bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective Pilot Study of B2A-Coated Ceramic Granules (Amplex) Compared to Autograft for Ankle and Hindfoot Arthrodesis
Authors: Glazebrook Mark , Younger Alastair , Wing Kevin , Lalonde Karl-Andre 
Published: March 2013

Background: To reduce fusion nonunion, autogenous bone graft is often incorporated into foot and ankle fusion procedures. B2A peptide-coated ceramic granules, with encouraging results in pilot studies of transforaminal lumbar interbody fusion, were here reformulated into Amplex with a coating concentration of 225 μg B2A/cm3 ceramic granules (B2A-granule) with the goal of eliminating autogenous bone graft in foot and ankle arthrodesis. The purpose of this study was to perform a multicenter prospective randomized pilot clinical trial designed to compare the safety and effectiveness of B2A-granule to autogenous bone graft in patients undergoing foot and ankle arthrodesis surgery. Methods: This study was a multicenter, prospective, randomized, pilot clinical trial designed to compare safety and effectiveness of B2A-granule to autogenous bone graft in patients undergoing foot and ankle arthrodesis surgery. Twenty-four patients were enrolled and randomized (1:1) into 2 groups: autogenous bone graft control and B2A-granule. Primary outcome measures at 6 months (with follow-up at 9 and 12 months) included radiographic fusion assessed by computerized tomography and Ankle Osteoarthritis Scale scores for pain and disability. Results: Radiographic fusion success rates were similar in both groups (100% in the B2A-granule group, 92% autograft). Both the B2A-granule group and the autograft group had improvements in the pain and disability scores over the course of the study. Graft harvest-site pain affected only autograft-treated patients. There were no adverse events attributed to the graft material in either the B2A-granule or autograft group. Conclusion: The results of this pilot study are supportive of a larger clinical trial to assess the safety and efficacy of B2A-granule as a bone graft substitute in foot and ankle fusions. Level of Evidence: Level II, prospective comparative study.
Empirical Bayes estimation of posterior probabilities of enrichment: A comparative study of five estimators of the local false discovery rate
Authors: Yang Zhenyu , Li Zuojing , Bickel David R 
Published: March 2013

AbstractBackgroundIn investigating differentially expressed genes or other selected features, researchers conduct hypothesis tests to determine which biological categories, such as those of the Gene Ontology (GO), are enriched for the selected features. Multiple comparison procedures (MCPs) are commonly used to prevent excessive false positive rates. Traditional MCPs, e.g., the Bonferroni method, go to the opposite extreme: strictly controlling a family-wise error rate, resulting in excessive false negative rates. Researchers generally prefer the more balanced approach of instead controlling the false discovery rate (FDR). However, the q-values that methods of FDR control assign to biological categories tend to be too low to reliably estimate the probability that a biological category is not enriched for the preselected features. Thus, we study an application of the other estimators of that probability, which is called the local FDR (LFDR).ResultsWe considered five LFDR estimators for detecting enriched GO terms: a binomial-based estimator (BBE), a maximum likelihood estimator (MLE), a normalized MLE (NMLE), a histogram-based estimator assuming a theoretical null hypothesis (HBE), and a histogram-based estimator assuming an empirical null hypothesis (HBE-EN). Since NMLE depends not only on the data but also on the specified value ofΠ0, the proportion of non-enriched GO terms, it is only advantageous when eitherΠ0is already known with sufficient accuracy or there are data for only 1 GO term. By contrast, the other estimators work without specifyingΠ0but require data for at least 2 GO terms. Our simulation studies yielded the following summaries of the relative performance of each of those four estimators. HBE and HBE-EN produced larger biases for 2, 4, 8, 32, and 100 GO terms than BBE and MLE. BBE has the lowest bias ifΠ0is 1 and if the number of GO terms is between 2 and 32. The bias of MLE is no worse than that of BBE for 100 GO terms even when the ideal number of components in its underlying mixture model is unknown, but has high bias when the number of GO terms is small compared to the number of estimated parameters. For unknown values ofΠ0, BBE has the lowest bias for a small number of GO terms (2-32 GO terms), and MLE has the lowest bias for a medium number of GO terms (100 GO terms).ConclusionsFor enrichment detection, we recommend estimating the LFDR by MLE given at least a medium number of GO terms, by BBE given a small number of GO terms, and by NMLE given either only 1 GO term or precise knowledge ofΠ0.
Multigenic nature of the mouse pulmonary adenoma progression 1locus
Authors: Dassano Alice , Noci Sara , Galbiati Federica , Colombo Francesca , Trincucci Gaia , Pettinicchio Angela , Dragani Tommaso A , Manenti Giacomo 
Published: March 2013

