bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is a Pattern of Increasing Biomarker Concentrations Important for Long-Term Risk Stratification in Acute Coronary Syndrome Patients Presenting Early after the Onset of Symptoms?
Authors: Kavsak Peter A , Newman Alice M , Ko Dennis T , Palomaki Glenn E , Lustig Viliam , MacRae Andrew R , Jaffe Allan S 
Published: March 2008

Abstract
Background: Guidelines for treatment of acute coronary syndrome (ACS) recommend observing a rise or fall in cardiac troponin (cTn) concentrations for assessing acute injury. It is unknown whether a rising pattern presages a more adverse long-term prognosis than elevations that do not change. The present study assessed whether a rising pattern of cardiac biomarkers was more prognostic than simple elevations.
Methods: We measured N-terminal pro-brain natriuretic peptide (NT-proBNP) (Roche), cTnT (Roche) and cTnI (Beckman Coulter) in 212 ACS patients. These biomarkers were measured in coincident EDTA and heparin plasma samples available from at least 2 different time points, an early first specimen obtained a median of 2 hours after onset of symptoms, interquartile range (IQR) 2–4 hours, and a later second specimen obtained at 9 hours, IQR 9–9 hours. The cTn concentration in the second specimen was used to classify myocardial necrosis (cTnI &gt;0.04 ug/L; cTnT &gt;0.01 ug/L). Outcomes [death, myocardial infarction (MI), heart failure (HF)] were obtained &gt;8 years after the initial presentation. For patients with myocardial necrosis and a cTn concentration ratio (second/first measured concentrations) ≥1.00, the concentration ratios and the absolute concentrations in the second specimen were used to assess prognosis after 4 years.
Results: In myocardial necrosis, the relative change (cTn2/cTn1) was greater for cTnI than for cTnT (P &lt;0.01), whereas the relative change in NT-proBNP was the same regardless of which troponin was used to classify necrosis (P = 0.71). The concentration ratio for cTnI, cTnT, and NT-proBNP was not useful for risk stratification (i.e., death/MI/HF; P ≥0.15).
Conclusions: A rise in cardiac troponin or NT-proBNP concentration in ACS patients presenting early after onset of pain is not helpful for long-term prognosis.
Increased Plasma Concentrations of Soluble ST2 are Predictive for 1-Year Mortality in Patients with Acute Destabilized Heart Failure
Authors: Mueller Thomas , Dieplinger Benjamin , Gegenhuber Alfons , Poelz Werner , Pacher Richard , Haltmayer Meinhard 
Published: March 2008

Abstract
Background: The soluble isoform of the interleukin-1 receptor family member ST2 (sST2) has been implicated in heart failure. The aim of the present study was to evaluate the capability of sST2 as a prognostic marker in patients with acute destabilized heart failure.
Methods: sST2 plasma concentrations were obtained in 137 patients with acute destabilized heart failure attending the emergency department of a tertiary care hospital. The endpoint was defined as all-cause mortality, and the study participants were followed up for 365 days.
Results: Of the 137 patients enrolled, 41 died and 96 survived during follow-up. At baseline the median sST2 plasma concentration was significantly higher in the patients who died than in those who survived (870 vs 342 ng/L, P &lt;0.001). Kaplan-Meier curve analyses demonstrated that the risk ratios for mortality were 2.45 (95% CI, 0.88–6.31; P = 0.086) and 6.63 (95% CI, 2.55–10.89; P &lt;0.001) in the second tercile (sST2, 300–700 ng/L; 11 deaths vs 34 survivors) and third tercile (sST2, &gt;700 ng/L; 25 deaths vs 21 survivors) of sST2 plasma concentrations compared with the first tercile (sST2, ≤300 ng/L; 5 deaths vs 41 survivors). In multivariable Cox proportional-hazards regression analyses, an sST2 plasma concentration in the upper tercile was a strong and independent predictor of all-cause mortality.
Conclusions: Increased sST2 concentrations determined in plasma samples drawn from patients with acute destabilized heart failure at their initial presentation indicate increased risk of future mortality. Increased sST2 plasma concentrations are independently and strongly associated with one-year all-cause mortality in these patients.
Multiplexed Assays for Detection of Mutations in PIK3CA
Authors: Board Ruth E , Thelwell Nicola J , Ravetto Paul F , Little Stephen , Ranson Malcolm , Dive Caroline , Hughes Andrew , Whitcombe David 
Published: March 2008

