bluuebunny/crossref_metadata_2025 huggingface dataset:
SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma
Authors: Vegliante Maria Carmela , Palomero Jara , Pérez-Galán Patricia , Roué Gaël , Castellano Giancarlo , Navarro Alba , Clot Guillem , Moros Alexandra , Suárez-Cisneros Helena , Beà Sílvia , Hernández Luis , Enjuanes Anna , Jares Pedro , Villamor Neus , Colomer Dolors , Martín-Subero José Ignacio , Campo Elias , Amador Virginia
Published: January 2013

Key Points

SOX11 silencing promotes the shift from a mature B cell into the initial plasmacytic differentiation phenotype in MCL. SOX11 promotes tumor growth of MCL cells in vivo, highlighting its implication in the aggressive behavior of conventional MCL.
B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ
Authors: Salzer Elisabeth , Santos-Valente Elisangela , Klaver Stefanie , Ban Sol A. , Emminger Wolfgang , Prengemann Nina Kathrin , Garncarz Wojciech , Müllauer Leonhard , Kain Renate , Boztug Heidrun , Heitger Andreas , Arbeiter Klaus , Eitelberger Franz , Seidel Markus G. , Holter Wolfgang , Pollak Arnold , Pickl Winfried F. , Förster-Waldl Elisabeth , Boztug Kaan
Published: January 2013

Key Points

PRKCD deficiency causes a novel primary immunodeficiency with B-cell deficiency and severe autoimmunity. Protein kinase C δ may represent a key factor controlling immune homeostasis and autoimmunity.
Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia
Authors: Jourdan Eric , Boissel Nicolas , Chevret Sylvie , Delabesse Eric , Renneville Aline , Cornillet Pascale , Blanchet Odile , Cayuela Jean-Michel , Recher Christian , Raffoux Emmanuel , Delaunay Jacques , Pigneux Arnaud , Bulabois Claude-Eric , Berthon Céline , Pautas Cécile , Vey Norbert , Lioure Bruno , Thomas Xavier , Luquet Isabelle , Terré Christine , Guardiola Philippe , Béné Marie C. , Preudhomme Claude , Ifrah Norbert , Dombret Hervé
Published: January 2013

Key Points

In adult patients with core binding factor AML, intensified induction is not associated with a better outcome in the context of intensive postremission therapy. Minimal residual disease, rather than KIT or FLT3 gene mutations, should be used to identify core binding factor AML patients at higher risk of relapse.
GSVA: gene set variation analysis for microarray and RNA-Seq data
Authors: Hänzelmann Sonja , Castelo Robert , Guinney Justin
Published: January 2013

Background

Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets.

Results

To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments.

Conclusions

GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded athttp://www.bioconductor.org.
Double restriction-enzyme digestion improves the coverage and accuracy of genome-wide CpG methylation profiling by reduced representation bisulfite sequencing
Authors: Wang Junwen , Xia Yudong , Li Lili , Gong Desheng , Yao Yu , Luo Huijuan , Lu Hanlin , Yi Na , Wu Honglong , Zhang Xiuqing , Tao Qian , Gao Fei
Published: January 2013

Background

Reduced representation bisulfite sequencing (RRBS) was developed to measure DNA methylation of high-CG regions at single base-pair resolution, and has been widely used because of its minimal DNA requirements and cost efficacy; however, the CpG coverage of genomic regions is restricted and important regions with low-CG will be ignored in DNA methylation profiling. This method could be improved to generate a more comprehensive representation.

Results

Based on in silico simulation of enzyme digestion of human and mouse genomes, we have optimized the current single-enzyme RRBS by applying double enzyme digestion in the library construction to interrogate more representative regions. CpG coverage of genomic regions was considerably increased in both high-CG and low-CG regions using the double-enzyme RRBS method, leading to more accurate detection of their average methylation levels and identification of differential methylation regions between samples. We also applied this double-enzyme RRBS method to comprehensively analyze the CpG methylation profiles of two colorectal cancer cell lines.

Conclusion

The double-enzyme RRBS increases the CpG coverage of genomic regions considerably over the previous single-enzyme RRBS method, leading to more accurate detection of their average methylation levels. It will facilitate genome-wide DNA methylation studies in multiple and complex clinical samples.
Comparative genome analysis of Spiroplasma melliferumIPMB4A, a honeybee-associated bacterium
Authors: Lo Wen-Sui , Chen Ling-Ling , Chung Wan-Chia , Gasparich Gail E , Kuo Chih-Horng
Published: January 2013

Background

The genus Spiroplasma contains a group of helical, motile, and wall-less bacteria in the class Mollicutes. Similar to other members of this class, such as the animal-pathogenic Mycoplasma and the plant-pathogenic ‘Candidatus Phytoplasma’, all characterized Spiroplasma species were found to be associated with eukaryotic hosts. While most of the Spiroplasma species appeared to be harmless commensals of insects, a small number of species have evolved pathogenicity toward various arthropods and plants. In this study, we isolated a novel strain of honeybee-associated S. melliferum and investigated its genetic composition and evolutionary history by whole-genome shotgun sequencing and comparative analysis with other Mollicutes genomes.