Abstract

Background
In an intercross between the SWR/J and BALB/c mouse strains, the pulmonary adenoma progression 1 (Papg1) locus on chromosome 4 modulates lung tumor size, one of several measures of lung tumor progression. This locus has not been fully characterized and defined in its extent and genetic content. Fine mapping of this and other loci affecting lung tumor phenotype is possible using recombinant inbred strains.

Results
A population of 376 mice, obtained by crossing mice of the SWR/J strain with CXBN recombinant inbred mice, was treated with a single dose of urethane and assayed for multiplicity of large lung tumors (N2lung). A genome-wide analysis comparing N2lung with 6364 autosomal SNPs revealed multiple peaks of association. The Papg1 locus had two peaks, at rs3654162 (70.574 Mb, -logP=2.8) and rs6209043 (86.606 Mb, -logP=2.7), joined by an interval of weaker statistical association; these data confirm the presence of Papg1 on chromosome 4 and reduce the mapping region to two stretches of ~6.8 and ~4.2 Mb, in the proximal and distal peaks, respectively. The distal peak included Cdkn2a, a gene already proposed as being involved in Papg1 function. Other loci possibly modulating N2lung were detected on chromosomes 5, 8, 9, 11, 15, and 19, but analysis for linkage disequilibrium of these putative loci with Papg1 locus suggested that only those on chromosomes 11 and 15 were true positives.

Conclusions
These findings suggest that Papg1 consists, most likely, of two distinct, nearby loci, and point to putative additional loci on chromosomes 11 and 15 modulating lung tumor size. Within Papg1, Cdkn2a appears to be a strong candidate gene while additional Papg1 genes await to be identified. Greater knowledge of the genetic and biochemical mechanisms underlying the germ-line modulation of lung tumor size in mice is relevant to other species, including humans, in that it may help identify new therapeutic targets in the fight against tumor progression.
Mutation spectrum in human colorectal cancers and potential functional relevance
Authors: Yin Hongzhuan , Liang Yichao , Yan Zhaopeng , Liu Baolin , Su Qi 
Published: March 2013

Abstract

Background
Somatic variants, which occur in the genome of all cells, are well accepted to play a critical role in cancer development, as their accumulation in genes could affect cell proliferations and cell cycle.

Methods
In order to understand the role of somatic mutations in human colorectal cancers, we characterized the mutation spectrum in two colorectal tumor tissues and their matched normal tissues, by analyzing deep-sequenced transcriptome data.

Results
We found a higher mutation rate of somatic variants in tumor tissues in comparison with normal tissues, but no trend was observed for mutation properties. By applying a series of stringent filters, we identified 418 genes with tumor specific disruptive somatic variants. Of these genes, three genes in mucin protein family (MUC2, MUC4, and MU12) are of particular interests. It has been reported that the expression of mucin proteins was correlated with the progression of colorectal cancer therefore somatic variants within those genes can interrupt their normal expression and thus contribute to the tumorigenesis.

