bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis
Authors: Judge Eoin P. , Fabre Aurelie , Adamali Huzaifa I. , Egan Jim J. 
Published: December 2011

The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue.55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients.Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing.Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.
Asthma and suicide-related adverse events: a review of observational studies
Authors: Iessa N. , Murray M.L. , Curran S. , Wong I.C.K. 
Published: December 2011

Suicide is a major public health concern. There are several risk factors associated with suicide. Chronic illnesses, such as asthma, have been linked to an increased risk of suicide-related events. This study reviews the evidence of an association between asthma and suicide using published epidemiological observational studies.An electronic search using PubMed and EMBASE was performed. Studies that investigated the association of asthma with suicide-related behaviour were selected. Studies were examined to form a descriptive analysis.Six observational studies met the selection criteria, of which at least one suicide-related adverse event was studied. Three studies investigated completed suicide, two suicide attempts and four suicide ideation. Two of the studies focused on individuals aged <18 yrs.Evidence from observational data support the hypothesis of an association between asthma and suicide-related behaviour (ideation, attempts and completion); however, epidemiological studies, with more objective measures and larger sample sizes, adjusting for a wider scope of suicide-related confounding factors (e.g.comorbidities), and with a longitudinal design, are needed for a more conclusive answer.
Cell cycle phase classification in 3D in vivo microscopy of Drosophila embryogenesis
Authors: Du Tie Hua , Puah Wee Choo , Wasser Martin 
Published: December 2011

Abstract

Background
Cell divisions play critical roles in disease and development. The analysis of cell division phenotypes in high content image-based screening and time-lapse microscopy relies on automated nuclear segmentation and classification of cell cycle phases. Automated identification of the cell cycle phase helps biologists quantify the effect of genetic perturbations and drug treatments. Most existing studies have dealt with 2D images of cultured cells. Few, if any, studies have addressed the problem of cell cycle classification in 3D image stacks of intact tissues.

Results
We developed a workflow for the automated cell cycle phase classification in 3D time-series image datasets of live Drosophila embryos expressing the chromatin marker histone-GFP. Upon image acquisition by laser scanning confocal microscopy and 3D nuclear segmentation, we extracted 3D intensity, shape and texture features from interphase nuclei and mitotic chromosomes. We trained different classifiers, including support vector machines (SVM) and neural networks, to distinguish between 5 cell cycles phases (Interphase and 4 mitotic phases) and achieved over 90% accuracy. As the different phases occur at different frequencies (58% of samples correspond to interphase), we devised a strategy to improve the identification of classes with low representation. To investigate which features are required for accurate classification, we performed feature reduction and selection. We were able to reduce the feature set from 42 to 9 without affecting classifier performance. We observed a dramatic decrease of classification performance when the training and testing samples were derived from two different developmental stages, the nuclear divisions of the syncytial blastoderm and the cell divisions during gastrulation. Combining samples from both developmental stages produced a more robust and accurate classifier.

Conclusions
Our study demonstrates that automated cell cycle phase classification, besides 2D images of cultured cells, can also be applied to 3D images of live tissues. We could reduce the initial 3D feature set from 42 to 9 without compromising performance. Robust classifiers of intact animals need to be trained with samples from different developmental stages and cell types. Cell cycle classification in live animals can be used for automated phenotyping and to improve the performance of automated cell tracking.
A comparative structural bioinformatics analysis of inherited mutations in β-D-Mannosidase across multiple species reveals a genotype-phenotype correlation
Authors: Huynh Thi , Khan Javed Mohammed , Ranganathan Shoba 
Published: December 2011

Abstract

Background
Lysosomal β-D-mannosidase is a glycosyl hydrolase that breaks down the glycosidic bonds at the non-reducing end of N-linked glycoproteins. Hence, it is a crucial enzyme in polysaccharide degradation pathway. Mutations in the MANBA gene that codes for lysosomal β-mannosidase, result in improper coding and malfunctioning of protein, leading to β-mannosidosis. Studying the location of mutations on the enzyme structure is a rational approach in order to understand the functional consequences of these mutations. Accordingly, the pathology and clinical manifestations of the disease could be correlated to the genotypic modifications.

