bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the treatment effect of IFN-β restored after the disappearance of neutralizing antibodies?
Authors: Sorensen PS , Koch-Henriksen N , Flachs EM , Bendtzen K 
Published: May 2008

Objective To establish whether multiple sclerosis (MS) patients, who have lost the therapeutic effect of interferon-beta (IFN-β) owing to neutralizing antibodies (NAbs) and subsequently revert from a NAb-positive to a NAb-negative state under continued IFN-β-1b therapy, regain clinical effect after reversion. Background Several studies have shown that a significant proportion of patients treated with IFN-β develop NAbs that hamper or abolish the therapeutic effect of IFN-β. However, some patients, who become NAb-positive under treatment with IFN-β-1b, may revert to a NAb-negative state under continuous treatment. Methods We identified 40 patients from the Danish IFN protocol, who fulfilled the criteria: NAb-positive status for at least 12 months followed by reversion to NAb-negative state for at least 12 months. For comparison, we included 64 matching cases that had remained NAb-negative during an observation time of at least 36 months. The two groups were clinically and demographically alike. We measured NAb-neutralizing capacity using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. A patient was defined as NAb-positive after two consecutive blood tests separated by at least 6 months. Reversion to a NAb-negative state required at least two consecutive negative tests. To allow for the confounding effect of time we employed a mixed Poisson model. Results Patients who had been NAb-positive and reverted to a NAb-negative state regained treatment effect with the relapse rate as before the NAb-positive period adjusting for the effect of time, and the relapse rate was the same as in the permanently NAb-negative patients in corresponding time periods. The relapse rate ratio comparing the NAb-positive with the NAb-negative periods was 1.98 (95% confidence interval: 1.32–2.97). Conclusion Under NAb-positive periods, the clinical effect of IFN-β was abolished. When NAbs disappeared spontaneously under continued treatment, patients regained the full effect of INF-β-1b therapy with no negative carry-over effect from the previous NAb-positive period.
Predictors of hospitals' organizational climates and nurses' intent to stay in Jordanian hospitals
Authors: Mrayyan Majd T. 
Published: May 2008

This paper aimed at studying variables of hospitals' organizational climates and nurses' intent to stay and determine predictors of the two concepts. A survey using a convenience sampling technique was used to collect data. A total of 362 nurses from three types of hospitals were recruited. Farly's Nursing Practice Environment Scale (NPES) was used to assess the organizational climates at Jordanian hospitals (Farly and Nyberg, 1990). McCain's Behavioral Commitment Scale (McCloskey, 1990) was used to measure nurses' intent to stay. Stepwise regression analyses were used to indicate predictors of hospitals' organizational climates and nurses' intent to stay. Quality of care and professionalism were major variables influenced hospitals' organizational climates. Nurses reported that they plan to keep their jobs for at least two or three years. Nurses' intent to stay, time commitment, types of hospitals and average daily census were predictors of hospitals' organizational climates. Predictors of nurses' intent to stay were hospitals' organizational climates, decision-making style, age and organizational structures. Managerial interventions that would create supportive work environments are needed to encourage nurses to stay longer at their jobs. These interventions include, but are not limited to, using participative management and supportive leadership, decreasing workload and employing nurses who work on a full-time basis.
Correlation between self-concept and health status aspects in haemodialysis patients at selected hospitals affiliated to Shaheed Beheshti University of Medical Sciences
Authors: Yaghmaie Farideh , Khalafi Ali , Majd Hamid Alavi , Khost Nderh 
Published: May 2008

Chronic renal failure (CRF) is an overwhelming disorder affecting physical, psychological and socioeconomic wellbeing of patients. Restoring health is a primary therapeutic goal and interventions are generally directed toward improving their quality of life (QOL). The concept of health is unique for every one and each individual considers it with respect to his/her own criteria. This concept is influenced by different physical, mental and social factors and is termed self-concept. A descriptive study was conducted to determine the correlation between self-concept quality and aspects of health status in haemodialysis patients referring to hospitals affiliated to Shaheed Beheshti University of Medical Sciences. One-hundred and thirteen patients between 15 and 65 with no history of kidney transplantation and at least one year's experience of haemodialysis, three times a week, participated in the study. A questionnaire in three parts to collect demographic, self-concept and health status data was used. It was validated by content validity index and its reliability was identified by internal consistency and test-retest methods. Findings showed a significant relation between self-concept and all aspects of health status except treatment and medication. The correlation between self-concept and health status shows that subjective patients' attitudes affect their own self image with regards to being healthy and running a productive and fruitful life. Thus, in addition to physical disorders resulting from CRF and haemodialysis and social conditions can affect their motivation and life experience.
Accessing elite nurses for research: reflections on the theoretical and practical issues of telephone interviewing
Authors: Harris Ruth , Kelly Daniel , Hunt Jane A , Plant Hilary , Kelley Kate , Richardson Alison , Sitzia John 
Published: May 2008

