bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Partial Pressure of Oxygen in Blood Samples on Measurement Performance in Glucose-Oxidase-Based Systems for Self-Monitoring of Blood Glucose
Authors: Baumstark Annette , Schmid Christina , Pleus Stefan , Haug Cornelia , Freckmann Guido 
Published: June 2016

Background: Partial pressure of oxygen (pO2) in blood samples can affect blood glucose (BG) measurements, particularly in systems that employ the glucose oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the impact of different pO2 values on the performance of five GOx systems and one glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the manufacturers to be sensitive to increased blood oxygen content, while the other three GOx systems are not. Methods: Aliquots of 20 venous samples were adjusted to the following pO2 values: <45, ∼70, and ≥150 mmHg. For each system, five consecutive measurements on each sample aliquot were performed using the same test strip lot. Relative differences between the mean BG results at pO2 ∼70 mmHg, which is considered to be similar to pO2 in capillary blood samples, and the mean BG result at pO2 <45 and ≥150 mmHg were calculated. Results: For all tested GOx systems, mean relative differences in the BG measurement results were between 6.1% and 22.6% at pO2 <45 mmHg and between −7.9% and −14.9% at pO2 ≥150 mmHg. For both pO2 levels, relative differences of all tested GOx systems were significant ( p < .0001). The GDH system showed mean relative differences of −1.0% and −0.4% at pO2 values <45 and ≥150 mmHg, respectively, which were not significant. Conclusions: These data suggest that capillary blood pO2 variations lead to clinically relevant BG measurement deviations in GOx systems, even in GOx systems that are not labeled as being oxygen sensitive.
Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo
Authors: Klueh Ulrike , Antar Omar , Qiao Yi , Kreutzer Donald L. 
Published: June 2016

Background: Glucose-sensor-induced tissue reactions (e.g., inflammation and wound healing) are known to negatively impact sensor function in vivo. The roles of cytokine networks in controlling these tissue reactions (i.e., sensor biofouling) is not understood. In the present study, we investigated the role of interleukin-1 receptor antagonist (IL-1Ra), a key anti-inflammatory antagonist of the proinflammatory interleukin-1 cytokines [i.e. interleukin-1 (IL-1) alpha and IL-1 beta] in controlling continuous glucose monitoring (CGM). Methods: To investigate the role of IL-1Ra in long-term CGM in vivo, we compared CGM in transgenic mice that overexpress IL-1Ra [interleukin-1 receptor antagonist overexpresser (IL-1Ra∼OE), B6.Cg-Tg (IL1rn)1Dih/J] or are deficient in IL-1Ra [interleukin-1 receptor antagonist knockout (IL-1Ra∼KO), B6.129S- IL1rntm1Dih/J] with mice that have normal levels of IL-1Ra (C57BL/6) over a 28-day time period. Results: Mean absolute relative difference (MARD) analysis of CGM results among the mice of varying IL-1Ra levels demonstrated that during the first 21 days, IL-1∼KO mice had the greatest tissue inflammation and the poorest sensor performance (i.e., higher MARD values) when compared with normal or IL-1Ra∼OE mice. By 28 days post-sensor implantation, the inflammatory reactions had subsided and were replaced by varying degrees of fibrosis. Conclusions: These data support our hypothesis on the importance of the IL-1 family of agonists and antagonists in controlling tissue reactions and sensor function in vivo. These data also suggest that local delivery of IL-1Ra genes or recombinant proteins (anakinra) or other IL-1 antagonists such as antibodies or soluble IL-1 receptors would suppress sensor-induced tissue reactions and likely enhance glucose sensor function by inhibiting inflammation and wound healing at sensor implantation sites.
Comparing UK and 20 Western countries' efficiency in reducing adult (55–74) cancer and total mortality rates 1989–2010: Cause for cautious celebration? A population-based study
Authors: Pritchard Colin , Hickish Tamas , Rosenorn-Lanng Emily , Wallace Mark 
Published: June 2016

Objective Every Western nation expends vast sums on health, especially for cancer; thus, the question is how efficient is the UK in reducing adult (55–74) cancer mortality rates and total mortality rates (TMR) compared to the other Western nations in the context of economic-input to health, the percentage of Gross-Domestic-Product-expenditure-on-Health. Design WHO mortality rates for baseline 3 years 1989–1991 and 2008–2010 were analysed, and confidence intervals determine any significant differences between the UK and other countries in reducing the mortalities. Efficiency ratios are calculated by dividing reduced mortality over the period by the average % of national income. Setting Twenty-one similar socio-economic Western countries. Participants The 21 countries’ general population. Main outcome measures Cancer mortality rates, total mortality rates Gross Domestic Product and Efficiency Ratios. Results Economic Input: In 1980, UK national income was 5.6% and the European average was 7.1%. By 2010, UK national income was 9.4% being equal 17th of 21 averaging 7.1% over the period. Europe’s 1980–2010 average of 8.4% yields a UK to Europe ratio of 1:1.18. Clinical output 1989–2010: UK Cancer Mortality Rates was the sixth highest, but equal sixth biggest fall, significantly greater than 14 other countries. UK Total Mortality Rates was the fifth highest but third biggest decline, significantly greater than 17 countries. UK’s cancer Efficiency Ratios is largest at 1:301 and second biggest for Total Mortality Rates at 1.1341; the USA ratios were 1:152 and 1:525, respectively. Conclusions UK reduced mortalities indicate that the NHS achieves proportionally more with relatively less, but UK needs to match European average Gross-Domestic-Product-expenditure-on-Health to meet future challenges.
Mineralogical and physico-chemical characteristics of Cameroonian smectitic clays after treatment with weakly sulfuric acid
Authors: Mache J.R. , Signing P. , Mbey J.A. , Razafitianamaharavo A. , Njopwouo D. , Fagel N. 
Published: June 2016

