bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning Sparse Representations for Fruit-Fly Gene Expression Pattern Image Annotation and Retrieval
Authors: Yuan Lei , Woodard Alexander , Ji Shuiwang , Jiang Yuan , Zhou Zhi-Hua , Kumar Sudhir , Ye Jieping
Published: May 2012

Background

Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.

Results

In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.

Conclusions

We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
Development of simple sequence repeat (SSR) markers from a genome survey of Chinese bayberry (Myrica rubra)
Authors: Jiao Yun , Jia Hui-min , Li Xiong-wei , Chai Ming-liang , Jia Hui-juan , Chen Zhe , Wang Guo-yun , Chai Chun-yan , van de Weg Eric , Gao Zhong-shan
Published: May 2012

Background

Chinese bayberry (Myrica rubraSieb. and Zucc.) is a subtropical evergreen tree originating in China. It has been cultivated in southern China for several thousand years, and annual production has reached 1.1 million tons. The taste and high level of health promoting characters identified in the fruit in recent years has stimulated its extension in China and introduction to Australia. A limited number of co-dominant markers have been developed and applied in genetic diversity and identity studies. Here we report, for the first time, a survey of whole genome shotgun data to develop a large number of simple sequence repeat (SSR) markers to analyse the genetic diversity of the common cultivated Chinese bayberry and the relationship with three otherMyricaspecies.

Results

The whole genome shotgun survey of Chinese bayberry produced 9.01Gb of sequence data, about 26x coverage of the estimated genome size of 323 Mb. The genome sequences were highly heterozygous, but with little duplication. From the initial assembled scaffold covering 255 Mb sequence data, 28,602 SSRs (≥5 repeats) were identified. Dinucleotide was the most common repeat motif with a frequency of 84.73%, followed by 13.78% trinucleotide, 1.34% tetranucleotide, 0.12% pentanucleotide and 0.04% hexanucleotide. From 600 primer pairs, 186 polymorphic SSRs were developed. Of these, 158 were used to screen 29 Chinese bayberry accessions and three otherMyricaspecies: 91.14%, 89.87% and 46.84% SSRs could be used inMyrica adenophora,Myrica nanaandMyrica cerifera,respectively. The UPGMA dendrogram tree showed that cultivatedMyrica rubrais closely related toMyrica adenophoraandMyrica nana, originating in southwest China, and very distantly related toMyrica cerifera, originating in America. These markers can be used in the construction of a linkage map and for genetic diversity studies inMyricaspecies.

Conclusion

Myrica rubrahas a small genome of about 323 Mb with a high level of heterozygosity. A large number of SSRs were identified, and 158 polymorphic SSR markers developed, 91% of which can be transferred to otherMyricaspecies.
Plasticity of DNA methylation in mouse T cell activation and differentiation
Authors: Li Yan , Chen Guobing , Ma Lina , Ohms Stephen J , Sun Chao , Shannon M Frances , Fan Jun Y
Published: May 2012

Background

Circulating CD4+ T helper cells are activated through interactions with antigen presenting cells and undergo differentiation into specific T helper cell subsets depending on the type of antigen encountered. In addition, the relative composition of the circulating CD4+ T cell population changes as animals mature with an increased percentage of the population being memory/effector type cells.

Results

Here, we report on the highly plastic nature of DNA methylation at the genome-wide level as T cells undergo activation, differentiation and aging. Of particular note were the findings that DNA demethylation occurred rapidly following T cell activation and that all differentiated T cell populations displayed lower levels of global methylation than the non-differentiated population. In addition, T cells from older mice had a reduced level of DNA methylation, most likely explained by the increase in the memory/effector cell fraction. Although significant genome-wide changes were observed, changes in DNA methylation at individual genes were restricted to specific cell types. Changes in the expression of enzymes involved in DNA methylation and demethylation reflect in most cases the changes observed in the genome-wide DNA methylation status.

