bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing theoretically-informed implementation interventions: Fine in theory, but evidence of effectiveness in practice is needed
Authors: Bhattacharyya Onil , Reeves Scott , Garfinkel Susan , Zwarenstein Merrick 
Published: February 2006

Abstract
The Improved Clinical Effectiveness through Behavioural Research Group (ICEBeRG) authors assert that a key weakness in implementation research is the unknown applicability of a given intervention outside its original site and problem, and suggest that use of explicit theory offers an effective solution. This assertion is problematic for three primary reasons. First, the presence of an underlying theory does not necessarily ease the task of judging the applicability of a piece of empirical evidence. Second, it is not clear how to translate theory reliably into intervention design, which undoubtedly involves the diluting effect of "common sense." Thirdly, there are many theories, formal and informal, and it is not clear why any one should be given primacy. To determine whether explicitly theory-based interventions are, on average, more effective than those based on implicit theories, pragmatic trials are needed. Until empirical evidence is available showing the superiority of theory-based interventions, the use of theory should not be used as a basis for assessing the value of implementation studies by research funders, ethics committees, editors or policy decision makers.
Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study
Authors: Rosenberg Lena U , Magnusson Cecilia , Lindström Emma , Wedrén Sara , Hall Per , Dickman Paul W 
Published: February 2006

Abstract
Introduction
Breast cancers of different histology have different clinical and prognostic features. There are also indications of differences in aetiology. We therefore evaluated the risk of the three most common histological subtypes in relation to menopausal hormone therapy and other breast cancer risk factors.

Methods
We used a population-based case-control study of breast cancer to evaluate menopausal hormone therapy and other breast cancer risk factors for risk by histological subtype. Women aged 50 to 74 years, diagnosed with invasive ductal (n = 1,888), lobular (n = 308) or tubular (n = 93) breast cancer in Sweden in 1993 to 1995 were compared with 3,065 age-frequency matched controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ductal, lobular, and tubular cancer.

Results
Women who had used medium potency estrogen alone were at increased risks of both ductal and lobular cancer. Medium potency estrogen-progestin was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were higher compared with ductal cancer. We found OR 5.6 (95% CI 3.2–9.7) for lobular cancer, OR 6.5 (95% CI 2.8–14.9) for tubular cancer and OR 2.3 (95% CI 1.6–3.3) for ductal cancer with ≥5 years use of medium potency estrogen-progestin therapy. Low potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, but the association was strongest for short-term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives were mostly similarly related to the risks of the three breast cancer subtypes. Recent alcohol consumption of > 10 g alcohol/day was associated with increased risk only for tubular cancer (OR 3.1, 95% CI 1.4–6.8).

Conclusion
Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer.
Systematic review of determinants of mortality in high frequency oscillatory ventilation in acute respiratory distress syndrome
Authors: Bollen Casper W , Uiterwaal Cuno SPM , van Vught Adrianus J 
Published: February 2006

Abstract
Introduction
Mechanical ventilation has been shown to cause lung injury and to have a significant impact on mortality in acute respiratory distress syndrome. Theoretically, high frequency oscillatory ventilation seems an ideal lung protective ventilation mode. This review evaluates determinants of mortality during use of high frequency oscillatory ventilation.

Methods
PubMed was searched for literature reporting randomized trials and cohort studies of high frequency ventilation in adult patients with acute respiratory distress syndrome. Data on mortality and determinants were extracted for patients treated with high frequency oscillatory ventilation. Linear regression analyses were conducted to produce graphical representations of adjusted effects of determinants of mortality.

Results
Cohorts of patients treated with high frequency oscillatory ventilation from two randomized trials and seven observational studies were included. Data from cohorts comparing survivors with non-survivors showed differences in age (42.3 versus 51.2 years), prior time on conventional mechanical ventilation (4.0 versus 6.2 days), APACHE II score (22.4 versus 26.1), pH (7.33 versus 7.26) and oxygenation index (26 versus 34). Each extra day on conventional ventilation was associated with a 20% higher mortality adjusted for age and APACHE II score (relative risk (RR) 1.20, 95% confidence interval (CI) 1.15–1.25). However, this association was confounded by differences in pH (pH adjusted RR 1.03, 95% CI 0.73–1.46). Oxygenation index seemed to have an independent effect on mortality (RR 1.10, 95% CI 0.95–1.28).

