bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL1 released from M2b macrophages is essentially required for the maintenance of their properties
Authors: Asai Akira , Nakamura Kiwamu , Kobayashi Makiko , Herndon David N , Suzuki Fujio 
Published: June 2012

Abstract
Increased susceptibility of mice 10–30 days postburn to MRSA infection is controlled through the intervention of CCL1-producing M2bMΦ, appearing in association with burn injuries.
Patients with 10–30 days postburn injury are greatly susceptible to infections. M1MΦ (IL-10−IL-12+ MΦ) are essential cells in host antibacterial innate immunity against MRSA infections. However, these effector cells are not easily generated in hosts who are carriers of M2bMΦ (IL-12−IL-10+CCL1+LIGHT+ MΦ). M2bMΦ are inhibitory on M1MΦ generation. In this study, the antibacterial resistance of mice, 10–30 days postburn injury against MRSA infection, was improved by the modulation of M2bMΦ activities. Unburned mice inoculated with MΦ preparations from mice, 10–30 days after burn injury, were susceptible to MRSA infection, whereas unburned mice, inoculated with MΦ preparations from the same mice that were previously treated with CCL1 antisense ODN, were resistant to the infection. M2bMΦ, isolated from Day 15 burn mice, lost their M2bMΦ properties 3 days after cultivation under frequent medium changes, whereas their M2bMΦ properties remained in the same cultures supplemented with rCCL1. In cultures, MΦ preparations from Day 15 burn mice treated with CCL1 antisense ODN did not produce CCL1 and did convert to M1MΦ after heat-killed MRSA stimulation. Also, Day 15 burn mice treated with the ODN became resistant against MRSA infection. These results indicate that CCL1 released from M2bMΦ is essentially required for the maintenance of their properties. The increased susceptibility of mice, 10–30 days after burn injury to MRSA infection, may be controlled through the intervention of CCL1 production by M2bMΦ appearing in association with severe burn injuries.
Transient CD8-memory contraction: a potential contributor to latent cytomegalovirus reactivation
Authors: Campbell Jonathan , Trgovcich Joanne , Kincaid Michelle , Zimmerman Peter D , Klenerman Paul , Sims Stuart , Cook Charles H 
Published: June 2012

Abstract
Heterologous antigen encounters can induce transient T-memory contraction, allowing cytomegaloviral recrudescence in latently infected immunocompetent hosts.
It is clear that latent CMV can reactivate in immunocompetent individuals, but the mechanism triggering such reactivations remains unclear. Recent clinical data suggest that reactivation can be subverted by CMV-specific T-memory. We therefore monitored CMV-specific T cells in immunocompetent mice with latent mCMV after a known reactivation trigger (LPS). LPS induced transient systemic contraction of mCMV-specific CD8 memory that was followed by transcriptional reactivation. Subsequent recovery of mCMV-specific T cells coincided with resumption of latency. These data suggest that bacterial antigen encounters can induce transient T-memory contraction, allowing viral recrudescence in hosts latently infected with herpes family viruses.
Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures
Authors: Baxendale Sarah , Holdsworth Celia J. , Meza Santoscoy Paola L. , Harrison Michael R. M. , Fox James , Parkin Caroline A. , Ingham Philip W. , Cunliffe Vincent T. 
Published: June 2012

Summary
The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca2+) flux in muscle cells as well as intense locomotor activity. We then screened a library of ~2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-induced transcription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities.
Beyond Diagnostic Accuracy: The Clinical Utility of Diagnostic Tests
Authors: Bossuyt Patrick MM , Reitsma Johannes B , Linnet Kristian , Moons Karel GM 
Published: June 2012

