bluuebunny/crossref_metadata_2025_split huggingface dataset:
GC-Content Normalization for RNA-Seq Data
Authors: Risso Davide , Schwartz Katja , Sherlock Gavin , Dudoit Sandrine 
Published: December 2011

Abstract

Background
Transcriptome sequencing (RNA-Seq) has become the assay of choice for high-throughput studies of gene expression. However, as is the case with microarrays, major technology-related artifacts and biases affect the resulting expression measures. Normalization is therefore essential to ensure accurate inference of expression levels and subsequent analyses thereof.

Results
We focus on biases related to GC-content and demonstrate the existence of strong sample-specific GC-content effects on RNA-Seq read counts, which can substantially bias differential expression analysis. We propose three simple within-lane gene-level GC-content normalization approaches and assess their performance on two different RNA-Seq datasets, involving different species and experimental designs. Our methods are compared to state-of-the-art normalization procedures in terms of bias and mean squared error for expression fold-change estimation and in terms of Type I error and p-value distributions for tests of differential expression. The exploratory data analysis and normalization methods proposed in this article are implemented in the open-source Bioconductor R package EDASeq.

Conclusions
Our within-lane normalization procedures, followed by between-lane normalization, reduce GC-content bias and lead to more accurate estimates of expression fold-changes and tests of differential expression. Such results are crucial for the biological interpretation of RNA-Seq experiments, where downstream analyses can be sensitive to the supplied lists of genes.
Structural characterization of helitrons and their stepwise capturing of gene fragments in the maize genome
Authors: Dong Yongbin , Lu Xiaomin , Song Weibin , Shi Lei , Zhang Mei , Zhao Hainan , Jiao Yinping , Lai Jinsheng 
Published: December 2011

Abstract

Background
As a newly identified category of DNA transposon, helitrons have been found in a large number of eukaryotes genomes. Helitrons have contributed significantly to the intra-specific genome diversity in maize. Although many characteristics of helitrons in the maize genome have been well documented, the sequence of an intact autonomous helitrons has not been identified in maize. In addition, the process of gene fragment capturing during the transposition of helitrons has not been characterized.

Results
The whole genome sequences of maize inbred line B73 were analyzed, 1,649 helitron-like transposons including 1,515 helAs and 134 helBs were identified. ZmhelA1, ZmhelB1 and ZmhelB2 all encode an open reading frame (ORF) with intact replication initiator (Rep) motif and a DNA helicase (Hel) domain, which are similar to previously reported autonomous helitrons in other organisms. The putative autonomous ZmhelB1 and ZmhelB2 contain an extra replication factor-a protein1 (RPA1) transposase (RPA-TPase) including three single strand DNA-binding domains (DBD)-A/-B/-C in the ORF. Over ninety percent of maize helitrons identified have captured gene fragments. HelAs and helBs carry 4,645 and 249 gene fragments, which yield 2,507 and 187 different genes respectively. Many helitrons contain mutilple terminal sequences, but only one 3'-terminal sequence had an intact "CTAG" motif. There were no significant differences in the 5'-termini sequence between the veritas terminal sequence and the pseudo sequence. Helitrons not only can capture fragments, but were also shown to lose internal sequences during the course of transposing.

Conclusions
Three putative autonomous elements were identified, which encoded an intact Rep motif and a DNA helicase domain, suggesting that autonomous helitrons may exist in modern maize. The results indicate that gene fragments captured during the transposition of many helitrons happen in a stepwise way, with multiple gene fragments within one helitron resulting from several sequential transpositions. In addition, we have proposed a potential mechanism regarding how helitrons with multiple termini are generated.
Comparison of ICD code-based diagnosis of obesity with measured obesity in children and the implications for health care cost estimates
Authors: Kuhle Stefan , Kirk Sara FL , Ohinmaa Arto , Veugelers Paul J 
Published: December 2011

Abstract

Background
Administrative health databases are a valuable research tool to assess health care utilization at the population level. However, their use in obesity research limited due to the lack of data on body weight. A potential workaround is to use the ICD code of obesity to identify obese individuals. The objective of the current study was to investigate the sensitivity and specificity of an ICD code-based diagnosis of obesity from administrative health data relative to the gold standard measured BMI.