Conclusion

We have demonstrated that DNA methylation is dynamic and flexible in CD4+ T cells and changes rapidly both in a genome-wide and in a targeted manner during T cell activation, differentiation. These changes are accompanied by parallel changes in the enzymatic complexes that have been implicated in DNA methylation and demethylation implying that the balance between these opposing activities may play a role in the maintaining the methylation profile of a given cell type but also allow flexibility in a cell population that needs to respond rapidly to environmental signals.
Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms - pediatric versus adult?
Authors: Kumar Nilay , Bashar Qumseya , Reddy Naveen , Sengupta Jyotirmoy , Ananthakrishnan Ashwin , Schroeder Abigail , Hogan Walter J , Venkatesan Thangam
Published: May 2012

Background

Cyclic Vomiting Syndrome (CVS) is a well-recognized functional gastrointestinal disorder in children but its presentation is poorly understood in adults. Genetic differences in pediatric-onset (presentation before age 18) and adult-onset CVS have been reported recently but their clinical features and possible differences in response to therapy have not been well studied.

Methods

This was a retrospective review of 101 CVS patients seen at the Medical College of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the diagnosis of CVS.

Results

Our study population comprised of 29(29%) pediatric-onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 ± 7 years) in the pediatric-onset group when compared to (5 ± 7 years) adult-onset CVS group (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group compared to adult-onset patients (0% vs. 23%, p = 0.004). Aside from these differences, the two groups were similar with regards to their clinical features and the time of onset of symptoms did not predict response to standard treatment. The majority of patients (86%) responded to treatment with tricyclic antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine. Non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of emergency department visits in the year prior to presentation, presence of disability and non-compliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response. (88% vs. 38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05).

Conclusion

Despite reported genetic differences, the clinical features and response to standard therapy in pediatric- and adult-onset CVS were mostly similar. Most patients (86%) responded to therapy and compliance was the only factor associated with a response.
Risk of inflammatory bowel disease following a diagnosis of irritable bowel syndrome
Authors: Porter Chad K , Cash Brooks D , Pimentel Mark , Akinseye Akintunde , Riddle Mark S
Published: May 2012

Background

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) symptoms often overlap. In some IBS cases there are subtle inflammatory changes similar to the immune-mediated pathophysiology of IBD, and the risk of both increases after infectious gastroenteritis (IGE).

Methods

To evaluate the effect of IBS and IGE on IBD risk utilizing US Department of Defense medical encounter data, active duty personnel with IBS were matched to subjects without IBS. Medical encounter history was analyzed to assess for incident IBD. IGE was identified from documented medical encounters and by self-report. Relative risks were calculated using Poisson regression models.

Results

We identified 9,341 incident IBS cases and 18,678 matched non-IBS subjects and found an 8.6-fold higher incidence (p < 0.0001) of IBD among those with IBS (238.1 per 100,000 person-years) compared to our referent population (27.8 per 100,000 person-years). In a subset (n = 2,205) of well-defined IBS cases, IBD risk was 15 times that of subjects without IBS. The median time between IBS and IBD diagnoses was 2.1 years. IGE also increased IBD risk approximately 2-fold ( p < 0.05) after controlling for IBS.

Conclusions

These data reflect a complex interaction between illness presentation and diagnosis of IBS and IBD and suggest intercurrent IGE may increase IBD risk in IBS patients. Additional studies are needed to determine whether IBS lies on the causal pathway for IBD or whether the two are on a pathophysiological spectrum of the same clinical illness. These data suggest consideration of risk reduction interventions for IGE among IBS patients at high disease risk.
Methylseleninic acid restricts tumor growth in nude mice model of metastatic breast cancer probably via inhibiting angiopoietin-2
Authors: Wu Xiaojing , Zhang Yidi , Pei Zengyang , Chen Si , Yang Xu , Chen Yin , Lin Degui , Ma Runlin Z
Published: May 2012

Background

Angiopoietin-2 (Ang-2) plays critical roles in vascular morphogenesis and its upregulation is frequently associated with various tumors. Previous studies showed that certain selenium compounds possess anti-tumor effects. However, the underlining mechanism has not been elucidated in detail. Plus, results of research on the anti-tumor effects of selenium compounds remain controversial.

Methods

We investigated levels of Ang-2 and vascular endothelial growth factor (VEGF) on the estrogen-independent bone metastatic mammary cancer (MDA-MB-231) cells in response to treatment by methylseleninic acid (MSeA), and further examined the effects of MSeA oral administration on xenograft mammary tumors of athymic nude mice by RT-PCR, Western, radioimmuno assay, and Immunohistochemistry.

