bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic detection of numerous gene duplications shared by animals, fungi and plants
Authors: Zhou Xiaofan , Lin Zhenguo , Ma Hong 
Published: April 2010

Abstract
Background
Gene duplication is considered a major driving force for evolution of genetic novelty, thereby facilitating functional divergence and organismal diversity, including the process of speciation. Animals, fungi and plants are major eukaryotic kingdoms and the divergences between them are some of the most significant evolutionary events. Although gene duplications in each lineage have been studied extensively in various contexts, the extent of gene duplication prior to the split of plants and animals/fungi is not clear.

Results
Here, we have studied gene duplications in early eukaryotes by phylogenetic relative dating. We have reconstructed gene families (with one or more orthogroups) with members from both animals/fungi and plants by using two different clustering strategies. Extensive phylogenetic analyses of the gene families show that, among nearly 2,600 orthogroups identified, at least 300 of them still retain duplication that occurred before the divergence of the three kingdoms. We further found evidence that such duplications were also detected in some highly divergent protists, suggesting that these duplication events occurred in the ancestors of most major extant eukaryotic groups.

Conclusions
Our phylogenetic analyses show that numerous gene duplications happened at the early stage of eukaryotic evolution, probably before the separation of known major eukaryotic lineages. We discuss the implication of our results in the contexts of different models of eukaryotic phylogeny. One possible explanation for the large number of gene duplication events is one or more large-scale duplications, possibly whole genome or segmental duplication(s), which provides a genomic basis for the successful radiation of early eukaryotes.
Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication
Authors: Vickers Andrew , Cronin Angel , Roobol Monique , Savage Caroline , Peltola Mari , Pettersson Kim , Scardino Peter T. , Schröder Fritz , Lilja Hans 
Published: April 2010

Purpose We previously reported that a panel of four kallikrein forms in blood—total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)—can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort. Patients and Methods The study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (≥ 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome. Results Addition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis. Conclusion We have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.
Intensity-Modulated Chemoradiotherapy Aiming to Reduce Dysphagia in Patients With Oropharyngeal Cancer: Clinical and Functional Results
Authors: Feng Felix Y. , Kim Hyungjin M. , Lyden Teresa H. , Haxer Marc J. , Worden Francis P. , Feng Mary , Moyer Jeffrey S. , Prince Mark E. , Carey Thomas E. , Wolf Gregory T. , Bradford Carol R. , Chepeha Douglas B. , Eisbruch Avraham 
Published: April 2010

Purpose To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures to reduce post-therapy dysphagia. Patients and Methods This was a prospective study of weekly chemotherapy (carboplatin dosed at one times the area under the curve [AUC, AUC 1] and paclitaxel 30 mg/m2) concurrent with IMRT aiming to spare noninvolved parts of the swallowing structures: pharyngeal constrictors, glottic and supraglottic larynx, and esophagus as well as the oral cavity and major salivary glands. Swallowing was assessed by patient-reported Swallowing and Eating Domain scores, observer-rated scores, and videofluoroscopy (VF) before therapy and periodically after therapy through 2 years. Results Overall, 73 patients with stages III to IV OPC participated. At a median follow-up of 36 months, 3-year disease-free and locoregional recurrence-free survivals were 88% and 96%, respectively. All measures of dysphagia worsened soon after therapy; observer-rated and patient-reported scores recovered over time, but VF scores did not. At 1 year after therapy, observer-rated dysphagia was absent or minimal (scores 0 to 1) in all patients except four: one who was feeding-tube dependent and three who required soft diet. From pretherapy to 12 months post-therapy, the Swallowing and Eating Domain scores worsened on average (± standard deviation) by 10 ± 21 and 13 ± 19, respectively (on scales of 0 to 100), and VF scores (on scale of 1 to 7) worsened from 2.9 ± 1.5 (mild dysphagia) to 4.1 ± 0.9 (mild/moderate dysphagia). Conclusion Chemoradiotherapy with IMRT aiming to reduce dysphagia can be performed safely for OPC and has high locoregional tumor control rates. On average, long-term patient-reported, observer-rated, and objective measures of swallowing were only slightly worse than pretherapy measures, representing potential improvement compared with previous studies.
Incidence and Clinical Complications of Myelodysplastic Syndromes Among United States Medicare Beneficiaries
Authors: Goldberg Stuart L. , Chen Er , Corral Mitra , Guo Amy , Mody-Patel Nikita , Pecora Andrew L. , Laouri Marianne 
Published: April 2010

