bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming health inequalities: a participative evaluation framework fit for the task
Authors: Themessl-Huber Markus , Lazenbatt Anne , Taylor Julie 
Published: April 2008

Aims: Healthcare providers are confronted with the claim that the distribution of health and healthcare provision is inherently unfair. There is also a growing awareness that the tools and methodologies applied in tackling health inequalities require further development. Evaluations as well as interventions usually focus on population-based indicators, but do not always provide guidance for frontline service evaluation and delivery. That is why the evaluation framework presented here focuses on facilitating local service development, service provider and user involvement, and the adequate representation of different population groups. Methods: A participative evaluation framework was constructed by drawing on six common success characteristics extrapolated from the published literature and policies on health inequalities. This framework was then applied to an intervention addressing women's psychosocial health needs in order to demonstrate its utility in practice. Results: The framework provides healthcare professionals with an evidence-based tool for evaluating projects or programmes targeting health inequalities in ways that are responsive to local contexts and stakeholders. Conclusion: This participative evaluation framework supports the identification of meaningful psychosocial and contextual indicators for assessing the diverse health and social needs of service users. It uses multi-dimensional indicators to assess health and social care needs, to inform local service development, and to facilitate the exchange of knowledge between researchers, service providers, and service users. The inherent responsiveness enables rigorous yet flexible action on local health inequalities.
Role of decorin in the antimyeloma effects of osteoblasts
Authors: Li Xin , Pennisi Angela , Yaccoby Shmuel 
Published: April 2008

AbstractBuilding on our previous report that osteoblasts and increased bone formation have a negative impact on myeloma cell growth in a subset of patients, we investigated the role of decorin, the main small leucine-rich proteoglycan (SLRP) expressed and produced by osteoblasts, in the antimyeloma effects of osteoblasts. In coculture experiments with osteoblasts, primary myeloma cell survival was significantly higher when decorin expression in osteoblasts was knocked down by short-hairpin RNA. Coculture experiments of myeloma cells and supporting osteoclasts in the presence of osteoblast-conditioned medium showed reduced myeloma cell survival, an effect that was attenuated by decorin-neutralizing antibody. Decorin overexpression in mesenchymal stem cells or use of recombinant decorin in coculture with osteoclasts reduced the ability of osteoclasts to support primary myeloma cell survival. The antimyeloma effect of decorin involved direct induction of apoptosis and activation of p21WAF. Decorin also inhibited myeloma cell-induced tube formation and osteoclast differentiation. Decorin expression was insignificantly lower in patients' than donors' osteoblasts and slightly increased by bortezomib. Certain SLRPs are involved in the antimyeloma effect of osteoblasts directly and indirectly through inhibition of angiogenesis and osteoclastogenesis; therefore, increasing endo-genous or exogenous SLRPs in myelomatous bone may help control myeloma.
H3 K79 dimethylation marks developmental activation of the β-globin gene but is reduced upon LCR-mediated high-level transcription
Authors: Sawado Tomoyuki , Halow Jessica , Im Hogune , Ragoczy Tobias , Bresnick Emery H. , Bender M. A. , Groudine Mark 
Published: April 2008

Abstract
Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired β-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Δ locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the β-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and ΔLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the ΔLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with β-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level β-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.
Circulating alpha1-antitrypsin in the general population: Determinants and association with lung function
Authors: Senn Oliver , Russi Erich W , Schindler Christian , Imboden Medea , von Eckardstein Arnold , Brändli Otto , Zemp Elisabeth , Ackermann-Liebrich Ursula , Berger Wolfgang , Rochat Thierry , Luisetti Maurizio , Probst-Hensch Nicole M , the SAPALDIA Team  
Published: April 2008

Abstract

Background
Severe alpha1-antitrypsin (AAT) deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1.

Methods
In 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels ≤ 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP.

Results
Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p < 0.001), that disappeared after adjustment for CRP (p = 0.28). In addition, the AAT and FEV1 association was modified by gender, menopausal status in women, and smoking.