Conclusions
Our findings provide evidence of the utility of RNA-Seq in mutation screening in cancer studies, and suggest a list of candidate genes for future colorectal cancer diagnosis and treatment.
Hyperparasitaemic human Plasmodium knowlesi infection with atypical morphology in peninsular Malaysia
Authors: Lee Wenn-Chyau , Chin Pek-Woon , Lau Yee-Ling , Chin Lit-Chein , Fong Mun-Yik , Yap Chee-Jiek , Supramaniam Raymond Raj , Mahmud Rohela 
Published: March 2013

Abstract

Plasmodium knowlesi is a potentially life-threatening zoonotic malaria parasite due to its relatively short erythrocytic cycle. Microscopic identification of P. knowlesi is difficult, with “compacted parasite cytoplasm” being one of the important identifying keys. This report is about a case of hyperparasitaemic human P. knowlesi infection (27% parasitaemia) with atypical amoeboid morphology. A peninsular Malaysian was admitted to the hospital with malaria. He suffered anaemia and acute kidney function impairment. Microscopic examination, assisted by nested PCR and sequencing confirmed as P. knowlesi infection. With anti-malarial treatment and several medical interventions, patient survived and recovered. One-month medical follow-up was performed after recovery and no recrudescence was noted. This case report highlights the extreme hyperparasitaemic setting, the atypical morphology of P. knowlesi in the patient’s erythrocytes, as well as the medical interventions involved in this successfully treated case.
A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype
Authors: Ellis Brian L , Hirsch Matthew L , Barker Jenny C , Connelly Jon P , Steininger Robert J , Porteus Matthew H 
Published: March 2013

Abstract

Background
The ability to deliver a gene of interest into a specific cell type is an essential aspect of biomedical research. Viruses can be a useful tool for this delivery, particularly in difficult to transfect cell types. Adeno-associated virus (AAV) is a useful gene transfer vector because of its ability to mediate efficient gene transduction in numerous dividing and quiescent cell types, without inducing any known pathogenicity. There are now a number of natural for that designed AAV serotypes that each has a differential ability to infect a variety of cell types. Although transduction studies have been completed, the bulk of the studies have been done in vivo, and there has never been a comprehensive study of transduction ex vivo/in vitro.

Methods
Each cell type was infected with each serotype at a multiplicity of infection of 100,000 viral genomes/cell and transduction was analyzed by flow cytometry + .

Results
We found that AAV1 and AAV6 have the greatest ability to transduce a wide range of cell types, however, for particular cell types, there are specific serotypes that provide optimal transduction.

Conclusions
In this work, we describe the transduction efficiency of ten different AAV serotypes in thirty-four different mammalian cell lines and primary cell types. Although these results may not be universal due to numerous factors such as, culture conditions and/ or cell growth rates and cell heterogeneity, these results provide an important and unique resource for investigators who use AAV as an ex vivo gene delivery vector or who work with cells that are difficult to transfect.
Molecular characterization of HTLV-1 gp46 glycoprotein from health carriers and HAM/TSP infected individuals
Authors: Mota-Miranda Aline C A , Barreto Fernanda K , Amarante Maria F C , Batista Everton , Monteiro-Cunha Joana P , Farre Lourdes , Galvão-Castro Bernardo , Alcantara Luiz C J 
Published: March 2013

AbstractBackgroundHuman T-cell Leukemia Virus type 1 (HTLV-1) is the etiological agent of tropical spastic paraparesis/HTLV-associated myelopathy (HAM/TSP) that can be identified in around 0.25%–3.8% of the infected population. Disease progression can be monitored by the proviral load and may depend on genetic factors, however, it is not well understood why some HTLV-1 infected people develop the disease while others do not. The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals.MethodsBlood samples were collected from 10 individuals, and DNA was extracted from PBMCs to measure the HTLV-1 proviral load. The gp46 coding sequences were amplified PCR, cloned and sequenced. The molecular characterization was performed using bioinformatics tools.ResultsThe median HTLV-1 proviral load of HC (n = 5) and HAM/TSP (n = 5) patients was similar (average 316,227 copies/106PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. Five frequent mutations were detected among groups (HAM/TSP and HC clone sequences). A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53–75 and 175–209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46.ConclusionsThe most common gp46 mutations were not associated clinical status because they were found in only one individual, except for the V247I mutation, that was found at viral clones from HAM/TSP ad HC individuals. Because of this, we cannot associate any of the gp46 found mutations with the clinical profile.
Lower ratio of high-molecular-weight adiponectin level to total may be associated with coronary high-risk plaque
Authors: Moroi Masao , Akter Shamima , Nakazato Ryo , Kunimasa Taeko , Masai Hirofumi , Furuhashi Tatsuhiko , Fukuda Hiroshi , Koda Eiichi , Sugi Kaoru , Jesmin Subrina 
Published: March 2013