Results

Treatment of MDA-MB-231 cells with MSeA caused significant reduction of Ang-2 mRNA transcripts and secretion of Ang-2 proteins by the cells. Level of VEGF protein was accordingly decreased following the treatment. Compared with the controls, oral administration of MSeA (3 mg/kg/day for 18 days) to the nude mice carrying MDA-MB-231 induced tumors resulted in significant reduction in xenograft tumor volume and weights, significant decrease in microvascular density, and promotion of vascular normalization by increasing pericytes coverage. As expected, level of VEGF was also decreased in MSeA treated tumors.

Conclusions

Our results point out that MSeA exerts its anti-tumor effects, at least in part, by inhibiting the Ang-2/Tie2 pathway, probably via inhibiting VEGF.
The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer
Authors: Sung Hyuna , Choi Ji-Yeob , Lee Sang-Ah , Lee Kyoung-Mu , Han Sohee , Jeon Sujee , Song Minkyo , Lee Yunhee , Park Sue K , Yoo Keun-Young , Noh Dong-Young , Ahn Sei-Hyun , Kang Daehee
Published: May 2012

Background

Although a number of experimental studies have suggested the role of lipocalin-2 (LCN2) and matrix metalloproteinase-9 (MMP-9) in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the levels of lipocalin-2 and MMP-9 and breast cancer survival.

Methods

Preoperative serum levels of lipocalin-2 and MMP-9 were measured in 303 breast cancer patients and 74 healthy controls recruited between 2004 and 2007. We examined the association between lipocalin-2 and MMP-9 levels and disease-free survival (DFS) using Cox proportional hazard regression model.

Results

The serum levels of lipocalin-2 and MMP-9 were not significantly different between patients and controls (P > 0.05). Elevated lipocalin-2 and MMP-9 levels were associated with reduced DFS of breast cancer ( P
trend = 0.029 and P
trend = 0.063, respectively). When lipocalin-2 and MMP-9 levels were categorized based on the combined risk score, patients with higher levels of both lipocalin-2 and MMP-9 exhibited poor DFS compared to patients with lower levels (P
trend = 0.004). Furthermore, these effects were profound in patients with BMI less than 25 kg/m2 (adjusted hazard ratio (aHR), 3.17; 95% confidence intervals (CI), 1.66-6.06, P
trend < 0.001) or lymph-node negative breast cancer (aHR, 5.36; 95% CI, 2.18-13.2, P
trend < 0.001).

Conclusions

Our study suggests that the elevated levels of lipocalin-2 and MMP-9 are associated with reduced breast cancer survival, particularly in patients with lower BMI and lymph-node negative breast cancers.
Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma
Authors: Lin Yu-Tsai , Chuang Hui-Ching , Chen Chang-Han , Armas Gian Luca , Chen Han-Ku , Fang Fu-Min , Huang Chao-Cheng , Chien Chih-Yen
Published: May 2012

Background

Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC).

Methods

The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays.

Results

We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26–87 years). The mean follow-up period was 67 months (range, 2–171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates.

Conclusions

High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future.
Osteo-cise: Strong Bones for Life: Protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures
Authors: Gianoudis Jenny , Bailey Christine A , Sanders Kerrie M , Nowson Caryl A , Hill Keith , Ebeling Peter R , Daly Robin M
Published: May 2012

Background

Osteoporosis affects over 220 million people worldwide, and currently there is no ‘cure’ for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition.

Methods/design

The Osteo-cise: Strong Bones for Life study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged ≥60 years will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month ‘research to practise’ translational phase. Participants will be randomly assigned to either the Osteo-cise intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed.

Discussion

The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture.

Trial registration

Australian New Zealand Clinical Trials Registry reference ACTRN12609000100291
Survey of patient and public perceptions of electronic health records for healthcare, policy and research: Study protocol
Authors: Luchenski Serena , Balasanthiran Anjali , Marston Cicely , Sasaki Kaori , Majeed Azeem , Bell Derek , Reed Julie E
Published: May 2012

Background

Immediate access to patients’ complete health records via electronic databases could improve healthcare and facilitate health research. However, the possible benefits of a national electronic health records (EHR) system must be balanced against public concerns about data security and personal privacy. Successful development of EHR requires better understanding of the views of the public and those most affected by EHR: users of the National Health Service. This study aims to explore the correlation between personal healthcare experience (including number of healthcare contacts and number and type of longer term conditions) and views relating to development of EHR for healthcare, health services planning and policy and health research.

