bluuebunny/crossref_metadata_2025_split huggingface dataset:
LICRED: A Versatile Drop‐In Vector for Rapid Generation of Redox‐Self‐Sufficient Cytochrome P450s
Authors: Sabbadin Federico , Hyde Ralph , Robin Aelig , Hilgarth Eva‐Maria , Delenne Marie , Flitsch Sabine , Turner Nicholas , Grogan Gideon , Bruce Neil C. 
Published: April 2010

AbstractCytochromes P450 (P450s) are a family of haem‐containing oxidases with considerable potential as tools for industrial biocatalysis. Organismal genomes are revealing thousands of gene sequences that encode P450s of as yet unknown function, the exploitation of which will require high‐throughput tools for their isolation and characterisation. In this report, a ligationindependent cloning vector “LICRED” is described that enables the high‐throughput generation of libraries of redox‐self‐sufficient P450s by fusing a range of P450 haem domains to the reductase of P450RhF (RhF‐Red) in a robust and generically applicable way. Cloning and expression of fusions of RhF‐Red with the haem domains of P450cam and P450‐XplA resulted in soluble, active, redox‐self‐sufficient, chimeric enzymes. In vitro studies also revealed that electron transfer from NADPH to haem was primarily intramolecular. The general applicability of the LICRED platform was then demonstrated through the creation of a library of RhF‐Red fusion constructs by using the diverse complement of P450 haem domains identified in the genome of Nocardia farcinica. The resultant fusion‐protein library was then screened against a panel of substrates; this revealed chimeric enzymes competent for the hydroxylation of testosterone and methyltestosterone, and the dealkylation of 7‐ethoxycoumarin.
Breast cancer risk estimation with artificial neural networks revisited
Authors: Ayer Turgay , Alagoz Oguzhan , Chhatwal Jagpreet , Shavlik Jude W. , Kahn Charles E. , Burnside Elizabeth S. 
Published: April 2010

AbstractBACKGROUND:Discriminating malignant breast lesions from benign ones and accurately predicting the risk of breast cancer for individual patients are crucial to successful clinical decisions. In the past, several artificial neural network (ANN) models have been developed for breast cancer‐risk prediction. All studies have reported discrimination performance, but not one has assessed calibration, which is an equivalently important measure for accurate risk prediction. In this study, the authors have evaluated whether an artificial neural network (ANN) trained on a large prospectively collected dataset of consecutive mammography findings can discriminate between benign and malignant disease and accurately predict the probability of breast cancer for individual patients.METHODS:Our dataset consisted of 62,219 consecutively collected mammography findings matched with the Wisconsin State Cancer Reporting System. The authors built a 3‐layer feedforward ANN with 1000 hidden‐layer nodes. The authors trained and tested their ANN by using 10‐fold cross‐validation to predict the risk of breast cancer. The authors used area the under the receiver‐operating characteristic curve (AUC), sensitivity, and specificity to evaluate discriminative performance of the radiologists and their ANN. The authors assessed the accuracy of risk prediction (ie, calibration) of their ANN by using the Hosmer‐Lemeshow (H‐L) goodness‐of‐fit test.RESULTS:Their ANN demonstrated superior discrimination (AUC, 0.965) compared with the radiologists (AUC, 0.939;P< .001). The authors' ANN was also well calibrated as shown by an H‐L goodness of fitP‐value of .13.CONCLUSIONS:The authors' ANN can effectively discriminate malignant abnormalities from benign ones and accurately predict the risk of breast cancer for individual abnormalities. Cancer 2010. © 2010 American Cancer Society.
A phase 3 randomized, placebo‐controlled, double‐blind, clinical trial of the effect of modafinil on cancer‐related fatigue among 631 patients receiving chemotherapy
Authors: Jean‐Pierre Pascal , Morrow Gary R. , Roscoe Joseph A. , Heckler Charles , Mohile Supriya , Janelsins Michelle , Peppone Luke , Hemstad Amy , Esparaz Benjamin T. , Hopkins Judith O. 
Published: April 2010