Purpose To determine the incidence and complications of myelodysplastic syndromes (MDS) among Medicare beneficiaries. Methods Retrospective review of 2003 Medicare Standard Analytic Files utilizing International Classification of Diseases for Oncology ninth edition CM code 238.7 to identify new MDS patients, with 3-year follow-up. Results Among 1,394,343 individuals in Medicare Standard Analytic Files age ≥ 65 years, 162 per 100,000 were coded as newly diagnosed MDS during 2003 yielding a calculated 45,000 new cases in the United States Medicare ≥ 65 years population. Patients with MDS were older (median age, 77 years), and over-represented by males. Among patients with MDS diagnosed during first quarter of 2003, 73.2% suffered cardiac-related events during 3-year follow-up, which exceeded the Medicare population (54.5%; P < .01) even when age adjusted (odds ratio, 2.10; P < .01). Significant increases in prevalence of diabetes (40.0% v 33.1%), dyspnea (49.4% v 28.5%), hepatic diseases (0.8% v 0.2%), and infections (sepsis: 22.5% v 6.1%) were noted in MDS (all P < .01) compared with the Medicare population. Patients with MDS requiring RBC transfusions had greater prevalence of these comorbidities. Acute myeloid leukemia developed within 3 years in 9.6%, with increased transformation among transfused (24.6%; P < .001). The 3-year Kaplan-Meier age-adjusted survival for MDS was 60.0%, which was significantly lower than the Medicare population (84.7%; hazard ratio, 3.08; P < .001), and mortality was further increased among transfused MDS (P < .01). In 2003, median payment for MDS was $16,181, compared to $1,575 for the Medicare population (P < .001). Conclusion MDS is a common hematologic malignancy of the elderly, which places patients at risk for comorbid conditions. Transfusion dependency identifies patients with MDS at additional increased risk of organ impairment and shortened survival.
Functional Activity of the OCT-1 Protein Is Predictive of Long-Term Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib
Authors: White Deborah L. , Dang Phuong , Engler Jane , Frede Amity , Zrim Stephanie , Osborn Michael , Saunders Verity A. , Manley Paul W. , Hughes Timothy P. 
Published: April 2010

Purpose Organic cation transporter-1 (OCT-1) activity (OA), a measure of the OCT-1–mediated influx of imatinib into CML mononuclear cells (MNCs), is predictive of major molecular response (MMR) at 12 and 24 months in patients with untreated CML. We now report the impact of OA on loss of response, disease transformation, and survival after 5 years of imatinib. Patients and Methods OA is defined as the difference in intracellular concentration of carbon-14–imatinib with and without OCT-1 inhibition. OA was measured in blood from 56 patients with untreated chronic-phase CML. Results More patients who had high OA (ie, > median OA value) achieved MMR by 60 months compared with patients who had low OA (89% v 55%; P = .007). A low OA was associated with a significantly lower overall survival (87% v 96%; P = .028) and event-free survival (EFS; 48% v 74%; P = .03) as well as a higher kinase domain mutation rate (21% v 4%; P = .047). These differences were highly significant in patients who averaged less than 600 mg/d of imatinib in the first 12 months but were not significant in patients averaging ≥ 600 mg/d. Patients with very low OA (ie, quartile 1) were the only group who developed leukemic transformation (21% in quartile 1 v 0% in all other quartiles; P = .002). Conclusion Measurement of OA pretherapy is a predictor for the long-term risk of resistance and transformation in patients with imatinib-treated CML. Early dose-intensity may reduce the negative prognostic impact of low OA. We propose that OA could be used to individualize dosage strategies for patients with CML to maximize molecular response and optimize long-term outcome.
High Expression of the Very Late Antigen-4 Integrin Independently Predicts Reduced Risk of Relapse and Improved Outcome in Pediatric Acute Myeloid Leukemia: A Report From the Children's Oncology Group
Authors: Walter Roland B. , Alonzo Todd A. , Gerbing Robert B. , Ho Phoenix A. , Smith Franklin O. , Raimondi Susana C. , Hirsch Betsy A. , Gamis Alan S. , Franklin Janet L. , Hurwitz Craig A. , Loken Michael R. , Meshinchi Soheil 
Published: April 2010