Abstract
Background: Mutations in the PIK3CA gene (phosphoinositide-3-kinase, catalytic, alpha polypeptide) have recently been described in a number of cancers, and their detection is currently limited because of the low sensitivity of conventional sequencing techniques.
Methods: We combined Amplification Refractory Mutation System (ARMS™; AstraZeneca) allele-specific PCR and Scorpions™ (DxS) to develop assays for tumor-borne PIK3CA mutations and used real-time PCR to develop high-throughput multiplexed assays for the most commonly reported PIK3CA mutants (H1047L, H1047R, E542K, E545K).
Results: These assays were more sensitive than sequencing and could detect 5 copies of mutant DNA in proportions as low as 0.1% of the total DNA. We assayed DNA extracted from human tumors and detected PIK3CA mutation frequencies of 10.2% in colorectal cancer, 38.7% in breast cancer, 1.9% in lung cancer, and 2.9% in melanoma. In contrast, sequencing detected only 53% of the mutations detected by our assay.
Conclusions: Multiplexed assays, which can easily be applied to clinical samples, have been developed for the detection of PIK3CA mutations.
CXCR4+/FLK-1+ Biomarkers Select a Cardiopoietic Lineage from Embryonic Stem Cells
Authors: Nelson Timothy J. , Faustino Randolph S. , Chiriac Anca , Crespo-Diaz Ruben , Behfar Atta , Terzic Andre 
Published: March 2008

Abstract
Pluripotent stem cells demonstrate an inherent propensity for unrestricted multi-lineage differentiation. Translation into regenerative applications requires identification and isolation of tissue-specified progenitor cells. From a comprehensive pool of 11,272 quality-filtered genes, profiling embryonic stem cells at discrete stages of cardiopoiesis revealed 736 transcripts encoding membrane-associated proteins, where 306 were specifically upregulated with cardiogenic differentiation. Bioinformatic dissection of exposed surface biomarkers prioritized the chemokine receptor cluster as the most significantly over-represented gene receptor family during pre cardiac induction, with CXCR4 uniquely associated with mesendoderm formation. CXCR4+ progenitors were sorted from the embryonic stem cell pool into mesoderm-restricted progeny according to co-expression with the early mesoderm marker Flk-1. In contrast to CXCR4−/Flk-1− cells, the CXCR4+/Flk-1+ subpopulation demonstrated overexpressed cardiac lineage transcription factors (Mef2C, Myocardin, Nkx2.5), whereas pluripotent genes (Oct4, Fgf4, Sox2) as well as neuroectoderm (Sox1) and endoderm alpha-fetoprotein markers were all depleted. In fact, the CXCR4+/Flk-1+ biomarker combination identified embryonic stem cell progeny significantly enriched with Mesp-1, GATA-4, and Tbx5, indicative of pre cardiac mesoderm and the primary heart field. Although the CXCR4+/Flk-1+ transcriptome shared 97% identity with the CXCR4−/Flk-1− counterpart, the 818 divergent gene set represented predominantly cardiovascular developmental functions and formed a primitive cardiac network. Differentiation of CXCR4+/Flk-1+ progenitors yielded nuclear translocation of myocardial transcription factors and robust sarcomerogenesis with nascent cardiac tissue demonstrating beating activity and calcium transients. Thus, the CXCR4/Flk-1 biomarker pair predicts the emergence of cardiogenic specification within a pluripotent stem cell pool, enabling targeted selection of cardiopoietic lineage.
Disclosure of potential conflicts of interest is found at the end of this article.
Androgenetic Embryonic Stem Cells Form Neural Progenitor Cells In Vivo and In Vitro
Authors: Dinger Timo C. , Eckardt Sigrid , Choi Soon Won , Camarero Guadelupe , Kurosaka Satoshi , Hornich Vroni , McLaughlin K. John , Müller Albrecht M. 
Published: March 2008