Methods/design

A multi-site cross-sectional self-complete questionnaire designed and piloted for use in waiting rooms was administered to patients from randomly selected outpatients’ clinics at a university teaching hospital (431 beds) and general practice surgeries from the four primary care trusts within the catchment area of the hospital. All patients entering the selected outpatients clinics and general practice surgeries were invited to take part in the survey during August-September 2011. Statistical analyses will be conducted using descriptive techniques to present respondents’ overall views about electronic health records and logistic regression to explore associations between these views and participants’ personal circumstances, experiences, sociodemographics and more specific views about electronic health records.

Discussion

The study design and implementation were successful, resulting in unusually high response rates and overall recruitment (85.5%, 5336 responses). Rates for face-to-face recruitment in previous work are variable, but typically lower (mean 76.7%, SD 20). We discuss details of how we collected the data to provide insight into how we obtained this unusually high response rate.
The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum
Authors: Chotivanich Kesinee , Mungthin Mathirut , Ruengweerayuth Ronnatrai , Udomsangpetch Rachanee , Dondorp Arjen M , Singhasivanon Pratap , Pukrittayakamee Sasithon , White Nicholas J
Published: May 2012

Background

Lumefantrine and atovaquone are highly lipophilic anti-malarial drugs. As a consequence absorption is increased when the drugs are taken together with a fatty meal, but the free fraction of active drug decreases in the presence of triglyceride-rich plasma lipoproteins. In this study, the consequences of lipidaemia on anti-malarial drug efficacy were assessed in vitro.

Methods

Serum was obtained from non-immune volunteers under fasting conditions and after ingestion of a high fat meal and used in standard Plasmodium falciparum in-vitro susceptibility assays. Anti-malarial drugs, including lumefantrine, atovaquone and chloroquine in five-fold dilutions (range 0.05 ng/ml – 1 ug/mL) were diluted in culture medium supplemented with fasting or post-prandial 10% donor serum. The in-vitro drug susceptibility of parasite isolates was determined using the 3H-hypoxanthine uptake inhibition method and expressed as the concentration which gave 50% inhibition of hypoxanthine uptake (IC50).

Results

Doubling plasma triglyceride concentrations (from 160 mg/dL to 320 mg/dL), resulted in an approximate doubling of the IC50 for lumefantrine (191 ng/mL to 465 ng/mL, P < 0.01) and a 20-fold increase in the IC50 for atovaquone (0.5 ng/mL to 12 ng/ml; P < 0.01). In contrast, susceptibility to the hydrophilic anti-malarial chloroquine did not change in relation to triglyceride content of the medium.

Conclusions

Lipidaemia reduces the anti-malarial activity of lipophilic anti-malarial drugs. This is an important confounder in laboratory in vitro testing and it could have therapeutic relevance.
Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase null mouse
Authors: Monteiro Jessica , Li Feng-Jun , MacLennan Mira , Rabalski Alexandra , Moghadasian Mohammed H , Nakamura Manabu T , Ma David WL
Published: May 2012

Background

Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid.

Objective

The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids.

Methodology

Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group).

Results

Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice.

Conclusions

Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.
Template method synthesis of mesoporous carbon spheres and its applications as supercapacitors
Authors: Wilgosz Karolina , Chen Xuecheng , Kierzek Krzysztof , Machnikowski Jacek , Kalenczuk Ryszard J , Mijowska Ewa
Published: May 2012

Mesoporous carbon spheres (MCS) have been fabricated from structured mesoporous silica sphere using chemical vapor deposition (CVD) with ethylene as a carbon feedstock. The mesoporous carbon spheres have a high specific surface area of 666.8 m2/g and good electrochemical properties. The mechanism of formation mesoporous carbon spheres (carbon spheres) is investigated. The important thing is a surfactant hexadecyl trimethyl ammonium bromide (CTAB), which accelerates the process of carbon deposition. An additional advantage of this surfactant is an increase the yield of product. These mesoporous carbon spheres, which have good electrochemical properties is suitable for supercapacitors.
A methodology for time-frequency image processing applied to the classification of non-stationary multichannel signals using instantaneous frequency descriptors with application to newborn EEG signals
Authors: Boashash Boualem , Boubchir Larbi , Azemi Ghasem
Published: May 2012

