bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.
Authors: Colombo-Benkmann Mario , Li Zhenpeng , Riemann Burkhard , Hengst Karin , Herbst Hermann , Keuser Roger , Groß Ute , Rondot Susanne , Raue Friedhelm , Senninger Norbert , Pützer Brigitte M , Frank-Raue Karin 
Published: April 2008

ContextFor rare and novelRETmutations associated with hereditary medullary thyroid carcinoma (MTC), clinical and functional studies are needed to classify theRETmutation into one of the three clinical risk groups.ObjectiveWe analyzed proliferative properties and clinical implications associated with theRETprotooncogene transmembrane domain mutation S649L.DesignThe transforming potential and mitogenic properties of S649L mutation were investigated clinically and by evaluating kinase activity, cell proliferation, and colony formation.PatientsFifteen individuals from five kindreds were identified as carriers of aRETprotooncogene mutation in exon 11 codon 649 (TCGSer→TTGLeu). In two out of five index patients, a secondRETmutation (C634W or V804L) was detected.ResultsEight gene carriers were operated on. Histology revealed MTC and C-cell hyperplasia in three index and three screening patients respectively. In all other gene carriers (aged 41–64 years), calcitonin levels were in the normal range, and pentagastrin-stimulated calcitonin levels were <100 pg/ml. Therefore, thyroidectomy had not yet been performed. In one index patient carrying the S649L mutation, hyperparathyroidism was confirmed histologically.RETS649L-expressing NIH3T3 cells exhibited a clear increase of phosphotyrosine and proliferation rate when compared with parental NIH3T3 cells but a significantly lower kinase activity and cell growth rate when compared withRETC634R-expressing cells. When compared withRETC634R, the S649L mutant showed moderate transforming potential with small-sized colonies.ConclusionsOur clinical and in vitro findings indicate that the transmembraneRETS649L mutation is associated with late-onset non-aggressive disease. Recommendations for prophylactic thyroidectomy should be individualized depending on stimulated calcitonin levels.
Centrally located body fat is related to appetitive hormones in healthy postmenopausal women.
Authors: Ritland Laura M , Alekel D Lee , Matvienko Oksana A , Hanson Kathy B , Stewart Jeanne W , Hanson Laura N , Reddy Manju B , Van Loan Marta D , Genschel Ulrike 
Published: April 2008

ObjectiveBody composition and energy homeostasis are thought to affect the appetitive hormones: adiponectin, leptin, insulin, and ghrelin. This study examined whether centrally located fat and/or overall adiposity were related to these appetitive hormones in healthy postmenopausal women.DesignOverall and regional body composition was assessed by dual-energy X ray absorptiometry in relation to plasma adiponectin, serum leptin, serum insulin, and plasma ghrelin in 242 postmenopausal women.ResultsRegression analyses revealed that the androidal-to-gynoidal fat mass ratio (18.0%), age (3.2%), and white blood cell count (1.8%) accounted for 28% of the variability in adiponectin (F=22.2;P<0.0001); androidal (waist+hip) fat mass (66.0%), androidal fat mass2(6.2%), whole-body lean mass (2.2%), and age (0.8%) accounted for 69% of the variability in leptin (F=102.5;P<0.0001). Regression analyses revealed that sagittal abdominal diameter (8.4%), glucose (5.4%), white blood cell count (2.6%), and dietary ω-3 fatty acids (2.0%) accounted for 32% of the variability in insulin (F=20.8;P<0.0001); waist circumference (12.7%), hip lean mass (2.0%), and white blood cell count (1.9%) accounted for 26% of the variability in ghrelin (F=20.7;P<0.0001). Our results indicated that centralized fat mass was the primary contributor to these appetitive hormones in healthy postmenopausal women.ConclusionSince central adiposity in postmenopausal women was related to appetitive hormones, minimizing weight gain during the menopausal transition may optimize appetitive hormones, thereby facilitating appetite control and weight maintenance.
Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.
Authors: Chakhtoura Zeina , Bachelot Anne , Samara-Boustani Dinane , Ruiz Jean-Charles , Donadille Bruno , Dulon Jérôme , Christin-Maître Sophie , Bouvattier Claire , Raux-Demay Marie-Charles , Bouchard Philippe , Carel Jean-Claude , Leger Juliane , Kuttenn Frédérique , Polak Michel , Touraine Philippe 
Published: April 2008