Abstract
Like any other medical technology or intervention, diagnostic tests should be thoroughly evaluated before their introduction into daily practice. Increasingly, decision makers, physicians, and other users of diagnostic tests request more than simple measures of a test's analytical or technical performance and diagnostic accuracy; they would also like to see testing lead to health benefits. In this last article of our series, we introduce the notion of clinical utility, which expresses—preferably in a quantitative form—to what extent diagnostic testing improves health outcomes relative to the current best alternative, which could be some other form of testing or no testing at all. In most cases, diagnostic tests improve patient outcomes by providing information that can be used to identify patients who will benefit from helpful downstream management actions, such as effective treatment in individuals with positive test results and no treatment for those with negative results. We describe how comparative randomized clinical trials can be used to estimate clinical utility. We contrast the definition of clinical utility with that of the personal utility of tests and markers. We show how diagnostic accuracy can be linked to clinical utility through an appropriate definition of the target condition in diagnostic-accuracy studies.
A Review on Metaanalysis of Biomarkers: Promises and Pitfalls
Authors: Lewington Sarah , Bragg Fiona , Clarke Robert 
Published: June 2012

Abstract

BACKGROUND
The last 30 years have seen an exponential increase in metaanalyses. By combining multiple studies, metaanalysis can provide an overview of the totality of evidence on a particular question and the statistical power needed to reduce random error and produce precise estimates of even modest effect sizes. This capability is of particular value when many small studies address similar questions [such as in the investigation of novel cardiovascular disease (CVD) biomarkers]. To provide reliable evidence, however, metaanalyses must be undertaken robustly.

CONTENT
In this review, we describe the major issues to consider when designing and conducting metaanalyses, including the design of constituent studies, selection criteria, assessment of exposures and disease outcomes, and control of bias and confounding. Some of the potential challenges and pitfalls associated with metaanalysis are examined, and their consequences are considered. We use 2 examples of novel biomarkers for CVD—homocysteine and triglycerides—to illustrate how metaanalyses of observational studies have contributed to, and on occasion hindered, our understanding; and how subsequent work has built upon these findings.

SUMMARY
Metaanalyses of observational studies, particularly metaanalyses of individual-participant data, have the power to provide robust evidence to support our understanding of the role of novel biomarkers for disease. The characteristic limitations and challenges of these studies, including their inability to detect causal associations, must be considered, however, and additional evidence from randomized controlled trials and genetic studies is frequently required to elucidate fully the role of novel biomarkers in predicting cardiovascular risk.
Biases Introduced by Choosing Controls to Match Risk Factors of Cases in Biomarker Research
Authors: Sullivan Pepe Margaret , Fan Jing , Seymour Christopher W , Li Christopher , Huang Ying , Feng Ziding 
Published: June 2012

Abstract

BACKGROUND
Selecting controls that match cases on risk factors for the outcome is a pervasive practice in biomarker research studies. Such matching, however, biases estimates of biomarker prediction performance. The magnitudes of these biases are unknown.

METHODS
We examined the prediction performance of biomarkers and improvements in prediction gained by adding biomarkers to risk factor information. Data simulated from bivariate normal statistical models and data from a study to identify critically ill patients were used. We compared true performance with that estimated from case control studies that do or do not use matching. ROC curves were used to quantify performance. We propose a new statistical method to estimate prediction performance from matched studies for which data on the matching factors are available for subjects in the population.

RESULTS
Performance estimated with standard analyses can be grossly biased by matching, especially when biomarkers are highly correlated with matching risk factors. In our studies, the performance of the biomarker alone was underestimated whereas the improvement in performance gained by adding the marker to risk factors was overestimated by 2–10-fold. We found examples for which the relative ranking of 2 biomarkers for prediction was inappropriately reversed by use of a matched design. The new approach to estimation corrected for bias in matched studies.

