bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD7-restricted activation of Fas-mediated apoptosis: a novel therapeutic approach for acute T-cell leukemia
Authors: Bremer Edwin , Cate Bram ten , Samplonius Douwe F. , de Leij Lou F. M. H. , Helfrich Wijnand 
Published: December 2005

AbstractAgonistic anti-Fas antibodies and multimeric recombinant Fas ligand (FasL) preparations show high tumoricidal activity against leukemic cells, but are unsuitable for clinical application due to unacceptable systemic toxicity. Consequently, new antileukemia strategies based on Fas activation have to meet the criterion of strictly localized action at the tumor-cell surface. Recent insight into the FasL/Fas system has revealed that soluble homotrimeric FasL (sFasL) is in fact nontoxic to normal cells, but also lacks tumoricidal activity. We report on a novel fusion protein, designated scFvCD7:sFasL, that is designed to have leukemia-restricted activity. ScFvCD7:sFasL consists of sFasL genetically linked to a high-affinity single-chain fragment of variable regions (scFv) antibody fragment specific for the T-cell leukemia-associated antigen CD7. Soluble homotrimeric scFvCD7:sFasL is inactive and acquires tumoricidal activity only after specific binding to tumor cell-surface-expressed CD7. Treatment of T-cell acute lymphoblastic leukemia (T-ALL) cell lines and patient-derived T-ALL, peripheral T-cell lymphoma (PTCL), and CD7-positive acute myeloid leukemia (AML) cells with homotrimeric scFvCD7:sFasL revealed potent CD7-restricted induction of apoptosis that was augmented by conventional drugs, farnesyl transferase inhibitor L-744832, and the proteasome inhibitor bortezomib (Velcade; Millenium, Cambridge, MA). Importantly, identical treatment did not affect normal human peripheral-blood lymphocytes (PBLs) and endothelial cells, with only moderate apoptosis in interleukin-2 (IL-2)/CD3-activated T cells. CD7-restricted activation of Fas in T-cell leukemic cells by scFvCD7:sFasL revitalizes interest in the applicability of Fas signaling in leukemia therapy.
GenClust: A genetic algorithm for clustering gene expression data
Authors: Di Gesú Vito , Giancarlo Raffaele , Lo Bosco Giosué , Raimondi Alessandra , Scaturro Davide 
Published: December 2005

Abstract
Background
Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering.

Results
GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means.

Conclusion
Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.
The largest subunit of RNA polymerase II from the Glaucocystophyta: functional constraint and short-branch exclusion in deep eukaryotic phylogeny
Authors: Stiller John W , Harrell Leslie 
Published: December 2005

AbstractBackgroundEvolutionary analyses of the largest subunit of RNA polymerase II (RPB1) have yielded important and at times provocative results. One particularly troublesome outcome is the consistent inference of independent origins of red algae and green plants, at odds with the more widely accepted view of a monophyletic Plantae comprising all eukaryotes with primary plastids. If the hypothesis of a broader kingdom Plantae is correct, then RPB1 trees likely reflect a persistent phylogenetic artifact. To gain a better understanding of RNAP II evolution, and the presumed artifact relating to green plants and red algae, we isolated and analyzedRPB1 from representatives of Glaucocystophyta, the third eukaryotic group with primary plastids.ResultsPhylogenetic analyses incorporating glaucocystophytes do not recover a monophyletic Plantae; rather they result in additional conflicts with the most widely held views on eukaryotic relationships. In particular, glaucocystophytes are recovered as sister to several amoebozoans with strong support. A detailed investigation shows that this clade can be explained by what we call "short-branch exclusion," a phylogenetic artifact integrally associated with "long-branch attraction." Other systematic discrepancies observed inRPB1 trees can be explained as phylogenetic artifacts; however, these apparent artifacts also appear in regions of the tree that support widely held views of eukaryotic evolution. In fact, most of the RPB1 tree is consistent with artifacts of rate variation among sequences and co-variation due to functional constraints related to C-terminal domain based RNAP II transcription.ConclusionOur results reveal how subtle and easily overlooked biases can dominate the overall results of molecular phylogenetic analyses of ancient eukaryotic relationships. Sources of potential phylogenetic artifact should be investigated routinely, not just when obvious "long-branch attraction" is encountered.
Coxiella burnetii vascular graft infection
Authors: Senn Laurence , Franciolli Mario , Raoult Didier , Moulin Alexandre , Von Segesser Ludwig , Calandra Thierry , Greub Gilbert 
Published: December 2005