PurposeTo evaluate the prognostic significance of the integrin cell adhesion molecule very late antigen-4 (VLA-4) in acute myeloid leukemia (AML).Patients and MethodsWe prospectively quantified VLA-4 expression in 216 patients enrolled onto COG-AAML03P1 by flow cytometry and correlated expression levels with disease characteristics and clinical outcome.ResultsVLA-4 mean fluorescence intensity (MFI) varied 35-fold (range, 30 to 1,110; median, 219.5). High VLA-4 expression (> median MFI), compared with low expression, was associated with younger age (7.1 v 12.1 years, respectively; P < .001), lower FLT3 internal tandem duplication prevalence (4% v 21%, respectively; P < .001), and higher likelihood of extramedullary disease (16% v 5%, respectively; P = .013). In low- and high-expression groups, rates of remission (89% v 80%, respectively; P = .137) and minimal residual disease (29% v 25%, respectively; P = .700) were similar. Patients with low VLA-4 expression, compared with high expression, had a higher relapse rate (RR; 44% ± 10% v 24% ± 9%, respectively; P = .011) and lower disease-free survival (DFS; 48% ± 11% v 67% ± 10%, respectively; P = .023) after 3 years. Multivariate analyses showed that low VLA-4 expression was an independent adverse prognostic factor for DFS (hazard ratio [HR] = 1.98; P = .038) and RR (HR = 2.77; P = .009). Subgroup analyses indicated that the prognostic role of VLA-4 expression was most prominent in patients with standard-risk AML, in whom low VLA-4 expression was associated with inferior DFS (34% ± 16% v 69% ± 14% for high expression; P = .011) and higher RR (61% ± 16% v 26% ± 14% for high expression; P = .009). A similar trend was seen in low-risk but not high-risk patients.ConclusionHigh VLA-4 expression is associated with better clinical outcome in pediatric AML and is an independent predictor of relapse that may refine our abilities to stratify patients without identifiable cytogenetic or molecular risk factors.
Results of Microsurgical Extra-Intracranial Arterial Bypass in the Treatment of Cerebral Ischemia
Authors: Yasargil Gazi M. , Yonekawa Yasuhiro 
Published: April 2010

Abstract
The authors report the operative and follow-up results (3 months to 9 years) of 86 consecutive extra-intracranial bypass operations on 84 patients with cerebral ischemia, emphasizing both the prophylactic role of the operation in preventing further catastrophic cerebral ischemia, and the low morbidity and mortality of the operation.
The Treatment of Intracranial Aneurysms by Injection with a Tissue Adhesive
Authors: Sheptak Peter E. , Zanetti Paul H. , Susen Anthony F. 
Published: April 2010

Abstract
The authors have developed a technique of occluding intracranial aneurysms by the direct injection of a tissue adhesive. Previous work in our laboratory had revealed the unusual intravascular characteristics and physiological properties of isobutyl-2-cyanoacrylate (IBC). These findings had indicated the feasibility of utilizing IBC in the treatment of intracranial aneurysms by its direct injection. We have now treated twenty patients by this method. Eighteen aneurysms were injected during open craniotomy and two were treated by closed stereotactic injection utilizing electronic radiography. Follow-up data, ranging from 1 to 6 years after operation, are available on these patients. Sixteen patients (80% of the series) have had good to excellent results. Our experience and the application of this technique as a potential tool in the treatment of intracranial aneurysms are discussed.
Cranial Computed Tomographic Demonstration of Intracranial Penetration by an Orbital Foreign Body
Authors: Lunsford Dade L. , Woodford Jack , Drayer Burton P. 
Published: April 2010

