bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

ABSTRACTEngineered 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

AbstractOpioid 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

AbstractRelatively 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

BackgroundInterventional cardiologists and staff are subject to unique physical demands that predispose them to distinct occupational health hazards not seen in other medical disciplines.MethodsTo 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).ResultsThere 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.ConclusionsThese 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.
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

ABSTRACTThe 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

BACKGROUNDThe objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer.METHODSThis 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).RESULTSThe 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.CONCLUSIONSIn 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

BACKGROUNDNVP‐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.METHODSDose 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.RESULTSTwenty‐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.CONCLUSIONSThis 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

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

BACKGROUNDElderly 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.METHODSPatients 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.RESULTSA 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).CONCLUSIONSRT 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

AbstractHierarchical 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.
One‐Pot UV‐Assisted Synthesis of Metal Phthalocyanine Nanocrystals
Authors: Saito Yuta , Higuchi Takeshi , Sugimori Hidekazu , Yabu Hiroshi 
Published: March 2015

AbstractMetal phthalocyanines (PCs) are promising materials for various applications, including pigments, color filters, photovoltaic devices, and nonlinear optics, owing to their specific light‐absorption properties and high stability to chemical and thermal degradation. Nanocrystals (NCs) of metal PCs have received much attention because the optical and electronic properties of metal PCs are improved considerably by decreasing the crystal size to the nanoscale. In this study, we demonstrated the direct synthesis of Cu and Zn PCs in nanosized micelles by irradiating precursors with UV light. The synthesized metal PC NCs were stably dispersed in water by adding polyethylene glycol as a stabilizer. The aqueous dispersions of PC NCs showed strong visible light absorption from 500 to 800 nm and high transparency at wavelengths in the non‐absorption region.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of losmapimod in healthy Japanese volunteers
Authors: Ino Hiroko , Takahashi Naoki , Terao Takumi , Igarashi Harue , Sarai Nobuaki 
Published: March 2015

AbstractThis phase 1 study characterized the safety, tolerability, pharmacokinetics, and pharmacodynamics of losmapimod and its metabolite GSK198602 following single and repeat doses of oral losmapimod in healthy Japanese volunteers. Subjects (n = 41) received single oral doses of losmapimod (2.5, 7.5, 20 mg) or matching placebo on 3 separate days (n = 20) or losmapimod 7.5 mg or matching placebo twice daily for 14 days (n = 21). Assessments included maximum observed plasma concentration (Cmax), time to Cmax (Tmax), apparent terminal‐phase half‐life (t1/)2, area under the curve (AUC), and change in C‐reactive protein and phosphorylated heat shock protein 27 levels. No serious adverse events occurred during the study, and there were no safety concerns regarding clinical laboratory parameters, 12‐lead electrocardiogram, or vital signs. The losmapimod Tmax was 3–4 hours, and the mean t1/2 was approximately 7.9–9.0 hours, with no appreciable difference in Tmax and apparent clearance following oral dosing between dosing regimens. Single and repeat oral doses of losmapimod were well tolerated in healthy Japanese volunteers. The Tmax of GSK198602 was similar to and t1/2 was slightly longer than those of losmapimod. Approximate dose‐proportional increases in exposure to losmapimod and GSK198602 were observed in AUC with single‐dose administration. Repeat‐dose trough concentrations reached steady state within 2 days, with an observed accumulation ratio of 1.56 and 1.91 for losmapimod and GSK198602, respectively.