bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL uptake
Authors: Amézaga Núria , Sanjurjo Lucía , Julve Josep , Aran Gemma , Pérez-Cabezas Begoña , Bastos-Amador Patricia , Armengol Carolina , Vilella Ramon , Escolà-Gil Joan Carles , Blanco-Vaca Francisco , Borràs Francesc E , Valledor Annabel F , Sarrias Maria-Rosa 
Published: December 2013

ABSTRACTAIM is expressed by macrophages in response to agonists of the nuclear receptors LXR/RXR. In mice, it acts as an atherogenic factor by protecting macrophages from the apoptotic effects of oxidized lipids. In humans, it is detected in atherosclerotic lesions, but no role related to atherosclerosis has been reported. This study aimed to investigate whether the role of hAIM extends beyond inhibiting oxidized lipid-induced apoptosis. To accomplish this goal, functional analysis with human monocytic THP1 cells and macrophages differentiated from peripheral blood monocytes were performed. It was found that hAIM reduced oxLDL-induced macrophage apoptosis and increased macrophage adhesion to endothelial ICAM-1 by enhancing LFA-1 expression. Furthermore, hAIM increased foam cell formation, as shown by Oil Red O and Nile Red staining, as well as quantification of cholesterol content. This was not a result of decreased reverse cholesterol transport, as hAIM did not affect the efflux significantly from [3H] Cholesterol-laden macrophages driven by plasma, apoA-I, or HDL2 acceptors. Rather, flow cytometry studies indicated that hAIM increased macrophage endocytosis of fluorescent oxLDL, which correlated with an increase in the expression of the oxLDLR CD36. Moreover, hAIM bound to oxLDL in ELISA and enhanced the capacity of HEK-293 cells expressing CD36 to endocytose oxLDL, as studied using immunofluorescence microscopy, suggesting that hAIM serves to facilitate CD36-mediated uptake of oxLDL. Our data represent the first evidence that hAIM is involved in macrophage survival, adhesion, and foam cell formation and suggest a significant contribution to atherosclerosis-related mechanisms in the macrophage.
Deep Molecular Response Is Reached by the Majority of Patients Treated With Imatinib, Predicts Survival, and Is Achieved More Quickly by Optimized High-Dose Imatinib: Results From the Randomized CML-Study IV
Authors: Hehlmann Rüdiger , Müller Martin C. , Lauseker Michael , Hanfstein Benjamin , Fabarius Alice , Schreiber Annette , Proetel Ulrike , Pletsch Nadine , Pfirrmann Markus , Haferlach Claudia , Schnittger Susanne , Einsele Hermann , Dengler Jolanta , Falge Christiane , Kanz Lothar , Neubauer Andreas , Kneba Michael , Stegelmann Frank , Pfreundschuh Michael , Waller Cornelius F. , Spiekermann Karsten , Baerlocher Gabriela M. , Ehninger Gerhard , Heim Dominik , Heimpel Hermann , Nerl Christoph , Krause Stefan W. , Hossfeld Dieter K. , Kolb Hans-Jochem , Hasford Joerg , Saußele Susanne , Hochhaus Andreas 
Published: December 2013

Purpose Deep molecular response (MR4.5) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR4.5 under different treatment modalities and whether MR4.5 predicts survival. Patients and Methods Patients from the randomized CML-Study IV were analyzed for confirmed MR4.5 which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR4.5 on survival. Results Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR4.5 after 9 years was 70% (median, 4.9 years); confirmed MR4.5 was 54%. MR4.5 was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR4.5 at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR4.5. No patient with confirmed MR4.5 has experienced progression. Conclusion MR4.5 is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.
Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium and Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity (N08CB/Alliance)
Authors: Loprinzi Charles L. , Qin Rui , Dakhil Shaker R. , Fehrenbacher Louis , Flynn Kathleen A. , Atherton Pamela , Seisler Drew , Qamar Rubina , Lewis Grant C. , Grothey Axel 
Published: December 2013

