bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of errors in segmented attenuation maps on PET quantification
Authors: Keereman Vincent , Van Holen Roel , Mollet Pieter , Vandenberghe Stefaan 
Published: October 2011

Purpose:Accurate attenuation correction is important for PET quantification. Often, a segmented attenuation map is used, especially in MRI‐based attenuation correction. As deriving the attenuation map from MRI images is difficult, different errors can be present in the segmented attenuation map. The goal of this paper is to determine the effect of these errors on quantification.Methods:The authors simulated the digital XCAT phantom using the GATE Monte Carlo simulation framework and a model of the Philips Gemini TF. A whole body scan was simulated, spanning an axial field of view of 70 cm. A total of fifteen lesions were placed in the lung, liver, spine, colon, prostate, and femur. The acquired data were reconstructed with a reference attenuation map and with different attenuation maps that were modified to reflect common segmentation errors. The quantitative difference between reconstructed images was evaluated.Results:Segmentation into five tissue classes, namely cortical bone, spongeous bone, soft tissue, lung, and air yielded errors below 5%. Large errors were caused by ignoring lung tissue (up to 45%) or cortical bone (up to 17%). The interpatient variability of lung attenuation coefficients can lead to errors of 10% and more. Up to 20% tissue misclassification from bone to soft tissue yielded errors below 5%. The same applies for up to 10% misclassification from lung to air.Conclusions:When using a segmented attenuation map, at least five different tissue types should be considered: cortical bone, spongeous bone, soft tissue, lung, and air. Furthermore, the interpatient variability of lung attenuation coefficients should be taken into account. Limited misclassification from bone to soft tissue and from lung to air is acceptable, as these do not lead to relevant errors.
The Coxiella burnetii Dot/Icm System Creates a Comfortable Home through Lysosomal Renovation
Authors: Newton Hayley J. , Roy Craig R. 
Published: October 2011

ABSTRACT

Understanding the molecular pathogenesis of
Coxiella burnetii
, the causative agent of human Q fever, has historically been hindered by the technical difficulties of genetically manipulating obligate intracellular bacteria. The recent development of culture conditions suitable for axenic propagation of
C. burnetii
has paved the way for the application of a range of genetic techniques to address key questions within the field. Recent studies using mutational analysis have revealed that the
C. burnetii
Dot/Icm type 4 secretion system (T4SS) is an important virulence determinant that is essential for renovation of a lysosome into a mature
Coxiella
-containing vacuole (CCV) permissive of intracellular replication. Interestingly, a mutant of
C. burnetii
deficient in Dot/Icm function was found to be capable of replicating within the parasitophorous vacuole created by
Leishmania amazonensis
, which indicates that
C. burnetii
replication is not dependent on the cohort of Dot/Icm effector proteins
per se
but rather that the collective actions of effectors are required to create the specialized niche supportive of replication. Thus, a role for the Dot/Icm T4SS during the intracellular life cycle of
C. burnetii
has been more clearly defined by these studies, which demonstrate that advances in genetic analysis should allow future studies to focus on the intricacies of Dot/Icm effector functions that facilitate development of the unique CCV.
Prospects for TIM3-Targeted Antitumor Immunotherapy
Authors: Ngiow Shin Foong , Teng Michele W.L. , Smyth Mark J. 
Published: October 2011

Abstract
New insights into the control of T-cell activation and proliferation have led to the identification of checkpoint proteins that either up- or downmodulate T-cell reactivity. Monoclonal antibody immunotherapies that are reactive with cytotoxic T lymphocyte antigen 4 or programmed death receptor 1 have shown promising therapeutic outcomes in mice and humans with established cancer, highlighting the fact that cancer immunotherapy using T-cell checkpoint inhibitors is one of the most promising new therapeutic approaches. T-cell immunoglobulin and mucin domain 3 (TIM3) is one of many similar inhibitory molecules that are gaining attention as targets, but it remains relatively poorly studied in oncology. This review discusses our recent probing of the mechanism of action of anti-TIM3 antibody against established spontaneous and experimental tumors in mice, in the context of the exciting possibility of rationally combining agents that promote tumor-specific T-cell activation, proliferation, effector function, and survival. Cancer Res; 71(21); 6567–71. ©2011 AACR.
New Strategies for Treatment of ALK-Rearranged Non–Small Cell Lung Cancers
Authors: Sasaki Takaaki , Jänne Pasi A. 
Published: October 2011