Conclusion
The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.
A new protein linear motif benchmark for multiple sequence alignment software
Authors: Perrodou Emmanuel , Chica Claudia , Poch Olivier , Gibson Toby J , Thompson Julie D 
Published: April 2008

AbstractBackgroundLinear motifs (LMs) are abundant short regulatory sites used for modulating the functions of many eukaryotic proteins. They play important roles in post-translational modification, cell compartment targeting, docking sites for regulatory complex assembly and protein processing and cleavage. Methods for LM detection are now being developed that are strongly dependent on scores for motif conservation in homologous proteins. However, most LMs are found in natively disordered polypeptide segments that evolve rapidly, unhindered by structural constraints on the sequence. These regions of modular proteins are difficult to align using classical multiple sequence alignment programs that are specifically optimised to align the globular domains. As a consequence, poor motif alignment quality is hindering efforts to detect new LMs.ResultsWe have developed a new benchmark, as part of the BAliBASE suite, designed to assess the ability of standard multiple alignment methods to detect and align LMs. The reference alignments are organised into different test sets representing real alignment problems and contain examples of experimentally verified functional motifs, extracted from the Eukaryotic Linear Motif (ELM) database. The benchmark has been used to evaluate and compare a number of multiple alignment programs. With distantly related proteins, the worst alignment program correctly aligns 48% of LMs compared to 73% for the best program. However, the performance of all the programs is adversely affected by the introduction of other sequences containing false positive motifs. The ranking of the alignment programs based on LM alignment quality is similar to that observed when considering full-length protein alignments, however little correlation was observed between LM and overall alignment quality for individual alignment test cases.ConclusionWe have shown that none of the programs currently available is capable of reliably aligning LMs in distantly related sequences and we have highlighted a number of specific problems. The results of the tests suggest possible ways to improve program accuracy for difficult, divergent sequences.
PARPST: a PARallel algorithm to find peptide sequence tags
Authors: Brunetti Sara , Lodi Elena , Mori Elisa , Stella Maria 
Published: April 2008

Abstract

Background
Protein identification is one of the most challenging problems in proteomics. Tandem mass spectrometry provides an important tool to handle the protein identification problem.

Results
We developed a work-efficient parallel algorithm for the peptide sequence tag problem. The algorithm runs on the concurrent-read, exclusive-write PRAM in O(n) time using log n processors, where n is the number of mass peaks in the spectrum. The algorithm is able to find all the sequence tags having score greater than a parameter or all the sequence tags of maximum length. Our tests on 1507 spectra in the Open Proteomics Database shown that our algorithm is efficient and effective since achieves comparable results to other methods.

Conclusions
The proposed algorithm can be used to speed up the database searching or to identify post-translational modifications, comparing the homology of the sequence tags found with the sequences in the biological database.
Mining small RNA structure elements in untranslated regions of human and mouse mRNAs using structure-based alignment
Authors: Khaladkar Mugdha , Liu Jianghui , Wen Dongrong , Wang Jason TL , Tian Bin 
Published: April 2008

Abstract

Background
UnTranslated Regions (UTRs) of mRNAs contain regulatory elements for various aspects of mRNA metabolism, such as mRNA localization, translation, and mRNA stability. Several RNA stem-loop structures in UTRs have been experimentally identified, including the histone 3' UTR stem-loop structure (HSL3) and iron response element (IRE). These stem-loop structures are conserved among mammalian orthologs, and exist in a group of genes encoding proteins involved in the same biological pathways. It is not known to what extent RNA structures like these exist in all mammalian UTRs.

Results
In this paper we took a systematic approach, named GLEAN-UTR, to identify small stem-loop RNA structure elements in UTRs that are conserved between human and mouse orthologs and exist in multiple genes with common Gene Ontology terms. This approach resulted in 90 distinct RNA structure groups containing 748 structures, with HSL3 and IRE among the top hits based on conservation of structure.

Conclusion
Our result indicates that there may exist many conserved stem-loop structures in mammalian UTRs that are involved in coordinate post-transcriptional regulation of biological pathways.
Association between Radiologists' Experience and Accuracy in Interpreting Screening Mammograms
Authors: Molins Eduard , Macià Francesc , Ferrer Francesc , Maristany Maria-Teresa , Castells Xavier 
Published: April 2008

Abstract

Background
Radiologists have been observed to differ, sometimes substantially, both in their interpretations of mammograms and in their recommendations for follow-up. The aim of this study was to determine how factors related to radiologists' experience affect the accuracy of mammogram readings.

Methods
We selected a random sample of screening mammograms from a population-based breast cancer screening program. The sample was composed of 30 women with histopathologically-confirmed breast cancer and 170 women without breast cancer after a 2-year follow-up (the proportion of cancers was oversampled). These 200 mammograms were read by 21 radiologists routinely interpreting mammograms, with different amount of experience, and by seven readers who did not routinely interpret mammograms. All readers were blinded to the results of the screening. A positive assessment was considered when a BI-RADS III, 0, IV, V was reported (additional evaluation required). Diagnostic accuracy was calculated through sensitivity and specificity.