Conclusion
Prolonged ventilation on conventional mechanical ventilation prior to high frequency oscillatory ventilation was not related to mortality. Oxygenation index was a determinant of mortality independent of other disease severity markers.
Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis
Authors: Chuang Chia-Chang , Shiesh Shu-Chu , Chi Chih-Hsien , Tu Yi-Fang , Hor Lien-I , Shieh Chi-Chang , Chen Ming-Feng 
Published: February 2006

Abstract
Introduction
We conducted the present study to evaluate the changes in serum total antioxidant capacity (TAC) in patients with severe sepsis and to investigate the association between serum TAC and clinical severity.

Method
This was a prospective observational study involving a sample of patients who met established criteria for severe sepsis and were admitted to the emergency department of a university teaching hospital. Serum TAC was determined using the total radical-trapping antioxidant parameter method. The levels of TAC, uric acid, albumin, and bilirubin in sera were obtained in the emergency department and evaluated to determine whether there were any correlations between the major antioxidant biomarkers and clinical severity of sepsis. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was used for clinical evaluation of the severity of sepsis.

Results
A total of 73 patients with sepsis, with a mean (± standard deviation) APACHE II score of 23.2 ± 8.2 and a mortality rate of 26.0%, were included. Seventy-six healthy individuals served as control individuals. Among the patients, serum TAC levels correlated significantly with APACHE II scores. Patients who died also had higher TAC than did those who survived. Serum uric acid levels correlated significantly with serum TAC and APACHE II scores in patients with severe sepsis.

Conclusion
Elevated serum TAC level may reflect clinical severity of sepsis. In addition, serum uric acid levels appear to contribute importantly to the higher TAC levels observed in patients with severe sepsis.
CC and CXC chemokine levels in children with meningococcal sepsis accurately predict mortality and disease severity
Authors: Vermont Clementien L , Hazelzet Jan A , de Kleijn Ester D , van den Dobbelsteen Germie PJM , Groot Ronald de 
Published: February 2006

Abstract
Introduction
Chemokines are a superfamily of small peptides involved in leukocyte chemotaxis and in the induction of cytokines in a wide range of infectious diseases. Little is known about their role in meningococcal sepsis in children and their relationship with disease severity and outcome.

Methods
Monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP) 1α, growth-related gene product (GRO)-α and interleukin (IL)-8 were measured in 58 children with meningococcal sepsis or septic shock on admission and 24 hours thereafter. Nine patients died. Serum chemokine levels of survivors and nonsurvivors were compared, and the chemokine levels were correlated with prognostic disease severity scores and various laboratory parameters.

Results
Extremely high levels of all chemokines were measured in the children's acute-phase sera. These levels were significantly higher in nonsurvivors compared with survivors and in patients with septic shock compared with patients with sepsis (P < 0.0001). The cutoff values of 65,407 pg/ml, 85,427 pg/ml and 460 pg/ml for monocyte chemoattractant protein, for IL-8 and for macrophage inflammatory protein 1α, respectively, all had 100% sensitivity and 94–98% specificity for nonsurvival. Chemokine levels correlated better with disease outcome and severity than tumor necrosis factor (TNF)-α and correlated similarly to interleukin (IL)-6. In available samples 24 hours after admission, a dramatic decrease of chemokine levels was seen.

