bluuebunny/crossref_metadata_2025 huggingface dataset:
Liquid li structure and dynamics: A comparison between OFDFT and second nearest‐neighbor embedded‐atom method
Authors: Chen Mohan , Vella Joseph R. , Panagiotopoulos Athanassios Z. , Debenedetti Pablo G. , Stillinger Frank H. , Carter Emily A.
Published: March 2015

The structure and dynamics of liquid lithium are studied using two simulation methods: orbital‐free (OF) first‐principles molecular dynamics (MD), which employs OF density functional theory (DFT), and classical MD utilizing a second nearest‐neighbor embedded‐atom method potential. The properties studied include the dynamic structure factor, the self‐diffusion coefficient, the dispersion relation, the viscosity, and the bond angle distribution function. Simulation results were compared to available experimental data when possible. Each method has distinct advantages and disadvantages. For example, OFDFT gives better agreement with experimental dynamic structure factors, yet is more computationally demanding than classical simulations. Classical simulations can access a broader temperature range and longer time scales. The combination of first‐principles and classical simulations is a powerful tool for studying properties of liquid lithium. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2841–2853, 2015
Comparison of epigenetic versus standard induction chemotherapy for newly diagnosed acute myeloid leukemia patients ≥60 years old
Authors: Gupta Neha , Miller Austin , Gandhi Shipra , Ford Laurie A. , Vigil Carlos E. , Griffiths Elizabeth A. , Thompson James E. , Wetzler Meir , Wang Eunice S.
Published: March 2015

Older patients with acute myeloid leukemia (AML) have poor outcomes with standard induction chemotherapy. We retrospectively reviewed our institute's experience with epigenetic (Epi) versus cytarabine‐ and anthracycline‐based intensive chemotherapy (IC) as induction in newly diagnosed AML patients aged 60 years and older. One hundred sixty‐seven patients (n = 84, IC;n = 83, Epi) were assessed; 69 patients received decitabine and 14 azacitidine. Baseline characteristics between the IC and Epi patient cohorts were not statistically different except for age, initial white blood cell count, and comorbidity index. Overall response rate (ORR, 50% vs. 28%, respectively,P < 0.01) and complete response rate (CRR, 43% vs. 20%, respectively,P < 0.01) were superior following IC vs. Epi. Although univariate analysis demonstrated longer overall survival after IC (10.7 vs. 9.1 months,P = 0.012), multivariate analysis showed no independent impact of induction treatment. Treatment‐related mortality was not statistically different in the two groups. Outcomes of patients with secondary, poor cytogenetic risk,FLT‐3mutated AML, or relapsed/refractory disease after IC or Epi were not significantly different. Outcomes of patients receiving IC versus a 10‐day decitabine regimen (n = 63) also were not significantly different. Our results suggest that IC and Epi therapy are clinically equivalent approaches for upfront treatment of older patients with AML and that other factors (feasibility, toxicity, cost, etc.) should drive treatment decisions. Prospective randomized trials to determine the optimal induction approach for specific patient subsets are needed. Am. J. Hematol. 90:639–646, 2015. © 2015 Wiley Periodicals, Inc.
Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin‐induced thrombocytopenia‐reactive antibodies or with true HIT (HIT‐reactive antibodies plus thrombocytopenia): An 11‐year experience
Authors: Palatianos George , Michalis Alkiviadis , Alivizatos Petros , Lacoumenda Stavroula , Geroulanos Stefanos , Karabinis Andreas , Iliopoulou Eugenia , Soufla Giannoula , Kanthou Chryso , Khoury Mazen , Sfyrakis Petros , Stavridis George , Astras George , Vassili Maria , Antzaka Christina , Marathias Katerina , Kriaras Ioannis , Tasouli Androniki , Papadopoulos Kyrillos , Katafygioti Marina , Matoula Nikoletta , Angelidis Antonios , Melissari Euthemia
Published: March 2015

Thrombocytopenia and thromboembolism(s) may develop in heparin immune‐mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11‐year period underwent preoperative HIT assessment by ELISA and a three‐point heparin‐induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT‐reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT‐positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT‐negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients’ own plasma and donor platelets. In parallel, the iloprost “target dose” was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the “target dose” identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified “target dose.” This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life‐threatening iloprost‐induced hypotension in patients diagnosed with HIT‐reactive antibodies or true HIT. Am. J. Hematol. 90:608–617, 2015. © 2015 Wiley Periodicals, Inc.
Modeling variation in early life mortality in the western lowland gorilla: Genetic, maternal and other effects
Authors: Ahsan Monica H. , Blomquist Gregory E.
Published: March 2015

