bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative evaluation of gene-set analysis methods
Authors: Liu Qi , Dinu Irina , Adewale Adeniyi J , Potter John D , Yasui Yutaka 
Published: November 2007

Abstract

Background
Multiple data-analytic methods have been proposed for evaluating gene-expression levels in specific biological pathways, assessing differential expression associated with a binary phenotype. Following Goeman and Bühlmann's recent review, we compared statistical performance of three methods, namely Global Test, ANCOVA Global Test, and SAM-GS, that test "self-contained null hypotheses" Via. subject sampling. The three methods were compared based on a simulation experiment and analyses of three real-world microarray datasets.

Results
In the simulation experiment, we found that the use of the asymptotic distribution in the two Global Tests leads to a statistical test with an incorrect size. Specifically, p-values calculated by the scaled χ
2 distribution of Global Test and the asymptotic distribution of ANCOVA Global Test are too liberal, while the asymptotic distribution with a quadratic form of the Global Test results in p-values that are too conservative. The two Global Tests with permutation-based inference, however, gave a correct size. While the three methods showed similar power using permutation inference after a proper standardization of gene expression data, SAM-GS showed slightly higher power than the Global Tests. In the analysis of a real-world microarray dataset, the two Global Tests gave markedly different results, compared to SAM-GS, in identifying pathways whose gene expressions are associated with p53 mutation in cancer cell lines. A proper standardization of gene expression variances is necessary for the two Global Tests in order to produce biologically sensible results. After the standardization, the three methods gave very similar biologically-sensible results, with slightly higher statistical significance given by SAM-GS. The three methods gave similar patterns of results in the analysis of the other two microarray datasets.

Conclusion
An appropriate standardization makes the performance of all three methods similar, given the use of permutation-based inference. SAM-GS tends to have slightly higher power in the lower α-level region (i.e. gene sets that are of the greatest interest). Global Test and ANCOVA Global Test have the important advantage of being able to analyze continuous and survival phenotypes and to adjust for covariates. A free Microsoft Excel Add-In to perform SAM-GS is available from http://www.ualberta.ca/~yyasui/homepage.html.
Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets
Authors: Grayson T Hilton , Ohms Stephen J , Brackenbury Therese D , Meaney Kate R , Peng Kaiman , Pittelkow Yvonne E , Wilson Susan R , Sandow Shaun L , Hill Caryl E 
Published: November 2007

Abstract

Background
Hypertension is a complex disease with many contributory genetic and environmental factors. We aimed to identify common targets for therapy by gene expression profiling of a resistance artery taken from animals representing two different models of hypertension. We studied gene expression and morphology of a saphenous artery branch in normotensive WKY rats, spontaneously hypertensive rats (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rats.

Results
Differential remodeling of arteries occurred in SHR and ACTH-treated rats, involving changes in both smooth muscle and endothelium. Increased expression of smooth muscle cell growth promoters and decreased expression of growth suppressors confirmed smooth muscle cell proliferation in SHR but not in ACTH. Differential gene expression between arteries from the two hypertensive models extended to the renin-angiotensin system, MAP kinase pathways, mitochondrial activity, lipid metabolism, extracellular matrix and calcium handling. In contrast, arteries from both hypertensive models exhibited significant increases in caveolin-1 expression and decreases in the regulators of G-protein signalling, Rgs2 and Rgs5. Increased protein expression of caveolin-1 and increased incidence of caveolae was found in both smooth muscle and endothelial cells of arteries from both hypertensive models.

Conclusion
We conclude that the majority of differences in gene expression found in the saphenous artery taken from rats with two different forms of hypertension reflect distinctive morphological and physiological alterations. However, changes in common to caveolin-1 expression and G protein signalling, through attenuation of Rgs2 and Rgs5, may contribute to hypertension through augmentation of vasoconstrictor pathways and provide potential targets for common drug development.
Identification and regulation of expression of a gene encoding a filamentous hemagglutinin-related protein in Bordetella holmesii
Authors: Link Stefanie , Schmitt Karin , Beier Dagmar , Gross Roy 
Published: November 2007

Abstract

Background

Bordetella holmesii is a human pathogen closely related to B. pertussis, the etiological agent of whooping cough. It is able to cause disease in immunocompromised patients, but also whooping cough-like symptoms in otherwise healthy individuals. However, virtually nothing was known so far about the underlying virulence mechanisms and previous attempts to identify virulence factors related to those of B. pertussis were not successful.