Conclusion
Initial-phase serum levels of chemokines in patients with meningococcal sepsis can predict mortality and can correlate strongly with disease severity. Chemokines may play a key role in the pathophysiology of meningococcal disease and are potentially new targets for therapeutic approaches.
Alternate transcription of the Toll-like receptor signaling cascade
Authors: Wells Christine A , Chalk Alistair M , Forrest Alistair , Taylor Darrin , Waddell Nic , Schroder Kate , Himes S Roy , Faulkner Geoffrey , Lo Sandra , Kasukawa Takeya , Kawaji Hideya , Kai Chikatoshi , Kawai Jun , Katayama Shintaro , Carninci Piero , Hayashizaki Yoshihide , Hume David A , Grimmond Sean M 
Published: February 2006

Abstract
Background
Alternate splicing of key signaling molecules in the Toll-like receptor (Tlr) cascade has been shown to dramatically alter the signaling capacity of inflammatory cells, but it is not known how common this mechanism is. We provide transcriptional evidence of widespread alternate splicing in the Toll-like receptor signaling pathway, derived from a systematic analysis of the FANTOM3 mouse data set. Functional annotation of variant proteins was assessed in light of inflammatory signaling in mouse primary macrophages, and the expression of each variant transcript was assessed by splicing arrays.

Results
A total of 256 variant transcripts were identified, including novel variants of Tlr4, Ticam1, Tollip, Rac1, Irak1, 2 and 4, Mapk14/p38, Atf2 and Stat1. The expression of variant transcripts was assessed using custom-designed splicing arrays. We functionally tested the expression of Tlr4 transcripts under a range of cytokine conditions via northern and quantitative real-time polymerase chain reaction. The effects of variant Mapk14/p38 protein expression on macrophage survival were demonstrated.

Conclusion
Members of the Toll-like receptor signaling pathway are highly alternatively spliced, producing a large number of novel proteins with the potential to functionally alter inflammatory outcomes. These variants are expressed in primary mouse macrophages in response to inflammatory mediators such as interferon-γ and lipopolysaccharide. Our data suggest a surprisingly common role for variant proteins in diversification/repression of inflammatory signaling.
Identification of signaling components required for the prediction of cytokine release in RAW 264.7 macrophages
Authors: Pradervand Sylvain , Maurya Mano R , Subramaniam Shankar 
Published: February 2006

Abstract
Background
Release of immuno-regulatory cytokines and chemokines during inflammatory response is mediated by a complex signaling network. Multiple stimuli produce different signals that generate different cytokine responses. Current knowledge does not provide a complete picture of these signaling pathways. However, using specific markers of signaling pathways, such as signaling proteins, it is possible to develop a 'coarse-grained network' map that can help understand common regulatory modules for various cytokine responses and help differentiate between the causes of their release.

Results
Using a systematic profiling of signaling responses and cytokine release in RAW 264.7 macrophages made available by the Alliance for Cellular Signaling, an analysis strategy is presented that integrates principal component regression and exhaustive search-based model reduction to identify required signaling factors necessary and sufficient to predict the release of seven cytokines (G-CSF, IL-1α, IL-6, IL-10, MIP-1α, RANTES, and TNFα) in response to selected ligands. This study provides a model-based quantitative estimate of cytokine release and identifies ten signaling components involved in cytokine production. The models identified capture many of the known signaling pathways involved in cytokine release and predict potentially important novel signaling components, like p38 MAPK for G-CSF release, IFNγ- and IL-4-specific pathways for IL-1a release, and an M-CSF-specific pathway for TNFα release.

Conclusion
Using an integrative approach, we have identified the pathways responsible for the differential regulation of cytokine release in RAW 264.7 macrophages. Our results demonstrate the power of using heterogeneous cellular data to qualitatively and quantitatively map intermediate cellular phenotypes.
Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites
Authors: Sargeant Tobias J , Marti Matthias , Caler Elisabet , Carlton Jane M , Simpson Ken , Speed Terence P , Cowman Alan F 
Published: February 2006

Abstract
Background
The apicomplexan parasite Plasmodium falciparum causes the most severe form of malaria in humans. After invasion into erythrocytes, asexual parasite stages drastically alter their host cell and export remodeling and virulence proteins. Previously, we have reported identification and functional analysis of a short motif necessary for export of proteins out of the parasite and into the red blood cell.

Results
We have developed software for the prediction of exported proteins in the genus Plasmodium, and identified exported proteins conserved between malaria parasites infecting rodents and the two major causes of human malaria, P. falciparum and P. vivax. This conserved 'exportome' is confined to a few subtelomeric chromosomal regions in P. falciparum and the synteny of these and surrounding regions is conserved in P. vivax. We have identified a novel gene family PHIST (for Plasmodium helical interspersed subtelomeric family) that shares a unique domain with 72 paralogs in P. falciparum and 39 in P. vivax; however, there is only one member in each of the three species studied from the P. berghei lineage.