Uncovering sources of variation in gorilla infant mortality informs conservation and life history research efforts. The international studbook for the western lowland gorilla provides information on a sample of captive gorillas large enough for which to analyze genetic, maternal, and various other effects on early life mortality in this critically endangered species. We assess the importance of variables such as sex, maternal parity, paternal age, and hand rearing with regard to infant survival. We also quantify the proportions of variation in mortality influenced by heritable variation and maternal effects from these pedigree and survival data using variance component estimation. Markov chain Monte Carlo simulations of generalized linear mixed models produce variance component distributions in an animal model framework that employs all pedigree information. Two models, one with a maternal identity component and one with both additive genetic and maternal identity components, estimate variance components for different age classes during the first 2 years of life. This is informative of the extent to which mortality risk factors change over time during gorilla infancy. Our results indicate that gorilla mortality is moderately heritable with the strongest genetic influence just after birth. Maternal effects are most important during the first 6 months of life. Interestingly, hand‐reared infants have lower mortality for the first 6 months of life. Aside from hand rearing, we found other predictors commonly used in studies of primate infant mortality to have little influence in these gorilla data. Am. J. Primatol. 77:666–678, 2015. © 2015 Wiley Periodicals, Inc.
Structures and Biosynthesis of Corvol Ethers—Sesquiterpenes from the Actinomycete Kitasatospora setae
Authors: Rabe Patrick , Pahirulzaman Khomaizon A. K. , Dickschat Jeroen S.
Published: March 2015

Here we present the functional characterization of a sesquiterpene cyclase from Kitasatospora setae. The enzyme converts the sesquiterpene precursor farnesyl diphosphate (FPP) into two previously unknown and unstable sesquiterpene ethers for which we propose the trivial names corvol ethers A and B. Both compounds were purified and their structures were determined by one‐ and two‐dimensional NMR spectroscopy. A biosynthetic mechanism for the FPP cyclization by the corvol ether synthase was proposed. The results from the incubation experiments of the corvol ether synthase with isotopically labeled precursors were in line with this mechanism, while alternative mechanisms could clearly be ruled out.
Iron oxide superparamagnetic nanocarriers bearing amphiphilic N‐heterocyclic choline analogues as potential antimicrobial agents
Authors: Zablotskaya Alla , Segal Izolda , Popelis Yuris , Mishnev Anatoly , Maiorov Mikhail , Zablotsky Dmitry , Blums Elmars , Nikolajeva Vizma , Eze Daina
Published: March 2015

Magnetic nanoparticles represent an advanced tool in biomedicine because they can be simultaneously functionalized and guided using a magnetic field. Iron oxide magnetic nanoparticles precoated with oleic acid and bearing novel antimicrobial N‐heterocyclic choline analogues, namely O‐, N‐ and O,N‐bis‐undecyl‐substituted N‐(2‐hydroxyethyl)‐1,2,3,4‐tetrahydroisoquinolinium derivatives, have been obtained as potential biomedical agents for drug delivery and antimicrobial therapy. Structural and size determinations for the novel synthesized magnetic nanosystems were carried out based upon magnetogranulometry, dynamic light‐scattering measurements and X‐ray diffraction analysis. The most expected iron oxide core diameter was 6.2–10.5 nm. The magnetization analyses showed that the particles are superparamagnetic at room temperature. Aqueous magnetic fluids of the synthesized nanoparticles were examined in vitro concerning Gram‐positive (Staphylococcus aureus MSCL 334, Bacillus cereus MSCL 330) and Gram‐negative (Escherichia coli MSCL 332, Pseudomonas aeruginosa MSCL 331, Proteus mirabilis MSCL 590) bacterial strains and fungi (Candida albicans MSCL 378, Aspergillus niger MSCL 324). It was found that the samples have magnetic properties and possess antimicrobial activity. The minimum inhibitory concentration against S. aureus for the most active magnetic fluid was determined as 16 µg ml−1. Copyright © 2015 John Wiley & Sons, Ltd.
A highly water‐dispersible and magnetically separable palladium catalyst based on functionalized poly(ethylene glycol)‐supported iminophosphine for Suzuki–Miyaura coupling in water
Authors: Liu Xiang , Zhao Xiaohua , Lu Ming
Published: March 2015

A magnetically separable Fe3O4@poly(ethylene glycol) (PEG)–iminophosphine palladium complex was successfully prepared by reacting a palladium complex containing the ligand 2‐(diphenylphosphino)benzaldehyde with amino‐functionalized PEG‐coated iron oxide nanoparticles. The novel catalyst was characterized using inductively coupled plasma atomic emission and Fourier transform infrared spectroscopies, transmission electron microscopy, vibrating sample magnetometry, X‐ray diffraction and thermogravimetric analysis. It showed high activity for the Suzuki–Miyaura coupling reaction in pure water. Furthermore, it was found that the highly water‐dispersible catalyst can be recovered by applying an external magnetic field and used in five consecutive runs without significant decrease in activity. Copyright © 2015 John Wiley & Sons, Ltd.
Factors Affecting Entry into Supply Chain Trade: An Analysis of Firms inSoutheastAsia
Authors: Wignaraja Ganeshan
Published: March 2015