Abstract
The identification of oncogenic alterations in subsets of patients with non–small cell lung cancer (NSCLC) is transforming clinical care. Genomic rearrangements in anaplastic lymphoma kinase (ALK) are detected in 3% to 7% of patients with NSCLC. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U.S. Food and Drug Administration. Crizotinib is currently under additional phase III clinical development as both initial and second-line therapy for advanced ALK-rearranged NSCLC. However, new challenges in the diagnosis and treatment of this subset of NSCLC have emerged, including the need to determine the most effective means of diagnosing ALK-rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review, we discuss current strategies for treatment and diagnosis, as well as the current knowledge about mechanisms of acquired resistance to crizotinib. Finally, we discuss the strategies that are underway to clinically overcome acquired drug resistance. Clin Cancer Res; 17(23); 7213–8. ©2011 AACR.
The Emergence of lncRNAs in Cancer Biology
Authors: Prensner John R. , Chinnaiyan Arul M. 
Published: October 2011

AbstractThe discovery of numerous noncoding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially the biology of diseases such as cancer. In humans, the identification of abundant long ncRNA (lncRNA) &gt;200 bp has catalyzed their characterization as critical components of cancer biology. Recently, roles for lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types, such as breast and prostate cancer. In this review, we highlight the emerging impact of ncRNAs in cancer research, with a particular focus on the mechanisms and functions of lncRNAs.Significance: lncRNAs represent the leading edge of cancer research. Their identity, function, and dysregulation in cancer are only beginning to be understood, and recent data suggest that they may serve as master drivers of carcinogenesis. Increased research on these RNAs will lead to a greater understanding of cancer cell function and may lead to novel clinical applications in oncology. Cancer Discovery; 1(5): 391–407. ©2011 AACR.
A Gene Expression Signature That Classifies Human Atherosclerotic Plaque by Relative Inflammation Status
Authors: Puig Oscar , Yuan Jeffrey , Stepaniants Sergey , Zieba Renata , Zycband Emanuel , Morris Mark , Coulter Silvija , Yu Xiang , Menke John , Woods John , Chen Fabian , Ramey Dena R. , He Xuanmin , O'Neill Edward A. , Hailman Eric , Johns Douglas G. , Hubbard Brian K. , Yee Lum Pek , Wright Samuel D. , DeSouza Mary M. , Plump Andrew , Reiser Vladimír 
Published: October 2011

Background—
Atherosclerosis is a complex disease requiring improvements in diagnostic techniques and therapeutic treatments. Both improvements will be facilitated by greater exploration of the biology of atherosclerotic plaque. To this end, we carried out large-scale gene expression analysis of human atherosclerotic lesions.

Methods and Results—
Whole genome expression analysis of 101 plaques from patients with peripheral artery disease identified a robust gene signature (1514 genes) that is dominated by processes related to Toll-like receptor signaling, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction, and lysosomal activity. Further analysis of gene expression in microdissected carotid plaque samples revealed that this signature is differentially expressed in macrophage-rich and smooth muscle cell–containing regions. A quantitative PCR gene expression panel and inflammatory composite score were developed on the basis of the atherosclerotic plaque gene signature. When applied to serial sections of carotid plaque, the inflammatory composite score was observed to correlate with histological and morphological features related to plaque vulnerability.

Conclusions—
The robust mRNA expression signature identified in the present report is associated with pathological features of vulnerable atherosclerotic plaque and may be useful as a source of biomarkers and targets of novel antiatherosclerotic therapies.
Depression and Rehospitalization Following Acute Myocardial Infarction
Authors: Reese Rebecca L. , Freedland Kenneth E. , Steinmeyer Brian C. , Rich Michael W. , Rackley Justin W. , Carney Robert M. 
Published: October 2011

Background—

Elevated scores on depression symptom questionnaires predict rehospitalization after acute myocardial infarction (AMI). Whether the
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
, depressive disorders predict rehospitalization after AMI is unknown.