Abstract
Uniparental zygotes with two paternal (androgenetic [AG]) or two maternal (gynogenetic [GG]; parthenogenetic [PG]) genomes are not able to develop into viable offspring but can form blastocysts from which embryonic stem cells (ESCs) can be derived. Although some aspects of the in vitro and in vivo differentiation potential of PG and GG ESCs of several species have been studied, the developmental capacity of AG ESCs is much less clear. Here, we investigate the potential of murine AG ESCs to undergo neural differentiation. We observed that AG ESCs differentiate in vitro into pan-neural progenitor cells (pnPCs) that further give rise to cells that express neuronal- and astroglial-specific markers. Neural progeny of in vitro-differentiated AG ESCs exhibited fidelity of expression of six imprinted genes analyzed, with the exception of Ube3a. Bisulfite sequencing for two imprinting control regions suggested that pnPCs predominantly maintained their methylation pattern. Following blastocyst injection of AG and biparental (normal fertilized [N]) ESCs, we found widespread and evenly distributed contribution of ESC-derived cells in both AG and N chimeric early fetal brains. AG and N ESC-derived cells isolated from chimeric fetal brains by fluorescence-activated cell sorting exhibited similar neurosphere-initiating cell frequencies and neural multilineage differentiation potential. Our results indicate that AG ESC-derived neural progenitor/stem cells do not differ from N neural progenitor/stem cells in their self-renewal and neural multilineage differentiation potential.
Disclosure of potential conflicts of interest is found at the end of this article.
Copy Number Variant Analysis of Human Embryonic Stem Cells
Authors: Wu Hao , Kim Kevin J. , Mehta Kshama , Paxia Salvatore , Sundstrom Andrew , Anantharaman Thomas , Kuraishy Ali I. , Doan Tri , Ghosh Jayati , Pyle April D. , Clark Amander , Lowry William , Fan Guoping , Baxter Tim , Mishra Bud , Sun Yi , Teitell Michael A. 
Published: March 2008

Abstract
Differences between individual DNA sequences provide the basis for human genetic variability. Forms of genetic variation include single-nucleotide polymorphisms, insertions/duplications, deletions, and inversions/translocations. The genome of human embryonic stem cells (hESCs) has been characterized mainly by karyotyping and comparative genomic hybridization (CGH), techniques whose relatively low resolution at 2–10 megabases (Mb) cannot accurately determine most copy number variability, which is estimated to involve 10%–20% of the genome. In this brief technical study, we examined HSF1 and HSF6 hESCs using array-comparative genomic hybridization (aCGH) to determine copy number variants (CNVs) as a higher-resolution method for characterizing hESCs. Our approach used five samples for each hESC line and showed four consistent CNVs for HSF1 and five consistent CNVs for HSF6. These consistent CNVs included amplifications and deletions that ranged in size from 20 kilobases to 1.48 megabases, involved seven different chromosomes, were both shared and unique between hESCs, and were maintained during neuronal stem/progenitor cell differentiation or drug selection. Thirty HSF1 and 40 HSF6 less consistently scored but still highly significant candidate CNVs were also identified. Overall, aCGH provides a promising approach for uniquely identifying hESCs and their derivatives and highlights a potential genomic source for distinct differentiation and functional potentials that lower-resolution karyotype and CGH techniques could miss.
Disclosure of potential conflicts of interest is found at the end of this article.
Insulin-Like Growth Factor-Binding Protein 2 Secreted by a Tumorigenic Cell Line Supports Ex Vivo Expansion of Mouse Hematopoietic Stem Cells
Authors: Huynh HoangDinh , Iizuka Satoru , Kaba Megan , Kirak Oktay , Zheng Junke , Lodish Harvey F. , Zhang Cheng Cheng 
Published: March 2008