Results

The whole-genome shotgun sequencing of S. melliferum IPMB4A produced a draft assembly that was ~1.1 Mb in size and covered ~80% of the chromosome. Similar to other Spiroplasma genomes that have been studied to date, we found that this genome contains abundant repetitive sequences that originated from plectrovirus insertions. These phage fragments represented a major obstacle in obtaining a complete genome sequence of Spiroplasma with the current sequencing technology. Comparative analysis of S. melliferum IPMB4A with other Spiroplasma genomes revealed that these phages may have facilitated extensive genome rearrangements in these bacteria and contributed to horizontal gene transfers that led to species-specific adaptation to different eukaryotic hosts. In addition, comparison of gene content with other Mollicutes suggested that the common ancestor of the SEM (Spiroplasma, Entomoplasma, and Mycoplasma) clade may have had a relatively large genome and flexible metabolic capacity; the extremely reduced genomes of present day Mycoplasma and ‘Candidatus Phytoplasma’ species are likely to be the result of independent gene losses in these lineages.

Conclusions

The findings in this study highlighted the significance of phage insertions and horizontal gene transfer in the evolution of bacterial genomes and acquisition of pathogenicity. Furthermore, the inclusion of Spiroplasma in comparative analysis has improved our understanding of genome evolution in Mollicutes. Future improvements in the taxon sampling of available genome sequences in this group are required to provide further insights into the evolution of these important pathogens of humans, animals, and plants.
Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis
Authors: Affara Muna , Sanders Debbie , Araki Hiromitsu , Tamada Yoshinori , Dunmore Benjamin J , Humphreys Sally , Imoto Seiya , Savoie Christopher , Miyano Satoru , Kuhara Satoru , Jeffries David , Print Cristin , Charnock-Jones D Stephen
Published: January 2013

Background

Apoptosis is a critical process in endothelial cell (EC) biology and pathology, which has been extensively studied at protein level. Numerous gene expression studies of EC apoptosis have also been performed, however few attempts have been made to use gene expression data to identify the molecular relationships and master regulators that underlie EC apoptosis. Therefore, we sought to understand these relationships by generating a Bayesian gene regulatory network (GRN) model.

Results

ECs were induced to undergo apoptosis using serum withdrawal and followed over a time course in triplicate, using microarrays. When generating the GRN, this EC time course data was supplemented by a library of microarray data from EC treated with siRNAs targeting over 350 signalling molecules.

The GRN model proposed Vasohibin-1 (VASH1) as one of the candidate master-regulators of EC apoptosis with numerous downstream mRNAs. To evaluate the role played by VASH1 in EC, we used siRNA to reduce the expression of VASH1. Of 10 mRNAs downstream of VASH1 in the GRN that were examined, 7 were significantly up- or down-regulated in the direction predicted by the GRN.Further supporting an important biological role of VASH1 in EC, targeted reduction of VASH1 mRNA abundance conferred resistance to serum withdrawal-induced EC death.

Conclusion

We have utilised Bayesian GRN modelling to identify a novel candidate master regulator of EC apoptosis. This study demonstrates how GRN technology can complement traditional methods to hypothesise the regulatory relationships that underlie important biological processes.
Transcriptome profile analysis of young floral buds of fertile and sterile plants from the self-pollinated offspring of the hybrid between novel restorer line NR1 and Nsa CMS line in Brassica napus
Authors: Yan Xiaohong , Dong Caihua , Yu Jingyin , Liu Wanghui , Jiang Chenghong , Liu Jia , Hu Qiong , Fang Xiaoping , Wei Wenhui
Published: January 2013

Background

The fertile and sterile plants were derived from the self-pollinated offspring of the F1 hybrid between the novel restorer line NR1 and the Nsa CMS line in Brassica napus. To elucidate gene expression and regulation caused by the A and C subgenomes of B. napus, as well as the alien chromosome and cytoplasm from Sinapis arvensis during the development of young floral buds, we performed a genome-wide high-throughput transcriptomic sequencing for young floral buds of sterile and fertile plants.