Methods and Results—

Participants (n=766) in an Enhancing Recovery and Coronary Heart Disease ancillary study were classified by diagnostic interview as having no depression, minor depression, or major depression after AMI. Cardiac rehospitalizations were tracked for up to 42 months. Cox proportional hazards regression was used to model the effect of depressive disorder on time to first cardiac rehospitalization, controlling for mortality risk factors. Logistic regression was used to compare the accuracy with which rehospitalization could be predicted by depression diagnosis or by the Beck Depression Inventory (BDI). Secondary analyses examined the effects of depression on the cumulative number of all-cause rehospitalizations, length of stay, and emergency department visits. Compared with patients without depression, patients with either minor or major depression were hospitalized sooner (minor depression adjusted hazard ratio, 2.22; 95% CI, 1.59–3.08;
P
<0.001; major depression adjusted hazard ratio, 2.54; 95% CI, 1.84–3.53;
P
<0.001), had more hospitalizations (minor,
P
<0.001; major,
P
<0.001) and emergency department visits (minor,
P
=0.003; major,
P
<0.001), and spent more days in the hospital (minor,
P
<0.001; major,
P
<0.001). The interview and questionnaire methods of assessing depression did not significantly differ in their overall accuracy of predicting rehospitalization.

Conclusions—
Depressive disorders increase the risk of rehospitalization after AMI. Future work should focus on developing multivariable models to predict risk of rehospitalization after AMI, and depression should be included in these.
African Easterly Wave Dynamics in a Mesoscale Numerical Model: The Upscale Role of Convection
Authors: Berry Gareth J. , Thorncroft Chris D. 
Published: October 2011

Abstract
To examine the dynamical role of convection in African easterly wave (AEW) life cycles the Weather Research and Forecasting (WRF) model is used to simulate the evolution of a single AEW from September 2004. The model simulations are validated against corresponding numerical weather prediction analyses and the mean fields closely resemble composite structures from previous studies. A potential vorticity (PV) thinking approach is used to highlight the interactions between dynamics and convection.
Organized deep convection embedded within the AEW has a large contribution to the synoptic-scale mean PV and energetics of the AEW. The PV tendency is maximized in the lower troposphere, consistent with the vertical gradient in diabatic heating rates in the areas of convection. By examining terms in the Lorenz energy cycle, it is shown that diabatic heating associated with convection is as important as adiabatic energy conversion in producing eddy available potential energy of the synoptic AEW, implying that AEWs are best described as hybrid adiabatic and diabatic structures. The net effect of convection is succinctly described using a simulation whereby the parameterizations associated with convection are switched off at the midpoint of the model run. This perturbation experiment shows that, although the AEW continues to propagate westward with a similar phase speed, the net PV value continually weakens with time. This result proves that convection is vital for the maintenance of the AEW as it propagates across West Africa and suggests that without active convection the synoptic AEW cannot persist for an extended length of time.
The Mechanical Impact of the Tibetan Plateau on the Seasonal Evolution of the South Asian Monsoon
Authors: Park Hyo-Seok , Chiang John C. H. , Bordoni Simona 
Published: October 2011

AbstractThe impact of the Tibetan Plateau on the South Asian monsoon is examined using a hierarchy of atmospheric general circulation models. During the premonsoon season and monsoon onset (April–June), when westerly winds over the Southern Tibetan Plateau are still strong, the Tibetan Plateau triggers early monsoon rainfall downstream, particularly over the Bay of Bengal and South China. The downstream moist convection is accompanied by strong monsoonal low-level winds. In experiments where the Tibetan Plateau is removed, monsoon onset occurs about a month later, but the monsoon circulation becomes progressively stronger and reaches comparable strength during the mature phase. During the mature and decaying phase of monsoon (July–September), when westerly winds over the Southern Tibetan Plateau almost disappear, monsoon circulation strength is not much affected by the presence of the Tibetan Plateau.A dry dynamical core with east–west-oriented narrow mountains in the subtropics consistently simulates downstream convergence with background zonal westerlies over the mountain. In a moist atmosphere, the mechanically driven downstream convergence is expected to be associated with significant moisture convergence. The authors speculate that the mechanically driven downstream convergence in the presence of the Tibetan Plateau is responsible for zonally asymmetric monsoon onset, particularly over the Bay of Bengal and South China.
Use of Ground Clutter to Monitor Polarimetric Radar Calibration
Authors: Borowska L. , Zrnic D. 
Published: October 2011