This article undertakes a comparative, firm‐level analysis of joining supply chain trade in fiveSoutheastAsian economies to improve our understanding of fragmentation of manufacturing across borders. The findings suggests that firm size (reflecting economies of scale to overcome entry costs) matters for joining supply chain trade with large firms playing the dominant role inSoutheastAsian economies. Meanwhile, small and medium‐sized enterprises (SMEs) make a small contribution to supply chain trade relatively to the sectors employment contribution. However, firm size is not the whole story. Efficiency—particularly investment in building technological capabilities and skills—and access to commercial bank credit also influence joining supply chain trade. The article suggests that governments can facilitateSMEsjoining supply chain trade through a market‐oriented strategy, modern physical infrastructure, streamlined regulations and efficient business support services.
IDENTIFICATION AND EXPRESSION ANALYSIS OF VITELLOGENIN RECEPTOR FROM THE WILD SILKWORM, Bombyx mandarina
Authors: Qian Cen , Fu Wei‐Wei , Wei Guo‐Qing , Wang Lei , Liu Qiu‐Ning , Dai Li‐Shang , Sun Yu , Zhu Bao‐Jian , Liu Chao‐Liang
Published: March 2015

The vitellogenin receptor (VgR) plays a key role on embryonic development in oviparous animals. Here, we cloned a VgR gene, which was identified from the wild silkworm Bombyx mandarina (BmaVgR) using reverse transcriptase polymerase chain reaction (RT‐PCR) and rapid amplification of cDNA ends (RACE). Sequence analysis revealed that BmaVgR is 5,861 bp long with an open reading frame encoded by 1,811 amino acid residues. The predicted amino acid sequence has 99.7 and 98.2% identity with the VgRs of Actias selene and Bombyx mori, respectively. The class B domain sequence of BmaVgR was cloned and expressed in Escherichia coli, and purified by a Ni‐NTA column. Polyclonal antibodies were produced against the purified recombinant protein, and titer of the antibody was about 1:12,800 measured by enzyme‐linked immunosorbent assay (ELISA). Western blot and RT‐qPCR showed that BmaVgR was expressed in the ovary and fat body of female larvae and the ovary of moth, and the expression level was highest at the third day and then declined from third day to seventh in fat body of pupa. After knockdown of the BmaVgR gene through RNA interference (RNAi), other three BmaVgR‐related genes (Vg, egg‐specific protein, and low molecular weight lipoprotein LP gene) were all downregulated significantly.
Shaping guanxi networks at work through instant messaging
Authors: Ou Carol X. J. , Davison Robert M.
Published: March 2015

Instant messaging (IM) has become increasingly prevalent in social life. However, the use of IM at work remains controversial, owing to its unclear benefits to organizations. In this study, we employ media performance theories and the concept model of communicative ecology to examine the impact of an IM tool on shaping guanxi (i.e., interpersonal relationship) networks in the workplace. Specifically, we propose that IM has the potential to enhance guanxi networks by improving communication quality and building interlocutors' mutual trust in the workplace. The conceptual model is validated with 253 survey responses collected from working professionals in China. The data indicate that communication quality and mutual trust contribute to the development of guanxi networks. The theoretical and practical implications of the findings are discussed.
How users employ various popular tags to annotate resources in social tagging: An empirical study
Authors: Pan Xuwei , He Shenglan , Zhu Xiyong , Fu Qingmiao
Published: March 2015

This paper focuses on exploring the usage patterns and regularities of co‐employment of various popular tags and their relationships with the activeness of users and the interest level of resources in social tagging. A hypernetwork for social tagging is constructed in which a tagging action is expressed as a hyperedge and the user, resource, and tag are expressed as nodes. Quantitative measures for the constructed hypernetwork are defined, including the hyperdegree and its distribution, the excess average hyperdegree, and the hyperdegree conditional probability distribution. Using the data set from Delicious, an empirical study was conducted. The empirical results show that multiple individual tags and one or very few popular tags are generally employed together in one tagging action, and the usage patterns and regularities of tags with varying popularity are correlated to both user activity and resource interest. The empirical results are further discussed and explained from the perspectives of tag functions and motivations. Finally, suggestions regarding the usage of various popular tags for both tagging users and service providers of social tagging are given.
On online collaboration and construction of shared knowledge: Assessing mediation capability in computer supported argument visualization tools
Authors: Iandoli Luca , Quinto Ivana , De Liddo Anna , Buckingham Shum Simon
Published: March 2015

CollaborativeComputer‐SupportedArgumentVisualization (CCSAV) has often been proposed as an alternative over more conventional, mainstream platforms for online discussion (e.g., online forums and wikis).CCSAVtools require users to contribute to the creation of a joint artifact (argument map) instead of contributing to a conversation. In this paper we assess empirically the effects of this fundamental design choice and show that the absence of conversational affordances and socially salient information in representation‐centric tools is detrimental to the users' collaboration experience. We report empirical findings from a study in which subjects using different collaborative platforms (a forum, an argumentation platform, and a socially augmented argumentation tool) were asked to discuss and predict the price of a commodity. By comparing users' experience across several metrics we found evidence that the collaborative performance decreases gradually when we remove conversational interaction and other types of socially salient information. We interpret these findings through theories developed in conversational analysis (common ground theory) and communities of practice and discuss design implications. In particular, we propose balancing the trade‐off between knowledge reification and participation in representation‐centric tools with the provision of social feedback and functionalities supporting meaning negotiation.
Association betweenMTHFRC677T polymorphism and neural tube defect risks: A comprehensive evaluation in three groups of NTD patients, mothers, and fathers
Authors: Yang Yi , Chen Jie , Wang Beiyu , Ding Chen , Liu Hao
Published: March 2015

Background

The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) gene has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). The association of the C677T polymorphism in theMTHFRgene and NTD susceptibility has been widely demonstrated, but the results are inconclusive. In this study, we performed a meta‐analysis in three groups to investigate the association between theMTHFRC677T polymorphism and NTD risk.