Conclusion
These data suggest radiation of genes encoding remodeling and virulence factors from a small number of loci in a common Plasmodium ancestor, and imply a closer phylogenetic relationship between the P. vivax and P. falciparum lineages than previously believed. The presence of a conserved 'exportome' in the genus Plasmodium has important implications for our understanding of both common mechanisms and species-specific differences in host-parasite interactions, and may be crucial in developing novel antimalarial drugs to this infectious disease.
Distinct patterns of SSR distribution in the Arabidopsis thalianaand rice genomes
Authors: Lawson Mark J , Zhang Liqing 
Published: February 2006

Abstract
Background
Simple sequence repeats (SSRs) in DNA have been traditionally thought of as functionally unimportant and have been studied mainly as genetic markers. A recent handful of studies have shown, however, that SSRs in different positions of a gene can play important roles in determining protein function, genetic development, and regulation of gene expression. We have performed a detailed comparative study of the distribution of SSRs in the sequenced genomes of Arabidopsis thaliana and rice.

Results
SSRs in different genic regions - 5'untranslated region (UTR), 3'UTR, exon, and intron - show distinct patterns of distribution both within and between the two genomes. Especially notable is the much higher density of SSRs in 5'UTRs compared to the other regions and a strong affinity towards trinucleotide repeats in these regions for both rice and Arabidopsis. On a genomic level, mononucleotide repeats are the most prevalent type of SSRs in Arabidopsis and trinucleotide repeats are the most prevalent type in rice. Both plants have the same most common mononucleotide (A/T) and dinucleotide (AT and AG) repeats, but have little in common for the other types of repeats.

Conclusion
Our work provides insight into the evolution and distribution of SSRs in the two sequenced model plant genomes of monocots and dicots. Our analyses reveal that the distributions of SSRs appear highly non-random and vary a great deal in different regions of the genes in the genomes.
Comparison of dot chromosome sequences from D. melanogaster and D. virilisreveals an enrichment of DNA transposon sequences in heterochromatic domains
Authors: Slawson Elizabeth E , Shaffer Christopher D , Malone Colin D , Leung Wilson , Kellmann Elmer , Shevchek Rachel B , Craig Carolyn A , Bloom Seth M , Bogenpohl James , Dee James , Morimoto Emiko TA , Myoung Jenny , Nett Andrew S , Ozsolak Fatih , Tittiger Mindy E , Zeug Andrea , Pardue Mary-Lou , Buhler Jeremy , Mardis Elaine R , Elgin Sarah CR 
Published: February 2006

Abstract
Background
Chromosome four of Drosophila melanogaster, known as the dot chromosome, is largely heterochromatic, as shown by immunofluorescent staining with antibodies to heterochromatin protein 1 (HP1) and histone H3K9me. In contrast, the absence of HP1 and H3K9me from the dot chromosome in D. virilis suggests that this region is euchromatic. D. virilis diverged from D. melanogaster 40 to 60 million years ago.

Results
Here we describe finished sequencing and analysis of 11 fosmids hybridizing to the dot chromosome of D. virilis (372,650 base-pairs) and seven fosmids from major euchromatic chromosome arms (273,110 base-pairs). Most genes from the dot chromosome of D. melanogaster remain on the dot chromosome in D. virilis, but many inversions have occurred. The dot chromosomes of both species are similar to the major chromosome arms in gene density and coding density, but the dot chromosome genes of both species have larger introns. The D. virilis dot chromosome fosmids have a high repeat density (22.8%), similar to homologous regions of D. melanogaster (26.5%). There are, however, major differences in the representation of repetitive elements. Remnants of DNA transposons make up only 6.3% of the D. virilis dot chromosome fosmids, but 18.4% of the homologous regions from D. melanogaster; DINE-1 and 1360 elements are particularly enriched in D. melanogaster. Euchromatic domains on the major chromosomes in both species have very few DNA transposons (less than 0.4 %).

