bluuebunny/crossref_metadata_2025_split huggingface dataset:
Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy
Authors: Kawaguchi Hidetoshi , El-Naggar Adel K. , Papadimitrakopoulou Vali , Ren Hening , Fan You-Hong , Feng Lei , Lee J. Jack , Kim Edward , Hong Waun Ki , Lippman Scott M. , Mao Li 
Published: January 2008

Purpose Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL. Patients and Methods Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed. Results Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information. Conclusion Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.
Individualized Prediction of Colon Cancer Recurrence Using a Nomogram
Authors: Weiser Martin R. , Landmann Ron G. , Kattan Michael W. , Gonen Mithat , Shia Jinru , Chou Joanne , Paty Philip B. , Guillem José G. , Temple Larissa K. , Schrag Deborah , Saltz Leonard B. , Wong W. Douglas 
Published: January 2008

Purpose Estimates of recurrence after curative colon cancer surgery are integral to patient care, forming the basis of cancer staging and treatment planning. The categoric staging system of the American Joint Committee on Cancer (AJCC) is commonly used to convey risk by grouping patients based on anatomic elements. Although easy to implement, there remains significant heterogeneity within each stage grouping. In the era of multimodality treatment, a more refined tool is needed to predict recurrence. Methods An institutional database of 1,320 patients with nonmetastatic colon cancer was used to develop a nomogram to estimate recurrence after curative surgery. Prognostic factors were assessed with multivariable analysis using Cox regression, whereas nonlinear continuous variables were modeled with cubic splines. The model was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve. Results The colon cancer recurrence nomogram predicted relapse with a concordance index of 0.77, improving on the stratification provided by either the AJCC fifth or sixth staging scheme. Factors in the model included patient age, tumor location, preoperative carcinoembryonic antigen, T stage, numbers of positive and negative lymph nodes, lymphovascular invasion, perineural invasion, and use of postoperative chemotherapy. Conclusion Using common clinicopathologic factors, the recurrence nomogram is better able to account for tumor and patient heterogeneity, thereby providing a more individualized outcome prognostication than that afforded by the AJCC categoric system. By identifying both the high- and low-risk patients within any particular stage, the nomogram is expected to aid in treatment planning and future trial design.
Restriction Site–Specific Methylation Studies of Imprinted Genes with Quantitative Real-Time PCR
Authors: Bruce Sara , Hannula-Jouppi Katariina , Lindgren Cecilia M , Lipsanen-Nyman Marita , Kere Juha 
Published: January 2008

Abstract
Background: Epigenetic studies, such as the measurement of DNA methylation, are important in the investigation of syndromes influenced by imprinted genes. Quick and accurate quantification of methylation at such genes can be of appreciable diagnostic aid.
Methods: We first digested genomic DNA with methylation-sensitive restriction enzymes and used DNA without digestion as a control and nonmethylated λ DNA as an internal control for digestion efficiency. We then performed quantitative real-time PCR analyses with 6 unique PCR assays to investigate 4 imprinting control regions on chromosomes 7 and 11 in individuals with uniparental disomy of chromosome 7 (UPD7) and in control individuals.
Results: Our validation of the method demonstrated both quantitative recovery and low methodologic imprecision. The imprinted loci on chromosome 7 behaved as expected in maternal UPD7 (100% methylation) and paternal UPD7 (&lt;10% methylation). In controls, the mean (SD) for percent methylation at 2 previously well-studied restriction sites were 46% (6%) for both H19 and KCNQ1OT1, a result consistent with the previously observed methylation rate of approximately 50%. The methylation percentages of all investigated imprinted loci were normally distributed, implying that the mean and SD can be used as a reference for screening methylation loss or gain.
Conclusion: The investigated loci are of particular importance for investigating the congenital Silver–Russell and Beckwith–Wiedemann syndromes; however, the method can also be applied to other imprinted regions. This method is easy to set up, has no PCR bias, requires small amounts of DNA, and can easily be applied to large patient populations for screening the loss or gain of methylation.
Systematic Search for Placental DNA-Methylation Markers on Chromosome 21: Toward a Maternal Plasma-Based Epigenetic Test for Fetal Trisomy 21
Authors: Chim Stephen S C , Jin Shengnan , Lee Tracy Y H , Lun Fiona M F , Lee Wing S , Chan Lisa Y S , Jin Yongjie , Yang Ningning , Tong Yu K , Leung Tak Y , Lau Tze K , Ding Chunming , Chiu Rossa W K , Lo Y M Dennis 
Published: January 2008