Abstract
A 9-year-old boy suffered intracerebral penetration by a stick driven into his right orbit. Diagnosis was obtained by cranial computed tomography (CT), and this test directed appropriate immediate surgical intervention. Combined orbital exploration and craniotomy was followed by a gratifying recovery. The importance of CT in orbital and possible intracranial trauma is stressed.
Usefulness of cell-free plasma DNA, procalcitonin and C-reactive protein as markers of infection in febrile patients
Authors: Moreira Vanessa García , Prieto Belén , Rodríguez Julia San Martín , Álvarez Francisco V 
Published: April 2010

Background Circulating nucleic acids were discovered more than 60 y ago. With the recent developments in the study of circulating nucleic acids, its application in the diagnostic field has increased. The objective of this study was to assess the usefulness of the quantification of cell-free plasma DNA (CF-DNA) concentration in the diagnosis of infections in febrile patients and as a prognostic marker in septic patients. Methods Concentrations of CF-DNA, procalcitonin (PCT) and C-reactive protein (CRP) were measured in 110 febrile patients who were clinically diagnosed with fever of unknown origin, localized infection, sepsis or septic shock. Results Concentrations of CF-DNA increase according to the severity of the infection. The best cut-off point for predicting infection was 2800 GE (genome equivalents)/mL (sensitivity: 95.0%; specificity: 96.7%) and 14,000 GE/mL for sepsis prediction (sensitivity: 77.8%; specificity: 94.6%). Higher concentrations of CF-DNA were found in exitus septic patients than in survivors. The diagnostic efficiency of CF-DNA was similar to PCT and higher than CRP in infectious processes. Conclusions Normal concentrations of CF-DNA can exclude the presence of an infection in febrile patients, and very high concentrations (>10-fold over the normal reference range) stratify the severity of infections, showing a high prognostic value to predict mortality in the absence of other causes for elevated CF-DNA.
Age-related differential diagnosis of vaginal bleeding in postmenopausal women: a series of 3047 symptomatic postmenopausal women
Authors: Burbos Nikolaos , Musonda Patrick , Giarenis Ilias , Shiner Alice M , Giamougiannis Panagiotis , Morris Edward , Nieto Joaquin J 
Published: April 2010

Objective The aim of this study is to identify the causes of vaginal bleeding in different age groups of postmenopausal women. Also, we attempt to estimate the incidence of postmenopausal vaginal bleeding and endometrial cancer in a defined geographical area. Study design The study was conducted at a gynaecological oncology centre in the United Kingdom, between February 2006 and May 2009. Patients were investigated according to established evidence-based departmental guidelines. Results During the study period 3047 women were referred with postmenopausal vaginal bleeding. In 1356 women (44.5%) the endometrial thickness measured less than 5 mm on transvaginal ultrasound scan. Benign histology was found in 1144 women (37.5%). Benign endometrial polyps were the cause of bleeding in 10.1% of the cases. The incidence of endometrial cancer in our study population was 5%. The rate of postmenopausal vaginal bleeding during the study period peaks at the age of 55–59 years (25.9/1000 postmenopausal women/year) and declines thereafter. The peak incidence of endometrial cancer during the study period (12.6/10,000 postmenopausal women/year) was seen between the ages of 60 and 64 years and similarly declines with increasing age. Conclusion To our knowledge, this is the first population-based estimation of the incidence of genital tract bleeding and endometrial cancer among postmenopausal women in the United Kingdom. The results of this study showing the age-related differential diagnosis can be used to inform clinical practice when counselling postmenopausal women with vaginal bleeding.
Women with recurrent postmenopausal bleeding should be re-investigated but are not more likely to have endometrial cancer
Authors: Ronghe Rashmi , Gaudoin Marco 
Published: April 2010