Conclusion
Combining these results with recent findings about RNAi, we suggest that specific repetitive elements, as well as density, play a role in determining higher-order chromatin packaging.
Evidence that Human Thyroid Cells Express Uncleaved, Single-Chain Thyrotropin Receptors on Their Surface
Authors: Chen Chun-Rong , Chazenbalk Gregorio D. , Wawrowsky Kolja A. , McLachlan Sandra M. , Rapoport Basil 
Published: February 2006

Abstract
The prevailing concept is that, in human thyroid tissue in vivo, all cell-surface TSH receptors (TSHR) cleave into disulfide linked A and B subunits. Because this viewpoint is based on studies using homogenized thyroid tissue and because of TSHR fragility, we studied TSHR subunit structure in intact thyroid cells, primary human thyrocyte cultures, FRTL-5 rat thyroid cells, and WRO (follicular) and NPA (papillary) thyroid cancer cell lines. To overcome the handicap of very low TSHR expression in thyroid cells, we generated a TSHR-expressing adenovirus (TSHR-Ad-RGD) with an integrin-binding RGD motif enabling efficient entry into cells lacking the coxsackie-adenovirus receptor. Two days after TSHR-Ad-RGD infection, [125I]TSH cross-linking to intact cells revealed uncleaved, single-chain TSHR as well as cleaved TSHR A subunits on the surface of all four thyroid cell types. The extent of TSHR cleavage, which is independent of the level of TSHR expression, was consistently lower in the human thyroid cancer cell lines than in the other cell lines. In flow cytometry studies after TSHR-Ad-RGD infection, strong signals were detected in all four thyroid cell types using a monoclonal antibody that primarily recognizes the uncleaved TSHR. Finally, using the same monoclonal antibody, confocal microscopy confirmed the presence of single-chain TSHR on TSHR-Ad-RGD-infected thyroid cells. In summary, TSH covalent cross-linking, flow cytometry, and confocal microscopy demonstrate the presence of uncleaved TSHR on the human thyrocyte surface. These data provide stronger evidence for this alternative than the contrary view based on the finding of only cleaved TSHR in homogenized thyroid cells.
Adiponectin Multimerization Is Dependent on Conserved Lysines in the Collagenous Domain: Evidence for Regulation of Multimerization by Alterations in Posttranslational Modifications
Authors: Richards Ayanthi A. , Stephens Tim , Charlton Hayley K. , Jones Alun , Macdonald Graeme A. , Prins Johannes B. , Whitehead Jonathan P. 
Published: February 2006

AbstractAdiponectin is a secreted, multimeric protein with insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Serum adiponectin consists of trimer, hexamer, and larger high-molecular-weight (HMW) multimers, and these HMW multimers appear to be the more bioactive forms. Multimer composition of adiponectin appears to be regulated; however, the molecular mechanisms involved are unknown. We hypothesize that regulation of adiponectin multimerization and secretion occurs via changes in posttranslational modifications (PTMs). Although a structural role for intertrimer disulfide bonds in the formation of hexamers and HMW multimers is established, the role of other PTMs is unknown. PTMs identified in murine and bovine adiponectin include hydroxylation of multiple conserved proline and lysine residues and glycosylation of hydroxylysines. By mass spectrometry, we confirmed the presence of these PTMs in human adiponectin and identified three additional hydroxylations on Pro71, Pro76, and Pro95. We also investigated the role of the five modified lysines in multimer formation and secretion of recombinant human adiponectin expressed in mammalian cell lines. Mutation of modified lysines in the collagenous domain prevented formation of HMW multimers, whereas a pharmacological inhibitor of prolyl- and lysyl-hydroxylases, 2,2′-dipyridyl, inhibited formation of hexamers and HMW multimers. Bacterially expressed human adiponectin displayed a complete lack of differentially modified isoforms and failed to form bona fide trimers and larger multimers. Finally, glucose-induced increases in HMW multimer production from human adipose explants correlated with changes in the two-dimensional electrophoresis profile of adiponectin isoforms. Collectively, these data suggest that adiponectin multimer composition is affected by changes in PTM in response to physiological factors.