Abstract
Background: The presence of fetal DNA in maternal plasma represents a source of fetal genetic material for noninvasive prenatal diagnosis; however, the coexisting background maternal DNA complicates the analysis of aneuploidy in such fetal DNA. Recently, the SERPINB5 gene on chromosome 18 was shown to exhibit different DNA-methylation patterns in the placenta and maternal blood cells, and the allelic ratio for placenta-derived hypomethylated SERPINB5 in maternal plasma was further shown to be useful for noninvasive detection of fetal trisomy 18.
Methods: To develop a similar method for the noninvasive detection of trisomy 21, we used methylation-sensitive single nucleotide primer extension and/or bisulfite sequencing to systematically search 114 CpG islands (CGIs)—76% of the 149 CGIs on chromosome 21 identified by bioinformatic criteria—for differentially methylated DNA patterns. The methylation index (MI) of a CpG site was estimated as the proportion of molecules methylated at that site.
Results: We identified 22 CGIs which were shown to contain CpG sites that were either completely unmethylated (MI = 0.00) in maternal blood cells and methylated in the placenta (MI range, 0.22–0.65), or completely methylated (MI = 1.00) in maternal blood cells and hypomethylated in the placenta (MI range, 0.00–0.75). We detected, for the first time, placental DNA-methylation patterns on chromosome 21 in maternal plasma during pregnancy and observed their postpartum clearance.
Conclusion: Twenty-two (19%) of the 114 studied CGIs on chromosome 21 showed epigenetic differences between samples of placenta and maternal blood cells; these CGIs may provide a rich source of markers for noninvasive prenatal diagnosis.
Noninvasive Prenatal Diagnosis of Fetal Chromosomal Aneuploidies by Maternal Plasma Nucleic Acid Analysis
Authors: Dennis Lo Y M , Chiu Rossa W K 
Published: January 2008

Abstract
Background: The discovery of circulating cell-free fetal nucleic acids in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. The potential application of this technology for the noninvasive prenatal detection of fetal chromosomal aneuploidies is an aspect of this field that is being actively investigated. The main challenge of work in this area is the fact that cell-free fetal nucleic acids represent only a minor fraction of the total nucleic acids in maternal plasma.
Methods and Results: We performed a review of the literature, which revealed that investigators have applied methods based on the physical and molecular enrichment of fetal nucleic acid targets from maternal plasma. The former includes the use of size fractionation of plasma DNA and the use of the controversial formaldehyde treatment method. The latter has been achieved through the development of fetal epigenetic and fetal RNA markers. The aneuploidy status of the fetus has been explored through the use of allelic ratio analysis of plasma fetal epigenetic and RNA markers. Digital PCR has been shown to offer high precision for allelic ratio and relative chromosome dosage analyses.
Conclusions: After a decade of work, the theoretical and practical feasibility of prenatal fetal chromosomal aneuploidy detection by plasma nucleic acid analysis has been demonstrated in studies using small sample sets. Larger scale independent studies will be needed to validate these initial observations. If these larger scale studies prove successful, it is expected that with further development of new fetal DNA/RNA markers and new analytical methods, molecular noninvasive prenatal diagnosis of the major chromosomal aneuploidies could become a routine practice in the near future.
IGF-1: Analytik und Referenzbereiche / Measurement of IGF-1 and reference ranges
Authors: Spilcke-Liss Elisabeth , Friedrich Nele , Wallaschofski Henri 
Published: January 2008