Results

In this study, equal amounts of total RNAs taken from young floral buds of sterile and fertile plants were sequenced using the Illumina/Solexa platform. After filtered out low quality data, a total of 2,760,574 and 2,714,441 clean tags were remained in the two libraries, from which 242,163 (Ste) and 253,507 (Fer) distinct tags were obtained. All distinct sequencing tags were annotated using all possible CATG+17-nt sequences of the genome and transcriptome of Brassica rapa and those of Brassica oleracea as the reference sequences, respectively. In total, 3231 genes of B. rapa and 3371 genes of B. oleracea were detected with significant differential expression levels. GO and pathway-based analyses were performed to determine and further to understand the biological functions of those differentially expressed genes (DEGs). In addition, there were 1089 specially expressed unknown tags in Fer, which were neither mapped to B. oleracea nor to B. rapa, and these unique tags were presumed to arise basically from the added alien chromosome of S. arvensis. Fifteen genes were randomly selected and their expression levels were confirmed by quantitative RT-PCR, and fourteen of them showed consistent expression patterns with the digital gene expression (DGE) data.

Conclusions

A number of genes were differentially expressed between the young floral buds of sterile and fertile plants. Some of these genes may be candidates for future research on CMS in Nsa line, fertility restoration and improved agronomic traits in NR1 line. Further study of the unknown tags which were specifically expressed in Fer will help to explore desirable agronomic traits from wild species.
Clinical utility and tolerability of JSPH-1 wireless esophageal pH monitoring system
Authors: Li Jun-Nan , Liu Chun-Lun , Tao Xiao-Hong
Published: January 2013

Background

Wireless esophageal pH monitoring system is an important approach for diagnosis of gastroesophageal reflux disease (GERD), the aim of this study is to test the tolerability and utility of the first wireless esophageal pH monitoring system made in China, and evaluate whether it is feasible for clinical application to diagnose GERD.

Methods

Thirty patients from Department of Gastroenterology of The First Affiliated Hospital of Chongqing Medical University who were suspected GERD underwent JSPH-1 pH capsule. The capsule was placed 5 cm proximal to the squamocolumnar junction (SCJ) by endoscopic determination, the data was recorded consecutively for 48 hours. Then all pH data was downloaded to a computer for analysis. The discomforts reported by patients were recorded.

Results

30 patients were placed JSPH-1 pH capsule successfully and completed 24-hour data recording, 29 patients completed 48-hour data recording. One patient complained of chest pain and required endoscopic removal. No complications and interference of daily activities were reported during data monitoring or follow-up period. 48-hour pH monitoring detected 15 patients of abnormal acid exposure, on day1 detected 9 patients, the difference had statistical significance (P<0.01). Positive symptom index (SI) was identified in 3 patients with normal pH data in both 24-hours. In total, 48-hour monitoring increased diagnosis of GERD in 9 patients.

Conclusion

48-hour esophageal pH monitoring with JSPH-1 wireless pH monitoring system is safe, well tolerated and effective. It can be feasible for clinical application to diagnose GERD.
GERD assessment including pH metry predicts a high response rate to PPI standard therapy
Authors: Kandulski Arne , Peitz Ulrich , Mönkemüller Klaus , Neumann Helmut , Weigt Jochen , Malfertheiner Peter
Published: January 2013

Background

Inadequate response to proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) is reported in up to 40%. Patients with non erosive reflux disease (NERD) have lower response rates compared to patients with erosive reflux disease (ERD); pH metry contributes to GERD diagnosis and is critical for proper diagnosis of NERD.

Aim of the study was to assess the need for doubling esomeprazole standard dose (40 mg) for 4 weeks in PPI naive patients with typical reflux symptoms and diagnosis of GERD based on endoscopy and 48 hours, wireless pH metry.

Methods

All patients underwent upper GI endoscopy. Symptoms were recorded with a structured questionnaire (RDQ) and acid exposure was determined by 48 hours, wireless pH monitoring (BRAVO). In case of abnormal acid exposure, patients received a short term treatment with esomeprazole 40 mg q.d. for 4 weeks. If symptoms persisted, patients underwent a second pH metry on PPI and the dose was increased to 40 mg b.i.d.

Results

31 consecutive patients with typical reflux symptoms underwent 48 hours pH monitoring. 22 patients (71%) had abnormal acid exposure, 9 patients had normal pH metry (29%). Of the 9 patients with normal pH metry, 2 were found with erosive esophagitis and 7 without endoscopic abnormalities.

24 patients with documented GERD received esomeprazole treatment. 21 patients achieved complete symptom resolution with 40 mg q.d. after 4 weeks (88%). Only 2 patients required doubling the dose of esomeprazole for complete symptom resolution, 1 patient remained with symptoms.

Conclusions

Patients with typical reflux symptoms and abnormal acid exposure have a high response rate to standard dose esomeprazole regardless of whether they have ERD or NERD.
Expression of M. tuberculosis-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis
Authors: Masood Kiran I , Rottenberg Martin E , Salahuddin Naseem , Irfan Muhammad , Rao Nisar , Carow Berit , Islam Muniba , Hussain Rabia , Hasan Zahra
Published: January 2013

Background

Appropriate immune activation of T cells and macrophages is central for the control ofMycobacterium tuberculosisinfections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules – 1 and 3 and CD4+CD25+FoxP3+T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB.M.tuberculosis-stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann–Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests.