Results
The wild-type and inherited mutations of β-mannosidase were studied across four different species, human, cow, goat and mouse employing a previously demonstrated comprehensive homology modeling and mutational mapping technique, which reveals a correlation between the variation of genotype and the severity of phenotype in β-mannosidosis. X-ray crystallographic structure of β-mannosidase from Bacteroides thetaiotaomicron was used as template for 3D structural modeling of the wild-type enzymes containing all the associated ligands. These wild-type models subsequently served as templates for building mutational structures. Truncations account for approximately 70% of the mutational cases. In general, the proximity of mutations to the active site determines the severity of phenotypic expressions. Mapping mutations to the MANBA gene sequence has identified five mutational hot-spots.

Conclusion
Although restrained by a limited dataset, our comprehensive study suggests a genotype-phenotype correlation in β-mannosidosis. A predictive approach for detecting likely β-mannosidosis is also demonstrated where we have extrapolated observed mutations from one species to homologous positions in other organisms based on the proximity of the mutations to the enzyme active site and their co-location from different organisms. Apart from aiding the detection of mutational hotspots in the gene, where novel mutations could be disease-implicated, this approach also provides a way to predict new disease mutations. Higher expression of the exoglycosidase chitobiase is said to play a vital role in determining disease phenotypes in human and mouse. A bigger dataset of inherited mutations as well as a parallel study of β-mannosidase and chitobiase activities in prospective patients would be interesting to better understand the underlying reasons for β-mannosidosis.
Prioritizing disease candidate genes by a gene interconnectedness-based approach
Authors: Hsu Chia-Lang , Huang Yen-Hua , Hsu Chien-Ting , Yang Ueng-Cheng 
Published: December 2011

Abstract

Background
Genome-wide disease-gene finding approaches may sometimes provide us with a long list of candidate genes. Since using pure experimental approaches to verify all candidates could be expensive, a number of network-based methods have been developed to prioritize candidates. Such tools usually have a set of parameters pre-trained using available network data. This means that re-training network-based tools may be required when existing biological networks are updated or when networks from different sources are to be tried.

Results
We developed a parameter-free method, interconnectedness (ICN), to rank candidate genes by assessing the closeness of them to known disease genes in a network. ICN was tested using 1,993 known disease-gene associations and achieved a success rate of ~44% using a protein-protein interaction network under a test scenario of simulated linkage analysis. This performance is comparable with those of other well-known methods and ICN outperforms other methods when a candidate disease gene is not directly linked to known disease genes in a network. Interestingly, we show that a combined scoring strategy could enable ICN to achieve an even better performance (~50%) than other methods used alone.

Conclusions
ICN, a user-friendly method, can well complement other network-based methods in the context of prioritizing candidate disease genes.
American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR
Authors: Dougherty Urszula , Mustafi Reba , Wang Yunwei , Musch Mark W , Wang Chong-Zhi , Konda Vani J , Kulkarni Anirudh , Hart John , Dawson Glyn , Kim Karen E , Yuan Chun-Su , Chang Eugene B , Bissonnette Marc 
Published: December 2011

Abstract

Background
Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth.

Methods
Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA.

Results
Ginseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth.

Conclusions
Ginseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis.
Bridging health technology assessment (HTA) with multicriteria decision analyses (MCDA): field testing of the EVIDEM framework for coverage decisions by a public payer in Canada
Authors: Tony Michèle , Wagner Monika , Khoury Hanane , Rindress Donna , Papastavros Tina , Oh Paul , Goetghebeur Mireille M 
Published: December 2011