Abstract

Background

Coxiella burnetii, the causative agent of Q fever, may cause culture-negative vascular graft infections. Very few cases of C. burnetii infection of a vascular graft have been reported. All were diagnosed by serology.

Case presentation
We report the first case of Coxiella burnetii vascular graft infection diagnosed by broad-range PCR and discuss the diagnostic approaches and treatment strategies of chronic C. burnetii infection.

Conclusion

C. burnetii should be considered as etiological agent in patients with a vascular graft and fever, abdominal pain, and laboratory signs of inflammation, with or without exposure history. Broad-range PCR should be performed on culture-negative surgical samples in patients with suspected infection of vascular graft.
Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes
Authors: Bento Jennifer L , Bowden Donald W , Mychaleckyj Josyf C , Hirakawa Shohei , Rich Stephen S , Freedman Barry I , Segade Fernando 
Published: December 2005

Abstract

Background
GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans.

Methods
Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM.

Results
Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls.

Conclusion
From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans.
Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer
Authors: El Saghir Nagi S , Otrock Zaher K , Bleik Jamal H 
Published: December 2005

Abstract

Background
Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use.

Case presentation
We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months.

Conclusion
Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.
Public perception of drinking water from private water supplies: focus group analyses
Authors: Jones Andria Q , Dewey Catherine E , Doré Kathryn , Majowicz Shannon E , McEwen Scott A , Waltner-Toews David , Henson Spencer J , Mathews Eric 
Published: December 2005

Abstract

Background
Over four million Canadians receive their drinking water from private water supplies, and numerous studies report that these supplies often exceed the minimal acceptable standards for contamination. Canadians in rural areas test their water intermittently, if at all, and treatment of water from private supplies is not common. Understanding the perceptions of drinking water among residents served by private systems will enable public health professionals to better target education and outreach activities, and to address the needs and concerns of residents in their jurisdictions. The purpose of this study was to explore the drinking water perceptions and self-described behaviours and needs of participants served by private water systems in the City of Hamilton, Ontario (Canada).

Methods
In September 2003, three focus group discussions were conducted; two with men and women aged 36–65 years, and one with men and women 20–35 years of age.

Results
Overall, participants had positive perceptions of their private water supplies, particularly in the older age group. Concerns included bacterial and chemical contamination from agricultural sources. Testing of water from private supplies was minimal and was done less frequently than recommended by the provincial government. Barriers to water testing included the inconvenience of the testing process, acceptable test results in the past, resident complacency and lack of knowledge. The younger participants greatly emphasized their need for more information on private water supplies. Participants from all groups wanted more information on water testing, and various media for information dissemination were discussed.

Conclusion
While most participants were confident in the safety of their private water supply, the factual basis for these opinions is uncertain. Improved dissemination of information pertaining to private water supplies in this population is needed. Observed differences in the concerns expressed by users of different water systems and age groups may suggest the need for targeted public education strategies. These focus groups provided significant insight into the public perception of private water supplies and the need for public health outreach activities; however, to obtain a more representative understanding of the perceptions in this population, it is important that a larger scale investigation be performed.
Standardisation of data from real-time quantitative PCR methods – evaluation of outliers and comparison of calibration curves
Authors: Burns Malcolm J , Nixon Gavin J , Foy Carole A , Harris Neil 
Published: December 2005

Abstract

Background
As real-time quantitative PCR (RT-QPCR) is increasingly being relied upon for the enforcement of legislation and regulations dependent upon the trace detection of DNA, focus has increased on the quality issues related to the technique. Recent work has focused on the identification of factors that contribute towards significant measurement uncertainty in the real-time quantitative PCR technique, through investigation of the experimental design and operating procedure. However, measurement uncertainty contributions made during the data analysis procedure have not been studied in detail. This paper presents two additional approaches for standardising data analysis through the novel application of statistical methods to RT-QPCR, in order to minimise potential uncertainty in results.