ObjectiveIt remains controversial whether long-term glucocorticoids are charged of bone demineralization in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The aim of this study was to know whether cumulative glucocorticoid dose from the diagnosis in childhood to adulthood in patients with CAH had a negative impact on bone mineral density (BMD).DesignThis was a retrospective study.MethodsThirty-eight adult patients with classical and non-classical CAH were included. BMD was measured in the lumbar spine and femoral neck. Total cumulative glucocorticoid (TCG) and total average glucocorticoid (TAG) doses were calculated from pediatric and adult files.ResultsWe showed a difference between final and target heights (−0.82±0.92 s.d. for women and −1.31±0.84 s.d. for men; P<0.001). Seventeen patients (44.7%) had bone demineralization (35.7% of women and 70% of men). The 28 women had higher BMD than the 10 men for lumbar (−0.26±1.20 vs −1.25±1.33 s.d.; P=0.02) and femoral T-scores (0.21±1.30 s.d. versus −1.08±1.10 s.d.; P=0.007). In the salt-wasting group, women were almost significantly endowed with a better BMD than men (P=0.053). We found negative effects of TCG, TAG on lumbar (P<0.001, P=0.002) and femoral T-scores (P=0.006, P<0.001), predominantly during puberty. BMI was protective on BMD (P=0.006).ConclusionThe TCG is an important factor especially during puberty for a bone demineralization in patients with 21-hydroxylase deficiency. The glucocorticoid treatment should be adapted particularly at this life period and preventive measures should be discussed in order to limit this effect.
Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.
Authors: Heemstra Karen A , van der Deure Wendy M , Peeters Robin P , Hamdy Neveen A , Stokkel Marcel P , Corssmit Eleonora P , Romijn Johannes A , Visser Theo J , Smit Johannes W 
Published: April 2008

ObjectiveIt has been proposed that TSH has thyroid hormone-independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for triiodothyronine (T3), free thyroxine (FT4), and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSH receptor (TSHR)-Asp727Glu polymorphism to these relationships.DesignWe performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma.MethodsWe measured BMD of the femoral neck and lumbar spine. FT4, T3, TSH, bone-specific alkaline phosphatase, procollagen type 1 aminoterminal propeptide levels, C-cross-linking terminal telopeptide of type I collagen, and urinary N-telopeptide of collagen cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay.ResultsWe found a significant, inverse correlation between serum TSH levels and indicators of bone turnover, which was independent of serum FT4and T3levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was, however, no longer significant after adjusting for body mass index.ConclusionWe conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed.
Impact of Myocardial Infarct Proteins and Oscillating Pressure on the Differentiation of Mesenchymal Stem Cells: Effect of Acute Myocardial Infarction on Stem Cell Differentiation
Authors: Chang Sung-A , Lee Eun Ju , Kang Hyun-Jae , Zhang Shu-Ying , Kim Ji-Hyun , Li Lian , Youn Seock-Won , Lee Choon-Soo , Kim Keum-Hyun , Won Joo-Yun , Sohn Jong-Woo , Park Kyung-Woo , Cho Hyun-Jai , Yang Sung-Eun , Oh Won Il , Yang Yoon Sun , Ho Won-Kyung , Park Young-Bae , Kim Hyo-Soo 
Published: April 2008

Abstract
Stem cell transplantation in acute myocardial infarction (AMI) has emerged as a promising therapeutic option. We evaluated the impact of AMI on mesenchymal stem cell (MSC) differentiation into cardiomyocyte lineage. Cord blood-derived human MSCs were exposed to in vitro conditions simulating in vivo environments of the beating heart with acute ischemia, as follows: (a) myocardial proteins or serum obtained from sham-operated rats, and (b) myocardial proteins or serum from AMI rats, with or without application of oscillating pressure. Expression of cardiac-specific markers on MSCs was greatly induced by the infarcted myocardial proteins, compared with the normal proteins. It was also induced by application of oscillating pressure to MSCs. Treatment of MSCs with infarcted myocardial proteins and oscillating pressure greatly augmented expression of cardiac-specific genes. Such expression was blocked by inhibitor of transforming growth factor β1 (TGF-β1) or bone morphogenetic protein-2 (BMP-2). In vitro cellular and electrophysiologic experiments showed that these differentiated MSCs expressing cardiomyocyte-specific markers were able to make a coupling with cardiomyocytes but not to selfbeat. The pathophysiologic significance of in vitro results was confirmed using the rat AMI model. The protein amount of TGF-β1 and BMP-2 in myocardium of AMI was significantly higher than that in normal myocardium. When MSCs were transplanted to the heart and analyzed 8 weeks later, they expressed cardiomyocyte-specific markers, leading to improved cardiac function. These in vitro and in vivo results suggest that infarct-related biological and physical factors in AMI induce commitment of MSCs to cardiomyocyte-like cells through TGF-β/BMP-2 pathways.
Disclosure of potential conflicts of interest is found at the end of this article.
Polycomb Repressive Complex 2 Is Dispensable for Maintenance of Embryonic Stem Cell Pluripotency
Authors: Chamberlain Stormy J. , Yee Della , Magnuson Terry 
Published: April 2008