CONCLUSIONS
To properly gauge prediction performance in the population or the improvement gained by adding a biomarker to known risk factors, matched case control studies must be supplemented with risk factor information from the population and must be analyzed with nonstandard statistical methods.
Clinically insignificant improvement of prostate cancer prediction by addition of sex steroid hormones and SHBG serum levels to serum PSA, fPSA%, and age in a screening setting
Authors: Heidegger Isabel , Popovscaia Marina , Ramoner Reinhold , Schäfer Georg , Stenzel Birgit , Bektic Jasmin , Horninger Wolfgang , Klocker Helmut 
Published: June 2012

Abstract
Various findings implicate sex hormones in prostate growth and development and also in prostate carcinogenesis. We investigated if addition of sex steroid hormone and sex hormone binding globulin (SHBG) serum levels to standard risk assessment parameters [prostate-specific antigen (PSA), free PSA percentage (fPSA%), and age] improves prostate cancer prediction in a PSA screening setting. Steroid hormones testosterone (T), free testosterone (fT), and estradiol (E2), and binding protein SHBG levels were measured in 762 men undergoing prostate biopsy due to suspect PSA serum levels. Prostate cancer was diagnosed in 286 (37.5%) of these men. Our data confirmed that PSA (mean BE=5.09; mean CA=6.05; p=1.24×10–5), fPSA% (mean BE=22.08; mean CA=18.67; p=1.97×10–7), and age (mean BE=60.64; mean CA=64.5; p=7.05×10–10) differentiate men with cancer (CA) and men with benign disease (BE), such as benign prostate hyperplasia. In addition, SHBG (mean BE=50.3; mean CA=54.9; p=0.008) also differed statistically significantly between these two groups. All hormones except E2 and tumor markers correlated significantly with age (T: ρ=–0.09; fT: ρ=–0.27; SHBG: ρ=0.21; PSA: ρ=0.32; and fPSA%: ρ=0.22). Furthermore, we found that PSA correlates with E2 (ρ=0.08), and fPSA% with SHBG (ρ=0.1) and fT (ρ=–0.09). Addition of hormones and SHBG to a baseline marker model including PSA, fPSA%, and age improved cancer prediction in three multivariate classification methods; however, the improvement was minimal. The best improvement by 0.8% was obtained in the logistic regression model with the addition of T and SHBG or of E2 and SHBG, or in the support vector machine model with the addition of SHBG and all steroid hormones to the combination of standard markers PSA, fPSA%, and age; however, this additional gain of accuracy is too small to justify the additional efforts and costs.
Numerical method for solving an inverse electrocardiography problem for a quasi stationary case
Authors: Denisov Alexander M. , Zakharov Eugene V. , Kalinin Alexander V. , Kalinin Vitaliy V. 
Published: June 2012

Abstract.
An inverse electrocardiography problem for a different time moment is studied. The realistic 3D geometry of human torso and chest medium with piecewise constant electrical conductivity are considered. A numerical method for solving the inverse electrocardiography problem at a given time moment is suggested. Results of comparison of numerical solutions to the inverse electrocardiography problems for a clinical data on torso surface and a clinical measurement inside of heart are given.
Association between Peritransplant Kidney Injury Biomarkers and 1-Year Allograft Outcomes
Authors: Hall Isaac E. , Doshi Mona D. , Reese Peter P. , Marcus Richard J. , Thiessen-Philbrook Heather , Parikh Chirag R. 
Published: June 2012

Summary

Background and objectives
Current tools to predict outcomes after kidney transplantation are inadequate. The objective of this study was to determine the association of perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 with poor 1-year allograft function (return to dialysis or estimated GFR<30 ml/min per 1.73 m2).

Design, setting, participants, & measurements
Neutrophil gelatinase-associated lipocalin and IL-18 from early post-transplant urine was measured in this prospective, multicenter study of deceased-donor kidney transplant recipients. The outcome of poor allograft function at 1 year relative to these biomarkers using multivariable logistic regression and net reclassification improvement was examined. Also, the interaction between delayed graft function and the biomarkers on the outcome were evaluated, and the change in biomarkers over consecutive days related to the outcome using trend tests was examined.