Purpose Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. Intravenous calcium and magnesium have been extensively used to reduce oxaliplatin-induced neurotoxicity. This trial was designed to definitively test whether calcium/magnesium decreases oxaliplatin-related neurotoxicity. Patients and Methods In all, 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous calcium/magnesium before and after oxaliplatin, a placebo before and after, or calcium/magnesium before and placebo after. The primary end point was cumulative neurotoxicity measured by the sensory scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 tool. Results There were no statistically significant neuropathy differences among the study arms as measured by the primary end point or additional measures of neuropathy, including clinician-determined measurement of the time to grade 2 neuropathy by using the National Cancer Institute Common Terminology Criteria for Adverse Events scale or an oxaliplatin-specific neuropathy scale. In addition, calcium/magnesium did not substantially decrease oxaliplatin-induced acute neuropathy. Conclusion This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity.
Influence of Conventional Cardiovascular Risk Factors and Lifestyle Characteristics on Cardiovascular Disease After Hematopoietic Cell Transplantation
Authors: Chow Eric J. , Baker K. Scott , Lee Stephanie J. , Flowers Mary E.D. , Cushing-Haugen Kara L. , Inamoto Yoshihiro , Khera Nandita , Leisenring Wendy M. , Syrjala Karen L. , Martin Paul J. 
Published: December 2013

Purpose To determine the influence of modifiable lifestyle factors on the risk of cardiovascular disease after hematopoietic cell transplantation (HCT). Patients and Methods HCT survivors of ≥ 1 year treated from 1970 to 2010 (n = 3,833) were surveyed from 2010 to 2011 on current cardiovascular health and related lifestyle factors (smoking, diet, recreational physical activity). Responses (n = 2,362) were compared with those from a matched general population sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192). Results Compared with NHANES participants, HCT survivors (median age, 55.9 years; median 10.8 years since HCT; 71.3% allogeneic) had higher rates of cardiomyopathy (4.0% v 2.6%), stroke (4.8% v 3.3%), dyslipidemia (33.9% v 22.3%), and diabetes (14.3% v 11.7%; P < .05 for all comparisons). Prevalence of hypertension was similar (27.9% v 30.0%), and survivors were less likely to have ischemic heart disease (6.1% v 8.9%; P < .01). Among HCT survivors, hypertension, dyslipidemia, and diabetes were independent risk factors for ischemic heart disease and cardiomyopathy, and smoking was associated with ischemic heart disease and diabetes (odds ratios [ORs], 1.8 to 2.1; P = .02). Obesity was a risk factor for post-transplantation hypertension, dyslipidemia, and diabetes (ORs ≥ 2.0; P < .001). In contrast, lower fruit/vegetable intake was associated with greater risk of dyslipidemia and diabetes (ORs, 1.4 to 1.8; P ≤ .01), and lower physical activity level was associated with greater risk of hypertension and diabetes (ORs, 1.4 to 1.5; P < .05). Healthier lifestyle characteristics among HCT survivors attenuated risk of all cardiovascular conditions assessed. Conclusion Attention of clinicians to conventional cardiovascular risk factors and modifiable lifestyle characteristics offers hope of reducing serious cardiovascular morbidity after HCT.
RNA Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Reduced Expression of Immune Function Genes in BRAF (V600E) Mutant vs BRAF Wild-Type Papillary Thyroid Carcinoma
Authors: Smallridge Robert C. , Chindris Ana-Maria , Asmann Yan W. , Casler John D. , Serie Daniel J. , Reddi Honey V. , Cradic Kendall W. , Rivera Michael , Grebe Stefan K. , Necela Brian M. , Eberhardt Norman L. , Carr Jennifer M. , McIver Bryan , Copland John A. , Thompson E. Aubrey 
Published: December 2013

Context:
The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression.

Objective:
RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status.

Design:
BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2–3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes.

Patients:
BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes.

Results:
RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR.

Conclusion:
BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent of tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of these newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-MUT and BRAF-WT tumors.
Additive, Epistatic, and Environmental Effects Through the Lens of Expression Variability QTL in a Twin Cohort
Authors: Wang Gang , Yang Ence , Brinkmeyer-Langford Candice L , Cai James J 
Published: December 2013