Abstract
Polycomb repressive complex 2 (PRC2) methylates histone H3 tails at lysine 27 and is essential for embryonic development. The three core components of PRC2, Eed, Ezh2, and Suz12, are also highly expressed in embryonic stem (ES) cells, where they are postulated to repress developmental regulators and thereby prevent differentiation to maintain the pluripotent state. We performed gene expression and chimera analyses on low- and high-passage Eednull ES cells to determine whether PRC2 is required for the maintenance of pluripotency. We report here that although developmental regulators are overexpressed in Eednull ES cells, both low- and high-passage cells are functionally pluripotent. We hypothesize that they are pluripotent because they maintain expression of critical pluripotency factors. Given that EED is required for stability of EZH2, the catalytic subunit of the complex, these data suggest that PRC2 is not necessary for the maintenance of the pluripotent state in ES cells. We propose a positive-only model of embryonic stem cell maintenance, where positive regulation of pluripotency factors is sufficient to mediate stem cell pluripotency.
Disclosure of potential conflicts of interest is found at the end of this article.
An Analysis of the Relative Power Characteristics of Analytical Procedures
Authors: Chen Yining , Leitch Robert A. 
Published: April 2008

The overall objective of this study is to analyze the relative effectiveness and efficiency of several analytical procedures. To accomplish this, we test the power characteristics of analytical procedures in simulated business and economic environments. The analytical procedures we test include the Martingale, Census X-11, ARIMA, and stepwise regression expectation models. The power characteristics are measured by both positive and negative testing approaches, with and without accompanying tests of details, and with simple and dispersed error seeding patterns.
The results suggest that the stepwise regression model outperforms X-11, ARIMA, and Martingale models in discriminating between the decision risks at zero and material error for both testing approaches. All models seem to perform better in terms of the aggregate slope for higher degrees of economic stability. The stepwise procedure either outperforms the other procedures for the positive approach or comes close to doing so for the negative approach in terms of reducing the risk of incorrectly concluding that an account is not in material error when it is indeed in material error.
The stepwise model combined with the negative approach exhibits the lowest risk of rejecting an account that is not materially misstated. The negative approach of testing, compared to the positive approach, seems to offer the auditor superior protection against not detecting a material error, while minimizing excessive audit work by correctly concluding that an account is not in material error if nonmaterial errors are present. When applied in conjunction with tests of details as well as when different error dispersion patterns are considered, all four analytical procedure models provide about the same level of assurance (effectiveness) in detecting material errors. The stepwise model, however, is the most efficient one in both of these scenarios in saving excessive audit work.
A Decision Aid for Assessing the Likelihood of Fraudulent Financial Reporting
Authors: Bell Timothy B. , Carcello Joseph V. 
Published: April 2008

The auditor's responsibility for detecting fraudulent financial reporting is of continuing importance to both the profession and society. The Auditing Standards Board has recently issued SAS No. 82, Consideration of Fraud in a Financial Statement Audit, which makes the auditor's responsibility for the detection of material fraud more explicit without increasing the level of responsibility.
Using a sample of 77 fraud engagements and 305 nonfraud engagements, we develop and test a logistic regression model that estimates the likelihood of fraudulent financial reporting for an audit client, conditioned on the presence or absence of several fraud-risk factors. The significant risk factors included in the final model are: weak internal control environment, rapid company growth, inadequate or inconsistent relative profitability, management places undue emphasis on meeting earnings projections, management lied to the auditors or was overly evasive, the ownership status (public vs. private) of the entity, and an interaction term between a weak control environment and an aggressive management attitude toward financial reporting. The logistic model was significantly more accurate than practicing auditors in assessing risk for the 77 fraud observations. There was not a significant difference between model assessments and those of practicing auditors for the sample of nonfraud cases.
These findings suggest that a relatively simple decision aid performs quite well in differentiating between fraud and nonfraud observations. Practitioners might consider using this model, or one developed using a similar procedure, in fulfilling the SAS No. 82 requirement to “assess the risk of material misstatement of the financial statements due to fraud.”
Evidence on the Effect of Financial and Nonfinancial Trends on Analytical Review
Authors: Cohen Jeffrey R. , Krishnamoorthy Ganesh , Wright Arnold M. 
Published: April 2008