Results
Experimental data was generated in order to develop the two aspects of data handling and analysis that can contribute towards measurement uncertainty in results. This paper describes preliminary aspects in standardising data through the application of statistical techniques to the area of RT-QPCR. The first aspect concerns the statistical identification and subsequent handling of outlying values arising from RT-QPCR, and discusses the implementation of ISO guidelines in relation to acceptance or rejection of outlying values. The second aspect relates to the development of an objective statistical test for the comparison of calibration curves.

Conclusion
The preliminary statistical tests for outlying values and comparisons between calibration curves can be applied using basic functions found in standard spreadsheet software. These two aspects emphasise that the comparability of results arising from RT-QPCR needs further refinement and development at the data-handling phase. The implementation of standardised approaches to data analysis should further help minimise variation due to subjective judgements. The aspects described in this paper will help contribute towards the development of a set of best practice guidelines regarding standardising handling and interpretation of data arising from RT-QPCR experiments.
Decorticate, decerebrate and opisthotonic posturing and seizures in Kenyan children with cerebral malaria
Authors: Idro Richard , Otieno Godfrey , White Steven , Kahindi Anderson , Fegan Greg , Ogutu Bernhards , Mithwani Sadik , Maitland Kathryn , Neville Brian GR , Newton Charles RJC 
Published: December 2005

Abstract

Background
Abnormal motor posturing is often observed in children with cerebral malaria, but the aetiology and pathogenesis is poorly understood. This study examined the risk factors and outcome of posturing in Kenyan children with cerebral malaria.

Methods
Records of children admitted to Kilifi district hospital with cerebral malaria from January, 1999 through December, 2001 were reviewed for posturing occurring on or after admission. The clinical characteristics, features of raised intracranial pressure, number of seizures and biochemical changes in patients that developed posturing was compared to patients who did not.

Results
Of the 417 children with complete records, 163 (39.1%) had posturing: 85 on admission and 78 after admission to hospital. Decorticate posturing occurred in 80, decerebrate in 61 and opisthotonic posturing in 22 patients. Posturing was associated with age ≥ 3 years (48.1 vs 35.8%, p = 0.01) and features of raised intracranial pressure on funduscopy (adjusted OR 2.1 95%CI 1.2–3.7, p = 0.009) but not other markers of severity of disease. Unlike decorticate posturing, decerebrate (adjusted OR 1.9 95%CI 1.0–3.5) and opisthotonic posturing (adjusted OR 2.9 95%CI 1.0–8.1) were, in addition, independently associated with recurrence of seizures after admission. Opisthotonus was also associated with severe metabolic acidosis (OR 4.2 95%CI 3.2–5.6, p < 0.001). Thirty one patients with posturing died. Of these, 19 (61.3%) had features suggestive of transtentorial herniation. Mortality and neurological deficits on discharge were greatest in those developing posturing after admission.

Conclusion
Abnormal motor posturing is a common feature of cerebral malaria in children. It is associated with features of raised intracranial pressure and recurrence of seizures, although intracranial hypertension may be the primary cause.
Assessment of erythrocyte phospholipid fatty acid composition as a biomarker for dietary MUFA, PUFA or saturated fatty acid intake in a controlled cross-over intervention trial
Authors: Poppitt Sally D , Kilmartin Paul , Butler Paul , Keogh Geraldine F 
Published: December 2005

Abstract

Background
Dietary intervention trials rely on self-reported measures of intake for assessment of energy and macronutrient composition. Dietary fat intake is of particular interest due to strong associations with pathophysiology. In epidemiological trials phospholipid fatty acid composition may reflect composition of habitual diet, although strong correlations have been identified only for essential polyunsaturated fatty acids (PUFAs). Preliminary evidence shows that saturated fatty acids (SFA) C15:0 and C17:0 may be acceptable biomarkers. This study measured changes in erythrocyte membrane fatty acids during a period of strictly controlled fat feeding to investigate their use as a short-term marker of compliance, particularly for intake of SFAs.