AbstractBACKGROUND:Cancer‐related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70% to 100% of cancer patients during and after treatment. The authors examined the effect of 200 mg of modafinil daily on the severity of cancer‐related fatigue.METHODS:The authors conducted a multicenter, randomized, double‐blind, placebo‐controlled, phase 3, clinical trial to examine the effect of modafinil on patient‐reported fatigue in cancer patients undergoing chemotherapy. A sample of 877 cancer patients beginning chemotherapy at 23 geographically separate University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) affiliates were assessed for fatigue. Patients who reported fatigue (N = 867) were randomly assigned to receive either 200 mg of oral modafinil (Provigil) daily or a placebo. Treatment began on Day 5 of Cycle 2 and ended after Day 7 of Cycle 4. Fatigue and depression were assessed during Cycles 2 to 4 by using psychometrically valid measures. Group differences (treatment vs control) in the worst level of fatigue during the previous week at Cycle 4 were examined by using an analysis of covariance (ANCOVA) adjusting for baseline fatigue (Cycle 2).RESULTS:There were 631 patients (315 modafinil, 316 placebo) who provided evaluable data. ANCOVA showed a significant interaction between treatment condition and baseline fatigue (P = .017), where patients with severe baseline fatigue (n = 458) benefited from modafinil, whereas patients with mild or moderate fatigue did not. Modafinil had no statistically significant effect on depression (P > .05).CONCLUSIONS:Modafinil may be useful in controlling cancer‐related fatigue in patients who present with severe fatigue but is not useful in patients with mild or moderate fatigue. Cancer 2010. © 2010 American Cancer Society.
Protein kinase gene expression profiling and in vitro functional experiments identify novel potential therapeutic targets in adult acute lymphoblastic leukemia
Authors: Messina Monica , Chiaretti Sabina , Tavolaro Simona , Peragine Nadia , Vitale Antonella , Elia Loredana , Sica Simona , Levis Alessandro , Guarini Anna , Foà Robin 
Published: April 2010

AbstractBACKGROUND:Despite recent improvements in the treatment of acute lymphoblastic leukemia (ALL), adult patients still have an overall poor outcome. The future of ALL management relies on the introduction of novel targeted therapies. The authors sought to assess if protein kinases (PKs), frequently deregulated in cancer, show an altered expression pattern and can be considered as suitable therapeutic targets in adult ALL.METHODS:The authors studied the PK gene expression profile by oligonucleotide arrays in 133 adult ALL samples at the onset of the disease and subsequently performed in vitro experiments to evaluate the sensitivity to first‐ and second‐generation PK inhibitors of a set of ALL cell lines, as well as of primary ALL cells.RESULTS:The study documents a distinctive PK signature for different adult ALL subgroups; the PKs identified include several tyrosine kinase (TK) genes, especially in E2A/PBX+ B‐lineage ALL (B‐ALL), B‐ALL without known molecular abnormalities, and T‐lineage ALL. Consistently, cell lines and primary samples belonging to these groups proved susceptible to TK inhibitors.CONCLUSIONS:These results indicate that second‐generation TK inhibitors may be effective in ALL subsets other than BCR/ABL+ B‐ALL and provide the rationale for testing the impact of the newly developed TK inhibitors in the management of adult ALL patients. Cancer 2010. © 2010 American Cancer Society.
Management of adult patients with acute lymphoblastic leukemia in first complete remission
Authors: Ram Ron , Gafter‐Gvili Anat , Vidal Liat , Paul Mical , Ben‐Bassat Isaac , Shpilberg Ofer , Raanani Pia 
Published: April 2010

AbstractBACKGROUND:The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission.METHODS:The authors conducted a systematic review and meta‐analysis of randomized trials, including patients with standard‐risk (SR) All and high‐risk (HR) ALL who received first postremission therapy. Outcomes assessed were all‐cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled.RESULTS:Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8‐0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68‐0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76‐1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37‐6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33‐0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms.CONCLUSIONS:Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL. Cancer 2010. © 2010 American Cancer Society.
Number of lymph nodes identified at axillary dissection
Authors: Boughey Judy C. , Donohue John H. , Jakub James W. , Lohse Christine M. , Degnim Amy C. 
Published: April 2010