AbstractBackgroundConsistent healthcare decisionmaking requires systematic consideration of decision criteria and evidence available to inform them. This can be tackled by combining multicriteria decision analysis (MCDA) and Health Technology Assessment (HTA). The objective of this study was to field-test a decision support framework (EVIDEM), explore its utility to a drug advisory committee and test its reliability over time.MethodsTramadol for chronic non-cancer pain was selected by the health plan as a case study relevant to their context. Based on extensive literature review, a by-criterion HTA report was developed to provide synthesized evidence for each criterion of the framework (14 criteria for the MCDA Core Model and 6 qualitative criteria for the Contextual Tool). During workshop sessions, committee members tested the framework in three steps by assigning: 1) weights to each criterion of the MCDA Core Model representing individual perspective; 2) scores for tramadol for each criterion of the MCDA Core Model using synthesized data; and 3) qualitative impacts of criteria of the Contextual Tool on the appraisal. Utility and reliability of the approach were explored through discussion, survey and test-retest. Agreement between test and retest data was analyzed by calculating intra-rater correlation coefficients (ICCs) for weights, scores and MCDA value estimates.ResultsThe framework was found useful by the drug advisory committee in supporting systematic consideration of a broad range of criteria to promote a consistent approach to appraising healthcare interventions. Directly integrated in the framework as a "by-criterion" HTA report, synthesized evidence for each criterion facilitated its consideration, although this was sometimes limited by lack of relevant data. Test-retest analysis showed fair to good consistency of weights, scores and MCDA value estimates at the individual level (ICC ranging from 0.676 to 0.698), thus lending some support for the reliability of the approach. Overall, committee members endorsed the inclusion of most framework criteria and revealed important areas of discussion, clarification and adaptation of the framework to the needs of the committee.ConclusionsBy promoting systematic consideration of all decision criteria and the underlying evidence, the framework allows a consistent approach to appraising healthcare interventions. Further testing and validation are needed to advance MCDA approaches in healthcare decisionmaking.
Direct synthesis and characterization of optically transparent conformal zinc oxide nanocrystalline thin films by rapid thermal plasma CVD
Authors: Pedersen Joachim D , Esposito Heather J , Teh Kwok Siong 
Published: December 2011

AbstractWe report a rapid, self-catalyzed, solid precursor-based thermal plasma chemical vapor deposition process for depositing a conformal, nonporous, and optically transparent nanocrystalline ZnO thin film at 130 Torr (0.17 atm). Pure solid zinc is inductively heated and melted, followed by ionization by thermal induction argon/oxygen plasma to produce conformal, nonporous nanocrystalline ZnO films at a growth rate of up to 50 nm/min on amorphous and crystalline substrates including Si (100), fused quartz, glass, muscovite, c- and a-plane sapphire (Al2O3), gold, titanium, and polyimide. X-ray diffraction indicates the grains of as-deposited ZnO to be highly textured, with the fastest growth occurring along the c-axis. The individual grains are observed to be faceted by (103) planes which are the slowest growth planes. ZnO nanocrystalline films of nominal thicknesses of 200 nm are deposited at substrate temperatures of 330°C and 160°C on metal/ceramic substrates and polymer substrates, respectively. In addition, 20-nm- and 200-nm-thick films are also deposited on quartz substrates for optical characterization. At optical spectra above 375 nm, the measured optical transmittance of a 200-nm-thick ZnO film is greater than 80%, while that of a 20-nm-thick film is close to 100%. For a 200-nm-thick ZnO film with an average grain size of 100 nm, a four-point probe measurement shows electrical conductivity of up to 910 S/m. Annealing of 200-nm-thick ZnO films in 300 sccm pure argon at temperatures ranging from 750°C to 950°C (at homologous temperatures between 0.46 and 0.54) alters the textures and morphologies of the thin film. Based on scanning electron microscope images, higher annealing temperatures appear to restructure the ZnO nanocrystalline films to form nanorods of ZnO due to a combination of grain boundary diffusion and bulk diffusion.PACS: films and coatings, 81.15.-z; nanocrystalline materials, 81.07.Bc; II-VI semiconductors, 81.05.Dz.
Assessing the ‘true’ effect of active antidepressant therapy v. placebo in major depressive disorder: use of a mixture model
Authors: Thase Michael E. , Larsen Klaus G. , Kennedy Sidney H. 
Published: December 2011

BackgroundThere is controversy about the implications of relatively small average drug–placebo differences observed in randomised controlled trials of antidepressant medications.AimsTo investigate whether efficacy is better understood as a large effect in a subgroup of patients.MethodThe mixture model was used to identify patient subgroups (patients benefiting or not benefiting from treatment) to directly model the skewness of Montgomery–åsberg Depression Rating Scale (MADRS) scores at week 8.ResultsThe MADRS scores improved by 15.9 points (95% CI 15.2–16.6) among patients who benefited from treatment. The proportion of patients who benefited from escitalopram and not from placebo treatment was 19.5%, corresponding to a number needed to treat of 5.ConclusionsThis model gave a considerably better fit to the data than the analysis of covariance model in which all patients were assumed to benefit from treatment. The small average antidepressant–placebo difference obscures a much larger effect in a clinically meaningful subgroup of patients.
Recessive Loss-of-Function Mutation in the Pacemaker HCN2 Channel Causing Increased Neuronal Excitability in a Patient with Idiopathic Generalized Epilepsy
Authors: DiFrancesco Jacopo C. , Barbuti Andrea , Milanesi Raffaella , Coco Stefania , Bucchi Annalisa , Bottelli Georgia , Ferrarese Carlo , Franceschetti Silvana , Terragni Benedetta , Baruscotti Mirko , DiFrancesco Dario 
Published: December 2011