Results
This was a randomised cross-over trial in which diet was provided and strictly controlled. 20 healthy, male subjects were given a 40 energy % (en%) fat diet, high in saturated (high-SFA, 20 en%) or unsaturated (high-USFA, 24 en%) fatty acids for 2 periods of 3 weeks. Subjects were residential during intervention with all food and beverages provided. Dietary composition was verified by direct chemical analysis. Blood samples were collected on days 1,7,14, 21 and analysed for red blood cell (RBC) membrane fatty acid composition. Pearson correlation showed RBC fatty acid composition to mimic dietary composition by 3 weeks, but the relationships were weak. Of the SFAs only RBC C16:0 decreased in response to decreased dietary content on high-USFA treatment (ANOVA, diet, P < 0.05). Of the USFAs, higher levels of C18:1 MUFA, C20:4 and C22:6 long chain PUFA on high-USFA diet lead to higher C18:1, C20:4 and C22:6 within RBCs (ANOVA, time*diet, P < 0.05). Pearson's correlation was significant between dietary and RBC fatty acids during the 21d dietary manipulation for C18:1, and C20:5, C22:6 only (P < 0.05).

Conclusion
RBC membrane fatty acids cannot reliably be used as an independent measure of compliance for dietary SFA intake in short-term studies. The MUFA oleic acid and PUFAs EPA and DHA may be more useful as markers of compliance during short term intervention trials.
Pacing stress echocardiography
Authors: Gligorova Suzana , Agrusta Marco 
Published: December 2005

Abstract

Background
High-rate pacing is a valid stress test to be used in conjunction with echocardiography; it is independent of physical exercise and does not require drug administration. There are two main applications of pacing stress in the echo lab: the noninvasive detection of coronary artery disease through induction of a regional transient dysfunction; and the assessment of contractile reserve through peak systolic pressure/ end-systolic volume relationship at increasing heart rates to assess global left ventricular contractility.

Methods
The pathophysiologic rationale of pacing stress for noninvasive detection of coronary artery disease is obvious, with the stress determined by a controlled increase in heart rate, which is a major determinant of myocardial oxygen demand, and thereby tachycardia may exceed a fixed coronary flow reserve in the presence of hemodynamically significant coronary artery disease. The use of pacing stress echo to assess left ventricular contractile reserve is less established, but promising. Positive inotropic interventions are mirrored by smaller end-systolic volumes and higher end-systolic pressures. An increased heart rate progressively increases the force of ventricular contraction (Bowditch treppe or staircase phenomenon). To build the force-frequency relationship, the force is determined at different heart rate steps as the ratio of the systolic pressure (cuff sphygmomanometer)/end-systolic volume index (biplane Simpson rule). The heart rate is determined from ECG.

Conclusion
Two-dimensional echocardiography during pacing is a useful tool in the detection of coronary artery disease. Because of its safety and ease of repeatability noninvasive pacing stress echo can be the first-line stress test in patients with permanent pacemaker.
The force-frequency can be defined as up- sloping (normal) when the peak stress pacing systolic pressure/end-systolic volume index is higher than baseline and intermediate stress values, biphasic with an initial up- sloping followed by a later down-sloping trend, or flat or negative when peak stress pacing systolic pressure/end-systolic volume index is equal or lower than baseline stress values. This approach is certainly highly feasible and allows a conceptually immaculate definition of contractility with prognostic usefulness, but its therapeutic implications remains to be established. Bowditch treppe, assessed with pacing stress, can be used to assess the optimal stimulation frequency and to optimise the patient's chronotropic response in programming rate-adaptive pacemakers.