AbstractBACKGROUND:Several reports have shown a significantly lower number of axillary lymph nodes (AxLNs) found at axillary lymph node dissection (ALND) after neoadjuvant chemotherapy. The objective of the current study was to investigate the factors affecting the number of AxLNs identified at ALND.METHODS:Medical records of patients seen at the study institution, a tertiary center, from 2004 to 2007 who underwent ALND for breast cancer were reviewed.RESULTS:Among the 698 patients who met study criteria, the mean number of AxLNs resected was 20.4. There were 649 (93%) patients with at least 10 AxLNs recovered. Seventy‐one (10%) patients received neoadjuvant chemotherapy and 627 (90%) underwent surgical resection first. The mean number of AxLNs in the patients treated with neoadjuvant chemotherapy was 21.9 (range, 4‐56 AxLNs) compared with 20.2 (range, 5‐65 AxLNs) in the group treated with surgical resection first (P = .13). The number of patients with <10 AxLNs found at ALND was 44 of 627 (7.0%) in the surgical resection first group and 5 of 71 (7.0%) in the neoadjuvant chemotherapy group (P = 1.0). The mean number of AxLNs was higher in the 599 (86%) ALNDs performed at the study center compared with the 99 cases from outside institutions (21.2 vs 15.2 AxLNs; P <.001). Among the cases performed at the study institution, 367 (61%) were performed by surgeons with oncologic training and 232 (39%) were not. Surgical oncologists recovered an average of 23 AxLNs, which was significantly higher than the 18.4 resected by the remaining surgeons (P <.001).CONCLUSIONS:The number of AxLNs recovered at ALND does not appear to be affected by neoadjuvant chemotherapy. Surgeons with oncologic training appear to retrieve more AxLNs. Cancer 2010. © 2010 American Cancer Society.
Ferromagnetic Tetranuclear and Pentanuclear Copper(II) Complexes Constructed from Cu2 Blocks
Authors: Fondo Matilde , Ocampo Noelia , García‐Deibe Ana M. , Sanmartín Jesús 
Published: April 2010

AbstractThe new complexes [(Cu2L1)2(p‐OOC‐C6H4‐COO)]·7H2O (1·7H2O), [(Cu2L2)2(p‐OOC‐C6H4‐COO)]·2H2O (2·2H2O), [(Cu2L1)2Cu(O2C‐CH2‐CO2)2]·9H2O (3·9H2O) and [(Cu2L2)2(OOC‐CH2‐COO)]·5.5H2O (4·5.5H2O) have been obtained by interaction of either [(Cu2L1)2(CO3)]·8H2O or [Cu2L2(OH)]·1.125H2O with the corresponding dicarboxylic acid. Recrystallisation of 1·7H2O in methanol/ethanol yields single crystals of 1·2EtOH·2H2O, whereas recrystallisation of 3·9H2O and 4·5.5H2O in methanol allows crystals of 3·9H2O and 4·5.5H2O·1.25MeOH, respectively, to be isolated, which were suitable for X‐ray diffraction studies. The X‐ray characterisation of 1·2EtOH·2H2O, 3·9H2O and 4·5.5H2O·1.25MeOH shows that both the Cu4 and Cu5 clusters can be understood as being built from two dinuclear [Cu2Lx]+ (x = 1 or 2) blocks with different connectors. Magnetic analyses of 1·7H2O, 3·9H2O and 4·5.5H2O reveal that the three complexes are ferromagnetic, and the magnetic exchange mediated by the carboxylate ligands is weak.
A Lipophilic, Fluorine‐Free, Thermostable, Inexpensive, S4‐Symmetric, Highly Soluble, Weakly Coordinating, Protolabile Aluminate (Eur. J. Inorg. Chem. 13/2010)
Authors: Straub Bernd F. , Wrede Michael , Schmid Karin , Rominger Frank 
Published: April 2010

AbstractThe cover picture shows a Madagascar day gecko (Phelsuma madagascariensis grandis) in a coconut with a locust on top. Gecko toes hold on to slithery and vertical surfaces due to van der Waals forces, which are also relevant for the lipophilic altebate anion (left space‐filling model). Its sterically demanding substituents shield the nucleophilic center, making diethyl ether a better hydrogen bond acceptor in comparison (middle X‐ray structure). The high symmetry and the positive (blue) partial charges on the molecular surface are reflected in the right fractal‐like model. Details are discussed in the Short Communication by B. F. Straub et al. on p. 1907 ff. Photograph by Michael Wrede, artwork by Bernd F. Straub.
Solvent‐Free Olefin Hydroformylation Using Hemispherical Diphosphites
Authors: Monnereau Laure , Sémeril David , Matt Dominique 
Published: April 2010