AbstractThe expression of a gene can vary across individuals in the general population, as well as between monozygotic twins. This variable expression is assumed to be due to the influence of both genetic and nongenetic factors. Yet little evidence supporting this assumption has been obtained from empirical data. In this study, we used expression data from a large twin cohort to investigate the influences of genetic and nongenetic factors on variable gene expression. We focused on a set of expression variability QTL (evQTL)—i.e., genetic loci associated with the variance, as opposed to the mean, of gene expression. We identified evQTL for 99, 56, and 79 genes in lymphoblastoid cell lines, skin, and fat, respectively. The differences in gene expression, measured by the relative mean difference (RMD), tended to be larger between pairs of dizygotic (DZ) twins than between pairs of monozygotic (MZ) twins, showing that genetic background influenced the expression variability. Furthermore, a more profound RMD was observed between pairs of MZ twins whose genotypes were associated with greater expression variability than the RMD found between pairs of MZ twins whose genotypes were associated with smaller expression variability. This suggests that nongenetic (e.g., environmental) factors contribute to the variable expression. Lastly, we demonstrated that the formation of evQTL is likely due to partial linkages between eQTL SNPs that are additively associated with the mean of gene expression; in most cases, no epistatic effect is involved. Our findings have implications for understanding divergent sources of gene expression variability.
School Violence, Mental Health, and Educational Performance in Uganda
Authors: Devries Karen M. , Child Jennifer C. , Allen Elizabeth , Walakira Eddy , Parkes Jenny , Naker Dipak 
Published: December 2013

BACKGROUND:
Violence against children from school staff is anecdotally common in low- and middle-income countries, but data on prevalence and associations with mental health and educational outcomes are lacking.

METHODS:
We report data from a cross-sectional survey conducted in June and July 2012 in Luwero District, Uganda. Forty-two primary schools representing 80% of students in the district were randomly selected; 100% agreed to participate. The International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool—Child Institutional; Strengths and Difficulties Questionnaire; and reading, spelling, and math tests were administered. We present descriptive statistics and logistic regression models, accounting for the complex sampling scheme used in the survey.

RESULTS:
We surveyed 3706 students and 577 school staff members; 93.3% (SE 1.0%) of boys and 94.2% (SE 1.6%) of girls attending primary school reported lifetime experience of physical violence from a school staff member, and &gt;50% reported experience in the past week. Past-week physical violence was associated with increased odds of poor mental health and, for girls, double the odds of poor educational performance (adjusted odds ratio = 1.78, 95% confidence interval = 1.19–2.66). For boys, significant interactions were present.

CONCLUSIONS:
Despite a ban on corporal punishment in Ugandan schools since 1997, the use of violence against students is widespread and associated with poor mental health and educational performance. School violence may be an important but overlooked contributor to disease burden and poor educational performance in low- and middle-income settings.
Exercise and Insulin Resistance in Youth: A Meta-Analysis
Authors: Fedewa Michael V. , Gist Nicholas H. , Evans Ellen M. , Dishman Rod K. 
Published: December 2013

BACKGROUND AND OBJECTIVES:
The prevalence of obesity and diabetes is increasing among children, adolescents, and adults. Although estimates of the efficacy of exercise training on fasting insulin and insulin resistance have been provided, for adults similar estimates have not been provided for youth. This systematic review and meta-analysis provides a quantitative estimate of the effectiveness of exercise training on fasting insulin and insulin resistance in children and adolescents.

METHODS:
Potential sources were limited to peer-reviewed articles published before June 25, 2013, and gathered from the PubMed, SPORTDiscus, Physical Education Index, and Web of Science online databases. Analysis was limited to randomized controlled trials by using combinations of the terms adolescent, child, pediatric, youth, exercise training, physical activity, diabetes, insulin, randomized trial, and randomized controlled trial. The authors assessed 546 sources, of which 4.4% (24 studies) were eligible for inclusion. Thirty-two effects were used to estimate the effect of exercise training on fasting insulin, with 15 effects measuring the effect on insulin resistance. Estimated effects were independently calculated by multiple authors, and conflicts were resolved before calculating the overall effect.

RESULTS:
Based on the cumulative results from these studies, a small to moderate effect was found for exercise training on fasting insulin and improving insulin resistance in youth (Hedges’ d effect size = 0.48 [95% confidence interval: 0.22–0.74], P &lt; .001 and 0.31 [95% confidence interval: 0.06–0.56], P &lt; .05, respectively).