Results
Mean age for the 153 recipients was 54 ± 13 years. Delayed graft function occurred in 42%, and 24 (16%) recipients had the 1-year outcome. Upper median values for neutrophil gelatinase-associated lipocalin and IL-18 on the first postoperative day had adjusted odds ratios (95% confidence interval) of 6.0 (1.5–24.0) and 5.5 (1.4–21.5), respectively. Net reclassification improvement (95% confidence interval) was significant for neutrophil gelatinase-associated lipocalin and IL-18 at 36% (1%–71%) and 45% (8%–83%), respectively. There was no significant interaction between biomarkers and delayed graft function on the outcome. Change in biomarkers moderately trended with the outcome.

Conclusions
Perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 are associated with poor 1-year allograft function, suggesting their potential for identifying patients for therapies that minimize the risk of additional injury.
Nonlinear Measures of Heart Rate Variability and Mortality Risk in Hemodialysis Patients
Authors: Suzuki Mari , Hiroshi Takahashi , Aoyama Toru , Tanaka Miho , Ishii Hideki , Kisohara Masaya , Iizuka Narushi , Murohara Toyoaki , Hayano Junichiro 
Published: June 2012

Summary

Background and objectives
Nonlinear measures of heart rate variability (HRV) have gained recent interest as powerful risk predictors in various clinical settings. This study examined whether they improve risk stratification in hemodialysis patients.

Design, setting, participants, & measurements
To assess heart rate turbulence, deceleration capacity, fractal scaling exponent (α1), and other conventional HRV measures, 281 hemodialysis patients underwent 24-hour electrocardiography between January 2002 and May 2004 and were subsequently followed up.

Results
During a median 87-month follow-up, 77 patients (27%) died. Age, left ventricular ejection fraction, serum albumin, C-reactive protein, and calcium × phosphate independently predicted mortality. Whereas all nonlinear HRV measures predicted mortality, only decreased scaling exponent α1 remained significant after adjusting for clinical risk factors (hazard ratio per a 0.25 decrement, 1.46; 95% confidence interval [95% CI], 1.16–1.85). The inclusion of α1 into a prediction model composed of clinical risk factors increased the C statistic from 0.84 to 0.87 (P=0.03), with 50.8% (95% CI, 20.2–83.7) continuous net reclassification improvement for 5-year mortality. The predictive power of α1 showed an interaction with age (P=0.02) and was particularly strong in patients aged <70 years (n=208; hazard ratio, 1.87; 95% CI, 1.38–2.53), among whom α1 increased the C statistic from 0.85 to 0.89 (P=0.01), with a 93.1% (95% CI, 59.3–142.0) continuous net reclassification improvement.

Conclusions
Scaling exponent α1 that reflects fractal organization of short-term HRV improves risk stratification for mortality when added to the prediction model by conventional risk factors in hemodialysis patients, particularly those aged <70 years.
Serum Albumin as Predictor of Nutritional Status in Patients with ESRD
Authors: Gama-Axelsson Thiane , Heimbürger Olof , Stenvinkel Peter , Bárány Peter , Lindholm Bengt , Qureshi Abdul Rashid 
Published: June 2012

Summary

Background and objectives
Serum albumin is a widely used biomarker of nutritional status in patients with CKD; however, its usefulness is debated. This study investigated serum albumin and its correlation with several markers of nutritional status in incident and prevalent dialysis patients.

Design, setting, participants, & measurements
In a cross-sectional study, serum albumin (bromocresol purple), and other biochemical (serum creatinine), clinical (subjective global assessment [SGA]), anthropometric (handgrip strength; skinfold thicknesses), and densitometry (dual-energy x-ray absorptiometry) markers of nutritional status were assessed in 458 incident (61% male; mean age, 54±13 years; GFR, 6.6±0.3 ml/min per 1.73 m2; recruited 1994–2010) and 383 prevalent (56% male; mean age, 62±14 years; recruited 1989–2004) dialysis patients.

