bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple system atrophy presenting as central sleep apnoea: Fig. 1.—
Authors: Cormican L.J. , Higgins S. , Davidson A.C. , Howard R. , Williams A.J. 
Published: July 2004

A 61‐yr-old male presented with apparent idiopathic central sleep apnoea but after 4 yrs developed features of autonomic, cerebellar and extrapyramidal dysfunction consistent with a diagnosis of multiple system atrophy (MSA).Though central sleep apnoea can occur in multiple sleep apnoea, it is less frequent than obstructive sleep apnoea and occurs in the later stages of the disease.The pathogenesis of MSA involves gliosis and neuronal cell loss in specific areas of the central nervous system. Central sleep apnoea in MSA may be due to the depletion of cholinergic neurons in the arcuate nucleus of the medulla by apoptosis.This is the first description of multiple system atrophy presenting as central sleep apnoea. The current authors believe that multiple system atrophy should be considered in the differential diagnosis of late onset central sleep apnoea and progressive hypoventilation.
Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema
Authors: Shaheen S.O. , Newson R.B. , Henderson A.J. , Emmett P.M. , Sherriff A. , Cooke M. ,   the ALSPAC Study Team
Published: July 2004

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated.In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30–42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0–6 months and 30–42 months, respectively (n=2,044), and with eczema at 18–30 months (n=2,173), were analysed.Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy.The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.
The TORCH (TOwards a Revolution in COPD Health) survival study protocol: Fig. 1.—
Authors:   The TORCH Study Group
Published: July 2004

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The “TOwards a Revolution in COPD Health” (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients.TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned tob.i.d.treatment with either SFC (50/500 µg), fluticasone propionate (500 µg), salmeterol (50 µg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures.The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the “TOwards a Revolution in COPD Health” study and explains the rationale behind it.
Effect of freezing of sputum samples on flow cytometric analysis of lymphocyte subsets
Authors: Jaksztat E. , Holz O. , Paasch K. , Kelly M.M. , Hargreave F.E. , Cox G. , Magnussen H. , Jörres R.A. 
Published: July 2004

Sputum samples should be processed shortly after induction to prevent cell degradation. For intermediate storage, freezing of homogenised samples or immediate fixation have been shown to be suitable for cytospins. The aim of this study was to investigate whether freezing or immediate fixation of sputum affect the analysis of lymphocyte subsets by flow cytometry.Selected plugs from 24 sputum samples were homogenised. One aliquot was processed immediately and analysed by flow cytometry. A second aliquot was homogenised, frozen at −20°C after addition of dimethylsulfoxide and stored for a median time of 6 days. In six samples a third aliquot was fixed in formalin after induction and stored for up to 72 h before further processing.Compared to immediate processing, percentages of total lymphocytes and T‐suppressor cells were elevated after being frozen, with a minor decrease in the T4/T8 ratio. Proportions of total lymphocytes, T‐helper and T‐suppressor cells correlated between native and frozen samples, intra-class correlation coefficients being 0.74, 0.85 and 0.70, respectively. The formalin-fixed aliquots could not be analysed with the antibodies used.In conclusion, freezing seems to be a suitable technique to store sputum samples for flow cytometry of CD3, CD4 and CD8 lymphocyte subsets. Its effects were minor compared to the variation between subjects.
Reduced inspiratory flow attenuates IL‐8 release and MAPK activation of lung overstretch
Authors: Kotani M. , Kotani T. , Li Z. , Silbajoris R. , Piantadosi C.A. , Huang Y-C.T. 
Published: July 2004

Lung overstretch involves mechanical factors, including large tidal volumes (VT), which induce inflammatory responses. The current authors hypothesised that inspiratory flow contributes to ventilator-induced inflammation.Buffer-perfused rabbit lungs were ventilated for 2 h with 21% O2+5% CO2, positive end-expiratory pressure of 2–3 cmH2O and randomly assigned to either: 1) normalVT(6 mL·kg−1) at respiratory rate (RR) 30, inspiration:expiration time ratio (I:E) 1:1, low inspiratory flow 6 mL·kg−1·s−1; 2) largeVT(12 mL·kg−1) at RR 30, I:E 1:1, high inspiratory flow 12 mL·kg−1·s−1(HRHF); 3) largeVTat RR 15, I:E 1:1, low inspiratory flow 6 mL·kg−1·s−1(LRLF); or 4) largeVTat RR 15, I:E 1:2.3, high inspiratory flow 10 mL·kg−1·s−1(LRHF). Physiological parameters, tumour necrosis factor (TNF)‐α, interleukin (IL)‐8 and activation of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK)1/2, p38 and stress-activated protein kinase (SAPK)/c‐Jun N‐terminal kinase (JNK)) were measured.HRHF increased weight gain, perfusate IL‐8 and phosphorylation of ERK1/2, p38 and SAPK/JNK. These responses were absent during LRLF but present during LRHF. Changes in TNF‐α were small. Tissue IL‐8 and phospho‐ERK1/2 staining was localised primarily to smooth muscle, adventitia and bronchial epithelium within larger bronchioles and arterioles.These results indicate that mild overstretch of perfused lungs during high inspiratory flow enhances inflammatory signalling by cells in lung regions most affected by strong turbulent airflow.
Structural characterization of genomes by large scale sequence-structure threading: application of reliability analysis in structural genomics
Authors: Cherkasov Artem , Ho Sui Shannan J , Brunham Robert C , Jones Steven JM 
Published: July 2004