Methods
Linkage of a population-based survey with anthropometric measures in elementary school children in 2003 with longitudinal administrative health data (physician visits and hospital discharges 1992-2006) from the Canadian province of Nova Scotia. Measured obesity was defined based on the CDC cut-offs applied to the measured BMI. An ICD code-based diagnosis obesity was defined as one or more ICD-9 (278) or ICD-10 code (E66-E68) of obesity from a physician visit or a hospital stay. Sensitivity and specificity were calculated and health care cost estimates based on measured obesity and ICD-based obesity were compared.

Results
The sensitivity of an ICD code-based obesity diagnosis was 7.4% using ICD codes between 2002 and 2004. Those correctly identified had a higher BMI and had higher health care utilization and costs.

Conclusions
An ICD diagnosis of obesity in Canadian administrative health data grossly underestimates the true prevalence of childhood obesity and overestimates the health care cost differential between obese and non-obese children.
Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial
Authors: Onland Wes , Offringa Martin , Cools Filip , De Jaegere Anne P , Rademaker Karin , Blom Henry , Cavatorta Eric , Debeer Anne , Dijk Peter H , van Heijst Arno F , Kramer Boris W , Kroon Andre A , Mohns Thilo , van Straaten Henrica L , te Pas Arjan B , Theyskens Claire , van Weissenbruch Mirjam M , van Kaam Anton H 
Published: December 2011

Abstract

Background
Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants.

Methods/Design
The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis.

Discussion
This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.

Trial registration number
Netherlands Trial Register (NTR): NTR2768
Comparison between two pedicle screw augmentation instrumentations in adult degenerative scoliosis with osteoporosis
Authors: Xie Yang , Fu Qiang , Chen Zi-qiang , Shi Zhi-cai , Zhu Xiao-dong , Wang Chuan-feng , Li Ming 
Published: December 2011

Abstract

Background
The operative treatment of adult degenerative scoliosis combined with osteoporosis increase following the epidemiological development. Studies have confirmed that screws in osteoporotic spines have significant lower-screw strength with more frequent screw movements within the vertebra than normal spines. Screws augmented with Polymethylmethacrylate (PMMA) or with autogenous bone can offer more powerful corrective force and significant advantages.

Methods
A retrospective analysis was conducted on 31 consecutive patients with degenerative lumbar scoliosis combined with osteoporosis who had surgery from December 2000. All had a minimum of 2-year follow-up. All patients had posterior approach surgery. 14 of them were fixed with pedicle screw by augmentation with Polymethylmethacrylate (PMMA) and the other 17 patients with autogenous bone. Age, sex and whether smoking were similar between the two groups. Surgical time, blood loss, blood transfusion, medical cost, post surgery ICU time, hospital day, length of oral pain medicines taken, Pre-and postoperative Oswestry disability index questionnaire and surgical revision were documented and compared. Preoperative, postoperative and final follow up Cobb angle, sagittal lumbar curve, correction rate, and Follow up Cobb loss were also compared.

Results
No significant differences were found between the autogenous bone group and Polymethylmethacrylate group with regards to all the targets above except for length of oral pain medicines taken and surgery cost. 2 patients were seen leakage during operation, but there is neither damage of nerve nor symptom after operation. No revision was needed.

Conclusion
Both augmentation pedicle screw with Polymethylmethacrylate (PMMA) and autogenous bone treating degenerative lumbar scoliosis combined with osteoporosis can achieve a good surgical result. Less oral pain medicines taken are the potential benefits of Polymethylmethacrylate augmentation, but that is at the cost of more medical spending.
Devolution and public perceptions and experience of health services in Pakistan: linked cross sectional surveys in 2002 and 2004
Authors: Ansari Umaira , Cockcroft Anne , Omer Khalid , Ansari Noor MD , Khan Amir , Chaudhry Ubaid Ullah , Andersson Neil 
Published: December 2011

Abstract

Background
The government of Pakistan introduced devolution in 2001. Responsibility for delivery of most health services passed from provincial to district governments. Two national surveys examined public opinions, use, and experience of health services in 2001 and 2004, to assess the impact of devolution on these services from the point of view of the public.