This article presents a general methodology for processing non-stationary signals for the purpose of classification and localization. The methodology combines methods adapted from three complementary areas: time-frequency signal analysis, multichannel signal analysis and image processing. The latter three combine in a new methodology referred to as multichannel time-frequency image processing which is applied to the problem of classifying electroencephalogram (EEG) abnormalities in both adults and newborns. A combination of signal related features and image related features are used by merging key instantaneous frequency descriptors which characterize the signal non-stationarities. The results obtained show that, firstly, the features based on time-frequency image processing techniques such as image segmentation, improve the performance of EEG abnormalities detection in the classification systems based on multi-SVM and neural network classifiers. Secondly, these discriminating features are able to better detect the correlation between newborn EEG signals in a multichannel-based newborn EEG seizure detection for the purpose of localizing EEG abnormalities on the scalp.
Multispectral texture characterization: application to computer aided diagnosis on prostatic tissue images
Authors: Khelifi Riad , Adel Mouloud , Bourennane Salah
Published: May 2012

Various approaches have been proposed in the literature for texture characterization of images. Some of them are based on statistical properties, others on fractal measures and some more on multi-resolution analysis. Basically, these approaches have been applied on mono-band images. However, most of them have been extended by including the additional information between spectral bands to deal with multi-band texture images. In this article, we investigate the problem of texture characterization for multi-band images. Therefore, we aim to add spectral information to classical texture analysis methods that only treat gray-level spatial variations. To achieve this goal, we propose a spatial and spectral gray level dependence method (SSGLDM) in order to extend the concept of gray level co-occurrence matrix (GLCM) by assuming the presence of texture joint information between spectral bands. Thus, we propose new multi-dimensional functions for estimating the second-order joint conditional probability density of spectral vectors. Theses functions can be represented in structure form which can help us to compute the occurrences while keeping the corresponding components of spectral vectors. In addition, new texture features measurements related to (SSGLDM) which define the multi-spectral image properties are proposed. Extensive experiments have been carried out on 624 textured multi-spectral images for use in prostate cancer diagnosis and quantitative results showed the efficiency of this method compared to the GLCM. The results indicate a significant improvement in terms of global accuracy rate. Thus, the proposed approach can provide clinically useful information for discriminating pathological tissue from healthy tissue.
IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils
Authors: Savarin Carine , Stohlman Stephen A , Hinton David R , Ransohoff Richard M , Cua Daniel J , Bergmann Cornelia C
Published: May 2012

Background

The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity.

Methods

Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-γ deficient (GKO) memory CD4+T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade.

Results

Transfer of GKO memory CD4+T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4+T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4+T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4+T cells provided a model to directly assess their contribution(s) to disease. Recipients of WT CD4+T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4+T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced.

Conclusions

These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of extensive neutrophil accumulation or GM-CSF upregulation. The results also suggest that IFN-γ overrides the detrimental IL-17 effector responses via a mechanism downstream of transcriptional regulation.
α7 nicotinic acetylcholine receptor-mediated neuroprotection against dopaminergic neuron loss in an MPTP mouse model via inhibition of astrocyte activation
Authors: Liu Yuan , Hu Jun , Wu Jie , Zhu Chenlei , Hui Yujian , Han Yaping , Huang Zuhu , Ellsworth Kevin , Fan Weimin
Published: May 2012

Background

Although evidence suggests that the prevalence of Parkinson’s disease (PD) is lower in smokers than in non-smokers, the mechanisms of nicotine-induced neuroprotection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) seems to be a crucial mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells, including astrocytes, and inhibition of astrocyte activation has been proposed as a novel strategy for the treatment of neurodegenerative disorders such as PD. The objective of the present study was to determine whether nicotine-induced neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model occurs via α7-nAChR-mediated inhibition of astrocytes.