Abstract
Successful hematopoietic stem cell (HSC) transplantation is often limited by the numbers of HSCs, and robust methods to expand HSCs ex vivo are needed. We previously showed that angiopoietin-like proteins (Angptls), a group of growth factors isolated from a fetal liver HSC-supportive cell population, improved ex vivo expansion of HSCs. Here, we demonstrate that insulin-like growth factor-binding protein 2 (IGFBP2), secreted by a tumorigenic cell line, also enhanced ex vivo expansion of mouse HSCs. On the basis of these findings, we established a completely defined, serum-free culture system for mouse HSCs, containing SCF, thrombopoietin, fibroblast growth factor 1, Angptl3, and IGFBP2. As measured by competitive repopulation analyses, there was a 48-fold increase in numbers of long-term repopulating mouse HSCs after 21 days of culture. This is the first demonstration that IGFBP2 stimulates expansion or proliferation of murine stem cells. Our finding also suggests that certain cancer cells synthesize proteins that can stimulate HSC expansion.
Disclosure of potential conflicts of interest is found at the end of this article.
Sustained Long-Term Engraftment and Transgene Expression of Peripheral Blood CD34+ Cells Transduced with Third-Generation Lentiviral Vectors
Authors: Tesio Melania , Gammaitoni Loretta , Gunetti Monica , Leuci Valeria , Pignochino Ymera , Jordaney Noela , Capellero Sonia , Cammarata Cristina , Caione Luisa , Migliaretti Giuseppe , Fagioli Franca , Tabilio Antonio , Aglietta Massimo , Piacibello Wanda 
Published: March 2008

Abstract
As mobilized peripheral blood (MPB) represents an attractive cell source for gene therapy, we investigated the ability of third-generation lentiviral vectors (LVs) to transfer the enhanced green fluorescent protein gene into MPB CD34+ cells in culture conditions allowing expansion of transplantable human hematopoietic stem cells. To date, few studies have reported transduction of MPB cells with vesicular stomatitis virus G pseudotyped LVs. The critical issue remains whether primitive, hematopoietic repopulating cells have, indeed, been transduced. In vitro (5 weeks' culture in FLT3 ligand + thrombopoietin + stem cell factor + interleukin 6) and in vivo (serial transplantation in NOD/SCID mice) experiments show that MPB CD34+ cells can be effectively long-term transduced by LV and maintain their proliferation, self-renewal, and multilineage differentiation potentials. We show that expansion following transduction improves the engraftment of transduced MPB CD34+ (4.6-fold expansion of SCID repopulating cells by limiting dilution studies). We propose ex vivo expansion after transduction as an effective tool to improve gene therapy protocols with MPB.
Disclosure of potential conflicts of interest is found at the end of this article.
Client Perceptions of MAS Quality as Measured by a Marketing-Based Service Quality Model
Authors: Turner Leslie D. , Aldhizer George R. , Shank Matthew D. 
Published: March 2008

Management Advisory Services (MAS) are an increasingly important part of the service mix for CPA firms. The growth of MAS relative to audit has been phenomenal over the past two decades. However, little research has been conducted on MAS provided by CPA firms. The primary purpose of this study was to examine the determinants of MAS quality from the client's perspective. To achieve this objective, 305 controllers of U.S. companies responded to a questionnaire regarding MAS provided by CPA firms. The questionnaire was designed using determinants from marketing and audit literature. Using these client perception dimensions, two types of MAS engagements were compared: those with an increase in cost during the engagement, and those with no increase in cost.
Descriptive and statistical results indicate that a 13-item service quality scale significantly differentiates client perceptions of MAS quality. The results also reflect dimensions of service quality that are similar to existing marketing and auditing studies. In addition, in the presence of cost overruns and intentional underbidding, clients perceive lower MAS quality. The implications of these results for the accounting profession are discussed.
The Financial Statement Effects of Eliminating the Pooling-of-Interests Method of Acquisition Accounting
Authors: Ayers Benjamin C. , Lefanowicz Craig E. , Robinson John R. 
Published: March 2008

Accounting standard setters have become increasingly concerned with the perceived manipulation of financial statements afforded by the pooling-of-interests (pooling) method of accounting for corporate acquisitions. While different restrictions have been discussed, in September 1999 the Financial Accounting Standards Board (FASB) issued an Exposure Draft to eliminate the pooling method. This study provides a basis for evaluating restrictions on the pooling method by analyzing the financial statement effects on pooling acquisitions made by public corporations over the period 1992 through 1997. Using these acquisitions we (1) quantify the scope of the “pooling problem,” (2) estimate the financial statement repercussions of eliminating the pooling method, and (3) examine the effects of restricting pooling accounting to business combinations meeting various “merger of equals” restrictions.
While our analysis does not address whether restrictions on the pooling method will influence the nature or level of acquisition activity, the results indicate that the pooling method generates enormous amounts of unrecognized assets, across individual acquisitions, and in aggregate. In addition, our results suggest that recording and amortizing these assets generate significant balance sheet and income statement effects that vary with industry. Regarding restrictions on the pooling method, our analysis indicates that size restrictions would significantly reduce the number and value of pooling acquisitions and unrecognized assets generated by these acquisitions.
The Relation between Perceived Treatment Discrimination and Job Satisfaction among African-American Accounting Professionals
Authors: Moyes Glen D. , Williams Patricia A. , Quigley Behnaz Z. 
Published: March 2008