AbstractWith rhodium complexes containing hemispherical diphosphite ligands derived from a calixarene skeleton, olefins can be hydroformylated efficiently undersolvent‐freeconditions. For example, in the hydroformylation of 1‐octene (T= 80 °C,P= 20 bar, olefin:Rh = 200 000:1) one of the catalysts investigated resulted in a TOF of 17290 mol (converted 1‐octene)·mol(Rh)–1·h–1, the regioselectivity towards the linear aldehyde reaching then 97.9 %.
Enantiomeric separation of cis‐bifenthrin by CD‐MEKC: Quantitative analysis in a commercial insecticide formulation
Authors: Pérez‐Fernández Virginia , García Maria Ángeles , Marina Maria Luisa 
Published: April 2010

AbstractThe first CE method enabling the enantiomeric separation of the synthetic pyrethroid cis‐bifenthrin (BF) was developed in this work. CD‐MEKC was the CE mode employed for this purpose. The influence of several experimental parameters such as temperature, voltage, type and concentration of surfactant (chiral and achiral) and CD was investigated. The use of the bile salt sodium cholate at a concentration of 100 mM in the presence of 20 mM heptakis (2,3,6‐tri‐O‐methyl)‐β‐CD enabled the separation of cis‐BF enantiomers in less than 10 min and with a resolution of 2.8. The analytical characteristics of the developed methodology were evaluated allowing its application to the quantitation of cis‐BF in a polyvalent commercial insecticide formulation.
The “Task B problem” and other considerations in developmental functional neuroimaging
Authors: Church Jessica A. , Petersen Steven E. , Schlaggar Bradley L. 
Published: April 2010

AbstractFunctional neuroimaging provides a remarkable tool to allow us to study cognition across the lifespan and in special populations in a safe way. However, experimenters face a number of methodological issues, and these issues are particularly pertinent when imaging children. This brief article discusses assessing task performance, strategies for dealing with group performance differences, controlling for movement, statistical power, proper atlas registration, and data analysis strategies. In addition, there will be discussion of two other topics that have important implications for interpreting fMRI data: the question of whether functional neuroanatomical differences between adults and children are the consequence of putative developmental neurovascular differences, and the issue of interpreting negative blood oxygenation‐level dependent (BOLD) signal change. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Endoscopic carbon dioxide laser diverticulostomy versus endoscopic staple‐assisted diverticulostomy to treat Zenker's diverticulum
Authors: Verhaegen Veronique J. O. , Feuth Ton , van den Hoogen Frank J. A. , Marres Henri A. M. , Takes Robert P. 
Published: April 2010

AbstractBackgroundThe 2 most frequently used endoscopic methods to treat Zenker's diverticulum are staple‐assisted and CO2 laser esophagodiverticulostomy.MethodsThe study centered around a retrospective evaluation of 107 patients with Zenker's diverticulum who were treated endoscopically by CO2 laser (n = 72) or staple‐assisted diverticulostomy (n = 35).ResultsPatients in the staple‐assisted group had a shorter duration of postoperative hospitalization, attributed to earlier oral intake, than patients in the CO2 laser group. There were no serious postoperative complications in either group. Postoperative fever and emphysema in the neck or mediastinum occurred more frequently in the CO2 laser group, but this did not lead to any complications. Most patients reported partial or complete relief of their symptoms and there was no significant difference in the number of reoperations between the 2 treatment groups.ConclusionsZenker's diverticulum was treated safely and effectively by the 2 endoscopic techniques, but the staple‐assisted method seemed to be the most favorable. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Perivascular expression of CXCL9 and CXCL12 in primary central nervous system lymphoma: T‐cell infiltration and positioning of malignant B cells
Authors: Venetz Daniel , Ponzoni Maurilio , Schiraldi Milena , Ferreri Andrés J.M. , Bertoni Francesco , Doglioni Claudio , Uguccioni Mariagrazia 
Published: April 2010