Methods

Both in vivo (MPTP) and in vitro (1-methyl-4-phenylpyridinium ion (MPP+) and lipopolysaccharide (LPS)) models of PD were used to investigate the role(s) of and possible mechanism(s) by which α7-nAChRs protect against dopaminergic neuron loss. Multiple experimental approaches, including behavioral tests, immunochemistry, and stereology experiments, astrocyte cell cultures, reverse transcriptase PCR, laser scanning confocal microscopy, tumor necrosis factor (TNF)-α assays, and western blotting, were used to elucidate the mechanisms of the α7-nAChR-mediated neuroprotection.

Results

Systemic administration of nicotine alleviated MPTP-induced behavioral symptoms, improved motor coordination, and protected against dopaminergic neuron loss and the activation of astrocytes and microglia in the substantia nigra. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured mouse astrocytes, pretreatment with nicotine suppressed MPP+-induced or LPS-induced astrocyte activation, as evidenced by both decreased production of TNF-α and inhibition of extracellular regulated kinase1/2 (Erk1/2) and p38 activation in astrocytes, and these effects were also reversed by MLA.

Conclusion

Taken together, our results suggest that α7-nAChR-mediated inhibition of astrocyte activation is an important mechanism underlying the protective effects of nicotine.
Nef functions in BLT mice to enhance HIV-1 replication and deplete CD4+CD8+ thymocytes
Authors: Zou Wei , Denton Paul W , Watkins Richard L , Krisko John F , Nochi Tomonori , Foster John L , Garcia J Victor
Published: May 2012

Background

The outcome of untreated HIV-1 infection is progression to AIDS and death in nearly all cases. Some important exceptions are the small number of patients infected with HIV-1 deleted for the accessory gene, nef. With these infections, disease progression is entirely suppressed or greatly delayed. Whether Nef is critical for high levels of replication or is directly cytotoxic remains controversial. The major problem in determining the role of Nef in HIV/AIDS has been the lack of tractable in vivo models where Nef’s complex pathogenic phenotype can be recapitulated.

Results

Intravenous inoculation (3000 to 600,000 TCIU) of BLT humanized mice with HIV-1LAI reproducibly establishes a systemic infection. HIV-1LAI (LAI) replicates to high levels (peak viral load in blood 8,200,000 ± 1,800,000 copies of viral RNA/ml, range 3,600,000 to 20,400,000; n = 9) and exhaustively depletes CD4+ T cells in blood and tissues. CD4+CD8+ thymocytes were also efficiently depleted but CD4+CD8- thymocytes were partially resistant to cell killing by LAI. Infection with a nef-deleted LAI (LAINefdd) gave lower peak viral loads (1,220,000 ± 330,000, range 27,000 to 4,240,000; n = 17). For fourteen of seventeen LAINefdd-infected mice, there was little to no loss of either CD4+ T cells or thymocytes. Both LAI- and LAINefdd-infected mice had about 8% of total peripheral blood CD8+ T cells that were CD38+HLA-DR+ compared <1% for uninfected mice. Three exceptional LAINefdd-infected mice that lost CD4+ T cells received 600,000 TCIU. All three exhibited peak viral loads over 3,000,000 copies of LAINefdd RNA/ml. Over an extended time course, substantial systemic CD4+ T cell loss was observed for the three mice, but there was no loss of CD4+CD8+ or CD4+CD8- thymocytes.

Conclusion

We conclude Nef is necessary for elevated viral replication and as a result indirectly contributes to CD4+ T cell killing. Further, Nef was not necessary for the activation of peripheral blood CD8+ T cells following infection. However, CD4+CD8+ thymocyte killing was dependent on Nef even in cases of elevated LAINefdd replication and T cell loss. This depletion of thymic T cell precursors may be a significant factor in the elevated pathogenicity of CXCR4 trophic HIV-1.
Pulmonary exposure to single-walled carbon nanotubes does not affect the early immune response against Toxoplasma gondii
Authors: Swedin Linda , Arrighi Romanico , Andersson-Willman Britta , Murray Ashley , Chen Yunying , Karlsson Mikael C I , Georén Susanna Kumlien , Tkach Alexey V , Shvedova Anna A , Fadeel Bengt , Barragan Antonio , Scheynius Annika
Published: May 2012

Background

Single-walled carbon nanotubes (SWCNT) trigger pronounced inflammation and fibrosis in the lungs of mice following administration via pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational setting may occur in conjunction with infections and this could yield enhanced or suppressed responses to the offending agent. Here, we studied whether the sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with the ubiquitous intracellular parasiteToxoplasma gondiiwould impact on the immune response of the host against the parasite.