Abstract

Background
Although high-molecular-weight (HMW) adiponectin is believed to protect against atherosclerosis, the association between HMW adiponectin and the composition of coronary plaques is unknown. We evaluated whether the HMW to total adiponectin ratio was associated with the presence of coronary plaque and its composition using multi-slice computed tomography coronary angiography (MSCTCA).

Methods
Serum total and HMW adiponectin levels were measured in 53 consecutive patients (age, 71) with >50% coronary artery stenosis detected by MSCTCA. A low-attenuation coronary plaque was defined as a plaque with a mean CT density <50 Hounsfield units. Multivariate logistic regression analyses were performed to evaluate the predictors of the presence of low-attenuation coronary plaques, which is thought to be high risk, on CT.

Results
Decreased serum levels of total as well as HMW adiponectin were significantly associated with the presence of at least one calcified or non-calcified coronary artery plaque (total adiponectin level: odds ratio 0.76, 95% CI 0.58–0.99, P = 0.048; HMW adiponectin level: odds ratio 0.65, 95% CI 0.42–0.99, P = 0.047). A low ratio of HMW to total adiponectin was significantly associated with the presence of low-attenuation coronary plaques (4.55, 1.94–21.90, P = 0.049). However, neither the total adiponectin nor the HMW adiponectin level was associated with the presence of low-attenuation coronary plaques.

Conclusion
Lower total or HMW adiponectin levels are associated with the presence of calcified and non-calcified coronary plaques, whereas a lower ratio of HMW to total adiponectin associated with the presence of low-attenuation coronary plaques (thought to be high risk). Measurement of total and HMW adiponectin levels and the HMW to total adiponectin ratio may be useful for risk stratification of coronary artery plaques.
Functional genetic characterization of salivary gland development in Aedes aegypti
Authors: Nguyen Chilinh , Andrews Emily , Le Christy , Sun Longhua , Annan Zeinab , Clemons Anthony , Severson David W , Duman-Scheel Molly 
Published: March 2013

AbstractBackgroundDespite the devastating global impact of mosquito-borne illnesses on human health, very little is known about mosquito developmental biology. In this investigation, functional genetic analysis of embryonic salivary gland development was performed inAedes aegypti, the dengue and yellow fever vector and an emerging model for vector mosquito development. Although embryonic salivary gland development has been well studied inDrosophila melanogaster, little is known about this process in mosquitoes or other arthropods.ResultsMosquitoes possess orthologs of many genes that regulateDrosophila melanogasterembryonic salivary gland development. The expression patterns of a large subset of these genes were assessed duringAe. aegyptidevelopment. These studies identified a set of molecular genetic markers for the developing mosquito salivary gland. Analysis of marker expression allowed for tracking of the progression ofAe. aegyptisalivary gland development in embryos. InDrosophila,the salivary glands develop from placodes located in the ventral neuroectoderm. However, inAe. aegypti,salivary marker genes are not expressed in placode-like patterns in the ventral neuroectoderm. Instead, marker gene expression is detected in salivary gland rudiments adjacent to the proventriculus. These observations highlighted the need for functional genetic characterization of mosquito salivary gland development. An siRNA- mediated knockdown strategy was therefore employed to investigate the role of one of the marker genes,cyclic-AMP response element binding protein A(Aae crebA),duringAe. aegyptisalivary gland development.These experiments revealed thatAae crebAencodes a key transcriptional regulator of the secretory pathway in the developingAe. aegyptisalivary gland.ConclusionsThe results of this investigation indicated that the initiation of salivary gland development inAe. aegyptisignificantly differs from that ofD. melanogaster. Despite these differences, some elements of salivary gland development, including the ability of CrebA to regulate secretory gene expression, are conserved between the two species. These studies underscore the need for further analysis of mosquito developmental genetics and may foster comparative studies of salivary gland development in additional insect species.
Road Traffic Noise and Self-Reported Sleep Disturbance: Results from a Cross-Sectional Study in Western India
Authors: Banerjee Dibyendu 
Published: March 2013