Abstract
It is suggested that urban ground clutter can have a role in monitoring calibration of reflectivity factor ZH and differential reflectivity ZDR on polarimetric radars. The median and average values of these variables are considered. Analysis of data from 1 month of cold season in Germany (X-band radar) and 3.5 hot days in Oklahoma (S-band radar) is presented. In the presence of up to moderate rain or snow a reflectivity threshold suffices for separating significant clutter from precipitation observed with an X-band radar. The same threshold was suitable on observations with an S-band radar in Oklahoma because heavy precipitation was not present. The tests suggest the scheme is worthy considering for operational monitoring of ZH as its median values at both locations were within the quantization interval of 0.5 dB. Environmental factors that can influence reflectivities from clutter are examined. The effects on ZDR can be significant. These are quantified in the data and possible uses for calibration and monitoring radar status are indicated.
Quantitative and qualitative analysis of nutrition and food safety information in school science textbooks of India
Authors: Subba Rao GM , Vijayapushapm T , Venkaiah K , Pavarala V 
Published: October 2011

Objective: To assess quantity and quality of nutrition and food safety information in science textbooks prescribed by the Central Board of Secondary Education (CBSE), India for grades I through X. Design: Content analysis. Methods: A coding scheme was developed for quantitative and qualitative analyses. Two investigators independently coded the data and inter-coder reliability was assessed using Cohen’s Kappa. The inferences were then reviewed by an expert group. Results: There was high agreement (Kappa = 0.89) between coders. Nutrition topics got > 10% pages in textbooks of grades I to VII, while they were omitted in subsequent grades. Food safety got a mere 1% of page allocation only in grades I to III books. Over 25% of biology illustrations related to nutrition in grades I, II and IV but not in others. Nutrition topics in textbooks beyond grade IV were repetitive and inconsistent. Some illustrations depicted uncommon foods and had urban bias. Conclusions: Nutrition and food safety content in science textbooks is low. Important topics such as nutritional needs during adolescence, obesity, unhealthy foods and food labelling are not covered. These findings provide direction for strengthening textbook content to promote nutrition education in schools.
Overexpression of LEF1 predicts unfavorable outcome in adult patients with B-precursor acute lymphoblastic leukemia
Authors: Kühnl Andrea , Gökbuget Nicola , Kaiser Martin , Schlee Cornelia , Stroux Andrea , Burmeister Thomas , Mochmann Liliana H. , Hoelzer Dieter , Hofmann Wolf-Karsten , Thiel Eckhard , Baldus Claudia D. 
Published: October 2011