This study examines the relation between perceived treatment discrimination and level of job satisfaction among African-American accounting professionals. Results of a survey of accounting graduates of a Historically and Predominantly Black University (HPBU) suggest a significant relation between these two factors. Unstructured interviews with African-American partners and managers in major accounting firms further support this finding. We conclude that although the profession actively recruits African-Americans, once inside the firm there continues to be diversity issues that need to be addressed. Not unexpectedly, survey results indicate that the majority of respondents who are most dissatisfied do not intend to remain in the profession.
Evidence from the study also suggests a positive relation between percentage of African-Americans in the firm and job satisfaction. In addition, written comments from respondents and interviews with African-American practitioners indicate that ethnicity remains an issue in the workplace. Accounting firms are attempting to address this issue through mentoring and diversity training.
Does AICPA Accreditation of Nonaudit Services Add Value? The Case of Personal Financial Planning
Authors: Mauldin D. Shawn , Wilder Mark , Stocks Morris H. 
Published: March 2008

The AICPA has taken the position that accreditation of CPAs in specific areas of practice is an important aspect of repositioning the CPA profession for the future. The AICPA currently offers two designations exclusively to CPAs, one of which is the Personal Financial Specialist (PFS) designation. However, the issue of accrediting CPAs by granting official AICPA designations is a complex and highly debated issue with opposing sides having compelling arguments supporting their positions.
CPAs and other professionals specializing in personal financial planning have opportunities to obtain designations other than the PFS. This paper examines the relative value of these alternative options for financial planners. Specifically, the research was designed to examine the differential effects of alternative financial-planning accreditations on users' perceptions. These perceptions relate to various professional attributes of a financial planner such as their knowledge and expertise, objectivity, and level of trust and ethics possessed. In addition, these perceptions relate to fees charged and the influence that the designation has on the public's choice of a financial planner.
Our results indicate that the CPA designation used in conjunction with the PFS designation is generally perceived to signal a higher level of professional attributes than the other designations examined in the study. In addition, a CPA with a PFS designation has a significantly greater influence on the public's choice of a financial planner than do the other designations. These results suggest that important benefits may accrue to CPAs from holding the PFS specialty accreditation.
The Economic Implications of Proposed Changes in the Accounting for Nuclear Decommissioning Costs
Authors: Boatsman James R. , Khurana Inder K. , Loudder Martha L. 
Published: March 2008

This paper analyzes the accounting effects of the proposed standard Accounting for Obligations Associated with the Retirement of Long-Lived Assets, and considers the economic effects of accounting data in electric utility rate-making. Specifically, we model the financial statement with respect to nuclear decommissioning costs and posit several likely scenarios for the economic implications for the affected firms, their electric consumers, and the rate regulators. The model reveals that the sign of the equity adjustment at adoption and the change in ongoing expense will depend on (1) the age of the plant, and (2) the ratio of the current cost estimate used to compute depreciation under the current practice and the estimated future decommissioning cost. When the model is applied to firms with nuclear plants, we find that the financial statement effects at adoption will be substantial for many firms, and that the ongoing effects of the standard will be to increase the reported expenses of decommissioning substantially.
These findings are of interest for three reasons: first, contrary to our data, many of the firms analyzed have stated in their annual reports that the adoption effects of the proposed standard will be immaterial; second, the standard may have a deleterious effect on established regulatory rate-making relationships by changing the basis for consumer rates; and third, the analysis suggests that some firms will be faced with either requesting rate increases or jeopardizing their eligibility for special regulatory accounting treatment. Any of these outcomes create potentially severe problems in an industry on the brink of monumental economic and structural change, that is, the transition from a regulated monopoly to competition.