Objectives We aimed to determine the prevalence of endometrial cancer in patients presenting with recurrent postmenopausal bleeding (PMB) after initial negative investigations. Study design This was a retrospective study carried out in a dedicated PMB clinic. All patients presenting with recurrent PMB between 1 January 2003 and 31 May 2009 were studied. All patients had transvaginal ultrasound, speculum examination and endometrial sampling attempted. Main outcome measure The prevalence of endometrial cancer in patients presenting with recurrent PMB after initial negative investigations. Results A total of 1536 women with PMB were seen over a period of 56 months. Sixty-six required definitive treatment after their first visit. One hundred and twenty-six re-presented with recurrent bleeding. The prevalence of endometrial cancer in women presenting for the first time with PMB was 3.04% whereas that in women presenting with recurrent PMB after initial negative investigations was 4%. One of these women re-presented within six months of initial visit and another within one year. All the other cancers were diagnosed more than one year after initial negative investigations (range 19.6–57.1 months). One woman had an endometrial cancer even though the endometrial thickness was less than 3 mm. Conclusions Women with recurrent PMB after initial negative investigations are no more likely to have endometrial cancer than those presenting for the first time but re-investigation is indicated if six months has elapsed.
GOAT: the master switch for the ghrelin system?
Authors: Romero Amparo , Kirchner Henriette , Heppner Kristy , Pfluger Paul T , Tschöp Matthias H , Nogueiras Ruben 
Published: April 2010

AbstractThe ghrelin–ghrelin receptor system is one of the most important mechanisms regulating energy balance and metabolism. Among other actions, central and peripheral administration of ghrelin increases food intake and adiposity. During the last years, many efforts have been made in the investigation of the cellular and molecular mechanisms modulating the effects of ghrelin. One particularity of this peptide hormone is its acylation at serine-3 with an eight-carbon fatty acid (octanoate), which confers its biological activity. Recent reports have demonstrated that the ghrelinO-acyltransferase (GOAT) is the enzyme that catalyzes ghrelin octanoylation. Therefore, all questions concerning the posttranslational acylation of ghrelin are of great interest for the complete understanding of this system. In this review, we summarize the discovery and characterization of GOAT, and remark the importance of GOAT as a novel and potential target that regulates the biological actions of ghrelin, revealing several therapeutical possibilities for the treatment of the metabolic syndrome.
A Fluorescence in Situ Hybridization System for Karyotyping Soybean
Authors: Findley Seth D , Cannon Steven , Varala Kranthi , Du Jianchang , Ma Jianxin , Hudson Matthew E , Birchler James A , Stacey Gary 
Published: April 2010

Abstract
The development of a universal soybean (Glycine max [L.] Merr.) cytogenetic map that associates classical genetic linkage groups, molecular linkage groups, and a sequence-based physical map with the karyotype has been impeded due to the soybean chromosomes themselves, which are small and morphologically homogeneous. To overcome this obstacle, we screened soybean repetitive DNA to develop a cocktail of fluorescent in situ hybridization (FISH) probes that could differentially label mitotic chromosomes in root tip preparations. We used genetically anchored BAC clones both to identify individual chromosomes in metaphase spreads and to complete a FISH-based karyotyping cocktail that permitted simultaneous identification of all 20 chromosome pairs. We applied these karyotyping tools to wild soybean, G. soja Sieb. and Zucc., which represents a large gene pool of potentially agronomically valuable traits. These studies led to the identification and characterization of a reciprocal chromosome translocation between chromosomes 11 and 13 in two accessions of wild soybean. The data confirm that this translocation is widespread in G. soja accessions and likely accounts for the semi-sterility found in some G. soja by G. max crosses.
On Relevance of Codon Usage to Expression of Synthetic and Natural Genes in Escherichia coli
Authors: Supek Fran , \#352;muc Tomislav 
Published: April 2010

Abstract
A recent investigation concluded that codon bias did not affect expression of green fluorescent protein (GFP) variants in Escherichia coli, while stability of an mRNA secondary structure near the 5′ end played a dominant role. We demonstrate that combining the two variables using regression trees or support vector regression yields a biologically plausible model with better support in the GFP data set and in other experimental data: codon usage is relevant for protein levels if the 5′ mRNA structures are not strong. Natural E. coli genes had weaker 5′ mRNA structures than the examined set of GFP variants and did not exhibit a correlation between the folding free energy of 5′ mRNA structures and protein expression.