Results
By use of a PCR approach we were able to identify a B. holmesii gene encoding a protein with significant sequence similarities to the filamentous hemagglutinin (FHA) of B. avium and to a lesser extent to the FHA proteins of B. pertussis, B. parapertussis, and B. bronchiseptica. For these human and animal pathogens FHA is a crucial virulence factor required for successful colonization of the host. Interestingly, the B. holmesii protein shows a relatively high overall sequence similarity with the B. avium protein, while sequence conservation with the FHA proteins of the human and mammalian pathogens is quite limited and is most prominent in signal sequences required for their export to the cell surface. In the other Bordetellae expression of the fhaB gene encoding FHA was shown to be regulated by the master regulator of virulence, the BvgAS two-component system. Recently, we identified orthologs of BvgAS in B. holmesii, and here we show that this system also contributes to regulation of fhaB expression in B. holmesii. Accordingly, the purified BvgA response regulator of B. holmesii was shown to bind specifically in the upstream region of the fhaB promoter in vitro in a manner similar to that previously described for the BvgA protein of B. pertussis. Moreover, by deletion analysis of the fhaB promoter region we show that the BvgA binding sites are relevant for in vivo transcription from this promoter in B. holmesii.

Conclusion
The data reported here show that B. holmesii is endowed with a factor highly related to filamentous hemagglutinin (FHA), a prominent virulence factor of the well characterized pathogenic Bordetellae. We show that like in the other Bordetellae the virulence regulatory BvgAS system is also involved in the regulation of fhaB expression in B. holmesii. Taken together these data indicate that in contrast to previous notions B. holmesii may in fact make use of virulence mechanisms related to those described for the other Bordetellae.
Tuberous sclerosis preclinical studies: timing of treatment, combination of a rapamycin analog (CCI-779) and interferon-gamma, and comparison of rapamycin to CCI-779
Authors: Messina Michael P , Rauktys Aubrey , Lee Laifong , Dabora Sandra L 
Published: November 2007

AbstractBackgroundTuberous Sclerosis Complex (TSC) is an autosomal dominant hamartoma disorder with variable expression for which treatment options are limited. TSC is caused by a mutation in either theTSC1orTSC2genes, whose products, hamartin and tuberin, function as negative regulators in the highly-conserved mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin (also known as sirolimus), an mTOR inhibitor, has been shown to reduce disease severity in rodent models of TSC and is currently being evaluated in clinical trials in human populations. The cytokine interferon-gamma (IFN-γ) is also a potential therapeutic agent for TSC. A high-expressing IFN-γ allele has been associated with reduced disease severity in human TSC patients and it has been shown in mouse models that treatment with exogenous IFN-γ reduces disease severity.ResultsHere, we examine the effects of treatingTsc2+/-mice at different time points with a rapamycin analog (CCI-779) as a single agent or with a combination of CCI-779 and IFN-γ. We observed that administering a short course of CCI-779 or CCI-779 plus IFN-γ reduced the severity of kidney lesions if administered after such lesions develop. As long as treatment is given after lesions arise, altering the time period during which treatment was given did not significantly impact the effect of the treatment on disease severity. We did not observe a significant benefit of combination therapy relative to treatment with a rapamycin analog alone inTsc2+/-mice. We also compared timing of treatment and two mTOR inhibitors (rapamycin and CCI-779) in nude mice bearingTsc2-/-tumors.ConclusionPreventing the genesis of TSC-related kidney lesions inTsc2+/-mice is not an effective treatment strategy; rather, the presence of growing tumors appears to be the most important factor when determining an appropriate treatment schedule. Treatment with rapamycin was more effective in reducing tumor growth and improving survival in nude mice bearingTsc2-/-tumors and also resulted in higher rapamycin levels in blood, brain, and kidney tissue than treatment with an equal milligram dose of CCI-779. We anticipate these results will influence future preclinical and clinical trials for TSC.
Psychiatric assessment of suicide attempters in Japan: a pilot study at a critical emergency unit in an urban area
Authors: Yamada Tomoki , Kawanishi Chiaki , Hasegawa Hana , Sato Ryoko , Konishi Akiko , Kato Daiji , Furuno Taku , Kishida Ikuko , Odawara Toshinari , Sugiyama Mitsugi , Hirayasu Yoshio 
Published: November 2007