Methods

C57BL/6 mice were pre-exposed by pharyngeal administration of SWCNT (80 + 80 μg/mouse) for two consecutive days followed by intravenous injection with either 1x103or 1x104green fluorescence protein and luciferase-expressingT. gondiitachyzoites. The dissemination ofT. gondiiwas monitored byin vivobioluminescence imaging in real time for 7 days and by plaque formation.The inflammatory response was analysed in bronchoalveolar lavage (BAL) fluid, and by assessment of morphological changes and immune responses in lung and spleen.

Results

There were no differences in parasite distribution between mice only inoculated withT. gondiior those mice pre-exposed for 2 days to SWCNT before parasite inoculum. Lung and spleen histology and inflammation markers in BAL fluid reflected the effects of SWCNT exposure andT. gondiiinjection, respectively. We also noted that CD11c positive dendritic cells but not F4/80 positive macrophages retained SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization ofT. gondiiwith CD11c or F4/80 positive cells could not be observed in lungs or spleen. Pre-exposure to SWCNT did not affect the splenocyte response toT. gondii.

Conclusions

Taken together, our data indicate that pre-exposure to SWCNT does not enhance or suppress the early immune response toT. gondiiin mice.
Resuscitation of very preterm infants with 30% vs. 65% oxygen at birth: study protocol for a randomized controlled trial
Authors: Rook Denise , Schierbeek Henk , van der Eijk Anne C , Longini Mariangela , Buonocore Giuseppe , Vento Maximo , van Goudoever Johannes B , Vermeulen Marijn J
Published: May 2012

Background

Resuscitation at birth with 100% oxygen is known to increase the oxidative burden with concomitant deleterious effects. Although fractions of inspired oxygen (FiO2) < 100% are widely used in preterm infants, starting resuscitation at a (too) low FiO2 may result in hypoxia. The objective of this study is to compare the safety and efficacy of resuscitating very preterm infants with an initial FiO2 of 30% versus 65%.

Methods/design

In this double-blind, randomized controlled trial, 200 very preterm infants with a gestational age < 32 weeks will be randomized to start resuscitation after birth with either 30% or 65% oxygen. The FiO2 will be adjusted based on oxygen saturation measured by pulse oximetry (SpO2) and pulse rate (which should be over 100 beats per minute) in order to achieve a target SpO2 of 88–94% at 10 min of life. The FiO2 and pulse oximetry data will be continuously recorded.

The primary outcome is survival without bronchopulmonary dysplasia, as assessed by a physiological test at 36 weeks postmenstrual age. The secondary outcomes include the time to achieve SpO2 > 88%, Apgar score at 5 min, cumulative O2 exposure, oxidative stress (as determined by glutathione synthesis and oxidative stress markers), retinopathy of prematurity, brain injury and neurodevelopmental outcome at 2 years of age.

This study will provide insight into determining the appropriate initial FiO2 to start resuscitation of very preterm infants.

Trial registration

http://www.trialregister.nl, NTR243.
Porous high-density polyethylene in facial reconstruction and revision rhinoplasty: a prospective cohort study
Authors: Mohammadi Shabahang , Ghourchian Shadi , Izadi Farzad , Daneshi Ahmad , Ahmadi Aslan
Published: May 2012

Introduction

Initial methods which used human tissues as reconstruction materials caused different problems including rejection, limited shapes and infection. In 1970s, PHDPE (Medpor®) was introduced by its exclusive advantageous including no donor site morbidity, easily shaped and the minimal foreign body reaction. Hereby, we report our experience of using Medpor® in facial reconstruction especially in frontal reconstruction and orbital rim with a large sample size.

Methods

This study was a prospective cohort study. Surgical techniques included using Medpor® in reconstruction of lamina papiracea (LP) (15 patients), frontal bone (15 patients), orbital rim (18 patients) and open rhinoplasty (8 patients). All interventions on LP were performed by endoscopic procedures. All frontal operations were carried out by bicoronal incision. In orbital defects, we used subciliary incision.