Zusammenfassung
Der Insulin-ähnliche Wachstumsfaktor IGF-1 (insulin-like growth factor 1) ist der ausschlaggebende Faktor zur Beurteilung des Wachstumshormonhaushalts. Da der IGF-1-Spiegel zahlreichen Einflüssen wie z. B. dem Alter, Geschlecht, genetischen Faktoren, der Ernährung oder Erkrankungen ausgesetzt ist, ist es notwendig, exakte normative Daten als Grundlage für die Diagnostik und Therapiekontrolle bei Patienten mit Störungen der Wachstumshormonachse zu haben. Obwohl die bisher genutzten Referenzwerte anhand großer Kohorten gesunder Personen entwickelt wurden, zeigt die Abhängigkeit dieser Werte von den verwendeten Labormethoden, dass methodenspezifische Referenzwerte für IGF-1 erforderlich sind.
Neuartiger Lymphozyten-Transformations-Test (LTT-MELISA®) zum Nachweis einer Lyme-Borreliose / A novel lymphocyte transformation test (LTT-MELISA®) for Lyme borreliosis
Authors: Valentine-Thon Elizabeth , Ilsemann Karsten , Sandkamp Martin 
Published: January 2008

Zusammenfassung
Die Diagnose einer aktiven Lyme-Borreliose (LB) stellt immer noch eine Herausforderung bei klinisch nicht eindeutigen, serologisch nicht zuordnungsfähigen und PCR-negativen Patienten dar. Verschiedene Lymphozyten-Transformations-Tests (LTT) wurden zur Feststellung einer zellulären Reaktivität eingesetzt, deren klinische Anwendbarkeit jedoch erheblich durch den Einsatz ungenügend definierter Borrelien-Antigene und nichtstandardisierter LTT-Verfahren eingeschränkt war. In der vorliegenden Studie stellen wir die Entwicklung und klinische Relevanz eines neuen LTT unter Einsatz eines validierten Verfahrens (MELISA®) und der Verwendung definierter rekombinanter Borrelien-Antigene vor. Nach einem initialen Screening von 244 Patienten mit Verdacht auf eine Borrelien-Infektion bzw. -Erkrankung wurden vier aussagefähige rekombinante Antigene ausgewählt: OspC (Borrelia afzelii), p41-int 1 (Borrelia garinii), p41-int 2 (B. afzelii) und p100 (B. afzelii). Anschließend wurden 30 seronegative gesunde Probanden im LTT-MELISA® untersucht, um die Spezifität festzustellen, 68 Patienten parallel analysiert, um die Reproduzierbarkeit zu überprüfen, und 54 Lymphozyten-reaktive, symptomatische Patienten vor und nach Antibiotikatherapie getestet, um die klinische Relevanz des Tests zu evaluieren. Die Mehrzahl (86,2%), der im initialen Screening untersuchten und LTT-MELISA®-positiven Patienten (36,9%), waren seropositiv und zeigten Symptome einer aktiven LB. Die Spezifität betrug 96,7%, die Reproduzierbarkeit 92,6%. Nach Therapie zeigten die meisten Patienten (90,7%) keine persistierende oder eine erheblich reduzierte Lymphozyten-Reaktivität, welche mit einer klinischen Besserung einherging. Der vorgestellte neuartige LTT-MELISA® scheint mit aktiver LB zu korrelieren und dürfte diagnostische Relevanz in der Abklärung klinisch und serologisch nicht eindeutiger Fälle aufweisen.
Evaluating Sustainability Using Standard Approaches: The BEES Tool
Authors: Lippiatt Barbara C. 
Published: January 2008