Results

In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC.M.tuberculosis-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression inM.tuberculosisstimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017).

Conclusions

The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB.
Prognostic utility of plasma S100A12 levels to establish a novel scoring system for predicting mortality in maintenance hemodialysis patients: a two-year prospective observational study in Japan
Authors: Shiotsu Yayoi , Mori Yasukiyo , Nishimura Masato , Hatta Tsuguru , Imada Naoki , Maki Noboru , Iida Kumiko , Iwamoto Noriyuki , Matsuoka Eiko , Tamagaki Keiichi , Kosaki Atsushi
Published: January 2013

Background

S100A12 protein is an endogenous receptor ligand for advanced glycation end products. In this study, the plasma S100A12 level was assessed as an independent predictor of mortality, and its utility in clinical settings was examined.

Methods

In a previous cross-sectional study, plasma S100A12 levels were measured in 550 maintenance hemodialysis patients to determine the association between S100A12 and the prevalence of cardiovascular diseases (CVD). In this prospective study, the risk of mortality within a two-year period was determined. An integer scoring system was developed to predict mortality on the basis of the plasma S100A12 levels.

Results

Higher plasma S100A12 levels (≥18.79 ng/mL) were more closely associated with higher all-cause mortality than lower plasma S100A12 levels (<18.79 ng/mL; P = 0.001). Multivariate Cox proportional hazards analysis revealed higher plasma S100A12 levels [hazard ratio (HR), 2.267; 95% confidence interval (CI), 1.195–4.302; P = 0.012], age ≥65 years (HR, 1.961; 95%CI, 1.017–3.781; P = 0.044), serum albumin levels <3.5 g/dL (HR, 2.198; 95%CI, 1.218–3.968; P = 0.012), and history of CVD (HR, 2.068; 95%CI, 1.146–3.732; P = 0.016) to be independent predictors of two-year all-cause mortality. The integer score was derived by assigning points to these factors and determining total scores. The scoring system revealed trends across increasing scores for predicting the all-cause mortality [c-statistic = 0.730 (0.656–0.804)]. The resulting model demonstrated good discriminative power for distinguishing the validation population of 303 hemodialysis patients [c-statistic = 0.721 (0.627–0.815)].

Conclusion

The results indicate that plasma S100A12 level is an independent predictor for two-year all-cause mortality. A simple integer scoring system was therefore established for predicting mortality on the basis of plasma S100A12 levels.
Prenatal micronutrient supplementation and postpartum depressive symptoms in a pregnancy cohort
Authors: Leung Brenda MY , Kaplan Bonnie J , Field Catherine J , Tough Suzanne , Eliasziw Misha , Gomez Mariel Fajer , McCargar Linda J , Gagnon Lisa ,   and the APrON Study Team
Published: January 2013

Background

Postpartum depression is a serious problem for women and their offspring. Micronutrient supplements are recommended for pregnant women because of their documented protective effects for the offspring, but their potential beneficial effects on maternal mental health are unknown. This study investigated the association between prenatal micronutrient supplementation and the risk for symptoms of postpartum depression in a longitudinal pregnancy cohort from the Alberta Pregnancy Outcomes and Nutrition (APrON) study.

Methods

Participants came from a cohort of the first 600 APrON women. Supplemental nutrient intake and symptoms of depression (measured with the Edinburgh Postnatal Depression Scale (EPDS)) were collected at each trimester and 12 weeks postpartum.

Results

Of the 475 participants who completed the EPDS at least twice in pregnancy and at 12 weeks postpartum, 416 (88%) scored <10 and 59 (12%) scored ≥10, where an EPDS ≥10 is considered to be “at least probable minor depression”. Mean nutrient intakes from supplements were higher in women with lower EPDS scores, particularly selenium (p = 0.0015) and omega-3s (p = 0.01). Bivariate analyses showed that several demographic and social/lifestyle variables were associated with EPDS ≥10: not having been born in Canada (p = 0.01), greater number of chronic conditions (p = 0.05), greater number of stressful life events during this pregnancy (p = 0.02), and lower prenatal and postnatal support (p = 0.0043 and p = 0.0001, respectively). Adjusting for covariates and nutrients known to be associated with postpartum depression, logistic regression showed that having a prenatal EPDS ≥ 10 increased the odds of postpartum depressive symptoms (second and third trimester OR = 3.29, 95% CI = 1.55 - 7.01, p = 0.004 and OR = 4.26, 95% CI = 2.05 - 8.85, p < 0.0001, respectively), while prenatal supplemental selenium (per 10 mcg, OR = 0.76, 95% CI = 0.74 - 0.78, p = 0.0019) and postnatal social support (OR = 0.87, 95% CI = 0.78 - 0.97, p = 0.0015) were protective.