Methods

A computer retrieval of PubMed, Cochrane Library, CBM, and Embase for papers on theMTHFRC677T polymorphism and NTD risk was performed. All data were analyzed with STATA (Version 13.0). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. A test for heterogeneity, a sensitivity analysis, and an assessment of publication bias were performed in our meta‐analysis.

Results

Forty articles were included in this meta‐analysis: 13 studies for Group A: 1329 NTD patients versus 2965 healthy controls; 34 studies for Group B: 3018 mothers with NTD progeny versus 8746 healthy controls; three studies for Group C: 157 fathers with NTD progeny versus 705 healthy controls. The analysis results show: allele contrast in NTD patients: OR = 1.445, 95% CI [1.186, 1.760]; allele contrast in mothers: OR = 1.342, 95% CI [1.166, 1.544]; allele contrast in fathers: OR = 1.062, 95% CI [0.821, 1.374].

Conclusion

We found no association between any of the fathers' genotypes and NTDs, whereas a significant correlation betweenMTHFRC677T polymorphism and NTD risk was found in NTD patients and in their mother. Birth Defects Research (Part A) 103:488–500, 2015. © 2015 Wiley Periodicals, Inc.
Y‐craniosynostosis by premature fusion of the metopic and coronal sutures: A new nosological entity or a variety of Saethre‐Chotzen syndrome?
Authors: di Rocco Federico , Benoit Alexandra , Vigneron Jacqueline , Segura Pascale Bach , Klein Olivier , Collet Corinne , Arnaud Eric
Published: March 2015

Background

New forms and varieties of craniosynostoses are continuously identified due to the current increased interest of clinicians and genetists especially since the introduction of microarray‐based comparative genomic hybridization (Array‐CGH) techniques in the diagnostic setting of patients with craniofacial anomalies.

Methods

In this report, we describe the case of an infant who associated the early fusion of the metopic and both the coronal sutures. The interaction of the early fusion of the anterior group of the main cranial sutures gave the infant a particular clinical phenotypes with a Y configuration of the frontal bone and a globally reduced size of the skull. Such a deformity was observed in utero and was subsequently confirmed by the postnatal imaging of the head.

Results

This phenotype was never described previously in antenatal period to our knowledge. The array‐CGH showed a heterozygous 9.0 Mb deletion in the chromosomal region 7p21.1p21.3 encompassing approximately 25 other genes, spanning from THSD7A to TWIST1/FERD3L.

Conclusion

This case further illustrates the variability of the clinical spectrum of craniofacial disorders associated with TWIST1 abnormalities. It is important to note that the Saethre‐Chotzen syndrome caused by microdeletion is generally characterized by a mental disability. However, of interest, the postoperative psychomotor development of the child considered hereby was within the normal limits. Birth Defects Research (Part A) 103:306–310, 2015. © 2015 Wiley Periodicals, Inc.
Blood and immune cell engineering: Cytoskeletal contractility and nuclear rheology impact cell lineage and localization
Authors: Shin Jae‐Won , Discher Dennis E.
Published: March 2015

Clinical success with human hematopoietic stem cell (HSC) transplantation establishes a paradigm for regenerative therapies with other types of stem cells. However, it remains generally challenging to therapeutically treat tissues after engineering of stem cells in vitro. Recent studies suggest that stem and progenitor cells sense physical features of their niches. Here, we review biophysical contributions to lineage decisions, maturation, and trafficking of blood and immune cells. Polarized cellular contractility and nuclear rheology are separately shown to be functional markers of a hematopoietic hierarchy that predict the ability of a lineage to traffic in and out of the bone marrow niche. These biophysical determinants are regulated by a set of structural molecules, including cytoplasmic myosin‐II and nuclear lamins, which themselves are modulated by a diverse range of transcriptional and post‐translational mechanisms. Small molecules that target these mechanobiological circuits, along with novel bioengineering methods, could prove broadly useful in programming blood and immune cells for therapies ranging from blood transfusions to immune attack of tumors.
Reverse attenuation in interaction terms due to covariate measurement error
Authors: Muff Stefanie , Keller Lukas F.
Published: March 2015

Covariate measurement error may cause biases in parameters of regression coefficients in generalized linear models. The influence of measurement error on interaction parameters has, however, only rarely been investigated in depth, and if so, attenuation effects were reported. In this paper, we show that also reverse attenuation of interaction effects may emerge, namely when heteroscedastic measurement error or sampling variances of a mismeasured covariate are present, which are not unrealistic scenarios in practice. Theoretical findings are illustrated with simulations. A Bayesian approach employing integrated nested Laplace approximations is suggested to model the heteroscedastic measurement error and covariate variances, and an application shows that the method is able to reveal approximately correct parameter estimates.
U937 cell apoptosis induced by arsenite is prevented by low concentrations of mitochondrial ascorbic acid with hardly any effect mediated by the cytosolic fraction of the vitamin
Authors: Guidarelli Andrea , Fiorani Mara , Azzolini Catia , Cerioni Liana , Scotti Maddalena , Cantoni Orazio
Published: March 2015