Abstract
Background
We establish that the occurrence of protein folds among genomes can be accurately described with a Weibull function. Systems which exhibit Weibull character can be interpreted with reliability theory commonly used in engineering analysis. For instance, Weibull distributions are widely used in reliability, maintainability and safety work to model time-to-failure of mechanical devices, mechanisms, building constructions and equipment.

Results
We have found that the Weibull function describes protein fold distribution within and among genomes more accurately than conventional power functions which have been used in a number of structural genomic studies reported to date.
It has also been found that the Weibull reliability parameter β for protein fold distributions varies between genomes and may reflect differences in rates of gene duplication in evolutionary history of organisms.

Conclusions
The results of this work demonstrate that reliability analysis can provide useful insights and testable predictions in the fields of comparative and structural genomics.
Two-stage normalization using background intensities in cDNA microarray data
Authors: Yoon Dankyu , Yi Sung-Gon , Kim Ju-Han , Park Taesung 
Published: July 2004

Abstract
Background
In the microarray experiment, many undesirable systematic variations are commonly observed. Normalization is the process of removing such variation that affects the measured gene expression levels. Normalization plays an important role in the earlier stage of microarray data analysis. The subsequent analysis results are highly dependent on normalization. One major source of variation is the background intensities. Recently, some methods have been employed for correcting the background intensities. However, all these methods focus on defining signal intensities appropriately from foreground and background intensities in the image analysis. Although a number of normalization methods have been proposed, no systematic methods have been proposed using the background intensities in the normalization process.

Results
In this paper, we propose a two-stage method adjusting for the effect of background intensities in the normalization process. The first stage fits a regression model to adjust for the effect of background intensities and the second stage applies the usual normalization method such as a nonlinear LOWESS method to the background-adjusted intensities. In order to carry out the two-stage normalization method, we consider nine different background measures and investigate their performances in normalization. The performance of two-stage normalization is compared to those of global median normalization as well as intensity dependent nonlinear LOWESS normalization. We use the variability among the replicated slides to compare performance of normalization methods.

Conclusions
For the selected background measures, the proposed two-stage normalization method performs better than global or intensity dependent nonlinear LOWESS normalization method. Especially, when there is a strong relationship between the background intensity and the signal intensity, the proposed method performs much better. Regardless of background correction methods used in the image analysis, the proposed two-stage normalization method can be applicable as long as both signal intensity and background intensity are available.
Integrated web service for improving alignment quality based on segments comparison
Authors: Plewczynski Dariusz , Rychlewski Leszek , Ye Yuzhen , Jaroszewski Lukasz , Godzik Adam 
Published: July 2004

Abstract
Background
Defining blocks forming the global protein structure on the basis of local structural regularity is a very fruitful idea, extensively used in description, and prediction of structure from only sequence information. Over many years the secondary structure elements were used as available building blocks with great success. Specially prepared sets of possible structural motifs can be used to describe similarity between very distant, non-homologous proteins. The reason for utilizing the structural information in the description of proteins is straightforward. Structural comparison is able to detect approximately twice as many distant relationships as sequence comparison at the same error rate.

Results
Here we provide a new fragment library for Local Structure Segment (LSS) prediction called FRAGlib which is integrated with a previously described segment alignment algorithm SEA. A joined FRAGlib/SEA server provides easy access to both algorithms, allowing a one stop alignment service using a novel approach to protein sequence alignment based on a network matching approach. The FRAGlib used as secondary structure prediction achieves only 73% accuracy in Q3 measure, but when combined with the SEA alignment, it achieves a significant improvement in pairwise sequence alignment quality, as compared to previous SEA implementation and other public alignment algorithms. The FRAGlib algorithm takes ~2 min. to search over FRAGlib database for a typical query protein with 500 residues. The SEA service align two typical proteins within circa ~5 min. All supplementary materials (detailed results of all the benchmarks, the list of test proteins and the whole fragments library) are available for download on-line at http://ffas.ljcrf.edu/darman/results/.