Abstract

Background
The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan.

Methods
Three hundred and twenty consecutive cases of attempted suicide who were admitted to an urban emergency department were interviewed, with the focus on psychosocial background and DSM-IV diagnosis. Moreover, they were divided into two groups according to the method of attempted suicide in terms of lethality, and the two groups were compared.

Results
Ninety-five percent of patients received a psychiatric diagnosis: 81% of subjects met the criteria for an axis I disorder. The most frequent diagnosis was mood disorder. The mean age was higher and living alone more common in the high-lethality group. Middle-aged men tended to have a higher prevalence of mood disorders.

Conclusion
This is the first large-scale study of cases of attempted suicide since the dramatic increase in suicides began in Japan. The identification and introduction of treatments for psychiatric disorders at emergency departments has been indicated to be important in suicide prevention.
Molecular dynamics simulation of human LOX-1 provides an explanation for the lack of OxLDL binding to the Trp150Ala mutant
Authors: Falconi Mattia , Biocca Silvia , Novelli Giuseppe , Desideri Alessandro 
Published: November 2007

Abstract

Background
Dimeric lectin-like oxidized low-density lipoprotein receptor-1 LOX-1 is the target receptor for oxidized low density lipoprotein in endothelial cells. In vivo assays revealed that in LOX-1 the basic spine arginine residues are important for binding, which is lost upon mutation of Trp150 with alanine. Molecular dynamics simulations of the wild-type LOX-1 and of the Trp150Ala mutant C-type lectin-like domains, have been carried out to gain insight into the severe inactivating effect.

Results
The mutation does not alter the dimer stability, but a different dynamical behaviour differentiates the two proteins. As described by the residues fluctuation, the dynamic cross correlation map and the principal component analysis in the wild-type the two monomers display a symmetrical motion that is not observed in the mutant.

Conclusion
The symmetrical motion of monomers is completely damped by the structural rearrangement caused by the Trp150Ala mutation. An improper dynamical coupling of the monomers and different fluctuations of the basic spine residues are observed, with a consequent altered binding affinity.
Atherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation
Authors: Hannawi Suad , Haluska Brian , Marwick Thomas H , Thomas Ranjeny 
Published: November 2007

AbstractRheumatoid arthritis (RA) patients have increased mortality and morbidity as a result of cardiovascular and cerebrovascular disease. What is not clear, however, is either how early accelerated atherosclerosis begins in RA or how soon risk factors must be rigorously controlled. Furthermore, given the strong relationship of vascular disease to RA mortality and of inflammation to the accelerated atherosclerosis associated with RA, it is important to evaluate indices that could serially and noninvasively quantify atherosclerotic disease in RA patients. The carotid intima-media thickness (cIMT) and plaque, measured by ultrasound, correlate closely with direct measurement of the local and systemic atherosclerotic burden. To investigate the presence of subclinical atherosclerosis in the early stages of RA, the cIMT and plaque were measured using carotid duplex scanning in 40 RA patients with disease duration < 12 months and in 40 control subjects matched for age, sex and established cardiovascular risk factors. Patients with RA had significantly higher average cIMT values and more plaque than the control group (cIMT 0.64 ± 0.13 mm versus 0.58 ± 0.09 mm, respectively; P = 0.03). In RA patients, the cIMT was predicted by age and C-reactive protein level at first presentation to the clinic (R2 = 0.64). C-reactive protein was associated with age of disease onset and history of smoking. Since inflammation has been shown to predate onset of clinical RA, the accelerated atherogenic process related to inflammation may precede RA symptom onset.
Variation in the PaO2/FiO2 ratio with FiO2: mathematical and experimental description, and clinical relevance
Authors: Karbing Dan S , Kjærgaard Søren , Smith Bram W , Espersen Kurt , Allerød Charlotte , Andreassen Steen , Rees Stephen E 
Published: November 2007