Results
In incident patients, serum albumin was correlated with age (β =−0.15; P<0.001), diabetes (β=−0.30; P<0.001), high-sensitivity C-reactive protein (β =−0.37; P<0.001), and urinary albumin excretion (β=−0.38; P<0.001) but less so with poor nutritional status (SGA score > 1; β=−0.19; P<0.001). In prevalent patients, serum albumin was correlated with age (β=−0.15; P<0.001), high-sensitivity C-reactive protein (β=−0.30; P<0.001), diabetes (β=−0.31; P<0.001), and SGA score > 1 (β=−0.16; P<0.001). In predicting nutritional status assessed by SGA and other markers, adding serum albumin to models that included age, sex, diabetes, and cardiovascular disease did not significantly increase explanatory power.

Conclusions
In incident and prevalent dialysis patients, serum albumin correlates poorly with several markers of nutritional status. Thus, its value as a reliable marker of nutritional status in patients with ESRD is limited.
Designing Continuous Auditing for a Highly Automated Procure-to-Pay Process
Authors: Borthick A. Faye 
Published: June 2012

ABSTRACTTo provide real-time assurance, auditors must rely on continuous auditing. Although the need for continuous auditing is readily apparent, not many auditors have experience in implementing or relying on it. The purpose of this writing is to illustrate how Chan and Vasarhelyi's (2011) stages of continuous auditing might be instantiated in a highly automated procure-to-pay process using the Krishnan et al. (2005) notation for representing controls in business process diagrams. In Stage 1, existing processes and controls are examined to identify the monitoring and testing that is suitable for continuous auditing and confirm sufficient data access. In Stage 2, metrics for evaluating transaction data are defined. In Stage 3, rule-based analytics are developed as benchmarks for determining internal control violations. In stage 4, an audit-by-exception approach is described for determining the level of material errors, omissions, and other anomalies.
One-step synthesis of solid sulfonic acid catalyst and its application in the acetalization of glycerol: crystal structure of cis-5-hydroxy-2-phenyl-1,3-dioxane trimer
Authors: Adam Farook , Batagarawa Muazu , Hello Kasim , Al-Juaid Salih 
Published: June 2012

AbstractA one-pot method was employed to immobilize sulfonic acid onto silica obtained from rice husk ash using 3-(mercaptopropyl)trimethoxysilane to form a solid catalyst denoted as RHASO3H. BET measurements of the catalyst showed the surface area to be 340 m2 g−1 with the average pore volume of 0.24 mL g−1 and the pore diameter of 2.9 nm. Acidity test of cation exchange capacity and pyridine adsorption studies revealed the presence of Brønsted acid sites on the catalyst surface. The catalyst was used in the acetalization reaction of glycerol with benzaldehyde. Under optimized conditions, the reaction showed the maximum conversion of 78 % after 8 h with 67 % selectivity towards the five membered ring isomer. Variation in the glycerol concentration had a significant effect on the reactants conversion. A single crystal X-ray study of one of the products proved the existence of a unique trimer formed by hydrogen bonding by the six-membered cis-isomer. The catalyst was several times recycled without any loss of its catalytic activity.
Mechanistic insights into the reaction of CF3CCl3 with SO3: Theory and experiment
Authors: Liu Zhi-Zheng , Chen Zhi-Rong , Yin Hong , Yuan Shen-Feng 
Published: June 2012

AbstractReaction mechanism of 1,1,1-trifluorotrichloroethane (CF3CCl3) and sulphur trioxide (SO3) in the presence of mercury salts (Hg2SO4 and HgSO4) was studied applying the density functional theory (DFT) at the UB3LYP/6-31+G(d,p) level. It was found that this reaction occurs in the free radical chain path as follows: mercury(I) sulphate free radical is generated by heat, causing CF3CCl3 to produce the CF3CCl2 free radical which reacts with SO3 leading to the formation of CF3CCl2OSO2 decomposing into CF3COCl and SO2Cl. The SO2Cl free radical triggers CF3CCl3 to regenerate CF3CCl2 which recycles the free radical growth reaction. This elementary reaction has the highest energy barrier and it is therefore the rate control step of the whole reaction path. Experiment data can confirm the existence of the mercury(I) salt free radical and the free radical initiation stage. So, mercury salts play the role of initiators not that of catalysts. The results agree well with our hypothesis.