Elite groups are interesting as they frequently are powerful (in terms of position, knowledge and influence) and enjoy considerable authority. It is important, therefore, to involve them in research concerned with understanding social contexts and processes. This is particularly pertinent in healthcare, where considerable strategic development and change are features of everyday practice that may be guided or perceived as being guided, by elites. This paper evolved from a study investigating the availability and role of nurses whose remit involved leading nursing research and development within acute NHS Trusts in two health regions in Southern England. The study design included telephone interviews with Directors of Nursing Services during which time the researchers engaged in a reflective analysis of their experiences of conducting research with an `elite' group. Important issues identified were the role of gatekeepers, engagement with elites and the use of the telephone interview method in this context. The paper examines these issues and makes a case for involving executive nurses in further research. The paper also offers strategies to help researchers design and implement telephone interview studies successfully to maximise access to the views and experiences of `hard to reach groups', such as elites, while minimising the associated disruption.
Emotion work and the ethics of novice insider research
Authors: Darra Susanne 
Published: May 2008

This paper relates to research practice and in particular, it explores the practice of insider research in a study carried out as part of a research training fellowship. The effects of research on the researcher and the researched are discussed and extracts from transcripts and a research diary are used to illustrate ethical dilemmas that may arise from such a study. The role of the novice researcher is central to the discussion and the concept of `emotion work' is used to illustrate the hidden consequences of seemingly innocuous insider research. The paper contributes to the body of knowledge relating to qualitative research methods, by combining reflection with emotion work and novice insider research. Despite it being largely about the novice researcher studying within her own profession, it raises important points that may be of interest to more experienced researchers working in other domains.
Vorinostat synergistically potentiates MK-0457 lethality in chronic myelogenous leukemia cells sensitive and resistant to imatinib mesylate
Authors: Dai Yun , Chen Shuang , Venditti Charis A. , Pei Xin-Yan , Nguyen Tri K. , Dent Paul , Grant Steven 
Published: May 2008

AbstractInteractions between the dual Bcr/Abl and aurora kinase inhibitor MK-0457 and the histone deacetylase inhibitor vorinostat were examined in Bcr/Abl+ leukemia cells, including those resistant to imatinib mesylate (IM), particularly those with the T315I mutation. Coadministration of vorinostat dramatically increased MK-0457 lethality in K562 and LAMA84 cells. Notably, the MK-0457/vorinostat regimen was highly active against primary CD34+ chronic myelogenous leukemia (CML) cells and Ba/F3 cells bearing various Bcr/Abl mutations (ie, T315I, E255K, and M351T), as well as IM-resistant K562 cells exhibiting Bcr/Abl-independent, Lyn-dependent resistance. These events were associated with inactivation and down-regulation of wild-type (wt) and mutated Bcr/Abl (particularly T315I). Moreover, treatment with MK-0457 resulted in accumulation of cells with 4N or more DNA content, whereas coadministration of vorinostat markedly enhanced aurora kinase inhibition by MK-0457, and preferentially killed polyploid cells. Furthermore, vorinostat also interacted with a selective inhibitor of aurora kinase A and B to potentiate apoptosis without modifying Bcr/Abl activity. Finally, vorinostat markedly induced Bim expression, while blockade of Bim induction by siRNA dramatically diminished the capacity of this agent to potentiate MK-0457 lethality. Together, these findings indicate that vorinostat strikingly increases MK-0457 activity against IM-sensitive and -resistant CML cells through inactivation of Bcr/Abl and aurora kinases, as well as by induction of Bim.
Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells
Authors: Laffont Sophie , Seillet Cyril , Ortaldo John , Coudert Jérôme D. , Guéry Jean-Charles 
Published: May 2008

AbstractNatural killer (NK)–cell alloreactivity is exploited in bone marrow transplantation to improve clinical outcome. Likewise, in solid organ transplantation, it has been recently shown that recipient NK cells may limit alloreactive T-cell responses through their capacity to prevent the persistence of graft-derived allogeneic dendritic cells (DCs). In a model of CD4+ T cell–mediated allogeneic skin graft rejection, we show that the absence of host NK-cell alloreactivity was characterized by enhanced expansion of alloreactive effector T lymphocytes, including Th2 cells, and massive eosinophilic infiltrates in the rejected tissues. In CD8+ T cell–deficient C57BL/6 (H-2b) recipients injected with allogeneic BALB/c (H-2d) DCs, we demonstrated that NK cells expressing the H-2Dd-specific Ly49D activating receptor were implicated in the regulation of alloreactive CD4+ T-cell responses. Moreover, we showed that Ly49D+ CD127− NK cells were recruited within DC draining lymph nodes and rapidly eliminated allogeneic H-2d DCs through the perforin pathway. In normal mice, we further demonstrated that NK cells by quickly eliminating allogeneic DCs strongly inhibited alloreactive CD8+ T-cell responses. Thus, NK cells act as early regulators of alloreactive T-cell priming in allotransplantation through their capacity to kill allogeneic DCs in draining lymph nodes.
Lack of nuclear factor-κB2/p100 causes a RelB-dependent block in early B lymphopoiesis
Authors: Guo Feng , Tänzer Simone , Busslinger Meinrad , Weih Falk 
Published: May 2008