Abstract
Introduction
Previous studies have shown through theoretical analyses that the ratio of the partial pressure of oxygen in arterial blood (PaO2) to the inspired oxygen fraction (FiO2) varies with the FiO2 level. The aim of the present study was to evaluate the relevance of this variation both theoretically and experimentally using mathematical model simulations, comparing these ratio simulations with PaO2/FiO2 ratios measured in a range of different patients.

Methods
The study was designed as a retrospective study using data from 36 mechanically ventilated patients and 57 spontaneously breathing patients studied on one or more occasions. Patients were classified into four disease groups (normal, mild hypoxemia, acute lung injury and acute respiratory distress syndrome) according to their PaO2/FiO2 ratio. On each occasion the patients were studied using four to eight different FiO2 values, achieving arterial oxygen saturations in the range 85–100%. At each FiO2 level, measurements were taken of ventilation, of arterial acid–base and of oxygenation status. Two mathematical models were fitted to the data: a one-parameter 'effective shunt' model, and a two-parameter shunt and ventilation/perfusion model. These models and patient data were used to investigate the variation in the PaO2/FiO2 ratio with FiO2, and to quantify how many patients changed disease classification due to variation in the PaO2/FiO2 ratio. An F test was used to assess the statistical difference between the two models' fit to the data. A confusion matrix was used to quantify the number of patients changing disease classification.

Results
The two-parameter model gave a statistically better fit to patient data (P < 0.005). When using this model to simulate variation in the PaO2/FiO2 ratio, disease classification changed in 30% of the patients when changing the FiO2 level.

Conclusion
The PaO2/FiO2 ratio depends on both the FiO2 level and the arterial oxygen saturation level. As a minimum, the FiO2 level at which the PaO2/FiO2 ratio is measured should be defined when quantifying the effects of therapeutic interventions or when specifying diagnostic criteria for acute lung injury and acute respiratory distress syndrome. Alternatively, oxygenation problems could be described using parameters describing shunt and ventilation/perfusion mismatch.
Europe's Enron: Royal Ahold, N.V.
Authors: Knapp Michael C. , Knapp Carol A. 
Published: November 2007

Royal Ahold, N.V., is a large multinational company based in The Netherlands that was founded in 1887 by Albert Heijn. Three generations of the Heijn family oversaw the company's retail grocery business. In 1989, the company hired a professional management team. The new management team expanded Royal Ahold's operations by purchasing grocery chains around the globe, resulting in the company becoming the third largest food retailer in the world. In 2000, the company diversified into the wholesaling segment of the huge food industry when it purchased U.S. Foodservice, a large food wholesaler based in Columbia, Maryland.
Royal Ahold's professional management team established aggressive earnings and revenue goals for the company each year and pressured their subordinates to achieve those goals. An incentive compensation plan awarded large year-end bonuses to managers of operating units that met or surpassed their financial goals. Royal Ahold's decentralized operations, when coupled with the strong incentives to achieve unrealistic earnings and revenue goals, created an environment in which fraud often flourishes.
In early 2003, Royal Ahold's independent auditors suspended their fiscal 2002 audit of the company when they discovered numerous potential irregularities in the company's accounting records. Subsequent investigations documented that the company had improperly included the operating results of foreign joint ventures in its consolidated financial statements, had accounted improperly for initial acquisition costs related to several of those joint ventures, and had materially overstated “promotional allowances” due from company vendors. The disclosure of the massive accounting fraud resulted in criminal and civil lawsuits being filed against the company and its top executives in both Europe and the United States.
This case examines accounting, auditing, and control issues pertinent to multinational companies. In addition, the case examines recent controversies arising between and among international regulatory agencies and rule-making bodies within the accounting and auditing disciplines. Finally, the case illustrates important risk factors commonly associated with financial statement fraud.
Preapplication of Orthodontic Forces to the Donor Teeth Affects Periodontal Healing of Transplanted Teeth
Authors: Suzaki Yusuke , Matsumoto Yoshiro , Kanno Zuisei , Soma Kunimichi 
Published: November 2007