Conclusions

Multiple factors, including supplementary selenium intake, are associated with the risk of postpartum depressive symptoms. Future research on dietary supplementation in pregnancy with special attention to selenium intake is warranted.
Plasma brain-derived neurotrophic factor levels, learning capacity and cognition in patients with first episode psychosis
Authors: de Azua Sonia Ruiz , Matute Carlos , Stertz Laura , Mosquera Fernando , Palomino Aitor , de la Rosa Iris , Barbeito Sara , Vega Patricia , Kapczinski Flávio , González-Pinto Ana
Published: January 2013

Background

Cognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls.

Methods

45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment.

Results

Plasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability, immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores.

Conclusion

Our results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.
Air ions and mood outcomes: a review and meta-analysis
Authors: Perez Vanessa , Alexander Dominik D , Bailey William H
Published: January 2013

Background

Psychological effects of air ions have been reported for more than 80 years in the media and scientific literature. This study summarizes a qualitative literature review and quantitative meta-analysis, where applicable, that examines the potential effects of exposure to negative and positive air ions on psychological measures of mood and emotional state.

Methods

A structured literature review was conducted to identify human experimental studies published through August, 2012. Thirty-three studies (1957–2012) evaluating the effects of air ionization on depression, anxiety, mood states, and subjective feelings of mental well-being in humans were included. Five studies on negative ionization and depression (measured using a structured interview guide) were evaluated by level of exposure intensity (high vs. low) using meta-analysis.

Results

Consistent ionization effects were not observed for anxiety, mood, relaxation/sleep, and personal comfort. In contrast, meta-analysis results showed that negative ionization, overall, was significantly associated with lower depression ratings, with a stronger association observed at high levels of negative ion exposure (mean summary effect and 95% confidence interval (CI) following high- and low-density exposure: 14.28 (95% CI: 12.93-15.62) and 7.23 (95% CI: 2.62-11.83), respectively). The response to high-density ionization was observed in patients with seasonal or chronic depression, but an effect of low-density ionization was observed only in patients with seasonal depression. However, no relationship between the duration or frequency of ionization treatment on depression ratings was evident.

Conclusions

No consistent influence of positive or negative air ionization on anxiety, mood, relaxation, sleep, and personal comfort measures was observed. Negative air ionization was associated with lower depression scores particularly at the highest exposure level. Future research is needed to evaluate the biological plausibility of this association.
Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats
Authors: Sárközy Márta , Zvara Ágnes , Gyémánt Nóra , Fekete Veronika , Kocsis Gabriella F , Pipis Judit , Szűcs Gergő , Csonka Csaba , Puskás László G , Ferdinandy Péter , Csont Tamás
Published: January 2013

Background

Metabolic syndrome (coexisting visceral obesity, dyslipidemia, hyperglycemia, and hypertension) is a prominent risk factor for cardiovascular morbidity and mortality, however, its effect on cardiac gene expression pattern is unclear. Therefore, we examined the possible alterations in cardiac gene expression pattern in male Zucker Diabetic Fatty (ZDF) rats, a model of metabolic syndrome.

Methods

Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were measured at 6, 16, and 25 wk of age in male ZDF and lean control rats. Oral glucose tolerance test was performed at 16 and 25 wk of age. At week 25, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 14921 genes. Expression of selected genes was confirmed by qRT-PCR.

Results

Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were significantly increased, glucose tolerance and insulin sensitivity were impaired in ZDF rats compared to leans. In hearts of ZDF rats, 36 genes showed significant up-regulation and 49 genes showed down-regulation as compared to lean controls. Genes with significantly altered expression in the heart due to metabolic syndrome includes functional clusters of metabolism (e.g. 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2; argininosuccinate synthetase; 2-amino-3-ketobutyrate-coenzyme A ligase), structural proteins (e.g. myosin IXA; aggrecan1), signal transduction (e.g. activating transcription factor 3; phospholipase A2; insulin responsive sequence DNA binding protein-1) stress response (e.g. heat shock 70kD protein 1A; heat shock protein 60; glutathione S-transferase Yc2 subunit), ion channels and receptors (e.g. ATPase, (Na+)/K+ transporting, beta 4 polypeptide; ATPase, H+/K+ transporting, nongastric, alpha polypeptide). Moreover some other genes with no definite functional clusters were also changed such as e.g. S100 calcium binding protein A3; ubiquitin carboxy-terminal hydrolase L1; interleukin 18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome.