Abstract
Aberrant activation of the Wnt pathway plays a pathogenetic role in various tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). LEF1, a key mediator of Wnt signaling, has been linked to leukemic transformation, and recurrent mutations of LEF1 have been identified in pediatric T-ALL. Here we evaluated the prognostic significance of LEF1 expression in B-precursor ALL patients. LEF1 expression was determined by quantitative real-time RT-PCR in 282 adult B-precursor ALL patients treated on 06/99 and 07/03 GMALL trials. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression levels (LEF1 high, Q4; n = 71; LEF1 low, Q1-Q3; n = 211). Patients with high LEF1 expression had a significantly shorter relapse-free survival (RFS) compared with low LEF1 expressers (5-year RFS: LEF1 high, 27%; LEF1 low, 47%; P = .05). Importantly, high LEF1 expression was also associated with inferior RFS in standard-risk patients and was independently predictive for RFS (P = .02) in multivariate analyses for this subgroup. Thus, high LEF1 expression identifies B-precursor ALL patients with inferior RFS, supporting a pathogenetic role of Wnt signaling in ALL. Standard-risk patients with high LEF1 expression might benefit from early treatment modifications and new molecular therapies, including agents targeting the Wnt pathway.
Mitochondrial genome sequence analysis: A custom bioinformatics pipeline substantially improves Affymetrix MitoChip v2.0 call rate and accuracy
Authors: Xie Hongbo M , Perin Juan C , Schurr Theodore G , Dulik Matthew C , Zhadanov Sergey I , Baur Joseph A , King Michael P , Place Emily , Clarke Colleen , Grauer Michael , Schug Jonathan , Santani Avni , Albano Anthony , Kim Cecilia , Procaccio Vincent , Hakonarson Hakon , Gai Xiaowu , Falk Marni J 
Published: October 2011

Abstract

Background
Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate and accuracy for the Affymetrix MitoChip v2.0 platform. We used this custom pipeline to analyze MitoChip v2.0 data from 24 DNA samples representing a broad range of tissue types (18 whole blood, 3 skeletal muscle, 3 cell lines), mutations (a 5.8 kilobase pair deletion and 6 known heteroplasmic mutations), and haplogroup origins. All results were compared to those obtained by at least one other mitochondrial DNA sequence analysis method, including Sanger sequencing, denaturing HPLC-based heteroduplex analysis, and/or the Illumina Genome Analyzer II next generation sequencing platform.

Results
An average call rate of 99.75% was achieved across all samples with our custom pipeline. Comparison of calls for 15 samples characterized previously by Sanger sequencing revealed a total of 29 discordant calls, which translates to an estimated 0.012% for the base call error rate. We successfully identified 4 known heteroplasmic mutations and 24 other potential heteroplasmic mutations across 20 samples that passed quality control.

Conclusions
Affymetrix MitoChip v2.0 analysis using our optimized MitoChip Filtering Protocol (MFP) bioinformatics pipeline now offers the high sensitivity and accuracy needed for reliable, high-throughput and cost-efficient whole mitochondrial genome sequencing. This approach provides a viable alternative of potential utility for both clinical diagnostic and research applications to traditional Sanger and other emerging sequencing technologies for whole mitochondrial genome analysis.
Efficacy and tolerance of the topical application of potassium hydroxide (10% and 15%) in the treatment of molluscum contagiosum: Randomized clinical trial: Research protocol
Authors: Marsal Josep R , Cruz Ines , Teixido Concepcio , Diez Olga , Martinez Mireia , Galindo Gisela , Real Jordi , Schoenenberger Joan A , Pera Helena 
Published: October 2011

Abstract

Background
Molluscum contagiosum is a non-severe pediatric viral infection. Because it is highly contagious and current treatments have negative aesthetic and psychological effects, we want to test an alternative treatment in the primary care setting, consisting of two different concentrations of potassium hydroxide solution.

Methods/design
The study design is a double-blind, randomized clinical trial, using three types of topical treatment. The treatment consist of daily applications of potassium hydroxide (KOH) in aqueous solution at 10% and 15% concentration, and a placebo administered in the control group. Four follow-up visits (at 15, 30, 45 and 60 days) are planned to evaluate treatment effectiveness and patient tolerance.
The main outcome measure of the trial will be the healing rate, defined as lesion disappearance in the affected zones after the topic application of the experimental treatment. Secondary measures will be the principal characteristics and evolution of the affected zone (surface area, number of lesions, size and density of lesions), treatment tolerance (hyperpigmentation, itching, burning, pain), recurrence rate and the natural evolution of lesions in the control group.

Discussion
KOH can potentially be an effective and safe treatment for MC in primary care, and can also reduce referrals to dermatologists and hospital pediatric departments. In addition, KOH may be a valid and less expensive alternative to current invasive treatments (surgical excision).

Trial Registration
ClinicalTrials.gov: NCT01348386