Background: Previous studies have provided evidence about chronic night noise exposure and sleep disturbance, which is indicator of more serious health conditions. Such studies have never been reported for the Indian population. This study aimed to further explore the association between nocturnal transportation noise exposure and self-reported sleep disturbances in an adult Indian population. Methods: The cross-sectional study used results from a pilot study, from a large scale social survey in the urban municipality of Asansol, an industrial city, situated in western India. The survey included responses from 221 adults (19–59 year old) residing within 100 meters buffer of the major and arterial roadways, with criteria of minimum 10 years stay in the study area. Association of self-reported sleep disturbance was studied by multiple logistic regression analysis with adjusting for age, gender and period of residence. Results: Sleep disturbance was more marked at levels of 61–65 dB(A) night noise exposure, OR (95% CI) 2.36 (1.13–4.94. For a 5dB(A) increase in night noise exposure, the OR (95% CI) was 1.30 (1.04–1.64). For every 10 years addition to age of the respondents, odds of sleep disturbance was estimated to increase by 1.17 over non-exposure individuals. Women reported higher sleep disturbance, OR (95% CI) 1.23 (0.65–1.92) in comparison to men A period of residence of 10 years in study area showed an OR (95% CI) of 1.33 (0.86–2.06) for sleep disturbance among exposed respondents. Further it was estimated with 95% confidence that the attributable fraction for sleep disturbance among those noise exposed within the population was 16% to 80%. Conclusions: The study results support an association between higher nocturnal road traffic noise and self-reported sleep disturbance in comparison to areas with quieter nights. Further sleep disturbance among women was significantly associated with higher night noise exposure.
Factors Influencing the 99th Percentile of Cardiac Troponin I Evaluated in Community-Dwelling Individuals at 70 and 75 Years of Age
Authors: Eggers Kai M , Lind Lars , Venge Per , Lindahl Bertil 
Published: March 2013

BACKGROUND
We aimed to investigate the effects of sex, prevalent cardiovascular disease (CVD), and aging on the 99th percentile of cardiac troponin I (cTnI).

METHODS
cTnI was measured using a high-sensitivity assay (Abbott Diagnostics) in 814 community-dwelling individuals at both 70 and 75 years of age. We determined the cTnI 99th percentiles separately using nonparametric methods in the total sample, in men and women, and in individuals with and without CVD.

RESULTS
The cTnI 99th percentile at baseline was 55.2 ng/L for the total cohort. Higher 99th percentiles were noted in men (69.3 ng/L) and individuals with CVD (74.5 ng/L). The cTnI 99th percentile in individuals free from CVD at baseline (n = 498) increased by 51% from 38.4 to 58.0 ng/L during the 5-year observation period. Relative increases ranging from 44% to 83% were noted across all subgroups. Male sex [odds ratio, 5.3 (95% CI, 1.5–18.3)], log-transformed N-terminal pro-B-type natriuretic peptide [odds ratio, 1.9 (95% CI, 1.2–3.0)], and left-ventricular mass index [odds ratio, 1.3 (95% CI, 1.1–1.5)] predicted increases in cTnI concentrations from below the 99th percentile (i.e., 38.4 ng/L) at baseline to concentrations above the 99th percentile at the age of 75 years.

CONCLUSIONS
cTnI concentration and its 99th percentile threshold depend strongly on the characteristics of the population being assessed. Among elderly community dwellers, higher concentrations were seen in men and individuals with prevalent CVD. Aging contributes to increasing concentrations, given the pronounced changes seen with increasing age across all subgroups. These findings should be taken into consideration when applying cTnI decision thresholds in clinical settings.