Abstract
Nuclear factor-κB (NF-κB) transcription factors regulate B-cell development and survival. However, whether they also have a role during early steps of B-cell differentiation is largely unclear. Here, we show that constitutive activation of the alternative NF-κB pathway in p100−/− knockin mice resulted in a block of early B-cell development at the transition from the pre–pro-B to the pro–B-cell stage due to enhanced RelB activity. Expression of the essential B-cell transcription factors EBF and in particular Pax5 was reduced in p100−/− B-cell precursors in a RelB-dependent manner, resulting in reduced mRNA levels of B lineage-specific genes. Moreover, enhanced RelB function in p100−/− B-cell precursors was accompanied by increased expression of B lineage–inappropriate genes, such as C/EBPα, correlating with a markedly increased myeloid differentiation potential of p100−/− progenitor B cells. Ectopic expression of Pax5 in hematopoietic progenitors restored early B-cell development in p100−/− bone marrow, suggesting that impaired early B lymphopoiesis in mice lacking the p100 inhibitor may be due to down-regulation of Pax5 expression. Thus, tightly controlled p100 processing and RelB activation is essential for normal B lymphopoiesis and lymphoid/myeloid lineage decision in bone marrow.
Application of the Linux cluster for exhaustive window haplotype analysis using the FBAT and Unphased programs
Authors: Mishima Hiroyuki , Lidral Andrew C , Ni Jun 
Published: May 2008

Abstract

Background
Genetic association studies have been used to map disease-causing genes. A newly introduced statistical method, called exhaustive haplotype association study, analyzes genetic information consisting of different numbers and combinations of DNA sequence variations along a chromosome. Such studies involve a large number of statistical calculations and subsequently high computing power. It is possible to develop parallel algorithms and codes to perform the calculations on a high performance computing (HPC) system. However, most existing commonly-used statistic packages for genetic studies are non-parallel versions. Alternatively, one may use the cutting-edge technology of grid computing and its packages to conduct non-parallel genetic statistical packages on a centralized HPC system or distributed computing systems. In this paper, we report the utilization of a queuing scheduler built on the Grid Engine and run on a Rocks Linux cluster for our genetic statistical studies.

Results
Analysis of both consecutive and combinational window haplotypes was conducted by the FBAT (Laird et al., 2000) and Unphased (Dudbridge, 2003) programs. The dataset consisted of 26 loci from 277 extended families (1484 persons). Using the Rocks Linux cluster with 22 compute-nodes, FBAT jobs performed about 14.4–15.9 times faster, while Unphased jobs performed 1.1–18.6 times faster compared to the accumulated computation duration.

Conclusion
Execution of exhaustive haplotype analysis using non-parallel software packages on a Linux-based system is an effective and efficient approach in terms of cost and performance.
Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation
Authors: Arikuma Takeshi , Yoshikawa Sumi , Azuma Ryuzo , Watanabe Kentaro , Matsumura Kazumi , Konagaya Akihiko 
Published: May 2008