CONCLUSIONS:
These results support the use of exercise training in the prevention and treatment of type 2 diabetes.
Understanding the Convection Heat-Transfer Mechanism in the Steam-Assisted-Gravity-Drainage Process
Authors: Irani Mazda , Gates Ian 
Published: December 2013

Summary
Steam-assisted gravity drainage (SAGD) is the preferred method to extract bitumen from Athabasca oil-sand reservoirs in western Canada. In SAGD, steam, injected outward from a horizontal injection well, loses its latent heat when it contacts the cold bitumen at the edge of a steam chamber. Consequently, the viscosity of the bitumen falls several orders of magnitude, enabling it to flow under gravity toward a horizontal production well directly below to the injection well. It is commonly believed that conduction is the dominant heat-transfer mechanism at the edge of the chamber. Heat transfer by convection is not considered in classic SAGD mathematical models such as the one derived by Butler. Researchers such as Butler and Stephens (1981), Reis (1992), Akin (2005), Liang (2005), Nukhaev et al. (2006), and Azad and Chalaturnyk (2010) considered the conduction from steam to cold reservoir to be the only heat-transfer component. Farouq-Ali (1997), Edmunds (1999a, b), Ito and Suzuki (1996, 1999), Ito et al. (1998), Sharma and Gates (2011), and Irani and Ghannadi (2013) questioned the assumption that thermal conduction dominates heat transfer at the edge of a SAGD chamber. Sharma and Gates (2011) and Irani and Ghannadi (2013) studied convective flux from condensate flow at the edge of an SAGD steam chamber. Irani and Ghannadi (2013) derived a new formulation that solves the energy balance and pressure-driven condensate flow normal to the steam-chamber interface into the cold bitumen reservoir and concluded that the assumption of conduction-dominated heat transfer is valid; however, all previous analyses do not include convective heat transfer arising from draining bitumen and condensate. Although a few researchers have studied convective flux from condensate flow at the edge of an SAGD steam chamber (e.g., Sharma and Gates 2011; Irani and Ghannadi 2013), there is a lack of understanding of bitumen and condensate drainage parallel to the edge of the chamber and of its effect on transverse heat transfer into the oil sand beyond the chamber. In this study, the relative roles of convective heat flux both parallel and normal to the edge of a steam chamber are examined. The results suggest that the convective heat flux associated with flow parallel to the chamber edge is minor compared with that normal to the edge.
Field Data on Accounting Error Rates and Audit Sampling
Authors: Durney Michael , Elder Randal J. , Glover Steven M. 
Published: December 2013

SUMMARY:
Changes in the accounting and auditing environments since the passage of Sarbanes-Oxley (SOX) and the creation of the Public Accounting Oversight Board (PCAOB) have likely impacted accounting population error rates and audit sampling procedures. We investigate accounting population error rates and auditor sampling performance for a unique proprietary post-SOX dataset of 160 audit sampling applications for a large auditing firm. Compared to previous research, we find that in the post-SOX period, accounting data error rates are significantly lower in magnitude and frequency, sample sizes are significantly larger, and auditor performance has improved in evaluating sample errors. The low error rates suggest criticisms in prior research regarding audit sampling techniques may not be a serious concern for most audit sampling applications. Furthermore, we provide evidence that auditors' application of audit sampling is more consistent with the requirements in professional standards than previously reported.
Usefulness of Doppler ultrasonography to assess digital vascular dynamics in horses with systemic inflammatory response syndrome or laminitis
Authors: Aguirre Carla N. , Talavera Jesús , Fernández del Palacio María Josefa 
Published: December 2013

Abstract
Objective—To evaluate the usefulness of Doppler ultrasonography as a method to assess changes in digital vascular dynamics in horses with systemic inflammatory response syndrome (SIRS) or laminitis.
Design—Cross-sectional study.
Animals—42 adult Andalusian horses.
Procedures—Group 1 included 9 healthy horses, group 2 included 19 horses with SIRS without (n = 9) or with (10) a palpable increase in digital pulse intensity, and group 3 included 14 horses with laminitis without (8) or with (6) radiographic evidence of rotation or distal displacement (sinking) of the third phalanx. Qualitative spectrum characteristics and quantitative Doppler measurements of the lateral palmar digital artery were obtained for horses in each group.
Results—4 spectra, characterized by a positive systolic peak followed by several positive diastolic peaks, were observed in group 1 horses, group 2 horses, and group 3 horses that lacked radiographic changes. In the group 3 horses that had radiographic changes, laminar blood flow was detected. Diameter of the lateral palmar digital artery was significantly larger in the group 3 horses than in the group 2 horses; blood flow was significantly higher in the group 2 horses that had an increase in digital pulse intensity than in the group 2 horses without an increase in digital pulse intensity; velocity-time integral and acceleration time were significantly lower in group 3 horses, compared with group 2 horses.
Conclusions and Clinical Relevance—Results suggested that Doppler ultrasonography may be a useful complementary tool to detect digital blood flow changes of horses with SIRS, especially if they have a palpable increase in digital pulse intensity, or laminitis.