AbstractSmectitic clays from the Sabga and Bana areas, western Cameroon were treated with sulfuric-acid solutions of various concentrations – 0.5, 0.7, 1.0 and 4.0 N – at 80°C for 2 h. The mineralogical, physicochemical and morphological characteristics of the samples treated were analysed using several techniques. The sulfuric acid caused structural modification of the dioctahedral smectite. The accessory minerals such as cristobalite, quartz, feldspars and anatase remained unaltered by the acid attack. The supernatant solutions after acid treatment contain Mg, Ca, K, Na, Si, Al and Fe as a result of partial dissolution of octahedral and tetrahedral cations. The activated clay samples exhibited a smaller cation exchange capacity (CEC) and the specific surface area (SSA) increased with increasing concentration of sulfuric acid, ranging from 65 to 134 m2/g for the sample from Bana and from 74 to 84 m2/g for the sample from Sabga. The different SSAvalues were affected by the relative abundance of smectite and cristobalite (SiO2/Al2O3 = 2.2 and 6.5, respectively, from Bana and Sabga). The activated clays from Bana and Sabga displayed interesting physicochemical and textural properties and can be considered as promising adsorbents for the bleaching of vegetable oils.
Synthesis of sodalite from Brazilian kaolin wastes
Authors: Maia Ana Áurea B. , Neves Roberto F. , Angélica Rômulo S. , Pöllmann Herbert 
Published: June 2016

AbstractKaolin wastes from the Capim and Jari regions (Brazil) were used to produce sodalite under the same conditions used in the Bayer process, in order to control its formation when necessary. Of the two kaolin source materials, the kaolinite from the Jari region was more reactive in the synthesis of sodalite, which is attributed to the low degree of structural order of this clay mineral which increased its reactivity. At a temperature of 150°C and with a Na/Al ratio of 2, although the kaolinite did not react completely, sodalitewas the primary reaction product. An increase in the temperature to 200°C provoked the complete reaction of the kaolinite only for the products in which carbonate and sulfate were used. With a Na/Al ratio >2 and for both of the temperatures, the kaolinite reacted completely to form sodalite.
Bagging survival tree procedure for variable selection and prediction in the presence of nonsusceptible patients
Authors: Mbogning Cyprien , Broët Philippe 
Published: June 2016

Abstract
Background
For clinical genomic studies with high-dimensional datasets, tree-based ensemble methods offer a powerful solution for variable selection and prediction taking into account the complex interrelationships between explanatory variables. One of the key component of the tree-building process is the splitting criterion. For survival data, the classical splitting criterion is the Logrank statistic. However, the presence of a fraction of nonsusceptible patients in the studied population advocates for considering a criterion tailored to this peculiar situation.

Results
We propose a bagging survival tree procedure for variable selection and prediction where the survival tree-building process relies on a splitting criterion that explicitly focuses on time-to-event survival distribution among susceptible patients.
A simulation study shows that our method achieves good performance for the variable selection and prediction. Different criteria for evaluating the importance of the explanatory variables and the prediction performance are reported. Our procedure is illustrated on a genomic dataset with gene expression measurements from early breast cancer patients.

Conclusions
In the presence of nonsusceptible patients among the studied population, our procedure represents an efficient way to select event-related explanatory covariates with potential higher-order interaction and identify homogeneous groups of susceptible patients.
A distributional approach to obtain adjusted comparisons of proportions of a population at risk
Authors: Sauzet Odile , Breckenkamp Jürgen , Borde Theda , Brenne Silke , David Matthias , Razum Oliver , Peacock Janet L. 
Published: June 2016

Abstract
Background
Dichotomisation of continuous data has statistical drawbacks such as loss of power but may be useful in epidemiological research to define high risk individuals.

Methods
We extend a methodology for the presentation of comparison of proportions derived from a comparison of means for a continuous outcome to reflect the relationship between a continuous outcome and covariates in a linear (mixed) model without losing statistical power. The so called “distributional method” is described and using perinatal data for illustration, results from the distributional method are compared to those of logistic regression and to quantile regression for three different outcomes.

Results
Estimates obtained using the distributional method for the comparison of proportions are consistently more precise than those obtained using logistic regression. For one of the three outcomes the estimates obtained from the distributional method and from logistic regression disagreed highlighting that the relationships between outcome and covariate differ conceptually between the two models.