AbstractBackgroundIn accordance with the increasing amount of information concerning individual differences in drug response and molecular interaction, the role ofin silicoprediction of drug interaction on the pathway level is becoming more and more important. However, in view of the interferences for the identification of new drug interactions, most conventional information models of a biological pathway would have limitations. As a reflection of real world biological events triggered by a stimulus, it is important to facilitate the incorporation of known molecular events for inferring (unknown) possible pathways and hypothetic drug interactions. Here, we propose a new Ontology-Driven Hypothetic Assertion (OHA) framework including pathway generation, drug interaction detection, simulation model generation, numerical simulation, and hypothetic assertion. Potential drug interactions are detected from drug metabolic pathways dynamically generated by molecular events triggered after the administration of certain drugs. Numerical simulation enables to estimate the degree of side effects caused by the predicted drug interactions. New hypothetic assertions of the potential drug interactions and simulation are deduced from the Drug Interaction Ontology (DIO) written in Web Ontology Language (OWL).ResultsThe concept of the Ontology-Driven Hypothetic Assertion (OHA) framework was demonstrated with known interactions between irinotecan (CPT-11) and ketoconazole. Four drug interactions that involved cytochrome p450 (CYP3A4) and albumin as potential drug interaction proteins were automatically detected from Drug Interaction Ontology (DIO). The effect of the two interactions involving CYP3A4 were quantitatively evaluated with numerical simulation. The co-administration of ketoconazole may increase AUC and Cmax of SN-38(active metabolite of irinotecan) to 108% and 105%, respectively. We also estimates the potential effects of genetic variations: the AUC and Cmax of SN-38 may increase to 208% and 165% respectively with the genetic variation UGT1A1*28/*28 which reduces the expression of UGT1A1 down to 30%.ConclusionThese results demonstrate that the Ontology-Driven Hypothetic Assertion framework is a promising approach forin silicoprediction of drug interactions. The following future researches for thein silicoprediction of individual differences in the response to the drug and drug interactions after the administration of multiple drugs: expansion of the Drug Interaction Ontology for other drugs, and incorporation of virtual population model for genetic variation analysis, as well as refinement of the pathway generation rules, the drug interaction detection rules, and the numerical simulation models.
Evolutionary conservation of DNA-contact residues in DNA-binding domains
Authors: Chang Yao-Lin , Tsai Huai-Kuang , Kao Cheng-Yan , Chen Yung-Chian , Hu Yuh-Jyh , Yang Jinn-Moon 
Published: May 2008

Abstract

Background
DNA-binding proteins are of utmost importance to gene regulation. The identification of DNA-binding domains is useful for understanding the regulation mechanisms of DNA-binding proteins. In this study, we proposed a method to determine whether a domain or a protein can has DNA binding capability by considering evolutionary conservation of DNA-binding residues.

Results
Our method achieves high precision and recall for 66 families of DNA-binding domains, with a false positive rate less than 5% for 250 non-DNA-binding proteins. In addition, experimental results show that our method is able to identify the different DNA-binding behaviors of proteins in the same SCOP family based on the use of evolutionary conservation of DNA-contact residues.

Conclusion
This study shows the conservation of DNA-contact residues in DNA-binding domains. We conclude that the members in the same subfamily bind DNA specifically and the members in different subfamilies often recognize different DNA targets. Additionally, we observe the co-evolution of DNA-contact residues and interacting DNA base-pairs.
A topological transformation in evolutionary tree search methods based on maximum likelihood combining p-ECR and neighbor joining
Authors: Guo Mao-Zu , Li Jian-Fu , Liu Yang 
Published: May 2008

Abstract

Background
Inference of evolutionary trees using the maximum likelihood principle is NP-hard. Therefore, all practical methods rely on heuristics. The topological transformations often used in heuristics are Nearest Neighbor Interchange (NNI), Subtree Prune and Regraft (SPR) and Tree Bisection and Reconnection (TBR). However, these topological transformations often fall easily into local optima, since there are not many trees accessible in one step from any given tree. Another more exhaustive topological transformation is p-Edge Contraction and Refinement (p-ECR). However, due to its high computation complexity, p-ECR has rarely been used in practice.

Results
To make the p-ECR move more efficient, this paper proposes a new method named p-ECRNJ. The main idea of p-ECRNJ is to use neighbor joining (NJ) to refine the unresolved nodes produced in p-ECR.

Conclusion
Experiments with real datasets show that p-ECRNJ can find better trees than the best known maximum likelihood methods so far and can efficiently improve local topological transforms in reasonable time.
Protein structural class prediction based on an improved statistical strategy
Authors: Gu Fei , Chen Hang , Ni Jun 
Published: May 2008

Abstract

Background
A protein structural class (PSC) belongs to the most basic but important classification in protein structures. The prediction technique of protein structural class has been developing for decades. Two popular indices are the amino-acid-frequency (AAF) based, and amino-acid-arrangement (AAA) with long-term correlation (LTC) – based indices. They were proposed in many works. Both indices have its pros and cons. For example, the AAF index focuses on a statistical analysis, while the AAA-LTC emphasizes the long-term, biological significance. Unfortunately, the datasets used in previous work were not very reliable for a small number of sequences with a high-sequence similarity.

Results
By modifying a statistical strategy, we proposed a new index method that combines probability and information theory together with a long-term correlation. We also proposed a numerically and biologically reliable dataset included more than 5700 sequences with a low sequence similarity. The results showed that the proposed approach has its high accuracy. Comparing with amino acid composition (AAC) index using a distance method, the accuracy of our approach has a 16–20% improvement for re-substitution test and about 6–11% improvement for cross-validation test. The values were about 23% and 15% for the component coupled method (CCM).

Conclusion
A new index method, combining probability and information theory together with a long-term correlation was proposed in this paper. The statistical method was improved significantly based on our new index. The cross validation test was conducted, and the result show the proposed method has a great improvement.