Abstract
Objective: To investigate how the preapplication of orthodontic forces to the donor teeth affects the periodontal healing after transplantation.
Materials and Methods: The orthodontic force (1.5 cN) was applied to the maxillary right molars of 6-week-old male Spraque-Dawley rats (n = 21) in the experimental side, and the left side of the same animals was used as the control. After 7 days, both right and left maxillary second molars were extracted or replanted. Periodontal conditions were evaluated in the histological specimens 7 days after applying orthodontic force (before and after extraction) and 14 days after replantation.
Results: The application of orthodontic force for 7 days significantly increased the periodontal ligament (PDL) space and also the width of the alveolar socket, which resulted in a rich attached PDL to the root surface of the extracted teeth. Significantly more root resorption was also detected in the control side without preapplication of orthodontic force 14 days after replantation. This root resorption might involve in the disruption of the PDL.
Conclusion: These results suggested that the preapplication of orthodontic force to the donor teeth increased the PDL width and eased the extraction, which might decrease root resorption after replantation.
An Epidemiological Study of Hyperdontia in American Blacks and Whites
Authors: Harris Edward F. , Clark Larkin L. 
Published: November 2007

AbstractObjective: To test the null hypothesis that American blacks do not have a higher frequency of extra permanent teeth than whites.Materials and Methods: Panoramic radiographs of adolescent orthodontic patients, either American whites (n = 1100) or American blacks (n = 600), were reviewed systematically.Results: The frequencies of supernumerary incisors, premolars, and molars were each significantly more common in blacks. While incisors are the most common extra teeth in whites (and extra molars are least common), just the opposite ranking occurs in blacks. Overall, the odds ratio was 8.8 (95% confidence limits = 3.9, 20.0), confirming that American blacks are significantly more likely (almost 9 times more likely) to possess extra permanent teeth than American whites.Conclusions: The hypothesis is rejected. Both the frequencies and the patterns of extra permanent teeth are significantly different in blacks and whites, suggesting different frequencies of the relevant (but unidentified) factors governing the developmental mechanisms that result in hyperdontia.
Orthopedic Treatment Outcomes in Class III Malocclusion
Authors: Toffol Laura De , Pavoni Chiara , Baccetti Tiziano , Franchi Lorenzo , Cozza Paola 
Published: November 2007

Abstract
Objective: To assess the scientific evidence on the effectiveness of early orthopedic treatment in Class III subjects.
Materials and Methods: A literature survey was performed by applying the Medline database (Entrez PubMed). The survey covered the period from January 1966 to December 2005 and used the Medical Subject Headings (MeSH). The following study types that reported data on the effects of Class III treatment with orthopedic appliances (facial mask, chincup, FR-3) on intermaxillary sagittal and vertical relationships were included: randomized clinical trials (RCTs), and prospective and retrospective longitudinal controlled clinical trials (CCTs) with untreated Class III controls.
Results: The search strategy resulted in 536 articles. After selection according to criteria for inclusion and exclusion, 19 articles qualified for the final review analysis. One RCT and 18 CCTs were retrieved.
Conclusion: The quality standard of the retrieved investigations ranged from low (four studies) to medium/high (five studies). Data derived from medium/high quality research described over 75% of success of orthopedic treatment of Class III malocclusion (RME and facial mask therapy) at a follow-up observation 5 years after the end of orthopedic treatment.