AbstractPrimary central nervous system lymphomas (PCNSL) are aggressive malignancies confined to the CNS, mostly of diffuse large B‐cell histotype. Despite improved understanding of the malignant B cells, little is known on the tumor microenvironment and on the response of the adaptive immunity against PCNSL. We investigated the phenotype of tumor infiltrating lymphocytes (TILs), and the expression of chemokines that could affect malignant B cells and trafficking of TILs. TILs and chemokine expression were evaluated by immunohistochemistry and in situ hybridization. Furthermore, we performed in vitro migration assays to analyze the migratory capacity of lymphocytes and malignant B cells toward chemokines and chemokine heterocomplexes. We show in 22 cases of PCNSL from immunocompetent patients that CD8+ T cells represent the majority of TILs in the tumor mass. They tend to accumulate in perivascular areas, show Granzyme B expression and proliferate in situ. Their localization and density correlates with the expression of the inflammatory chemokine CXCL9, which is transcribed and translated by perivascular macrophages and pericytes in the perivascular microenvironment. Moreover, CXCL9 and CXCL12 are coexpressed on the tumor vasculature and form heterocomplexes. In the presence of CXCL9, CXCL12‐induced migration is enhanced not only on CXCR4+/CXCR3+/CD8+ T cells but also on CXCR4+/CXCR3− malignant B cells. These findings indicate the presence of a strong chemoattractant stimulus in the perivascular microenvironment, which might serve as regulator for the recruitment of TILs and for the angiocentric positioning of malignant B cells in the perivascular cuff.
An alternative splicing isoform of eukaryotic initiation factor 4H promotes tumorigenesis in vivo and is a potential therapeutic target for human cancer
Authors: Wu Di , Matsushita Kazuyuki , Matsubara Hisahiro , Nomura Fumio , Tomonaga Takeshi 
Published: April 2010

AbstractDeregulation of protein synthesis plays a critical role in cell transformation. Several translation initiation factors (eIFs) have been implicated in malignant transformation; thus, suppression of eIFs could be a potential cancer therapy if cancer cells are selectively killed without damaging healthy cells. One of the potential molecular targets is a cancer‐specific splicing variant. We have previously shown that one of the splicing variants of eIF4H (isoform 1) was overexpressed in primary human colorectal cancer. Our study aimed to explore whether eIF4H isoform 1 contributes to carcinogenesis and could be an efficient molecular target for human cancer therapy. We found that its overexpression in immortalized mouse fibroblasts, NIH3T3 cells, generated tumors in nude mice. Conversely, suppression of eIF4H isoform 1 expression using specific siRNA inhibited the proliferation of colon cancer cells in vitro and subcutaneously implanted tumor in vivo. Strikingly, eIF4H isoform 1 specific siRNA showed no effect on the growth of immortalized human fibroblasts. More interestingly, ectopic expression of eIF4H isoform 1 greatly increased the cyclin D1 level. On the other hand, cyclin D1 decreased by shRNA‐mediated suppression of eIF4H isoform 1. Moreover, cotransfection of eIF4H isoform 1 siRNA and cyclin D1 expression plasmid was able to reverse the growth suppression effect of eIF4H isoform 1 knockdown. These results suggest that eIF4H isoform 1 plays an important role in carcinogenesis through the activation of oncogenic signaling and could be a promising molecular target for cancer therapy.
A functional TNFRSF5 polymorphism and risk of non‐Hodgkin lymphoma, a pooled analysis
Authors: Nieters Alexandra , Bracci Paige M. , de Sanjosé Silvia , Becker Nikolaus , Maynadié Marc , Benavente Yolanda , Foretova Lenka , Cocco Pierluigi , Staines Anthony , Holly Elizabeth A. , Boffetta Paolo , Brennan Paul , Skibola Christine F. 
Published: April 2010

AbstractInteraction between CD40 and its ligand, CD154, has a key function in immune regulation. Recent experimental data support a role of deregulated CD40 signalling in lymphomagenesis. Data from earlier studies that are part of this pooling study implicate a functional polymorphism (−1C>T, rs1883832) in the TNFRSF5 gene encoding CD40 in the etiology of follicular lymphoma. Here, the association of this variant with non‐Hodgkin lymphoma (NHL) risk was replicated in a European multicenter study of 855 NHL cases and 1,206 controls. In the combined analysis of 2,617 cases and 3,605 controls, carrying the TT genotype was associated with an increased risk for all NHL (OR = 1.4; p for linear trend = 0.00009), diffuse large B‐cell lymphoma (OR = 1.6; p for linear trend = 0.002) and follicular lymphoma (OR = 1.6; p for linear trend = 0.001). These data suggest a possible role of this functional polymorphism in lymphomas originating within the germinal center.