Arsenite directly triggers cytochrome c and Smac/DIABLO release in mitochondria isolated from U937 cells. These effects were not observed in mitochondria pre‐exposed for 15 min to 10 µM L‐ascorbic acid (AA). In other experiments, intact cells treated for 24–72 h with arsenite were found to die by apoptosis through a mechanism involving mitochondrial permeability transition. Pre‐exposure (15 min) to low micromolar concentrations of AA and dehydroascorbic acid (DHA), resulting in identical cytosolic levels of the vitamin, had a diverse impact on cell survival, as cytoprotection was only observed after treatment with AA. Also the mitochondrial accumulation of the vitamin was restricted to AA exposure. An additional indication linking cytoprotection to the mitochondrial fraction of the vitamin was obtained in experiments measuring susceptibility to arsenite in parallel with loss of mitochondrial and cytosolic AA at different times after vitamin exposure. Finally, we took advantage of our recent findings that DHA potently inhibits AA transport to demonstrate that DHA abolishes all the protective effects of AA, under the same conditions in which the mitochondrial accumulation of the vitamin is prevented without affecting the overall cellular accumulation of the vitamin. © 2015 BioFactors, 41(2):101–110, 2015
Retinol binding protein‐4 predicts incident diabetes in Asian Indian men with prediabetes
Authors: Ram Jagannathan , Snehalatha Chamukuttan , Selvam Sundaram , Nanditha Arun , Shetty Ananth Samith , Godsland Ian F. , Johnston Desmond G. , Ramachandran Ambady
Published: March 2015

The association of retinol binding protein‐4 (RBP4) with incident type 2 diabetes (T2DM) in Asian Indian middle‐aged men with impaired glucose tolerance (IGT) was studied. This was an ancillary analysis of a subsample from a cohort of participants with IGT in a 2 year prospective diabetes prevention program in India. For this analysis, 71 incident T2DM and 76 non‐diabetic cases (non‐progressors) based on the final glycemic outcome were selected. Baseline serum RBP4 was measured using competitive enzyme immunoassay. Correlations of RBP4 with relevant anthropometric and biochemical variables and also its association with diabetes were assessed using appropriate statistical analyses. Participants who developed T2DM had higher levels of serum RBP4 (21.3 [IQR: 17.7–24.9] µg/mL) compared with non‐progressors (17.3 [IQR: 13.1–21.0] µg/mL; P = 0.001). Levels of RBP4 were lower than in Caucasians. Stepwise linear regression analysis showed that body mass index (BMI), systolic blood pressure, triglycerides, and HbA1c had independent associations with RBP4 levels. Multiple logistic regression analyses showed that RBP4 was independently associated with incident diabetes (odds ratio [OR] [95%confidence interval (CI)]: 1.69 [1.18–2.41]; P = 0.004). Adjustment for study group, age, BMI, waist circumference, 2 H plasma glucose, triglycerides, gamma glutamyl transferase, and insulin resistance weakened the significance of its association (OR [95%CI]: 1.65 [1.03–2.66]; P = 0.038).The results of this preliminary analyses showed that baseline serum RBP4 levels were independently associated with incident diabetes in Asian Indian men with IGT. It may be used as an additional predictor of future diabetes. © 2015 BioFactors, 41(3):160–165, 2015
Multiplexed gene transfer to a human T‐cell line by combining Sleeping Beauty transposon system with methotrexate selection
Authors: Kacherovsky Nataly , Liu Gary W. , Jensen Michael C. , Pun Suzie H.
Published: March 2015

Engineered human T‐cells are a promising therapeutic modality for cancer immunotherapy. T‐cells expressing chimeric antigen receptors combined with additional genes to enhance T‐cell proliferation, survival, or tumor targeting may further improve efficacy but require multiple stable gene transfer events. Methods are therefore needed to increase production efficiency for multiplexed engineered cells. In this work, we demonstrate multiplexed, non‐viral gene transfer to a human T‐cell line with efficient selection (∼50%) of cells expressing up to three recombinant open reading frames. The efficient introduction of multiple genes to T‐cells was achieved using the Sleeping Beauty transposon system delivered in minicircles by nucleofection. We demonstrate rapid selection for engineered cells using methotrexate (MTX) and a mutant human dihydrofolate reductase resistant to methotrexate‐induced metabolic inhibition. Preferential amplification of cells expressing multiple transgenes was achieved by two successive rounds of increasing MTX concentration. This non‐viral gene transfer method with MTX step selection can potentially be used in the generation of clinical‐grade T‐cells housing multiplexed genetic modifications. Biotechnol. Bioeng. 2015;112: 1429–1436. © 2015 Wiley Periodicals, Inc.
UHPLC‐MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma
Authors: Kyle Amy Redmond , Carmical Jennifer , Shah Darshan , Pryor Jason , Brown Stacy
Published: March 2015

Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC‐MS/MS method using solid‐phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.
Family history of cancer and childhood rhabdomyosarcoma: a report from the Children's Oncology Group and the Utah Population Database
Authors: Lupo Philip J. , Danysh Heather E. , Plon Sharon E. , Curtin Karen , Malkin David , Hettmer Simone , Hawkins Douglas S. , Skapek Stephen X. , Spector Logan G. , Papworth Karin , Melin Beatrice , Erhardt Erik B. , Grufferman Seymour , Schiffman Joshua D.
Published: March 2015

Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case–control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Children's Oncology Group (COG). Population‐based controls (n = 322) were pair‐matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (ORs) and 95% confidence intervals (CI). Having a first‐degree relative with a cancer history was more common in RMS cases than controls (ORs = 1.39, 95% CI: 0.97–1.98). Notably, this association was stronger among those with embryonal RMS (ORs = 2.44, 95% CI: 1.54–3.86). Moreover, having a first‐degree relative who was younger at diagnosis of cancer (<30 years) was associated with a greater risk of RMS (ORs = 2.37, 95% CI: 1.34–4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first‐degree relative with cancer, and among those whose relatives were diagnosed with cancer at <30 years of age.
Occupational health hazards of interventional cardiologists in the current decade: Results of the 2014 SCAI membership survey
Authors: Klein Lloyd W. , Tra Yolande , Garratt Kirk N. , Powell Wayne , Lopez‐Cruz Georgina , Chambers Charles , Goldstein James A. ,   On Behalf of the Society for Cardiovascular Angiography and Interventions
Published: March 2015

Background

Interventional cardiologists and staff are subject to unique physical demands that predispose them to distinct occupational health hazards not seen in other medical disciplines.

Methods

To characterize the prevalence of these occupational health problems, The Society for Cardiovascular Angiography and Interventions (SCAI) surveyed its members by email. Inquiries included age, years of invasive practice, and diagnostic and interventional cases per year. Questions focused on orthopedic (spine, hips, knees, and ankles) and radiation‐associated problems (cataracts and cancers).

Results

There were 314 responses. Responders were on average busy and experienced, performing a mean of 380 ± 249 diagnostic and 200 ± 129 interventional cases annually. Of the responders, 6.9% of operators have had to limit their caseload because of radiation exposure and 9.3% have had a health‐related period of absence. Furthermore, 153 (49.4%) operators reported at least one orthopedic injury: 24.7% cervical spine disease, 34.4% lumbar spine problems, and 19.6% hip, knee or ankle joint problems. Age was most significantly correlated with orthopedic illnesses: cervical injuries (χ2 = 150.7, P < 0.0001); hip/knee or ankle injuries (χ2 = 80.9, P < 0.0001); lumbar injuries (χ2 = 147.0, P < 0.0001); and any orthopedic illness (χ2 = 241.2, P < 0.0001). Annual total caseload was also associated: the estimated change in the odds of orthopedic illness for each additional total caseload quintile is 1.0013 (1.0001, 1.0026). There is a small but substantial incidence of cancer.

Conclusions

These findings are consistent with, and extend the findings, of a prior 2004 SCAI survey, in documenting a substantial prevalence of orthopedic complications among active interventional cardiologists, which persists despite increased awareness. © 2015 Wiley Periodicals, Inc.
Aluminum pigments encapsulated with hybrid silica film with carboxyl groups and their stability and dispersibility in aqueous media
Authors: Pi Pihui , Liu Chao , Wen Xiufang , Cheng Jiang , Xu Shouping , Li Qiong
Published: March 2015

Aluminum pigments encapsulated with hybrid SiO2 film with carboxyl (–COOH) groups were prepared through a sol‐gel process of tetraethoxysilane (TEOS) and vinyl triethoxysilane (VTES), followed by radical copolymerization of methyl methacrylate (MMA) and acrylic acid (AA) with the vinyl group of VTES. The composite aluminum pigments were characterized by means of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X‐ray photoelectron spectroscopy (XPS). Their stability in acid media as well as dispersibility in water were also evaluated. It was found that VTES and TEOS could simultaneously hydrolyze and condense with hydroxyl groups on the surface of aluminum particles to form inorganic‐organic hybrid films, and copolymerization of MMA and AA could provide the film surface with –COOH groups. This helps the composite aluminum pigments disperse better in water than raw aluminum pigments (raw Al) counterparts. Compared with the serious corrosion problem of raw Al, which generated about 113 mL H2 in acid media of pH=1 in 30 days, the composite aluminum pigments showed much better anticorrosion performance (with only about 0.5 mL H2). The waterborne coatings made with this composite aluminum pigments showed great improvements on adhesive performance and stability in 0.1 mol/L H2SO4 or NaOH media.
Estimation of occupational exposure to static magnetic fields due to usual movements in magnetic resonance units
Authors: Hartwig Valentina , Vanello Nicola , Giovannetti Giulio , Landini Luigi , Santarelli Maria Filomena
Published: March 2015