Results
Average specificity was higher in radiologists routinely interpreting mammograms with regard to radiologists who did not (66% vs 56%; p < .001). Multivariate analysis based on routine readers alone showed that specificity was higher among radiologists who followed-up cases for which they recommended further workup (feedback) (OR 1.37; 95% CI 1.03 to 1.85), those spending less than 25% of the working day on breast radiology (OR 1.49; 95% CI 1.18 to 1.89), and those aged more than 45 years old (OR 1.33; 95% CI 1.12 to 1.59); the variable of average annual volume of mammograms interpreted by radiologists, classified as more or less than 5,000 mammograms per year, was not statistically significant (OR 1.06; 95% CI 0.90 to 1.25).

Conclusion
Among radiologists who read routinely, volume is not associated with better performance when interpreting screening mammograms, although specificity decreased in radiologists not routinely reading mammograms. Follow-up of cases for which further workup is recommended might reduce variability in mammogram readings and improve the quality of breast cancer screening programs.
Clinically immune hosts as a refuge for drug-sensitive malaria parasites
Authors: Klein Eili Y , Smith David L , Boni Maciej F , Laxminarayan Ramanan 
Published: April 2008

Abstract

Background
Mutations in Plasmodium falciparum that confer resistance to first-line antimalarial drugs have spread throughout the world from a few independent foci, all located in areas that were likely characterized by low or unstable malaria transmission. One of the striking differences between areas of low or unstable malaria transmission and hyperendemic areas is the difference in the size of the population of immune individuals. However, epidemiological models of malaria transmission have generally ignored the role of immune individuals in transmission, assuming that they do not affect the fitness of the parasite. This model reconsiders the role of immunity in the dynamics of malaria transmission and its impact on the evolution of antimalarial drug resistance under the assumption that immune individuals are infectious.

Methods
The model is constructed as a two-stage susceptible-infected-susceptible (SIS) model of malaria transmission that assumes that individuals build up clinical immunity over a period of years. This immunity reduces the frequency and severity of clinical symptoms, and thus their use of drugs. It also reduces an individual's level of infectiousness, but does not impact the likelihood of becoming infected.

Results
Simulations found that with the introduction of resistance into a population, clinical immunity can significantly alter the fitness of the resistant parasite, and thereby impact the ability of the resistant parasite to spread from an initial host by reducing the effective reproductive number of the resistant parasite as transmission intensity increases. At high transmission levels, despite a higher basic reproductive number, R
0, the effective reproductive number of the resistant parasite may fall below the reproductive number of the sensitive parasite.

Conclusion
These results suggest that high-levels of clinical immunity create a natural ecological refuge for drug-sensitive parasites. This provides an epidemiological rationale for historical patterns of resistance emergence and suggests that future outbreaks of resistance are more likely to occur in low- or unstable-transmission settings. This finding has implications for the design of drug policies and the formulation of malaria control strategies, especially those that lower malaria transmission intensity.
Selective killing of HIV-1-positive macrophages and T cells by the Rev-dependent lentivirus carrying anthrolysin O from Bacillus anthracis
Authors: Young Jessica , Tang Zhongwei , Yu Quan , Yu Dongyang , Wu Yuntao 
Published: April 2008