Results

From all 56 patients, 1 case had primitive neuroectodermal tumor (PNET) of maxillary sinus. In that case, reconstruction of inferior orbital rim was not successful and extrusion was occurred after radiotherapy. In rhinoplasty and other experiences no extrusion or infection were detected within the next 1 to 3 years of follow up. There were not any palpable and visible irregularities under the skin in our experiences.

Conclusions

In this study the patients did not experience any complications during the follow up periods and the satisfaction was remarkable. Gathering these data gives rise to future review studies which can provide more organized evidences for replacing classic reconstructive methods by the presented material.
Cherubism: best clinical practice
Authors: Papadaki Maria E , Lietman Steven A , Levine Michael A , Olsen Bjorn R , Kaban Leonard B , Reichenberger Ernst J
Published: May 2012

Cherubism is a skeletal dysplasia characterized by bilateral and symmetric fibro-osseous lesions limited to the mandible and maxilla. In most patients, cherubism is due to dominant mutations in theSH3BP2gene on chromosome 4p16.3. Affected children appear normal at birth. Swelling of the jaws usually appears between 2 and 7 years of age, after which, lesions proliferate and increase in size until puberty. The lesions subsequently begin to regress, fill with bone and remodel until age 30, when they are frequently not detectable.

Fibro-osseous lesions, including those in cherubism have been classified as quiescent, non-aggressive and aggressive on the basis of clinical behavior and radiographic findings. Quiescent cherubic lesions are usually seen in older patients and do not demonstrate progressive growth. Non-aggressive lesions are most frequently present in teenagers. Lesions in the aggressive form of cherubism occur in young children and are large, rapidly growing and may cause tooth displacement, root resorption, thinning and perforation of cortical bone.

Because cherubism is usually self-limiting, operative treatment may not be necessary. Longitudinal observation and follow-up is the initial management in most cases. Surgical intervention with curettage, contouring or resection may be indicated for functional or aesthetic reasons. Surgical procedures are usually performed when the disease becomes quiescent. Aggressive lesions that cause severe functional problems such as airway obstruction justify early surgical intervention.
Absence of amyloid β oligomers at the postsynapse and regulated synaptic Zn2+ in cognitively intact aged individuals with Alzheimer’s disease neuropathology
Authors: Bjorklund Nicole L , Reese Lindsay C , Sadagoparamanujam V-M , Ghirardi Valeria , Woltjer Randall L , Taglialatela Giulio
Published: May 2012

Background

Early cognitive impairment in Alzheimer Disease (AD) is thought to result from the dysfunctional effect of amyloid beta (Aβ) oligomers targeting the synapses. Some individuals, however, escape cognitive decline despite the presence of the neuropathologic features of AD (Aβ plaques and neurofibrillary tangles). We term this group Non-Demented with AD Neuropathology or NDAN. The present study illustrates one putative resistance mechanism involved in NDAN cases which may suggest targets for the effective treatment of AD.

Results

Here we describe the localization of Aβ oligomers at the postsynapse in hippocampi from AD cases. Notably, however, we also found that while present in soluble fractions, Aβ oligomers are absent from hippocampal postsynapses in NDAN cases. In addition, levels of phosphorylated (active) CREB, a transcription factor important for synaptic plasticity, are normal in NDAN individuals, suggesting that their synapses are functionally intact. Analysis of Zn2+showed that levels were increased in both soluble fractions and synaptic vesicles in AD hippocampi, paralleled by a decrease of expression of the synaptic vesicle Zn2+transporter, ZnT3. Conversely, in NDAN individuals, levels of Zn2+in soluble fractions were significantly lower than in AD, whereas in synaptic vesicles the levels of Zn2+were similar to AD, but accompanied by preserved expression of the ZnT3.

Conclusions

Taken together, these data illustrate that despite substantial AD neuropathology, Aβ oligomers, and increased synaptic vesicle Zn2+, susceptible brain tissue in these aged NDAN individuals features, as compared to symptomatic AD subjects, significantly lower total Zn2+levels and no association of Aβ oligomers with the postsynapse, which collectively may promote the maintenance of intact cognitive function.