Conclusion
When an outcome follows the required condition of distribution shift between exposure groups, the results of a linear regression model can be followed by the corresponding comparison of proportions at risk. This dual approach provides more precise estimates than logistic regression thus avoiding the drawback of the usual dichotomisation of continuous outcomes.
Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia
Authors: Krull Kevin R. , Cheung Yin Ting , Liu Wei , Fellah Slim , Reddick Wilburn E. , Brinkman Tara M. , Kimberg Cara , Ogg Robert , Srivastava Deokumar , Pui Ching-Hon , Robison Leslie L. , Hudson Melissa M. 
Published: June 2016

Purpose To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol. Patients and Methods This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education. Results Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue. Conclusion Survivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function.
Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study
Authors: Lesokhin Alexander M. , Ansell Stephen M. , Armand Philippe , Scott Emma C. , Halwani Ahmad , Gutierrez Martin , Millenson Michael M. , Cohen Adam D. , Schuster Stephen J. , Lebovic Daniel , Dhodapkar Madhav , Avigan David , Chapuy Bjoern , Ligon Azra H. , Freeman Gordon J. , Rodig Scott J. , Cattry Deepika , Zhu Lili , Grosso Joseph F. , Bradley Garelik M. Brigid , Shipp Margaret A. , Borrello Ivan , Timmerman John 
Published: June 2016

Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti–PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.
Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis
Authors: Ghosh Nilanjan , Karmali Reem , Rocha Vanderson , Ahn Kwang Woo , DiGilio Alyssa , Hari Parameswaran N. , Bachanova Veronika , Bacher Ulrike , Dahi Parastoo , de Lima Marcos , D’Souza Anita , Fenske Timothy S. , Ganguly Siddhartha , Kharfan-Dabaja Mohamed A. , Prestidge Tim D. , Savani Bipin N. , Smith Sonali M. , Sureda Anna M. , Waller Edmund K. , Jaglowski Samantha , Herrera Alex F. , Armand Philippe , Salit Rachel B. , Wagner-Johnston Nina D. , Fuchs Ephraim , Bolaños-Meade Javier , Hamadani Mehdi 
Published: June 2016

Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.
Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score–Weighted Analysis From the National Cancer Data Base
Authors: Seisen Thomas , Sun Maxine , Leow Jeffrey J. , Preston Mark A. , Cole Alexander P. , Gelpi-Hammerschmidt Francisco , Hanna Nawar , Meyer Christian P. , Kibel Adam S. , Lipsitz Stuart R. , Nguyen Paul L. , Bellmunt Joaquim , Choueiri Toni K. , Trinh Quoc-Dien 
Published: June 2016

Purpose Evidence from studies of other malignancies has indicated that aggressive local treatment (LT), even in the presence of metastatic disease, is beneficial. Against a backdrop of stagnant mortality rates for metastatic urothelial carcinoma of the bladder (mUCB) at presentation, we hypothesized that high-intensity LT of primary tumor burden, defined as the receipt of radical cystectomy or ≥ 50 Gy of radiation therapy delivered to the bladder, affects overall survival (OS). Patients and Methods We identified 3,753 patients within the National Cancer Data Base who received multiagent systemic chemotherapy combined with high-intensity versus conservative LT for primary mUCB. Patients who received no LT, transurethral resection of the bladder tumor alone, or < 50 Gy of radiation therapy delivered to the bladder were included in the conservative LT group. Inverse probability of treatment weighting (IPTW) –adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients who received high-intensity versus conservative LT. Results Overall, 297 (7.91%) and 3,456 (92.09%) patients with mUCB received high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the high-intensity LT group than in the conservative LT group (14.92 [interquartile range, 9.82 to 30.72] v 9.95 [interquartile range, 5.29 to 17.08] months, respectively; P < .001). Furthermore, in IPTW-adjusted Cox regression analysis, high-intensity LT was associated with a significant OS benefit (hazard ratio, 0.56; 95% CI, 0.48 to 0.65; P < .001). Conclusion We report an OS benefit for individuals with mUCB treated with high-intensity versus conservative LT. Although the findings are subject to the usual biases related to the observational study design, these preliminary data warrant further consideration in randomized controlled trials, particularly given the poor prognosis associated with mUCB.
Safety and Efficacy of Durvalumab (MEDI4736), an Anti–Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer
Authors: Massard Christophe , Gordon Michael S. , Sharma Sunil , Rafii Saeed , Wainberg Zev A. , Luke Jason , Curiel Tyler J. , Colon-Otero Gerardo , Hamid Omid , Sanborn Rachel E. , O’Donnell Peter H. , Drakaki Alexandra , Tan Winston , Kurland John F. , Rebelatto Marlon C. , Jin Xiaoping , Blake-Haskins John A. , Gupta Ashok , Segal Neil H. 
Published: June 2016

Purpose To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). Methods A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1–positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. Results A total of 61 patients (40 PD-L1–positive, 21 PD-L1–negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1–positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1–negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). Conclusion Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily pretreated.