Abstract
In support of the ASTM International, Symposium on Common Ground, Consensus Building and Continual Improvement, this paper describes the BEES (Building for Environmental and Economic Sustainability) software that integrates standard approaches for selecting cost-effective, environmentally-preferable building products. Version 4.0 of the Windows-based decision support software, aimed at designers, builders, and product manufacturers, includes actual environmental and economic performance data for over 230 building products across a range of functional applications. BEES measures the environmental performance of building products using the environmental life-cycle assessment approach specified in International Organization for Standardization (ISO) 14040 standards. All stages in the life of a product are analyzed: raw material acquisition, manufacture, transportation, installation, use, and waste management. Economic performance is measured using the ASTM International standard life-cycle cost method (E 917), which covers the costs of initial investment, replacement, operation, maintenance and repair, and disposal. Environmental and economic performance are combined into an overall performance measure using the ASTM standard for Multiattribute Decision Analysis (E 1765). For the entire BEES analysis, building products are defined and classified based on the ASTM standard classification for building elements known as UNIFORMAT II (E 1557).
Estimating the Per-Base-Pair Mutation Rate in the YeastSaccharomyces cerevisiae
Authors: Lang Gregory I , Murray Andrew W 
Published: January 2008

AbstractAlthough mutation rates are a key determinant of the rate of evolution they are difficult to measure precisely and global mutations rates (mutations per genome per generation) are often extrapolated from the per-base-pair mutation rate assuming that mutation rate is uniform across the genome. Using budding yeast, we describe an improved method for the accurate calculation of mutation rates based on the fluctuation assay. Our analysis suggests that the per-base-pair mutation rates at two genes differ significantly (3.80 × 10−10 at URA3 and 6.44 × 10−10 at CAN1) and we propose a definition for the effective target size of genes (the probability that a mutation inactivates the gene) that acknowledges that the mutation rate is nonuniform across the genome.
Determination of Mitochondrial Genetic Diversity in Mammals
Authors: Nabholz Benoit , Mauffrey Jean-François , Bazin Eric , Galtier Nicolas , Glemin Sylvain 
Published: January 2008

Abstract
Mitochondrial DNA (mtDNA) is one of the most popular population genetic markers. Its relevance as an indicator of population size and history has recently been questioned by several large-scale studies in animals reporting evidence for recurrent adaptive evolution, at least in invertebrates. Here we focus on mammals, a more restricted taxonomic group for which the issue of mtDNA near neutrality is crucial. By analyzing the distribution of mtDNA diversity across species and relating it to allozyme diversity, life-history traits, and taxonomy, we show that (i) mtDNA in mammals does not reject the nearly neutral model; (ii) mtDNA diversity, however, is unrelated to any of the 14 life-history and ecological variables that we analyzed, including body mass, geographic range, and The World Conservation Union (IUCN) categorization; (iii) mtDNA diversity is highly variable between mammalian orders and families; (iv) this taxonomic effect is most likely explained by variations of mutation rate between lineages. These results are indicative of a strong stochasticity of effective population size in mammalian species. They suggest that, even in the absence of selection, mtDNA genetic diversity is essentially unpredictable, knowing species biology, and probably uncorrelated to species abundance.
Naive Application of Permutation Testing Leads to Inflated Type I Error Rates
Authors: Churchill G A , Doerge R W 
Published: January 2008

AbstractFailure to account for family structure within populations or in complex mating designs via uninformed applications of permutation testing will lead to inflated type I error rates. Careful consideration of the design factors is essential since some situations allow several valid permutation strategies, and the choice that maximizes statistical power will not always be intuitive.
cin-4, a Gene With Homology to Topoisomerase II, Is Required for Centromere Resolution by Cohesin Removal From Sister Kinetochores During Mitosis
Authors: Stanvitch Gerald , Moore Landon L 
Published: January 2008

Abstract
The back-to-back geometry of sister kinetochores is essential in preventing loss or damage of chromosomes during mitosis. Kinetochore orientation is generated in part by a process of resolving kinetochores at the centromere (centromere resolution) prior to spindle interactions. Because few of the genes required for centromere resolution are known, we used Caenorhabditis elegans to screen for conditional mutants defective in orienting sister kinetochores during mitosis. C. elegans is ideal for such screens because its chromosomes are holocentric. Here we identified an essential gene, cin-4, required for centromere resolution and for removal of cohesin from sites near sister kinetochores during mitosis. Given that compromised cohesin function restores centromere resolution in the absence of cin-4, CIN-4 likely acts to remove cohesin from the CENP-A chromatin enabling centromere resolution. CIN-4 has a high amino acid identity to the catalytic domain of topoisomerase II, suggesting a partial gene duplication of the C. elegans topoisomerase II gene, top-2. Similar to CIN-4, TOP-2 is also required for centromere resolution; however, the loss of TOP-2 is phenotypically distinct from the loss of CIN-4, suggesting that CIN-4 and TOP-2 are topoisomerase II isoforms that perform separate essential functions in centromere structure and function.
An Accurate Model for Genetic Hitchhiking
Authors: Eriksson Anders , Fernström Pontus , Mehlig Bernhard , Sagitov Serik 
Published: January 2008