Methods
A stratified random cluster sample drawn in 2001 and revisited in 2004 included households in all districts. Field teams administered a questionnaire covering views about available health services, use of government and private health services, and experience and satisfaction with the service. Focus groups in each community discussed reasons behind the findings, and district nazims (elected mayors) and administrators commented about implementation of devolution. Multivariate analysis, with an adjustment for clustering, examined changes over time, and associations with use and satisfaction with services in 2004.

Results
Few of 57,321 households interviewed in 2002 were satisfied with available government health services (23%), with a similar satisfaction (27%) among 53,960 households in 2004. Less households used government health services in 2004 (24%) than in 2002 (29%); the decrease was significant in the most populous province. In 2004, households were more likely to use government services if they were satisfied with the services, poorer, or less educated. The majority of users of government health services were satisfied; the increase from 63% to 67% between 2002 and 2004 was significant in two provinces. Satisfaction in 2004 was higher among users of private services (87%) or private unqualified practitioners (78%). Users of government services who received all medicines from the facility or who were given an explanation of their condition were more likely to be satisfied. Focus groups explained that people avoid government health services particularly because of bad treatment from staff, and unavailable or poor quality medicines. District nazims and administrators cited problems with implementation of devolution, especially with transfer of funds.

Conclusions
Under devolution, the public did not experience improved government health services, but devolution was not fully implemented as intended. An ongoing social audit process could provide a basis for local and national accountability of health services.
CYP2J3 Gene Delivery Reduces Insulin Resistance via Upregulation of eNOS in Fructose-treated Rats
Authors: Xu Xizhen , Tu Ling , Wang Luyun , Fang Xiaosai , Wang Dao Wen 
Published: December 2011

Abstract
Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs) which play important roles in various pathophysiological processes. Interestingly, CYP-derived eicosanoids are vasodilatory, at least in part through their ability to activate eNOS and subsequent NO release. This study investigated the roles of eNOS in CYP2J3 gene delivery reducing blood pressure and improving insulin resistance in fructose-treated rats. CYP2J3 overexpression in vivo increased EET generation, reduced blood pressure and reversed insulin resistance as determined by insulin resistance index (HOMA-IR). Furthermore, administration of eNOS inhibitor L-NMMA significantly and partially abolished the beneficial effects of CYP2J3 gene delivery on hypertension and insulin resistance induced by fructose intake, and possible mechanism is associated with increased ET-1, ETA-receptor mRNA expression and reduced sensitivity of insulin to peripheral tissues and organs characterized by reduced activity of IRS-1/PI3K/AKT and AMPK signalling pathways. These data provide direct evidence that CYP2J3-derived EETs may alleviate insulin resistance at least in part through upregulated eNOS expression.
Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
Authors: Carlsson Anja M , Ngasala Billy E , Dahlström Sabina , Membi Christopher , Veiga Isabel M , Rombo Lars , Abdulla Salim , Premji Zul , Gil J Pedro , Björkman Anders , Mårtensson Andreas 
Published: December 2011

Abstract

Background
This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa.

Methods
A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2.

Results
PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families.

Conclusion
PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa.
The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375.
A modified Mann iterative scheme by generalized f-projection for a countable family of relatively quasi-nonexpansive mappings and a system of generalized mixed equilibrium problems
Authors: Saewan Siwaporn , Kumam Poom 
Published: December 2011

AbstractThe purpose of this paper is to introduce a new hybrid projection method based on modified Mann iterative scheme by the generalized f-projection operator for a countable family of relatively quasi-nonexpansive mappings and the solutions of the system of generalized mixed equilibrium problems. Furthermore, we prove the strong convergence theorem for a countable family of relatively quasi-nonexpansive mappings in a uniformly convex and uniform smooth Banach space. Finally, we also apply our results to the problem of finding zeros of
B
-monotone mappings and maximal monotone operators. The results presented in this paper generalize and improve some well-known results in the literature.2000 Mathematics Subject Classification: 47H05; 47H09; 47H10.
TLR3 signaling is either protective or pathogenic for the development of Theiler's virus-induced demyelinating disease depending on the time of viral infection
Authors: Jin Young-Hee , Kaneyama Tomoki , Kang Min Hyung , Kang Hyun Seok , Koh Chang-Sung , Kim Byung S 
Published: December 2011

