentrations of each analyte. The inter‐day and inter‐person accuracies were within −13.3∼14.9%, and −10.1∼13.0%, respectively, and the inter‐day and inter‐person precisions were less than 12.9%. The method was reliable and efficient for the screening and quantification of abused illicit drugs in routine urine analysis.
Determination of metoprolol in human plasma and urine by high‐performance liquid chromatography with fluorescence detection
Authors: Yilmaz Bilal , Asci Ali , Arslan Sakir 
Published: May 2010

AbstractA simple, specific and sensitive HPLC method has been developed for the determination of metoprolol in human plasma and urine. Separation of metoprolol and atenolol (internal standard) was achieved on an Ace C18 column (5 μm, 250 mm×4.6 mm id) using fluorescence detection with λex=276 nm and λem=296 nm. The mobile phase consists of methanol–water (50:50, v/v) containing 0.1% TFA. The analysis was performed in less than 10 min with a flow rate of 1 mL/min. The assay was linear over the concentration range of 3 – 200 and 5 – 300 ng/mL for plasma and urine, respectively. The LOD were 1.0 and 1.5 ng/mL for plasma and urine, respectively. The LOQ were 3.0 and 5.0 ng/mL for plasma and urine, respectively. The extraction recoveries were found to be 95.6 ± 1.53 and 96.4 ± 1.75% for plasma and urine, respectively. Also, the method was successfully applied to three patients with hypertension who had been given an oral tablet of 100 mg metoprolol.
Predicting the risk of severe bacterial infection in children with chemotherapy‐induced febrile neutropenia
Authors: Macher Emilie , Dubos François , Garnier Nathalie , Delebarre Mathilde , De Berranger Eva , Thebaud Estelle , Mazingue Françoise , Leblond Pierre , Martinot Alain 
Published: May 2010

AbstractBackgroundThe prognosis of febrile neutropenia (FN) in childhood cancer has been considerably improved by the intensification of treatment, including systematic hospitalization and broad‐spectrum antibiotics. As only few children present with a severe bacterial infection (SBI), clinical decision rules have been developed to distinguish those at risk for SBI. The aim of this study was to evaluate the reproducibility of six clinical decision rules proposed in the literature and to compare their performance.MethodsThis retrospective two‐center cohort study included all episodes of chemotherapy‐induced FN in children admitted between January 2005 and December 2006. Each rule was applied to our patients. Their sensitivity (Se) and specificity (Sp) were calculated and compared with the authors' results, to assess reproducibility. The most predictive rule was defined in advance as that yielding 100% Se, the highest Sp, and the greatest simplicity for bedside application.ResultsThree hundred seventy‐seven episodes of FN in 167 patients were collected; 64 episodes were associated with SBI, including 36 with bacteremia. Four of the six rules were reproducible, but none were able to be validated. The most predictive rule for bacteremia had 96% Se (95% confidence interval (CI): 79–99%) and 25% Sp (95% CI: 19–33%), and the most predictive rule for SBI had 95% Se (95% CI: 87–98%), but no power of discrimination (Sp = 5%, 95% CI: 3–8%).ConclusionThis study emphasizes the difficulty in identifying standardized decision rules in the management of a condition with numerous clinical variables like FN. Pediatr Blood Cancer. 2010;55:662–667. © 2010 Wiley‐Liss, Inc.