AbstractBackgroundThe ability of Human Immunodeficiency Virus (HIV) to persist in the body has proven to be a long-standing challenge to virus eradication. Current antiretroviral therapy cannot selectively destroy infected cells; it only halts active viral replication. With therapeutic cessation or interruption, viral rebound occurs, and invariably, viral loads return to pre-treatment levels. The natural reservoirs harboring replication-competent HIV-1 include CD4 T cells and macrophages. In particular, cells from the macrophage lineage resist HIV-1-mediated killing and support sustained viral production. To develop a complementary strategy to target persistently infected cells, this proof-of-concept study explores an HIV-1 Rev-dependent lentiviral vector carrying a bacterial hemolysin,anthrolysin O(anlO) fromBacillus anthracis, to achieve selective killing of HIV-1- infected cells.ResultsWe demonstrate that in the Rev-dependent lentiviral vector,anlOexpression is exclusively dependent on Rev, a unique HIV-1 protein present only in infected cells. Intracellular expression and oligomerization of AnlO result in membrane pore formation and cytolysis. We have further overcome a technical hurdle in producing a Revdependent AnlO lentivirus, through the use of β-cyclodextrin derivatives to inhibit direct killing of producer cells by AnlO. Using HIV-1-infected macrophages and T cells as a model, we demonstrate that this Rev-dependent AnlO lentivirus diminishes HIV-1- positive cells.ConclusionThe Rev-dependent lentiviral vector has demonstrated its specificity in targeting persistently infected cells. The choice ofanlOas the first suicidal gene tested in this vector is based on its cytolytic activity in macrophages and T cells. We conclude that Rev-regulated expression of suicidal genes in HIV-1-positive cells is possible, although futurein vivodelivery of this system needs to address numerous safety issues.
The role of immunohistochemistry in medullomyoblastoma – a case series highlighting divergent differentiation
Authors: Sachdeva Man Updesh S , Vankalakunti Mahesha , Rangan Aruna , Radotra Bishan D , Chhabra Rajesh , Vasishta Rakesh K 
Published: April 2008

Abstract

Aims
To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation.

Methods
A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructral analysis was done on tissue obtained from paraffin blocks in 2 cases.

Results
Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search.

Conclusion
Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.
Neuropilin-1 is a receptor for transforming growth factor β-1, activates its latent form, and promotes regulatory T cell activity
Authors: Glinka Yelena , Prud’homme Gérald J 
Published: April 2008

AbstractNeuropilin-1 (Nrp1) is a multifunctional protein, identified principally as a receptor for the class 3 semaphorins and members of the vascular endothelial growth factor (VEGF) family, but it is capable of other interactions. It is a marker of regulatory T cells (Tr), which often carry Nrp1 and latency-associated peptide (LAP)-TGF-β1 (the latent form). The signaling TGF-β1 receptors bind only active TGF-β1, and we hypothesized that Nrp1 binds the latent form. Indeed, we found that Nrp1 is a high-affinity receptor for latent and active TGF-β1. Free LAP, LAP-TGF-β1, and active TGF-β1 all competed with VEGF165 for binding to Nrp1. LAP has a basic, arginine-rich C-terminal motif similar to VEGF and peptides that bind to the b1 domain of Nrp1. A C-terminal LAP peptide (QSSRHRR) bound to Nrp1 and inhibited the binding of VEGF and LAP-TGF-β1. We also analyzed the effects of Nrp1/LAP-TGF-β1 coexpression on T cell function. Compared with Nrp1– cells, sorted Nrp1+ T cells had a much greater capacity to capture LAP-TGF-β1. Sorted Nrp1– T cells captured soluble Nrp1-Fc, and this increased their ability to capture LAP-TGF-β1. Conventional CD4+CD25–Nrp1– T cells coated with Nrp1-Fc/LAP-TGF-β1 acquired strong Tr activity. Moreover, LAP-TGF-β was activated by Nrp1-Fc and also by a peptide of the b2 domain of Nrp1 (RKFK; similar to a thrombospondin-1 peptide). Breast cancer cells, which express Nrp1, also captured and activated LAP-TGF-β1 in a Nrp1-dependent manner. Thus, Nrp1 is a receptor for TGF-β1, activates its latent form, and is relevant to Tr activity and tumor biology.
Repeat prescribing processes in primary care: a qualitative study
Authors: Saastamoinen Leena Katariina , Enlund Hannes , Klaukka Timo Juhani 
Published: April 2008

Abstract

Objective
To investigate the characteristics, local agreements and changes regarding repeat prescribing processes in primary health care in Finland.

Setting
Twenty-eight municipal health centres nationwide.

Method
Twenty-eight physicians and 28 medical receptionists were given semi-structured telephone interviews about repeat prescribing practices. The repeat prescribing process of each health centre was displayed as a flow chart and the processes were classified according to the quality of the practical flow and the medication review.

Key findings
There are various ways of carrying out repeat prescribing in different health centres. In some centres, a review of the medications is recognised as part of the repeat prescribing process, but in others there is no systematic review of the patients' medication. Repeat prescribing is often performed in a busy atmosphere. Repeat prescribing systems have evolved over time without proper management, and few local guidelines exist.

Conclusions
There is a need to reorganise the repeat prescribing systems in primary health care. A regular review of long-term medications, in particular, needs to become a part of the repeat prescribing process. There is a need for both local and national guidelines.