Conclusions

Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome.
Dietary pattern and leisure time activity of overweight and normal weight children in Germany: sex-specific differences
Authors: Maier Ina B , Özel Yelda , Wagnerberger Sabine , Bischoff Stephan C , Bergheim Ina
Published: January 2013

Background

Several studies indicate that dietary pattern and leisure time activities of adults not only differ between sexes but also between overweight and normal weight individuals. The aim of the present study was to determine if sex-specific differences in dietary pattern and leisure time activity already exist and are associated with weight status in young childhood.

Methods

Nutritional intake, anthropometric parameters, leisure time activities and socio- demographical factors were assessed in 100 overweight and 51 normal weight children (81 girls and 70 boys), aged 5–8 years.

Results

In general, independent of body weight, boys ate more cheese while girls consumed more vegetables and spent more time with sedentary activities. Moreover, regardless of sex, total energy and macronutrient intake did not differ between normal weight and overweight children. Also, time spent with sportive activities did not differ between groups; however, overweight boys spent significantly more leisure time with sedentary activities than normal weight boys. Furthermore, BMI of mothers and time spent with sedentary activities were identified as independent risk factors for the development of overweight when performing multiple regression analyses.

Conclusions

Taken together, results of our study suggest that already at young age sex influences dietary pattern independent of body weight. Furthermore, an increased time spent with sedentary activities and an elevated maternal BMI were found to be associated with an elevated body weight in children. (Trial registration: NCT01306396)
Robust online tracking via adaptive samples selection with saliency detection
Authors: Yan Jia , Chen Xi , Zhu Qiu Ping
Published: January 2013

Online tracking has shown to be successful in tracking of previously unknown objects. However, there are two important factors which lead to drift problem of online tracking, the one is how to select the exact labeled samples even when the target locations are inaccurate, and the other is how to handle the confusors which have similar features with the target. In this article, we propose a robust online tracking algorithm with adaptive samples selection based on saliency detection to overcome the drift problem. To deal with the problem of degrading the classifiers using mis-aligned samples, we introduce the saliency detection method to our tracking problem. Saliency maps and the strong classifiers are combined to extract the most correct positive samples. Our approach employs a simple yet saliency detection algorithm based on image spectral residual analysis. Furthermore, instead of using the random patches as the negative samples, we propose a reasonable selection criterion, in which both the saliency confidence and similarity are considered with the benefits that confusors in the surrounding background are incorporated into the classifiers update process before the drift occurs. The tracking task is formulated as a binary classification via online boosting framework. Experiment results in several challenging video sequences demonstrate the accuracy and stability of our tracker.
Biodegradation of high concentrations of benzene vapors in a two phase partition stirred tank bioreactor
Authors: Karimi Ali , Golbabaei Farideh , Neghab Masoud , Pourmand Mohammad Reza , Nikpey Ahmad , Mohammad Kazem , Mehrnia Momammad Reza
Published: January 2013

The present study examined the biodegradation rate of benzene vapors in a two phase stirred tank bioreactor by a bacterial consortium obtained from wastewater of an oil industry refinery house. Initially, the ability of the microbial consortium for degrading benzene was evaluated before running the bioreactor. The gaseous samples from inlet and outlet of bioreactor were directly injected into a gas chromatograph to determine benzene concentrations. Carbone oxide concentration at the inlet and outlet of bioreactor were also measured with a CO2 meter to determine the mineralization rate of benzene. Influence of the second non-aqueous phase (silicon oil) has been emphasized, so at the first stage the removal efficiency (RE) and elimination capacity (EC) of benzene vapors were evaluated without any organic phase and in the second stage, 10% of silicon oil was added to bioreactor media as an organic phase. Addition of silicon oil increased the biodegradation performance up to an inlet loading of 5580 mg/m3, a condition at which, the elimination capacity and removal efficiency were 181 g/m3/h and 95% respectively. The elimination rate of benzene increased by 38% in the presence of 10% of silicone oil. The finding of this study demonstrated that two phase partition bioreactors (TPPBs) are potentially effective tools for the treatment of gas streams contaminated with high concentrations of poorly water soluble organic contaminant, such as benzene.
GATA4 and DcR1 methylation in glioblastomas
Authors: Vaitkienė Paulina , Skiriutė Daina , Skauminas Kęstutis , Tamašauskas Arimantas
Published: January 2013

Background

Epigenetic silencing of tumor suppressor genes plays important role in gliomagenesis. Recently, GATA4 and DcR1 were suggested to be a tumor suppressor genes involved in tumorigenesis in various types of human cancers. However, up to now the methylation frequency of GATA4 and DcR1 genes has not been determined in glioblastoma. In this study, we investigated methylation of GATA4 and DcR1 promoters and their association with patient prognosis in glioblastoma.