The purpose of this work is to estimate the induced electric field E due to movements of magnetic resonance (MR) workers in static magnetic field. Different operator walking speeds and paths are taken into account, based on real‐world scenarios for a 3T MR scanner. The spectral components of magnetic field gradient are estimated to verify the compliance with the specific International Commission on Non‐Ionizing Radiation Protection safety guidelines for MR workers. The induced electric fields on the chosen paths are estimated using a previously described software tool based on an analytical model. Finally, a real situation is considered in which an operator performs the patient preparation for a brain MR examination. From the spectral components of the motion‐induced magnetic field gradient, it is possible to see that the highest values are concentrated on frequencies below 1 Hz. For the basic paths considered, the worst‐case scenario is a walking perpendicular to the magnet cylinder along the x‐axis. For the example of a real path, the critical zone where the worker exposure is highest is highlighted. The results of this study could be used for training MR workers to follow correct behavior in the scanner room to avoid high‐exposure scenarios. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 44B: 75–81, 2015
Health system delay and its effect on clinical stage of breast cancer: Multicenter study
Authors: Unger‐Saldaña Karla , Miranda Alfonso , Zarco‐Espinosa Gelasio , Mainero‐Ratchelous Fernando , Bargalló‐Rocha Enrique , Miguel Lázaro‐León Jesús
Published: March 2015

BACKGROUND

The objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer.

METHODS

This was a cross‐sectional study of 886 patients who were referred to 4 of the largest public cancer hospitals in Mexico City for the evaluation of a probable breast cancer. Data on time intervals, sociodemographic factors, and clinical stage at diagnosis were retrieved. A logistic regression model was used to estimate the average marginal effects of delay on the probability of being diagnosed with advanced breast cancer (stages III and IV).

RESULTS

The median time between problem identification and the beginning of treatment was 7 months. The subinterval with the largest delay was that between the first medical consultation and diagnosis (median, 4 months). Only 15% of the patients who had cancer were diagnosed with stage 0 and I disease, and 48% were diagnosed with stage III and IV disease. Multivariate analyses confirmed independent correlations for the means of problem identification, patient delay, health system delay, and age with a higher probability that patients would begin cancer treatment in an advanced stage.

CONCLUSIONS

In the sample studied, the majority of patients with breast cancer began treatment after a delay. Both patient delays and provider delays were associated with advanced disease. Research aimed at identifying specific access barriers to medical services is much needed to guide the design of tailored health policies that go beyond the promotion of breast care awareness and screening participation to include improvements in health services that facilitate access to timely diagnosis and treatment. Cancer 2015;121:2198–2206.
Phase 1/1B trial of the heat shock protein 90 inhibitor NVP‐AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma
Authors: Seggewiss‐Bernhardt Ruth , Bargou Ralf C. , Goh Yeow Tee , Stewart A. Keith , Spencer Andrew , Alegre Adrian , Bladé Joan , Ottmann Oliver G. , Fernandez‐Ibarra Cristina , Lu Hong , Pain Scott , Akimov Mikhail , Iyer Swaminathan Padmanabhan
Published: March 2015

BACKGROUND

NVP‐AUY922 (AUY; Luminespib) with or without bortezomib showed preclinical activity against multiple myeloma (MM) cells. This phase 1/1B study assessed NVP‐AUY922 alone and with bortezomib in patients with relapsed or refractory MM.

METHODS

Dose escalation was guided by an adaptive Bayesian logistic regression model. In phase 1, patients who progressed after 2 to 4 prior therapies received NVP‐AUY922 intravenously once weekly. In phase 1B, patients who progressed after 2 or fewer prior therapies received NVP‐AUY922 plus bortezomib. The primary objective was to determine the maximum tolerated dose (MTD) of NVP‐AUY922.

RESULTS

Twenty‐four patients received NVP‐AUY922 monotherapy at doses of 8 to 70 mg/m2. One dose‐limiting toxicity (DLT) was observed (grade 3 blurred vision at 70 mg/m2); no MTD was reached. The recommended phase 2 dose was 70 mg/m2. The most frequent drug‐related adverse events (AEs) were diarrhea, nausea, and ocular toxicities. Grade 3/4 AEs were uncommon (<10%). Eight patients discontinued treatment because of AEs; 5 had ocular toxicities (≥45 mg/m2). The best response was stable disease in 66.7% of the patients. There were no partial or complete responses. Five patients received NVP‐AUY922 (which was started at 50 mg/m2) plus bortezomib (1.3 mg/m2). Three of these patients experienced DLT. No further dose escalation was performed; the MTD for NVP‐AUY922 plus bortezomib was not established.

CONCLUSIONS

This study showed disease stabilization with NVP‐AUY922 in patients with relapsed or refractory MM. The MTD for NVP‐AUY922 was not reached, but reversible ocular toxicity has been reported at high dose levels. Bortezomib at the standard recommended dose plus NVP‐AUY922 was not tolerated. Cancer 2015;121:2185–2192. © 2015 American Cancer Society.
Long‐term impact of androgen‐deprivation therapy on physical function and quality of life
Authors: Alibhai Shabbir M. H. , Breunis Henriette , Timilshina Narhari , Naglie Gary , Tannock Ian , Krahn Murray , Warde Padraig , Fleshner Neil E. , Canning Sarah Duff , Tomlinson George
Published: March 2015

BACKGROUND

This study examined the impact of androgen‐deprivation therapy (ADT) on physical function and quality of life (QOL) over 36 months.