AbstractBackgroundWe have previously shown that toll-like receptor 3 (TLR3)-mediated signaling plays an important role in the induction of innate cytokine responses to Theiler's murine encephalomyelitis virus (TMEV) infection. In addition, cytokine levels produced after TMEV infection are significantly higher in the glial cells of susceptible SJL mice compared to those of resistant C57BL/6 mice. However, it is not known whether TLR3-mediated signaling plays a protective or pathogenic role in the development of demyelinating disease.MethodsSJL/J and B6;129S-Tlr3tm1Flv/J (TLR3KO-B6) mice, and TLR3KO-SJL mice that TLR3KO-B6 mice were backcrossed to SJL/J mice for 6 generations were infected with Theiler's murine encephalomyelitis virus (2 × 105PFU) with or without treatment with 50 μg of poly IC. Cytokine production and immune responses in the CNS and periphery of infected mice were analyzed.ResultsWe investigated the role of TLR3-mediated signaling in the protection and pathogenesis of TMEV-induced demyelinating disease. TLR3KO-B6 mice did not develop demyelinating disease although they displayed elevated viral loads in the CNS. However, TLR3KO-SJL mice displayed increased viral loads and cellular infiltration in the CNS, accompanied by exacerbated development of demyelinating disease, compared to the normal littermate mice. Late, but not early, anti-viral CD4+and CD8+T cell responses in the CNS were compromised in TLR3KO-SJL mice. However, activation of TLR3 with poly IC prior to viral infection also exacerbated disease development, whereas such activation after viral infection restrained disease development. Activation of TLR3 signaling prior to viral infection hindered the induction of protective IFN-γ-producing CD4+and CD8+T cell populations. In contrast, activation of these signals after viral infection improved the induction of IFN-γ-producing CD4+and CD8+T cells. In addition, poly IC-pretreated mice displayed elevated PDL-1 and regulatory FoxP3+CD4+T cells in the CNS, while poly IC-post-treated mice expressed reduced levels of PDL-1 and FoxP3+CD4+T cells.ConclusionsThese results suggest that TLR3-mediated signaling during viral infection protects against demyelinating disease by reducing the viral load and modulating immune responses. In contrast, premature activation of TLR3 signal transduction prior to viral infection leads to pathogenesis via over-activation of the pathogenic immune response.
Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide
Authors: Park Sook-Eun , Lawson Marcus , Dantzer Robert , Kelley Keith W , McCusker Robert H 
Published: December 2011

AbstractCentrally administered insulin-like growth factor (IGF)-I has anti-depressant activity in several rodent models, including lipopolysaccharide (LPS)-induced depression. In this study we tested the ability of IGF-I and GPE (the N-terminal tri-peptide derived from IGF-I) to alter depression-like behavior induced by intraperitoneal (i.p.) administration of LPS in a preventive and curative manner. In the first case, IGF-I (1 μg) or GPE (5 μg) was administered i.c.v. to CD-1 mice followed 30 min later by 330 μg/kg body weight i.p. LPS. In the second case, 830 μg/kg body weight LPS was given 24 h prior to either IGF-I or GPE. When administered i.p., LPS induced full-blown sickness assessed as a loss of body weight, decrease in food intake and sickness behavior. None of these indices were affected by IGF-I or GPE. LPS also induced depression-like behavior; assessed as an increased duration of immobility in the tail suspension and forced swim tests. When administered before or after LPS, IGF-I and GPE abrogated the LPS response; attenuating induction of depression-like behaviors and blocking preexistent depression-like behaviors. Similar to previous work with IGF-I, GPE decreased brain expression of cytokines in response to LPS although unlike IGF-I, GPE did not induce the expression of brain-derived neurotrophic factor (BDNF). LPS induced expression of tryptophan dioxygenases, IDO1, IDO2 and TDO2, but expression of these enzymes was not altered by GPE. Thus, both IGF-I and GPE elicit specific improvement in depression-like behavior independent of sickness, an action that could be due to their anti-inflammatory properties.