The hyperpolarization-activatedIhcurrent, coded for by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, controls synaptic integration and intrinsic excitability in many brain areas. Because of their role in pacemaker function, defective HCN channels are natural candidates for contributing to epileptogenesis. Indeed,Ihis pathologically altered after experimentally induced seizures, and several independent data indicate a link between dysfunctional HCN channels and different forms of epilepsy. However, direct evidence for functional changes of defective HCN channels correlating with the disease in human patients is still elusive.By screening families with epilepsy for mutations inHcn1andHcn2genes, we found a recessive loss-of-function point mutation in the gene coding for the HCN2 channel in a patient with sporadic idiopathic generalized epilepsy. Of 17 screened members of the same family, the proband was the only one affected and homozygous for the mutation.The mutation (E515K) is located in the C-linker, a region known to affect channel gating. Functional analysis revealed that homomeric mutant, but not heteromeric wild-type/mutant channels, have a strongly inhibited function caused by a large negative shift of activation range and slowed activation kinetics, effectively abolishing the HCN2 contribution to activity. After transfection into acutely isolated newborn rat cortical neurons, homomeric mutant, but not heteromeric wild type/mutant channels, lowered the threshold of action potential firing and strongly increased cell excitability and firing frequency when compared with wild-type channels.This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.
Visual Pathway for the Optokinetic Reflex in Infant Macaque Monkeys
Authors: Distler Claudia , Hoffmann Klaus-Peter 
Published: December 2011

The horizontal optokinetic nystagmus (hOKN) in primates is immature at birth. To elucidate the early functional state of the visual pathway for hOKN, retinal slip neurons were recorded in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of 4 anesthetized infant macaques. These neurons were direction selective for ipsiversive stimulus movement shortly after birth [postnatal day 9 (P9)], although at a lower direction selectivity index (DSI). The DSI in the older infants (P12, P14, P60) was not different from adults. A total of 96% of NOT-DTN neurons in P9, P12, and P14 were binocular, however, significantly more often dominated by the contralateral eye than in adults. Already in the youngest animals, NOT-DTN neurons were well tuned to different stimulus velocities; however, tuning was truncated toward lower stimulus velocities when compared with adults.As early as at P12, electrical stimulation in V1 elicited orthodromic responses in the NOT-DTN. However, the incidence of activated neurons was much lower in infants (40–60% of the tested NOT-DTN neurons) than in adults (97%). Orthodromic latencies from V1 were significantly longer in P12–P14 (x= 12.2 ± 8.9 ms) than in adults (x= 3.51 ± 0.81 ms). At the same age, electrical stimulation in motion-sensitive area MT was more efficient in activating NOT-DTN neurons (80% of the tested cells) and yielded shorter latencies than in V1 (x= 7.8 ± 3.02 ms; adultx= 2.99 ± 0.85 ms).The differences in discharge rate between neurons in the NOT-DTN contra- and ipsilateral to the stimulated eye are equivalent to the gain asymmetry between monocularly elicited OKN in temporonasal and nasotemporal direction at the various ages.
Real-time Avionics Optimization
Authors: Eisenbrand Friedrich , Niemeier Martin , Skutella Martin , Verschae José , Wiese Andreas 
Published: December 2011

Abstract
We report on the solution of a difficult optimization problem which arises in avionics industry. When constructing the on-board controlling-network of an airplane, the engineers need to solve a computationally highly complex problem. The goal is to assign periodic tasks to the processors on the plane and define a schedule for each processor. Current state-of-the-art approaches to tackle the problem are by far not powerful enough to solve instances of real-world size. With the help of the powerful algorithm engineering paradigm we analyzed the mathematical properties of the scheduling problem and designed sophisticated software based on the structural insights. We were able to design a model that outperformed current state-of-the-art approaches by several orders of magnitude. In particular, we could solve industrial size real-world instances to optimality. Our methods lead, for the first time, to an industrial strength tool to schedule aircraft sized instances.