AbstractWe suggest a simple deterministic approximation for the growth of the favored-allele frequency during a selective sweep. Using this approximation we introduce an accurate model for genetic hitchhiking. Only when Ns &lt; 10 (N is the population size and s denotes the selection coefficient) are discrepancies between our approximation and direct numerical simulations of a Moran model notable. Our model describes the gene genealogies of a contiguous segment of neutral loci close to the selected one, and it does not assume that the selective sweep happens instantaneously. This enables us to compute SNP distributions on the neutral segment without bias.
Integrating Phylogenetic and Population Genetic Analyses of Multiple Loci to Test Species Divergence Hypotheses in Passerina Buntings
Authors: Carling Matt D , Brumfield Robb T 
Published: January 2008

Abstract
Phylogenetic and population genetic analyses of DNA sequence data from 10 nuclear loci were used to test species divergence hypotheses within Passerina buntings, with special focus on a strongly supported, but controversial, sister relationship between Passerina amoena and P. caerulea inferred from a previous mitochondrial study. Here, a maximum-likelihood analysis of a concatenated 10-locus data set, as well as minimize-deep-coalescences and maximum-likelihood analyses of the locus-specific gene trees, recovered the traditional sister relationship between P. amoena and P. cyanea. In addition, a more recent divergence time estimate between P. amoena and P. cyanea than between P. amoena and P. caerulea provided evidence for the traditional sister relationship. These results provide a compelling example of how lineage sorting stochasticity can lead to incongruence between gene trees and species trees, and illustrate how phylogenetic and population genetic analyses can be integrated to investigate evolutionary relationships between recently diverged taxa.
Quantitative Trait Loci for Grain Yield and Adaptation of Durum Wheat (Triticum durum Desf.) Across a Wide Range of Water Availability
Authors: Maccaferri Marco , Sanguineti Maria Corinna , Corneti Simona , Ortega José Luis Araus , Salem Moncef Ben , Bort Jordi , DeAmbrogio Enzo , del Moral Luis Fernando Garcia , Demontis Andrea , El-Ahmed Ahmed , Maalouf Fouad , Machlab Hassan , Martos Vanessa , Moragues Marc , Motawaj Jihan , Nachit Miloudi , Nserallah Nasserlehaq , Ouabbou Hassan , Royo Conxita , Slama Amor , Tuberosa Roberto 
Published: January 2008

Abstract
Grain yield is a major goal for the improvement of durum wheat, particularly in drought-prone areas. In this study, the genetic basis of grain yield (GY), heading date (HD), and plant height (PH) was investigated in a durum wheat population of 249 recombinant inbred lines evaluated in 16 environments (10 rainfed and 6 irrigated) characterized by a broad range of water availability and GY (from 5.6 to 58.8 q ha−1). Among the 16 quantitative trait loci (QTL) that affected GY, two major QTL on chromosomes 2BL and 3BS showed significant effects in 8 and 7 environments, with R2 values of 21.5 and 13.8% (mean data of all 16 environments), respectively. In both cases, extensive overlap was observed between the LOD profiles of GY and PH, but not with those for HD. QTL specific for PH were identified on chromosomes 1BS, 3AL, and 7AS. Additionally, three major QTL for HD on chromosomes 2AS, 2BL, and 7BS showed limited or no effects on GY. For both PH and GY, notable epistasis between the chromosome 2BL and 3BS QTL was detected across several environments.