Conclusions
The joined FRAGlib/SEA server will be a valuable tool both for molecular biologists working on protein sequence analysis and for bioinformaticians developing computational methods of structure prediction and alignment of proteins.
The FU gene and its possible protein isoforms
Authors: Østerlund Torben , Everman David B , Betz Regina C , Mosca Monica , Nöthen Markus M , Schwartz Charles E , Zaphiropoulos Peter G , Toftgård Rune 
Published: July 2004

Abstract
Background
FU is the human homologue of the Drosophila gene fused whose product fused is a positive regulator of the transcription factor Cubitus interruptus (Ci). Thus, FU may act as a regulator of the human counterparts of Ci, the GLI transcription factors. Since Ci and GLI are targets of Hedgehog signaling in development and morphogenesis, it is expected that FU plays an important role in Sonic, Desert and/or Indian Hedgehog induced cellular signaling.

Results
The FU gene was identified on chromosome 2q35 at 217.56 Mb and its exon-intron organization determined. The human developmental disorder Syndactyly type 1 (SD1) maps to this region on chromosome 2 and the FU coding region was sequenced using genomic DNA from an affected individual in a linked family. While no FU mutations were found, three single nucleotide polymorphisms were identified. The expression pattern of FU was thoroughly investigated and all examined tissues express FU. It is also clear that different tissues express transcripts of different sizes and some tissues express more than one transcript. By means of nested PCR of specific regions in RT/PCR generated cDNA, it was possible to verify two alternative splicing events. This also suggests the existence of at least two additional protein isoforms besides the FU protein that has previously been described. This long FU and a much shorter isoform were compared for the ability to regulate GLI1 and GLI2. None of the FU isoforms showed any effects on GLI1 induced transcription but the long form can enhance GLI2 activity. Apparently FU did not have any effect on SUFU induced inhibition of GLI.

Conclusions
The FU gene and its genomic structure was identified. FU is a candidate gene for SD1, but we have not identified a pathogenic mutation in the FU coding region in a family with SD1. The sequence information and expression analyses show that transcripts of different sizes are expressed and subjected to alternative splicing. Thus, mRNAs may contain different 5'UTRs and encode different protein isoforms. Furthermore, FU is able to enhance the activity of GLI2 but not of GLI1, implicating FU in some aspects of Hedgehog signaling.
Age-associated alterations in CXCL1 chemokine expression by murine B cells
Authors: Hu Lina , Dixit Vishwa Deep , de Mello-Coelho Valeria , Taub Dennis D 
Published: July 2004

Abstract
Background
The CXCL1 chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), have been shown to play a role in a number of pathophysiological disease states including endotoxin-induced inflammation and bacterial meningitis. While the expression of these chemokines has been identified in a variety of cell types in the mouse, little is known about their expression with murine B-lymphocytes.

Results
Here, we demonstrate that highly purified murine splenic B cells are capable of expressing both MIP-2 and KC protein and mRNA upon activation with lipopolysaccharide (LPS) but not in response to anti-μ and anti-CD40 in combination with interleukin-4 (IL-4) stimulation. Moreover, these chemokines are expressed at higher levels in B cells derived from young (4 m) compared to old (24–29 m) mice. Upon fractionation into distinct B-cell subsets, we found that the expression of MIP-2 and KC by aged follicular (FO) B cells is significantly decreased when compared to the same cells from younger mice, while only MIP-2 production was found to be diminished in aged marginal zone (MZ) B cells. Interestingly, MIP-2 and KC production by newly formed (NF) B cells did not significantly differ with age. Moreover, the potential relevance of these findings is supported by the poor ability of LPS-activated aged B cells to specifically mediate CXCL1-dependent leukocyte recruitment when compared to younger B cells.

Conclusion
Overall, the decreased expression of CXCL1 chemokines by aged B cells in response to LPS may have potential implications on the secondary recruitment of leukocytes to sites of microbial infections and inflammation possibly contributing to the increased susceptibility of older subjects to pathogen challenge.
Family-based clusters of cognitive test performance in familial schizophrenia
Authors: Hoti Fabian , Tuulio-Henriksson Annamari , Haukka Jari , Partonen Timo , Holmström Lasse , Lönnqvist Jouko 
Published: July 2004

Abstract
Background
Cognitive traits derived from neuropsychological test data are considered to be potential endophenotypes of schizophrenia. Previously, these traits have been found to form a valid basis for clustering samples of schizophrenia patients into homogeneous subgroups. We set out to identify such clusters, but apart from previous studies, we included both schizophrenia patients and family members into the cluster analysis. The aim of the study was to detect family clusters with similar cognitive test performance.