Methods

Methylation status of GATA4 and DcR1 promoters was investigated by methylation specific PCR in 99 glioblastoma patients. Statistical analyses were conducted to investigate the association between clinical variables and overall survival time.

Results

GATA4 and DcR1 were aberrantly methylated in 23.2% and 27.6% of glioblastoma tumors, but not in normal brain. GATA4 promoter hypermethylation showed significant association with patients age (p = 0.027). Relationship between genes promoter methylation and glioblastoma patient survival was not determined.

Conclusions

The present work demonstrated that GATA4 and DcR1 promoter hypermethylation is tumor specific event in glioblastoma but they promoter methylation cannot be considered as a prognostic marker of glioblastoma survival.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1381170351801852
Hypofractionated radiotheapy using helical tomotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis
Authors: Kim Ji-Yoon , Yoo Eun-Jung , Jang Jeong-Won , Kwon Jung-Hyun , Kim Ki-Jun , Kay Chul-Seung
Published: January 2013

Background

We want to evaluate the efficacy of helical tomotherapy (HT) for treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).

Methods

We treated 35 patients for unresectable HCC combined with PVTT in whom other treatment modalities were not indicated. The tumor thrombi involved the main trunk of the portal vein in 18 patients (51.4%) and the first or second order branches in 17 patients (48.6%). A median dose of 50 Gy (range: 45–60 Gy) was delivered in 10 fractions. Capecitabine was given concomitantly at a dose of 600 mg/m2 twice daily during radiotherapy.

Results

The responses were evaluated via computed tomography. There was a complete response (CR) in 5 patients (14.3%), partial response (PR) in 10 patients (28.6%), stable disease (SD) in 18 patients (51.4%) and progressive disease (PD) in 2 patients (5.7%). The Child-Pugh classification (A vs B) and the Japan integrated staging (JIS) score (2 vs 3) were statistically significant parameters that predicted the response of PVTT (p = 0.010 and p = 0.026, respectively). The median survival, one and two year survival rate of all patients was 12.9 months, 51.4% and 22.2%, respectively. The patients with tumor thrombi in the main portal trunk showed statistically inferior overall survival than patients with tumor thrombi in the portal vein branches (9.8 versus 16.6 months, respectively, p = 0.036). The responders’ median survival was 13.9 months, double 6.9 months as the median survival of the non-responders. No radiation induced liver disease or treatment related mortality was not appeared.

Conclusions

Hypofractionated radiotherapy with HT was effective not only for tumor response but also for survival in the advanced HCC patients with PVTT. And stricter patient selection by Child-Pugh classification and JIS score may maximize the potential benefits of this treatment.
Partial protoporphyrinogen oxidase (PPOX) gene deletions, due to different Alu-mediated mechanisms, identified by MLPA analysis in patients with variegate porphyria
Authors: Barbaro Michela , Kotajärvi Maire , Harper Pauline , Floderus Ylva
Published: January 2013

Variegate porphyria (VP) is an autosomal dominantly inherited hepatic porphyria. The genetic defect in the PPOX gene leads to a partial defect of protoporphyrinogen oxidase, the penultimate enzyme of heme biosynthesis. Affected individuals can develop cutaneous symptoms in sun-exposed areas of the skin and/or neuropsychiatric acute attacks. The identification of the genetic defect in VP families is of crucial importance to detect the carrier status which allows counseling to prevent potentially life threatening neurovisceral attacks, usually triggered by factors such as certain drugs, alcohol or fasting.

In a total of 31 Swedish VP families sequence analysis had identified a genetic defect in 26. In the remaining five families an extended genetic investigation was necessary. After the development of a synthetic probe set, MLPA analysis to screen for single exon deletions/duplications was performed.

We describe here, for the first time, two partial deletions within the PPOX gene detected by MLPA analysis. One deletion affects exon 5 and 6 (c.339-197_616+320del1099) and has been identified in four families, most probably after a founder effect. The other extends from exon 5 to exon 9 (c.339-350_987+229del2609) and was found in one family. We show that both deletions are mediated by Alu repeats.

Our findings emphasize the usefulness of MLPA analysis as a complement to PPOX gene sequencing analysis for comprehensive genetic diagnostics in patients with VP.
Withholding or continuing beta-blocker treatment before dipyridamole myocardial perfusion imaging for the diagnosis of coronary artery disease? A randomized clinical trial
Authors: Fallahi Babak , Beiki Davood , Akbarpour Saeed , Gholamrezanezhad Ali , Fard-Esfahani Armaghan , Akhzari Fariba , Izadyar Sina , Esmaeli Javad , Saghari Mohsen , Eftekhari Mohammad
Published: January 2013

Background

Although it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI).

Methods

As a randomized clinical trial, one hundred twenty patients (103 male and 17 female) with angiographically confirmed CAD who were on long-term beta blocker therapy (≥3 months) enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60) in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60) without discontinuation of beta-blockers prior to DMPI.