METHODS

Eighty‐seven men with nonmetastatic prostate cancer (PC) who were starting continuous ADT and 2 control groups (86 PC controls without ADT and 86 healthy controls), matched by age and education, were enrolled. Physical function was assessed with the 6‐minute walk test (6MWT), grip strength, and Timed Up and Go (TUG) test. QOL was measured with the 36‐Item Short Form Health Survey of the Medical Outcomes Study. Subjects were assessed at the baseline and at 3, 6, 12, 18, 24, 30, and 36 months. Mixed effects regression models were fitted with adjustments for baseline covariates.

RESULTS

The 6MWT distance improved initially and then stabilized in both control groups but remained unchanged for ADT users (P = .0030). Grip strength remained stable in control groups but declined sharply in the ADT group by 3 months and then remained stable to 36 months (P = .0041). TUG scores declined gradually in the ADT group over 36 months but were unchanged in control groups (P = .0008). Aggregate physical QOL declined in ADT users over time but remained stable in control groups (P = .0001). Aggregate mental QOL was stable in all groups. Declines seen in the first year of ADT use generally persisted over 36 months and were independent of age.

CONCLUSIONS

Previously noted physical side effects over the first 12 months of ADT persisted or continued to worsen over an additional 2 years with no evidence of recovery. Exercise interventions to counteract these declines may be warranted. Cancer 2015;121:2350–2357. © 2015 American Cancer Society.
The evolving role of adjuvant radiotherapy for elderly women with early‐stage breast cancer
Authors: Rutter Charles E. , Lester‐Coll Nataniel H. , Mancini Brandon R. , Corso Christopher D. , Park Henry S. , Yeboa Debra N. , Gross Cary P. , Evans Suzanne B.
Published: March 2015

BACKGROUND

Elderly patients with early‐stage breast cancer (ESBC) derive a local control benefit from radiotherapy (RT) after lumpectomy, without any apparent effect on overall survival. Therefore, the use of RT is controversial. In the current study, the authors characterized updated trends in RT for elderly patients with estrogen receptor (ER)‐positive ESBC.

METHODS

Patients aged ≥70 years with ER‐positive ESBC measuring ≤2 cm after lumpectomy with negative resection margins and known RT details were identified in the National Cancer Data Base. Patients were classified by year of diagnosis and segregated into 3 groups relative to the initial publication and updated presentation of the Cancer and Leukemia Group B (CALGB) 9343 trial. RT use overall, prescription of hypofractionated RT, and use of boost RT were compared between groups using logistic regression analysis, and the influence of clinicopathologic covariates was determined with multivariable logistic regression analysis.

RESULTS

A total of 122,796 elderly patients with ER‐positive ESBC who were diagnosed between 1998 and 2011 were identified. Overall, 84,649 patients (68.9%) received adjuvant RT, with a decline observed between successive cohorts (71.3% in the pre‐initial publication cohort, 69.5% in the pre‐update cohort, and 64.7% in the post‐update cohort; P <.001). Hypofractionated RT use increased among treated patients over time (P<.001). Boost RT was used in 67.5% of patients, with a decline noted between the pre‐update and post‐update cohorts (68.7% vs 57.7%; P<.001). Overall RT use as well as use of boost RT were found to be lower among older patients and those with lower‐grade or smaller tumors (P<.001), whereas hypofractionated RT was used more commonly in these groups (P<.001).

CONCLUSIONS

RT use appears to have declined in elderly patients with ER‐positive ESBC, a finding that is reflective of evidence‐based practice integrating mature trial data. Further research is needed to develop tools to aid in the decision‐making process regarding the delivery or avoidance of RT in this setting. Cancer 2015;121:2331–2340. © 2015 American Cancer Society.
Hierarchical Pt/NiO Hollow Microspheres with Enhanced Catalytic Performance
Authors: Qi Lifang , Cheng Bei , Ho Wingkei , Liu Gang , Yu Jiaguo
Published: March 2015

Hierarchical macro‐mesoporous Pt/NiO hollow microspheres are synthesized and used for catalytic decomposition of formaldehyde in air at room temperature. The uncalcined Pt‐Ni(OH)2 sample exhibits low catalytic activity. The Pt/NiO sample heated at 300 °C shows significantly enhanced catalytic activity. The Pt/NiO sample at 400 °C exhibits the highest catalytic activity, mainly due to its bimodal macro‐mesoporous structure with open and accessible pores, which provides a large specific surface for HCHO adsorption and Pt dispersion, enables the fast diffusion and transport of gas molecules, and ensures the accessibility of active sites on Pt nanoparticles for gas molecules. Moreover, all Pt/NiO hollow spheres have higher catalytic activity than Pt‐decorated commercial NiO. The prepared hierarchical macro‐mesoporous Pt/NiO nanocomposite hollow microspheres should also find applications in adsorption, photocatalysis, electrocatalysis, separation, and purification processes.