Methods
Test scores from 54 randomly selected families comprising at least two siblings with schizophrenia spectrum disorders, and at least two unaffected family members were included in a complete-linkage cluster analysis with interactive data visualization.

Results
A well-performing, an impaired, and an intermediate family cluster emerged from the analysis. While the neuropsychological test scores differed significantly between the clusters, only minor differences were observed in the clinical variables.

Conclusions
The visually aided clustering algorithm was successful in identifying family clusters comprising both schizophrenia patients and their relatives. The present classification method may serve as a basis for selecting phenotypically more homogeneous groups of families in subsequent genetic analyses.
Evaluation of reporting timeliness of public health surveillance systems for infectious diseases
Authors: Jajosky Ruth Ann , Groseclose Samuel L 
Published: July 2004

Abstract
Background
Timeliness is a key performance measure of public health surveillance systems. Timeliness can vary by disease, intended use of the data, and public health system level. Studies were reviewed to describe methods used to evaluate timeliness and the reporting timeliness of National Notifiable Diseases Surveillance System (NNDSS) data was evaluated to determine if this system could support timely notification and state response to multistate outbreaks.

Methods
Published papers that quantitatively measured timeliness of infectious disease surveillance systems operating in the U.S. were reviewed. Median reporting timeliness lags were computed for selected nationally notifiable infectious diseases based on a state-assigned week number and various date types. The percentage of cases reported within the estimated incubation periods for each disease was also computed.

Results
Few studies have published quantitative measures of reporting timeliness; these studies do not evaluate timeliness in a standard manner. When timeliness of NNDSS data was evaluated, the median national reporting delay, based on date of disease onset, ranged from 12 days for meningococcal disease to 40 days for pertussis. Diseases with the longer incubation periods tended to have a higher percentage of cases reported within its incubation period. For acute hepatitis A virus infection, which had the longest incubation period of the diseases studied, more than 60% of cases were reported within one incubation period for each date type reported. For cryptosporidiosis, Escherichia coli O157:H7 infection, meningococcal disease, salmonellosis, and shigellosis, less than 40% of cases were reported within one incubation period for each reported date type.

Conclusion
Published evaluations of infectious disease surveillance reporting timeliness are few in number and are not comparable. A more standardized approach for evaluating and describing surveillance system timeliness should be considered; a recommended methodology is presented. Our analysis of NNDSS reporting timeliness indicated that among the conditions evaluated (except for acute hepatitis A infection), the long reporting lag and the variability across states limits the usefulness of NNDSS data and aberration detection analysis of those data for identification of and timely response to multistate outbreaks. Further evaluation of the factors that contribute to NNDSS reporting timeliness is warranted.
Pressure‐dependent seismic response of fractured rock
Authors: Kozlov Evgenii A. 
Published: July 2004

Effects of external stress and pore pressure variations on the seismic signature of fractured rocks remain of interest to geoscientists and practicing geophysicists. Commonly, the effects are modeled theoretically, assuming fracture faces to be rough surfaces contacting each other via the surface asperities. The model proposed here differs from other models of this kind in that (1) fracture roughness is described by a single parameter and (2) a controlled degree of hydraulic connectivity between fractures and equant pores is introduced. This adds to the model's convenience and makes it applicable to a wide variety of reservoirs. The model predictions of seismic velocities in fractured rock at variable stress are consistent with experimental data. For fixed effective stress, the model predictions coincide with those obtained using the model with ellipsoidal fractures of certain average aspect ratio and the same fracture porosity.Apart from known effects, the model introduced predicts an amplification of the stress variation influence on fracturing‐induced anisotropy with an increase of connected equant porosity, a decrease of VP/VSwith effective stress, and implicit frequency dependence of the VP/VSrelation. It is also shown that amplitude versus offset (AVO) anomalies caused by fluid replacement can be seriously distorted if the fluid replacement is accompanied by significant variations of pore pressure, as, for example, at intense gas production. Neglecting these effects can lead to erroneous conclusions on shear modulus dependence on the pore fluid type. Qualitatively, in rocks with azimuthally aligned fracturing, the increase of effective stress affects AVO gradient in about the same way as the increase of water saturation parameter Vw. In contrast, the AVO intercept is not affected by variations of effective stress, while fluid replacement effect on the intercept is significant. Potentially, this can help distinguish the effects of pore pressure variations and fluid replacement on the AVO attributes.