Results

No significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility) in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096). Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001); however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898). The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7%) was not statistically different from group B (90%).

Conclusion

Beta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.
The not-so-neutral role of microRNAs in neutrophil biology
Authors: Gantier Michael P
Published: January 2013

The role of microRNAs (miRNAs) as fine-tuners of gene expression is now well established in most aspects of cellular biology. Critically, it is becoming apparent that characterization of miRNA regulation could further the understanding of elusive cellular processes. Here, I briefly review the current literature assessing the role of miRNAs in the modulation of neutrophil biology and discuss how the definition of such miRNA regulation could help in the better understanding of neutrophil function.
Maternal and Umbilical Cord Levels of T4, FT4, TSH, TPOAb, and TgAb in Term Infants and Neurodevelopmental Outcome at 5.5 Years
Authors: Williams Fiona L. R. , Watson Jennifer , Ogston Simon A. , Visser Theo J. , Hume Robert , Willatts Peter
Published: January 2013

Context:

Relatively little is known in euthyroid populations about the changes in maternal thyroid hormones during pregnancy, the nature of the relationship to cord thyroid hormone levels, and subsequent infant neurodevelopment.

Objectives:

The aim of the study was to describe the relationship between maternal and cord thyroid hormone parameters and to describe their associations with neurodevelopment at 5.5 years.

Design:

We conducted a follow-up of women and their children born at or over 37 weeks' gestation.

Main Outcomes:

We measured maternal levels of TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), T4, and free T4 (FT4) at 10 and 34 weeks and at delivery, and cord levels of T4, FT4, TPOAb, and TgAb. The association of cord thyroid hormone parameters with McCarthy scale scores adjusted for the major confounders of neurodevelopment.

Results:

Fifteen percent of the women were TPOAb-positive, and 12% were TgAb-positive; the proportion of women with mildly elevated TSH levels increased during pregnancy with the maximum (14%) at delivery. Lower perceptual performance and motor scores were found with TgAb-positive women and lower perceptual performance scores with TgAb-positive cord levels; otherwise, unadjusted maternal levels of TPOAb, TgAb, and TSH and unadjusted cord levels of FT4, TPOAb, and TgAb were not associated with neurodevelopment at 5.5 years. Low cord T4 levels were associated with significant increments in four McCarthy scales: General Cognitive Index, Verbal, Quantitative, and Memory scales—increments that persisted after adjustment at 11.4, 7.8, 7.6, and 7.8 points, respectively.

Conclusions:

Lower levels of cord T4 were associated with increments in the McCarthy scales in the domains that tested cognitive and verbal abilities at 5.5 years.
Taking the Measure of Global Space
Authors: Smith Bruce R.
Published: January 2013

Euclidean geometry instructs us to think of space in visual terms as points, lines, and shapes, but a more adventurous geometry would take into account the subjectivity of the perceiver. When we try out that approach on Shakespeare and his contemporaries, situating them within the built environment of the 1599 Globe Theater, we discover not one measure of space but ten: (1) geographical, (2) temporal, (3) fictional, (4) characterological, (5) social, (6) political, (7) interpersonal, (8) performative, (9) receptive, and (10) phenomenal. The confluence of the ten measures of space is marked by a preposition, as. With one hand, as gestures toward a situation here; with the other hand, it points toward something else over there. The paradox of theater is that it is neither here nor there, but both at the same time.
pbx is required for pole and eye regeneration in planarians
Authors: Chen Chun-Chieh G. , Wang Irving E. , Reddien Peter W.
Published: January 2013

Planarian regeneration involves regionalized gene expression that specifies the body plan. After amputation, planarians are capable of regenerating new anterior and posterior poles, as well as tissues polarized along the anterior-posterior, dorsal-ventral and medial-lateral axes. Wnt and several Hox genes are expressed at the posterior pole, whereas Wnt inhibitory genes, Fgf inhibitory genes, and prep, which encodes a TALE-family homeodomain protein, are expressed at the anterior pole. We found that Smed-pbx (pbx for short), which encodes a second planarian TALE-family homeodomain transcription factor, is required for restored expression of these genes at anterior and posterior poles during regeneration. Moreover, pbx(RNAi) animals gradually lose pole gene expression during homeostasis. By contrast, pbx was not required for initial anterior-posterior polarized responses to wounds, indicating that pbx is required after wound responses for development and maintenance of poles during regeneration and homeostatic tissue turnover. Independently of the requirement for pbx in pole regeneration, pbx is required for eye precursor formation and, consequently, eye regeneration and eye replacement in homeostasis. Together, these data indicate that pbx promotes pole formation of body axes and formation of regenerative progenitors for eyes.