In conducting analytical procedures, auditors may use both financial information and nonfinancial information such as general economic conditions, technological changes in the client's industry, and new products from competitors. While there has been extensive research on the impact of financial information (e.g., Biggs and Wild 1985), there has been little consideration of how auditors use nonfinancial information. Further, little is known about how these forms of evidence are integrated.
The purpose of this study is to examine the relative consideration of financial and nonfinancial trends in two analytical review tasks: establishing the level of audit scope and generating hypotheses. As noted by Koonce (1993), prior studies have examined analytical review phases separately and, thus, have contributed to our understanding in a piecemeal fashion.
Seventy-eight auditors participated in an experiment with the independent variables reflecting financial trend (stable or decline) and nonfinancial trend (stable or decline). Increased risk and auditor training associated with financial information suggest that greater focus will be placed on financial rather than nonfinancial information.
The results suggest that auditors place heavier reliance on financial trends than nonfinancial trends in establishing the overall level of audit scope. Further, auditors apparently utilize nonfinancial information as corroborating evidence. The results also reveal that a greater number of hypotheses are generated when financial or nonfinancial trends signal a decline than when they signal a stable environment, and the greatest number of hypotheses are generated when both financial and nonfinancial information indicate a decline.
The findings also indicate that a greater number of hypotheses are generated as a result of financial information than nonfinancial information. Further, results reveal that a large and essentially equal number of hypotheses were generated when either financial or nonfinancial trends indicate a decline, suggesting that auditors consider nonfinancial information in the hypothesis-generation stage of the analytical review process. Thus, if we look at the audit-scope phase in isolation it appears that auditors may not sufficiently consider nonfinancial information. However, in the hypothesis-generation stage, both financial and nonfinancial trends affected the quantity of hypotheses generated. Thus, it is important for researchers to look at multiple stages of the analytical review process concurrently.
Auditors' Consideration of Corporate Governance and Management Control Philosophy in Preplanning and Planning Judgments
Authors: Cohen Jeffrey R. , Hanno Dennis M. 
Published: April 2008

The professional literature (e.g., COSO 1992, POB 1993), recent auditing standards (e.g., SAS Nos. 78 and 82), and prior research (e.g., Beasley 1996; Beasley et al. 1999; Dechow et al. 1996) highlight the importance of corporate governance and management control philosophy in ensuring the integrity of the financial-reporting process. We examine the link between these two macro-level factors and both preplanning (e.g., client acceptance, business risk judgments) and planning judgments (e.g., extent and timing of testing).
Ninety-six auditors evaluated a hypothetical client with corporate governance and management control philosophy characteristics that were either strong or weak. More experienced auditors performed preplanning (client acceptance) judgments, while the remaining auditors performed planning judgments related to the extent and timing of substantive testing. As predicted, management control philosophy and the governance structure did affect the preplanning and planning judgments, with a stronger effect observed for management control philosophy. While the results for judgments related to the extent of testing were consistent with professional guidance, auditors lacked consensus in judging the effect on the timing of tests. The results provide insight into the effect of two important elements of the control environment on preplanning and planning judgments and could prove useful in the development of work papers and risk assessment models.
An Examination of Audit Report Lag for Banks: A Panel Data Approach
Authors: Henderson B. Charlene , Kaplan Steven E. 
Published: April 2008

This study investigates the determinants of audit report lag (ARL) for a sample of banks. Researchers have been interested in the determinants of ARL, in part, because it impacts the timeliness of public disclosures. However, prior ARL research has relied exclusively on regression analysis of cross-sectional samples of companies from many industries. In addition to focusing exclusively on banks, panel data analysis is introduced and compared with cross-sectional analysis to demonstrate its power in dynamic settings and its potential to improve estimation.
Results reveal important differences between cross-sectional analysis and panel data analysis. First, bank size is negatively related to ARL in cross-section but positively related to ARL using panel data analysis. The cross-sectional size estimate is subject to omitted variables bias, and furthermore, cross-sectional analysis fails to capture variation in size over time in relation to ARL. Panel data analysis both accounts for omitted variables and captures the dynamics of the relationship between size and ARL. As well, the panel data model's explanatory power far exceeds that of the cross-sectional model. This is primarily due to the panel model's use of firm-specific intercepts that both capture the role of reporting tradition and eliminate heterogeneity bias. Thus, panel data analysis proves to be a powerful tool in the analysis of ARL.
An Investigation of Multidimensional Knowledge Structure and Computer Auditor Performance
Authors: Curtis Mary B. , Viator Ralph E. 
Published: April 2008

This study assesses the internal control knowledge structure dimensions and antecedents, as well as the relationship between structure and performance, for a set of computer auditors. The study extends prior research in two ways. First, in an effort to investigate the impact of multiple knowledge structures on auditor performance, a multidimensional model is employed through the use of multidimensional scaling (MDS). An added benefit of this methodology is that it facilitates the evaluation of the extent of auditor knowledge structure. Second, a more complete understanding of the influence of experience and education on auditor performance is gained through investigating the role of knowledge structure as a mediator.
Results suggest that computer auditors employ both control objective and transaction flow structural dimensions simultaneously, as well as a third dimension not previously identified, which represents the degree of computerization of a particular procedure. Transaction flow was identified as the dominant structural dimension for most computer auditors.
Computer auditor knowledge structures were found to be associated with college education and prior computer information systems (CIS) work experience. The extent (weight) of auditors' control objective and transaction flow dimensions was related to their performance on an internal control review task. However, no significant interactions were found.